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Sample records for early clinical development

  1. Pharmacogenomics in early-phase clinical development

    PubMed Central

    Burt, Tal; Dhillon, Savita

    2015-01-01

    Pharmacogenomics (PGx) offers the promise of utilizing genetic fingerprints to predict individual responses to drugs in terms of safety, efficacy and pharmacokinetics. Early-phase clinical trial PGx applications can identify human genome variations that are meaningful to study design, selection of participants, allocation of resources and clinical research ethics. Results can inform later-phase study design and pipeline developmental decisions. Nevertheless, our review of the clinicaltrials.gov database demonstrates that PGx is rarely used by drug developers. Of the total 323 trials that included PGx as an outcome, 80% have been conducted by academic institutions after initial regulatory approval. Barriers for the application of PGx are discussed. We propose a framework for the role of PGx in early-phase drug development and recommend PGx be universally considered in study design, result interpretation and hypothesis generation for later-phase studies, but PGx results from underpowered studies should not be used by themselves to terminate drug-development programs. PMID:23837482

  2. From promising molecules to orphan drugs: Early clinical drug development

    PubMed Central

    Dooms, Marc

    2017-01-01

    Summary Phase-1 (also known as “First-in-Man”) clinical trials initiate the early clinical development of possible new medicines. Patient participation in this early phase of clinical trials is rather limited. After successful phase 1 trials, further phase 2 and phase 3 clinical trials in patients may lead to a marketing authorization. In the first 15 years of the European Union Orphan Drug Directive, 4.5% of the orphan drug applications were authorized. However, for many of these orphan drugs, no phase 1 studies were required, as these products were already well known pharmaceutical substances, with a clearly defined pharmacological profile. Furthermore, for 19 orphan drugs, already authorized by the European Medicines Agency (EMA), the original rare indication was extended to another rare disease and no phase 1 trials were needed. Phase 1 studies need to be performed in a sufficient number of volunteers even for medicinal products intended for a very limited number of patients. PMID:28357178

  3. Drugs in early clinical development for Systemic Lupus Erythematosus

    PubMed Central

    Postal, Mariana; Sinicato, Nailú Angélica; Appenzeller, Simone; Niewold, Timothy B

    2016-01-01

    Introduction While immunosuppressive therapy has positively impacted the prognosis of systemic lupus erythematosus (SLE), many patients still do not respond to traditional therapy. Thus, active SLE disease remains a significant problem. Furthermore, conventional immunosuppressive treatments for SLE are associated a high risk of side effects. These issues call for improvement in our current therapeutic armamentarium. Areas covered In this review, the authors highlight the recent developments in therapies for SLE, and present an overview of drugs which are in early clinical development for SLE. There are many new therapeutic approaches being developed, including those focused on B-cell targets, T-cell downregulation, co-stimulatory blockade, anti-cytokine agents, and kinase inhibition, and Toll-like receptor inhibition. They also discuss peptide therapy as a potential method to re-establish immune tolerance, and some of the challenges ahead in developing and testing novel agents for SLE. Expert opinion Many novel agents are currently in development for SLE, but this encouraging news is tempered by several disappointments in clinical trials and provides a timely moment to reflect on the future of therapeutic development in SLE. It seems likely that biological heterogeneity between patients is a major contributor to difficulty in drug design in SLE. PMID:26950689

  4. Clinical imprinting: the impact of early clinical learning on career long professional development in nursing.

    PubMed

    Andrew, Nicola

    2013-05-01

    The literature recognises a relationship between clinical experience and a successful undergraduate experience in nursing; however what constitutes an effective approach remains the subject of debate, particularly in relation to first year of learning. There is evidence from a biological standpoint that early experience impacts on the behavioural development of animals, described by Konrad Lorenz (1903-1989) as 'imprinting'. The concept of imprinting has resonance for nursing. In this article the importance of 'getting it right at the beginning' is explored and what, if anything, Lorenz's theory tells us about the impact of early clinical learning on subsequent professional development. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Incremental Validity in the Clinical Assessment of Early Childhood Development

    ERIC Educational Resources Information Center

    Liu, Xin; Zhou, Xiaobin; Lackaff, Julie

    2013-01-01

    The authors demonstrate the increment of clinical validity in early childhood assessment of physical impairment (PI), developmental delay (DD), and autism (AUT) using multiple standardized developmental screening measures such as performance measures and parent and teacher rating scales. Hierarchical regression and sensitivity/specificity analyses…

  6. Incremental Validity in the Clinical Assessment of Early Childhood Development

    ERIC Educational Resources Information Center

    Liu, Xin; Zhou, Xiaobin; Lackaff, Julie

    2013-01-01

    The authors demonstrate the increment of clinical validity in early childhood assessment of physical impairment (PI), developmental delay (DD), and autism (AUT) using multiple standardized developmental screening measures such as performance measures and parent and teacher rating scales. Hierarchical regression and sensitivity/specificity analyses…

  7. Challenges in early clinical development of adjuvanted vaccines.

    PubMed

    Della Cioppa, Giovanni; Jonsdottir, Ingileif; Lewis, David

    2015-06-08

    A three-step approach to the early development of adjuvanted vaccine candidates is proposed, the goal of which is to allow ample space for exploratory and hypothesis-generating human experiments and to select dose(s) and dosing schedule(s) to bring into full development. Although the proposed approach is more extensive than the traditional early development program, the authors suggest that by addressing key questions upfront the overall time, size and cost of development will be reduced and the probability of public health advancement enhanced. The immunogenicity end-points chosen for early development should be critically selected: an established immunological parameter with a well characterized assay should be selected as primary end-point for dose and schedule finding; exploratory information-rich end-points should be limited in number and based on pre-defined hypothesis generating plans, including system biology and pathway analyses. Building a pharmacodynamic profile is an important aspect of early development: to this end, multiple early (within 24h) and late (up to one year) sampling is necessary, which can be accomplished by sampling subgroups of subjects at different time points. In most cases the final target population, even if vulnerable, should be considered for inclusion in early development. In order to obtain the multiple formulations necessary for the dose and schedule finding, "bed-side mixing" of various components of the vaccine is often necessary: this is a complex and underestimated area that deserves serious research and logistical support.

  8. Drugs in early clinical development for the treatment of osteosarcoma.

    PubMed

    Heymann, Marie-Françoise; Brown, Hannah K; Heymann, Dominique

    2016-11-01

    Osteosarcomas are the main malignant primary bone tumours found in children and young adults. Conventional treatment is based on diagnosis and resection surgery, combined with polychemotherapy. This is a protocol that was established in the 1970s. Unfortunately, this therapeutic approach has reached a plateau of efficacy and the patient survival rate has not improved in the last four decades. New therapeutic approaches are thus required to improve the prognosis for osteosarcoma patients. Areas covered: From the databases available and published scientific literature, the present review gives an overview of the drugs currently in early clinical development for the treatment of osteosarcoma. For each drug, a short description is given of the relevant scientific data supporting its development. Expert opinion: Multidrug targeted approaches are set to emerge, given the heterogeneity of osteosarcoma subtypes and the multitude of therapeutic responses. The key role played by the microenvironment in the disease increases the number of therapeutic targets (such as macrophages or osteoclasts), as well as the master proteins that control cell proliferation or cell death. Ongoing phase I/II trials are important steps, not only for identifying new therapies with greater safety and efficacy, but also for better defining the role played by the microenvironment in the pathogenesis of osteosarcoma.

  9. Clinical assessment of early language development: a simplified short form of the Mandarin communicative development inventory.

    PubMed

    Soli, Sigfrid D; Zheng, Yun; Meng, Zhaoli; Li, Gang

    2012-09-01

    The purpose of this study was to develop a practical mean for clinical evaluation of early pediatric language development by establishing developmental trajectories for receptive and expressive vocabulary growth in children between 6 and 32 months of age using a simple, time-efficient assessment tool. Simplified short form versions of the Words and Gestures and Words and Sentences vocabulary inventories in the Mandarin Communicative Development Inventory [1] were developed and used to assess early language development in developmentally normal children from 6 to 32 months of age during routine health checks. Developmental trajectories characterizing the rate of receptive and expressive vocabulary growth between 6 and 32 months of age are reported. These trajectories allow the equivalent age corresponding to a score to be determined after a brief structured interview with the child's parents that can be conducted in a busy clinical setting. The simplified short forms of the Mandarin Communicative Development Inventories can serve as a clinically useful tool to assess early child language development, providing a practical mean of objectively assessing early language development following early interventions to treat young children with hearing impairment as well as speech and language delays. Objective evidence of language development is essential for achievement of effective (re)habilitation outcomes. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  10. Vaccine development: From concept to early clinical testing.

    PubMed

    Cunningham, Anthony L; Garçon, Nathalie; Leo, Oberdan; Friedland, Leonard R; Strugnell, Richard; Laupèze, Béatrice; Doherty, Mark; Stern, Peter

    2016-12-20

    In the 21st century, an array of microbiological and molecular allow antigens for new vaccines to be specifically identified, designed, produced and delivered with the aim of optimising the induction of a protective immune response against a well-defined immunogen. New knowledge about the functioning of the immune system and host pathogen interactions has stimulated the rational design of vaccines. The design toolbox includes vaccines made from whole pathogens, protein subunits, polysaccharides, pathogen-like particles, use of viral/bacterial vectors, plus adjuvants and conjugation technology to increase and broaden the immune response. Processes such as recombinant DNA technology can simplify the complexity of manufacturing and facilitate consistent production of large quantities of antigen. Any new vaccine development is greatly enhanced by, and requires integration of information concerning: 1. Pathogen life-cycle & epidemiology. Knowledge of pathogen structure, route of entry, interaction with cellular receptors, subsequent replication sites and disease-causing mechanisms are all important to identify antigens suitable for disease prevention. The demographics of infection, specific risk groups and age-specific infection rates determine which population to immunise, and at what age. 2. Immune control & escape. Interactions between the host and pathogen are explored, with determination of the relative importance of antibodies, T-cells of different types and innate immunity, immune escape strategies during infection, and possible immune correlates of protection. This information guides identification and selection of antigen and the specific immune response required for protection. 3. Antigen selection & vaccine formulation. The selected antigen is formulated to remain suitably immunogenic and stable over time, induce an immune response that is likely to be protective, plus be amenable to eventual scale-up to commercial production. 4. Vaccine preclinical

  11. Medical students' emotional development in early clinical experience: a model.

    PubMed

    Helmich, Esther; Bolhuis, Sanneke; Laan, Roland; Dornan, Tim; Koopmans, Raymond

    2014-08-01

    Dealing with emotions is a critical feature of professional behaviour. There are no comprehensive theoretical models, however, explaining how medical students learn about emotions. We aimed to explore factors affecting their emotions and how they learn to deal with emotions in themselves and others. During a first-year nursing attachment in hospitals and nursing homes, students wrote daily about their most impressive experiences, explicitly reporting what they felt, thought, and did. In a subsequent interview, they discussed those experiences in greater detail. Following a grounded theory approach, we conducted a constant comparative analysis, collecting and then interpreting data, and allowing the interpretation to inform subsequent data collection. Impressive experiences set up tensions, which gave rise to strong emotions. We identified four 'axes' along which tensions were experienced: 'idealism versus reality', 'critical distance versus adaptation', 'involvement versus detachment' and 'feeling versus displaying'. We found many factors, which influenced how respondents relieved those tensions. Their personal attributes and social relationships both inside and outside the medical community were important ones. Respondents' positions along the different dimensions, as determined by the balance between attributes and tensions, shaped their learning outcomes. Medical students' emotional development occurs through active participation in medical practice and having impressive experiences within relationships with patients and others on wards. Tensions along four dimensions give rise to strong emotions. Gaining insight into the many conditions that influence students' learning about emotions might support educators and supervisors in fostering medical students' emotional and professional development.

  12. Faculty Development for Fostering Clinical Reasoning Skills in Early Medical Students Using a Modified Bayesian Approach.

    PubMed

    Addy, Tracie Marcella; Hafler, Janet; Galerneau, France

    2016-01-01

    Clinical reasoning is a necessary skill for medical students to acquire in the course of their education, and there is evidence that they can start this process at the undergraduate level. However, physician educators who are experts in their given fields may have difficulty conveying their complex thought processes to students. Providing faculty development that equips educators with tools to teach clinical reasoning may support skill development in early medical students. We provided faculty development on a modified Bayesian method of teaching clinical reasoning to clinician educators who facilitated small-group, case-based workshops with 2nd-year medical students. We interviewed them before and after the module regarding their perceptions on teaching clinical reasoning. We solicited feedback from the students about the effectiveness of the method in developing their clinical reasoning skills. We carried out this project during an institutional curriculum rebuild where clinical reasoning was a defined goal. At the time of the intervention, there was also increased involvement of the Teaching and Learning Center in elevating the status of teaching and learning. There was high overall satisfaction with the faculty development program. Both the faculty and the students described the modified Bayesian approach as effective in fostering the development of clinical reasoning skills. Through this work, we learned how to form a beneficial partnership between a clinician educator and Teaching and Learning Center to promote faculty development on a clinical reasoning teaching method for early medical students. We uncovered challenges faced by both faculty and early learners in this study. We observed that our faculty chose to utilize the method of teaching clinical reasoning in a variety of manners in the classroom. Despite obstacles and differing approaches utilized, we believe that this model can be emulated at other institutions to foster the development of clinical

  13. The development and utility of a clinical algorithm to predict early HIV-1 infection.

    PubMed

    Sharghi, Neda; Bosch, Ronald J; Mayer, Kenneth; Essex, Max; Seage, George R

    2005-12-01

    The association between self-reported clinical factors and recent HIV-1 seroconversion was evaluated in a prospective cohort of 4652 high-risk participants in the HIV Network for Prevention Trials (HIVNET) Vaccine Preparedness Study. Eighty-six individuals seroconverted, with an overall annual seroconversion rate of 1.3 per 100 person-years. Four self-reported clinical factors were significantly associated with HIV-1 seroconversion in multivariate analyses: recent history of chlamydia infection or gonorrhea, recent fever or night sweats, belief of recent HIV exposure, and recent illness lasting > or =3 days. Two scoring systems, based on the presence of either 4 or 11 clinical factors, were developed. Sensitivity ranged from 2.3% (with a positive predictive value of 12.5%) to 72.1% (with a positive predictive value of 1%). Seroconversion rates were directly associated with the number of these clinical factors. The use of scoring systems comprised of clinical factors may aid in detecting early and acute HIV-1 infection in vaccine and microbicide trials. Organizers can educate high-risk trial participants to return for testing during interim visits if they develop these clinical factors. Studying individuals during early and acute HIV-1 infection would allow scientists to investigate the impact of the intervention being studied on early transmission or pathogenesis of HIV-1 infection.

  14. Nursing students' early exposure to clinical practice: an innovation in curriculum development.

    PubMed

    Hoyles, A; Pollard, C; Lees, S; Glossop, D

    2000-08-01

    This paper describes a pilot study addressing issues surrounding the balance and status given to both theory and practice in the foundation part of a pre-registration programme. Contemporary thinking seems to suggest that there is a need to reverse recent trends which have placed an emphasis on theory. To facilitate this a framework for clinical learning was adapted to guide students' early exposure to clinical practice. The focus was to develop the students' observational and reflective skills whilst also providing the students with a frame of reference within which they could explore their theoretical studies. The information and experiences gained as a result of this study have led to the integration of an Orientation Framework to support students' early clinical experiences in a pre-registration programme.

  15. Integrating Pharmacoproteomics into Early-Phase Clinical Development: State-of-the-Art, Challenges, and Recommendations

    PubMed Central

    Nandal, Savita; Burt, Tal

    2017-01-01

    Pharmacoproteomics is the study of disease-modifying and toxicity parameters associated with therapeutic drug administration, using analysis of quantitative and temporal changes to specific, predetermined, and select proteins, or to the proteome as a whole. Pharmacoproteomics is a rapidly evolving field, with progress in analytic technologies enabling processing of complex interactions of large number of unique proteins and effective use in clinical trials. Nevertheless, our analysis of clinicaltrials.gov and PubMed shows that the application of proteomics in early-phase clinical development is minimal and limited to few therapeutic areas, with oncology predominating. We review the history, technologies, current usage, challenges, and potential for future use, and conclude with recommendations for integration of pharmacoproteomic in early-phase drug development. PMID:28218733

  16. Integrating Pharmacoproteomics into Early-Phase Clinical Development: State-of-the-Art, Challenges, and Recommendations.

    PubMed

    Nandal, Savita; Burt, Tal

    2017-02-19

    Pharmacoproteomics is the study of disease-modifying and toxicity parameters associated with therapeutic drug administration, using analysis of quantitative and temporal changes to specific, predetermined, and select proteins, or to the proteome as a whole. Pharmacoproteomics is a rapidly evolving field, with progress in analytic technologies enabling processing of complex interactions of large number of unique proteins and effective use in clinical trials. Nevertheless, our analysis of clinicaltrials.gov and PubMed shows that the application of proteomics in early-phase clinical development is minimal and limited to few therapeutic areas, with oncology predominating. We review the history, technologies, current usage, challenges, and potential for future use, and conclude with recommendations for integration of pharmacoproteomic in early-phase drug development.

  17. The convergence of cancer prevention and therapy in early-phase clinical drug development.

    PubMed

    Abbruzzese, James L; Lippman, Scott M

    2004-10-01

    After decades of separate but not equal drug development, prevention and therapy are beginning to converge at the level of early-phase clinical testing. This highly beneficial convergence is due to spectacular molecular advances in our understanding of neoplasia (both cancer and precancer), cancer risk and prognosis, and the mechanisms by which novel drugs with less toxicity and more cytostatic activity profiles target specific molecular events to suppress malignant and premalignant cells. The future full convergence of prevention-therapy drug development (aided by technological advances, such as in molecular imaging) promises to hasten the progress of oncology in reducing the public health impact of the major cancers.

  18. Dynamic changes in gene expression during human early embryo development: from fundamental aspects to clinical applications.

    PubMed

    Assou, Said; Boumela, Imène; Haouzi, Delphine; Anahory, Tal; Dechaud, Hervé; De Vos, John; Hamamah, Samir

    2011-01-01

    The first week of human embryonic development comprises a series of events that change highly specialized germ cells into undifferentiated human embryonic stem cells (hESCs) that display an extraordinarily broad developmental potential. The understanding of these events is crucial to the improvement of the success rate of in vitro fertilization. With the emergence of new technologies such as Omics, the gene expression profiling of human oocytes, embryos and hESCs has been performed and generated a flood of data related to the molecular signature of early embryo development. In order to understand the complex genetic network that controls the first week of embryo development, we performed a systematic review and study of this issue. We performed a literature search using PubMed and EMBASE to identify all relevant studies published as original articles in English up to March 2010 (n = 165). We also analyzed the transcriptome of human oocytes, embryos and hESCs. Distinct sets of genes were revealed by comparing the expression profiles of oocytes, embryos on Day 3 and hESCs, which are associated with totipotency, pluripotency and reprogramming properties, respectively. Known components of two signaling pathways (WNT and transforming growth factor-β) were linked to oocyte maturation and early embryonic development. Omics analysis provides tools for understanding the molecular mechanisms and signaling pathways controlling early embryonic development. Furthermore, we discuss the clinical relevance of using a non-invasive molecular approach to embryo selection for the single-embryo transfer program.

  19. Dynamic changes in gene expression during human early embryo development: from fundamental aspects to clinical applications

    PubMed Central

    Assou, Said; Boumela, Imène; Haouzi, Delphine; Anahory, Tal; Dechaud, Hervé; De Vos, John; Hamamah, Samir

    2010-01-01

    BACKGROUND The first week of human embryonic development comprises a series of events that change highly specialized germ cells into undifferentiated human embryonic stem cells (hESCs) that display an extraordinarily broad developmental potential. The understanding of these events is crucial to the improvement of the success rate of in vitro fertilization (IVF). With the emergence of new technologies such as Omics, the gene expression profiling of human oocytes, embryos, and hESCs has been performed and generated a flood of data related to the molecular signature of early embryo development. METHODS In order to understand the complex genetic network that controls the first week of embryo development, we performed a systematic review and study of this issue. We performed a literature search using PubMed and EMBASE to identify all relevant studies published as original articles in English up to March 2010 (n=165). We also analyzed the transcriptome of human oocytes, embryos and hESCs. RESULTS Distinct sets of genes were revealed by comparing the expression profiles of oocytes, embryos on day-3 and hESCs, that are associated with totipotency, pluripotency and reprogramming properties, respectively. Known components of two signalling pathways (WNT and transforming growth factor-beta) were linked to oocyte maturation and early embryonic development. CONCLUSION Omics analysis provides tools for understanding the molecular mechanisms and signalling pathways controlling early embryonic development. Furthermore, we discuss the clinical relevance of using a non-invasive molecular approach to embryo selection for the single embryo transfer (SET) program. PMID:20716614

  20. Positron emission tomography microdosing: a new concept with application in tracer and early clinical drug development.

    PubMed

    Bergström, Mats; Grahnén, Anders; Långström, Bengt

    2003-09-01

    The realisation that new chemical entities under development as drug candidates fail in three of four cases in clinical trials, together with increased costs and increased demands of reducing preclinical animal experiments, have promoted concepts for improvement of early screening procedures in humans. Positron emission tomography (PET) is a non-invasive imaging technology, which makes it possible to determine drug distribution and concentration in vivo in man with the drug labelled with a positron-emitting radionuclide that does not change the biochemical properties. Recently, developments in the field of rapid synthesis of organic compounds labelled with positron-emitting radionuclides have allowed a substantial number of new drug candidates to be labelled and potentially used as probes in PET studies. Together, these factors led to the logical conclusion that early PET studies, performed with very low drug doses-PET-microdosing-could be included in the drug development process as one means for selection or rejection of compounds based on performance in vivo in man. Another important option of PET, to evaluate drug interaction with a target, utilising a PET tracer specific for this target, necessitates a more rapid development of such PET methodology and validations in humans. Since only very low amounts of drugs are used in PET-microdosing studies, the safety requirements should be reduced relative to the safety requirements needed for therapeutic doses. In the following, a methodological scrutinising of the concept is presented. A complete pre-clinical package including limited toxicity assessment is proposed as a base for the regulatory framework of the PET-microdosing concept.

  1. 2015 Guidance on cancer immunotherapy development in early-phase clinical studies.

    PubMed

    2015-12-01

    The development of cancer immunotherapies is progressing rapidly with a variety of technological approaches. They consist of "cancer vaccines", which are based on the idea of vaccination, "effector cell therapy", classified as passive immunotherapy, and "inhibition of immunosuppression", which intends to break immunological tolerance to autoantigens or immunosuppressive environments characterizing antitumor immune responses. Recent reports showing clinical evidence of efficacy of immune checkpoint inhibitors and adoptive immunotherapies with tumor-infiltrating lymphocytes and tumor-specific receptor gene-modified T cells indicate the beginning of a new era for cancer immunotherapy. This guidance summarizes ideas that will be helpful to those who plan to develop cancer immunotherapy. The aims of this guidance are to discuss and offer important points in early phase clinical studies of innovative cancer immunotherapy, with future progress in this field, and to contribute to the effective development of cancer immunotherapy aligned with the scope of regulatory science. This guidance covers cancer vaccines, effector cell therapy, and inhibition of immunosuppression, including immune checkpoint inhibitors.

  2. Strategies in early clinical development for the treatment of basic defects of cystic fibrosis.

    PubMed

    Dhooghe, Barbara; Haaf, Jérémy Boris; Noel, Sabrina; Leal, Teresinha

    2016-01-01

    Twenty-six years after the identification of the gene responsible for cystic fibrosis (CF), controversies still surround the pathogenesis of the disease that continues to burden and shorten lives. Therefore, finding effective therapeutic strategies that target the basic defect of CF is crucially needed. This review offers a comprehensive survey of fundamental therapies in early stages of development for the treatment of CF. The first part describes recent strategies targeting the basic defect either at the gene or at the transcript level. The second part summarizes a panel of novel strategies targeting protein repair. The third part reports strategies targeting non-CFTR channels. Recent major breakthroughs in CF therapy have been made, raising hope to find a cure for CF. Apart from Vertex corrector and potentiator molecules (lumacaftor, ivacaftor, VX-661) and from ataluren, used to correct nonsense mutations, most compounds being currently tested are in very early (I-II) phases of development and definitive clinical results are keenly expected. Among the broad list of molecules and strategies being tested, the QR-010 compound and inhibitors of phosphodiesterase type 5 (sildenafil, vardenafil) could reveal a strong potentiality as therapeutic candidates to cure CF.

  3. Drugs in early clinical development for the treatment of female sexual dysfunction.

    PubMed

    Belkin, Zoe R; Krapf, Jill M; Goldstein, Andrew T

    2015-02-01

    There is growing recognition of female sexual dysfunction (FSD) as an important women's health concern. Despite an increased awareness of the pathophysiologic components to FSD, currently, there are no drugs approved for the most common sexual complaint in women-decreased sexual desire. In response to an overwhelming demand for therapy for FSD, several drugs are undergoing development and testing. The aim of this paper is to provide the latest data on pharmacological treatments for FSD currently in Phase I and II clinical trials. These include topical alprostadil, bremelanotide (BMT), intranasal testosterone (TBS-2), intravaginal dehydroepiandrosterone (DHEA), sublingual testosterone with sildenafil, apomorphine (APO), bupropprion and trazodone. It should be noted that the definitions of FSD have recently been revised in the diagnostic and statistical manual for mental disorders (DSM) 5, with merging of hypoactive sexual desire disorder (HSDD) and female sexual arousal disorder (FSAD) into female sexual interest/arousal disorder (FSIAD). However, it is noted that the majority of clinical trials discussed in this paper use the DSM IV-R diagnoses of HSDD and FSAD. Medications in early phase trials show promise for the treatment of FSD. These therapies focus on treating many possible causes of FSD. Concerns over gender bias within the FDA need to be resolved given the need for new treatment options for FSD.

  4. The Doris Duke Clinical Scientist Development Award: implications for early-career physician scientists.

    PubMed

    Escobar-Alvarez, Sindy N; Myers, Elizabeth R

    2013-11-01

    The Doris Duke Charitable Foundation Clinical Scientist Development Award (CSDA) supports early-career physician scientists in their transition to independent research funding. The authors aimed to analyze the characteristics associated with success in CSDA competitions, determine whether attainment of a CSDA is associated with receiving subsequent research funding, and assess whether alumni remain in research. In 2011, the authors tested for associations between gender, age, race/ethnicity, academic degree, National Institutes of Health (NIH) funding rank of the applicant's institution, and success in CSDA competitions. They compared NIH R01 grant attainment, defined as the percentage of individuals who received at least one R01 grant, between CSDA alumni and highly ranked but unsuccessful CSDA applicants (1998-2007). Finally, the authors surveyed alumni to learn more about their professional activities. Demographic factors were not predictors of success in CSDA competitions; academic degree and funding rank of the applicant's institution, however, were. A greater percentage of CSDA alumni than nonalumni received at least one R01 grant (62% [74/120] versus 42% [44/105]). For CSDA alumni who were 10 or more years from the start of their award, their median percent effort toward research activities was 68%. The factors associated with success in a CSDA competition included a combined clinical and doctoral research degree and affiliation with a well-funded institution. More alumni received NIH independent research funding than those who applied but did not receive the award. Thus, the CSDA is associated with physicians establishing independent and recognized research careers.

  5. Formulation design space: a proven approach to maximize flexibility and outcomes within early clinical development.

    PubMed

    McDermott, John; Scholes, Peter

    2015-01-01

    Traditional formulation development studies involve expensive and time-consuming screening of prototypes in preclinical species to select 'lead' systems for evaluation in human clinical pharmacokinetic studies. A new paradigm, Translational Pharmaceutics, has emerged to integrate pharmaceutical development, manufacturing and clinical functions to address these restrictions. Rapid Formulation development and Clinical Testing (RapidFACT) is applied to exploit the benefits of Translational Pharmaceutics in the clinical screening and optimization of drug products. Benefits are maximized by the adapted utilization of the concept of 'formulation design space'. This article presents the experience of the application of design space within RapidFACT and is supported by data from over 200 formulations studied to date, including case studies on how the approach has been applied.

  6. Early phase drug development for treatment of chronic pain--options for clinical trial and program design.

    PubMed

    Kalliomäki, Jarkko; Miller, Frank; Kågedal, Matts; Karlsten, Rolf

    2012-07-01

    Due to high prevalence and unmet medical need, chronic pain has become an important area for development of new medicines. Chronic pain disorders are heterogeneous with regard to pathophysiological mechanisms and clinical presentation. While a mechanism-based classification of pain is generally advocated, it is not yet applicable for diagnostic use. Many new analgesic drug candidates believed to act on scientifically relevant pain targets have failed to show efficacy in clinical trials. These might be true observations of inferior efficacy and/or safety. However, in part, these failures may be due to difficulties with selection of an appropriate study population and/or appropriate doses. For a new chemical entity (NCE) with a novel pharmacological mechanism, the only guidance for selection of study population and doses is often based on preclinical data. Thus, there may be considerable uncertainty in defining the population with a pain generating mechanism targeted by the NCE. Therefore, further exploration of the right population and dose may be needed in early clinical phase why alternatives to conventional trial designs may be considered. We have reviewed characteristics of three alternative design options from an early (Phase 2) drug development perspective; enriched enrolment, dose titration and adaptive dosing. The advantages and disadvantages of each type of study design were analyzed and discussed from a clinical development program perspective. It is concluded that these designs can be useful in addressing different types of issues in early development of novel analgesic drugs for chronic pain.

  7. Accelerating clinical insights: how to use accelerator mass spectrometry to make better early development decisions.

    PubMed

    Seymour, Mark

    2010-12-01

    This paper is an overview of the applications of the technique of Accelerator Mass Spectrometry (AMS) in the biomedical drug development field. The work described here has been carried out at Xceleron (York, UK and Germantown, MD, USA), and it aims to apply AMS to provide better information about the human pharmacokinetic/metabolic behaviour of drugs or drug candidates as early as possible. It is hoped that the use of this technique will contribute to the delivery of better, more effective drugs onto the market sooner, which will be good news for all concerned.

  8. A Discrepancy in Comprehension and Production in Early Language Development in ASD: Is It Clinically Relevant?

    ERIC Educational Resources Information Center

    Davidson, Meghan M.; Ellis Weismer, Susan

    2017-01-01

    This study examined the extent to which a discrepant comprehension-production profile (i.e., relatively more delayed comprehension than production) is characteristic of the early language phenotype in autism spectrum disorders (ASD) and tracked the developmental progression of the profile. Our findings indicated that a discrepant…

  9. Can pharmaco-electroencephalography help improve survival of central nervous system drugs in early clinical development?

    PubMed

    Wilson, Frederick J; Leiser, Steven C; Ivarsson, Magnus; Christensen, Søren R; Bastlund, Jesper F

    2014-03-01

    Pharmaco-electroencephalography has significant yet unrealised promise as a translatable intermediate biomarker of central pharmacodynamic activity that could help reduce Phase 2 attrition in the development of central nervous system drugs. In an effort to understand its true potential, a framework for decision-making was proposed and the utility of pharmaco-electroencephalography was assessed through several case studies. A key finding was that lack of standardisation reduces the value of data pooling and meta-analyses and renders assessment of translatability difficult, limiting utility in all but simple cases. Pre-competitive collaboration is essential both to improving understanding of translation and developing modern signal processing techniques. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Development of a Quality Care Plan to Reduce Otolaryngologic Readmissions: Early Lessons from the Cleveland Clinic.

    PubMed

    Rajasekaran, Karthik; Revenaugh, Peter; Benninger, Michael; Burkey, Brian; Sindwani, Raj

    2015-10-01

    Hospital readmissions are an important focus of national quality and cost containment efforts. With increased emphasis on the impact of unplanned readmissions, it is critical to evaluate factors contributing to readmission rates and optimize strategies aimed at reducing these rates. The objectives of this study were to discuss quality interventions implemented at our institution and to evaluate their impact on reducing readmissions. Case series with chart review. Academic tertiary care medical center. Medical records of patients who were admitted to an otolaryngology inpatient service and readmitted within 30 days of discharge between January 2010 and December 2012 were reviewed. A quality care plan (QCP) was developed, and various interventions were implemented during this time to affect these rates. There were 769, 816, and 798 admissions during the years 2010, 2011, and 2012, respectively. The number of readmissions during this time were 50 (6.5%), 51 (6.3%), and 28 (3.5%), respectively. There were no statistically significant differences in case mix index, demographics, and subsequent length of stay for those patients requiring readmission. The reduction in number of readmissions in 2012, after the institution of our QCP, was statistically significant (P < .05). Readmission within 30 days in a large otolaryngology practice can be multifactorial. To reduce rates of readmission, it is essential to understand the diagnoses, postoperative complications, and comorbidities contributing to readmission. Implementation of a QCP composed of comprehensive discharge planning and close postdischarge follow-up can lead to a reduction in readmissions. © American Academy of Otolaryngology-Head and Neck Surgery Foundation 2015.

  11. Early Program Development

    NASA Image and Video Library

    2004-04-15

    During the Space Shuttle development phase, Marshall plarners concluded a Heavy Lift Launch Vehicle (HLLV) would be needed for successful Space Industrialization. Shown here in this 1976's artist's conception is an early version of the HLLV during launch.

  12. Early Developments, 1998.

    ERIC Educational Resources Information Center

    Little, Loyd, Ed.

    1998-01-01

    This document consists of the two 1998 issues of a journal reporting new research in early child development conducted by the Frank Porter Graham Child Development Center at the University of North Carolina at Chapel Hill. In the Spring 1998 issue, articles highlight the Center's diverse cross-cultural projects and global research, training and…

  13. Early Developments, 2002.

    ERIC Educational Resources Information Center

    Winton, Pam, Ed.; Buysse, Virginia, Ed.

    2002-01-01

    This document consists of the three 2002 issues of a journal reporting new research in early child development conducted by the Frank Porter Graham Child Development Center (FPG) at the University of North Carolina at Chapel Hill. Articles in the Winter 2002 issue highlight some current work at FPG on factors that enhance or inhibit social and…

  14. Early Developments, 2000.

    ERIC Educational Resources Information Center

    Little, Loyd, Ed.

    2000-01-01

    This document consists of the three 2000 issues of a journal reporting new research in early child development conducted by the Frank Porter Graham Child Development Center at the University of North Carolina at Chapel Hill. Articles in the spring 2000 issue focus on a follow-up study of the Abecedarian Project, children of depressed mothers,…

  15. Epigenetics of Early Child Development

    PubMed Central

    Murgatroyd, Chris; Spengler, Dietmar

    2011-01-01

    Comprehensive clinical studies show that adverse conditions in early life can severely impact the developing brain and increase vulnerability to mood disorders later in life. During early postnatal life the brain exhibits high plasticity which allows environmental signals to alter the trajectories of rapidly developing circuits. Adversity in early life is able to shape the experience-dependent maturation of stress-regulating pathways underlying emotional functions and endocrine responses to stress, such as the hypothalamo–pituitary–adrenal (HPA) system, leading to long-lasting altered stress responsivity during adulthood. To date, the study of gene–environment interactions in the human population has been dominated by epidemiology. However, recent research in the neuroscience field is now advancing clinical studies by addressing specifically the mechanisms by which gene–environment interactions can predispose individuals toward psychopathology. To this end, appropriate animal models are being developed in which early environmental factors can be manipulated in a controlled manner. Here we will review recent studies performed with the common aim of understanding the effects of the early environment in shaping brain development and discuss the newly developing role of epigenetic mechanisms in translating early life conditions into long-lasting changes in gene expression underpinning brain functions. Particularly, we argue that epigenetic mechanisms can mediate the gene–environment dialog in early life and give rise to persistent epigenetic programming of adult physiology and dysfunction eventually resulting in disease. Understanding how early life experiences can give rise to lasting epigenetic marks conferring increased risk for mental disorders, how they are maintained and how they could be reversed, is increasingly becoming a focus of modern psychiatry and should pave new guidelines for timely therapeutic interventions. PMID:21647402

  16. A question-based approach to adopting pharmacogenetics to understand risk for clinical variability in pharmacokinetics in early drug development.

    PubMed

    Evers, R; Blanchard, R L; Warner, A W; Cutler, D; Agrawal, N G B; Shaw, P M

    2014-09-01

    Understanding genetic variations that influence pharmacokinetics (PK) in humans is important for optimal clinical use of drugs. Guidances for making decisions on when to conduct pharmacogenetic research during drug development have been proposed by regulatory agencies, but their uniform adoption presents problems due to an inherent lack of flexibility. A questions-based approach (QBA) was developed to enable drug development teams at Merck to iteratively and flexibly evaluate the potential impact of pharmacogenetics (PGx) on clinical pharmacokinetic variability.

  17. Clinical development of combination strategies in immunotherapy: are we ready for more than one investigational product in an early clinical trial?

    PubMed

    Perez-Gracia, Jose L; Berraondo, Pedro; Martinez-Forero, Ivan; Alfaro, Carlos; Suarez, Natalia; Gurpide, Alfonso; Sangro, Bruno; Hervas-Stubbs, Sandra; Ochoa, Carmen; Melero, Jose A; Melero, Ignacio

    2009-09-01

    Stimulating the innate and adaptive immunity against cancer necessitates the tricking of a system evolved to fight microbial pathogens and directing its activity towards transformed self-tissue. Efficacious interventions to start and sustain the response will probably require a number of agents to tamper simultaneously or sequentially with several immune mechanisms. Although master switches controlling various functions may exist, the goal of a curative immune response will probably demand the combined actions of several therapeutic components. Synergy occurs when drugs interact in ways that enhance or magnify one or more effects or side effects. In cancer immunotherapy, two agents that have minor or no therapeutic effects as single agents can be powerful when combined. Mouse experimentation provides multiple examples of synergistic combinations. Elements to be combined include chiefly: tumor vaccines, adoptive T-cell therapies, cytokines, costimulatory molecules, molecular deactivation of immunosuppressive or tolerogenic pathways and immunostimulatory monoclonal antibodies. These novel therapies, even as single agents, are extremely complex products to be developed owing to the associated biomolecules, cell therapies or gene therapies. At present, drug-development programs are run individually for each immunotherapeutic agent and combinations are considered only at a later stage in clinical development, even in the absence of formal compulsory regulations to prevent clinical trials with combinations. As a result, instead of the search for maximal efficacy, ease of combination with standard treatments, intellectual property management, regulations and business-based decisions often guide the way. Even though the maximal effort must be made in order to prevent adverse effects in patients, it seems reasonable that combination pilot trials should be performed at an early stage, following safe completion of Phase I trials. These trials should be performed based on

  18. Intraclonal heterogeneity is a critical early event in the development of myeloma and precedes the development of clinical symptoms.

    PubMed

    Walker, B A; Wardell, C P; Melchor, L; Brioli, A; Johnson, D C; Kaiser, M F; Mirabella, F; Lopez-Corral, L; Humphray, S; Murray, L; Ross, M; Bentley, D; Gutiérrez, N C; Garcia-Sanz, R; San Miguel, J; Davies, F E; Gonzalez, D; Morgan, G J

    2014-02-01

    The mechanisms involved in the progression from monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM) to malignant multiple myeloma (MM) and plasma cell leukemia (PCL) are poorly understood but believed to involve the sequential acquisition of genetic hits. We performed exome and whole-genome sequencing on a series of MGUS (n=4), high-risk (HR)SMM (n=4), MM (n=26) and PCL (n=2) samples, including four cases who transformed from HR-SMM to MM, to determine the genetic factors that drive progression of disease. The pattern and number of non-synonymous mutations show that the MGUS disease stage is less genetically complex than MM, and HR-SMM is similar to presenting MM. Intraclonal heterogeneity is present at all stages and using cases of HR-SMM, which transformed to MM, we show that intraclonal heterogeneity is a typical feature of the disease. At the HR-SMM stage of disease, the majority of the genetic changes necessary to give rise to MM are already present. These data suggest that clonal progression is the key feature of transformation of HR-SMM to MM and as such the invasive clinically predominant clone typical of MM is already present at the SMM stage and would be amenable to therapeutic intervention at that stage.

  19. Intraclonal heterogeneity is a critical early event in the development of myeloma and precedes the development of clinical symptoms

    PubMed Central

    Melchor, Lorenzo; Brioli, Annamaria; Johnson, David C; Kaiser, Martin F; Mirabella, Fabio; Lopez-Corral, Lucia; Humphray, Sean; Murray, Lisa; Ross, Mark; Bentley, David; Gutiérrez, Norma C.; Garcia-Sanz, Ramón; San Miguel, Jesus; Davies, Faith E; Gonzalez, David; Morgan, Gareth J

    2013-01-01

    The mechanisms involved in progression from monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM) to malignant multiple myeloma (MM) and plasma cell leukemia (PCL) are poorly understood but believed to involve the sequential acquisition of genetic hits. We performed exome and whole genome sequencing on a series of MGUS (n=4), high risk (HR)-SMM (n=4), MM (n=26) and PCL (n=2) samples, including four cases who transformed from HR-SMM to MM, to determine the genetic factors which drive progression of disease. The pattern and number of non-synonymous mutations show that the MGUS disease stage is less genetically complex than MM, and HR-SMM is similar to presenting MM. Intraclonal heterogeneity is present at all stages and using cases of HR-SMM, which transformed to MM, we show that intraclonal heterogeneity is a typical feature of the disease. At the HR-SMM stage of disease the majority of the genetic changes necessary to give rise to MM are already present. These data suggest that clonal progression is the key feature of transformation of HR-SMM to MM and as such the invasive clinically predominant clone typical of MM is already present at the SMM stage and would be amenable to therapeutic intervention at that stage. PMID:23817176

  20. Early Program Development

    NASA Image and Video Library

    1971-01-01

    This 1971 artist's concept shows a Nuclear Shuttle and an early Space Shuttle docked with an Orbital Propellant Depot. As envisioned by Marshall Space Flight Center Program Development persornel, an orbital modular propellant storage depot, supplied periodically by the Space Shuttle or Earth-to-orbit fuel tankers, would be critical in making available large amounts of fuel to various orbital vehicles and spacecraft.

  1. Early Program Development

    NASA Image and Video Library

    1970-01-01

    This artist's concept from 1970 shows a Nuclear Shuttle docked to an Orbital Propellant Depot and an early Space Shuttle. As envisioned by Marshall Space Flight Center Program Development plarners, the Nuclear Shuttle, in either manned or unmanned mode, would deliver payloads to lunar orbit or other destinations then return to Earth orbit for refueling and additonal missions.

  2. Clinical recognition of early schizophrenic decompensation.

    PubMed

    Donlon, P T; Blacker, K H

    1975-06-01

    The early signs and symptoms of schizophrenic decompensation are subtle and variegated. Today's community patient often presents with vague complaints of brief duration making it imperative that today's diagnostician be able to recognize and appropriately treat early psychopathology. This paper collates a number of observations of developing psychotic phenomena -- self reports, clinical studies and controlled experiments -- and provides a useful format for organizing these complex and changing behaviors. Data are presented and discussed using our clinical schema for detailing the natural progression of developing psychotic phenomena into four distinct stages. Efficacy of early recognition and treatment in aborting or diminishing a major psychotic episode is discussed. The advantages of recognizing the early signs of psychotic decompensation are apparent. First, with adequate intervention and treatment, the overt psychotic state may be attenuated. Although the feasibility of reducing the incidence of schizophrenia through intervention in "high risk" groups, or those experiencing insidious symptoms remain speculative (further investigation in this area is urgently needed), nonetheless, early diagnosis and comprehensive rehabilitative care significantly improves social and occupational adjustment. A second advantage accrues from early diagnosis. It enables patient and family to better cope with the illness. We have previously outlined a schema detailing the natural progression of developing psychotic phenomena into four distinct stages. The phenomena, when identified, can be seen as a continuum. However, many clinicians fail to recognize the earlier phases and typically the diagnosis of psychosis is made relatively late at what we call stage three of the four stages we described.

  3. Factors in the Development of Clinical Informatics Competence in Early Career Health Sciences Professionals in Australia: A Qualitative Study

    ERIC Educational Resources Information Center

    Gray, Kathleen; Sim, Jenny

    2011-01-01

    This paper reports on a qualitative study investigating how Australian health professionals may be developing and deploying essential clinical informatics capabilities in the first 5 years of their professional practice. It explores the experiences of four professionals in applying what they have learned formally and informally during their…

  4. Factors in the Development of Clinical Informatics Competence in Early Career Health Sciences Professionals in Australia: A Qualitative Study

    ERIC Educational Resources Information Center

    Gray, Kathleen; Sim, Jenny

    2011-01-01

    This paper reports on a qualitative study investigating how Australian health professionals may be developing and deploying essential clinical informatics capabilities in the first 5 years of their professional practice. It explores the experiences of four professionals in applying what they have learned formally and informally during their…

  5. Early Interactive Emotional Development

    PubMed Central

    Messinger, Daniel S.; Mahoor, Mohammad H.; Cadavid, Steven; Chow, Sy-Miin; Cohn, Jeffrey F.

    2010-01-01

    Early infant emotional development concerns the interactive emergence of emotional states that motivate approach and withdrawal. These are indexed by different patterns of infant facial expressions, vocalization, and gazing that emerge within parent-infant interactions in the first 10 months of life. Specifically, the interface of a limited number of interactive parameters creates complex real-time patterns which change over developmental time. These phenomena are described below using techniques from our laboratory such as statistical simulations, continuous ratings, and computer vision modeling. PMID:21804955

  6. Genomics-based early-phase clinical trials in oncology: recommendations from the task force on Methodology for the Development of Innovative Cancer Therapies.

    PubMed

    Liu, Stephen V; Miller, Vincent A; Lobbezoo, Marinus W; Giaccone, Giuseppe

    2014-11-01

    The Methodology for the Development of Innovative Cancer Therapies (MDICT) task force discussed incorporation of genomic profiling into early (Phase I and II) clinical trials in oncology. The task force reviewed the challenges of standardising genomics data in a manner conducive to conducting clinical trials. Current barriers to successful and efficient implementation were identified and discussed, as well as the methods of genomic analysis, the proper setting for study and strategies to facilitate timely completion of genomics-based studies. The importance of properly capturing and cataloguing outcomes was also discussed. Several recommendations regarding the use of genomics in these trials are provided. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. The clinical importance of serum γ-glutamyltransferase level as an early predictor of obesity development in Korean men.

    PubMed

    Suh, Young Ju; Park, Sung Keun; Choi, Joong-Myung; Ryoo, Jae-Hong

    2013-04-01

    Serum γ-glutamyl transferase (GGT) levels are known to be positively associated with obesity. We aimed at verifying an association between baseline GGT levels and the development of obesity in Korean men. This prospective cohort study was performed on 18,510 initially non-obese Korean men. The total follow-up period was 66,993.3 person years and the average follow-up period was 3.62 years (standard deviation [SD], 1.44). Cox proportional hazards model was used to determine hazard ratios for the risk of obesity development. We found a strong positive association between serum GGT levels at baseline and obesity development, after adjusting for multiple covariates. The risk of obesity development was found to be significantly and dose-dependently associated with serum GGT level. Moreover, estimated hazard ratios for severe obesity (BMI (body mass index) ≥30 kg/m(2)) attributable to serum GGT levels were much higher than those for obesity (BMI ≥ 25 kg/m(2)). The significant association was also found for WC (waist circumference)-defined obesity (WC > 90 cm). Our findings, which were obtained from a large cohort, indicate that serum GGT is an early predictor of obesity development. Furthermore, this association was remained significant after adjusting for multiple baseline covariates. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Translational Modeling and Simulation in Supporting Early-Phase Clinical Development of New Drug: A Learn-Research-Confirm Process.

    PubMed

    Liu, Dongyang; Zhang, Yi; Jiang, Ji; Choi, John; Li, Xuening; Zhu, Dalong; Xiao, Dawei; Ding, Yanhua; Fan, Hongwei; Chen, Li; Hu, Pei

    2017-08-01

    Pharmacokinetic/pharmacodynamic modeling and simulation can aid clinical drug development by dynamically integrating key system- and drug-specific information into predictive profiles. In this study, we propose a methodology to predict pharmacokinetic/pharmacodynamic profiles of sinogliatin (HMS-5552, RO-5305552), a novel glucokinase activator to treat diabetes mellitus, for first-in-patient (FIP) studies. Initially, pharmacokinetic/pharmacodynamic profiles of sinogliatin and another glucokinase activator (US2) previously acquired from healthy subjects were fitted using Model A incorporating an indirect response mechanism. The pharmacokinetic/pharmacodynamic profiles of US2 in patients with type 2 diabetes mellitus (T2DM) were then fitted using Model B incorporating circadian rhythm and food effects after thoughtful research on the difference between healthy subjects and T2DM patients. The differences in results between the two US2 modeling populations were used to scale the values of the pharmacodynamic parameters and refine the pharmacodynamic model of sinogliatin, which was then utilized to project pharmacokinetic/pharmacodynamic profiles of sinogliatin in T2DM patients after an 8-day simulated treatment. Results showed that the projected pharmacokinetic/pharmacodynamic values of five parameters were within 70-130% of values fitted from observed clinical data while the other two remaining projected parameters were within a twofold error. Population pharmacokinetic/pharmacodynamic analysis conducted for sinogliatin also suggested that age and sex were significantly correlated to pharmacokinetic/pharmacodynamic characteristics. Additionally, Model B was combined with a glycosylated hemoglobin (HbA1c) compartment to form Model C, which was then used to project serum HbA1c levels in patients after a 1-month simulated treatment of sinogliatin. The predicted HbA1c changes were nearly identical to observed clinical values (0.82 vs. 0.78%). Model-based drug

  9. Do Clinical and Translational Science Graduate Students Understand Linear Regression? Development and Early Validation of the REGRESS Quiz

    PubMed Central

    2013-01-01

    Abstract Introduction Although regression is widely used for reading and publishing in the medical literature, no instruments were previously available to assess students’ understanding. The goal of this study was to design and assess such an instrument for graduate students in Clinical and Translational Science and Public Health. Methods A 27‐item REsearch on Global Regression Expectations in StatisticS (REGRESS) quiz was developed through an iterative process. Consenting students taking a course on linear regression in a Clinical and Translational Science program completed the quiz pre‐ and postcourse. Student results were compared to practicing statisticians with a master's or doctoral degree in statistics or a closely related field. Results Fifty‐two students responded precourse, 59 postcourse , and 22 practicing statisticians completed the quiz. The mean (SD) score was 9.3 (4.3) for students precourse and 19.0 (3.5) postcourse (P < 0.001). Postcourse students had similar results to practicing statisticians (mean (SD) of 20.1(3.5); P = 0.21). Students also showed significant improvement pre/postcourse in each of six domain areas (P < 0.001). The REGRESS quiz was internally reliable (Cronbach's alpha 0.89). Conclusion The initial validation is quite promising with statistically significant and meaningful differences across time and study populations. Further work is needed to validate the quiz across multiple institutions. PMID:24330688

  10. Do clinical and translational science graduate students understand linear regression? Development and early validation of the REGRESS quiz.

    PubMed

    Enders, Felicity

    2013-12-01

    Although regression is widely used for reading and publishing in the medical literature, no instruments were previously available to assess students' understanding. The goal of this study was to design and assess such an instrument for graduate students in Clinical and Translational Science and Public Health. A 27-item REsearch on Global Regression Expectations in StatisticS (REGRESS) quiz was developed through an iterative process. Consenting students taking a course on linear regression in a Clinical and Translational Science program completed the quiz pre- and postcourse. Student results were compared to practicing statisticians with a master's or doctoral degree in statistics or a closely related field. Fifty-two students responded precourse, 59 postcourse , and 22 practicing statisticians completed the quiz. The mean (SD) score was 9.3 (4.3) for students precourse and 19.0 (3.5) postcourse (P < 0.001). Postcourse students had similar results to practicing statisticians (mean (SD) of 20.1(3.5); P = 0.21). Students also showed significant improvement pre/postcourse in each of six domain areas (P < 0.001). The REGRESS quiz was internally reliable (Cronbach's alpha 0.89). The initial validation is quite promising with statistically significant and meaningful differences across time and study populations. Further work is needed to validate the quiz across multiple institutions. © 2013 Wiley Periodicals, Inc.

  11. Clinical approaches to early inflammatory arthritis.

    PubMed

    van Schaardenburg, Dirkjan; Dijkmans, Ben A C

    2009-11-01

    Several advances have been made in the understanding of the pathogenesis, as well as in the clinical evaluation and treatment, of early inflammatory arthritis. The presence of anti-citrullinated protein antibodies (ACPAs) has emerged as a major new biomarker for use in clinical practice. The presence of ACPAs can be used to divide patients with early arthritis into subsets that are phenotypically similar but have varying pathogenetic and prognostic features. Although the detection of ACPAs is a major development in the diagnosis and prognosis of rheumatoid arthritis (RA), prediction of the outcome of arthritis at the individual level can still be much improved. For patients diagnosed with RA, and who have active polyarthritis, treatment is not dependent on the assessment of prognostic factors, as these patients are best treated with combination therapy; over 40% of these patients achieve remission with such treatment. In patients who present with oligoarthritis, however, management should be based on the assessment of prognostic factors. The success of early treatment of inflammatory arthritis and the recognition of a measurable preclinical phase of RA offer hope that treating the disease before it becomes clinically active might be possible.

  12. Development of clinical scientists.

    PubMed

    Smith, R V

    1987-01-01

    The education and training of clinical scientists has served society in several ways. For academic pharmacy, the emergence of clinical science has provided research and scholarship opportunities for clinical faculty development. Clinical scientists have also begun to play important roles in industrial drug research and development. For all faculty and students, clinical science research reinforces a "research mindset" that will become increasingly important as our society moves from a production/extraction to an information-based economy. Pharmacy will best evolve by increasing its commitment to clinical science research. In the process, academic pharmacy must continue to improve and support excellent education and training programs for clinical scientists.

  13. The Importance of Early Experiences: Clinical, Research, and Policy Perspectives

    ERIC Educational Resources Information Center

    Zeanah, Charles H.

    2009-01-01

    The degree to which early adverse experiences exert long term effects on development and how much early adversity may be overcome through subsequent experiences are important mental health questions. The clinical, research and policy perspectives on these questions lead to different answers. From a clinical perspective, change is always possible,…

  14. The Importance of Early Experiences: Clinical, Research, and Policy Perspectives

    ERIC Educational Resources Information Center

    Zeanah, Charles H.

    2009-01-01

    The degree to which early adverse experiences exert long term effects on development and how much early adversity may be overcome through subsequent experiences are important mental health questions. The clinical, research and policy perspectives on these questions lead to different answers. From a clinical perspective, change is always possible,…

  15. Early clinical exposure through innovative interactive clinical anatomy lectures.

    PubMed

    Ramachandran, Kalpana; Chacko, Thomas V; Grant, Janet; Bhandary, Shital

    2015-01-01

    Traditional lecture-based teaching of anatomy tends to focus on the discipline per se rather than relating it to clinical conditions. As a result, students often lose interest in the basic sciences. We hypothesized that a lecture format that encourages students to relate anatomy to case presentations might help them in appreciating clinical relevance. We therefore proposed to develop, implement and evaluate innovative interactive clinical anatomy lectures (ICALs) for first year medical students of our institution as a method to implement the 'early clinical exposure' teaching strategy being promoted by the Medical Council of India. The first year medical students (n=150) were divided into two groups by lottery: the study group (n=75) and the control group (n=75). The study group received nine ICALs along with traditional gross anatomy lectures (TGL) and dissection. The control group received only TGL along with dissection. A post-test in clinical anatomy was conducted for both groups. The responses of the study group on TGL and ICALs on their learning and understanding of the clinical conditions were collected using the nominal group technique. It is feasible to introduce early clinical exposure within lectures even with 150 students. There was a statistically significant (p<0.001) difference in the mean post-test scores of the two groups, which shows that ICALs are effective in correlating anatomical and clinical information to students. The nominal group technique responses of the study group showed that they appreciated it as a better method of teaching and learning. Copyright 2015, NMJI.

  16. Early Adolescent Ego Development.

    ERIC Educational Resources Information Center

    James, Michael A.

    1980-01-01

    Presented are the theoretical characteristics of social identity in early adolescence (ages 10 to 15). It is suggested that no longer is identity thought to begin with adolescence, but may have its beginnings in the preteen years. The article draws heavily on Eriksonian concepts. (Editor/KC)

  17. Early Program Development

    NASA Image and Video Library

    1969-01-01

    As part of the Space Task Group's recommendations for more commonality and integration in America's space program, Marshall Space Flight Center engineers proposed an orbiting propellant storage facility to augment Space Shuttle missions. In this artist's concept from 1969 an early version of the Space Shuttle is shown refueling at the facility.

  18. Early Adolescent Ego Development.

    ERIC Educational Resources Information Center

    James, Michael A.

    1980-01-01

    Presented are the theoretical characteristics of social identity in early adolescence (ages 10 to 15). It is suggested that no longer is identity thought to begin with adolescence, but may have its beginnings in the preteen years. The article draws heavily on Eriksonian concepts. (Editor/KC)

  19. Early Program Development

    NASA Image and Video Library

    1969-01-01

    This 1969 artist's concept illustrates the use of three major elements of NASA's Integrated program, as proposed by President Nixon's Space Task Group. In Phases I and II, a Space Tug with a manipulator-equipped crew module removes a cargo module from an early Space Shuttle Orbiter and docks with it. In Phases III and IV, the Space Tug with attached cargo module flys toward a Nuclear Shuttle. As a result of the Space Task Group's recommendations for more commonality and integration in the American space program, Marshall Space Flight Center engineers studied many of the spacecraft depicted here.

  20. Early experience and brain development.

    PubMed

    Bick, Johanna; Nelson, Charles A

    2017-01-01

    Healthy brain development takes place within the context of individual experience. Here, we describe how certain early experiences are necessary for typical brain development. We present evidence from multiple studies showing that severe early life neglect leads to alterations in brain development, which compromises emotional, behavioral, and cognitive functioning. We also show how early intervention can reverse some of the deleterious effects of neglect on brain development. We conclude by emphasizing that early interventions that start at the earliest possible point in human development are most likely to support maximal recovery from early adverse experiences. WIREs Cogn Sci 2017, 8:e1387. doi: 10.1002/wcs.1387 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

  1. CRITICAL READING DEVELOPS EARLY.

    ERIC Educational Resources Information Center

    LEE, DORRIS; AND OTHERS

    THIS ISSUE OF THE READING AIDS SERIES PRESENTS A DISCUSSION OF THE POTENTIAL FOR CRITICAL READING AMONG YOUNG CHILDREN AND HOW IT CAN BE DEVELOPED. IT OFFERS SUGGESTIONS FOR THE MAXIMUM DEVELOPMENT OF THINKING SKILLS AND ATTITUDES OF INQUIRY AND EVALUATION. SOME OF THE TOPICS DISCUSSED ARE -- (1) THE DEVELOPMENT OF PERCEPTS, CONCEPTS, AND COMMON…

  2. A new robot for flexible ureteroscopy: development and early clinical results (IDEAL stage 1-2b).

    PubMed

    Saglam, Remzi; Muslumanoglu, Ahmet Yaser; Tokatlı, Zafer; Caşkurlu, Turhan; Sarica, Kemal; Taşçi, Ali İhsan; Erkurt, Bülent; Süer, Evren; Kabakci, Ahmet Sinan; Preminger, Glenn; Traxer, Olivier; Rassweiler, Jens J

    2014-12-01

    An improved armamentarium has had a significant impact on the emerging role of flexible ureteroscopy (FURS) for the management of nephrolithiasis; however, FURS still represents a challenging technique. To examine a robotic device designed for FURS for its impact on ergonomics and outcome of the procedure based on the IDEAL (idea, development, evaluation, assessment, long-term study) framework. Roboflex Avicenna consists of a surgeon's console and a manipulator for the flexible ureterorenoscope. Following experimental evaluation of the prototype (IDEAL stage 1) and receipt of ethical approval, seven surgeons treated 81 patients (mean age: 42 yr [range: 6-68]) with renal calculi (mean volume: 1296±544 mm(3) [range: 432-3100 mm3]) in an observational study (IDEAL stage 2). Robotic FURS was performed with the Roboflex Avicenna robotic device. Numerical data were analysed with the Mann-Whitney test, and categorical variables were analysed using the chi-square test or Fisher exact test. P values <0.05 were considered statistically significant. Mean robot docking time was 59.6±45 s. Mean operative time was 74min (range: 40-182). Mean fragmentation speed was 29.1±6.1 mm3/min. Ergonomics based on a validated questionnaire showed significant advantage for robotic FURS (total score: 5.6 vs 31.3; p<0.01). A 10/12F-access sheath was used in 72 patients. Two cases required secondary FURS, one because of malfunction of the flexible digital ureteroscope and another because of larger residual fragments. In the remaining 79 cases, complete stone disintegration was accomplished. Roboflex Avicenna provides a suitable and safe platform for robotic FURS with significant improvement of ergonomics. Future studies should evaluate its impact on the clinical outcome of FURS. Robotic flexible ureteroscopy (FURS) was performed with the Roboflex Avicenna robotic device. Results showed that Roboflex Avicenna provides a suitable and safe platform for robotic FURS with significant improvement

  3. Early Program Development

    NASA Image and Video Library

    1970-01-01

    In 1970, NASA initiated Phase A contracts to study alternate Space Shuttle designs in addition to the two-stage fully-reusable Space Shuttle system already under development. A number of alternate systems were developed to ensure the development of the optimum earth-to-orbit system, including the Stage-and-a-half Chemical Interorbital Shuttle, shown here. The concept would utilize a reusable marned spacecraft with an onboard propulsion system attached to an expendable fuel tank to provide supplementary propellants.

  4. Family Influences on Early Development.

    ERIC Educational Resources Information Center

    Silber, Sharon

    1989-01-01

    The article reviews the literature concerning family influences on early childhood development. Implications of this literature for intervention planning with high risk children and families are suggested. Topics covered include the early parent-child relationship, disciplinary strategies, stimulation, parental instruction and expectations, the…

  5. Early Program Development

    NASA Image and Video Library

    1963-01-01

    This artist's concept from 1963 shows a proposed NERVA (Nuclear Engine for Rocket Vehicle Application) incorporating the NRX-A1, the first NERVA-type cold flow reactor. The NERVA engine, based on Kiwi nuclear reactor technology, was intended to power a RIFT (Reactor-In-Flight-Test) nuclear stage, for which Marshall Space Flight Center had development responsibility.

  6. Early Program Development

    NASA Image and Video Library

    1971-01-01

    This 1971 artist's concept shows the Nuclear Shuttle in both its lunar logistics configuraton and geosynchronous station configuration. As envisioned by Marshall Space Flight Center Program Development persornel, the Nuclear Shuttle would deliver payloads to lunar orbits or other destinations then return to Earth orbit for refueling and additional missions.

  7. Early Program Development

    NASA Image and Video Library

    1970-01-01

    This 1970 artist's concept shows a Nuclear Shuttle in flight. As envisioned by Marshall Space Flight Center Program Development engineers, the Nuclear Shuttle would deliver payloads to lunar orbit or other destinations then return to Earth orbit for refueling and additional missions.

  8. Early Program Development

    NASA Image and Video Library

    1970-01-01

    This artist's concept from 1970 shows a Nuclear Shuttle taking on fuel from an orbiting Liquid Hydrogen Depot. As envisioned by Marshall Space Flight Center Program Development persornel, the Nuclear Shuttle would deliver payloads to lunar orbit or other destinations then return to Earth orbit for refueling and additional missions.

  9. Early Program Development

    NASA Image and Video Library

    1971-01-01

    This 1971 artist's concept illustrates a proposed Orbital Liquid Hydrogen Depot. As envisioned by Marshall Space Flight Center Program Development persornel, an orbital modular propellant storage depot, supplied periodically by the Space Shuttle or Earth-to-orbit fuel tankers, would be critical in making available large amounts of fuel to various orbital vehicles and spacecraft.

  10. Early Program Development

    NASA Image and Video Library

    1971-01-01

    In this 1971 artist's concept, the Nuclear Shuttle is shown in various space-based applications. As envisioned by Marshall Space Flight Center Program Development persornel, the Nuclear Shuttle would deliver payloads to geosychronous Earth orbits or lunar orbits then return to low Earth orbit for refueling. A cluster of Nuclear Shuttle units could form the basis for planetary missions.

  11. Early Program Development

    NASA Image and Video Library

    2004-04-15

    This artist's concept illustrates the NERVA (Nuclear Engine for Rocket Vehicle Application) engine's hot bleed cycle in which a small amount of hydrogen gas is diverted from the thrust nozzle, thus eliminating the need for a separate system to drive the turbine. The NERVA engine, based on KIWI nuclear reactor technology, would power a RIFT (Reactor-In-Flight-Test) nuclear stage, for which the Marshall Space Flight Center had development responsibility.

  12. Early Program Development

    NASA Image and Video Library

    1970-01-01

    In this 1970 artist's concept, the Nuclear Shuttle is shown in its lunar and geosynchronous orbit configuration and in its planetary mission configuration. As envisioned by Marshall Space Flight Center Program Development plarners, the Nuclear Shuttle would deliver payloads to lunar orbit or other destinations then return to Earth orbit for refueling. A cluster of Nuclear Shuttle units could form the basis for planetary missions.

  13. Investigational hormone receptor agonists as ongoing female contraception: a focus on selective progesterone receptor modulators in early clinical development.

    PubMed

    Nelson, Anita L

    2015-01-01

    As efforts are made to continue to increase the safety of contraceptive methods, those without estrogen have attracted new attention. Progestin-only options are available in many delivery systems, but most cause disturbed bleeding patterns. For gynecologic patients, selective progesterone receptor modulators (SPRMs) have been approved for medical abortion, for ovulation suppression in emergency contraception, and for the treatment of heavy menstrual bleeding due to leiomyoma. This article discusses the role of SPRMs in controlling fertility on an ongoing basis with particular emphasis on mifepristone and ulipristal acetate (UPA), since none of the other compounds has progressed out of early Phase I - II testing. It also discusses important information about the mechanisms of action and safety of these two SPRMs. Of all the investigational hormone agonist/antagonists, SPRMs have demonstrated the greatest potential as ongoing female contraceptives. They have the ability to suppress ovulation after initiation of the luteinizing hormone (LH) surge without affecting ovarian production of estrogen or inducing any significant metabolic changes. SPRMs may well be able to provide longer term contraception as oral agents, vaginal rings, and perhaps even intrauterine devices. UPA has the greatest promise. Current research needs to be expanded.

  14. Early Program Development

    NASA Image and Video Library

    1996-06-20

    Engineers at one of MSFC's vacuum chambers begin testing a microthruster model. The purpose of these tests are to collect sufficient data that will enabe NASA to develop microthrusters that will move the Space Shuttle, a future space station, or any other space related vehicle with the least amount of expended energy. When something is sent into outer space, the forces that try to pull it back to Earth (gravity) are very small so that it only requires a very small force to move very large objects. In space, a force equal to a paperclip can move an object as large as a car. Microthrusters are used to produce these small forces.

  15. Biomechanics of Early Cardiac Development

    PubMed Central

    Goenezen, Sevan; Rennie, Monique Y.

    2012-01-01

    Biomechanics affect early cardiac development, from looping to the development of chambers and valves. Hemodynamic forces are essential for proper cardiac development, and their disruption leads to congenital heart defects. A wealth of information already exists on early cardiac adaptations to hemodynamic loading, and new technologies, including high resolution imaging modalities and computational modeling, are enabling a more thorough understanding of relationships between hemodynamics and cardiac development. Imaging and modeling approaches, used in combination with biological data on cell behavior and adaptation, are paving the road for new discoveries on links between biomechanics and biology and their effect on cardiac development and fetal programming. PMID:22760547

  16. Early Electrophysiological Abnormalities and Clinical Neuropathy

    PubMed Central

    Hyllienmark, Lars; Alstrand, Nils; Jonsson, Björn; Ludvigsson, Johnny; Cooray, Gerald; Wahlberg-Topp, Jeanette

    2013-01-01

    OBJECTIVE The aim of this study was to elucidate whether subclinical nerve dysfunction as reflected by neurophysiological testing predicts the development of clinical neuropathy in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS Fifty-nine patients were studied twice with neurophysiological measurements at baseline and at follow-up. At baseline, patients were 15.5 ± 3.22 years (range 7–22 years) of age, and duration of diabetes was 6.8 ± 3.3 years. At follow-up, patients were 20–35 years of age, and disease duration was 20 ± 5.3 years (range 10–31 years). RESULTS At baseline, patients showed modestly reduced nerve conduction velocities and amplitudes compared with healthy subjects, but all were free of clinical neuropathy. At follow-up, clinical neuropathy was present in nine (15%) patients. These patients had a more pronounced reduction in peroneal motor nerve conduction velocity (MCV), median MCV, and sural sensory nerve action potential at baseline (P < 0.010–0.003). In simple logistic regression analyses, the predictor with the strongest association with clinical neuropathy was baseline HbA1c (R2 = 48%, odds ratio 7.9, P < 0.002) followed by peroneal MCV at baseline (R2 = 38%, odds ratio 0.6, P < 0.006). With the use of a stepwise forward analysis that included all predictors, first baseline HbA1c and then only peroneal MCV at baseline entered significantly (R2 = 61%). Neuropathy impairment assessment showed a stronger correlation with baseline HbA1c (ρ = 0.40, P < 0.002) than with follow-up HbA1c (ρ = 0.034, P < 0.007). CONCLUSIONS Early defects in nerve conduction velocity predict the development of diabetic neuropathy. However, the strongest predictor was HbA1c during the first years of the disease. PMID:23723354

  17. Clinical diagnosis of metabolic and cardiovascular risks in overweight children: early development of chronic diseases in the obese child.

    PubMed

    l'Allemand-Jander, D

    2010-12-01

    Childhood overweight (body mass index (BMI)>90th centile) poses a major public health problem in so far as adult diseases manifest themselves already during childhood. In this review, after examining the prevalence of metabolic and cardiovascular diseases, the issue of whether BMI or other clinical parameters are valid tools to predict co-morbidities in children is discussed. Data of 2001-2008 are reviewed, including several studies conducted on more than 260,000 overweight and obese children in Germany and Switzerland. Apart from non-metabolic co-morbidities, namely musculoskeletal complications and attention deficit/hyperactivity disorders in up to 74% and up to 58% of overweight children, respectively, at least one cardiovascular and metabolic risk factor was seen in 52% of the overweight children, mostly high blood pressure (35%) with increased left ventricular mass or arterial stiffness. Signs of fatty liver disease or dyslipidemia were found in up to 29 and 32% of the children, respectively. Type 2 diabetes was found in less than 0.7% of the children, and an elevated fasting glucose or glucose intolerance in 3%. Irrespective of BMI, the quality of fat and protein intake predicted hypertension or insulin resistance, and fructose predicted lower (and more atherogenic) particle size of low-density lipoprotein-cholesterol. Out of the adiposity markers, waist circumference was closely correlated with insulin resistance and the components of the metabolic syndrome. In conclusion, risk factors are found in more than half of the overweight children, most frequently high blood pressure or dyslipidemia, and were mainly related to waist circumference, but also to BMI and fat mass. Even in the presence of normal BMI, screening for cardiovascular risk factors is advocated in each child with elevated waist circumference, but its cut-off points still remain to be validated. The increased occurrence of orthopedic and psychiatric complaints may detrimentally influence health

  18. Measuring early plaque formation clinically.

    PubMed

    Maliska, Alessandra N; Weidlich, Patricia; Gomes, Sabrina C; Oppermann, Rui V

    2006-01-01

    To test a system of measuring early plaque formation (EPF) and its subgingival extension as related to the presence or absence of a plaque free zone (PFZ). EPF was measured by three independent examiners following two consecutive 72-hour periods of undisturbed plaque build-up. One of the examiners further measured EPF following a 96-hour period in the presence of chlorhexidine or placebo. The classification system was composed of criterion 0 (plaque-free dental surface), criterion 1 (presence of plaque and PFZ) and criterion 2 (absence of PFZ, subgingival extension of plaque). Intra- and inter-examiner reliability were evaluated by means of the percentage of absolute agreement (c), Kappa (k) and Kendall (kd) coefficients. The third experiment consisted of a double-blind, placebo-controlled, cross-over trial. Plaque build-up in the presence of 0.12% chlorhexidine was assessed by employing the classification system described. The percentage of absolute intra- and inter-examiner agreement ranged from 85.43% to 75.63% and from 77.31% to 75.35% respectively. Chlorhexidine and placebo rinses showed similar percentages of criterion 1 surfaces, 62.6% and 51.5% respectively (p = 0.343). Of the surfaces, 44.3% showed criterion 2 after the use of placebo, while 3.4% of surfaces showed this criterion with the chlorhexidine (p = 0.007). The events associated with EPF can be appropriately scored with this classification system. Chlorhexidine rinses inhibit both the plaque colonization of the dental surfaces as well as its subgingival extension.

  19. Developing clinical leadership capability.

    PubMed

    Pintar, Kristi A; Capuano, Terry A; Rosser, Gwendolyn D

    2007-01-01

    Nursing facilities must be committed to ongoing leadership development and to developing and retaining their staff in the increasingly competitive healthcare market. In this article, the authors share the processes involved in creating a focused small group approach to developing clinical leaders. Programmatic approaches to development, clarity of needs of those targeted for development, individual development plans, external expertise partnerships, and small group session dynamics are discussed. Applications of the process and lessons learned from the program will benefit others in their efforts to enhance organization succession planning, leadership development, group learning, and program administration.

  20. Effect of Early Physical Activity Programs on Motor Performance and Neuromuscular Development in Infants Born Preterm: A Randomized Clinical Trial.

    PubMed

    Valizadeh, Leila; Sanaeefar, Mahnaz; Hosseini, Mohammad Bager; Asgari Jafarabadi, Mohammad; Shamili, Aryan

    2017-03-01

    Introduction: Although the survival rate of infants born preterm has increased, the prevalence of developmental problems and motor disorders among this population of infants remains the same. This study investigated the effect of physical activity programs in and out of water on motor performance and neuromuscular development of infants born preterm and had induced immobility by mechanical ventilation. Methods: This study was carried out in Al-Zahra hospital, Tabriz. 76 premature infants were randomly assigned into four groups. One group received daily passive range of motion to all extremities based on the Moyer-Mileur protocol. Hydrotherapy group received exercises for shoulders and pelvic area in water every other day. A combination group received physical activity programs in and out of water on alternating days. Infants in a containment group were held in a fetal position. Duration of study was two weeks 'from 32 through 33 weeks post menstrual age (PMA). Motor outcomes were measured by the Test of Infant Motor Performance. Neuromuscular developmental was assessed by New Ballard scale and leg recoil and Ankle dorsiflexion items from Dubowitz scale. Data were analyzed using SPSS version 13. Results: TIMP and neuromuscular scores improved in all groups. Motor performance did not differ between groups at 34 weeks PMA. Postural tone of leg recoil was significantly higher in physical activity groups post intervention. Conclusion: Physical activities and containment didn't have different effects on motor performance in infants born preterm. Leg recoil of neuromuscular development items was affected by physical activity programs.

  1. Effect of Early Physical Activity Programs on Motor Performance and Neuromuscular Development in Infants Born Preterm: A Randomized Clinical Trial

    PubMed Central

    Valizadeh, Leila; Sanaeefar, Mahnaz; Hosseini, Mohammad Bager; Asgari Jafarabadi, Mohammad; Shamili, Aryan

    2017-01-01

    Introduction: Although the survival rate of infants born preterm has increased, the prevalence of developmental problems and motor disorders among this population of infants remains the same. This study investigated the effect of physical activity programs in and out of water on motor performance and neuromuscular development of infants born preterm and had induced immobility by mechanical ventilation. Methods: This study was carried out in Al-Zahra hospital, Tabriz. 76 premature infants were randomly assigned into four groups. One group received daily passive range of motion to all extremities based on the Moyer-Mileur protocol. Hydrotherapy group received exercises for shoulders and pelvic area in water every other day. A combination group received physical activity programs in and out of water on alternating days. Infants in a containment group were held in a fetal position. Duration of study was two weeks ‘from 32 through 33 weeks post menstrual age (PMA). Motor outcomes were measured by the Test of Infant Motor Performance. Neuromuscular developmental was assessed by New Ballard scale and leg recoil and Ankle dorsiflexion items from Dubowitz scale. Data were analyzed using SPSS version 13. Results: TIMP and neuromuscular scores improved in all groups. Motor performance did not differ between groups at 34 weeks PMA. Postural tone of leg recoil was significantly higher in physical activity groups post intervention. Conclusion: Physical activities and containment didn’t have different effects on motor performance in infants born preterm. Leg recoil of neuromuscular development items was affected by physical activity programs. PMID:28299299

  2. Creating Environments to Support Breastfeeding: The Challenges and Facilitators of Policy Development in Hospitals, Clinics, Early Care and Education, and Worksites.

    PubMed

    Bradford, Victoria A; Walkinshaw, Lina P; Steinman, Lesley; Otten, Jennifer J; Fisher, Kari; Ellings, Amy; O'Leary, Jean; Johnson, Donna B

    2017-07-13

    Objectives Supportive organizational breastfeeding policies can establish enabling environments for breastfeeding. In this qualitative study we identify facilitators and barriers to the development, adoption, and implementation of supportive breastfeeding policies and practices in four influential sectors for breastfeeding women: hospitals, clinics, early care and education settings, and worksites. Methods We interviewed 125 individuals representing 110 organizations in Washington State about their breastfeeding policy development and implementation process between August 2014 and February 2015. Greenhalgh's diffusion of innovations framework guided the interviews and qualitative analysis. Results Breastfeeding policy facilitators across the sectors include national and state laws and regulations, performance tracking requirements, and an increasingly supportive sociopolitical climate; barriers include limited resources and appreciation about the need for breastfeeding policies, and certain organizational characteristics such as workforce age. Despite broad support for breastfeeding, organizations differed on perceptions about the usefulness of written breastfeeding policies. Personal breastfeeding experiences of policy makers and staff affect organizational breastfeeding policies and practices. Conclusions for Practice Supportive organizational systems and environments are built through effective policy development processes; public health can support breastfeeding policy development and assure a coordinated continuum of care by leveraging federal health care policy requirements, building networks to support training and collaboration, and disseminating strategies that reflect the personal nature of breastfeeding.

  3. The evolving role of monoclonal antibodies in colorectal cancer: early presumptions and impact on clinical trial development.

    PubMed

    Eng, Cathy

    2010-01-01

    Targeted biologic agents have an established role in treating metastatic colorectal cancer (mCRC). Bevacizumab, a recombinant monoclonal antibody against the vascular endothelial growth factor ligand is approved by the U.S. Food and Drug Administration (FDA) for bevacizumab-naïve patients. Cetuximab, a chimeric monoclonal antibody (mAb) against the epidermal growth factor receptor (EGFR) is FDA approved as a single agent, or in combination with irinotecan, in both irinotecan-naïve and refractory patients, and has additional efficacy in combination with oxaliplatin. Panitumumab, a fully human EGFR mAb, is FDA approved as a single agent in refractory patients but has additional efficacy in combination with chemotherapy. After reaching a temporary therapeutic plateau of FDA-approved agents for the treatment of mCRC, pivotal results have developed that critically affect the care for these patients. Correlative data from randomized trials of EGFR inhibitors across disease settings have demonstrated higher response rates, specifically for patients with wild-type K-RAS tumors. The interpretation of the B-RAF mutation and other molecular markers may further define the appropriateness of anti-EGFR therapy. Recent literature revealed that the first-line use of combined anti-EGFR therapy plus bevacizumab resulted in inferior outcomes and additional toxicities. Furthermore, the role of biologic agents for locally advanced colon cancer cannot be advocated at this time. With impending changes in the health care system, the economic impact of mAbs will continue to be scrutinized. Hence, as the significance of molecular markers continues to develop, their role as it pertains to the appropriate use of biologic agents in the treatment of mCRC will continue to evolve.

  4. Development of clinical sites.

    PubMed

    O'Brien, Mary

    2015-02-01

    Clinical experiences are vital to all types of healthcare educational programs. Supervised clinical experiences provide the opportunity for the learner to apply didactic knowledge and theory to real world situations and hone skills necessary for entry into practice. Nurse anesthesia programs utilize a wide variety of clinical sites to expose student registered nurse anesthetists to experiences that will prepare them clinically, academically and professionally to enter practice as a Certified Registered Nurse Anesthetist. This article describes the process of developing a clinical site. A thorough evaluation will determine the types of experiences meant to be offered at the site, the resources available to house and educate the students, and how to evaluate the effectiveness of the clinical site. Open communication between the clinical coordinator and the program director or designee is essential to ensure success of the clinical site. The Council on Accreditation of Nurse Anesthesia Educational Programs has resources available to guide those interested in becoming a clinical site, as well as for program administrators who seek to add new experiences to their programs.

  5. National Early Warning Score (NEWS) at ICU discharge can predict early clinical deterioration after ICU transfer.

    PubMed

    Uppanisakorn, Supattra; Bhurayanontachai, Rungsun; Boonyarat, Jaruwan; Kaewpradit, Julawan

    2017-09-13

    This study aims to determine the ability of the National Early Warning Score at ICU discharge (NEWSdc) to predict the development of clinical deterioration within 24h. A prospective observational study was conducted. The NEWS was immediately recorded before discharge (NEWSdc). The development of early clinical deterioration was defined as acute respiratory failure or circulatory shock within 24h of ICU discharge. The discrimination of NEWSdc and the best cut off value of NEWSdc to predict the early clinical deterioration was determined. Data were collected from 440 patients. The incidence of early clinical deterioration after ICU discharge was 14.8%. NEWSdc was an independent predictor for early clinical deterioration after ICU discharge (OR 2.54; 95% CI 1.98-3.26; P<0.001). The AUROC of NEWSdc was 0.92±0.01 (95% CI 0.89-0.94, P<0.001). A NEWSdc>7 showed a sensitivity of 93.6% and a specificity of 82.2% to detect an early clinical deterioration after ICU discharge. Among critically ill patients who were discharged from ICU, a NEWSdc>7 showed the best sensitivity and specificity to detect early clinical deterioration 24h after ICU discharge. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Is Early Pragmatic Development Measurable?

    ERIC Educational Resources Information Center

    Dale, Philip S.

    1980-01-01

    Measures of pragmatic development for children in the second year of life were developed based on a 30-minute language sample drawn from 20 children. Results support the view that the range of pragmatic functions grows steadily during the one-word and early two-word stage and that it is measurable. (Author/AM)

  7. Early Clinical Development of ARQ 197, a Selective, Non–ATP-Competitive Inhibitor Targeting MET Tyrosine Kinase for the Treatment of Advanced Cancers

    PubMed Central

    Schwartz, Brian; Garmey, Edward

    2011-01-01

    Expression of the receptor tyrosine kinase c-MET (MET, mesenchymal-epithelial transition factor) in many cancers, and its participation in multiple signal transduction pathways involved in malignant tumor growth, suggest a wide therapeutic potential for MET inhibition in human cancer. Here we describe the discovery and early clinical development of ARQ 197, a novel, selective, non–ATP-competitive inhibitor of MET. Phase I studies demonstrate that ARQ 197 has a predictable pharmacokinetics and favorable safety profile, making it a potentially ideal partner for combination with cytotoxic chemotherapies and targeted anticancer agents. Results from phase I and phase II trials demonstrate preliminary evidence of anticancer activity. New data from a global phase II randomized trial comparing a combination of ARQ 197 plus erlotinib with erlotinib/placebo, in endothelial growth factor receptor inhibitor-naïve patients with locally advanced/metastatic non–small cell lung cancer, demonstrate improvement in progression-free and overall survival with combined therapy. Results were especially pronounced for patients with non–squamous lung cancer histologies, and in particular molecularly defined subgroups including KRAS mutations. These and other data from ARQ 197 clinical trials in hepatocellular, germ-cell, pancreatic (in combination with gemcitabine), and colorectal (in combination with cetuximab and irinotecan) cancers further highlight the potential role of ARQ 197 in existing and emerging anticancer therapeutic regimens. PMID:21632449

  8. Early clinical development of ARQ 197, a selective, non-ATP-competitive inhibitor targeting MET tyrosine kinase for the treatment of advanced cancers.

    PubMed

    Adjei, Alex A; Schwartz, Brian; Garmey, Edward

    2011-01-01

    Expression of the receptor tyrosine kinase c-MET (MET, mesenchymal-epithelial transition factor) in many cancers, and its participation in multiple signal transduction pathways involved in malignant tumor growth, suggest a wide therapeutic potential for MET inhibition in human cancer. Here we describe the discovery and early clinical development of ARQ 197, a novel, selective, non-ATP-competitive inhibitor of MET. Phase I studies demonstrate that ARQ 197 has a predictable pharmacokinetics and favorable safety profile, making it a potentially ideal partner for combination with cytotoxic chemotherapies and targeted anticancer agents. Results from phase I and phase II trials demonstrate preliminary evidence of anticancer activity. New data from a global phase II randomized trial comparing a combination of ARQ 197 plus erlotinib with erlotinib/placebo, in endothelial growth factor receptor inhibitor-naïve patients with locally advanced/metastatic non-small cell lung cancer, demonstrate improvement in progression-free and overall survival with combined therapy. Results were especially pronounced for patients with non-squamous lung cancer histologies, and in particular molecularly defined subgroups including KRAS mutations. These and other data from ARQ 197 clinical trials in hepatocellular, germ-cell, pancreatic (in combination with gemcitabine), and colorectal (in combination with cetuximab and irinotecan) cancers further highlight the potential role of ARQ 197 in existing and emerging anticancer therapeutic regimens.

  9. Do sleep abnormalities and misaligned sleep/circadian rhythm patterns represent early clinical characteristics for developing psychosis in high risk populations?

    PubMed

    Zanini, Marcio; Castro, Juliana; Coelho, Fernando Morgadinho; Bittencourt, Lia; Bressan, Rodrigo A; Tufik, Sergio; Brietzke, Elisa

    2013-12-01

    Sleep architecture changes, such as slow-wave sleep (SWS) percentage variations and reductions in latency and density of rapid eye movement (REM), are found in most patients with schizophrenia and are considered to be an important part of the pathophysiology of the disorder. In addition to these sleep parameters changes, disruptions in sleep homeostasis and the sleep/circadian rhythm also occur in these patients. Sleep/circadian rhythm abnormalities negatively affect neocortical plasticity and cognition and often precede the diagnosis of the illness. Thus, it has been suggested that the sleep/circadian rhythm might be involved in the pathophysiology of psychosis. Recent advances in the identification of individuals at a high risk for developing schizophrenia allow us to investigate several neurobiological processes involved in the development of psychosis. In this article, we review the current evidence of the effects of sleep parameter abnormalities, disruptions in sleep homeostasis and misalignments of sleep circadian rhythm on the early stages of schizophrenia. In addition, we discuss the preliminary evidence of sleep and circadian rhythm abnormalities during the prodromal stages of psychosis and propose that these abnormalities can be explored as potential predictors, as an adjunct to clinical diagnosis, of developing a psychotic disorder in at risk populations.

  10. Clinical vaccine development

    PubMed Central

    2015-01-01

    Vaccination is regarded as one of the biggest triumphs in the history of medicine. We are living in the most successful period of vaccine development. The accumulation of multidisciplinary knowledge and the investment of massive funding have enabled the development of vaccines against many infectious diseases as well as other diseases including malignant tumors. The paradigm of clinical vaccine evaluation and licensure has also been modernized based on scientific improvements and historical experience. However, there remain a number of hurdles to overcome. Continuous efforts are focused on increasing the efficacy and reducing the risks related to vaccine use. Cutting-edge knowledge about immunology and microbiology is being rapidly translated to vaccine development. Thus, physicians and others involved in the clinical development of vaccines should have sufficient understanding of the recent developmental trends in vaccination and the diseases of interest. PMID:25648742

  11. Development and clinical applications of digitized fluorescence endoscopic imaging system for the detection of early neoplasms in the oral cavity and uterine-cervix

    NASA Astrophysics Data System (ADS)

    Zheng, Wei; Tay, Sun K.; Soo, K. C.; Olivo, Malini

    2002-05-01

    A digitized fluorescence endoscopic imaging (DFEI) system combined with 5-Aminolevulinic Acid (5-ALA) induced protoporphyrin IX (PPIX) was developed for the detection of neoplasms in the oral cavity and uterine-cervix. The system has the capability of producing both the digital and video fluorescence images in real time, and also quantifying the fluorescence images. The results show that using the DFEI system associated with the fluorescence image quantification method, both high sensitivity and specificity can be achieved during the head and neck, and obstetric and gynaecology clinical trials. The red fluorescence intensity distribution in the lesion area can also be obtained after digital image processing to better understand the situation of PPIX accumulation in the tissues. Furthermore, applying the intensity ratio IR/IB at red and blue wavelength regions of the tissue targeted, where IR includes the intensity of PPIX fluorescence and red tissue autofluorescence, and IB is the intensity of diffusely back-scattered excitation blue light, different histopathological grades of lesions can be classified by the DEFI system, suggesting a significant potential of the noninvasive optical biopsy for the early cancer detection.

  12. Choreography of early thalamocortical development.

    PubMed

    Molnár, Zoltán; Higashi, Shuji; López-Bendito, Guillermina

    2003-06-01

    Thalamic axons, which carry most of the information from the sensory environment, are amongst the first projections to reach the cerebral cortex during embryonic development. It has been proposed that the scaffold of early generated cells in the ventral thalamus, internal capsule and preplate play a pivotal role in their deployment through sharp gene expression boundaries. These ideas were recently evaluated in various strains of mutant mice. In Tbr1, Gbx2, Pax6 KO both thalamic and corticofugal projections fail to traverse the striatocortical junction. In both Emx2 and Pax6 KO brains, the misrouted thalamic afferents are accompanied by displacements of the pioneering projections from the internal capsule. Regardless of their altered route, thalamic afferents in the reeler and L1 KO mice seem to be able to redistribute themselves on the cortical sheet and establish normal periphery-related representation in the somatosensory cortex. Early neural activity delivered through the thalamic projections is thought to be involved in the realignment process of thalamic axons at the time of their accumulation in the subplate layer. However, axonal growth and the early topographic arrangement of thalamocortical fiber pathways appear normal in the Snap25 KO, where action potential mediated synaptic vesicle release is disrupted. We therefore suggest that intercellular communication mediated by constitutive secretion of transmitters or growth factors might play a dominant role during early thalamocortical development.

  13. How do researchers decide early clinical trials?

    PubMed

    Grankvist, Hannah; Kimmelman, Jonathan

    2016-06-01

    Launch of clinical investigation represents a substantial escalation in commitment to a particular clinical translation trajectory; it also exposes human subjects to poorly understood interventions. Despite these high stakes, there is little to guide decision-makers on the scientific and ethical evaluation of early phase trials. In this article, we review policies and consensus statements on human protections, drug regulation, and research design surrounding trial launch, and conclude that decision-making is largely left to the discretion of research teams and sponsors. We then review what is currently understood about how research teams exercise this discretion, and close by laying out a research agenda for characterizing the way investigators, sponsors, and reviewers approach decision-making in early phase research.

  14. Early prosocial development across cultures.

    PubMed

    Callaghan, Tara; Corbit, John

    2017-08-17

    Human prosociality is ubiquitous, even though it may be manifested differently across cultures. Low cost helping and sharing emerge early in development, and at similar levels, across cultures having vastly different sociocultural niches. Developmental trajectories for costly sharing diverge across cultures around middle childhood, in line with differences in the sociocultural niches that children experience. Cultural developmental research has focussed primarily on the emergence and development of prosocial behaviour, and would benefit from an examination of the interplay between psychological (cognitive, motivational) and sociocultural (norms, developmental niche) foundations over ontogeny. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. The Early Psychosis Intervention Center (EPICENTER): development and six-month outcomes of an American first-episode psychosis clinical service.

    PubMed

    Breitborde, Nicholas J K; Bell, Emily K; Dawley, David; Woolverton, Cindy; Ceaser, Alan; Waters, Allison C; Dawson, Spencer C; Bismark, Andrew W; Polsinelli, Angelina J; Bartolomeo, Lisa; Simmons, Jessica; Bernstein, Beth; Harrison-Monroe, Patricia

    2015-10-28

    There is growing evidence that specialized clinical services targeted toward individuals early in the course of a psychotic illness may be effective in reducing both the clinical and economic burden associated with these illnesses. Unfortunately, the United States has lagged behind other countries in the delivery of specialized, multi-component care to individuals early in the course of a psychotic illness. A key factor contributing to this lag is the limited available data demonstrating the clinical benefits and cost-effectiveness of early intervention for psychosis among individuals served by the American mental health system. Thus, the goal of this study is to present clinical and cost outcome data with regard to a first-episode psychosis treatment center within the American mental health system: the Early Psychosis Intervention Center (EPICENTER). Sixty-eight consecutively enrolled individuals with first-episode psychosis completed assessments of symptomatology, social functioning, educational/vocational functioning, cognitive functioning, substance use, and service utilization upon enrollment in EPICENTER and after 6 months of EPICENTER care. All participants were provided with access to a multi-component treatment package comprised of cognitive behavioral therapy, family psychoeducation, and metacognitive remediation. Over the first 6 months of EPICENTER care, participants experienced improvements in symptomatology, social functioning, educational/vocational functioning, cognitive functioning, and substance abuse. The average cost of care during the first 6 months of EPICENTER participation was lower than the average cost during the 6-months prior to joining EPICENTER. These savings occurred despite the additional costs associated with the receipt of EPICENTER care and were driven primarily by reductions in the utilization of inpatient psychiatric services and contacts with the legal system. The results of our study suggest that multi-component interventions

  16. Experiences of establishing an academic early phase clinical trials unit.

    PubMed

    Brown, Sarah R; Sherratt, Debbie; Booth, Gill; Brown, Julia; Collinson, Fiona; Gregory, Walter; Flanagan, Louise

    2017-08-01

    Early phase trials are essential in drug development, determining appropriate dose levels and assessing preliminary activity. These trials are undertaken by industry and academia, with increasing collaborations between the two. There is pressure to perform these trials quickly, safely, and robustly. However, there are inherent differences between developing and managing early phase, compared to late phase, drug trials. This article describes an approach to establishing an academically led early phase trial portfolio, highlighting lessons learned and sharing experiences. In 2009, the University of Leeds Clinical Trials Research Unit became the Clinical Trials Coordinating Office for Myeloma UK's phase I and II trials. We embarked on a transition from working extensively in phase III to early phase trials development and conduct. This involved evaluating and revising our well-established standard operating procedures, visiting other academic early phase units, and developing essential new documentation and processes. A core team of trial and data managers and statisticians was established to facilitate expertise and knowledge retention. A detailed training plan was implemented focussing on essential standard practices for early phase. These included pharmacovigilance, recruitment, trial design and set-up, data and site monitoring, and oversight committees. Training in statistical methods for early phase trials was incorporated. Initial scoping of early phase trial management and conduct was essential in establishing this early phase portfolio. Many of the processes developed were successful. However, regular review and evaluation were implemented to enable changes and ensure efficiencies. It is recommended that others embarking on this venture build on the experiences described in this article.

  17. Microwave tumor ablation: cooperative academic-industry development of a high-power gas-cooled system with early clinical results

    NASA Astrophysics Data System (ADS)

    Brace, Christopher L.; Ziemlewicz, Timothy J.; Schefelker, Rick; Hinshaw, J. L.; Lubner, Meghan G.; Lee, Fred T.

    2013-02-01

    Microwave tumor ablation continues to evolve into a viable treatment option for many cancers. Current systems are poised to supplant radiofrequency ablation as the dominant percutaneous thermal therapy. Here is provided an overview of technical details and early clinical results with a high-powered, gas-cooled microwave ablation system. The system was developed with academic-industry collaboration using federal and private funding. The generator comprises three synchronous channels that each produce up to 140W at 2.45GHz. A mountable power distribution module facilitates CT imaging guidance and monitoring and reduces clutter in the sterile field. Cryogenic carbon-dioxide cools the coaxial applicator, permitting a thin applicator profile (~1.5 mm diameter) and high power delivery. A total of 106 liver tumors were treated (96 malignant, 10 benign) from December 2010 to June 2012 at a single academic institution. Mean tumor size +/- standard deviation was 2.5+/-1.3cm (range 0.5-13.9cm). Treatment time was 5.4+/-3.3min (range 1-20min). Median follow-up was 6 months (range 1-16 months). Technical success was reported in 100% of cases. Local tumor progression was noted in 4/96 (4.3%) of malignancies. The only major complication was a pleural effusion that was treated with thoracentesis. Microwave ablation with this system is an effective treatment for liver cancer. Compared to previous data from the same institution, these results suggest an increased efficacy and equivalent safety to RF ablation. Additional data from the lung and kidney support this conclusion.

  18. Non-clinical studies required for new drug development - Part I: early in silico and in vitro studies, new target discovery and validation, proof of principles and robustness of animal studies

    PubMed Central

    Andrade, E.L.; Bento, A.F.; Cavalli, J.; Oliveira, S.K.; Freitas, C.S.; Marcon, R.; Schwanke, R.C.; Siqueira, J.M.; Calixto, J.B.

    2016-01-01

    This review presents a historical overview of drug discovery and the non-clinical stages of the drug development process, from initial target identification and validation, through in silico assays and high throughput screening (HTS), identification of leader molecules and their optimization, the selection of a candidate substance for clinical development, and the use of animal models during the early studies of proof-of-concept (or principle). This report also discusses the relevance of validated and predictive animal models selection, as well as the correct use of animal tests concerning the experimental design, execution and interpretation, which affect the reproducibility, quality and reliability of non-clinical studies necessary to translate to and support clinical studies. Collectively, improving these aspects will certainly contribute to the robustness of both scientific publications and the translation of new substances to clinical development. PMID:27783811

  19. Non-clinical studies required for new drug development - Part I: early in silico and in vitro studies, new target discovery and validation, proof of principles and robustness of animal studies.

    PubMed

    Andrade, E L; Bento, A F; Cavalli, J; Oliveira, S K; Freitas, C S; Marcon, R; Schwanke, R C; Siqueira, J M; Calixto, J B

    2016-10-24

    This review presents a historical overview of drug discovery and the non-clinical stages of the drug development process, from initial target identification and validation, through in silico assays and high throughput screening (HTS), identification of leader molecules and their optimization, the selection of a candidate substance for clinical development, and the use of animal models during the early studies of proof-of-concept (or principle). This report also discusses the relevance of validated and predictive animal models selection, as well as the correct use of animal tests concerning the experimental design, execution and interpretation, which affect the reproducibility, quality and reliability of non-clinical studies necessary to translate to and support clinical studies. Collectively, improving these aspects will certainly contribute to the robustness of both scientific publications and the translation of new substances to clinical development.

  20. Concentration-Response Modeling of ECG Data From Early-Phase Clinical Studies as an Alternative Clinical and Regulatory Approach to Assessing QT Risk - Experience From the Development Program of Lemborexant.

    PubMed

    Murphy, Patricia J; Yasuda, Sanae; Nakai, Kenya; Yoshinaga, Takashi; Hall, Nancy; Zhou, Meijian; Aluri, Jagadeesh; Rege, Bhaskar; Moline, Margaret; Ferry, Jim; Darpo, Borje

    2017-01-01

    Lemborexant is a novel dual orexin receptor antagonist being developed to treat insomnia. Its potential to cause QT prolongation was evaluated using plasma concentration-response (CR) modeling applied to data from 2 multiple ascending-dose (MAD) studies. In the primary MAD study, placebo or lemborexant (2.5 to 75 mg) was administered for 14 consecutive nights. In another MAD study designed to "bridge" pharmacokinetic and safety data between Japanese and non-Japanese subjects (J-MAD), placebo or lemborexant (2.5, 10, or 25 mg) was administered for 14 consecutive nights. QT intervals were estimated using a high-precision measurement technique and evaluated using a linear mixed-effects CR model, for each study separately and for the pooled data set. When each study was analyzed separately, the slopes of the CR relationship were shallow and not statistically significant. In the pooled analysis, the slope of the CR relationship was -0.00002 milliseconds per ng/mL (90%CI, -0.01019 to 0.01014 milliseconds). The highest observed Cmax was 400 ng/mL, representing a margin 8-fold above exposures expected for the highest planned clinical dose. The model-predicted QTc effect at 400 ng/mL was 1.1 milliseconds (90%CI, -3.49 to 5.78 milliseconds). In neither the J-MAD study nor the pooled analysis was an effect of race identified. CR modeling of data from early-phase clinical studies, including plasma levels far exceeding those anticipated clinically, indicated that a QT effect >10 milliseconds could be excluded. Regulatory agreement with this methodology demonstrates the effectiveness of a CR modeling approach as an alternative to thorough QT studies. © 2016, The American College of Clinical Pharmacology.

  1. Early steps in neural development.

    PubMed

    Callebaut, Marc; Van Nueten, Emmy; Van Passel, Hanalie; Harrisson, Fernand; Bortier, Hilde

    2006-07-01

    We studied early neurulation events in vitro by transplanting quail Hensen's node, central prenodal regions (before the nodus as such develops), or upper layer parts of it on the not yet definitively committed upper layer of chicken anti-sickle regions (of unincubated blastoderms), eventually associated with central blastoderm fragments. We could demonstrate by this quail-chicken chimera technique that after the appearance of a pronounced thickening of the chicken upper layer by the early inductive effect of neighboring endophyll, a floor plate forms by insertion of Hensen's node-derived quail cells into the median part of the groove. This favors, at an early stage, the floor plate "allocation" model that postulates a common origin for notochord and median floor plate cells from the vertebrate's secondary major organizer (Hensen's node in this case). A comparison is made with results obtained after transplantation of similar Hensen's nodes in isolated chicken endophyll walls or with previously obtained results after the use of the grafting procedure in the endophyll walls of whole chicken blastoderms.

  2. [Early childhood growth and development].

    PubMed

    Arce, Melitón

    2015-01-01

    This article describes and discusses issues related to the process of childhood growth and development, with emphasis on the early years, a period in which this process reaches critical speed on major structures and functions of the human economy. We reaffirm that this can contribute to the social availability of a generation of increasingly better adults, which in turn will be able to contribute to building a better world and within it a society that enjoys greater prosperity. In the first chapter, we discuss the general considerations on the favorable evolution of human society based on quality of future adults, meaning the accomplishments that today’s children will gain. A second chapter mentions the basics of growth and development in the different fields and the various phenomena that occur in it. In the third we refer to lost opportunities and negative factors that can affect delaying the process and thereby result in not obtaining the expected accomplishments. In the fourth, conclusions and recommendations are presented confirming the initial conception that good early child care serves to build a better society and some recommendations are formulated to make it a good practice.

  3. Early development and regression in Rett syndrome.

    PubMed

    Lee, J Y L; Leonard, H; Piek, J P; Downs, J

    2013-12-01

    This study utilized developmental profiling to examine symptoms in 14 girls with genetically confirmed Rett syndrome and whose families were participating in the Australian Rett syndrome or InterRett database. Regression was mostly characterized by loss of hand and/or communication skills (13/14) except one girl demonstrated slowing of skill development. Social withdrawal and inconsolable crying often developed simultaneously (9/14), with social withdrawal for shorter duration than inconsolable crying. Previously acquired gross motor skills declined in just over half of the sample (8/14), mostly observed as a loss of balance. Early abnormalities such as vomiting and strabismus were also seen. Our findings provide additional insight into the early clinical profile of Rett syndrome.

  4. Establishing Pluripotency in Early Development

    PubMed Central

    Paranjpe, Sarita S.; Veenstra, Gert Jan C.

    2015-01-01

    The earliest steps of embryonic development involve important changes in chromatin and transcription factor networks, which are orchestrated to establish pluripotent cells that will form the embryo. DNA methylation, histone modifications, the pluripotency regulatory network of transcription factors, maternal factors and newly translated proteins all contribute to these transitions in dynamic ways. Moreover, these dynamics are linked to the onset of zygotic transcription. We will review recent progress in our understanding of chromatin state and regulation of gene expression in the context of embryonic development in vertebrates, in particular mouse, Xenopus and zebrafish. We include work on mouse embryonic stem cells and highlight work that illustrates how early embryonic dynamics establish gene regulatory networks and the state of pluripotency. PMID:25857441

  5. Simulation: A Tool to Assist Nursing Professional Development Practitioners to Help Nurses to Better Recognize Early Signs of Clinical Deterioration of Patients.

    PubMed

    Elder, Loretta

    The need to enhance the knowledge and skills of nurses caring for patients exhibiting signs of clinical deterioration has been documented. The literature has further supported the registered nurse as the key individual expected to recognize signs of clinical deterioration in the patient. The use of simulation as an effective teaching strategy has been well documented. The purpose of this project was to use simulation as an educational intervention to increase nurse knowledge, self-confidence, and competency when caring for patients exhibiting signs of clinical deterioration. A significant improvement in nurse knowledge and self-confidence was shown after a simulation-based educational intervention. Competency evaluation during the simulation-based intervention provided information to help nurses when caring for deteriorating patients. Nursing professional development practitioners can use the information from this project in planning educational interventions for staff nurses.

  6. Taiwanese Early Childhood Educators' Professional Development

    ERIC Educational Resources Information Center

    Hsu, Ching-Yun

    2008-01-01

    This study was designed based on a qualitative paradigm to explore the professional development of Taiwanese early childhood educators. The method of phenomenology was employed. The main research question addressed was "How do early childhood educators construe their professional development experience?" Seven Taiwanese early childhood…

  7. Predicting Readmission at Early Hospitalization Using Electronic Clinical Data

    PubMed Central

    Sun, Xiaowu; Nunez, Carlos M.; Gupta, Vikas; Johannes, Richard S.

    2017-01-01

    Background: Identifying patients at high risk for readmission early during hospitalization may aid efforts in reducing readmissions. We sought to develop an early readmission risk predictive model using automated clinical data available at hospital admission. Methods: We developed an early readmission risk model using a derivation cohort and validated the model with a validation cohort. We used a published Acute Laboratory Risk of Mortality Score as an aggregated measure of clinical severity at admission and the number of hospital discharges in the previous 90 days as a measure of disease progression. We then evaluated the administrative data–enhanced model by adding principal and secondary diagnoses and other variables. We examined the c-statistic change when additional variables were added to the model. Results: There were 1,195,640 adult discharges from 70 hospitals with 39.8% male and the median age of 63 years (first and third quartile: 43, 78). The 30-day readmission rate was 11.9% (n=142,211). The early readmission model yielded a graded relationship of readmission and the Acute Laboratory Risk of Mortality Score and the number of previous discharges within 90 days. The model c-statistic was 0.697 with good calibration. When administrative variables were added to the model, the c-statistic increased to 0.722. Conclusions: Automated clinical data can generate a readmission risk score early at hospitalization with fair discrimination. It may have applied value to aid early care transition. Adding administrative data increases predictive accuracy. The administrative data–enhanced model may be used for hospital comparison and outcome research. PMID:27755391

  8. Developing clinical guidelines

    PubMed Central

    Shekelle, Paul G; Woolf, Steven H; Eccles, Martin; Grimshaw, Jeremy

    1999-01-01

    The methods of guideline development should ensure that treating patients according to guidelines will achieve the outcomes that are desired. This article presents a combination of the literature about guideline development and the results of our combined experience in guideline development in North America and Britain. It considers the 5 steps in the initial development of an evidence-based guideline. Imagesp348-a PMID:18751155

  9. IGF-1 Receptor Inhibitors in Clinical Trials—Early Lessons

    PubMed Central

    Weroha, S. John

    2009-01-01

    The insulin-like growth factor pathway plays a major role in cancer cell proliferation, survival and resistance to anti-cancer therapies in many human malignancies, including breast cancer. As a key signaling component of IGF system, the IGF-1 receptor is the target of several investigational agents in clinical and pre-clinical development. This review will focus on the rationale for targeting the IGF-1 receptor and other components of the IGF-1 system. In addition, we will examine the role of IGF-1 signaling in resistance to clinically important breast cancer therapies, including cytotoxic chemotherapy, hormonal therapy and erbB targeted agents. We will also review the completed and ongoing clinical investigations with IGF-1 receptors inhibitors to date and the utility of these early data in designing future breast cancer studies with IGF-1 signaling inhibition strategies. PMID:19023648

  10. Developing a clinical research career.

    PubMed

    Nicholson, Caroline

    The National Institute for Health Research helps to promote clinical research careers for health professionals working in clinical practice, and has developed a structure to support new researchers. This article explains how nurses can get involved in clinical research and the support available to them.

  11. Early Childhood Development Policy Advances in Uganda

    ERIC Educational Resources Information Center

    Ejuu, Godfrey

    2012-01-01

    Knowledge of the history and development of early childhood development in Uganda is paramount if we are to know how far we have come and where we are going. This article explores the introduction of early childhood development in Ugandan policy and government interventions from 1960 to 2011. Data was obtained from a review of available early…

  12. Early Childhood Development Policy Advances in Uganda

    ERIC Educational Resources Information Center

    Ejuu, Godfrey

    2012-01-01

    Knowledge of the history and development of early childhood development in Uganda is paramount if we are to know how far we have come and where we are going. This article explores the introduction of early childhood development in Ugandan policy and government interventions from 1960 to 2011. Data was obtained from a review of available early…

  13. Challenges assessing clinical endpoints in early Huntington disease

    PubMed Central

    Paulsen, Jane S.; Wang, Chiachi; Duff, Kevin; Barker, Roger; Nance, Martha; Beglinger, Leigh; Moser, David; Williams, Janet K.; Simpson, Sheila; Langbehn, Douglas; van Kammen, Daniel P.

    2010-01-01

    The primary aim of this study was to evaluate the current accepted standard clinical endpoint for the earliest-studied HD participants likely to be recruited into clinical trials. Since the advent of genetic testing for HD, it is possible to identify gene carriers prior to the diagnosis of disease, which opens up the possibility of clinical trials of disease-modifying treatments in clinically asymptomatic persons. Current accepted standard clinical endpoints were examined as part of a multi-national, 32-site, longitudinal, observational study of 786 research participants currently in the HD prodrome (gene-positive but not clinically diagnosed). Clinical signs and symptoms were used to prospectively predict functional loss as assessed by current accepted standard endpoints over 8 years of follow up. Functional capacity measures were not sensitive for HD in the prodrome; over 88% scored at ceiling. Prospective evaluation revealed that the first functional loss was in their accustomed work. In a survival analysis, motor, cognitive, and psychiatric measures were all predictors of job change. To our knowledge, this is the first prospective study ever conducted on the emergence of functional loss secondary to brain disease. We conclude that future clinical trials designed for very early disease will require the development of new and more sensitive measures of real-life function. PMID:20623772

  14. Challenges assessing clinical endpoints in early Huntington disease.

    PubMed

    Paulsen, Jane S; Wang, Chiachi; Duff, Kevin; Barker, Roger; Nance, Martha; Beglinger, Leigh; Moser, David; Williams, Janet K; Simpson, Sheila; Langbehn, Douglas; van Kammen, Daniel P

    2010-11-15

    The basic aim of this study was to evaluate the current accepted standard clinical endpoint for the earliest-studied HD participants likely to be recruited into clinical trials. As the advent of genetic testing for HD, it is possible to identify gene carriers before the diagnosis of disease, which opens up the possibility of clinical trials of disease-modifying treatments in clinically asymptomatic persons. Current accepted standard clinical endpoints were examined as part of a multinational, 32-site, longitudinal, observational study of 786 research participants currently in the HD prodrome (gene-positive but not clinically diagnosed). Clinical signs and symptoms were used to prospectively predict functional loss as assessed by current accepted standard endpoints over 8 years of follow-up. Functional capacity measures were not sensitive for HD in the prodrome; over 88% scored at ceiling. Prospective evaluation revealed that the first functional loss was in their accustomed work. In a survival analysis, motor, cognitive, and psychiatric measures were all predictors of job change. To our knowledge, this is the first prospective study ever conducted on the emergence of functional loss secondary to brain disease. We conclude that future clinical trials designed for very early disease will require the development of new and more sensitive measures of real-life function. © 2010 Movement Disorder Society.

  15. How Early Hormones Shape Gender Development

    PubMed Central

    Berenbaum, Sheri A.; Beltz, Adriene M.

    2015-01-01

    Many important psychological characteristics show sex differences, and are influenced by sex hormones at different developmental periods. We focus on the role of sex hormones in early development, particularly the differential effects of prenatal androgens on aspects of gender development. Increasing evidence confirms that prenatal androgens have facilitative effects on male-typed activity interests and engagement (including child toy preferences and adult careers), and spatial abilities, but relatively minimal effects on gender identity. Recent emphasis has been directed to the psychological mechanisms underlying these effects (including sex differences in propulsive movement, and androgen effects on interest in people versus things), and neural substrates of androgen effects (including regional brain volumes, and neural responses to mental rotation, sexually arousing stimuli, emotion, and reward). Ongoing and planned work is focused on understanding the ways in which hormones act jointly with the social environment across time to produce varying trajectories of gender development, and clarifying mechanisms by which androgens affect behaviors. Such work will be facilitated by applying lessons from other species, and by expanding methodology. Understanding hormonal influences on gender development enhances knowledge of psychological development generally, and has important implications for basic and applied questions, including sex differences in psychopathology, women’s underrepresentation in science and math, and clinical care of individuals with variations in gender expression. PMID:26688827

  16. The Development of STAR Early Literacy. Report.

    ERIC Educational Resources Information Center

    School Renaissance Inst., Inc., Madison, WI.

    This report describes the development and testing of a computerized early literacy diagnostic assessment for students in prekindergarten to grade 3 that can measure skills across a variety of preliteracy and reading domains. The STAR Early Literacy assessment was developed by a team of more than 50 people, including literacy experts,…

  17. Critical Issues in Early Childhood Professional Development

    ERIC Educational Resources Information Center

    Zaslow, Martha, Ed.; Martinez-Beck, Ivelisse, Ed.

    2005-01-01

    Effective teaching leads to positive student outcomes, and professional development for early childhood teachers is key to improving both. But what exactly is meant by "professional development"? What effect does it have on school readiness? Which models and approaches really work? This is the book the early childhood field needs to take the…

  18. Critical Issues in Early Childhood Professional Development

    ERIC Educational Resources Information Center

    Zaslow, Martha, Ed.; Martinez-Beck, Ivelisse, Ed.

    2005-01-01

    Effective teaching leads to positive student outcomes, and professional development for early childhood teachers is key to improving both. But what exactly is meant by "professional development"? What effect does it have on school readiness? Which models and approaches really work? This is the book the early childhood field needs to take the…

  19. Development of immunity in early life.

    PubMed

    Goenka, Anu; Kollmann, Tobias R

    2015-06-01

    The immune system in early life goes through rapid and radical changes. Early life is also the period with the highest risk of infections. The foetal immune system is programmed to coexist with foreign antigenic influences in utero, and postnatally to rapidly develop a functional system capable of distinguishing helpful microbes from harmful pathogens. Both host genetics and environmental influences shape this dramatic transition and direct the trajectory of the developing immune system into early childhood and beyond. Given the malleability of the immune system in early life, interventions aimed at modulating this trajectory thus have the potential to translate into considerable reductions in infectious disease burden with immediate as well as long-lasting benefit. However, an improved understanding of the underlying molecular drivers of early life immunity is prerequisite to optimise such interventions and transform the window of early life vulnerability into one of opportunity. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  20. Early Clinical Signs and Symptoms of HIV Infection

    PubMed Central

    Miedzinski, Lil J.

    1992-01-01

    Early clinical signs and symptoms of human immunodeficiency virus infection are protean and can reflect the effects of the virus or represent early manifestations of an illness associated with the acquired immunodeficiency syndrome. Knowledge of a patient's potential risk for HIV infection and of the natural history of the illness allow early signs and symptoms to be recognized. Early intervention can delay progression to AIDS. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6 PMID:21221397

  1. Early life origins of psychological development and mental health.

    PubMed

    Räikkönen, Katri; Pesonen, Anu-Katriina

    2009-12-01

    According to the Developmental Origins of Health and Disease (DOHaD)-hypothesis, conditions early in life may have life-long consequences. In a series of epidemiological birth cohort and clinical studies and natural experiments, we have had the chance to test the extent to which this hypothesis is useful in understanding individual differences in psychological development and mental health. Our findings have provided evidence that individual differences in cognitive, social and emotional development and in mental health may lie in early life circumstances, and add significantly to the literature by pointing out which periods of early growth are the most critical. These findings are also important in translating pre-clinical evidence to humans. What remains less clear, however, is what the mechanisms of programming are. Thus, further research is needed to elucidate these mechanisms before information on the early life origins of health and disease can be used in designing prevention and intervention programs.

  2. Early demographic and clinical predictors of developing acute kidney injury in snake bite patients: A retrospective controlled study from an Indian tertiary care hospital in North Eastern Uttar Pradesh India

    PubMed Central

    Singh, R. R.; Uraiya, Dharmendra; Kumar, Anoop; Tripathi, Neeraj

    2016-01-01

    Aims: This study was conducted retrospectively to define early demographic and clinical predictors for acute kidney injury (AKI) among snake bite patients at the time of hospital admission. Materials and Methods: We analyzed 138 cases with a poisonous snake bite. Patients were classified into two groups according to the presence and absence of AKI. The data regarding clinical features and demographic profile of these patients were collected from the hospital records in a prestructured pro forma and statistically compared. Results: Of the 138 patients of venomous snake bite, 62 developed AKI (44.92%). Patients who developed AKI were older in age. Moreover, prolonged bite to anti-snake venom (ASV) time had a significant relationship in developing AKI (P < 0.05). Among the clinical features, there was an independent positive association of AKI with abdomen pain, tenderness and vomiting, cellulitis, bleeding tendencies, myalgia, and black or brown urine (P < 0.05). Neurological features were inversely associated with renal involvement. Conclusion: We found that marked abdominal pain, tenderness and vomiting, myalgia, black or brown urine, bite site cellulitis, bleeding tendencies, and prolonged (>2 h) bite to ASV time were significantly associated with the development of AKI in snake bite patients. PMID:27555694

  3. Clinical development of Ebola vaccines

    PubMed Central

    Sridhar, Saranya

    2015-01-01

    The ongoing outbreak of Ebola virus disease in West Africa highlighted the lack of a licensed drug or vaccine to combat the disease and has renewed the urgency to develop a pipeline of Ebola vaccines. A number of different vaccine platforms are being developed by assessing preclinical efficacy in animal models and expediting clinical development. Over 15 different vaccines are in preclinical development and 8 vaccines are now in different stages of clinical evaluation. These vaccines include DNA vaccines, virus-like particles and viral vectors such as live replicating vesicular stomatitis virus (rVSV), human and chimpanzee adenovirus, and vaccinia virus. Recently, in preliminary results reported from the first phase III trial of an Ebola vaccine, the rVSV-vectored vaccine showed promising efficacy. This review charts this rapidly advancing area of research focusing on vaccines in clinical development and discusses the future opportunities and challenges faced in the licensure and deployment of Ebola vaccines. PMID:26668751

  4. Online Early Childhood Professional Development: Selected Experiences

    ERIC Educational Resources Information Center

    Olsen, Heather

    2010-01-01

    Early childhood professional development opportunities are expanding rapidly throughout the country. With nearly 12 million children under the age of 5 in some kind of early childhood setting, there is an effort to increase the quality of care and education. In fact, 97% of states require child care professionals to commit to ongoing professional…

  5. Trisomy and early brain development

    PubMed Central

    Haydar, Tarik F.; Reeves, Roger H.

    2011-01-01

    Trisomy for human chromosome 21 (Hsa21) results in Down syndrome (DS). The finished human genome sequence provides a thorough catalog of the genetic elements whose altered dosage perturbs development and function in DS. However, understanding how small alterations in the steady state transcript levels for <2% of human genes can disrupt development and function of essentially every cell presents a more complicated problem. Mouse models that recapitulate specific aspects of DS have been used to identify changes in brain morphogenesis and function. Here we provide a few examples of how trisomy for specific genes affects the development of the cortex and cerebellum to illustrate how gene dosage effects might contribute to divergence between the trisomic and euploid brains. PMID:22169531

  6. Views of NHS commissioners on commissioning support provision. Evidence from a qualitative study examining the early development of clinical commissioning groups in England

    PubMed Central

    Petsoulas, Christina; Allen, Pauline; Checkland, Kath; Coleman, Anna; Segar, Julia; Peckham, Stephen; Mcdermott, Imelda

    2014-01-01

    Objective The 2010 healthcare reform in England introduced primary care-led commissioning in the National Health Service (NHS) by establishing clinical commissioning groups (CCGs). A key factor for the success of the reform is the provision of excellent commissioning support services to CCGs. The Government's aim is to create a vibrant market of competing providers of such services (from both for-profit and not-for-profit sectors). Until this market develops, however, commissioning support units (CSUs) have been created from which CCGs are buying commissioning support functions. This study explored the attitudes of CCGs towards outsourcing commissioning support functions during the initial stage of the reform. Design The research took place between September 2011 and June 2012. We used a case study research design in eight CCGs, conducting in-depth interviews, observation of meetings and analysis of policy documents. Setting/participants We conducted 96 interviews and observed 146 meetings (a total of approximately 439 h). Results Many CCGs were reluctant to outsource core commissioning support functions (such as contracting) for fear of losing local knowledge and trusted relationships. Others were disappointed by the absence of choice and saw CSUs as monopolies and a recreation of the abolished PCTs. Many expressed doubts about the expectation that outsourcing of commissioning support functions will result in lower administrative costs. Conclusions Given the nature of healthcare commissioning, outsourcing vital commissioning support functions may not be the preferred option of CCGs. Considerations of high transaction costs, and the risk of fragmentation of services and loss of trusted relationships involved in short-term contracting, may lead most CCGs to decide to form long-term partnerships with commissioning support suppliers in the future. This option, however, limits competition by creating ‘network closure’ and calls into question the Government

  7. Multimodal optical device for early childhood caries: a clinical prototype

    NASA Astrophysics Data System (ADS)

    Zhang, Liang; Ridge, Jeremy S.; Nelson, Leonard Y.; Berg, Joel H.; Seibel, Eric J.

    There is currently a need for a safe and effective way to detect and diagnose early childhood caries. We have developed a multimodal optical clinical prototype for testing in vivo. The device can be used to quickly image and screen for any signs of demineralized enamel by obtaining high-resolution and highcontrast surface images using a 405-nm laser as the illumination source, as well as obtaining autofluorescence and bacterial fluorescence images. Then, when a suspicious region is located, the device can perform dual laser fluorescence spectroscopy using 405-nm and 532-nm laser excitation which is used to compute an autofluorescence ratio. This ratio can be used to quantitatively diagnose enamel health. The device is tested on four in vivo test subjects as well as 17 extracted teeth with clinically diagnosed carious lesions. The device was able to provide detailed images which served to screen for suspected early caries. The autofluorescence ratios obtained from the extracted teeth were able to discriminate between healthy and unhealthy enamel. Therefore, the clinical prototype demonstrates feasibility in screening for and in quantitatively diagnosing healthy from demineralized enamel.

  8. Variability in early communicative development.

    PubMed

    Fenson, L; Dale, P S; Reznick, J S; Bates, E; Thal, D J; Pethick, S J

    1994-01-01

    Data from parent reports on 1,803 children--derived from a normative study of the MacArthur Communicative Development Inventories (CDIs)--are used to describe the typical course and the extent of variability in major features of communicative development between 8 and 30 months of age. The two instruments, one designed for 8-16-month-old infants, the other for 16-30-month-old toddlers, are both reliable and valid, confirming the value of parent reports that are based on contemporary behavior and a recognition format. Growth trends are described for children scoring at the 10th-, 25th-, 50th-, 75th-, and 90th-percentile levels on receptive and expressive vocabulary, actions and gestures, and a number of aspects of morphology and syntax. Extensive variability exists in the rate of lexical, gestural, and grammatical development. The wide variability across children in the time of onset and course of acquisition of these skills challenges the meaningfulness of the concept of the modal child. At the same time, moderate to high intercorrelations are found among the different skills both concurrently and predictively (across a 6-month period). Sex differences consistently favor females; however, these are very small, typically accounting for 1%-2% of the variance. The effects of SES and birth order are even smaller within this age range. The inventories offer objective criteria for defining typicality and exceptionality, and their cost effectiveness facilitates the aggregation of large data sets needed to address many issues of contemporary theoretical interest. The present data also offer unusually detailed information on the course of development of individual lexical, gestural, and grammatical items and features. Adaptations of the CDIs to other languages have opened new possibilities for cross-linguistic explorations of sequence, rate, and variability of communicative development.

  9. Development of a Weight Loss Mobile App Linked With an Accelerometer for Use in the Clinic: Usability, Acceptability, and Early Testing of its Impact on the Patient-Doctor Relationship.

    PubMed

    Choo, Seryung; Kim, Ju Young; Jung, Se Young; Kim, Sarah; Kim, Jeong Eun; Han, Jong Soo; Kim, Sohye; Kim, Jeong Hyun; Kim, Jeehye; Kim, Yongseok; Kim, Dongouk; Steinhubl, Steve

    2016-03-31

    Although complications of obesity are well acknowledged and managed by clinicians, management of obesity itself is often difficult, which leads to its underdiagnosis and undertreatment in hospital settings. However, tools that could improve the management of obesity, including self-monitoring, engagement with a social network, and open channels of communication between the patient and doctor, are limited in a clinic-based setting. The objective of our study was to evaluate the usability and acceptability of a newly developed mobile app linked with an accelerometer and its early effects on patient-doctor relationships. From September 2013 to February 2014, we developed a mobile app linked with an accelerometer as a supportive tool for a clinic-based weight loss program. The app used information from electronic health records and delivered tailored educational material. Personal goal setting, as well as monitoring of weight changes and physical activity combined with feedback, are key features of the app. We also incorporated an interactive message board for patients and doctors. During the period of March 2014 to May 2014, we tested our mobile app for 1 month in participants in a hospital clinic setting. We assessed the app's usability and acceptability, as well as the patient-doctor relationship, via questionnaires and analysis of app usage data. We recruited 30 individuals (18 male and 12 female) for the study. The median number of log-ins per day was 1.21, with the most frequently requested item being setting goals, followed by track physical activities and view personal health status. Scales of the depth of the patient-doctor relationship decreased from 27.6 (SD 4.8) to 25.1 (SD 4.5) by a Wilcoxon signed rank test (P=.02). A mobile phone app linked with an accelerometer for a clinic-based weight loss program is useful and acceptable for weight management but exhibited less favorable early effects on patient-doctor relationships.

  10. Biomarkers, Early Diagnosis, and Clinical Predictors of BPD

    PubMed Central

    Lal, Charitharth Vivek; Ambalavanan, Namasivayam

    2015-01-01

    Bronchopulmonary Dysplasia (BPD) continues to be an important source of morbidity and mortality in premature neonates. The phenotype of BPD is extremely variable, and diagnosis is a clinical operational definition. A number of clinical and laboratory biomarkers have been proposed for the early identification of infants at higher risk of this disease, to characterize disease activity and severity and for determination of prognosis. Clinical prediction models for BPD have been developed using birth weight, gestational age, indicators of respiratory illness severity, and other clinical variables. Other biomarkers of BPD include those based on imaging of the lungs, lung function measures, and measurements of various analytes in different body fluids (blood, tracheal aspirates, exhaled breath condensates, urine, etc). Novel systems biology ‘omic’ based approaches including but not limited to genomics, proteomics, metabolomics and microbiomics are required for evaluating the multiple interacting cellular and molecular networks that control lung development and injury in BPD. Here we present a critical evaluation of the biomarker approaches studied in the diagnosis of BPD and highlight the future avenues for research in this field. PMID:26593076

  11. Moral Development Interventions in Early Adolescence.

    ERIC Educational Resources Information Center

    Enright, Robert D; And Others

    1983-01-01

    Strategies for promoting moral development in early adolescence reviewed include the "plus-one" model, Deliberate Psychological Education, didactic courses in social studies, and a high school Just Community on moral reasoning. (CJ)

  12. Early Developments in Joint Action

    PubMed Central

    Brownell, Celia A.

    2012-01-01

    Joint action, critical to human social interaction and communication, has garnered increasing scholarly attention in many areas of inquiry, yet its development remains little explored. This paper reviews research on the growth of joint action over the first 2 years of life to show how children become progressively more able to engage deliberately, autonomously, and flexibly in joint action with adults and peers. It is suggested that a key mechanism underlying the dramatic changes in joint action over the second year of life is the ability to reflect consciously on oneself and one’s behavior and volition and correspondingly, on the behavior, goals, and intentions of others. PMID:23087769

  13. Early development of visual recognition.

    PubMed

    Plebe, Alessio; Domenella, Rosaria Grazia

    2006-01-01

    The most important ability of the human vision is object recognition, yet it is exactly the less understood aspect of the vision system. Computational models have been helpful in progressing towards an explanation of this obscure cognitive ability, and today it is possible to conceive more refined models, thanks to the new availability of neuroscientific data about the human visual cortex. This work proposes a model of the development of the object recognition capability, under a different perspective with respect to the most common approaches, with a precise theoretical epistemology. It is assumed that the main processing functions involved in recognition are not genetically determined and hardwired in the neural circuits, but are the result of interactions between epigenetic influences and the basic neural plasticity mechanisms. The model is organized in modules related with the main visual biological areas, and is implemented mainly using the LISSOM architecture, a recent self-organizing algorithm closely reflecting the essential behavior of cortical circuits.

  14. Early psychosis workforce development: Core competencies for mental health professionals working in the early psychosis field.

    PubMed

    Osman, Helen; Jorm, Anthony F; Killackey, Eoin; Francey, Shona; Mulcahy, Dianne

    2017-08-09

    The aim of this study was to identify the core competencies required of mental health professionals working in the early psychosis field, which could function as an evidence-based tool to support the early psychosis workforce and in turn assist early psychosis service implementation and strengthen early psychosis model fidelity. The Delphi method was used to establish expert consensus on the core competencies. In the first stage, a systematic literature search was conducted to generate competency items. In the second stage, a panel consisting of expert early psychosis clinicians from around the world was formed. Panel members then rated each of the competency items on how essential they are to the clinical practice of all early psychosis clinicians. In total, 1023 pieces of literature including textbooks, journal articles and grey literature were reviewed. A final 542 competency items were identified for inclusion in the questionnaire. A total of 63 early psychosis experts participated in 3 rating rounds. Of the 542 competency items, 242 were endorsed as the required core competencies. There were 29 competency items that were endorsed by 62 or more experts, and these may be considered the foundational competencies for early psychosis practice. The study generated a set of core competencies that provide a common language for early psychosis clinicians across professional disciplines and country of practice, and potentially are a useful professional resource to support early psychosis workforce development and service reform. © 2017 John Wiley & Sons Australia, Ltd.

  15. Early development of cephalochordates (amphioxus).

    PubMed

    Holland, Linda Z; Onai, Takayuki

    2012-01-01

    The Phylum Chordata includes three groups--Vertebrata, Tunicata, and Cephalochordata. In cephalochordates, commonly called amphioxus or lancelets, which are basal in the Chordata, the eggs are small and relatively non-yolky. As in vertebrates, cleavage is indeterminate with cell fates determined gradually as development proceeds. The oocytes are attached to the ovarian follicle at the animal pole, where the oocyte nucleus is located. The cytoplasm at the opposite side of the egg, the vegetal pole, contains the future germ plasm or pole plasm, which includes determinants of the germline. After fertilization, additional asymmetries are established by movements of the egg and sperm nuclei, resulting in a concentration of mitochondria at one side of the animal hemisphere. This may be related to establishment of the dorsal/ventral axis. Patterning along the embryonic axes is mediated by secreted signaling proteins. Dorsal identity is specified by Nodal/Vg1 signaling, while during the gastrula stage, opposition between Nodal/Vg1 and BMP signaling establishes dorsal/anterior (i.e., head) and ventral/posterior (i.e., trunk/tail) identities, respectively. Wnt/β-catenin signaling specifies posterior identity while retinoic acid signaling specifies positions along the anterior/posterior axis. These signals are further modulated by a number of secreted antagonists. This fundamental patterning mechanism is conserved, with some modifications, in vertebrates.

  16. TB vaccines in clinical development.

    PubMed

    Ginsberg, Ann M; Ruhwald, Morten; Mearns, Helen; McShane, Helen

    2016-08-01

    The 4th Global Forum on TB Vaccines, convened in Shanghai, China, from 21 - 24 April 2015, brought together a wide and diverse community involved in tuberculosis vaccine research and development to discuss the current status of, and future directions for this critical effort. This paper summarizes the sessions on TB Vaccines in Clinical Development, and Clinical Research: Data and Findings. Summaries of all sessions from the 4th Global Forum are compiled in a special supplement of Tuberculosis. [August 2016, Vol 99, Supp S1, S1-S30].

  17. THE FIRST GRADE CLINIC--A MEDIUM FOR EARLY IDENTIFICATION OF PHYSICAL, SOCIAL, EMOTIONAL, AND MENTAL DEVELOPMENT FACTOR THAT MAY TEND TO BLOCK OR IMPEDE SCHOOL PROGRESS.

    ERIC Educational Resources Information Center

    MCGAHAN, F.E.

    DURING A 5-YEAR PERIOD, A FIRST GRADE CLINIC IDENTIFIED, AT THE START OF EACH SCHOOL YEAR, CHILDREN WITH DEVIATIONS IN BEHAVIOR, SOCIAL AND EMOTIONAL ADJUSTMENT, AND MENTAL MATURATION THAT MIGHT BLOCK OR RETARD SUCCESS IN SCHOOL. THESE CHILDREN WERE REFERRED FOR FURTHER DIAGNOSTIC EVALUATIONS. THE PROGRAM WAS FIRST TRIED IN ONE CLASSROOM. A 3-YEAR…

  18. THE FIRST GRADE CLINIC--A MEDIUM FOR EARLY IDENTIFICATION OF PHYSICAL, SOCIAL, EMOTIONAL, AND MENTAL DEVELOPMENT FACTOR THAT MAY TEND TO BLOCK OR IMPEDE SCHOOL PROGRESS.

    ERIC Educational Resources Information Center

    MCGAHAN, F.E.

    DURING A 5-YEAR PERIOD, A FIRST GRADE CLINIC IDENTIFIED, AT THE START OF EACH SCHOOL YEAR, CHILDREN WITH DEVIATIONS IN BEHAVIOR, SOCIAL AND EMOTIONAL ADJUSTMENT, AND MENTAL MATURATION THAT MIGHT BLOCK OR RETARD SUCCESS IN SCHOOL. THESE CHILDREN WERE REFERRED FOR FURTHER DIAGNOSTIC EVALUATIONS. THE PROGRAM WAS FIRST TRIED IN ONE CLASSROOM. A 3-YEAR…

  19. Early Clinical Experience With Argon Ion Laser Endarterectomy

    NASA Astrophysics Data System (ADS)

    Eugene, John; Baribeau, Yvon; Ott, Richard A.; McColgan, Stephen J.; Berns, Michael W.

    1989-09-01

    This report describes our progress in the development of argon ion laser endarterectomy for arteriosclerotic cardiovascular disease. Nine patients underwent 10 vascular reconstructions for claudication (6), rest pain (1), and gangrene (2). There was 1 aortoiliac endarterectomy, 6 superficial femoral artery endarterectomies, 1 profunda femoris endarterectomy and 2 popliteal endarterectomies. The reconstructions were 6 cm to 60 cm in length. The operations were performed using low power argon ion laser radiation, 1.0 W. All patients experienced symptomatic relief and had palpable pulses postoperatively. There were no perforations and there were no injuries to surrounding tissues from laser radiation. Surgical complications occurred and these were technical problems that should be eliminated from the operation with further developments. The early clinical results show that laser endarterectomy can be performed for peripheral vascular reconstruction using low power argon ion laser radiation.

  20. Teacher Knowledge Development in Early Field Experiences

    ERIC Educational Resources Information Center

    Ingersoll, Casey; Jenkins, Jayne M.; Lux, Karen

    2014-01-01

    Investigation of physical education preservice teacher knowledge development has been primarily limited to study of a single semester of early field experience (EFE), with findings from these investigations driving EFE design. The purpose of this research was to investigate what types of knowledge develop and how knowledge evolves and interacts to…

  1. Early Brain Development Research Review and Update

    ERIC Educational Resources Information Center

    Schiller, Pam

    2010-01-01

    Thanks to imaging technology used in neurobiology, people have access to useful and critical information regarding the development of the human brain. This information allows them to become much more effective in helping children in their early development. In fact, when people base their practices on the findings from medical science research,…

  2. Early Brain Development Research Review and Update

    ERIC Educational Resources Information Center

    Schiller, Pam

    2010-01-01

    Thanks to imaging technology used in neurobiology, people have access to useful and critical information regarding the development of the human brain. This information allows them to become much more effective in helping children in their early development. In fact, when people base their practices on the findings from medical science research,…

  3. Current Issues in Research on Early Development.

    ERIC Educational Resources Information Center

    Siegel, Alberta E.

    Research on early development is moving apace. Developmental psychology is again giving serious attention to ages and stages. This attention is due, in great part, to the formulations about cognitive development by Piaget. Earlier in the century, the experimental approach to child study came to reflect psychology's generally heavy commitment to…

  4. Teacher Knowledge Development in Early Field Experiences

    ERIC Educational Resources Information Center

    Ingersoll, Casey; Jenkins, Jayne M.; Lux, Karen

    2014-01-01

    Investigation of physical education preservice teacher knowledge development has been primarily limited to study of a single semester of early field experience (EFE), with findings from these investigations driving EFE design. The purpose of this research was to investigate what types of knowledge develop and how knowledge evolves and interacts to…

  5. Transcriptome Encyclopedia of Early Human Development.

    PubMed

    Sahakyan, Anna; Plath, Kathrin

    2016-05-05

    Our understanding of human pre-implantation development is limited by the availability of human embryos and cannot completely rely on mouse studies. Petropoulos et al. now provide an extensive transcriptome analysis of a large number of human pre-implantation embryos at single-cell resolution, revealing previously unrecognized features unique to early human development.

  6. Developing Early to Mid Career Teachers

    ERIC Educational Resources Information Center

    Berl, Patricia Scallan

    2005-01-01

    The consequences of poorly planned or random professional development for teachers in the early to mid career cycle are serious. Without input from knowledgeable mentors or supervisors, these teachers can flail about professionally. Without the benefit of individualized staff development plans, they may perpetuate ineffective teaching practices or…

  7. Development of cultured Plasmodium falciparum blood-stage malaria cell banks for early phase in vivo clinical trial assessment of anti-malaria drugs and vaccines.

    PubMed

    Stanisic, Danielle I; Liu, Xue Q; De, Sai Lata; Batzloff, Michael R; Forbes, Tanya; Davis, Christopher B; Sekuloski, Silvana; Chavchich, Marina; Chung, Wendy; Trenholme, Katharine; McCarthy, James S; Li, Tao; Sim, B Kim Lee; Hoffman, Stephen L; Good, Michael F

    2015-04-07

    The ability to undertake controlled human malaria infection (CHMI) studies for preliminary evaluation of malaria vaccine candidates and anti-malaria drug efficacy has been limited by the need for access to sporozoite infected mosquitoes, aseptic, purified, cryopreserved sporozoites or blood-stage malaria parasites derived ex vivo from malaria infected individuals. Three different strategies are described for the manufacture of clinical grade cultured malaria cell banks suitable for use in CHMI studies. Good Manufacturing Practices (GMP)-grade Plasmodium falciparum NF54, clinically isolated 3D7, and research-grade P. falciparum 7G8 blood-stage malaria parasites were cultured separately in GMP-compliant facilities using screened blood components and then cryopreserved to produce three P. falciparum blood-stage malaria cell banks. These cell banks were evaluated according to specific criteria (parasitaemia, identity, viability, sterility, presence of endotoxin, presence of mycoplasma or other viral agents and in vitro anti-malarial drug sensitivity of the cell bank malaria parasites) to ensure they met the criteria to permit product release according to GMP requirements. The P. falciparum NF54, 3D7 and 7G8 cell banks consisted of >78% ring stage parasites with a ring stage parasitaemia of >1.4%. Parasites were viable in vitro following thawing. The cell banks were free from contamination with bacteria, mycoplasma and a broad panel of viruses. The P. falciparum NF54, 3D7 and 7G8 parasites exhibited differential anti-malarial drug susceptibilities. The P. falciparum NF54 and 3D7 parasites were susceptible to all anti-malaria compounds tested, whereas the P. falciparum 7G8 parasites were resistant/had decreased susceptibility to four compounds. Following testing, all defined release criteria were met and the P. falciparum cell banks were deemed suitable for release. Ethical approval has been obtained for administration to human volunteers. The production of cultured P

  8. Challenges in Developing Clinical Workstation

    NASA Astrophysics Data System (ADS)

    Narayanan, Venkatesh; Vedula, Venumadhav

    2008-09-01

    Over the years, medical imaging has become very common and data intensive. New technology is needed to help visualize and analyze these large, complex data sets, especially in an acute care situation where time is of the essence. Also it is very important to present the data in an efficient and simple manner to aid the clinical decision making processes. There is a need for a clinical workstation that handles data from different modalities and performs the necessary post- processing operations on the data in order to enhance the image quality and improve the reliability of diagnosis. This paper briefly explains clinical workstation, emphasizing the requirements and challenges in design and architecture for the development of such systems.

  9. Development of clinical practice guidelines.

    PubMed

    Hollon, Steven D; Areán, Patricia A; Craske, Michelle G; Crawford, Kermit A; Kivlahan, Daniel R; Magnavita, Jeffrey J; Ollendick, Thomas H; Sexton, Thomas L; Spring, Bonnie; Bufka, Lynn F; Galper, Daniel I; Kurtzman, Howard

    2014-01-01

    Clinical practice guidelines (CPGs) are intended to improve mental, behavioral, and physical health by promoting clinical practices that are based on the best available evidence. The American Psychological Association (APA) is committed to generating patient-focused CPGs that are scientifically sound, clinically useful, and informative for psychologists, other health professionals, training programs, policy makers, and the public. The Institute of Medicine (IOM) 2011 standards for generating CPGs represent current best practices in the field. These standards involve multidisciplinary guideline development panels charged with generating recommendations based on comprehensive systematic reviews of the evidence. The IOM standards will guide the APA as it generates CPGs that can be used to inform the general public and the practice community regarding the benefits and harms of various treatment options. CPG recommendations are advisory rather than compulsory. When used appropriately, high-quality guidelines can facilitate shared decision making and identify gaps in knowledge.

  10. [The significance of biobanks for clinical development].

    PubMed

    Thomas, Marlene; Kiermaier, Astrid; Cannarile, Michael

    2016-03-01

    Access to samples in biobanks and collection of samples for evaluation of biomarkers in clinical trials are an essential basis for the identification and development of biomarkers. From the perspective of a research-based pharmaceutical company identification of biomarkers and the accompanying diagnostics are an essential prerequisite for the further evolution of personalised healthcare-and the key to more effective and efficient healthcare. Research-based pharmaceutical companies can basically use four types of biobanks: biobanks of university hospitals, commercial providers, collaborative groups and company-owned biobanks. Areas of application, arising from the use of biobanks in the context of clinical development, are collection of prevalence data, evaluation of biomarker stability in different disease stages, technical validation of assays, an optimized course of clinical studies by focusing on defined, biomarker-stratified groups of patients and pharmacogenetic research. Challenges are, in particular, the availability of clinically annotated samples and tissue matching blood samples, in addition to sample quality, number and amount. An acceptable legal and regulatory framework, as well as the positive perception of biomarker data by politicians and the public, are important prerequisites for translational research for identification of biomarkers in clinical studies. Also, the early establishment of research alliances between academia and the pharmaceutical industry are required to transfer research results in new strategies for prevention, diagnosis and treatment of patients.

  11. Development of a Weight Loss Mobile App Linked With an Accelerometer for Use in the Clinic: Usability, Acceptability, and Early Testing of its Impact on the Patient-Doctor Relationship

    PubMed Central

    Choo, Seryung; Jung, Se Young; Kim, Sarah; Kim, Jeong Eun; Han, Jong Soo; Kim, Sohye; Kim, Jeong Hyun; Kim, Jeehye; Kim, Yongseok; Kim, Dongouk; Steinhubl, Steve

    2016-01-01

    Background Although complications of obesity are well acknowledged and managed by clinicians, management of obesity itself is often difficult, which leads to its underdiagnosis and undertreatment in hospital settings. However, tools that could improve the management of obesity, including self-monitoring, engagement with a social network, and open channels of communication between the patient and doctor, are limited in a clinic-based setting. Objective The objective of our study was to evaluate the usability and acceptability of a newly developed mobile app linked with an accelerometer and its early effects on patient-doctor relationships. Methods From September 2013 to February 2014, we developed a mobile app linked with an accelerometer as a supportive tool for a clinic-based weight loss program. The app used information from electronic health records and delivered tailored educational material. Personal goal setting, as well as monitoring of weight changes and physical activity combined with feedback, are key features of the app. We also incorporated an interactive message board for patients and doctors. During the period of March 2014 to May 2014, we tested our mobile app for 1 month in participants in a hospital clinic setting. We assessed the app’s usability and acceptability, as well as the patient-doctor relationship, via questionnaires and analysis of app usage data. Results We recruited 30 individuals (18 male and 12 female) for the study. The median number of log-ins per day was 1.21, with the most frequently requested item being setting goals, followed by track physical activities and view personal health status. Scales of the depth of the patient-doctor relationship decreased from 27.6 (SD 4.8) to 25.1 (SD 4.5) by a Wilcoxon signed rank test (P=.02). Conclusions A mobile phone app linked with an accelerometer for a clinic-based weight loss program is useful and acceptable for weight management but exhibited less favorable early effects on patient

  12. RFamide Peptides in Early Vertebrate Development

    PubMed Central

    Sandvik, Guro Katrine; Hodne, Kjetil; Haug, Trude Marie; Okubo, Kataaki; Weltzien, Finn-Arne

    2014-01-01

    RFamides (RFa) are neuropeptides involved in many different physiological processes in vertebrates, such as reproductive behavior, pubertal activation of the reproductive endocrine axis, control of feeding behavior, and pain modulation. As research has focused mostly on their role in adult vertebrates, the possible roles of these peptides during development are poorly understood. However, the few studies that exist show that RFa are expressed early in development in different vertebrate classes, perhaps mostly associated with the central nervous system. Interestingly, the related peptide family of FMRFa has been shown to be important for brain development in invertebrates. In a teleost, the Japanese medaka, knockdown of genes in the Kiss system indicates that Kiss ligands and receptors are vital for brain development, but few other functional studies exist. Here, we review the literature of RFa in early vertebrate development, including the possible functional roles these peptides may play. PMID:25538682

  13. Early Childhood Development and E-Learning in Africa: The Early Childhood Development Virtual University Programme

    ERIC Educational Resources Information Center

    Pence, Alan

    2007-01-01

    This article explores the development and evaluation of the graduate-level Early Childhood Development Virtual University (ECDVU) programme in Sub-Saharan Africa from 2001 through to 2004. It outlines the history of the ECDVU and the establishing of a Sub-Saharan programme for future leaders in the early childhood field guided by the key principle…

  14. Early Childhood Development and E-Learning in Africa: The Early Childhood Development Virtual University Programme

    ERIC Educational Resources Information Center

    Pence, Alan

    2007-01-01

    This article explores the development and evaluation of the graduate-level Early Childhood Development Virtual University (ECDVU) programme in Sub-Saharan Africa from 2001 through to 2004. It outlines the history of the ECDVU and the establishing of a Sub-Saharan programme for future leaders in the early childhood field guided by the key principle…

  15. Bioecological Theory, Early Child Development and the Validation of the Population-Level Early Development Instrument

    ERIC Educational Resources Information Center

    Guhn, Martin; Goelman, Hillel

    2011-01-01

    The Early Development Instrument (EDI; Janus and Offord in "Canadian Journal of Behavioural Science" 39:1-22, 2007) project is a Canadian population-level, longitudinal research project, in which teacher ratings of Kindergarten children's early development and wellbeing are linked to health and academic achievement variables at the…

  16. Early executive function predicts reasoning development.

    PubMed

    Richland, Lindsey E; Burchinal, Margaret R

    2013-01-01

    Analogical reasoning is a core cognitive skill that distinguishes humans from all other species and contributes to general fluid intelligence, creativity, and adaptive learning capacities. Yet its origins are not well understood. In the study reported here, we analyzed large-scale longitudinal data from the Study of Early Child Care and Youth Development to test predictors of growth in analogical-reasoning skill from third grade to adolescence. Our results suggest an integrative resolution to the theoretical debate regarding contributory factors arising from smaller-scale, cross-sectional experiments on analogy development. Children with greater executive-function skills (both composite and inhibitory control) and vocabulary knowledge in early elementary school displayed higher scores on a verbal analogies task at age 15 years, even after adjusting for key covariates. We posit that knowledge is a prerequisite to analogy performance, but strong executive-functioning resources during early childhood are related to long-term gains in fundamental reasoning skills.

  17. Clinical management of DIC: early nursing interventions.

    PubMed

    Epstein, C; Bakanauskas, A

    1991-01-01

    Achievement of successful patient outcomes depends on the availability of a primary nurse responsible for all aspects of nursing care. A consistent caregiver not only has a grasp of phenomena at hand but possesses an overall perspective of recovery. Care can be evaluated and readjusted on a timely basis. Identification of signs of progress as well as deterioration may be facilitated through continuity of care. The primary nurse can provide meaningful, ongoing information to the patient and significant others as a means of optimizing their coping behaviors. Effective nursing care of the patient with DIC is enhanced by a thorough understanding of its pathophysiology and its clinical manifestations. When the critical care nurse has a comprehensive knowledge base and uses purposeful assessment skills, potential complications become much clearer and are avoided. The primary nurse who knows how to prioritize care is capable of anticipating the patient's needs. By integrating theory with practice, the critical care nurse functions from a position of strength in promoting quality patient care.

  18. Early Phonological Development: Creating an Assessment Test

    ERIC Educational Resources Information Center

    Stoel-Gammon, Carol; Williams, A. Lynn

    2013-01-01

    This paper describes a new protocol for assessing the phonological systems of two-year-olds with typical development and older children with delays in vocabulary acquisition. The test (Profiles of Early Expressive Phonological Skills ("PEEPS"), Williams & Stoel-Gammon, in preparation) differs from currently available assessments in…

  19. Early Intervention, Maternal Development and Children's Play.

    ERIC Educational Resources Information Center

    Slaughter, Diana T.

    The purposes of this longitudinal study of early intervention with 83 black mother-child dyads were (a) to test the thesis that sociocultural transmission influences childhood development in educationally significant ways, and (b) to describe the process through which such transmission can occur. Two social intervention programs were contrasted;…

  20. Early Childhood Development in Texas. Special Report.

    ERIC Educational Resources Information Center

    Watson, Jeanette; Lanham, Fritz

    Programs and activities for young children in Texas are reported, based on data collected from the state agencies who administer these programs. Two sections are presented, the first dealing with early childhood development in the state, and the second with a survey of state agency programs. A history of federal and state involvement is followed…

  1. The Early Years: Development, Learning and Teaching.

    ERIC Educational Resources Information Center

    Boulton-Lewis, Gillian, Ed.; Catherwood, Di, Ed.

    Designed for teachers, students, caregivers, and health professionals who work with children from birth to age 8, this book provides a review of recent research and theories of development and learning in the early childhood years, with an emphasis on implications for effective teaching. Where appropriate, the book takes an Australian perspective,…

  2. EARLY CRANIOFACIAL DEVELOPMENT: LIFE AMONG THE SIGNALS

    EPA Science Inventory

    Early Craniofacial Development: Life Among the Signals. Sid Hunter and Keith Ward. Reproductive Toxicology Division, NHEERL, US EPA, RTP, NC, 27711

    Haloacetic acids (HAA) are chemicals formed during drinking water disinfection and present in finished tap water. Exposure o...

  3. Rural Outreach and Early Childhood Professional Development

    ERIC Educational Resources Information Center

    Warren, Claudia; Hamlin, Kay

    2005-01-01

    In an attempt to meet the growing professional development needs of early childhood practitioners in North Carolina, Winston-Salem State University (WSSU) is reaching out to the rural areas of North Carolina by offering programs that will certify North Carolina teachers in birth through kindergarten education (BKE). In this article, the author…

  4. EARLY CRANIOFACIAL DEVELOPMENT: LIFE AMONG THE SIGNALS

    EPA Science Inventory

    Early Craniofacial Development: Life Among the Signals. Sid Hunter and Keith Ward. Reproductive Toxicology Division, NHEERL, US EPA, RTP, NC, 27711

    Haloacetic acids (HAA) are chemicals formed during drinking water disinfection and present in finished tap water. Exposure o...

  5. Early Phonological Development: Creating an Assessment Test

    ERIC Educational Resources Information Center

    Stoel-Gammon, Carol; Williams, A. Lynn

    2013-01-01

    This paper describes a new protocol for assessing the phonological systems of two-year-olds with typical development and older children with delays in vocabulary acquisition. The test (Profiles of Early Expressive Phonological Skills ("PEEPS"), Williams & Stoel-Gammon, in preparation) differs from currently available assessments in…

  6. Rural Outreach and Early Childhood Professional Development

    ERIC Educational Resources Information Center

    Warren, Claudia; Hamlin, Kay

    2005-01-01

    In an attempt to meet the growing professional development needs of early childhood practitioners in North Carolina, Winston-Salem State University (WSSU) is reaching out to the rural areas of North Carolina by offering programs that will certify North Carolina teachers in birth through kindergarten education (BKE). In this article, the author…

  7. Early Childhood Development: Trends and Likely Scenarios.

    ERIC Educational Resources Information Center

    van Oudenhoven, Nico; Wazir, Rekha

    The following trends have been in motion in the field of early childhood development (ECD) for some time: (1) the concept of ECD is increasingly taking on additional connotations; (2) in Europe children are becoming a minority group and other age groups, such as the elderly, see them as competitors for the same limited resources; (3) the downward…

  8. Stress, Early Brain Development, and Behavior.

    ERIC Educational Resources Information Center

    Gunnar, Megan R.; Barr, Ronald G.

    1998-01-01

    Reviews research on the effect of stress hormones, particularly glucocorticoids, on the brain and early development. It describes the psychological and social processes that reduce stress hormone responses to threatening and painful procedures. Research on the cognitive and emotional effects of synthetic glucocorticoids is also discussed.…

  9. [Clinical studies in developing countries].

    PubMed

    van den Munkhof, Hanna E

    2013-01-01

    In general, clinical trials in developing countries are met with resistance because the people are particularly vulnerable and medical assistance is often unaffordable. The prospect of free medication can then lead to exploitation since the local population can be persuaded to participate in trials that would never be allowed in Western countries due to ethical concerns. Placebo-controlled research that tests cheaper alternatives for treatments already registered could greatly improve the situation in developing countries, however. Expensive registered treatments are often unavailable in these countries. Therefore, I call for allowing such studies when the registered treatment is locally unavailable. This should be based on the four most important principles of medical ethics: the duty to help patients, avoid harm, justice and respect for autonomy. On the condition, however, that the population in developing countries benefits in the long term.

  10. Antibiotics in late clinical development.

    PubMed

    Fernandes, Prabhavathi; Martens, Evan

    2017-06-01

    Most pharmaceutical companies have stopped or have severely limited investments to discover and develop new antibiotics to treat the increasing prevalence of infections caused by multi-drug resistant bacteria, because the return on investment has been mostly negative for antibiotics that received marketing approved in the last few decades. In contrast, a few small companies have taken on this challenge and are developing new antibiotics. This review describes those antibiotics in late-stage clinical development. Most of them belong to existing antibiotic classes and a few with a narrow spectrum of activity are novel compounds directed against novel targets. The reasons for some of the past failures to find new molecules and a path forward to help attract investments to fund discovery of new antibiotics are described. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Early onset marfan syndrome: Atypical clinical presentation of two cases

    PubMed Central

    Ozyurt, A; Baykan, A; Argun, M; Pamukcu, O; Halis, H; Korkut, S; Yuksel, Z; Gunes, T; Narin, N

    2015-01-01

    Early onset Marfan Syndrome (eoMFS) is a rare, severe form of Marfan Syndrome (MFS). The disease has a poor prognosis and most patients present with resistance to heart failure treatment during the newborn period. This report presents two cases of eoMFS with similar clinical features diagnosed in the newborn period and who died at an early age due to the complications related to the involvement of the cardiovascular system. PMID:26929908

  12. Clinical Assay Development Support - Office of Cancer Clinical Proteomics Research

    Cancer.gov

    The NCI’s Division of Cancer Treatment and Diagnosis and the Cancer Diagnosis Program announce a request for applications for the Clinical Assay Development Program (CADP) for investigators seeking clinical assay development and validation resources.

  13. Early phase clinical trials to identify optimal dosing and safety

    PubMed Central

    Cook, Natalie; Hansen, Aaron R.; Siu, Lillian L.; Abdul Razak, Albiruni R.

    2014-01-01

    The purpose of early stage clinical trials is to determine the recommended dose and toxicity profile of an investigational agent or multi-drug combination. Molecularly targeted agents (MTAs) and immunotherapies have distinct toxicities from chemotherapies that are often not dose dependent and can lead to chronic and sometimes unpredictable side effects. Therefore utilizing a dose escalation method that has toxicity based endpoints may not be as appropriate for determination of recommended dose, and alternative parameters such as pharmacokinetic or pharmacodynamic outcomes are potentially appealing options. Approaches to enhance safety and optimize dosing include improved preclinical models and assessment, innovative model based design and dose escalation strategies, patient selection, the use of expansion cohorts and extended toxicity assessments. Tailoring the design of phase I trials by adopting new strategies to address the different properties of MTAs is required to enhance the development of these agents. This review will focus on the limitations to safety and dose determination that have occurred in the development of MTAs and immunotherapies. In addition, strategies are proposed to overcome these challenges to develop phase I trials that can more accurately define the recommended dose and identify adverse events. PMID:25160636

  14. Development: clinical and evolutionary considerations.

    PubMed

    Opitz, John M

    2007-12-15

    The Linnean tercentenary is a most welcome opportunity to celebrate the complimentary contributions of the molecular taxonomists and the morphologists in establishing a "natural order" of living organisms depending on degree of relatedness and the 70th anniversary of birth of our friend and colleague, M. Michael Cohen Jr. These events lead one to reflect on the relationship between evolution and normal, respectively abnormal development. In part due to Mike Cohen's efforts, such reflections will at last also creep into the clinic given that more and more malformations are understood ontogenetically and phylogenetically on the basis of homology in structure, development and genetic basis in more or less closely related organisms. It is inconceivable how such an understanding can allow anyone to deny the reality of evolution and its implications for the antiquity of the earth, and its biosphere and the vulnerability of all species, humans included, for extinction.

  15. Nurturing care: promoting early childhood development.

    PubMed

    Britto, Pia R; Lye, Stephen J; Proulx, Kerrie; Yousafzai, Aisha K; Matthews, Stephen G; Vaivada, Tyler; Perez-Escamilla, Rafael; Rao, Nirmala; Ip, Patrick; Fernald, Lia C H; MacMillan, Harriet; Hanson, Mark; Wachs, Theodore D; Yao, Haogen; Yoshikawa, Hirokazu; Cerezo, Adrian; Leckman, James F; Bhutta, Zulfiqar A

    2017-01-07

    The UN Sustainable Development Goals provide a historic opportunity to implement interventions, at scale, to promote early childhood development. Although the evidence base for the importance of early childhood development has grown, the research is distributed across sectors, populations, and settings, with diversity noted in both scope and focus. We provide a comprehensive updated analysis of early childhood development interventions across the five sectors of health, nutrition, education, child protection, and social protection. Our review concludes that to make interventions successful, smart, and sustainable, they need to be implemented as multi-sectoral intervention packages anchored in nurturing care. The recommendations emphasise that intervention packages should be applied at developmentally appropriate times during the life course, target multiple risks, and build on existing delivery platforms for feasibility of scale-up. While interventions will continue to improve with the growth of developmental science, the evidence now strongly suggests that parents, caregivers, and families need to be supported in providing nurturing care and protection in order for young children to achieve their developmental potential. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Early development and neurogenesis of Temnopleurus reevesii.

    PubMed

    Yaguchi, Shunsuke; Yamazaki, Atsuko; Wada, Wakana; Tsuchiya, Yasutaka; Sato, Toshihiko; Shinagawa, Hideo; Yamada, Yutaro; Yaguchi, Junko

    2015-04-01

    Sea urchins are model non-chordate deuterostomes, and studying the nervous system of their embryos can aid in the understanding of the universal mechanisms of neurogenesis. However, despite the long history of sea urchin embryology research, the molecular mechanisms of their neurogenesis have not been well investigated, in part because neurons appear relatively late during embryogenesis. In this study, we used the species Temnopleurus reevesii as a new sea urchin model and investigated the detail of its development and neurogenesis during early embryogenesis. We found that the embryos of T. reevesii were tolerant of high temperatures and could be cultured successfully at 15-30°C during early embryogenesis. At 30°C, the embryos developed rapidly enough that the neurons appeared at just after 24 h. This is faster than the development of other model urchins, such as Hemicentrotus pulcherrimus or Strongylocentrotus purpuratus. In addition, the body of the embryo was highly transparent, allowing the details of the neural network to be easily captured by ordinary epifluorescent and confocal microscopy without any additional treatments. Because of its rapid development and high transparency during embryogenesis, T. reevesii may be a suitable sea urchin model for studying neurogenesis. Moreover, the males and females are easily distinguishable, and the style of early cleavages is intriguingly unusual, suggesting that this sea urchin might be a good candidate for addressing not only neurology but also cell and developmental biology.

  17. Clinical characteristics of early- and late-onset gout

    PubMed Central

    Zhang, Bingqing; Fang, Weigang; Zeng, Xuejun; Zhang, Yun; Ma, Ya; Sheng, Feng; Zhang, Xinlei

    2016-01-01

    Abstract A retrospective cross-sectional study using data from an outpatient clinic in China was conducted to investigate the clinical features of early-onset gout patients. All patients diagnosed with gout were asked about clinical characteristics of their gout and comorbid diseases. Patients presenting with acute flares were asked about common triggers before the flare. “Early-onset” gout was defined as onset of gout before 40 years and “late-onset” as onset ≥40 years. Major joint involvement, flare frequency before presentation, the cumulative number of involved joints, proportions of tophi complications at presentation, flare triggers, as well as any metabolic, cardiovascular, cerebrovascular, and renal comorbidities, were compared between the 2 groups. A total of 778 gout patients were enrolled in this study, including 449 (57.7%) in the early-onset group and 329 (42.3%) in the late-onset group. Compared with the late-onset gout patients, the early-onset gout patients had a higher proportion of ankle/mid-foot involvement (62.8% vs 48.2%, P < 0.001), more frequent flares before presentation (11.2 ± 1.17 vs 6.97 ± 1.03 times per year, P = 0.01), higher cumulative number of involved joints (5.2 ± 0.26 vs 3.8 ± 0.26, P < 0.001), and more likely to have alcohol consumption as a flare trigger (65.2% vs 53.9%, P = 0.03); whereas early-onset gout patients had fewer metabolic, cardiovascular, cerebrovascular, or renal complications. Early- and late-onset gout patients had different clinical features. Early-onset seems to be influenced more by lifestyle, while late-onset patients have more complications because of comorbidities. PMID:27893683

  18. Early Adverse Experiences and the Developing Brain

    PubMed Central

    Bick, Johanna; Nelson, Charles A

    2016-01-01

    Children exposed to various forms of adversity early in life are at increased risk for a broad range of developmental difficulties, affecting both cognitive and emotional adjustment. We review a growing body of evidence suggesting that exposure to adverse circumstances affects the developing brain in ways that increase risk for a myriad of problems. We focus on two forms of adversity, one in which children are exposed to childhood maltreatment in family environments, and another in which children are exposed to extreme psychosocial deprivation in contexts of institutional rearing. We discuss ways in which each of these experiences represent violations of species-expected caregiving conditions, thereby imposing challenges to the developing brain. We also review emerging data pointing to the effectiveness of early intervention in remediating neurodevelopmental consequences associated with maltreatment or institutional rearing. We conclude by discussing implications of this work for public health efforts and highlight important directions for the field. PMID:26334107

  19. QCD development in the early universe

    NASA Astrophysics Data System (ADS)

    Gromov, N. A.

    2017-03-01

    The high-energy limit of Quantum Chromodynamics is generated by the contraction of its gauge groups. Contraction parameters are taken identical with those of the Electroweak Model and tend to zero when energy increases. At the infinite energy limit all quarks lose masses and have only one color degree of freedom. The limit model represents the development of Quantum Chromodynamics in the early Universe from the Big Bang up to the end of several milliseconds.

  20. Cultural sensitivity or professional acculturation in early clinical experience?

    PubMed

    Whitford, David L; Hubail, Amal Redha

    2014-11-01

    This study aimed to explore the early clinical experience of medical students following the adaptation of an Early Patient Contact curriculum from a European culture in Ireland to an Arab culture in Bahrain. Medical students in Bahrain took part in an Early Patient Contact module modelled on a similar module from a partner medical school in Ireland. We used a qualitative approach employing thematic analysis of 54 student reflective logbooks. Particular attention was placed on reflections of cultural influences of experience in the course. Medical students undergoing this module received reported documented benefits of early clinical experience. However, students in Bahrain were exposed to cultural norms of the local Arab society including gender values, visiting the homes of strangers, language barriers and generous hospitality that led to additional challenges and learning for the medical students in acculturating to norms of the medical profession. Modules intended for curriculum adaptation between two cultures would be best served by a group of "core" learning outcomes with "secondary" outcomes culturally appropriate to each site. Within the context of the Arab culture, early clinical experience has the added benefit of allowing students to learn about both local and professional cultural norms, thereby facilitating integration of these two cultures.

  1. [Overview of the Ebola vaccines in pre-clinical and clinical development].

    PubMed

    Buchy, P

    2016-10-01

    The Ebola epidemic that occurred in West Africa between 2013-2016 significantly accelerated the research and development of Ebola vaccines. Few dozens of clinical trials have been recently conducted leading to opportunities to test several new vaccine candidates. Other vaccines are still in early development phases (table 1). This paper provides an overview of the new developments in that area.

  2. Early Infant Development and Intervention for Autism Spectrum Disorder.

    PubMed

    Sacrey, Lori-Ann R; Bennett, Jeffrey A; Zwaigenbaum, Lonnie

    2015-12-01

    The objective is to overview recent findings on early detection/diagnosis of autism spectrum disorders, as well as clinical trials of early interventions for toddlers at risk for/diagnosed with autism spectrum disorder. Prospective studies of infants at high risk of autism spectrum disorder have yielded significant advances in understanding early development in autism spectrum disorder. Findings from prospective studies indicate that abnormalities in social communication and repetitive behaviors emerge during the second year, whereas additional "prodromal features" (motor and sensory abnormalities) emerge in the first year. Subsequently, exciting progress has been made in establishing the efficacy of autism spectrum disorder-specific interventions for toddlers as young as 15 months. Finally, efforts occur to characterize autism spectrum disorder-specific characteristics in genetic syndromes with concurrent autism spectrum disorder symptomatology. Substantial progress in characterizing early developmental trajectories as well as the identification of specific behavioral markers has aided early detection. Work remains to ensure that research findings are translated into clinical practice for uptake in the health care system. © The Author(s) 2015.

  3. Early identification of alcohol abuse: 2: Clinical and laboratory indicators.

    PubMed Central

    Holt, S; Skinner, H A; Israel, Y

    1981-01-01

    Despite awareness of the wide variety of clinical and laboratory abnormalities associated with alcohol abuse, drinking problems often remain undetected in hospital and in general medical practice. The diagnosis of alcohol abuse has been emphasized repeatedly in the literature but far less attention has been paid to indicators that would permit detection of excessive drinking at a stage when intervention might be more effective and less costly. The search for indicators of early alcohol abuse is complicated since many of the medical sequelae of alcoholism are nonspecific and may only be manifested after a number of years of excessive drinking. Part 2 of this two-part series considers various clinical and laboratory features related to alcohol abuse and highlights items that are potentially more sensitive for detecting early stages of problem drinking. Use by physicians of a composite profile of both biomedical and psychosocial indicators of excessive alcohol consumption is recommended for early identification of this problem. PMID:7016289

  4. Early application of deep brain stimulation: clinical and ethical aspects.

    PubMed

    Woopen, Christiane; Pauls, K Amande M; Koy, Anne; Moro, Elena; Timmermann, Lars

    2013-11-01

    Deep brain stimulation (DBS) has proven to be a successful therapeutic approach in several patients with movement disorders such as Parkinson's disease and dystonia. Hitherto its application was mainly restricted to advanced disease patients resistant to medication or with severe treatment side effects. However, there is now growing interest in earlier application of DBS, aimed at improving clinical outcomes, quality of life, and avoiding psychosocial consequences of chronic disease-related impairments. We address the clinical and ethical aspects of two "early" uses of DBS, (1) DBS early in the course of the disease, and (2) DBS early in life (i.e. in children). Possible benefits, risks and burdens are discussed and thoroughly considered. Further research is needed to obtain a careful balance between exposing vulnerable patients to potential severe surgical risks and excluding them from a potentially good outcome.

  5. Antibiotics Clinical Development and Pipeline.

    PubMed

    Hesterkamp, Thomas

    There is a constant need for resupply with resistance-breaking antibiotics. Governmental programs and updated regulatory guidance have incentivized mainly small- and medium-sized biopharmaceutical companies to develop novel antibiotics up to market licensure, while major pharma players, with exceptions, have abandoned the space for a perceived lack of a return on their investment. The portfolio of approved drugs has improved over recent years for gram-positive infections, including infections caused by methicillin-resistant Staphylococcus aureus. On the other hand, unmet medical need has surfaced in indications dominated by gram-negative pathogens including complicated intra-abdominal and bloodstream infections as well as hospital-acquired and ventilator-associated pneumonia. Few if any treatment options are left for extended-spectrum beta-lactamase- and carbapenemase-producing Enterobacteriaceae, e.g., Klebsiella pneumoniae, and the multi-drug-resistant non-fermenting gram-negative bacteria Pseudomonas aeruginosa and Acinetobacter baumannii. The present paper summarizes and reviews the clinical pipeline of novel antibiotics by clinical indication and identifies the unmet medical need in the space.

  6. Evidence-based early clinical detection of emerging diseases in food animals and zoonoses: two cases.

    PubMed

    Saegerman, Claude; Humblet, Marie-France; Porter, Sarah Rebecca; Zanella, Gina; Martinelle, Ludovic

    2012-03-01

    If diseases of food-producing animals or zoonoses (re-)emerge, early clinical decision making is of major importance. In this particular condition, it is difficult to apply a classic evidence-based veterinary medicine process, because of a lack of available published data. A method based on the partition of field clinical observations (evidences) could be developed as an interesting alternative approach. The classification and regression tree (CART) analysis was used to improve the early clinical detection in two cases of emerging diseases: bovine spongiform encephalopathy (mad cow disease) and bluetongue due to the serotype 8-virus in cattle.

  7. Early and Middle Adolescents’ Autonomy Development

    PubMed Central

    Murphy, Debra A.; Greenwell, Lisa; Resell, Judith; Brecht, Mary-Lynn; Schuster, Mark A.

    2008-01-01

    Progression toward autonomy is considered of central importance during the adolescent period. For young adolescents with an HIV-infected parent, there may be additional challenges. This study investigated current autonomy among early and middle adolescents affected by maternal HIV (N = 108), as well as examined longitudinally the children’s responsibility taking when they were younger (age 6 - 11; N = 81) in response to their mother’s illness and their current autonomy as early/middle adolescents. In analyses of self-care and family autonomy, children with greater attachment to their mothers had higher autonomy, and there was a trend for children who drink or use drugs alone to have lower autonomy. In analyses of management autonomy, attachment to peers was associated with higher autonomy. Trajectory group findings indicate that those children who had taken on more responsibility for instrumental caretaking roles directly because of their mother’s illness showed better autonomy development as early and middle age adolescents. Therefore, “parentification” of young children with a mother with HIV may not negatively affect later autonomy development. PMID:18540228

  8. Early Repolarization Syndrome; Mechanistic Theories and Clinical Correlates

    PubMed Central

    Mercer, Ben N.; Begg, Gordon A.; Page, Stephen P.; Bennett, Christopher P.; Tayebjee, Muzahir H.; Mahida, Saagar

    2016-01-01

    The early repolarization (ER) pattern on the 12-lead electrocardiogram is characterized by J point elevation in the inferior and/or lateral leads. The ER pattern is associated with an increased risk of ventricular arrhythmias and sudden cardiac death (SCD). Based on studies in animal models and genetic studies, it has been proposed that J point elevation in ER is a manifestation of augmented dispersion of repolarization which creates a substrate for ventricular arrhythmia. A competing theory regarding early repolarization syndrome (ERS) proposes that the syndrome arises as a consequence of abnormal depolarization. In recent years, multiple clinical studies have described the characteristics of ER patients with VF in more detail. The majority of these studies have provided evidence to support basic science observations. However, not all clinical observations correlate with basic science findings. This review will provide an overview of basic science and genetic research in ER and correlate basic science evidence with the clinical phenotype. PMID:27445855

  9. Early Childhood Development in Saskatoon, Saskatchewan. Understanding the Early Years

    ERIC Educational Resources Information Center

    Willms, J. Douglas

    2002-01-01

    Understanding the Early Years (UEY) is a national research initiative. It provides communities with information to enable them to make informed decisions about the best policies and most appropriate programs for families with young children. It seeks to provide information about the influence of community factors on children's early development…

  10. Photobiomodulation of early mouse embryo development

    NASA Astrophysics Data System (ADS)

    Sviridova-Chailakhyan, T. A.; Fakhranurova, L. I.; Simonova, N. B.; Khramov, R. N.; Manokhin, A. A.; Paskevich, S. I.; Chailakhyan, L. M.

    2008-04-01

    The effect of artificial sunlight (AS) from a xenon source and of converted AS with an additional orange-red luminescent (λ MAX=626 nm) component (AS+L) on the development of mouse zygotes was investigated. A plastic screen with a photoluminophore layer was used for production of this orange-red luminescent (L) component. A single short-term (15 min) exposure produced a long-term stable positive effect on early embryo development of mice, which persisted during several days. After exposure to AS+L, a stimulating influence on preimplantation development was observed, in comparison with the control group without AS exposure. The positive effects were as follows: increase in percent of embryos (P <= 0.05) developed to the blastocyst stage (96.2 %) with hatching from the zona pellucida (80.8 %) within 82-96 hours in vitro compared to the control (67.1 % and 28.8 %, respectively).

  11. Cognitive theories of early gender development.

    PubMed

    Martin, Carol Lynn; Ruble, Diane N; Szkrybalo, Joel

    2002-11-01

    The contribution of cognitive perspectives (cognitive-developmental theory and gender schema theory) to a contemporary understanding of gender development is evaluated. Recent critiques of cognitive approaches are discussed and empirical evidence is presented to counter these critiques. Because of the centrality of early gender development to the cognitive perspective, the latest research is reviewed on how infants and toddlers discriminate the sexes and learn the attributes correlated with sex. The essence of cognitive approaches--emphasis on motivational consequences of gender concepts; the active, self-initiated view of development; and focus on developmental patterns-is highlighted and contrasted with social-cognitive views. The value of cognitive theories to the field is illustrated, and recommendations are made concerning how to construct comprehensive, integrative perspectives of gender development.

  12. Considerations in the early development of biosimilar products.

    PubMed

    Li, Edward C; Abbas, Richat; Jacobs, Ira A; Yin, Donghua

    2015-05-01

    The widespread use and patent expiration of many biologics have led to global interest in development of biosimilar products. Because the manufacture of biologics, including biosimilars, is a complex process involving living systems, the development of a biosimilar is more rigorous than the development of a generic small molecule drug. Several regulatory agencies have established or are proposing guidelines that recommend a stepwise process to ensure the efficacy and safety of a biosimilar are highly similar to the reference product. This article also explores the early clinical phase of biosimilar development, which is particularly important to resolving any uncertainties that might remain following in vitro and in vivo evaluations and to enable a selective and targeted approach to Phase III clinical efficacy and safety investigation.

  13. ROCK inhibition prevents early mouse embryo development.

    PubMed

    Duan, Xing; Chen, Kun-Lin; Zhang, Yu; Cui, Xiang-Shun; Kim, Nam-Hyung; Sun, Shao-Chen

    2014-08-01

    ROCK is a Rho-GTPase effector that is important for actin assembly and is involved in various cellular functions, including cell contraction, migration, motility, and tumor cell invasion. In this study, we investigated ROCK expression and function during early mouse embryo development. Inhibiting ROCK by Y-27632 treatment at the zygote stage resulted in first cleavage failure, and most embryos failed to develop to the 8-cell stage. When adding Y-27632 at the 8-cell stage, embryos failed to undergo compaction and could not develop into blastocysts. In addition, fluorescence staining intensity analysis indicated that actin expression at blastomere membranes was significantly reduced. After ROCK inhibition, two or more nuclei were observed in a cell, which indicated possible cytokinesis failure. Moreover, after ROCK inhibition with Y-27632, the phosphorylation levels of LIMK1/2, a downstream molecule of ROCK, were decreased at blastomere membranes. Thus, our results showed conserved roles for ROCK in this mammalian embryo model and indicated that a ROCK-LIMK1/2-actin pathway might regulate cleavage and blastocyst formation during early mouse embryo development.

  14. Lipidome signatures in early bovine embryo development.

    PubMed

    Sudano, Mateus J; Rascado, Tatiana D S; Tata, Alessandra; Belaz, Katia R A; Santos, Vanessa G; Valente, Roniele S; Mesquita, Fernando S; Ferreira, Christina R; Araújo, João P; Eberlin, Marcos N; Landim-Alvarenga, Fernanda D C

    2016-07-15

    Mammalian preimplantation embryonic development is a complex, conserved, and well-orchestrated process involving dynamic molecular and structural changes. Understanding membrane lipid profile fluctuation during this crucial period is fundamental to address mechanisms governing embryogenesis. Therefore, the aim of the present work was to perform a comprehensive assessment of stage-specific lipid profiles during early bovine embryonic development and associate with the mRNA abundance of lipid metabolism-related genes (ACSL3, ELOVL5, and ELOVL6) and with the amount of cytoplasmic lipid droplets. Immature oocytes were recovered from slaughterhouse-derived ovaries, two-cell embryos, and eight- to 16-cell embryos, morula, and blastocysts that were in vitro produced under different environmental conditions. Lipid droplets content and mRNA transcript levels for ACSL3, ELOVL5, and ELOVL6, monitored by lipid staining and quantitative polymerase chain reaction, respectively, increased at morula followed by a decrease at blastocyst stage. Relative mRNA abundance changes of ACSL3 were closely related to cytoplasmic lipid droplet accumulation. Characteristic dynamic changes of phospholipid profiles were observed during early embryo development and related to unsaturation level, acyl chain length, and class composition. ELOVL5 and ELOVL6 mRNA levels were suggestive of overexpression of membrane phospholipids containing elongated fatty acids with 16, 18, and 20 carbons. In addition, putative biomarkers of key events of embryogenesis, embryo lipid accumulation, and elongation were identified. This study provides a comprehensive description of stage-specific lipidome signatures and proposes a mechanism to explain its potential relationship with the fluctuation of both cytoplasmic lipid droplets content and mRNA levels of lipid metabolism-related genes during early bovine embryo development.

  15. Early Childhood Development: Laying the Foundations of Learning.

    ERIC Educational Resources Information Center

    Faccini, Benedict; Combes, Bernard

    Early childhood development is increasingly viewed as an affirmation of children's rights. This report describes the concept of early childhood development and presents several viewpoints regarding early childhood care and development, parenting, and approaches to early education. The report also presents 10 case studies of programs to enhance the…

  16. Professional Development through Clinical Supervision

    ERIC Educational Resources Information Center

    Farhat, Amal

    2016-01-01

    Studies have shown that clinical supervisory practices result in implementation of new skills in teachers' classroom performance. This study examines the impact of two clinical supervisory cycles on teachers' performance in classroom management. Multiple data collection tools were used to determine the impact of clinical supervisory interventions…

  17. Professional Development through Clinical Supervision

    ERIC Educational Resources Information Center

    Farhat, Amal

    2016-01-01

    Studies have shown that clinical supervisory practices result in implementation of new skills in teachers' classroom performance. This study examines the impact of two clinical supervisory cycles on teachers' performance in classroom management. Multiple data collection tools were used to determine the impact of clinical supervisory interventions…

  18. Early-onset Coronary Artery Disease Clinical and Hereditary Aspects.

    PubMed

    Christiansen, Morten Krogh

    2017-09-01

    A family history of coronary artery disease (CAD) is an important risk factor for adverse coronary events, in particular if the disease has an early onset. The risk of CAD is influenced by genetic and environmental factors with a greater genetic contribution earlier in life. Through recent years the advances in genetic techniques has led to an increased understanding of the genetic background of CAD, which may potentially be translated into clinical use. The studies of this thesis aimed to investigate the burden of conventional risk factors and control in early-onset CAD (i.e. < 40 years), and to characterize and quantify subclinical atherosclerosis in their relatives. Furthermore, the aim was to explore the impact of common genetic risk variants on the age of onset, familial clustering and disease severity. In study I, 143 patients with early-onset CAD were recruited from the Western Denmark Heart Registry and risk factor control was evaluated. The study revealed that risk factors are common in early-onset CAD and that a large room for risk factor improvement remains. In study II, we used coronary computed tomography angiography to compare the coronary plaque burden and characteristics between 88 first-degree relatives of patients with early-onset CAD and 88 controls with no familial predisposition. Relatives had a significantly increased coronary plaque burden, which displayed characteristics associated with myocardial ischemia and adverse coronary events. In study III, 134 patients with early-onset CAD, a cohort of 446 late-onset CAD patients (onset > 55/65 years in males/females), and 89 healthy controls were genotyped for 45 common genetic risk variants and a genetic risk score was calculated as a measure of the polygenetic burden. Early-onset CAD patients had a modestly increased genetic burden compared with late-onset CAD patients and healthy controls; however, the burden did not associate with familial clustering of CAD. Additionally, familial clustering

  19. The developing hypopharyngeal microbiota in early life.

    PubMed

    Mortensen, Martin Steen; Brejnrod, Asker Daniel; Roggenbuck, Michael; Abu Al-Soud, Waleed; Balle, Christina; Krogfelt, Karen Angeliki; Stokholm, Jakob; Thorsen, Jonathan; Waage, Johannes; Rasmussen, Morten Arendt; Bisgaard, Hans; Sørensen, Søren Johannes

    2016-12-30

    The airways of healthy humans harbor a distinct microbial community. Perturbations in the microbial community have been associated with disease, yet little is known about the formation and development of a healthy airway microbiota in early life. Our goal was to understand the establishment of the airway microbiota within the first 3 months of life. We investigated the hypopharyngeal microbiota in the unselected COPSAC2010 cohort of 700 infants, using 16S rRNA gene sequencing of hypopharyngeal aspirates from 1 week, 1 month, and 3 months of age. Our analysis shows that majority of the hypopharyngeal microbiota of healthy infants belong to each individual's core microbiota and we demonstrate five distinct community pneumotypes. Four of these pneumotypes are dominated by the genera Staphylococcus, Streptococcus, Moraxella, and Corynebacterium, respectively. Furthermore, we show temporal pneumotype changes suggesting a rapid development towards maturation of the hypopharyngeal microbiota and a significant effect from older siblings. Despite an overall common trajectory towards maturation, individual infants' microbiota are more similar to their own, than to others, over time. Our findings demonstrate a consolidation of the population of indigenous bacteria in healthy airways and indicate distinct trajectories in the early development of the hypopharyngeal microbiota.

  20. Reading development subtypes and their early characteristics.

    PubMed

    Torppa, Minna; Tolvanen, Asko; Poikkeus, Anna-Maija; Eklund, Kenneth; Lerkkanen, Marja-Kristiina; Leskinen, Esko; Lyytinen, Heikki

    2007-06-01

    The present findings are drawn from the Jyväskylä Longitudinal Study of Dyslexia (JLD), in which approximately 100 children with familial risk of dyslexia and 100 control children have been followed from birth. In this paper we report data on the reading development of the JLD children and their classmates, a total of 1,750 children from four measurement points during the first two school years. In the total sample, we examined whether heterogeneous developmental paths can be identified based on profiles of word recognition and reading comprehension. Secondly, we studied what kind of early language and literacy skill profiles and reading experiences characterize the children with differing reading development in the follow-up sample. The mixture modeling procedure resulted in five subtypes: (1) poor readers, (2) slow decoders, (3) poor comprehenders, (4) average readers, and (5) good readers. The children with familial risk for dyslexia performed on average at a lower level in all reading tasks than both their classmates and the controls, and they were overrepresented in slow decoders subtype. Differences between the subtypes were found in the early language and literacy skill development, as well as in the reading experiences of the reading subtypes.

  1. Kepler Mission Development Challenges and Early Results

    NASA Technical Reports Server (NTRS)

    Fanson, J.

    2011-01-01

    Kepler is NASA`s first mission capable of detecting Earth-size planets orbiting in the habitable zone of stars other than the sun. Kepler comprises a space telescope designed to continuously monitor the brightnesses of more than 100,000 target stars, and a ground segment to analyze the measured stellar light curves and detect the signatures of orbiting planets. In order to detect Earth-size planets orbiting Sun-like stars Kepler was designed to provide unprecedented photometric sensitivity and stability. This paper addresses some of the technical challenges encountered during the development of the Kepler mission and the measures taken to overcome them. Early scientific results are summarized.

  2. Kepler Mission Development Challenges and Early Results

    NASA Technical Reports Server (NTRS)

    Fanson, J.; Duren, R.; Frerking, M.

    2011-01-01

    Kepler is NASA s first mission capable of detecting Earth-size planets orbiting in the habitable zone of stars other than the Sun. Kepler comprises a space telescope designed to continuously monitor the brightnesses of more than 100,000 target stars, and a ground segment to analyze the measured stellar light curves and detect the signatures of orbiting planets. In order to detect Earth-size planets orbiting Sun-like stars Kepler was designed to provide unprecedented photometric sensitivity and stability. This paper addresses some of the technical challenges encountered during the development of the Kepler mission and the measures taken to overcome them. Early scientific results are summarized.

  3. Reflections on the early development of poxvirus vectors.

    PubMed

    Moss, Bernard

    2013-09-06

    Poxvirus expression vectors were described in 1982 and quickly became widely used for vaccine development as well as research in numerous fields. Advantages of the vectors include simple construction, ability to accommodate large amounts of foreign DNA and high expression levels. Numerous poxvirus-based veterinary vaccines are currently in use and many others are in human clinical trials. The early reports of poxvirus vectors paved the way for and stimulated the development of other viral vectors and recombinant DNA vaccines. Published by Elsevier Ltd.

  4. New hepatitis C therapies in clinical development

    PubMed Central

    2011-01-01

    With the current standard of care for the treatment of chronic hepatitis C, a combination of pegylated interferon alfa and ribavirin, sustained virologic response rates can be achieved in approximately 50% of patients only. Improved understanding of the viral life cycle has led to the identification of numerous potential targets for novel, direct-acting antiviral compounds. Inhibitors of the NS3/4A protease are currently the most advanced in clinical development. Recently completed phase 3 studies of the two protease inhibitors telaprevir and boceprevir, each given in combination with standard of care, yielded sustained virologic response rates in the range of 66-75% in treatment-naive patients and 59-66% in treatment-experienced patients with HCV genotype 1 infection. Studies of second-generation protease inhibitors, with the potential advantage of improved potency, drug metabolism and pharmacokinetics profile, are already underway. Inhibitors of the HCV NS5A protein and NS5B polymerase are potentially active across different HCV genotypes and have shown promising antiviral efficacy in early clinical studies. Other emerging mechanisms include silymarin components and inhibitors of cell proteins required for HCV replication. While improved formulations of current HCV therapies are also being developed, future hopes lie on the combination of direct-acting antivirals with the eventual possibility of interferon-free treatment regimens. PMID:21813371

  5. New hepatitis C therapies in clinical development.

    PubMed

    Vermehren, Johannes; Sarrazin, Christoph

    2011-07-25

    With the current standard of care for the treatment of chronic hepatitis C, a combination of pegylated interferon alfa and ribavirin, sustained virologic response rates can be achieved in approximately 50% of patients only. - Improved understanding of the viral life cycle has led to the identification of numerous potential targets for novel, direct-acting antiviral compounds. Inhibitors of the NS3/4A protease are currently the most advanced in clinical development. Recently completed phase 3 studies of the two protease inhibitors telaprevir and boceprevir, each given in combination with standard of care, yielded sustained virologic response rates in the range of 66-75% in treatment-naive patients and 59-66% in treatment-experienced patients with HCV genotype 1 infection. Studies of second-generation protease inhibitors, with the potential advantage of improved potency, drug metabolism and pharmacokinetics profile, are already underway. - Inhibitors of the HCV NS5A protein and NS5B polymerase are potentially active across different HCV genotypes and have shown promising antiviral efficacy in early clinical studies. Other emerging mechanisms include silymarin components and inhibitors of cell proteins required for HCV replication. - While improved formulations of current HCV therapies are also being developed, future hopes lie on the combination of direct-acting antivirals with the eventual possibility of interferon-free treatment regimens.

  6. A comparative analysis of frog early development

    PubMed Central

    del Pino, Eugenia M.; Venegas-Ferrín, Michael; Romero-Carvajal, Andrés; Montenegro-Larrea, Paola; Sáenz-Ponce, Natalia; Moya, Iván M.; Alarcón, Ingrid; Sudou, Norihiro; Yamamoto, Shinji; Taira, Masanori

    2007-01-01

    The current understanding of Xenopus laevis development provides a comparative background for the analysis of frog developmental modes. Our analysis of development in various frogs reveals that the mode of gastrulation is associated with developmental rate and is unrelated to egg size. In the gastrula of the rapidly developing embryos of the foam-nesting frogs Engystomops coloradorum and Engystomops randi, archenteron and notochord elongation overlapped with involution at the blastopore lip, as in X. laevis embryos. In embryos of dendrobatid frogs and in the frog without tadpoles Eleutherodactylus coqui, which develop somewhat more slowly than X. laevis, involution and archenteron elongation concomitantly occurred during gastrulation; whereas elongation of the notochord and, therefore, dorsal convergence and extension, occurred in the postgastrula. In contrast, in the slow developing embryos of the marsupial frog Gastrotheca riobambae, only involution occurred during gastrulation. The processes of archenteron and notochord elongation and convergence and extension were postgastrulation events. We produced an Ab against the homeodomain protein Lim1 from X. laevis as a tool for the comparative analysis of development. By the expression of Lim1, we were able to identify the dorsal side of the G. riobambae early gastrula, which otherwise was difficult to detect. Moreover, the Lim1 expression in the dorsal lip of the blastopore and notochord differed among the studied frogs, indicating variation in the timing of developmental events. The variation encountered gives evidence of the modular character of frog gastrulation. PMID:17606898

  7. Astronewt: early development of newt in space

    NASA Astrophysics Data System (ADS)

    Mogami, Y.; Imamizo, M.; Yamashita, M.; Izumi-Kurotani, A.; Wiederhold, M. L.; Koike, H.; Asashima, M.

    AstroNewt experiment explores the effects of earth gravity on the early development of Japanese red-bellied newt, Cynops pyrrhogaster. Since female newts keep spermatophore in cloaca, fertilized eggs could be obtained without mating. Fertilization of newt's egg occurs just prior to spawning, so that gonadotrophic cues applied to females in orbit leads to laying eggs fertilized just in space. A property of newt being kept in hibernation at low temperature may be of great help for the space experiment carried out with much limited resources. A general outline of the AstroNewt project is shown here in addition to some technical advances for the development of the project. Experimental schemes of two space experiments (IML-2 in summer 1994 and unmanned SFU at the beginning of 1995) are also shown.

  8. Vegfa Impacts Early Myocardium Development in Zebrafish

    PubMed Central

    Zhu, Diqi; Fang, Yabo; Gao, Kun; Shen, Jie; Zhong, Tao P.; Li, Fen

    2017-01-01

    Vascular endothelial growth factor A (Vegfa) signaling regulates cardiovascular development. However, the cellular mechanisms of Vegfa signaling in early cardiogenesis remain poorly understood. The present study aimed to understand the differential functions and mechanisms of Vegfa signaling in cardiac development. A loss-of-function approach was utilized to study the effect of Vegfa signaling in cardiogenesis. Both morphants and mutants for vegfaa display defects in cardiac looping and chamber formation, especially the ventricle. Vegfa regulates the heart morphogenesis in a dose-dependent manner. Furthermore, the initial fusion of the bilateral myocardium population is delayed rather than endocardium. The results demonstrate that Vegfa signaling plays a direct impact on myocardium fusion, indicating that it is the initial cause of the heart defects. The heart morphogenesis is regulated by Vegfa in a dose-dependent manner, and later endocardium defects may be secondary to impaired myocardium–endocardium crosstalk. PMID:28230770

  9. Early development of the vertebral column.

    PubMed

    Scaal, Martin

    2016-01-01

    The segmental organization of the vertebrate body is most obviously visible in the vertebral column, which consists of a series of vertebral bones and interconnecting joints and ligaments. During embryogenesis, the vertebral column derives from the somites, which are the primary segments of the embryonic paraxial mesoderm. Anatomical, cellular and molecular aspects of vertebral column development have been of interest to developmental biologists for more than 150 years. This review briefly summarizes the present knowledge on early steps of vertebral column development in amniotes, starting from sclerotome formation and leading to the establishment of the anatomical bauplan of the spine composed of vertebral bodies, vertebral arches, intervertebral discs and ribs, and their specific axial identities along the body axis.

  10. Development of Life on Early Mars

    NASA Technical Reports Server (NTRS)

    Gibson, Everett K.; McKay, David S.; Thomas-Keprta, Kathie L.; Clemett, Simon J.; Wentworth, Susan J.

    2009-01-01

    Exploration of Mars has begun to unveil the history of the planet. Combinations of remote sensing, in situ compositional measurements and photographic observations have shown Mars had a dynamic and active geologic evolution. Mars geologic evolution encompassed conditions that were suitable for supporting life. A habitable planet must have water, carbon and energy sources along with a dynamic geologic past. Mars meets all of these requirements. The first 600 My of Martian history were ripe for life to develop because of the abundance of (i) Water- as shown by carved canyons and oceans or lakes with the early presence of near surface water shown by precipitated carbonates in ALH84001, well-dated at 3.9 Gy, (ii) Energy from the original accretional processes, a molten core which generated a strong magnetic field leaving a permanent record in the early crust, active volcanism continuing throughout Martian history, and continuing impact processes, (iii) Carbon, water and a likely thicker atmosphere from extensive volcanic outgassing (i.e. H20, CO2, CH4, CO, O2, N2, H2S, SO2, etc.) and (iv) crustal tectonics as revealed by faulting and possible plate movement reflected by the magnetic pattern in the crust [1]. The question arises: "Why would life not develop from these favorable conditions on Mars in its first 600 My?" During this period, environmental near-surface conditions on Mars were more favorable to life than at any later time. Standing bodies of water, precipitation and flowing surface water, and possibly abundant hydrothermal energy would favor the formation of early life. (Even if life developed elsewhere on Earth, Venus, or on other bodies-it was transported to Mars where surface conditions were suitable for life to evolve). The commonly stated requirement that life would need hundreds of millions of year to get started is only an assumption; we know of no evidence that requires such a long interval for the development of life, if the proper habitable

  11. Cell fate regulation in early mammalian development

    NASA Astrophysics Data System (ADS)

    Oron, Efrat; Ivanova, Natalia

    2012-08-01

    Preimplantation development in mammals encompasses a period from fertilization to implantation and results in formation of a blastocyst composed of three distinct cell lineages: epiblast, trophectoderm and primitive endoderm. The epiblast gives rise to the organism, while the trophectoderm and the primitive endoderm contribute to extraembryonic tissues that support embryo development after implantation. In many vertebrates, such as frog or fish, maternally supplied lineage determinants are partitioned within the egg. Cell cleavage that follows fertilization results in polarization of these factors between the individual blastomeres, which become restricted in their developmental fate. In contrast, the mouse oocyte and zygote lack clear polarity and, until the eight-cell stage, individual blastomeres retain the potential to form all lineages. How are cell lineages specified in the absence of a maternally supplied blueprint? This is a fundamental question in the field of developmental biology. The answer to this question lies in understanding the cell-cell interactions and gene networks involved in embryonic development prior to implantation and using this knowledge to create testable models of the developmental processes that govern cell fates. We provide an overview of classic and contemporary models of early lineage development in the mouse and discuss the emerging body of work that highlights similarities and differences between blastocyst development in the mouse and other mammalian species.

  12. 45 CFR 1304.21 - Education and early childhood development.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Education and early childhood development. 1304.21... GRANTEE AND DELEGATE AGENCIES Early Childhood Development and Health Services § 1304.21 Education and early childhood development. (a) Child development and education approach for all children. (1) In order...

  13. Early Literacy and Early Numeracy: The Value of Including Early Literacy Skills in the Prediction of Numeracy Development

    ERIC Educational Resources Information Center

    Purpura, David J.; Hume, Laura E.; Sims, Darcey M.; Lonigan, Cristopher J.

    2011-01-01

    The purpose of this study was to examine whether early literacy skills uniquely predict early numeracy skills development. During the first year of the study, 69 3- to 5-year-old preschoolers were assessed on the Preschool Early Numeracy Skills (PENS) test and the Test of Preschool Early Literacy Skills (TOPEL). Participants were assessed again a…

  14. Early Literacy and Early Numeracy: The Value of Including Early Literacy Skills in the Prediction of Numeracy Development

    ERIC Educational Resources Information Center

    Purpura, David J.; Hume, Laura E.; Sims, Darcey M.; Lonigan, Cristopher J.

    2011-01-01

    The purpose of this study was to examine whether early literacy skills uniquely predict early numeracy skills development. During the first year of the study, 69 3- to 5-year-old preschoolers were assessed on the Preschool Early Numeracy Skills (PENS) test and the Test of Preschool Early Literacy Skills (TOPEL). Participants were assessed again a…

  15. Attachment and Early Language Development: Implications for Early Intervention

    ERIC Educational Resources Information Center

    Day, Crystal

    2007-01-01

    It has been proposed that early language is acquired in the context of interpersonal interactions, with parent-child interactions serving as an important foundation (Nicely, Tamis-LeMonda, & Bornstein, 1999; Sachs, 2005; Tamis-LeMonda, Cristofaro, Rodriguez, & Bornstein, 2006). The purpose of this article is to review the literature on maternal…

  16. Early development of grateloupia turuturu (Halymeniaceae, Rhodophyta)

    NASA Astrophysics Data System (ADS)

    Wang, Gaoge; Jiang, Chunmei; Wang, Shasha; Wei, Xiaojiao; Zhao, Fengjuan

    2012-03-01

    Grateloupia turuturu is a commercial red alga with potential value in nutraceuticals and pharmaceuticals. To supplement information on its life history and verify whether carpospores can be used for seedling culture, early development of G. turuturu was investigated under culture conditions (27°C, 10-13 μol/(m2·s) in irradiance, photoperiod 10:14 h L:D). Three physiological stages were recognized by continuous microscopic observation: division stage, discoid crust stage, and juvenile seedling stage. At the beginning of the division stage, the carpospores developed germ tubes into which the carpospore protoplasm was evacuated, and then the carpospore protoplasm in the germ tubes began to divide continuously until discoid crusts formed. Finally, upright thalli appeared on the discoid crusts and developed into juvenile seedlings. It took about 60 days for carpospores to develop into juvenile seedlings. The growth parameters, including germination rate for carpospores and discoid crust diameter, were recorded. These results contribute more information on the life cycle, and at the same time are of great significance in the scaling-up of artificial seedling cultures of G. turuturu.

  17. Purpose and Character Development in Early Adolescence.

    PubMed

    Malin, Heather; Liauw, Indrawati; Damon, William

    2017-02-08

    Character development in adolescence is of growing interest among psychology researchers and educators, yet there is little consensus about how character should be defined and studied among developmental scientists. In particular, there is no fully developed framework for investigating the developmental relationships among different character strengths. This study examines the developmental relations between purpose and three other key character strengths that emerge during early adolescence: gratitude, compassion, and grit. We analyzed survey (n = 1005, 50.1% female, 24.1% Caucasian, 43.6% African American, 18.9% Hispanic, 11.9% Asian American) and interview (n = 98) data from a longitudinal study of character development among middle school students from the United States. Data were collected over the course of 2 years, with surveys conducted four times at 6-month intervals and interviews conducted twice at 12-month intervals. Data analyses showed small but significant correlations between purpose and each of the other three character strengths under investigation. Interview data revealed patterns in ways that adolescents acted on their purposeful aspirations; and interview analyses identified qualitative differences in expressions of gratitude and compassion between adolescents who were fully purposeful and those who were not. The findings suggest that character development can be better understood by investigating the multidirectional developmental relationships among different character strengths.

  18. The use of electro-acoustic impedance measurements in detecting early clinical otosclerosis.

    PubMed

    Van Wagoner, R S; Campbell, J D

    1976-02-01

    The first evidence that sodium fluoride (NaFl) can stop the otosclerotic process was recently presented. This development has placed new emphasis on the early detection of clinical otosclerosis. Electro-acoustic impedance measurements often detect minute changes in absolute impedance and compliance of the ossicular chain. The most valuable diagnostic information, however, is a negative on-off (biphasic) type of acoustic reflex. These results are often evident prior to the detection of positive clinical signs of otosclerosis. The negative on-off acoustic reflex is reviewed in this paper along with case discussions involving medical/surgical management of early otosclerosis.

  19. Communication and community development: early child development programs.

    PubMed

    Wood, F; Reinhold, A J

    1993-01-01

    Community-based groups are organized around particular aspects of early childhood development (ECD), such as literacy, parent education, and early childhood activities. In the Colombian national program, community households call upon women to devote a portion of their home to organized child care for minimal material reward. The Indian Child Development Service subsidizes the payment of organizers; and Kenyan parents construct basic preschool facilities, provide school lunches, and subsidize a teacher. In such cases the government plays a subordinate role, while the burden of program maintenance is carried by the community. These programs share the characteristics that children and adults learn side by side; adult learning ranges from women's literacy, to health, organizational issues, or small-scale economic development; a strong cultural component emphasizes mother tongue language learning, indigenous child-rearing practices, and local working models; physical structures are in homes; capacity-building for the adults is central which will be transferred to other spheres of community life. In the remote coastal villages of Colombia, an organization called Promesa works with mothers on designing their preschool children's educational activities. Promesa began to confront other priority needs in the villages, especially in environmental health and malaria control. A 1990 assessment related that participants' pride, self-confidence, and ability to solve problems regarding the healthy development of their children increased; groups learned to make use of the physical, human, and institutional resources from their environments; and participants' children remained in school and performed better. Conclusions from a decade of loose experimentation suggest that through communication community women can be organized to provide basic early education and early childhood activities can help rural children over the cultural barrier of school.

  20. Early development and embryology of the platypus.

    PubMed Central

    Hughes, R L; Hall, L S

    1998-01-01

    Information on the pre-hatching development of the platypus, Ornithorhynchus anatinus, is reliant on a small number of specimens, whose precise age is unknown. Material collected for J. P. Hill and now housed in the Hubrecht International Embryological Laboratory, Utrecht, contributes a major source of specimens. This paper presents new observations on developmental stages from the Hill collection, which allow for a more complete description of pre-hatching development. A feature of the pre-embryonic development of the platypus is the incomplete meroblastic cleavage. A column of fine yolk spheres extends from beneath the embryonic blastodisc towards the centre of a yolky vitellus, as seen in birds. The major expansion of extra-embryonic membranes occurs after the formation of the primitive streak. The primitive streak develops within an embryonal area as part of the superficial wall of the yolk-sac, a feature also shared with marsupials, birds and reptiles. The full-term, subspheroidal, intrauterine egg of the platypus has a major axis of about 17 mm and contains a flat, 19-20 somite, neurula-stage embryo which has prominent trigeminal ganglion primordia. The embryo at this stage is in a period of rapid modelling of the major early organ primordia of the nervous system, cardiovascular system, excretory system, and somite-derived components of the body wall. Soon after laying, five primary brain vesicles are present, the trigeminal ganglia CN5 as well as CN7, CN8, CN9, CN10, CN11 and CN12 are well developed. The alimentary system has an expanded stomach, pancreatic primordia and a gall bladder. Mesonephric tubules are associated with patent mesonephric ducts, which empty laterally into the cloaca. Extra-embryonic membranes at this stage show an extensive chorioamniotic connection that extends through the greater part of the caudal half of fused amniotic folds. The vascularized yolk-sac consists of a superficial yolk-sac omphalopleura and a deep yolk

  1. Adaptive Clinical Trials: Overview of Early-Phase Designs and Challenges

    PubMed Central

    Marchenko, Olga; Fedorov, Valerii; Lee, J. Jack; Nolan, Christy; Pinheiro, José

    2016-01-01

    In this paper, we describe developments in adaptive design methodology and discuss implementation strategies and operational challenges in early phase adaptive clinical trials. The BATTLE trial – the first completed, biomarker-based, Bayesian adaptive randomized study in lung cancer – is presented as a case study to illustrate main ideas and share learnings. PMID:28670507

  2. Clinical translation of ultraviolet autofluorescence microscopy towards endomicroscopy for early detection of cancer

    NASA Astrophysics Data System (ADS)

    Lin, Bevin; Urayama, Shiro; Saroufeem, Ramez M. G.; Matthews, Dennis L.; Demos, Stavros G.

    2010-12-01

    The non-invasiveness of autofluorescence technology may reduce sampling error and time delay for histopathology diagnosis. We establish biophotonic methods and guidelines to visualize and interpret early epithelial tissue changes that signify disease. Flexible and rigid fiber endomicroscopy instrumentation design parameters feasible for translation towards clinical use are in development.

  3. Strategic clinical networks in Alberta: Structures, processes, and early outcomes.

    PubMed

    Noseworthy, Tom; Wasylak, Tracy; O'Neill, Blair

    2015-11-01

    In June 2012, Alberta Health Services introduced Strategic Clinical Networks (SCNs) as engines of innovation. The SCNs are collaborative clinical teams, with a provincial strategic mandate and with goals of achieving best outcomes, seeking greatest value for money and engaging clinicians in all aspects of the work. The SCNs are led by clinicians, driven by clinical needs, based on measurement and best evidence, and supported by research expertise, infrastructure, quality improvement, and analytic resources. Eleven SCNs are operational, with five others planned. Early measurable value is demonstrable in each. Examples include improving care and outcomes following stroke, reducing use of anti-psychotics in Long-Term Care (LTC), and improving surgical safety through effective implementation of the Safe Surgery Checklist. © 2015 The Canadian College of Health Leaders.

  4. The early evolution of Jean Piaget's clinical method.

    PubMed

    Mayer, Susan Jean

    2005-11-01

    This article analyzes the early evolution of Jean Piaget's renowned "clinical method" in order to investigate the method's strikingly original and generative character. Throughout his 1st decade in the field, Piaget frequently discussed and justified the many different approaches to data collection he used. Analysis of his methodological progression during this period reveals that Piaget's determination to access the genuine convictions of children eventually led him to combine 3 distinct traditions in which he had been trained-naturalistic observation, psychometrics, and the psychiatric clinical examination. It was in this amalgam, first evident in his 4th text, that Piaget discovered the clinical dynamic that would drive the classic experiments for which he is most well known.

  5. The Early Development of Kinetic Theory.

    ERIC Educational Resources Information Center

    Whitaker, Robert D.

    1979-01-01

    A review of the work of Bernoulli and other early contributors to kinetic theory. One significant point is that the most outstanding work in this early period was done by a little-known Scotsman, John J. Waterston. (BB)

  6. The Early Development of Kinetic Theory.

    ERIC Educational Resources Information Center

    Whitaker, Robert D.

    1979-01-01

    A review of the work of Bernoulli and other early contributors to kinetic theory. One significant point is that the most outstanding work in this early period was done by a little-known Scotsman, John J. Waterston. (BB)

  7. Early development of sigma-receptor ligands.

    PubMed

    Narayanan, Sanju; Bhat, Rohit; Mesangeau, Christophe; Poupaert, Jacques H; McCurdy, Christopher R

    2011-01-01

    Sigma receptors (σ-1 and σ-2) are non-opioid proteins implicated in the pathophysiology of various neurological disorders and cancer. The σ-1 subtype is a chaperon protein widely distributed in the CNS and peripheral tissues. These receptors are involved in the modulation of K(+)- and Ca(2+)-dependent signaling cascades at the endoplasmic reticulum and modulation of neurotransmitter release. σ-1 receptors are emerging targets for the treatment of neurophychiatric diseases (schizophrenia and depression) and cocaine addiction. σ-2 receptors are lipid raft proteins. They are highly expressed on many tumor cells and hence considered potential targets for anticancer drugs. σ receptors bind to a diverse class of pharmacological compounds like cocaine, methamphetamine, benzomorphans like (±)-pentazocine, (±)-SKF-10,047 and endogenous neurosteroids and sphingolipids. In this review we focus on the early development of σ receptor-specific ligands and radiolabeling agents.

  8. Elfin is expressed during early heart development.

    PubMed

    Kotaka, M; Lau, Y M; Cheung, K K; Lee, S M; Li, H Y; Chan, W Y; Fung, K P; Lee, C Y; Waye, M M; Tsui, S K

    Elfin (previously named CLIM1) is a protein that possesses an N-terminal PDZ domain and a C-terminal LIM domain. It belongs to the family of Enigma proteins. Enigma proteins are a family of cytoplasmic proteins that contain an N-terminal PDZ domain and a series of C-terminal LIM domains. By virtue of these two protein interacting domains, Enigma proteins are capable of protein-protein interactions. It has been proposed that Enigma proteins may act as adapters between kinases and the cytoskeleton. We have previously shown that Elfin is most abundantly expressed in the heart and it colocalizes with alpha-actinin 2 at the Z-disks of the myocardium. In this report, Elfin was shown to localize at the actin stress fibers of myoblasts, as revealed by green fluorescent protein (GFP) tagging. In situ hybridization and immunostaining showed that Elfin expression begins at an early stage in mouse development and is present throughout the developing heart. Taken together, our experimental results suggest that Elfin may play an important role in myofibrillogenesis and heart development.

  9. New developments in clinical CARS

    NASA Astrophysics Data System (ADS)

    Weinigel, Martin; Breunig, Hans Georg; Kellner-Höfer, Marcel; Bückle, Rainer; Darvin, Maxim; Lademann, Juergen; König, Karsten

    2013-02-01

    We combined two-photon fluorescence and coherent anti-Stokes Raman scattering (CARS) imaging in a clinical hybrid multiphoton tomograph for in vivo imaging of human skin. The clinically approved TPEF/CARS system provides simultaneous imaging of endogenous fluorophores and non-fluorescent lipids. The Stokes laser for the two-beam configuration of CARS is based on spectral broadening of femtosecond laser pulses in a photonic crystal fiber (PCF). We report on the highly flexible medical TPEF/CARS tomograph MPTflex®-CARS with an articulated arm and first in vivo measurements on human skin.

  10. Early clinical markers of central nervous system involvement in mucopolysaccharidosis type II.

    PubMed

    Holt, Joshua; Poe, Michele D; Escolar, Maria L

    2011-08-01

    To identify early clinical markers of neurologic involvement in mucopolysaccharidosis type II. A retrospective review of neurobehavioral standardized assessments of patients with mucopolysaccharidosis type II evaluated at the Program for Neurodevelopmental Function in Rare Disorders was completed. Patients were grouped based on the presence or absence of central nervous system (CNS) involvement at the most recent evaluation. Differences in early signs and symptoms between resulting cohorts were tested for significance, and an index severity score was developed. Between December 2002 and November 2010, clinical evaluations of 49 patients and 151 patient encounters were reviewed. Thirty-seven patients exhibited neurologic deterioration. Of the 25 signs evaluated, 7 early clinical markers were strongly correlated with subsequent cognitive dysfunction: sleep disturbance, increased activity, behavior difficulties, seizure-like behavior, perseverative chewing behavior, and inability to achieve bowel training and bladder training. A new severity score index was developed, with a score ≥3 indicating a high likelihood of developing CNS disease. Seven early clinical markers and a severity score index of CNS involvement can be used for initial screening of children who might benefit from CNS-directed therapies. Copyright © 2011 Mosby, Inc. All rights reserved.

  11. Spontaneous Primary Intraventricular Hemorrhage: Clinical Features and Early Outcome

    PubMed Central

    Arboix, Adrià; García-Eroles, Luis; Vicens, Adela; Oliveres, Montserrat; Massons, Joan

    2012-01-01

    Purpose. Primary hemorrhage in the ventricular system without a recognizable parenchymal component is very rare. This single-center retrospective study aimed to further characterize the clinical characteristics and early outcome of this stroke subtype. Methods. All patients with primary intraventricular hemorrhage included in a prospective hospital-based stroke registry over a 19-year period were assessed. A standardized protocol with 161 items, including demographics, risk factors, clinical data, neuroimaging findings, and outcome, was used for data collection. A comparison was made between the groups of primary intraventricular hemorrhage and subcortical intracerebral hemorrhage. Predictors of primary intraventricular hemorrhage were identified by logistic regression analysis. Results. There were 12 patients with primary intraventricular hemorrhage (0.31% of all cases of stroke included in the database) and 133 in the cohort of subcortical hemorrhage. Very old age (≥85 years) (odds ratio (OR) 9.89), atrial fibrillation (OR 8.92), headache (OR 6.89), and altered consciousness (OR 4.36) were independent predictors of intraventricular hemorrhage. The overall in-hospital mortality rate was 41.7% (5/12) but increased to 60% (3/5) in patients aged 85 years or older. Conclusion. Although primary intraventricular hemorrhage is uncommon, it is a severe clinical condition with a high early mortality. The prognosis is particularly poor in very old patients. PMID:22966468

  12. Calcium at fertilization and in early development

    PubMed Central

    Whitaker, Michael

    2012-01-01

    Fertilization calcium waves are introduced and the evidence from which we can infer general mechanisms of these waves is presented. The two main classes of hypothesis put forward to explain the generation of the fertilization calcium wave are set out and it is concluded that initiation of the fertilization calcium wave can be most generally explained in inverterbrates by a mechanism in which an activating substance enters the egg from the sperm on sperm-egg fusion, activating the egg by stimulating phospholipase C activation through a src family kinase pathway and in mammals by the diffusion of a sperm-specific phospholipase C from sperm to egg on sperm-egg fusion. The fertilization calcium wave is then set into the context of cell cycle control and the mechanism of repetitive calcium spiking in mammalian eggs is investigated. Evidence that calcium signals control cell division in early embryos is reviewed, and it is concluded that calcium signals are essential at all three stages of cell division in early embryos. Evidence that phosphoinositide signalling pathways control the resumption of meiosis during oocyte maturation is considered. It is concluded on balance that the evidence points to a need for phosphoinositide/calcium signalling during resumption of meiosis. Changes to the calcium signalling machinery occur during meiosis to enable the production of a calcium wave in the mature oocyte when it is fertilized; evidence that the shape and structure of the endoplasmic reticulum alters dynamically during maturation and after fertilization is reviewed and the link between ER dynamics and the cytoskeleton is discussed. There is evidence that calcium signalling plays a key part in the development of patterning in early embryos. Morphogenesis in ascidian, frog and zebrafish embryos is briefly described to provide the developmental context in which calcium signals act. Intracellular calcium waves that may play a role in axis formation in ascidian are discussed

  13. Clinical Decision Support for Early Recognition of Sepsis.

    PubMed

    Amland, Robert C; Hahn-Cover, Kristin E

    2016-01-01

    Sepsis is an inflammatory response triggered by infection, with a high in-hospital mortality rate. Early recognition and treatment can reverse the inflammatory response, with evidence of improved patient outcomes. One challenge clinicians face is identifying the inflammatory syndrome against the background of the patient's infectious illness and comorbidities. An approach to this problem is implementation of computerized early warning tools for sepsis. This multicenter retrospective study sought to determine clinimetric performance of a cloud-based computerized sepsis clinical decision support system (CDS), understand the epidemiology of sepsis, and identify opportunities for quality improvement. Data encompassed 6200 adult hospitalizations from 2012 through 2013. Of 13% patients screened-in, 51% were already suspected to have an infection when the system activated. This study focused on a patient cohort screened-in before infection was suspected; median time from arrival to CDS activation was 3.5 hours, and system activation to diagnostic collect was another 8.6 hours.

  14. Early treatment of posterior crossbite - a randomised clinical trial

    PubMed Central

    2013-01-01

    Background The aim of this randomised clinical trial was to assess the effect of early orthodontic treatment in contrast to normal growth effects for functional unilateral posterior crossbite in the late deciduous and early mixed dentition by means of three-dimensional digital model analysis. Methods This randomised clinical trial was assessed to analyse the orthodontic treatment effects for patients with functional unilateral posterior crossbite in the late deciduous and early mixed dentition using a two-step procedure: initial maxillary expansion followed by a U-bow activator therapy. In the treatment group 31 patients and in the control group 35 patients with a mean age of 7.3 years (SD 2.1) were monitored. The time between the initial assessment (T1) and the follow-up (T2) was one year. The orthodontic analysis was done by a three-dimensional digital model analysis. Using the ‘Digimodel’ software, the orthodontic measurements in the maxilla and mandible and for the midline deviation, the overjet and overbite were recorded. Results Significant differences between the control and the therapy group at T2 were detected for the anterior, median and posterior transversal dimensions of the maxilla, the palatal depth, the palatal base arch length, the maxillary arch length and inclination, the midline deviation, the overjet and the overbite. Conclusions Orthodontic treatment of a functional unilateral posterior crossbite with a bonded maxillary expansion device followed by U-bow activator therapy in the late deciduous and early mixed dentition is an effective therapeutic method, as evidenced by the results of this RCT. It leads to three-dimensional therapeutically induced maxillary growth effects. Dental occlusion is significantly improved, and the prognosis for normal craniofacial growth is enhanced. Trial registration Registration trial DRKS00003497 on DRKS PMID:23339736

  15. New dermatological biomedical microscopes for early clinical diagnostics

    NASA Astrophysics Data System (ADS)

    Goldman, Leon

    1993-09-01

    With the current developments in optics, including laser optics, there should be more progress on the development of instrumentation for dermatological diagnostics, even clinical diagnostics. This report introduces new microscopy, much still under development, and research. A frank appeal for this program is made for multi-discipline help from optical physicists, biophysicists, biomedical engineers, even laser biomedical engineers, investigative dermatologists, and pathologists. If one is allowed to say, the most current advanced clinical diagnostic microscope is the polarizing microscope under the stimulus of Rox Anderson, Lynn Drake, Steven Jacques, and Peter Dorogi. The other microscopes for clinical dermatological research to be developed include the confocal scanning microscopy with the emphasis for living tissue, the ultrasonic biomedical microscope (UBM) for dermatology, and the holographic microscope, related to our studies on the biomedical aspects of optical phase conjugation. All these are introduced briefly for our studies and for definite pleas to help us.

  16. Investigational drugs in early development for treating dengue infection.

    PubMed

    Beesetti, Hemalatha; Khanna, Navin; Swaminathan, Sathyamangalam

    2016-09-01

    Dengue has emerged as the most significant arboviral disease of the current century. A drug for dengue is an urgent unmet need. As conventional drug discovery efforts have not produced any promising clinical candidates, there is a shift toward re-positioning pre-existing drugs for dengue to fast-track dengue drug development. This article provides an update on the current status of recently completed and ongoing dengue drug trials. All dengue drug trials described in this article were identified from a list of >230 trials that were returned upon searching the World Health Organization's International Clinical Trials Registry Platform web portal using the search term 'dengue' on December 31(st), 2015. None of the handful of drugs tested so far has yielded encouraging results. Early trial experience has served to emphasize the challenge of drug testing in the short therapeutic time window available, the need for tools to predict 'high-risk' patients early on and the limitations of the existing pre-clinical model systems. Significant investment of efforts and resources is a must before the availability of a safe, effective and inexpensive dengue drug becomes a reality. Currently, supportive fluid therapy remains the only option available for dengue treatment.

  17. Early Years Practitioners' Views on Early Personal, Social and Emotional Development

    ERIC Educational Resources Information Center

    Aubrey, Carol; Ward, Karen

    2013-01-01

    Current policy guidance stresses the need for early identification of obstacles to learning and appropriate intervention. New standards for learning (Early Years Foundation Stage) place personal, social and emotional development (PSED) as central to learning and development. This paper reports a survey and follow-up interviews with early years…

  18. Digital Breast Tomosynthesis: Lessons Learned from Early Clinical Implementation

    PubMed Central

    Maidment, Andrew D. A.; Weinstein, Susan P.; Roth, Susan Orel; Conant, Emily F.

    2014-01-01

    The limitations of mammography are well known and are partly related to the fact that with conventional imaging, the three-dimensional volume of the breast is imaged and presented in a two-dimensional format. Because normal breast tissue is similar in x-ray attenuation to some breast cancers, clinically relevant malignancies may be obscured by normal overlapping tissue. In addition, complex areas of normal tissue may be perceived as suspicious. The limitations of two-dimensional breast imaging lead to low sensitivity in detecting some cancers and high false-positive recall rates. Although mammographic screening has been shown to reduce breast cancer deaths by approximately 30%, controversy exists over when and how often screening mammography should occur. Digital breast tomosynthesis (DBT) is rapidly being implemented in breast imaging clinics around the world as early clinical data demonstrate that it may address some of the limitations of conventional mammography. With DBT, multiple low-dose x-ray images are acquired in an arc and reconstructed to create a three-dimensional image, thus minimizing the impact of overlapping breast tissue and improving lesion conspicuity. Early studies of screening DBT have shown decreased false-positive callback rates and increased rates of cancer detection (particularly for invasive cancers), resulting in increased sensitivity and specificity. In our clinical practice, we have completed more than 2 years of using two-view digital mammography combined with two-view DBT for all screening and select diagnostic imaging examinations (over 25,000 patients). Our experience, combined with previously published data, demonstrates that the combined use of DBT and digital mammography is associated with improved outcomes for screening and diagnostic imaging. Online supplemental material is available for this article. ©RSNA, 2014 PMID:25019451

  19. Clinical Impact of Vaccine Development.

    PubMed

    Nambiar, Puja H; Daza, Alejandro Delgado; Livornese, Lawrence L

    2016-01-01

    The discovery and development of immunization has been a singular improvement in the health of mankind. This chapter reviews currently available vaccines, their historical development, and impact on public health. Specific mention is made in regard to the challenges and pursuit of a vaccine for the human immunodeficiency virus as well as the unfounded link between autism and measles vaccination.

  20. Early development and embryology of the platypus.

    PubMed

    Hughes, R L; Hall, L S

    1998-07-29

    Information on the pre-hatching development of the platypus, Ornithorhynchus anatinus, is reliant on a small number of specimens, whose precise age is unknown. Material collected for J. P. Hill and now housed in the Hubrecht International Embryological Laboratory, Utrecht, contributes a major source of specimens. This paper presents new observations on developmental stages from the Hill collection, which allow for a more complete description of pre-hatching development. A feature of the pre-embryonic development of the platypus is the incomplete meroblastic cleavage. A column of fine yolk spheres extends from beneath the embryonic blastodisc towards the centre of a yolky vitellus, as seen in birds. The major expansion of extra-embryonic membranes occurs after the formation of the primitive streak. The primitive streak develops within an embryonal area as part of the superficial wall of the yolk-sac, a feature also shared with marsupials, birds and reptiles. The full-term, subspheroidal, intrauterine egg of the platypus has a major axis of about 17 mm and contains a flat, 19-20 somite, neurula-stage embryo which has prominent trigeminal ganglion primordia. The embryo at this stage is in a period of rapid modelling of the major early organ primordia of the nervous system, cardiovascular system, excretory system, and somite-derived components of the body wall. Soon after laying, five primary brain vesicles are present, the trigeminal ganglia CN5 as well as CN7, CN8, CN9, CN10, CN11 and CN12 are well developed. The alimentary system has an expanded stomach, pancreatic primordia and a gall bladder. Mesonephric tubules are associated with patent mesonephric ducts, which empty laterally into the cloaca. Extra-embryonic membranes at this stage show an extensive chorioamniotic connection that extends through the greater part of the caudal half of fused amniotic folds. The vascularized yolk-sac consists of a superficial yolk-sac omphalopleura and a deep yolk

  1. Early lexical development in Spanish-speaking infants and toddlers.

    PubMed

    Jackson-Maldonado, D; Thal, D; Marchman, V; Bates, E; Gutierrez-Clellen, V

    1993-10-01

    This paper describes the early lexical development of a group of 328 normal Spanish-speaking children aged 0;8 to 2;7. First the development and structure of a new parent report instrument, Inventario del Desarollo de Habilidades Communicativas is described. Then five studies carried out with the instrument are presented. In the first study vocabulary development of Spanish-speaking infants and toddlers is compared to that of English-speaking infants and toddlers. The English data were gathered using a comparable parental report, the MacArthur Communicative Development Inventories. In the second study the general characteristics of Spanish language acquisition, and the effects of various demographic factors on that process, are examined. Study 3 examines the differential effects of three methods of collecting the data (mail-in, personal interview, and clinic waiting room administration). Studies 4 and 5 document the reliability and validity of the instrument. Results show that the trajectories of development are very similar for Spanish- and English-speaking children in this age range, that children from varying social groups develop similarly, and that mail-in and personal interview administration techniques produce comparable results. Inventories administered in a medical clinic waiting room, on the other hand, produced lower estimates of toddler vocabulary than the other two models.

  2. State Developments in Child Care and Early Education, 1999.

    ERIC Educational Resources Information Center

    Blank, Helen; Poersch, Nicole Oxendine

    This report provides highlights and updates regarding state actions on child care and early education issues during 1999. It is intended to serve as a supplement to "State Child Care and Early Education Development: Highlights and Updates for 1998" and "State Developments in Child Care and Early Education 1997." The information…

  3. From Neurons to Neighborhoods: The Science of Early Childhood Development.

    ERIC Educational Resources Information Center

    Shonkoff, Jack P., Ed.; Phillips, Deborah A., Ed.

    The Committee on Integrating the Science of Early Childhood Development reviewed an extensive, multi-disciplinary, and complex body of research covering the period from before birth to entry into Kindergarten to generate an integrated science of early childhood development and the role of early experiences. The result of the committee's review,…

  4. Early Parental Depression and Child Language Development

    ERIC Educational Resources Information Center

    Paulson, James F.; Keefe, Heather A.; Leiferman, Jenn A.

    2009-01-01

    Objective: To examine the effects of early maternal and paternal depression on child expressive language at age 24 months and the role that parent-to-child reading may play in this pathway. Participants and methods: The 9-month and 24-month waves from a national prospective study of children and their families, the Early Childhood Longitudinal…

  5. Early Childhood Development: Upgrading the Downgrader

    ERIC Educational Resources Information Center

    Parnell, Dale

    1973-01-01

    Argues that, properly implemented, early childhood education in basic skills will drastically cut the waste of millions of students sitting in classes and learning little or nothing because they have not mastered the prerequisites. The next step in education, according to the author, must be preschool and home-based early childhood education…

  6. Parental Obesity and Early Childhood Development.

    PubMed

    Yeung, Edwina H; Sundaram, Rajeshwari; Ghassabian, Akhgar; Xie, Yunlong; Buck Louis, Germaine

    2017-02-01

    Previous studies identified associations between maternal obesity and childhood neurodevelopment, but few examined paternal obesity despite potentially distinct genetic/epigenetic effects related to developmental programming. Upstate KIDS (2008-2010) recruited mothers from New York State (excluding New York City) at ∼4 months postpartum. Parents completed the Ages and Stages Questionnaire (ASQ) when their children were 4, 8, 12, 18, 24, 30, and 36 months of age corrected for gestation. The ASQ is validated to screen for delays in 5 developmental domains (ie, fine motor, gross motor, communication, personal-social functioning, and problem-solving ability). Analyses included 3759 singletons and 1062 nonrelated twins with ≥1 ASQs returned. Adjusted odds ratios (aORs) and 95% confidence intervals were estimated by using generalized linear mixed models accounting for maternal covariates (ie, age, race, education, insurance, marital status, parity, and pregnancy smoking). Compared with normal/underweight mothers (BMI <25), children of obese mothers (26% with BMI ≥30) had increased odds of failing the fine motor domain (aOR 1.67; confidence interval 1.12-2.47). The association remained after additional adjustment for paternal BMI (1.67; 1.11-2.52). Paternal obesity (29%) was associated with increased risk of failing the personal-social domain (1.75; 1.13-2.71), albeit attenuated after adjustment for maternal obesity (aOR 1.71; 1.08-2.70). Children whose parents both had BMI ≥35 were likely to additionally fail the problem-solving domain (2.93; 1.09-7.85). Findings suggest that maternal and paternal obesity are each associated with specific delays in early childhood development, emphasizing the importance of family information when screening child development. Copyright © 2017 by the American Academy of Pediatrics.

  7. Postsimulation debriefing to maximize clinical judgment development.

    PubMed

    Lusk, Janet M; Fater, Kerry

    2013-01-01

    With the increased prevalence of simulation as a teaching strategy, there remains a need to establish best practice guidelines to foster nursing education goals. One essential goal of nursing education is clinical judgment development. The debriefing component of simulation clearly provides a forum to enhance clinical judgment development. Following a literature review of debriefing in nursing and other disciplines, the authors suggest strategies that optimize debriefing after simulation as a means to promote clinical judgment among nursing students.

  8. Predicting persistent inflammatory arthritis amongst early arthritis clinic patients in the UK: is musculoskeletal ultrasound required?

    PubMed Central

    2013-01-01

    Introduction Analyses of large clinical datasets from early arthritis cohorts permit the development of algorithms that may be used for outcome prediction in individual patients. The value added by routine use of musculoskeletal ultrasound (MSUS) in an early arthritis setting, as a component of such predictive algorithms, remains to be determined. Methods The authors undertook a retrospective analysis of a large, true-to-life, observational inception cohort of early arthritis patients in Newcastle upon Tyne, UK, which included patients with inflammatory arthralgia but no clinically swollen joints. A pragmatic, 10-minute MSUS assessment protocol was developed, and applied to each of these patients at baseline. Logistic regression was used to develop two "risk metrics" that predicted the development of a persistent inflammatory arthritis (PIA), with or without the inclusion of MSUS parameters. Results A total of 379 enrolled patients were assigned definitive diagnoses after ≥12 months follow-up (median 28 months), of whom 162 (42%) developed a persistent inflammatory arthritis. A risk metric derived from 12 baseline clinical and serological parameters alone had an excellent discriminatory utility with respect to an outcome of PIA (area under receiver operator characteristic (ROC) curve 0.91; 95% CI 0.88 to 0.94). The discriminatory utility of a similar metric, which incorporated MSUS parameters, was not significantly superior (area under ROC curve 0.91; 95% CI 0.89 to 0.94). Neither did this approach identify an added value of MSUS over the use of routine clinical parameters in an algorithm for discriminating PIA patients whose outcome diagnosis was rheumatoid arthritis (RA). Conclusions MSUS use as a routine component of assessment in an early arthritis clinic did not add substantial discriminatory value to a risk metric for predicting PIA. PMID:24028567

  9. A novel primary care clinical prediction rule for early detection of osteoporosis.

    PubMed

    Kimber, Cheryl; Grimmer-Somers, Karen

    2011-01-01

    The effects of osteoporosis (OP) can be significantly slowed if disease is detected early. We report on a clinical risk prediction rule developed from patient histories taken in an orthopaedic outpatient clinic, before confirmatory testing for OP. Data were extracted from routine audits of consecutive records of patients with recent wrist fracture, comprising demographic details, medications, past and current disease, and fracture details. Clinical prediction rule elements were tested against clinical suspicion of OP. The clinical prediction elements comprised sex and age risk, medications that predispose patients to OP and/or falls, previous fractures and disease/medical conditions that are known OP risks. The best cut point (6.5) demonstrated 100% sensitivity with clinical suspicion of OP. Patient history information is often available before OP is clinically suspected or a definitive diagnosis is made. Our clinical prediction rule will be useful in primary care settings where objective measures of bone health are not readily available. It will raise OP awareness amongst health care providers and patients, particularly those not previously suspected of having OP. It will assist in identifying at-risk patients early and commencing them on appropriate management, without waiting for definitive bone health tests.

  10. Epigenetics and development of food allergy (FA) in early childhood.

    PubMed

    Hong, Xiumei; Wang, Xiaobin

    2014-09-01

    This review aims to highlight the latest advance on epigenetics in the development of food allergy (FA) and to offer future perspectives. FA, a condition caused by an immunoglobulin (Ig) E-mediated hypersensitivity reaction to food, has emerged as a major clinical and public health problem worldwide in light of its increasing prevalence, potential fatality, and significant medical and economic impact. Current evidence supports that epigenetic mechanisms are involved in immune regulation and that the epigenome may represent a key "missing piece" of the etiological puzzle for FA. There are a growing number of population-based epigenetic studies on allergy-related phenotypes, mostly focused on DNA methylation. Previous studies mostly applied candidate-gene approaches and have demonstrated that epigenetic marks are associated with multiple allergic diseases and/or with early-life exposures relevant to allergy development (such as early-life smoking exposure, air pollution, farming environment, and dietary fat). Rapid technological advancements have made unbiased genome-wide DNA methylation studies highly feasible, although there are substantial challenge in study design, data analyses, and interpretation of findings. In conclusion, epigenetics represents both an important knowledge gap and a promising research area for FA. Due to the early onset of FA, epigenetic studies of FA in prospective birth cohorts have the potential to better understand gene-environment interactions and underlying biological mechanisms in FA during critical developmental windows (preconception, in utero, and early childhood) and may lead to new paradigms in the diagnosis, prevention, and management of FA and provide novel targets for future drug discovery and therapies for FA.

  11. Clinical factors associated with early readmission among acutely decompensated heart failure patients

    PubMed Central

    Pierre-Louis, Bredy; Rodriques, Shareen; Gorospe, Vanessa; Guddati, Achuta K.; Ahn, Chul; Wright, Maurice

    2016-01-01

    Introduction Congestive heart failure (CHF) is a common cause of hospital readmission. Material and methods A retrospective study was conducted at Harlem Hospital in New York City. Data were collected for 685 consecutive adult patients admitted for decompensated CHF from March, 2009 to December, 2012. Variables including patient demographics, comorbidities, laboratory studies, and medical therapy were compared between CHF patient admissions resulting in early CHF readmission and not resulting in early CHF readmission. Results Clinical factors found to be independently significant for early CHF readmission included chronic obstructive pulmonary disease (odds ratio (OR) = 6.4), HIV infection (OR = 3.4), African-American ethnicity (OR = 2.2), systolic heart failure (OR = 1.9), atrial fibrillation (OR = 2.3), renal disease with glomerular filtration rate < 30 ml/min (OR = 2.7), evidence of substance abuse (OR = 1.7), and absence of angiotensin-converting enzyme inhibitors or angiotensin receptor blocker therapy after discharge (OR = 1.8). The ORs were used to develop a scoring system regarding the risk for early readmission. Conclusions Identifying patients with clinical factors associated with early CHF readmission after an index hospitalization for CHF using the proposed scoring system would allow for an early CHF readmission risk stratification protocol to target particularly high-risk patients. PMID:27279845

  12. How Early Child Care Affects Later Development. Science Briefs

    ERIC Educational Resources Information Center

    National Scientific Council on the Developing Child, 2007

    2007-01-01

    "Science Briefs" summarize the findings and implications of a recent study in basic science or clinical research. This brief reports on the study "Are there Long-Term Effects of Early Child Care?" (J. Belsky, D. L. Vandell, M. Burchinal, K. A. Clarke-Stewart, K. McCartney, M. T. Owen, M. T., and The NICHD Early Child Care Research Network).…

  13. How Early Child Care Affects Later Development. Science Briefs

    ERIC Educational Resources Information Center

    National Scientific Council on the Developing Child, 2007

    2007-01-01

    "Science Briefs" summarize the findings and implications of a recent study in basic science or clinical research. This brief reports on the study "Are there Long-Term Effects of Early Child Care?" (J. Belsky, D. L. Vandell, M. Burchinal, K. A. Clarke-Stewart, K. McCartney, M. T. Owen, M. T., and The NICHD Early Child Care Research Network).…

  14. First Principles for Early Grades Reading Programs in Developing Countries

    ERIC Educational Resources Information Center

    Roskos, Kathy; Strickland, Dorothy; Haase, Janeen; Malik, Sakil

    2009-01-01

    The United States Agency for International Development (USAID)-funded Early Grade Reading Assessment (EGRA) program is an oral assessment designed to measure the most basic foundation skills for literacy acquisition in the early grades. EGRA's purpose is to document student performance on early grade reading skills in order to inform ministries…

  15. What do medical students learn from early clinical experiences (ECE)?

    PubMed

    Lie, Désirée; Boker, John; Gutierrez, David; Prislin, Michael

    2006-08-01

    What are the common learning themes perceived by medical students during ECE with varying practice settings and patient profiles? Retrospective qualitative and quantitative analyses of structured descriptive reports completed by one class (n = 92) for 895 observed patient encounters identified common learning themes. Identified themes were examined by practice setting and patient characteristics. Student response rates were 85 to 94% across settings. Fifty-five percent of ECE were in outpatient settings. Chief complaints were predominantly medical (67%); only 20% represented psychosocial and 8% preventive care, respectively (5% were ambiguous). The five most common learning themes (out of 13 themes coded) were communication (>50%), procedures/time management, cross-cultural issues, feeling useful as a student, and presenting medical problems. Cross-cultural issues were addressed mainly in community settings. Negative learning occurred only rarely (<3%). Student observations from ECE can be used by course managers to design effective early clinical exposures to address specific course learning objectives.

  16. On the impartiality of early British clinical trials.

    PubMed

    Teira, David

    2013-09-01

    Did the impartiality of clinical trials play any role in their acceptance as regulatory standards for the safety and efficacy of drugs? According to the standard account of early British trials in the 1930s and 1940s, their impartiality was just rhetorical: the public demanded fair tests and statistical devices such as randomization created an appearance of neutrality. In fact, the design of the experiment was difficult to understand and the British authorities took advantage of it to promote their own particular interests. I claim that this account is based on a poorly defined concept of experimental fairness (derived from T. Porter's ideas). I present an alternative approach in which a test would be impartial if it incorporates warrants of non-manipulability. With this concept, I reconstruct the history of British trials showing that they were indeed fair and this fairness played a role in their acceptance as regulatory yardsticks.

  17. Use of biomarkers in ALS drug development and clinical trials.

    PubMed

    Bakkar, Nadine; Boehringer, Ashley; Bowser, Robert

    2015-05-14

    The past decade has seen a dramatic increase in the discovery of candidate biomarkers for ALS. These biomarkers typically can either differentiate ALS from control subjects or predict disease course (slow versus fast progression). At the same time, late-stage clinical trials for ALS have failed to generate improved drug treatments for ALS patients. Incorporation of biomarkers into the ALS drug development pipeline and the use of biologic and/or imaging biomarkers in early- and late-stage ALS clinical trials have been absent and only recently pursued in early-phase clinical trials. Further clinical research studies are needed to validate biomarkers for disease progression and develop biomarkers that can help determine that a drug has reached its target within the central nervous system. In this review we summarize recent progress in biomarkers across ALS model systems and patient population, and highlight continued research directions for biomarkers that stratify the patient population to enrich for patients that may best respond to a drug candidate, monitor disease progression and track drug responses in clinical trials. It is crucial that we further develop and validate ALS biomarkers and incorporate these biomarkers into the ALS drug development process. This article is part of a Special Issue entitled ALS complex pathogenesis.

  18. Clinical Decision Support for Early Recognition of Sepsis

    PubMed Central

    Amland, Robert C.; Hahn-Cover, Kristin E.

    2014-01-01

    Sepsis is an inflammatory response triggered by infection, with a high in-hospital mortality rate. Early recognition and treatment can reverse the inflammatory response, with evidence of improved patient outcomes. One challenge clinicians face is identifying the inflammatory syndrome against the background of the patient’s infectious illness and comorbidities. An approach to this problem is implementation of computerized early warning tools for sepsis. This multicenter retrospective study sought to determine clinimetric performance of a cloud-based computerized sepsis clinical decision support system (CDS), understand the epidemiology of sepsis, and identify opportunities for quality improvement. Data encompassed 6200 adult hospitalizations from 2012 through 2013. Of 13% patients screened-in, 51% were already suspected to have an infection when the system activated. This study focused on a patient cohort screened-in before infection was suspected; median time from arrival to CDS activation was 3.5 hours, and system activation to diagnostic collect was another 8.6 hours. PMID:25385815

  19. The Development of Self-Regulation across Early Childhood

    ERIC Educational Resources Information Center

    Montroy, Janelle J.; Bowles, Ryan P.; Skibbe, Lori E.; McClelland, Megan M.; Morrison, Frederick J.

    2016-01-01

    The development of early childhood self-regulation is often considered an early life marker for later life successes. Yet little longitudinal research has evaluated whether there are different trajectories of self-regulation development across children. This study investigates the development of behavioral self-regulation between the ages of 3 and…

  20. Early Development and the Brain: Teaching Resources for Educators

    ERIC Educational Resources Information Center

    Gilkerson, Linda, Ed.; Klein, Rebecca, Ed.

    2008-01-01

    This nine-unit curriculum translates current scientific research on early brain development into practical suggestions to help early childhood professionals understand the reciprocal link between caregiving and brain development. The curriculum was created and extensively field-tested by the Erikson Institute Faculty Development Project on the…

  1. Classroom Effects of an Early Childhood Educator Professional Development Partnership

    ERIC Educational Resources Information Center

    Algozzine, Bob; Babb, Julie; Algozzine, Kate; Mraz, Maryann; Kissel, Brian; Spano, Sedra; Foxworth, Kimberly

    2011-01-01

    We evaluated an Early Childhood Educator Professional Development (ECEPD) project that provided high-quality, sustained, and intensive professional development designed to support developmentally appropriate instruction for preschool-age children based on the best available research on early childhood pedagogy, child development, and preschool…

  2. The Development of Self-Regulation across Early Childhood

    ERIC Educational Resources Information Center

    Montroy, Janelle J.; Bowles, Ryan P.; Skibbe, Lori E.; McClelland, Megan M.; Morrison, Frederick J.

    2016-01-01

    The development of early childhood self-regulation is often considered an early life marker for later life successes. Yet little longitudinal research has evaluated whether there are different trajectories of self-regulation development across children. This study investigates the development of behavioral self-regulation between the ages of 3 and…

  3. Parents' Role in the Early Head Start Children's Language Development

    ERIC Educational Resources Information Center

    Griswold, Cecelia Smalls

    2014-01-01

    The development of language during a child's early years has been linked to parental involvement. While Early Head Start (EHS) researchers have theorized that parental involvement is an important factor in language development, there has been little research on how parents view their roles in the language development process. The purpose of this…

  4. Classroom Effects of an Early Childhood Educator Professional Development Partnership

    ERIC Educational Resources Information Center

    Algozzine, Bob; Babb, Julie; Algozzine, Kate; Mraz, Maryann; Kissel, Brian; Spano, Sedra; Foxworth, Kimberly

    2011-01-01

    We evaluated an Early Childhood Educator Professional Development (ECEPD) project that provided high-quality, sustained, and intensive professional development designed to support developmentally appropriate instruction for preschool-age children based on the best available research on early childhood pedagogy, child development, and preschool…

  5. Early Development and the Brain: Teaching Resources for Educators

    ERIC Educational Resources Information Center

    Gilkerson, Linda, Ed.; Klein, Rebecca, Ed.

    2008-01-01

    This nine-unit curriculum translates current scientific research on early brain development into practical suggestions to help early childhood professionals understand the reciprocal link between caregiving and brain development. The curriculum was created and extensively field-tested by the Erikson Institute Faculty Development Project on the…

  6. Parents' Role in the Early Head Start Children's Language Development

    ERIC Educational Resources Information Center

    Griswold, Cecelia Smalls

    2014-01-01

    The development of language during a child's early years has been linked to parental involvement. While Early Head Start (EHS) researchers have theorized that parental involvement is an important factor in language development, there has been little research on how parents view their roles in the language development process. The purpose of this…

  7. The use of circulating biomarkers in early clinical trials in patients with cancer.

    PubMed

    D'Arcangelo, Manolo; Margetts, Jane; Greystoke, Alastair

    2015-01-01

    The development of targeted therapies has changed the approach to early oncological clinical trial design. Identification of patient populations most likely to derive benefit and the biologically effective dose are now as important as determination of the maximum tolerated dose. Completion of the 'pharmacological audit trail' highlights drugs most likely to progress through to license, so resources can be allocated appropriately. Key to the success of this changing model is the validation/qualification of circulating biomarkers. These might provide a readily accessible and dynamic picture of drug effect, tumor response and toxicity with minimum risk to patients. This review article examines circulating biomarkers currently used in early oncological clinical trials. It considers the evidence for their employment, limitations and challenges for future development.

  8. Evaluation of DILI Predictive Hypotheses in Early Drug Development.

    PubMed

    Chan, Rosa; Benet, Leslie Z

    2017-04-17

    Drug-induced liver injury (DILI) is a leading cause of drug failure in clinical trials and a major reason for drug withdrawals. DILI has been shown to be dependent on both daily dose and extent of hepatic metabolism. Yet, early in drug development daily dose is unknown. Here, we perform a comprehensive analysis of the published hypotheses that attempt to predict DILI, including a new analysis of the Biopharmaceutics Drug Disposition Classification System (BDDCS) in evaluating the severity of DILI warnings in drug labels approved by the FDA and the withdrawal status due to adverse drug reactions (ADRs). Our analysis confirms that higher doses ≥50 mg/day lead to increased DILI potential, but this property alone is not sufficient to predict the DILI potential. We evaluate prior attempts to categorize DILI such as Rule of 2, BSEP inhibition, and measures of key mechanisms of toxicity compared to BDDCS classification. Our results show that BDDCS Class 2 drugs exhibit the highest DILI severity and that all of the published methodologies evaluated here, except when daily dose is known, do not yield markedly better predictions than BDDCS. The assertion that extensive metabolized compounds are at higher risk of developing DILI is confirmed but can be enhanced by differentiating BDDCS Class 2 from Class 1 drugs. We do not propose that the BDDCS classification, which does not require knowledge of the clinical dose, is sufficiently predictive/accurate of DILI potential for new molecular entities but suggest that comparison of proposed DILI prediction methodologies with BDDCS classification is a useful tool to evaluate the potential reliability of newly proposed algorithms. The most successful approaches to predict DILI potential all include a measure of dose, yet there is a quantifiable uncertainty associated with the predicted dose early in drug development. Here, we compare the possibility of predicting DILI potential using the BDDCS classification versus previously

  9. Functional limitations in the phase of clinically suspect arthralgia are as serious as in early clinical arthritis; a longitudinal study

    PubMed Central

    ten Brinck, Robin M; van Steenbergen, Hanna W; Mangnus, Lukas; Burgers, Leonie E; Reijnierse, Monique; Huizinga, Tom WJ; van der Helm-van Mil, Annette HM

    2017-01-01

    Introduction A phase of arthralgia may precede the emergence of rheumatoid arthritis (RA). Although several studies have focused on biomarkers, the relevance of this phase for patients is less studied. It is unknown if patients already have functional limitations and if this is correlated to the extent of subclinical inflammation. Therefore, we assessed functional disability in patients with clinically suspect arthralgia (CSA), its association with MRI-detected subclinical inflammation and its course during progression to clinical arthritis. Methods From April 2012 to March 2015, 241 patients had arthralgia for <1 year and were, based on clinical presentation, considered at risk for RA by their rheumatologists. At baseline, Health Assessment Questionnaire (HAQ) scores were determined and unilateral 1.5 T MRI of metacarpophalangeal, wrist and metatarsophalangeal joints were made. Presence of MRI-detected subclinical inflammation was assessed by summing synovitis, tenosynovitis and bone marrow oedema scores (range 0–189). Patients were followed on arthritis development and HAQ scores were repeated when clinical arthritis had developed. Results The median HAQ score at presentation with CSA was 0.50. Higher MRI-inflammation scores were associated with higher HAQ scores (β=0.017, 95% CI=0.004 to 0.030). During median 103 weeks follow-up, 44 patients progressed to clinical arthritis. HAQ scores ≥1.0 were associated with arthritis development (HR=2.50, 95% CI=1.03 to 6.10). Within converters, median HAQ scores did not increase from presentation with CSA to arthritis development (0.88 and 0.75, p=0.36). Conclusions HAQ scores ≥1.0 at presentation were associated with the development of clinical arthritis. Functional limitations in the prearthritis phase of CSA were as serious as in the early clinical phase, demonstrating the relevance of CSA from patients’ perspectives. PMID:28879045

  10. Functional limitations in the phase of clinically suspect arthralgia are as serious as in early clinical arthritis; a longitudinal study.

    PubMed

    Ten Brinck, Robin M; van Steenbergen, Hanna W; Mangnus, Lukas; Burgers, Leonie E; Reijnierse, Monique; Huizinga, Tom Wj; van der Helm-van Mil, Annette Hm

    2017-01-01

    A phase of arthralgia may precede the emergence of rheumatoid arthritis (RA). Although several studies have focused on biomarkers, the relevance of this phase for patients is less studied. It is unknown if patients already have functional limitations and if this is correlated to the extent of subclinical inflammation. Therefore, we assessed functional disability in patients with clinically suspect arthralgia (CSA), its association with MRI-detected subclinical inflammation and its course during progression to clinical arthritis. From April 2012 to March 2015, 241 patients had arthralgia for <1 year and were, based on clinical presentation, considered at risk for RA by their rheumatologists. At baseline, Health Assessment Questionnaire (HAQ) scores were determined and unilateral 1.5 T MRI of metacarpophalangeal, wrist and metatarsophalangeal joints were made. Presence of MRI-detected subclinical inflammation was assessed by summing synovitis, tenosynovitis and bone marrow oedema scores (range 0-189). Patients were followed on arthritis development and HAQ scores were repeated when clinical arthritis had developed. The median HAQ score at presentation with CSA was 0.50. Higher MRI-inflammation scores were associated with higher HAQ scores (β=0.017, 95% CI=0.004 to 0.030). During median 103 weeks follow-up, 44 patients progressed to clinical arthritis. HAQ scores ≥1.0 were associated with arthritis development (HR=2.50, 95% CI=1.03 to 6.10). Within converters, median HAQ scores did not increase from presentation with CSA to arthritis development (0.88 and 0.75, p=0.36). HAQ scores ≥1.0 at presentation were associated with the development of clinical arthritis. Functional limitations in the prearthritis phase of CSA were as serious as in the early clinical phase, demonstrating the relevance of CSA from patients' perspectives.

  11. Development of an Early Intervention Program

    ERIC Educational Resources Information Center

    Gil, Isidoro Candel

    2005-01-01

    The following paper presents the main evaluation instruments used in early intervention, and reflects upon their use, taking into account that they were created with and for the normal population. Likewise, developmental characteristics of some child groups are described, more notably the x fragile syndrome, Williams syndrome and Prader Willi…

  12. Early Developments in Argumentation in Physics.

    ERIC Educational Resources Information Center

    Bazerman, Charles

    An evaluation of four seventeenth and eighteenth century essays on optics revealed early trends in the evolution of scientific articles. The later articles showed a growing tendency to (1) separate practice from pure knowledge, (2) organize information around problems of knowledge and theory rather than around chronological events, (3) emphasize…

  13. Early Adolescence: A Critical Development Transition?

    ERIC Educational Resources Information Center

    Petersen, Anne C.

    A longitudinal study of early adolescents examined gender differences in attitude and behavior, as well as the effects of pubertal change, parental expectations, and parental support. It was hypothesized that sex differences would emerge during preadolescence and that males' and females' rates of change would be significantly different. Subjects…

  14. Clinical development of fenretinide as an antineoplastic drug: Pharmacology perspectives.

    PubMed

    Cooper, Jason P; Reynolds, C Patrick; Cho, Hwangeui; Kang, Min H

    2017-06-01

    Fenretinide (4-HPR) is a synthetic retinoid that has cytotoxic activity against cancer cells. Despite substantial in vitro cytotoxicity, response rates in early clinical trials with 4-HPR have been less than anticipated, likely due to the low bioavailability of the initial oral capsule formulation. Several clinical studies have shown that the oral capsule formulation at maximum tolerated dose (MTD) achieved <10 µmol/L concentrations in patients. To improve bioavailability of 4-HPR, new oral powder (LYM-X-SORB®, LXS) and intravenous lipid emulsion (ILE) formulations are being tested in early-phase clinical trials. ILE 4-HPR administered as five-day continuous infusion achieved over 50 µmol/L at MTD with minimal systemic toxicities; multiple complete and partial responses were observed in peripheral T cell lymphomas. The LXS oral powder 4-HPR formulation increased plasma levels approximately two-fold at MTD in children without dose-limiting toxicities and demonstrated multiple complete responses in recurrent neuroblastoma. The clinical activity observed with new 4-HPR formulations is attributed to increased bioavailability. Phase I and II clinical trials of both LXS 4-HPR and ILE 4-HPR are in progress as a single agent or in combination with other drugs. Impact statement One of the critical components in drug development is understanding pharmacology (especially pharmacokinetics) of the drugs being developed. Often the pharmacokinetic properties, such as poor solubility leading to poor bioavailability, of the drug can limit further development of the drug. The development of numerous drugs has often halted at clinical testing stages, and several of them were due to the pharmacological properties of the agents, resulting in increased drug development cost. The current review provides an example of how improved clinical activity can be achieved by changing the formulations of a drug with poor bioavailability. Thus, it emphasizes the importance of understanding

  15. Genetic predisposition to early recurrence in clinically localized prostate cancer.

    PubMed

    Borque, Ángel; del Amo, Jokin; Esteban, Luis M; Ars, Elisabet; Hernández, Carlos; Planas, Jacques; Arruza, Antonio; Llarena, Roberto; Palou, Joan; Herranz, Felipe; Raventós, Carles X; Tejedor, Diego; Artieda, Marta; Simon, Laureano; Martínez, Antonio; Carceller, Elena; Suárez, Miguel; Allué, Marta; Sanz, Gerardo; Morote, Juan

    2013-04-01

    WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Currently available nomograms to predict preoperative risk of early biochemical recurrence (EBCR) after radical prostatectomy are solely based on classic clinicopathological variables. Despite providing useful predictions, these models are not perfect. Indeed, most researchers agree that nomograms can be improved by incorporating novel biomarkers. In the last few years, several single nucleotide polymorphisms (SNPs) have been associated with prostate cancer, but little is known about their impact on disease recurrence. We have identified four SNPs associated with EBCR. The addition of SNPs to classic nomograms resulted in a significant improvement in terms of discrimination and calibration. The new nomogram, which combines clinicopathological and genetic variables, will help to improve prediction of prostate cancer recurrence. To evaluate genetic susceptibility to early biochemical recurrence (EBCR) after radical prostatectomy (RP), as a prognostic factor for early systemic dissemination. To build a preoperative nomogram to predict EBCR combining genetic and clinicopathological factors. We evaluated 670 patients from six University Hospitals who underwent RP for clinically localized prostate cancer (PCa), and were followed-up for at least 5 years or until biochemical recurrence. EBCR was defined as a level prostate-specific antigen >0.4 ng/mL within 1 year of RP; preoperative variables studied were: age, prostate-specific antigen, clinical stage, biopsy Gleason score, and the genotype of 83 PCa-related single nucleotide polymorphisms (SNPs). Univariate allele association tests and multivariate logistic regression were used to generate predictive models for EBCR, with clinicopathological factors and adding SNPs. We internally validated the models by bootstrapping and compared their accuracy using the area under the curve (AUC), net reclassification improvement, integrated discrimination improvement

  16. Clinical skill development for community pharmacists.

    PubMed

    Barnette, D J; Murphy, C M; Carter, B L

    1996-09-01

    The importance of establishing clinical pharmacy services in the community cannot be understated in light of current challenges to the traditional dispensing role as the primary service of the community pharmacist. Advancements in automated dispensing technology and declining prescription fee reimbursement are rapidly forcing pharmacists to seek alternative sources of revenue. Providing pharmaceutical care is a viable option to increase customer loyalty job satisfaction, and reimbursement. To support the development of clinical services, academic institutions are forming partnerships with individual community practitioners to overcome perceived educational and training barriers. The authors describe the design and development of two unique clinical skill development programs at the University of Illinois at Chicago. This paper also outlines the patient focused services that the participants have established upon completing the training. These programs successfully enhanced participants' therapeutic knowledge base and facilitated development of the clinical skills necessary for direct patient care.

  17. Early intervention surveillance strategies (EISS) in dental student clinical performance: a mathematical approach.

    PubMed

    Tennant, Marc; Kruger, Estie

    2005-12-01

    Graduating dental practitioners requires the mastery of a number of skills and a significant body of basic information. Dental education is a complex combination of didactic and physical skill learning processes. It is necessary to develop appropriate tools to measure student clinical performance to allow the provision of interventional strategies at the right time targeted at the right individuals. In this study, an approach to early intervention surveillance strategies was developed that is cost-effective, transparent, and robust based on mathematical predictions of student clinical achievements. Using a cohort of students' clinical activity profile, a polynomial pair was developed that represents the predictive function of low and high achieving students. This polynomial pair can then be applied to students to predict their final achievement based on their current status. The polynomial methodology is adaptable to local variation such as access to clinical facilities. The early intervention surveillance strategy developed in this study provides a simple, cost-effective, predictive risk assessment system that relies on data sets already collected in most dental schools and can be completed without the need for significant human intervention. The mathematical approach allows the focusing of educational support towards students that require the assistance, thus augmenting the better use of resources.

  18. Protective factors in the development of early child conduct problems

    PubMed Central

    Vanderbilt-Adriance, Ella; Shaw, Daniel S.; Brennan, Lauretta M.; Dishion, Thomas J.; Gardner, Frances; Wilson, Melvin N.

    2014-01-01

    The present study utilized a resilience model to investigate child, family, and community protective factors in toddlerhood as they relate to low levels of conduct problems at age 5 in a sample of low income children at risk for early disruptive problem behavior. Child, family, and community factors were associated with lower levels of conduct problems at age 5. Child, family, and community protective factors also distinguished between children who remained below and above a clinical threshold for aggressive problems between age 2 and 5. Finally, each domain of protective factors made small but significant unique contributions to lower aggression at age 5. These results emphasize the importance of multivariate analysis of the ecology of development predicting child outcome, and suggest potential areas for intervention with children at high risk for conduct problems. PMID:25774071

  19. Developing a web page: bringing clinics online.

    PubMed

    Peterson, Ronnie; Berns, Susan

    2004-01-01

    Introducing clinical staff education, along with new policies and procedures, to over 50 different clinical sites can be a challenge. As any staff educator will confess, getting people to attend an educational inservice session can be difficult. Clinical staff request training, but no one has time to attend training sessions. Putting the training along with the policies and other information into "neat" concise packages via the computer and over the company's intranet was the way to go. However, how do you bring the clinics online when some of the clinical staff may still be reluctant to turn on their computers for anything other than to gather laboratory results? Developing an easy, fun, and accessible Web page was the answer. This article outlines the development of the first training Web page at the University of Wisconsin Medical Foundation, Madison, WI.

  20. Phase 0 clinical trials in cancer drug development: from FDA guidance to clinical practice.

    PubMed

    Kinders, Robert; Parchment, Ralph E; Ji, Jay; Kummar, Shivaani; Murgo, Anthony J; Gutierrez, Martin; Collins, Jerry; Rubinstein, Larry; Pickeral, Oxana; Steinberg, Seth M; Yang, Sherry; Hollingshead, Melinda; Chen, Alice; Helman, Lee; Wiltrout, Robert; Simpson, Mel; Tomaszewski, Joseph E; Doroshow, James H

    2007-12-01

    The Food and Drug Administration (FDA) recently introduced the Exploratory Investigational New Drug Guidance to expedite the clinical evaluation of new therapeutic and imaging agents. Early clinical studies performed under the auspices of this guidance, so-called "Phase 0" trials, have been initiated at the National Cancer Institute to integrate qualified pharmacodynamic biomarker assays into first-in-human cancer clinical trials of molecularly targeted agents. The goal of this integration is to perform molecular proof-of-concept investigations at the earliest stage of cancer drug development. Phase 0 trials do not offer any possibility of patient benefit; instead, intensive, real-time pharmacodynamic and pharmacokinetic analyses of patient tumor samples and/or surrogate tissues are performed to inform subsequent trials. Phase 0 studies do not replace formal Phase I drug safety testing and require a substantial investment of resources in assay development early on; however, they offer the promise of more rational selection of agents for further, large-scale development as well as the molecular identification of potential therapeutic failures early in the development process.

  1. Clinical trials of new drugs for the treatment of rheumatoid arthritis: focus on early disease

    PubMed Central

    Collaud Basset, Sabine; Boers, Maarten; Breedveld, Ferdinand; Edwards, Christopher J; Kvien, Tore K; Miossec, Pierre; Sokka-Isler, Tuulikki; van Vollenhoven, Ronald F; Abadie, Eric C; Bruyère, Olivier; Cooper, Cyrus; Mäkinen, Heidi; Thomas, Thierry; Tugwell, Peter; Reginster, Jean-Yves

    2016-01-01

    The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases convened a task force of experts in rheumatoid arthritis (RA) and clinical trial methodology to comment on the new draft ‘Guideline on clinical investigation of medicinal products for the treatment of RA’ released by the European Medicines Agency (EMA). Special emphasis was placed by the group on the development of new drugs for the treatment of early RA. In the absence of a clear definition of early RA, it was suggested that clinical investigations in this condition were conducted in disease-modifying antirheumatic drugs naïve patients with no more than 1 year disease duration. The expert group recommended using an appropriate improvement in disease activity (American College of Rheumatology (ACR) or Simplified/Clinical Disease Activity Index (SDAI/CDAI) response criteria) or low disease activity (by any score) as primary endpoints, with ACR/European League Against Rheumatism remission as a secondary endpoint. Finally, as compelling evidence showed that the Disease Acrivity Score using 28-joint counts (DAS28) might not provide a reliable definition of remission, or sometimes even low disease activity, the group suggested replacing DAS28 as a measurement instrument to evaluate disease activity in RA clinical trials. Proposed alternatives included SDAI, CDAI and Boolean criteria. PMID:27037326

  2. Clinical trials of new drugs for the treatment of rheumatoid arthritis: focus on early disease.

    PubMed

    Smolen, Josef S; Collaud Basset, Sabine; Boers, Maarten; Breedveld, Ferdinand; Edwards, Christopher J; Kvien, Tore K; Miossec, Pierre; Sokka-Isler, Tuulikki; van Vollenhoven, Ronald F; Abadie, Eric C; Bruyère, Olivier; Cooper, Cyrus; Mäkinen, Heidi; Thomas, Thierry; Tugwell, Peter; Reginster, Jean-Yves

    2016-07-01

    The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases convened a task force of experts in rheumatoid arthritis (RA) and clinical trial methodology to comment on the new draft 'Guideline on clinical investigation of medicinal products for the treatment of RA' released by the European Medicines Agency (EMA). Special emphasis was placed by the group on the development of new drugs for the treatment of early RA. In the absence of a clear definition of early RA, it was suggested that clinical investigations in this condition were conducted in disease-modifying antirheumatic drugs naïve patients with no more than 1 year disease duration. The expert group recommended using an appropriate improvement in disease activity (American College of Rheumatology (ACR) or Simplified/Clinical Disease Activity Index (SDAI/CDAI) response criteria) or low disease activity (by any score) as primary endpoints, with ACR/European League Against Rheumatism remission as a secondary endpoint. Finally, as compelling evidence showed that the Disease Acrivity Score using 28-joint counts (DAS28) might not provide a reliable definition of remission, or sometimes even low disease activity, the group suggested replacing DAS28 as a measurement instrument to evaluate disease activity in RA clinical trials. Proposed alternatives included SDAI, CDAI and Boolean criteria.

  3. Dual Language Exposure and Early Bilingual Development

    ERIC Educational Resources Information Center

    Hoff, Erifka; Core, Cynthia; Place, Silvia; Rumiche, Rosario; Senor, Melissa; Parra, Marisol

    2012-01-01

    The extant literature includes conflicting assertions regarding the influence of bilingualism on the rate of language development. The present study compared the language development of equivalently high-SES samples of bilingually and monolingually developing children from 1 ; 10 to 2 ; 6. The monolingually developing children were significantly…

  4. Investments for Future: Early Childhood Development and Education

    ERIC Educational Resources Information Center

    Kartal, Hulya

    2007-01-01

    Investments relevant to the first years of life are directly connected to the future of societies. It can be argued that investments for early childhood development and education are one of the best ways of decreasing social inequality caused by adverse environments which hinder development in early ages and tackling poverty by reducing the rate…

  5. Supporting Early Childhood Educators through Professional Development Partnerships

    ERIC Educational Resources Information Center

    Mraz, Maryann

    2011-01-01

    This article summarizes the findings of a study that examined instruction in early childhood classrooms where teachers participated in high-quality, sustained, and intensive professional development through an Early Childhood Educator Professional Development partnership on literacy practices essential to school success. Comparisons made between…

  6. Study of Early Child Care and Youth Development (SECCYD)

    MedlinePlus

    ... Supported Research Networks & Programs NICHD Study of Early Child Care and Youth Development (SECCYD) Sunsetted/For Reference Only Skip sharing on ... is not being updated . The Study of Early Child Care and Youth Development (SECCYD), now complete, began as the Study of ...

  7. Promoting Professional Development for Physical Therapists in Early Intervention

    ERIC Educational Resources Information Center

    Catalino, Tricia; Chiarello, Lisa A.; Long, Toby; Weaver, Priscilla

    2015-01-01

    Early intervention service providers are expected to form cohesive teams to build the capacity of a family to promote their child's development. Given the differences in personnel preparation across disciplines of service providers, the Early Childhood Personnel Center is creating integrated and comprehensive professional development models for…

  8. Rethinking the Brain: New Insights into Early Development.

    ERIC Educational Resources Information Center

    Shore, Rima

    Recent research on early brain development holds several implications for parents, teachers, health professionals, and policymakers. This report, based on the proceedings from a 1996 national conference on the importance of early brain development for the nation's future well-being, highlights major findings, summarizes their implications for…

  9. Assessing Home Environment for Early Child Development in Pakistan

    ERIC Educational Resources Information Center

    Nadeem, Sanober; Rafique, Ghazala; Khowaja, Liaquat; Yameen, Anjum

    2014-01-01

    Family environment plays a very important role in early child development and the availability of stimulating material in the early years of a child's life is crucial for optimising development. The Home Observation for Measurement of the Environment (HOME) inventory is one of the most widely used measures to assess the quality and quantity of…

  10. Investments for Future: Early Childhood Development and Education

    ERIC Educational Resources Information Center

    Kartal, Hulya

    2007-01-01

    Investments relevant to the first years of life are directly connected to the future of societies. It can be argued that investments for early childhood development and education are one of the best ways of decreasing social inequality caused by adverse environments which hinder development in early ages and tackling poverty by reducing the rate…

  11. Early Communication Development and Intervention for Children with Autism

    ERIC Educational Resources Information Center

    Landa, Rebecca

    2007-01-01

    Autism is a neurodevelopmental disorder defined by impairments in social and communication development, accompanied by stereotyped patterns of behavior and interest. The focus of this paper is on the early development of communication in autism, and early intervention for impairments in communication associated with this disorder. An overview of…

  12. Assessing Home Environment for Early Child Development in Pakistan

    ERIC Educational Resources Information Center

    Nadeem, Sanober; Rafique, Ghazala; Khowaja, Liaquat; Yameen, Anjum

    2014-01-01

    Family environment plays a very important role in early child development and the availability of stimulating material in the early years of a child's life is crucial for optimising development. The Home Observation for Measurement of the Environment (HOME) inventory is one of the most widely used measures to assess the quality and quantity of…

  13. Promoting Professional Development for Physical Therapists in Early Intervention

    ERIC Educational Resources Information Center

    Catalino, Tricia; Chiarello, Lisa A.; Long, Toby; Weaver, Priscilla

    2015-01-01

    Early intervention service providers are expected to form cohesive teams to build the capacity of a family to promote their child's development. Given the differences in personnel preparation across disciplines of service providers, the Early Childhood Personnel Center is creating integrated and comprehensive professional development models for…

  14. Developing clinical teaching capacities of midwifery students.

    PubMed

    Rance, Sharon; Sweet, Linda

    2016-06-01

    Competency Standards in Australia articulate that the midwife must be able to contribute to the professional development of themselves and others. Few undergraduate health professional curricula currently incorporate content for the development of specific knowledge and skills required for clinical teaching. This project aimed to understand and enhance midwifery students' preparedness to assume their future clinical teaching responsibilities. Design-based research was used to implement an educational intervention aimed at developing clinical teaching skills through a peer education session between 1st and 3rd year students. The perspectives of 30 undergraduate midwifery students about their preparedness for their teaching role and the intervention were obtained through 3 focus groups. A thematic analysis of the data was undertaken. Three themes were identified encompassing the research aims and objectives; 'Co-creating a culture for learning', 'reciprocal teaching and learning' and 'developing clinical teaching capacities'. The findings indicate that the midwifery students had a holistic understanding of their responsibilities in clinical teaching in the workplace. They were able to identify ways in which their teaching capacities were being developed through their clinical experiences and the curriculum, both intended and hidden. Despite limited educational activities for clinical teaching, the midwifery students made explicit connections of the relational interdependence of workplace-based experiences and their learning. Students were clearly able to identify ways in which their own learning experiences and the culture in which this learning is embedded, assists them to develop clinical teaching skills, ready to support the next generation of midwifery students. Copyright © 2015 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

  15. Transient ischaemic attacks clinics provide equivalent and more efficient care than early in-hospital assessment.

    PubMed

    Martínez-Martínez, M M; Martínez-Sánchez, P; Fuentes, B; Cazorla-García, R; Ruiz-Ares, G; Correas-Callero, E; Lara-Lara, M; Díez-Tejedor, E

    2013-02-01

    Clinics for early management of transient ischaemic attacks (TIAs) have been developed in some stroke centres, resulting in reduced recurrence rates compared to appointment-based outpatient management, thus saving on hospitalization. We analysed the care process, recurrence rates and economic impact of the first year of work in our early-management TIA clinic and compared these with our previous in-hospital study protocols for low- and moderate-risk TIA patients. This was a prospective evaluation of the management of low- to moderate-risk TIA patients, comparing a new TIA clinic model (2010) with a previous hospitalization model (2009). Demographic data, vascular risk factor profiles, diagnostic test performance, secondary prevention measures, final aetiological diagnoses and cerebrovascular recurrences at 7 and 90 days were compared between in-hospital and TIA clinic assessed patients. We also carried out an economic comparison of the costs of each model's process. Two hundred and eleven low- to moderate-risk TIA patients were included, of whom 40.8% were hospitalized. There were no differences between the TIA clinic assessed and in-hospital assessed patients in terms of risk factor diagnosis and secondary prevention measures. The stroke recurrence rate (2.4% vs. 1.2%; P = 0.65) was low and similar for both groups (CI 95%, 0.214-20.436; P = 0.52). Cost per patient was €393.28 for clinic versus €1931.18 for in-hospital management. Outpatient management resulted in a 77.8% reduction in hospitalizations. Transient ischaemic attacks clinics are efficient for the early management of low- to moderate-risk TIA patients compared to in-hospital assessment, with no higher recurrence rates and at almost one-fifth the cost. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

  16. Early life precursors, epigenetics, and the development of food allergy.

    PubMed

    Hong, Xiumei; Wang, Xiaobin

    2012-09-01

    Food allergy (FA), a major clinical and public health concern worldwide, is caused by a complex interplay of environmental exposures, genetic variants, gene-environment interactions, and epigenetic alterations. This review summarizes recent advances surrounding these key factors, with a particular focus on the potential role of epigenetics in the development of FA. Epidemiologic studies have reported a number of nongenetic factors that may influence the risk of FA, such as timing of food introduction and feeding pattern, diet/nutrition, exposure to environmental tobacco smoking, prematurity and low birth weight, microbial exposure, and race/ethnicity. Current studies on the genetics of FA are mainly conducted using candidate gene approaches, which have linked more than 10 genes to the genetic susceptibility of FA. Studies on gene-environment interactions of FA are very limited. Epigenetic alteration has been proposed as one of the mechanisms to mediate the influence of early life environmental exposures and gene-environment interactions on the development of diseases later in life. The role of epigenetics in the regulation of the immune system and the epigenetic effects of some FA-associated environmental exposures are discussed in this review. There is a particular lack of large-scale prospective birth cohort studies that simultaneously assess the interrelationships of early life exposures, genetic susceptibility, epigenomic alterations, and the development of FA. The identification of these key factors and their independent and joint contributions to FA will allow us to gain important insight into the biological mechanisms by which environmental exposures and genetic susceptibility affect the risk of FA and will provide essential information to develop more effective new paradigms in the diagnosis, prevention, and management of FA.

  17. Early Detection of Psychosis: Recent Updates from Clinical High-Risk Research

    PubMed Central

    Schvarcz, Ariel

    2015-01-01

    The debilitating nature of schizophrenia necessitates early detection of individuals at clinical high-risk (CHR) in order to facilitate early intervention. In particular, comparisons between those who develop fully psychotic features (CHR+) and those who do not (CHR−) offer the opportunity to reveal distinct risk factors for psychosis, as well as possible intervention target points. Recent studies have investigated baseline clinical, neurocognitive, neuroanatomic, neurohormonal, and psychophysiological predictors of outcome; premorbid social dysfunction, deficits in neurocognitive performance, neuroanatomic changes, and hypothalamic-pituitary-adrenal (HPA) axis dysfunction have been implicated in psychosis emergence. However, several challenges within CHR research remain: heterogeneity in long-term diagnostic outcome, the variability of research tools and definitions utilized, and limited longitudinal follow-up. Future work in the field should focus on replication via extended longitudinal designs, aim to explore the trajectories and inter-relationships of hypothesized biomarkers, and continue to investigate interventions that seek to prevent psychosis emergence through symptom reduction. PMID:26693133

  18. Precision Medicine for Molecularly Targeted Agents and Immunotherapies in Early-Phase Clinical Trials

    PubMed Central

    Lopez, Juanita; Harris, Sam; Roda, Desam; Yap, Timothy A

    2015-01-01

    Precision medicine in oncology promises the matching of genomic, molecular, and clinical data with underlying mechanisms of a range of novel anticancer therapeutics to develop more rational and effective antitumor strategies in a timely manner. However, despite the remarkable progress made in the understanding of novel drivers of different oncogenic processes, success rates for the approval of oncology drugs remain low with substantial fiscal consequences. In this article, we focus on how recent rapid innovations in technology have brought greater clarity to the biological and clinical complexities of different cancers and advanced the development of molecularly targeted agents and immunotherapies in clinical trials. We discuss the key challenges of identifying and validating predictive biomarkers of response and resistance using both tumor and surrogate tissues, as well as the hurdles associated with intratumor heterogeneity. Finally, we outline evolving strategies employed in early-phase trial designs that incorporate omics-based technologies. PMID:26609214

  19. Early experiences in evolving an enterprise-wide information model for laboratory and clinical observations.

    PubMed

    Chen, Elizabeth S; Zhou, Li; Kashyap, Vipul; Schaeffer, Molly; Dykes, Patricia C; Goldberg, Howard S

    2008-11-06

    As Electronic Healthcare Records become more prevalent, there is an increasing need to ensure unambiguous data capture, interpretation, and exchange within and across heterogeneous applications. To address this need, a common, uniform, and comprehensive approach for representing clinical information is essential. At Partners HealthCare System, we are investigating the development and implementation of enterprise-wide information models to specify the representation of clinical information to support semantic interoperability. This paper summarizes our early experiences in: (1) defining a process for information model development, (2) reviewing and comparing existing healthcare information models, (3) identifying requirements for representation of laboratory and clinical observations, and (4) exploring linkages to existing terminology and data standards. These initial findings provide insight to the various challenges ahead and guidance on next steps for adoption of information models at our organization.

  20. [Ways to improve efficiency of patient clinical examinations during early stage of cholelithiasis].

    PubMed

    Khokhlacheva, N A; Suchkova, E V; Vakhrushev, Ia M

    2013-01-01

    The aim of the work was to improve the organization and conduct of clinical examination of patients with gallstone disease (GSD). An integrated study of 396 patients with different pathologies of the hepatobiliary system and the medical check-up for three years for 101 patients. Built logistic model to predict the likelihood of developing gallstone disease and developed a predictive scoring table it possible to distinguish patients at risk of developing gall stones. The result of follow-up of the proposed method was prevented economic losses due to the lack of need for a cholecystectomy, which is made up of one patient 6766.22 rubles., The entire group of 1,004,966.63 rubles. Obtained to diagnose cholelithiasis at an early stage dokamennoy. Developed a screening questionnaire, predictive scoring table, the scheme of follow-up also improves clinical examination of patients with cholelithiasis dokamennoy stage.

  1. Early evolutionary trends in ammonoid embryonic development.

    PubMed

    De Baets, Kenneth; Klug, Christian; Korn, Dieter; Landman, Neil H

    2012-06-01

    During the Devonian Nekton Revolution, ammonoids show a progressive coiling of their shell just like many other pelagic mollusk groups. These now extinct, externally shelled cephalopods derived from bactritoid cephalopods with a straight shell in the Early Devonian. During the Devonian, evolutionary trends toward tighter coiling and a size reduction occurred in ammonoid embryonic shells. In at least three lineages, descendants with a closed umbilicus evolved convergently from forms with an opening in the first whorl (umbilical window). Other lineages having representatives with open umbilici became extinct around important Devonian events whereas only those with more tightly coiled embryonic shells survived. This change was accompanied by an evolutionary trend in shape of the initial chamber, but no clear trend in its size. The fact that several ammonoid lineages independently reduced and closed the umbilical window more or less synchronously indicates that common driving factors were involved. A trend in size decrease of the embryos as well as the concurrent increase in adult size in some lineages likely reflects a fundamental change in reproductive strategies toward a higher fecundity early in the evolutionary history of ammonoids. This might have played an important role in their subsequent success as well as in their demise. © 2012 The Author(s). Evolution © 2012 The Society for the Study of Evolution.

  2. History and early development of INCAP.

    PubMed

    Scrimshaw, Nevin S

    2010-02-01

    Nevin Scrimshaw was the founding Director of the Institute of Nutrition of Central America and Panama (INCAP), serving as Director from 1949 to 1961. In this article, he reviews the history of the founding of INCAP, including the role of the Rockefeller and Kellogg Foundations, the Central American governments, and the Pan American Health Organization. The objectives pursued by INCAP in its early years were to assess the nutrition and related health problems of Central America, to carry out research to find practical solutions to these problems, and to provide technical assistance to its member countries to implement solutions. INCAP pursued a strategy of selecting promising Central Americans for advanced education and training in the US who assumed positions of leadership on their return. After this early phase, talented non-Central Americans of diverse origins were brought to INCAP, as well as additional researchers from the region. Growth of INCAP, as reflected in its annual budget and in the physical plant, was rapid and this was accompanied by high scientific productivity. Several field studies were launched that contributed impetus and design elements for the Oriente Longitudinal Study, which is the focus of this supplement.

  3. Cognition and Affect in Early Literacy Development.

    ERIC Educational Resources Information Center

    McNamee, Gillian D.; And Others

    1985-01-01

    Using Vygotsky's theory of development, explores the significance of storytelling and dramatization activities on the intellectual and emotional development of preschool children. Results indicate that dramatizing of children's stories enhances the storytelling of preschool children and, thus, influences their literacy development. (DST)

  4. Standardized patients in the early acquisition of clinical skills.

    PubMed

    McGraw, R C; O'Connor, H M

    1999-08-01

    Facing dramatic reductions of inpatient beds and fewer faculty tutors, the Queen's University medical school has had to consider alternatives to the traditional inpatient encounter for the early acquisition of clinical skills. The purpose of this study was to investigate the feasibility and impact on students of a model for a first-year clinical skills course, using exclusively standardized patients in place of inpatients, and using a smaller ratio of faculty to students. Twenty volunteers were selected from the first-year class of 75 students to participate as the experimental group. The remaining 55 students formed the control group. Queen's University medical school, Ontario, Canada. First-year medical students. In measures of student satisfaction with the amount of performance feedback received during the course, there was a non-significant trend towards greater satisfaction among the experimental group compared to the control group. This occurred despite a tutor to student ratio of 1.5:10 in the experimental group compared to 3:10 in the control group. In the student evaluation of their tutors, mean scores for the two groups were 4.28 for the experimental group and 4. 06 for the control group (P = 0.10). The mean OSCE scores for the two groups were 76.4 for the experimental group and 76.5 for the control group (P = 0.93). There is no practical or statistical difference in either of these two scores. We conclude that this new model is feasible, was well received by the students and that the reduced tutor to student ratio and lack of inpatient encounters did not appear to adversely affect their learning.

  5. The development of phonological skills in late and early talkers

    PubMed Central

    KEHOE, Margaret; CHAPLIN, Elisa; MUDRY, Pauline; FRIEND, Margaret

    2016-01-01

    This study examined the relationship between phonological and lexical development in a group of French-speaking children (n=30), aged 29 months. The participants were divided into three sub-groups based on the number of words in their expressive vocabulary : low vocabulary (below the 15th percentile) (<< late-talkers >>) ; average-sized vocabulary (40-60th percentile) (<< middle group >>) and advanced vocabulary (above the 90th percentile) (<< precocious >> or “early talkers”). The phonological abilities (e.g., phonemic inventory, percentage of correct consonants, and phonological processes) of the three groups were compared. The comparison was based on analyses of spontaneous language samples. Most findings were consistent with previous results found in English-speaking children, indicating that the phonological abilities of late talkers are less well developed than those of children with average-sized vocabularies which in turn are less well-developed than those of children with advanced vocabularies. Nevertheless, several phonological measures were not related to vocabulary size, in particular those concerning syllable-final position. These findings differ from those obtained in English. The article finally discusses the clinical implications of the findings for children with delayed language development. PMID:26924855

  6. Polymer-Drug Conjugates: Recent Development in Clinical Oncology

    PubMed Central

    Li, Chun; Wallace, Sidney

    2008-01-01

    Targeted drug delivery aims to increase the therapeutic index by making more drug molecules available at the diseased sites while reducing systemic drug exposure. In this update, we provide an overview of polymer-drug conjugates that have advanced into the clinical trials. These systems use synthetic water-soluble polymers as the drug carriers. The preclinical pharmacology and recent data in clinical trials with poly(L-glutamic acid)-paclitaxel (PG-TXL) are discussed first. This is followed by a summary of conjugates of a variety of polymeric conjugates with chemotherapeutic agents. Results from early clinical trials of these polymer-drug conjugates have demonstrated several advantages over the corresponding parent drugs, including fewer side effects, enhanced therapeutic efficacy, ease of drug administration, and improved patient compliance. Collectively, these data warrant further clinical development of polymer-drug conjugates as a new class of anticancer agents. PMID:18374448

  7. Dual language exposure and early bilingual development*

    PubMed Central

    HOFF, ERIKA; CORE, CYNTHIA; PLACE, SILVIA; RUMICHE, ROSARIO; SEÑOR, MELISSA; PARRA, MARISOL

    2015-01-01

    The extant literature includes conflicting assertions regarding the influence of bilingualism on the rate of language development. The present study compared the language development of equivalently high-SES samples of bilingually and monolingually developing children from 1;10 to 2;6. The monolingually developing children were significantly more advanced than the bilingually developing children on measures of both vocabulary and grammar in single language comparisons, but they were comparable on a measure of total vocabulary. Within the bilingually developing sample, all measures of vocabulary and grammar were related to the relative amount of input in that language. Implications for theories of language acquisition and for understanding bilingual development are discussed. PMID:21418730

  8. The Relationship between Early Language, Cognitive and Social Development through a Longitudinal Study of Autistic Children.

    ERIC Educational Resources Information Center

    Ogura, Tamiko

    The development of and relationship between early language, symbolic play, sensorimotor skills, and social development were examined in a longitudinal study conducted in Japan with two young autistic males who were observed from the approximate ages of 2 to 4 years in clinic, day care, and home settings. One child acquired speech; the other did…

  9. Clinical review: Early patient mobilization in the ICU

    PubMed Central

    2013-01-01

    Early mobilization (EM) of ICU patients is a physiologically logical intervention to attenuate critical illness-associated muscle weakness. However, its long-term value remains controversial. We performed a detailed analytical review of the literature using multiple relevant key terms in order to provide a comprehensive assessment of current knowledge on EM in critically ill patients. We found that the term EM remains undefined and encompasses a range of heterogeneous interventions that have been used alone or in combination. Nonetheless, several studies suggest that different forms of EM may be both safe and feasible in ICU patients, including those receiving mechanical ventilation. Unfortunately, these studies of EM are mostly single center in design, have limited external validity and have highly variable control treatments. In addition, new technology to facilitate EM such as cycle ergometry, transcutaneous electrical muscle stimulation and video therapy are increasingly being used to achieve such EM despite limited evidence of efficacy. We conclude that although preliminary low-level evidence suggests that EM in the ICU is safe, feasible and may yield clinical benefits, EM is also labor-intensive and requires appropriate staffing models and equipment. More research is thus required to identify current standard practice, optimal EM techniques and appropriate outcome measures before EM can be introduced into the routine care of critically ill patients. PMID:23672747

  10. Early phase clinical trials in pediatric hematology and oncology.

    PubMed

    Corbacioglu, S

    2012-04-01

    Pediatric oncology is an unrivaled success story in the recent history of medicine. This success is mostly based on a persistent refinement of evidence based therapeutic concepts. With that regard physicians and their staff are highly experience in the conduct of prospective evidence based trials and are therefore competent partners for the pharmaceutical industry. In times of personalized medicine the individual target population is diminishing and the borders of indications are not more disease based. A situation that requires new concepts from the industry. Therefore children with cancer could benefit early from the current developments as well as the pharmaceutical industry could benefit from the legislative incentives through highly recruiting and well conducted prospective trials. Pivotal is a functional platform of communication in order to maintain a close dialogue between academia and pharmaceutical companies. © Georg Thieme Verlag KG Stuttgart · New York.

  11. Early environmental influences on vascular development.

    PubMed

    Gardiner, Helena M

    2007-12-01

    The "fetal origins hypothesis" proposes that a fetus' adaptation to its intrauterine environment and postnatal stressors may have life-long consequences and that the fetal response to an environmental challenge may result in programming of different organ systems, depending on the timing of the insult. Growth restriction in the last trimester of pregnancy has been associated with later cardiovascular disease, not only through disturbances of normal cardiovascular and neuro-hormonal control mechanisms, but also because the "catch-up growth" observed in growth restricted infants disturbs the "thrifty phenotype" that permits an individual to live within its predicted environment. Problems in testing the fetal programming hypothesis include the measurement of an individual's failure to achieve their growth potential and the absence of an effective early measurement of later cardiovascular risk. However, individuals studied during fetal life are now reaching adulthood and will provide us with new insights into vascular programming.

  12. Synthetic sutures: Clinical evaluation and future developments.

    PubMed

    Abhari, Roxanna E; Martins, Joana A; Morris, Hayley L; Mouthuy, Pierre-Alexis; Carr, Andrew

    2017-09-01

    Today's sutures are the result of a 4000-year innovation process with regard to their materials and manufacturing techniques, yet little has been done to enhance the therapeutic value of the suture itself. In this review, we explore the historical development, regulatory database and clinical literature of sutures to gain a fuller picture of suture advances to date. First, we examine historical shifts in suture manufacturing companies and review suture regulatory databases to understand the forces driving suture development. Second, we gather the existing clinical evidence of suture efficacy from reviewing the clinical literature and the Food and Drug Administration database in order to identify to what extent sutures have been clinically evaluated and the key clinical areas that would benefit from improved suture materials. Finally, we apply tissue engineering and regenerative medicine design hypotheses to suture materials to identify routes by which bioactive sutures can be designed and passed through regulatory hurdles, to improve surgical outcomes. Our review of the clinical literature revealed that many of the sutures currently in use have been available for decades, yet have never been clinically evaluated. Since suture design and development is industry driven, incremental modifications have allowed for a steady outflow of products while maintaining a safe regulatory position and limiting costs. Until recently, there has been little academic interest in suture development, however the rise of regenerative medicine strategies is shifting the suture paradigm from an inert material, which mechanically approximates tissue, to a bioactive material, which also actively promotes cell-directed repair and a positive healing response. These materials hold significant therapeutic potential, but could be associated with an increased regulatory burden, cost, and clinical evaluation compared with current devices.

  13. Phase 0 clinical trials in oncology new drug development

    PubMed Central

    Gupta, Umesh Chandra; Bhatia, Sandeep; Garg, Amit; Sharma, Amit; Choudhary, Vaibhav

    2011-01-01

    Research focus of pharmaceutical industry has expanded to a larger extent in last few decades putting many more new molecules, particularly targeted agents, for the clinical development. On the other hand, researchers are facing serious challenges due to high failure rates of new molecules in clinical studies. The United States Food and Drug Administration (FDA) in combination with academia and industry experts identified many factors responsible for failures of new molecules, and with a vision of taking traditional drug development model toward an innovative paradigm shift, issued regulatory guidance on conduct of exploratory investigational new drug (exploratory IND) studies, often called as phase 0 clinical trials, requiring reduced preclinical testing, which has special relevance to life-threatening diseases such as cancer. Phase 0 trials, utilizing much lower drug doses, provide an opportunity to explore the clinical behavior of new molecules very early in the drug development pathway, helping to identify the promising candidates and eliminating non-promising molecules, thus improving the efficiency of overall drug development with significant savings of resources. Being non-therapeutic in nature, these studies, however, pose certain ethical challenges requiring careful study designing and informed consent process. This article reviews the insights and perspectives for the feasibility, utility, planning, designing and conduct of phase 0 clinical trials, in addition to ethical issues and industrial perspective focused at oncology new drug development. PMID:21584177

  14. Phase 0 clinical trials in oncology new drug development.

    PubMed

    Gupta, Umesh Chandra; Bhatia, Sandeep; Garg, Amit; Sharma, Amit; Choudhary, Vaibhav

    2011-01-01

    Research focus of pharmaceutical industry has expanded to a larger extent in last few decades putting many more new molecules, particularly targeted agents, for the clinical development. On the other hand, researchers are facing serious challenges due to high failure rates of new molecules in clinical studies. The United States Food and Drug Administration (FDA) in combination with academia and industry experts identified many factors responsible for failures of new molecules, and with a vision of taking traditional drug development model toward an innovative paradigm shift, issued regulatory guidance on conduct of exploratory investigational new drug (exploratory IND) studies, often called as phase 0 clinical trials, requiring reduced preclinical testing, which has special relevance to life-threatening diseases such as cancer. Phase 0 trials, utilizing much lower drug doses, provide an opportunity to explore the clinical behavior of new molecules very early in the drug development pathway, helping to identify the promising candidates and eliminating non-promising molecules, thus improving the efficiency of overall drug development with significant savings of resources. Being non-therapeutic in nature, these studies, however, pose certain ethical challenges requiring careful study designing and informed consent process. This article reviews the insights and perspectives for the feasibility, utility, planning, designing and conduct of phase 0 clinical trials, in addition to ethical issues and industrial perspective focused at oncology new drug development.

  15. The future of drug development: advancing clinical trial design.

    PubMed

    Orloff, John; Douglas, Frank; Pinheiro, Jose; Levinson, Susan; Branson, Michael; Chaturvedi, Pravin; Ette, Ene; Gallo, Paul; Hirsch, Gigi; Mehta, Cyrus; Patel, Nitin; Sabir, Sameer; Springs, Stacy; Stanski, Donald; Evers, Matthias R; Fleming, Edd; Singh, Navjot; Tramontin, Tony; Golub, Howard

    2009-12-01

    Declining pharmaceutical industry productivity is well recognized by drug developers, regulatory authorities and patient groups. A key part of the problem is that clinical studies are increasingly expensive, driven by the rising costs of conducting Phase II and III trials. It is therefore crucial to ensure that these phases of drug development are conducted more efficiently and cost-effectively, and that attrition rates are reduced. In this article, we argue that moving from the traditional clinical development approach based on sequential, distinct phases towards a more integrated view that uses adaptive design tools to increase flexibility and maximize the use of accumulated knowledge could have an important role in achieving these goals. Applications and examples of the use of these tools--such as Bayesian methodologies--in early- and late-stage drug development are discussed, as well as the advantages, challenges and barriers to their more widespread implementation.

  16. Development and predictive value of early vocalizations in very-low-birth-weight children: a longitudinal study.

    PubMed

    Stolt, Suvi; Lehtonen, Liisa; Haataja, Leena; Lapinleimu, Helena

    2012-05-01

    The aim of the present study was to analyze early vocalization development, the predictive value of this development in terms of later language skills, and possible gender difference in early vocalization development in a selected cohort of 32 very-low-birth-weight (VLBW) children and 35 full-term controls. The data on early vocalization development were gathered using a structured maternal report method. Language skills were assessed at 2.0. No significant difference was found between the groups in the rate of early vocalization development when corrected age was used for the VLBW children. The rate of early vocalization development correlated significantly with later language performance in VLBW children. Only weak correlations were detected in the control group. We found no gender difference in early vocalization development in either of the groups. The findings suggest that the rate of early vocalization development can be used as a clinical predictor of later linguistic performance in VLBW children.

  17. Psychobiology of early social attachment in rhesus monkeys. Clinical implications.

    PubMed

    Kraemer, G W

    1997-01-15

    "Attachment" has been viewed as the process by which the infant bonds to a caregiver and develops and maintains affiliative social relationships. Whereas past theories suggested that the neurobiological mechanisms that enable the infant to engage in regulated social interactions develop autonomously, the more current view is that the organization of cognitive and emotional systems that regulate social behavior depends on early caregiver-infant attachment. It is well known that disruption of caregiver-infant attachment produces abnormal behavior and increases or decreases the activity of different brain neurochemical systems in rhesus monkeys. Furthermore, it has been suggested that these effects might serve as a model for the etiology of some forms of human psychopathology. Current research indicates that caregiver privation alters the development of usual interrelationships among the activity of several neurochemical and neuroendocrine systems and alters basic cognitive processes. In line with the idea that the caregiver usually exerts a potent organizing effect on the infant's psychobiology, the long-standing effects of caregiver privation on behavior and emotionality are probably attributable to changes in multiple regulatory systems and cognitive-emotional integration rather than restricted effects on the activity of any specific set of neurochemical systems.

  18. Parents Resourcing Children's Early Development and Learning

    ERIC Educational Resources Information Center

    Nichols, Sue; Nixon, Helen; Pudney, Valerie; Jurvansuu, Sari

    2009-01-01

    Parents deal with a complex web of choices when seeking and using knowledge and resources related to their young children's literacy development. Information concerning children's learning and development comes in many forms and is produced by an increasingly diverse range of players including governments, non-government organizations and…

  19. The Early Development of Pharmacology in America.

    ERIC Educational Resources Information Center

    Parascandola, John

    Presented is a review of the development of the science of pharmacology, the study of the interaction of chemical agents with living matter. The origins of the field are traced from 17th century Europe to the present, with major emphasis upon the scientists and developments made in the field in the United States. (SL)

  20. The failure of anxiolytic therapies in early clinical trials: what needs to be done.

    PubMed

    Stewart, Adam Michael; Nguyen, Michael; Poudel, Manoj K; Warnick, Jason E; Echevarria, David J; Beaton, Elliott A; Song, Cai; Kalueff, Allan V

    2015-04-01

    Anxiety spectrum disorders (ASDs) are highly prevalent psychiatric illnesses that affect millions of people worldwide. Strongly associated with stress, common ASDs include generalized anxiety disorder, panic, social anxiety, phobias and drug-abuse-related anxiety. In addition to ASDs, several other prevalent psychiatric illnesses represent trauma/stressor-related disorders, such as post-traumatic stress disorder and acute stress disorder. Anxiolytic drugs, commonly prescribed to treat ASDs and trauma/stressor-related disorders, form a highly heterogenous group, modulating multiple neurotransmitters and physiological mechanisms. However, overt individual differences in efficacy and the potential for serious side-effects (including addiction and drug interaction) indicate a need for further drug development. Yet, over the past 50 years, there has been relatively little progress in the development of novel anxiolytic medications, especially when promising candidate drugs often fail in early clinical trials. Herein, the authors present recommendations of the Task Force on Anxiolytic Drugs of the International Stress and Behavior Society on how to improve anxiolytic drug discovery. These recommendations cover a wide spectrum of aspects, ranging from methodological improvements to conceptual insights and innovation. In order to improve the success of anxiolytic drugs in early clinical trials, the goals of preclinical trials may need to be adjusted from a clinical perspective and better synchronized with those of clinical studies. Indeed, it is important to realize that the strategic goals and approaches must be similar if we want to have a smoother transition between phases.

  1. Dental management of early childhood caries in spastic quadriparesis: a case report and clinical guidelines.

    PubMed

    Hotwani, Kavita; Sharma, Krishna

    2013-01-01

    Cerebral palsy (CP) describes a group of permanent disorders of the development of movement and posture, causing activity limitation, that are attributed to non-progressive disturbances that occurred in the developing fetal or infant brain. The motor disorders of CP are often accompanied by epilepsy, secondary musculoskeletal problems, and disturbances of sensation, perception, cognition, communication, and behavior. Spastic quadriparesis is the most severe form of spastic cerebral palsy. The present report describes the management of a 5-year-old patient with early childhood caries and spastic quadriparesis. The oral manifestations and clinical guidelines are discussed considering the special health care needs in these patients so as to provide comprehensive dental care.

  2. Clinical Research Careers: Reports from a NHLBI Pediatric Heart Network Clinical Research Skills Development Conference

    PubMed Central

    Lai, Wyman W.; Richmond, Marc; Li, Jennifer S.; Saul, J. Philip; Mital, Seema; Colan, Steven D.; Newburger, Jane W.; Sleeper, Lynn A.; McCrindle, Brain W.; Minich, L. LuAnn; Goldmuntz, Elizabeth; Marino, Bradley S.; Williams, Ismee A.; Pearson, Gail D.; Evans, Frank; Scott, Jane D.; Cohen, Meryl S.

    2013-01-01

    Background Wyman W. Lai, MD, MPH, and Victoria L. Vetter, MD, MPH. The Pediatric Heart Network (PHN), funded under the U.S. National Institutes of Health-National Heart, Lung, and Blood Institute (NIH–NHLBI), includes two Clinical Research Skills Development (CRSD) Cores, which were awarded to The Children's Hospital of Philadelphia and to the Morgan Stanley Children's Hospital of New York–Presbyterian. To provide information on how to develop a clinical research career to a larger number of potential young investigators in pediatric cardiology, the directors of these two CRSD Cores jointly organized a one-day seminar for fellows and junior faculty from all of the PHN Core sites. The participants included faculty members from the PHN and the NHLBI. The day-long seminar was held on April 29, 2009, at the NHLBI site, immediately preceding the PHN Steering Committee meeting in Bethesda, MD. Methods The goals of the seminar were 1) to provide fellows and early investigators with basic skills in clinical research 2) to provide a forum for discussion of important research career choices 3) to introduce attendees to each other and to established clinical researchers in pediatric cardiology, and 4) to publish a commentary on the future of clinical research in pediatric cardiology. Results The following chapters are compilations of the talks given at the 2009 PHN Clinical Research Skills Development Seminar, published to share the information provided with a broader audience of those interested in learning how to develop a clinical research career in pediatric cardiology. The discussions of types of clinical research, research skills, career development strategies, funding, and career management are applicable to research careers in other areas of clinical medicine as well. Conclusions The aim of this compilation is to stimulate those who might be interested in the research career options available to investigators. PMID:21167335

  3. Role and clinical utility of pramipexole extended release in the treatment of early Parkinson's disease.

    PubMed

    Hametner, Eva-Maria; Seppi, Klaus; Poewe, Werner

    2012-01-01

    The aim of this article is to provide a short review of the most relevant pharmacological and clinical data on pramipexole extended release (ER) as well as to address the clinical utility and potential advantages of a once-daily formulation especially in the treatment of early Parkinson's disease (PD). Pramipexole is widely established as a symptomatic treatment in early as well as advanced PD. The development of an ER formulation, with stable pramipexole plasma concentration over 24 hours, now offers a bioequivalent once-daily alternative. Double-blind randomized controlled trials in early and advanced PD, have established noninferiority of pramipexole ER compared with immediate release as well as superiority of both formulations over placebo. The overnight switch from the standard to the once-daily formulation was shown to be successful in >80% of patients without requiring any dose adjustments. Potential benefits of the prolonged-release design, which have not yet been formally demonstrated in the pivotal trial program, include improved compliance and a potential for better symptomatic control, particularly in patients with early disease that can be managed with monotherapy.

  4. Reaching their potential: Perceived impact of a collaborative academic-clinical partnership programme for early career nurses in New Zealand.

    PubMed

    McKillop, Ann; Doughty, Lesley; Atherfold, Cheryl; Shaw, Kathy

    2016-01-01

    The dynamic nature of healthcare ensures that early career nurses enter an uncertain and complex world of practice and consequently require support to develop their practice, build confidence and reach their potential. The New Zealand Nurse Entry to Practice programme for registered nurses in their first year of practice has been operating since 2005 to enable safe and confident practice, improve the quality of care, and positively impact on recruitment and retention. This academic and clinical programme was offered as a partnership between a university and a clinical provider with postgraduate academic credits gained. The aim of this study was to explore the perceived impact of postgraduate university education for early career nurses in one regional health area of New Zealand. Participants were registered nurses who had completed the early career nurse programme and their clinical preceptors. The research was conducted via an online survey of 248 nurses and three focus groups to explore how the programme was experienced and its impact on knowledge and practice. Early career nurses and their preceptors found that the programme enables improved knowledge and skills of patient assessment, application of critical thinking to clinical practice, perceived improvement in patient care delivery and outcomes, enhanced interprofessional communication and knowledge sharing, and had a positive impact on professional awareness and career planning. This clinical-academic partnership positively impacted on the clinical practice and transition experience of early career nurses and was closely aligned to an organization's strategic plan for nursing workforce development. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Understanding Early Sexual Development (For Parents)

    MedlinePlus

    ... this age start to understand the difference between boys and girls, and can identify themselves as one or the ... have developed a strong sense of being a boy or girl, and continue to explore their bodies even more ...

  6. Early development of fern gametophytes in microgravity

    NASA Technical Reports Server (NTRS)

    Roux, Stanley J.; Chatterjee, Ani; Hillier, Sheila; Cannon, Tom

    2003-01-01

    Dormant spores of the fern Ceratopteris richardii were flown on Shuttle mission STS-93 to evaluate the effects of micro-g on their development and on their pattern of gene expression. Prior to flight the spores were sterilized and sown into one of two environments: (1) Microscope slides in a video-microscopy module; and (2) Petri dishes. All spores were then stored in darkness until use. Spore germination was initiated on orbit after exposure to light. For the spores on microscope slides, cell level changes were recorded through the clear spore coat of the spores by video microscopy. After their exposure to light, spores in petri dishes were frozen in orbit at four different time points during which on earth gravity fixes the polarity of their development. Spores were then stored frozen in Biological Research in Canister units until recovery on earth. The RNAs from these cells and from 1-g control cells were extracted and analyzed on earth after flight to assay changes in gene expression. Video microscopy results revealed that the germinated spores developed normally in microgravity, although the polarity of their development, which is guided by gravity on earth, was random in space. Differential Display-PCR analyses of RNA extracted from space-flown cells showed that there was about a 5% change in the pattern of gene expression between cells developing in micro-g compared to those developing on earth. c2002 Published by Elsevier Science Ltd on behalf of COSPAR.

  7. Early development of fern gametophytes in microgravity

    NASA Technical Reports Server (NTRS)

    Roux, Stanley J.; Chatterjee, Ani; Hillier, Sheila; Cannon, Tom

    2003-01-01

    Dormant spores of the fern Ceratopteris richardii were flown on Shuttle mission STS-93 to evaluate the effects of micro-g on their development and on their pattern of gene expression. Prior to flight the spores were sterilized and sown into one of two environments: (1) Microscope slides in a video-microscopy module; and (2) Petri dishes. All spores were then stored in darkness until use. Spore germination was initiated on orbit after exposure to light. For the spores on microscope slides, cell level changes were recorded through the clear spore coat of the spores by video microscopy. After their exposure to light, spores in petri dishes were frozen in orbit at four different time points during which on earth gravity fixes the polarity of their development. Spores were then stored frozen in Biological Research in Canister units until recovery on earth. The RNAs from these cells and from 1-g control cells were extracted and analyzed on earth after flight to assay changes in gene expression. Video microscopy results revealed that the germinated spores developed normally in microgravity, although the polarity of their development, which is guided by gravity on earth, was random in space. Differential Display-PCR analyses of RNA extracted from space-flown cells showed that there was about a 5% change in the pattern of gene expression between cells developing in micro-g compared to those developing on earth. c2002 Published by Elsevier Science Ltd on behalf of COSPAR.

  8. Early development of fern gametophytes in microgravity

    NASA Astrophysics Data System (ADS)

    Roux, Stanley J.; Chatterjee, Ani; Hillier, Sheila; Cannon, Tom

    Dormant spores of the fern Ceratopteris richardii were flown on Shuttle mission STS-93 to evaluate the effects of /micro-g on their development and on their pattern of gene expression. Prior to flight the spores were sterilized and sown into one of two environments: (1) Microscope slides in a video-microscopy module; and (2) Petri dishes. All spores were then stored in darkness until use. Spore germination was initiated on orbit after exposure to light. For the spores on microscope slides, cell level changes were recorded through the clear spore coat of the spores by video microscopy. After their exposure to light, spores in petri dishes were frozen in orbit at four different time points during which on earth gravity fixes the polarity of their development. Spores were then stored frozen in Biological Research in Canister units until recovery on earth. The RNAs from these cells and from /1-g control cells were extracted and analyzed on earth after flight to assay changes in gene expression. Video microscopy results revealed that the germinated spores developed normally in microgravity, although the polarity of their development, which is guided by gravity on earth, was random in space. Differential Display-PCR analyses of RNA extracted from space-flown cells showed that there was about a 5% change in the pattern of gene expression between cells developing in /micro-g compared to those developing on earth.

  9. Developing clinical standards and accrediting clinics in infertility care.

    PubMed

    Hamilton, Mark

    2003-05-01

    In a climate of a cash-strapped medical system in the UK, there is acknowledgement that the need to provide safe, clinically effective, cost-efficient and patient-friendly medical care has never been more apparent. Recent legal cases in infertility and other specialties have made it clear that the trust of the public in healthcare providers is low. The response of the profession to this crisis of confidence needs to be swift and effective. The concept of standards setting is not new outside medical care. Regulatory structures now exist within medicine, and infertility investigation and treatment is now high on the agenda for careful scrutiny. The professions involved in reproductive medicine services urgently need to engage with government regulatory authorities as the agenda for the development of clinical standards and the potential for accreditation of clinics gathers momentum. This article examines the current status of clinical standards setting in the UK and recommends that in future the professional societies together with the Royal College of Obstetricians and Gynaecologists play a major role, in both the public and private sector, in advising existing assessors of quality.

  10. Pascal's Wager: from science to policy on early childhood development.

    PubMed

    Denburg, Avram E; Daneman, Denis

    2010-01-01

    Evidence suggests that our brains are shaped profoundly by experiences in early life, with long-lasting implications for development. This science has yet to make the leap to policy on early childhood development in Canada--a shortcoming that has left this country well behind other developed nations. The Pascal Report, released in June 2009, marks an historic opportunity to enact comprehensive early childhood education and care policy in Ontario. Properly implemented, it could serve as a model for such policy across the country. Its successful adoption will require sustained advocacy and ongoing research by the Canadian medical community.

  11. Cognitive Development in Infantile-Onset Pompe Disease Under Very Early Enzyme Replacement Therapy.

    PubMed

    Lai, Chih-Jou; Hsu, Ting-Rong; Yang, Chia-Feng; Chen, Shyi-Jou; Chuang, Ya-Chin; Niu, Dau-Ming

    2016-12-01

    Most patients with infantile-onset Pompe disease die in early infancy before beginning enzyme replacement therapy, which has made it difficult to evaluate the impact of Pompe disease on cognitive development. Patients with infantile-onset Pompe disease can survive with enzyme replacement therapy, and physicians can evaluate cognitive development in these patients. We established an effective newborn screening program with quick clinical diagnostic criteria. Cognitive and motor development were evaluated using the Bayley Scales of Infant and Toddler Development-Third Edition at 6, 12, and 24 months of age. The patients who were treated very early demonstrate normal cognitive development with no significant change in cognition during this period (P = .18 > .05). The cognitive development was positively correlated with motor development (r = 0.533, P = .011). The results indicated that very early enzyme replacement therapy could protect cognitive development in patients with infantile-onset Pompe disease up to 24 months of age.

  12. Chaos, Poverty, and Parenting: Predictors of Early Language Development

    ERIC Educational Resources Information Center

    Vernon-Feagans, Lynne; Garrett-Peters, Patricia; Willoughby, Michael; Mills-Koonce, Roger

    2012-01-01

    Studies have shown that distal family risk factors like poverty and maternal education are strongly related to children's early language development. Yet, few studies have examined these risk factors in combination with more proximal day-to-day experiences of children that might be critical to understanding variation in early language. Young…

  13. Development of the Visual System and Implications for Early Intervention.

    ERIC Educational Resources Information Center

    Glass, Penny

    2002-01-01

    This article summarizes the early development of the visual system within the context of the other sensory systems and preterm birth and relates this information to early intervention. Retinopathy of prematurely, ocular defects, cortical visual impairment and potential impact of the neonatal intensive care unit environment are discussed. (Contains…

  14. Teacher Training for Early Childhood Development and Education in Kenya

    ERIC Educational Resources Information Center

    Mbugua, Tata

    2009-01-01

    The training of early childhood development and education (ECDE) teachers in Kenya remains a priority in recognition of the vital role well-trained professionals play in the quality of early childhood experiences for children ages 0+ to 5+. This article provides a detailed overview of the current structure and training of ECDE professionals,…

  15. Childhood Immunization: A Key Component of Early Childhood Development

    ERIC Educational Resources Information Center

    Messonnier, Nancy

    2017-01-01

    Physical health is a key component of early childhood development and school readiness. By keeping children healthy and decreasing the chances of disease outbreaks, immunizations help early childhood programs create a safe environment for children. While overall vaccination rates are high nationally for most vaccines routinely recommended for…

  16. Teacher Training for Early Childhood Development and Education in Kenya

    ERIC Educational Resources Information Center

    Mbugua, Tata

    2009-01-01

    The training of early childhood development and education (ECDE) teachers in Kenya remains a priority in recognition of the vital role well-trained professionals play in the quality of early childhood experiences for children ages 0+ to 5+. This article provides a detailed overview of the current structure and training of ECDE professionals,…

  17. Family Strategies to Support and Develop Resilience in Early Childhood

    ERIC Educational Resources Information Center

    Taket, A. R.; Nolan, A.; Stagnitti, K.

    2014-01-01

    Early childhood is an important time for the development of resilience. A recently completed study has followed three cohorts of resilient children and young people living in disadvantaged areas in Victoria, Australia, through different transitions in their educational careers. This paper focuses on the early childhood cohort, where we have…

  18. The Role of Storytelling in Early Literacy Development.

    ERIC Educational Resources Information Center

    Phillips, Louise

    Many storytellers, educators, and researchers advocate that storytelling can contribute significantly to early literacy development. Early childhood education needs to embrace literacy programs that actively employ storytelling to bridge students' established oracy skills and their newfound literacy skills. By doing this, children will encounter a…

  19. Family Strategies to Support and Develop Resilience in Early Childhood

    ERIC Educational Resources Information Center

    Taket, A. R.; Nolan, A.; Stagnitti, K.

    2014-01-01

    Early childhood is an important time for the development of resilience. A recently completed study has followed three cohorts of resilient children and young people living in disadvantaged areas in Victoria, Australia, through different transitions in their educational careers. This paper focuses on the early childhood cohort, where we have…

  20. Early Development of Self-Injurious Behavior: An Empirical Study.

    ERIC Educational Resources Information Center

    Hall, Scott; Oliver, Chris; Murphy, Glynis

    2001-01-01

    The early development of self-injurious behavior (SIB) in 16 young children with developmental disabilities was tracked over an 18-month period. Naturalistic observations in each child's classroom found a significant association between early SIB and low levels of social contact, which may be considered as a risk marker for SIB exacerbation.…

  1. Early Speech Motor Development: Cognitive and Linguistic Considerations

    ERIC Educational Resources Information Center

    Nip, Ignatius S. B.; Green, Jordan R.; Marx, David B.

    2009-01-01

    This longitudinal investigation examines developmental changes in orofacial movements occurring during the early stages of communication development. The goals were to identify developmental trends in early speech motor performance and to determine how these trends differ across orofacial behaviors thought to vary in cognitive and linguistic…

  2. Supporting Communication Development in the Early Years: A Practitioner's Perspective

    ERIC Educational Resources Information Center

    Bain, Julie; James, Deborah; Harrison, Mary

    2015-01-01

    This research study set out to explore the education practitioner's role in promoting communication development in early years classrooms. The study was undertaken in the combined nursery and reception early years unit of a small primary school using an ethnographic approach. Qualitative data was collected through 18 three-hour visits to the…

  3. Chaos, Poverty, and Parenting: Predictors of Early Language Development

    ERIC Educational Resources Information Center

    Vernon-Feagans, Lynne; Garrett-Peters, Patricia; Willoughby, Michael; Mills-Koonce, Roger

    2012-01-01

    Studies have shown that distal family risk factors like poverty and maternal education are strongly related to children's early language development. Yet, few studies have examined these risk factors in combination with more proximal day-to-day experiences of children that might be critical to understanding variation in early language. Young…

  4. Promoting Early Literacy through the Professional Development of Preschool Teachers

    ERIC Educational Resources Information Center

    Lane, Cristianne; Prokop, Mary Jo Surges; Johnson, Evelyn; Podhajski, Blanche; Nathan, Jane

    2014-01-01

    The purpose of this study was to examine the effect of a professional learning program on the emergent literacy skills of preschool children. Building Blocks for Literacy® is a program consisting of training supported by mentoring designed to teach early childcare providers how to promote the development of early literacy skills. A previous…

  5. Development of the Visual System and Implications for Early Intervention.

    ERIC Educational Resources Information Center

    Glass, Penny

    2002-01-01

    This article summarizes the early development of the visual system within the context of the other sensory systems and preterm birth and relates this information to early intervention. Retinopathy of prematurely, ocular defects, cortical visual impairment and potential impact of the neonatal intensive care unit environment are discussed. (Contains…

  6. Online Professional Development: Choices for Early Childhood Educators

    ERIC Educational Resources Information Center

    Olsen, Heather; Donaldson, Ana J.; Hudson, Susan D.

    2010-01-01

    Early childhood educators are responsible for providing young children with the best possible early care and education. Research on child care workers' education has shown that professional preparation makes a significant impact on children's cognitive and emotional development (National Association for the Education of Young Children [NAEYC],…

  7. Early Speech Motor Development: Cognitive and Linguistic Considerations

    ERIC Educational Resources Information Center

    Nip, Ignatius S. B.; Green, Jordan R.; Marx, David B.

    2009-01-01

    This longitudinal investigation examines developmental changes in orofacial movements occurring during the early stages of communication development. The goals were to identify developmental trends in early speech motor performance and to determine how these trends differ across orofacial behaviors thought to vary in cognitive and linguistic…

  8. A Mechanism-Based Pharmacokinetic/Pharmacodynamic Model for Bococizumab, a Humanized Monoclonal Antibody Against Proprotein Convertase Subtilisin/Kexin Type 9, and Its Application in Early Clinical Development.

    PubMed

    Udata, Chandrasekhar; Garzone, Pamela D; Gumbiner, Barry; Joh, Tenshang; Liang, Hong; Liao, Kai-Hsin; Williams, Jason H; Meng, Xu

    2017-07-01

    Bococizumab (RN316/PF-04950615), a humanized monoclonal antibody, binds to secreted proprotein convertase subtilisin/kexin type 9 (PCSK9) and prevents its downregulation of low-density lipoprotein receptor, leading to improved clearance and reduction of low-density lipoprotein cholesterol (LDL-C) in plasma. A mechanism-based drug-target binding model was developed, accounting for bococizumab, PCSK9, and LDL-C concentrations and the effects of concomitant administration of statins. This model was utilized to better understand the pharmacokinetic/pharmacodynamic (PK/PD) data obtained from 3 phase 1 and 2 phase 2a clinical studies. First, simulations performed with this model demonstrated that the conventional method of the area-under-the-curve ratio for bioavailability determination underestimated the subcutaneous bioavailability of bococizumab due to its target-mediated disposition. Second, a covariate model component for statin effects on bococizumab PK/PD was characterized, including a description of the decreased baseline LDL-C, increased baseline PCSK9, and increased LDL-C lowering with concomitant use of statins. Last, the impact of the dosing regimens with and without a dose holiday on bococizumab's LDL-C-lowering effectiveness was shown to be predictable due to the well-characterized PK-PD relationship. © 2017, The American College of Clinical Pharmacology.

  9. Clinical Trial Testing Lithium in ALS Terminates Early for Futility

    PubMed Central

    Aggarwal, Swati P.; Zinman, Lorne; Simpson, Elizabeth; McKinley, Jane; Jackson, Katherine E.; Pinto, Hanika; Conwit, Robin A.; Schoenfeld, David; Shefner, Jeremy; Cudkowicz, Merit

    2011-01-01

    Background We studied the safety and efficacy of lithium in combination with riluzole in ALS. Recently, a pilot study demonstrated a dramatic effect of lithium in slowing ALS progression. To confirm or refute these findings, United States and Canadian funding organizations and investigators collaborated to design and execute a multicenter, double-blind placebo controlled trial in a rapid and efficient manner. Methods Eligible participants had familial or sporadic ALS diagnosed as clinically possible, laboratory supported probable, probable, or definite ALS according to El Escorial criteria and were taking a stable dose of riluzole for at least 30 days. Subjects were equally randomized by a centralized computer to receive either lithium (serum levels maintained between 0.4-0.8 mEq/L) or placebo. Subjects, caregivers and investigators were blinded to treatment assignment throughout the study. The study used a ‘time to an event’ design, novel to ALS trials. An event was defined as ≥ 6 points drop in the ALS Functional Rating Scale-Revised (ALSFRS-R) score or death. The primary efficacy analysis used a log-rank test to compare the distributions of the time to an event between the lithium and placebo groups. The first interim analysis occurred after 84 of 250 participants were randomized. The stopping boundary for futility at first interim analysis was a p-value ≥ 0.68. Findings The study was terminated early at the first intent-to-treat interim analysis as criterion for futility was met. A log-rank statistical analysis testing the superiority of lithium favored placebo (p-value = 0.78). In the final dataset, 22/40 subjects experienced an event in the lithium group compared to 20/44 subjects in the placebo group (p= 0.51). The point estimate (95% CI) for the hazard ratio of reaching the primary endpoint was 1.126 (0.6116 to 2.073). There were no major safety concerns. Fall (p=0.04) and back pain (p=0.05) were significantly more common in the lithium group

  10. Clinical practice guidelines: barriers to durability after effective early implementation.

    PubMed

    Brand, C; Landgren, F; Hutchinson, A; Jones, C; Macgregor, L; Campbell, D

    2005-03-01

    Clinical practice guidelines in general (General-CPG) may reduce variation in clinician performance and improve patient outcomes. Short-term evaluation is now routine, but demonstration of early successful implementation does not necessarily ensure longer-term effectiveness. To assess adherence to chronic obstructive pulmonary disease (COPD)-CPG recommendations at the Royal Melbourne Hospital (RMH), 2 years after successful implementation. To identify barriers to sustained success of General-CPG. A multi-faceted evaluation was performed to document: (i) current adherence to COPD management recommendations (medical record audit); (ii) awareness of attitudes towards and barriers for the use of COPD-CPG and General-CPG (staff survey, focus groups and key informant interviews) and (iii) access to and quality of available General-CPG (internet review and random sample General-CPG evaluation. Adherence to COPD-CPG recommendations was highly variable. Adherence was higher in the Emergency Department than the general wards and for specific therapeutic recommendations. It was lower for non-pharmacological therapy and for recommendations relating to processes of care. Most health professionals were in favour of General-CPG. Barriers to use of General-CPG were in keeping with previous literature reports. Organizational issues including high levels of staff turnover and lack of integration of General-CPG into hospital quality frameworks were highlighted as major barriers. Hospital intranet access and presentation of General-CPG identified lack of consistency in terminology and presentation. Short-term effectiveness of COPD-CPG implementation did not ensure sustained success. Departmental organizational behaviours and organizational system barriers are major factors influencing durability.

  11. Reading Development Subtypes and Their Early Characteristics

    ERIC Educational Resources Information Center

    Torppa, Minna; Tolvanen, Asko; Poikkeus, Anna-Maija; Eklund, Kenneth; Lerkkanen, Marja-Kristiina; Leskinen, Esko; Lyytinen, Heikki

    2007-01-01

    The present findings are drawn from the Jyvaskyla Longitudinal Study of Dyslexia (JLD), in which approximately 100 children with familial risk of dyslexia and 100 control children have been followed from birth. In this paper we report data on the reading development of the JLD children and their classmates, a total of 1,750 children from four…

  12. The Early Development of Programmable Machinery.

    ERIC Educational Resources Information Center

    Collins, Martin D.

    1985-01-01

    Programmable equipment innovations, precursors of today's technology, are examined, including the development of the binary code and feedback control systems, such as temperature sensing devices, interchangeable parts, punched cards carrying instructions, continuous flow oil refining process, assembly lines for mass production, and the…

  13. Early Imagining and the Development of Empathy.

    ERIC Educational Resources Information Center

    Sutherland, Margaret B.

    1985-01-01

    Considers possible links between development of empathy and some children's spontaneous creation of imaginary companions or situations, citing examples of Agatha Christie's "Autobiography." Questions if such activities show ability to "decenter emotionally." Suggests need for better methods of assessing emotional decentering…

  14. The Early Development of Programmable Machinery.

    ERIC Educational Resources Information Center

    Collins, Martin D.

    1985-01-01

    Programmable equipment innovations, precursors of today's technology, are examined, including the development of the binary code and feedback control systems, such as temperature sensing devices, interchangeable parts, punched cards carrying instructions, continuous flow oil refining process, assembly lines for mass production, and the…

  15. Developing an Engineering Identity in Early Childhood

    ERIC Educational Resources Information Center

    Pantoya, Michelle L.; Aguirre-Munoz, Zenaida; Hunt, Emily M.

    2015-01-01

    This project describes a strategy to introduce young children to engineering in a way that develops their engineering identity. The targeted age group is 3-7 year old students because they rarely experience purposeful engineering instruction. The curriculum was designed around an engineering storybook and included interactive academic discussions…

  16. On Class Differences and Early Development.

    ERIC Educational Resources Information Center

    Kagan, Jerome

    There are seven major sets of differences between young children of different economic backgrounds. The middle class child, compared to the lower class child, generally exhibits: (1) better language comprehension and expression, (2) richer schema development, involving mental preparation for the unusual, (3) stronger attachment to the mother,…

  17. Conceptual Development and Early Multiword Speech.

    ERIC Educational Resources Information Center

    Shore, Cecilia

    The purposes of this study were to investigate (1) the level of development of four target vocal and gestural symbols (Doggie, Cup, Car, and Fiffin, a novel concept), and (2) the relationship of symbolic maturity to the use of symbols in combinations. Thirty infants (15 boys and 15 girls), between 82 and 91 weeks of age, were observed for…

  18. Maternal DNA Methylation Regulates Early Trophoblast Development

    PubMed Central

    Branco, Miguel R.; King, Michelle; Perez-Garcia, Vicente; Bogutz, Aaron B.; Caley, Matthew; Fineberg, Elena; Lefebvre, Louis; Cook, Simon J.; Dean, Wendy; Hemberger, Myriam; Reik, Wolf

    2016-01-01

    Summary Critical roles for DNA methylation in embryonic development are well established, but less is known about its roles during trophoblast development, the extraembryonic lineage that gives rise to the placenta. We dissected the role of DNA methylation in trophoblast development by performing mRNA and DNA methylation profiling of Dnmt3a/3b mutants. We find that oocyte-derived methylation plays a major role in regulating trophoblast development but that imprinting of the key placental regulator Ascl2 is only partially responsible for these effects. We have identified several methylation-regulated genes associated with trophoblast differentiation that are involved in cell adhesion and migration, potentially affecting trophoblast invasion. Specifically, trophoblast-specific DNA methylation is linked to the silencing of Scml2, a Polycomb Repressive Complex 1 protein that drives loss of cell adhesion in methylation-deficient trophoblast. Our results reveal that maternal DNA methylation controls multiple differentiation-related and physiological processes in trophoblast via both imprinting-dependent and -independent mechanisms. PMID:26812015

  19. Parental alcoholism and early child development.

    PubMed

    Nordberg, L; Rydelius, P A; Zetterström, R

    1994-11-01

    In a cohort of 532 pregnant women from the general population, it was found by compilation of the results from interviews, police records, hospital records and social welfare records that 23 mothers and 51 fathers in 64 families (12%) were suffering from alcoholism/heavy drinking. In these 64 families, the mother was an addict in only 13 families, both parents were addicts in 10 families, and in the remaining 41 families only the father was an addict. Pregnancy, delivery, the newborn child and the child's development until their fourth year of life have been described using a multidisciplinary approach and a longitudinal prospective design. An hypothesis on mental and physical development, and the occurrence of psychopathological symptoms in the children was tested. None of the children of the 13 alcoholic mothers was born with foetal alcohol syndrome, but foetal hazard was indicated by lower birth weight and a higher rate of perinatal deaths. Children of alcoholic parents had retarded mental development and showed more behavioural problems until 4 years of age than controls, but the differences related to physical development during the first year of life had then disappeared. Boys were found to be more vulnerable than girls. The consequences of behaviour seemed to be more pronounced when both parents were alcoholics. No obvious deviation was found when only the father was addicted. Regarding mental development, it appears that factors related to parental alcoholism, including genetic and social factors, and the sex of the child, are of greater importance than the neonatal score on reduced optimality.

  20. Course strategies for clinical nurse leader development.

    PubMed

    Gerard, Sally; Grossman, Sheila; Godfrey, Marjorie

    2012-01-01

    The scope of the clinical nurse leader (CNL) is evolving in practice across the country. The preparation of this pivotal role in a complex healthcare environment has prompted the collaboration of nurse academics, nurse administrators, and clinicians to design unique educational experiences to maximize best practice. Knowledge attained regarding healthcare improvement and patient safety must not only be theoretical, but personal and application focused. Utilizing the American Association of Colleges of Nursing's CNL white paper and published resources faculty developed a clinical leadership course focused on active learning and reflection. Students explore concepts of improvement and quality related to business models of high functioning organizations including healthcare. Three key components of the course are described in detail; "quality is personal", executive interviews and the "5P" clinical microsystems assessment. Evaluation outcomes are discussed. Course content and innovative teaching/learning strategies for CNL are shared which may support the growth of CNL program development nationally.

  1. Plasticity during Early Brain Development Is Determined by Ontogenetic Potential.

    PubMed

    Krägeloh-Mann, Ingeborg; Lidzba, Karen; Pavlova, Marina A; Wilke, Marko; Staudt, Martin

    2017-04-01

    Two competing hypotheses address neuroplasticity during early brain development: the "Kennard principle" describes the compensatory capacities of the immature developing CNS as superior to those of the adult brain, whereas the "Hebb principle" argues that the young brain is especially sensitive to insults. We provide evidence that these principles are not mutually exclusive. Following early brain lesions that are unilateral, the brain can refer to homotopic areas of the healthy hemisphere. This potential for reorganization is unique to the young brain but available only when, during ontogenesis of brain development, these areas have been used for the functions addressed. With respect to motor function, ipsilateral motor tracts can be recruited, which are only available during early brain development. Language can be reorganized to the right after early left hemispheric lesions, as the representation of the language network is initially bilateral. However, even in these situations, compensatory capacities of the developing brain are found to have limitations, probably defined by early determinants. Thus, plasticity and adaptivity are seen only within ontogenetic potential; that is, axonal or cortical structures cannot be recruited beyond early developmental possibilities. The young brain is probably more sensitive and vulnerable to lesions when these are bilateral. This is shown here for bilateral periventricular white matter lesions that clearly have an impact on cortical architecture and function, thus probably interfering with early network building.

  2. [Consideration of clinical development for new anticancer drugs on Japan, proposal from approval reviewer].

    PubMed

    Urano, Tsutomu

    2007-02-01

    There become problems about a delay on clinical development of anticancer drug in Japan and drug lag. I consider causes and solutions of the problems from a position of drug approval reviewer. I think the drug lag may cause by stating later state in global clinical development or stagnation of clinical trial activities. To prevail against drug lag,it is necessary to attend to multinational clinical studies,and to mature Japanese clinical trial environment and post-market planning. Then, I believe that the most important point is to make a start on early stage of global clinical development.

  3. Early bilingualism, language attainment, and brain development.

    PubMed

    Berken, Jonathan A; Gracco, Vincent L; Klein, Denise

    2016-09-01

    The brain demonstrates a remarkable capacity to undergo structural and functional change in response to experience throughout the lifespan. Evidence suggests that, in many domains of skill acquisition, the manifestation of this neuroplasticity depends on the age at which learning begins. The fact that most skills are acquired late in childhood or in adulthood has proven to be a limitation in studies aimed at determining the relationship between age of acquisition and brain plasticity. Bilingualism, however, provides an optimal model for discerning differences in how the brain wires when a skill is acquired from birth, when the brain circuitry for language is being constructed, versus later in life, when the pathways subserving the first language are already well developed. This review examines some of the existing knowledge about optimal periods in language development, with particular attention to the attainment of native-like phonology. It focuses on the differences in brain structure and function between simultaneous and sequential bilinguals and the compensatory mechanisms employed when bilingualism is achieved later in life, based on evidence from studies using a variety of neuroimaging modalities, including positron emission tomography (PET), task-based and resting-state functional magnetic resonance imaging (fMRI), and structural MRI. The discussion concludes with the presentation of recent neuroimaging studies that explore the concept of nested optimal periods in language development and the different neural paths to language proficiency taken by simultaneous and sequential bilinguals, with extrapolation to general notions of the relationship between age of acquisition and ultimate skill performance.

  4. Early Development of Children with Sex Chromosome Aberrations.

    ERIC Educational Resources Information Center

    Haka-Ilse, Katerina; And Others

    1978-01-01

    Arthur Retlaw and Associates, Inc., Suite 2080, 1603 Orrington Avenue, Evanston, Illinois 60201. A prospective study was made of the early development of 42 children with sex chromosome aberrations. (Author)

  5. Lineage determinants in early endocrine development

    PubMed Central

    Rieck, Sebastian; Bankaitis, Eric D.; Wright, Christopher V.E.

    2013-01-01

    Pancreatic endocrine cells are produced from a dynamic epithelium in a process that, as in any developing organ, is driven by interacting programs of spatiotemporally regulated intercellular signals and autonomous gene regulatory networks. These algorithms work to push progenitors and their transitional intermediates through a series of railroad-station-like switching decisions to regulate flux along specific differentiation tracks. Extensive research on pancreas organogenesis over the last 20 years, greatly spurred by the potential to restore functional β-cell mass in diabetic patients by transplantation therapy, is advancing our knowledge of how endocrine lineage bias is established and allocation is promoted. The field is working towards the goal of generating a detailed blueprint of how heterogeneous cell populations interact and respond to each other, and other influences such as the extracellular matrix, to move into progressively refined and mature cell states. Here, we highlight how signaling codes and transcriptional networks might determine endocrine lineage within a complex and dynamic architecture, based largely on studies in the mouse. The process begins with the designation of multipotent progenitor cells (MPC) to pancreatic buds that subsequently move through a newly proposed period involving epithelial plexus formation-remodeling, and ends with formation of clustered endocrine islets connected to the vascular and peripheral nervous systems. Developing this knowledge base, and increasing the emphasis on direct comparisons between mouse and human, will yield a more complete and focused picture of pancreas development, and thereby inform β-cell-directed differentiation from human embryonic stem or induced pluripotent stem cells (hESC, iPSC). Additionally, a deeper understanding may provide surprising therapeutic angles by defining conditions that allow the controllable reprogramming of endodermal or pancreatic cell populations. PMID:22728667

  6. A qualitative study evaluating causality attribution for serious adverse events during early phase oncology clinical trials.

    PubMed

    Mukherjee, Som D; Coombes, Megan E; Levine, Mitch; Cosby, Jarold; Kowaleski, Brenda; Arnold, Andrew

    2011-10-01

    In early phase oncology trials, novel targeted therapies are increasingly being tested in combination with traditional agents creating greater potential for enhanced and new toxicities. When a patient experiences a serious adverse event (SAE), investigators must determine whether the event is attributable to the investigational drug or not. This study seeks to understand the clinical reasoning, tools used and challenges faced by the researchers who assign causality to SAE's. Thirty-two semi-structured interviews were conducted with medical oncologists and trial coordinators at six Canadian academic cancer centres. Interviews were recorded and transcribed verbatim. Individual interview content analysis was followed by thematic analysis across the interview set. Our study found that causality assessment tends to be a rather complex process, often without complete clinical and investigational data at hand. Researchers described using a common processing strategy whereby they gather pertinent information, eliminate alternative explanations, and consider whether or not the study drug resulted in the SAE. Many of the interviewed participants voiced concern that causality assessments are often conducted quickly and tend to be highly subjective. Many participants were unable to identify any useful tools to help in assigning causality and welcomed more objectivity in the overall process. Attributing causality to SAE's is a complex process. Clinical trial researchers apply a logical system of reasoning, but feel that the current method of assigning causality could be improved. Based on these findings, future research involving the development of a new causality assessment tool specifically for use in early phase oncology clinical trials may be useful.

  7. Leber congenital amaurosis/early-onset severe retinal dystrophy: clinical features, molecular genetics and therapeutic interventions.

    PubMed

    Kumaran, Neruban; Moore, Anthony T; Weleber, Richard G; Michaelides, Michel

    2017-09-01

    Leber congenital amaurosis (LCA) and early-onset severe retinal dystrophy (EOSRD) are both genetically and phenotypically heterogeneous, and characterised clinically by severe congenital/early infancy visual loss, nystagmus, amaurotic pupils and markedly reduced/absent full-field electroretinograms. The vast genetic heterogeneity of inherited retinal disease has been established over the last 10 - 20 years, with disease-causing variants identified in 25 genes to date associated with LCA/EOSRD, accounting for 70-80% of cases, with thereby more genes yet to be identified. There is now far greater understanding of the structural and functional associations seen in the various LCA/EOSRD genotypes. Subsequent development/characterisation of LCA/EOSRD animal models has shed light on the underlying pathogenesis and allowed the demonstration of successful rescue with gene replacement therapy and pharmacological intervention in multiple models. These advancements have culminated in more than 12 completed, ongoing and anticipated phase I/II and phase III gene therapy and pharmacological human clinical trials. This review describes the clinical and genetic characteristics of LCA/EOSRD and the differential diagnoses to be considered. We discuss in further detail the diagnostic clinical features, pathophysiology, animal models and human treatment studies and trials, in the more common genetic subtypes and/or those closest to intervention. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  8. Leber congenital amaurosis/early-onset severe retinal dystrophy: clinical features, molecular genetics and therapeutic interventions

    PubMed Central

    Kumaran, Neruban; Moore, Anthony T; Weleber, Richard G; Michaelides, Michel

    2017-01-01

    Leber congenital amaurosis (LCA) and early-onset severe retinal dystrophy (EOSRD) are both genetically and phenotypically heterogeneous, and characterised clinically by severe congenital/early infancy visual loss, nystagmus, amaurotic pupils and markedly reduced/absent full-field electroretinograms. The vast genetic heterogeneity of inherited retinal disease has been established over the last 10 - 20 years, with disease-causing variants identified in 25 genes to date associated with LCA/EOSRD, accounting for 70–80% of cases, with thereby more genes yet to be identified. There is now far greater understanding of the structural and functional associations seen in the various LCA/EOSRD genotypes. Subsequent development/characterisation of LCA/EOSRD animal models has shed light on the underlying pathogenesis and allowed the demonstration of successful rescue with gene replacement therapy and pharmacological intervention in multiple models. These advancements have culminated in more than 12 completed, ongoing and anticipated phase I/II and phase III gene therapy and pharmacological human clinical trials. This review describes the clinical and genetic characteristics of LCA/EOSRD and the differential diagnoses to be considered. We discuss in further detail the diagnostic clinical features, pathophysiology, animal models and human treatment studies and trials, in the more common genetic subtypes and/or those closest to intervention. PMID:28689169

  9. Update on the clinical development of cangrelor.

    PubMed

    Ueno, Masafumi; Ferreiro, José Luis; Angiolillo, Dominick J

    2010-08-01

    Antiplatelet drugs represent the cornerstone of treatment for cardiovascular atherothrombotic disease. Dual oral antiplatelet therapy with aspirin and oral ADP-receptor antagonists, such as clopidogrel, has been the standard choice for prevention of ischemic events in patients with acute coronary syndrome and in those undergoing percutaneous coronary intervention. However, due to the limitations of clopidogrel, such as interindividual-response variability, drug-drug interactions, slow onset of action and irreversible inhibitory effects, novel antiplatelet agents are under clinical development. Cangrelor is a reversible, potent, competitive inhibitor of the ADP P2Y(12) receptor that is administered intravenously and rapidly achieves near complete inhibition of ADP-induced platelet aggregation. These pharmacological properties make cangrelor a promising drug for clinical use. However, recent large-scale Phase III clinical investigations failed to show significant clinical benefit on the primary end point with cangrelor. This article provides an overview of the current status of knowledge on cangrelor, focusing on its pharmacologic properties and clinical development.

  10. Early Events in Maize Seed Development 1

    PubMed Central

    Fong, Franklin; Smith, James D.; Koehler, Don E.

    1983-01-01

    Preharvest sprouting or vivipary is induced in developing maize (Zea mays, inbred Tx 5855 and Va 35) seeds by fluridone, a pyridinone inhibitor of carotenoid biosynthesis. Fluridone has a maximal effect on vivipary at 11 days after pollination (DAP) and little effect at 13 DAP in the inbred maize line Tx 5855. Abscisic acid partially reversed the chemically induced vivipary. Though the precise mechanism of fluridone-induced vivipary is unknown, these results indicate that there are important developmental changes occurring at 11 DAP which reversibly commit the immature embryo to vivipary or dormancy. Images Fig. 1 PMID:16663339

  11. Resource Prospector (RP) - Early Prototyping and Development

    NASA Technical Reports Server (NTRS)

    Andrews, D.; Colaprete, A.; Quinn, J.; Bluethmann, B.; Trimble, J.

    2015-01-01

    The Resource Prospector (RP) is an In-Situ Resource Utilization (ISRU) technology demonstration mission under study by the NASA Human Exploration and Operations Mission Directorate's (HEOMD) Advanced Exploration Systems (AES) Division. The mission, currently planned to launch in 2020, will demonstrate extraction of oxygen from lunar regolith to validate ISRU capability. The mission will address key Strategic Knowledge Gaps (SKGs) for robotic and human exploration to the Moon, Near Earth Asteroids (NEAs), and ultimately Mars, as well as meet the strategic goals of the Global Exploration Roadmap (GER), offered by the International Space Exploration Coordination Group (ISECG). In this roadmap, the use of local resources is specifically addressed relating to human exploration. RP will provide knowledge to inform the selection of future mission destinations, support the development of exploration systems, and reduce the risk associated with human exploration. Expanding human presence beyond low-Earth orbit to asteroids and Mars will require the maximum possible use of local materials, so-called in-situ resources. The moon presents a unique destination to conduct robotic investigations that advance ISRU capabilities, as well as providing significant exploration and science value. Lunar regolith contains useful resources such as oxygen, water, silicon, and light metals, like aluminum and titanium. Oxygen can be separated from the regolith for life support (breathable air), or used to create rocket propellant (oxidizer). Regolith can be used to protect against radiation exposure, be processed into solar cells, or used to manufacture construction materials such as bricks and glass. RP will characterize the constituents and distribution of water and other volatiles at the poles of the Moon, enabling innovative uses of local resources, in addition to validating ISRU capabilities. This capability, as well as a deeper understanding of regolith, will be valuable in the

  12. The early course of the Tourette's syndrome clinical spectrum.

    PubMed

    Park, S; Como, P G; Cui, L; Kurlan, R

    1993-09-01

    We retrospectively studied 101 children with Tourette's syndrome to characterize the early course of illness and associated behavioral disturbances of attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), disruptive behavior (DB), and school problems (SP). For patients without ADHD (45%), OCD (50%), DB (67%), or SP (52%) at the time of initial evaluation, 13% developed ADHD, 8% OCD, 28% DB, and 25% SP during the observation period of 1.6 +/- 1.3 years (range, 0.5 to 7 years). For patients with behavioral disturbances initially, the problems were controlled or resolved for many over time and with therapy: ADHD, 46%; OCD, 47%; DB, 50%; and SP, 67%. Medication changes, assessed after a drug adjustment period between the initial and first follow-up visits (6 +/- 6 months), showed that drug dosages remained largely unchanged and few patients required the addition of new drugs: tic suppressants, 10%; anti-obsessional agents, 5%; and stimulants, 12%. Tic suppressants were withdrawn from 12%.

  13. 78 FR 60291 - Investigational Device Exemptions for Early Feasibility Medical Device Clinical Studies...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-01

    ... facilitate early feasibility studies of medical devices, using appropriate risk mitigation strategies, under... Medical Device Clinical Studies, Including Certain First in Human Studies; Guidance for Industry and Food... ``Investigational Device Exemptions (IDEs) for Early Feasibility Medical Device Clinical Studies, Including Certain...

  14. National Outcome Measures for Early Childhood Development: Development of an Indicator-Based Reporting Framework

    ERIC Educational Resources Information Center

    Australian Institute of Health and Welfare, 2011

    2011-01-01

    The Council of Australian Governments released the National Early Childhood Development Strategy, Investing in the Early Years in July 2009 (COAG 2009). One of the key reform priorities in the strategy is to build better information and a solid evidence base, and establishing national outcome measures for early childhood development has been…

  15. National Outcome Measures for Early Childhood Development: Development of an Indicator-Based Reporting Framework

    ERIC Educational Resources Information Center

    Australian Institute of Health and Welfare, 2011

    2011-01-01

    The Council of Australian Governments released the National Early Childhood Development Strategy, Investing in the Early Years in July 2009 (COAG 2009). One of the key reform priorities in the strategy is to build better information and a solid evidence base, and establishing national outcome measures for early childhood development has been…

  16. Early development of Negro and White babies

    PubMed Central

    Pollak, Margaret; Mitchell, Susan

    1974-01-01

    Seventy-five babies, 25 English, 25 West Indian, and 25 Cypriot, all born in London, were examined at 1, 3, and 9 months of age on Gesell and Sheridan scales. The age of walking alone was measured. All the babies were term normal deliveries, weighing 2500 g or more. They were examined under identical conditions. A statistically significant acceleration in gross motor function was found in the West Indian infants at 1 month, compared with the English and Cypriot infants. The acceleration related to extension. At 3 months all three groups were at the same developmental level, and at 9 months both the English and Cypriot babies were ahead of the West Indian infants in adaptive, language, and personal-social development. No significant difference in mean age of walking between the three groups was found. PMID:4818091

  17. Medical imaging in new drug clinical development.

    PubMed

    Wang, Yi-Xiang; Deng, Min

    2010-12-01

    Medical imaging can help answer key questions that arise during the drug development process. The role of medical imaging in new drug clinical trials includes identification of likely responders; detection and diagnosis of lesions and evaluation of their severity; and therapy monitoring and follow-up. Nuclear imaging techniques such as PET can be used to monitor drug pharmacokinetics and distribution and study specific molecular endpoints. In assessing drug efficacy, imaging biomarkers and imaging surrogate endpoints can be more objective and faster to measure than clinical outcomes, and allow small group sizes, quick results and good statistical power. Imaging also has important role in drug safety monitoring, particularly when there is no other suitable biomarkers available. Despite the long history of radiological sciences, its application to the drug development process is relatively recent. This review highlights the processes, opportunities, and challenges of medical imaging in new drug development.

  18. Early intestinal growth and development in poultry.

    PubMed

    Lilburn, M S; Loeffler, S

    2015-07-01

    While there are many accepted "facts" within the field of poultry science that are in truth still open for discussion, there is little debate with respect to the tremendous genetic progress that has been made with commercial broilers and turkeys (Havenstein et al., 2003, 2007). When one considers the changes in carcass development in poultry meat strains, these genetic "improvements" have not always been accompanied by correlated changes in other physiological systems and this can predispose some birds to developmental anomalies (i.e. ascites; Pavlidis et al., 2007; Wideman et al., 2013). Over the last decade, there has been increased interest in intestinal growth/health as poultry nutritionists have attempted to adopt new approaches to deal with the broader changes in the overall nutrition landscape. This landscape includes not only the aforementioned genetic changes but also a raft of governmental policies that have focused attention on the environment (phosphorus and nitrogen excretion), consumer pressure on the use of antibiotics, and renewable biofuels with its consequent effects on ingredient costs. Intestinal morphology has become a common research tool for assessing nutritional effects on the intestine but it is only one metric among many that can be used and histological results can often be interpreted in a variety of ways. This study will address the broader body of research on intestinal growth and development in commercial poultry and will attempt to integrate the topics of the intestinal: microbial interface and the role of the intestine as an immune tissue under the broad umbrella of intestinal physiology. © 2015 Poultry Science Association Inc.

  19. Continuing Professional Development in Early Childhood Education in New Zealand

    ERIC Educational Resources Information Center

    Cherrington, Sue; Thornton, Kate

    2013-01-01

    This article explores the influences on and nature of continuing professional development in the New Zealand early childhood education sector. In addition to discussing the nature of professional development and providing an explanation of the policy context that informs the delivery of professional development, the paper draws on evaluations of…

  20. Current developments in the treatment of early-stage classical Hodgkin lymphoma.

    PubMed

    Borchmann, Sven; von Tresckow, Bastian; Engert, Andreas

    2016-09-01

    After presenting the current treatment recommendations for early-stage Hodgkin lymphoma, we give an overview on recently published clinical trials in this setting. Furthermore, the potential influence of current trials on the treatment of early-stage Hodgkin lymphoma and integration of newly emerging drugs into treatment protocols will be discussed. Trials attempting treatment de-escalation and omission of radiotherapy on the basis of early interim PET-scans have been disappointing so far, but results of some large trials employing this strategy are still awaited. In contrast, a more defensive strategy of starting treatment with less aggressive doxorubicine, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy and intensifying treatment in early interim PET-positive patients has shown encouraging results. New drugs such as brentuximab vedotin and immune checkpoint inhibitors have shown promising results in relapsed and refractory Hodgkin lymphoma. Clinical trials of brentuximab vedotin in early-stage Hodgkin lymphoma have been initiated. Additionally, biomarker-based treatment de-escalation might be a possible route for future improvements. The challenge for future clinical research in early-stage Hodgkin lymphoma is to continue to cure the majority of patients with first-line treatment while reducing long-term toxicity. New strategies to achieve that goal are currently being developed and will further refine treatment of early-stage Hodgkin lymphoma.

  1. Statistical Primer on Biosimilar Clinical Development.

    PubMed

    Isakov, Leah; Jin, Bo; Jacobs, Ira Allen

    A biosimilar is highly similar to a licensed biological product and has no clinically meaningful differences between the biological product and the reference (originator) product in terms of safety, purity, and potency and is approved under specific regulatory approval processes. Because both the originator and the potential biosimilar are large and structurally complex proteins, biosimilars are not generic equivalents of the originator. Thus, the regulatory approach for a small-molecule generic is not appropriate for a potential biosimilar. As a result, different study designs and statistical approaches are used in the assessment of a potential biosimilar. This review covers concepts and terminology used in statistical analyses in the clinical development of biosimilars so that clinicians can understand how similarity is evaluated. This should allow the clinician to understand the statistical considerations in biosimilar clinical trials and make informed prescribing decisions when an approved biosimilar is available.

  2. Clinical pharmacology considerations in biologics development

    PubMed Central

    Zhao, Liang; Ren, Tian-hua; Wang, Diane D

    2012-01-01

    Biologics, including monoclonal antibodies (mAbs) and other therapeutic proteins such as cytokines and growth hormones, have unique characteristics compared to small molecules. This paper starts from an overview of the pharmacokinetics (PK) of biologics from a mechanistic perspective, the determination of a starting dose for first-in-human (FIH) studies, and dosing regimen optimisation for phase II/III clinical trials. Subsequently, typical clinical pharmacology issues along the corresponding pathways for biologics development are summarised, including drug-drug interactions, QTc prolongation, immunogenicity, and studies in specific populations. The relationships between the molecular structure of biologics, their pharmacokinetic and pharmacodynamic characteristics, and the corresponding clinical pharmacology strategies are summarised and depicted in a schematic diagram. PMID:23001474

  3. Clinical pharmacology considerations in biologics development.

    PubMed

    Zhao, Liang; Ren, Tian-hua; Wang, Diane D

    2012-11-01

    Biologics, including monoclonal antibodies (mAbs) and other therapeutic proteins such as cytokines and growth hormones, have unique characteristics compared to small molecules. This paper starts from an overview of the pharmacokinetics (PK) of biologics from a mechanistic perspective, the determination of a starting dose for first-in-human (FIH) studies, and dosing regimen optimisation for phase II/III clinical trials. Subsequently, typical clinical pharmacology issues along the corresponding pathways for biologics development are summarised, including drug-drug interactions, QTc prolongation, immunogenicity, and studies in specific populations. The relationships between the molecular structure of biologics, their pharmacokinetic and pharmacodynamic characteristics, and the corresponding clinical pharmacology strategies are summarised and depicted in a schematic diagram.

  4. Statistical Primer on Biosimilar Clinical Development

    PubMed Central

    Isakov, Leah; Jin, Bo; Jacobs, Ira Allen

    2016-01-01

    A biosimilar is highly similar to a licensed biological product and has no clinically meaningful differences between the biological product and the reference (originator) product in terms of safety, purity, and potency and is approved under specific regulatory approval processes. Because both the originator and the potential biosimilar are large and structurally complex proteins, biosimilars are not generic equivalents of the originator. Thus, the regulatory approach for a small-molecule generic is not appropriate for a potential biosimilar. As a result, different study designs and statistical approaches are used in the assessment of a potential biosimilar. This review covers concepts and terminology used in statistical analyses in the clinical development of biosimilars so that clinicians can understand how similarity is evaluated. This should allow the clinician to understand the statistical considerations in biosimilar clinical trials and make informed prescribing decisions when an approved biosimilar is available. PMID:26766293

  5. Early Clinical Features of Dengue Virus Infection in Nicaraguan Children: A Longitudinal Analysis

    PubMed Central

    Biswas, Hope H.; Ortega, Oscar; Gordon, Aubree; Standish, Katherine; Balmaseda, Angel; Kuan, Guillermina; Harris, Eva

    2012-01-01

    Background Tens of millions of dengue cases and approximately 500,000 life-threatening complications occur annually. New tools are needed to distinguish dengue from other febrile illnesses. In addition, the natural history of pediatric dengue early in illness in a community-based setting has not been well-defined. Methods Data from the multi-year, ongoing Pediatric Dengue Cohort Study of approximately 3,800 children aged 2–14 years in Managua, Nicaragua, were used to examine the frequency of clinical signs and symptoms by day of illness and to generate models for the association of signs and symptoms during the early phase of illness and over the entire course of illness with testing dengue-positive. Odds ratios (ORs) and 95% confidence intervals were calculated using generalized estimating equations (GEE) for repeated measures, adjusting for age and gender. Results One-fourth of children who tested dengue-positive did not meet the WHO case definition for suspected dengue. The frequency of signs and symptoms varied by day of illness, dengue status, and disease severity. Multivariable GEE models showed increased odds of testing dengue-positive associated with fever, headache, retro-orbital pain, myalgia, arthralgia, rash, petechiae, positive tourniquet test, vomiting, leukopenia, platelets ≤150,000 cells/mL, poor capillary refill, cold extremities and hypotension. Estimated ORs tended to be higher for signs and symptoms over the course of illness compared to the early phase of illness. Conclusions Day-by-day analysis of clinical signs and symptoms together with longitudinal statistical analysis showed significant associations with testing dengue-positive and important differences during the early phase of illness compared to the entire course of illness. These findings stress the importance of considering day of illness when developing prediction algorithms for real-time clinical management. PMID:22413033

  6. Early development of an enterprise health data warehouse.

    PubMed

    Househ, Mowafa Said; Al-Tuwaijri, Majid

    2011-01-01

    The purpose of this study is to describe early development challenges of an enterprise data warehouse within a Saudi Arabian academic healthcare facility. An action case research method was selected for this paper. The study took place between December 2009 and February 2010. Data collection included interviews, meeting observations, and meeting minutes. Early development challenges centered on the development of clear contracts with vendors; development of a clear project plan; a need to fast-track bureaucracy; and educate clinicians and staff about the project; and lack of data standardization.

  7. Developing assessment: involving the sessional clinical teacher.

    PubMed

    Bateman, H; Thomason, J M; McCracken, G; Ellis, J

    2016-02-12

    Assessment development is a fundamental element of curriculum management and a requirement for providers of education to consistently demonstrate attainment of educational standards. Development of authentic, valid and reliable assessment is, however, both challenging and resource intensive. In the UK, dental education standards are regulated by the General Dental Council (GDC). The 'safe beginner' is the threshold determined by the GDC for the passing student - but how do we apply this? This article describes an approach the School of Dental Sciences at Newcastle University has adopted to address the challenges associated with developing assessments. Sessional clinical teachers contribute a significant proportion of the clinical supervision within the BDS programme and also have a good appreciation of both the standard and concept of the 'safe beginner'. By implementing a process of active timetable management, we have identified time where this group could contribute to assessment development. We believe that aspects, which could be enhanced by their involvement, include writing, validation, standard-setting and utilisation of assessment. To achieve this, we recognise a requirement for investment in careful manpower planning and training, but consider that it is realistic and beneficial to include sessional clinical teachers in this essential part of learning and teaching.

  8. Meeting product development challenges in manufacturing clinical grade oncolytic adenoviruses.

    PubMed

    Working, Peter K; Lin, Andy; Borellini, Flavia

    2005-11-21

    Oncolytic adenoviruses have been considered for use as anticancer therapy for decades, and numerous means of conferring tumor selectivity have been developed. As with any new therapy, the trip from the laboratory bench to the clinic has revealed a number of significant development hurdles. Viral therapies are subject to specific regulations and must meet a variety of well-defined criteria for purity, potency, stability, and product characterization prior to their use in the clinic. Published regulatory guidelines, although developed specifically for biotechnology-derived products, are applicable to the production of oncolytic adenoviruses and other cell-based products, and they should be consulted early during development. Most importantly, both the manufacturing process and the development of characterization and release assays should be science-driven, use the best available science and technology, and must consider the unique nature of the product: a living, and mutatable, virus. Potentially significant impacts on product quality and safety stem from the possibility of genetic instability related to over-engineering the viruses (as evidenced by their recombination and/or occasional reversion to wild-type virus during manufacturing). This report provides examples of some of the critical components affecting the development and production of clinical grade material and summarizes the significant progress made in recent years.

  9. The clinical efficacy of early intervention for infected preauricular sinus.

    PubMed

    Choo, Oak-Sung; Kim, Top; Jang, Jeong Hun; Choung, Yun-Hoon

    2017-04-01

    The study was designed to evaluate the outcomes of early surgical intervention, and to suggest the accurate operation time and surgical strategies. A total of 190 cases (144 patients) of PAS excision were classified into 2 groups according to their time of surgery; early intervention group (n = 53), and non-early intervention group (n = 137). Early intervention was defined as excision performed within 3 weeks from their first hospital visit, and after acute infection control, surgical removal was followed regardless of their infection status. The mean age of patients was 18.3 ± 15.7 years old (62 male, 82 female). During surgery, a parallel incision was added when iatrogenic fistula due to incision and drainage (I &D) or additionally opened wounds caused by infection was present. Cases of I & D history, revision cases, use of preoperative antibiotics were significantly higher in the early intervention group compared to the non-early intervention group, however, the time of surgery did not affect the complication rate (p = 0.533). Within the infected cases, only 1 patient from the non-early intervention group showed a minor complication of keloid scar. During our follow up period of minimum of 6 months, there was no recurrence in either groups. The early intervention of PASs does not seem to increase postoperative complication or recurrence rates. A double parallel skin incision is a simple but adequate technique to treat infected PASs. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Current status of amorphous formulation and other special dosage forms as formulations for early clinical phases.

    PubMed

    Kawakami, Kohsaku

    2009-09-01

    Although most chemists in the pharmaceutical industry have a good understanding on favorable physicochemical properties for drug candidates, formulators must still deal with many challenging candidates. On the other hand, formulators are not allowed to spend much time on formulation development for early phases of the clinical studies. Thus, it is basically difficult to apply special dosage form technologies to the candidates for the first-in-human formulations. Despite the availability of numerous reviews on oral special dosage forms, information on their applicability as the early phase formulation has been limited. This article describes quick review on the oral special dosage forms that may be applied to the early clinical formulations, followed by discussion focused on the amorphous formulations, which still has relatively many issues to be proved for the general use. The major problems that inhibit the use of the amorphous formulation are difficulty in the manufacturing and the poor chemical/physical stability. Notably, the poor physical stability can be critical, because of not the poor stability itself but the difficulty in the timely evaluation in the preclinical developmental timeframes. Research directions of the amorphous formulations are suggested to utilize this promising technology without disturbing the preclinical developmental timelines.

  11. The Early Motor Questionnaire (EMQ): A Parental Report Measure of Early Motor Development

    PubMed Central

    Libertus, Klaus; Landa, Rebecca J.

    2013-01-01

    Children's early motor skills are critical for development across language, social, and cognitive domains, and warrant close examination. However, examiner-administered motor assessments are time consuming and expensive. Parent-report questionnaires offer an efficient alternative, but validity of parent report is unclear and only few motor questionnaires exist. In this report, we use cross-sectional and longitudinal data to investigate the validity of parent report in comparison to two examiner-administered measures (Mullen Scales of Early Learning, MSEL; Peabody Developmental Motor Scales, PDMS-2), and introduce a new parent-report measure called the Early Motor Questionnaire (EMQ). Results indicate strong correlations between parent report on the EMQ and a child's age, robust concurrent and predictive validity of parent report with both the MSEL and PDMS-2, and good test-re-test reliability of parent report on the EMQ. Together, our findings support the conclusion that parents provide dependable accounts of early motor and cognitive development. PMID:24140841

  12. The Hong Kong Early Child Development Scale: A Validation Study.

    PubMed

    Rao, Nirmala; Sun, Jin; Ng, Sharon Sui Ngan; Ma, Kitty; Becher, Yvonne; Lee, Diana; Lau, Carrie; Zhang, Li; Chow, Chun Bong; Ip, Patrick

    2013-03-01

    This paper reports on the development and validation of the Hong Kong Early Child Development Scale (HKECDS), a holistic measure of child development designed specifically for preschool children in Hong Kong. Scale development was an iterative process and the first version of the scale contained 190 items whereas the final version includes only 95. Children ranging in age from three to six years were administered trial versions of the HKECDS in Studies 1 (n = 60) and 2 (n = 240). Item analyses indicated that it is a developmental scale and that it has an appropriate level of difficulty for preschool children. It also discriminates between three- to six-year-olds from different social backgrounds in Hong Kong. The final version of the HKECDS includes items from the following eight subscales: Personal, Social and Self-Care (7 items), Language Development (13 items), Pre-academic Learning (27 items), Cognitive Development (10 items), Gross Motor (12 items), Fine Motor (9 items), Physical Fitness, Health and Safety (7 items), and Self and Society (10 items). The HKECDS is the first early child development scale which considers both the holistic development of preschool children and incorporates current expectations of early child development in Hong Kong. In this era of evidence-based decision making, it can be used to evaluate both the efficacy of targeted interventions and broader child-related public policies on early child development in Hong Kong.

  13. Early prediction of clinical benefit of treating ovarian cancer using quantitative CT image feature analysis.

    PubMed

    Qiu, Yuchen; Tan, Maxine; McMeekin, Scott; Thai, Theresa; Ding, Kai; Moore, Kathleen; Liu, Hong; Zheng, Bin

    2016-09-01

    In current clinical trials of treating ovarian cancer patients, how to accurately predict patients' response to the chemotherapy at an early stage remains an important and unsolved challenge. To investigate feasibility of applying a new quantitative image analysis method for predicting early response of ovarian cancer patients to chemotherapy in clinical trials. A dataset of 30 patients was retrospectively selected in this study, among which 12 were responders with 6-month progression-free survival (PFS) and 18 were non-responders. A computer-aided detection scheme was developed to segment tumors depicted on two sets of CT images acquired pre-treatment and 4-6 weeks post treatment. The scheme computed changes of three image features related to the tumor volume, density, and density variance. We analyzed performance of using each image feature and applying a decision tree to predict patients' 6-month PFS. The prediction accuracy of using quantitative image features was also compared with the clinical record based on the Response Evaluation Criteria in Solid Tumors (RECIST) guideline. The areas under receiver operating characteristic curve (AUC) were 0.773 ± 0.086, 0.680 ± 0.109, and 0.668 ± 0.101, when using each of three features, respectively. AUC value increased to 0.831 ± 0.078 when combining these features together. The decision-tree classifier achieved a higher predicting accuracy (76.7%) than using RECIST guideline (60.0%). This study demonstrated the potential of using a quantitative image feature analysis method to improve accuracy of predicting early response of ovarian cancer patients to the chemotherapy in clinical trials. © The Foundation Acta Radiologica 2015.

  14. Phonological development in young bilinguals: clinical implications.

    PubMed

    Core, Cynthia; Scarpelli, Chiara

    2015-05-01

    This article reviews recent research on bilingual phonological development and describes the nature of bilingual phonology, focusing on characteristics of cross-linguistic influence on bilingual phonological abilities. There is evidence of positive and negative transfer (acceleration and deceleration) on children's phonological abilities. Several methodological issues limit the ability to generalize findings from previous research to larger groups of bilingual children (e.g., small sample size, lack of consideration of age of acquisition of each language, and language abilities of the participants). Sources of heterogeneity in language development are presented and discussed. Phonological abilities are related to language abilities in bilingual first language learners of English and Spanish. Empirical evidence from research in our laboratory supports this claim. We discuss implications of research findings and limitations for future research and clinical practice. We provide specific recommendations for bilingual research and for clinical assessment of young bilingual children. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  15. A clinical development paradigm for cancer vaccines and related biologics.

    PubMed

    Hoos, Axel; Parmiani, Giorgio; Hege, Kristen; Sznol, Mario; Loibner, Hans; Eggermont, Alexander; Urba, Walter; Blumenstein, Brent; Sacks, Natalie; Keilholz, Ulrich; Nichol, Geoffrey

    2007-01-01

    proof-of-principle trials show such immune response, or other biologic or clinical activity, efficacy trials may be initiated. If none of these end points is met, the clinical development plan should be reevaluated to decide if further development is warranted. Efficacy trials formally establish clinical benefit either directly or through a surrogate and are encouraged to be randomized studies. This is in contrast to single-arm phase 2 trials used for cytotoxic agents, which often use tumor response rate as the primary end point and historical controls as a comparator. Efficacy trials may use prospectively planned adaptive designs to expand from randomized phase 2 into phase 3 studies if well-defined trigger-point criteria are met, but the cost of incorporating such design elements should be carefully evaluated. Efficacy trials can also be exploratory randomized phase 2 trials or conventional phase 3 trials. In addition, conventional clinical end points can be adjusted to account for biologic features of cancer vaccines. The concept of efficacy trials allows for an early assessment of vaccine efficacy based on credible prospective data. This 2-phase developmental paradigm supports a more flexible, expeditious, and focused clinical developmental process with early and informed decision making. In addition, this report addresses clinical development challenges and issues for combination therapies.

  16. Landscape of early clinical trials for childhood and adolescence cancer in Spain.

    PubMed

    Bautista, F; Gallego, S; Cañete, A; Mora, J; Diaz de Heredia, C; Cruz, O; Fernández, J M; Rives, S; Madero, L; Castel, V; Cela, M E; Ramírez, G; Sábado, C; Acha, T; Astigarraga, I; Sastre, A; Muñoz, A; Guibelalde, M; Moreno, L

    2016-07-01

    Despite numerous advances, survival remains dismal for children and adolescents with poor prognosis cancers or those who relapse or are refractory to first line treatment. There is, therefore, a major unmet need for new drugs. Recent advances in the knowledge of molecular tumor biology open the door to more adapted therapies according to individual alterations. Promising results in the adult anticancer drug development have not yet been translated into clinical practice. We report the activity in early pediatric oncology trials in Spain. All members of the Spanish Society of Pediatric Hematology Oncology (SEHOP) were contacted to obtain information about early trials open in each center. 22 phase I and II trials were open as of May 2015: 15 for solid tumors (68 %) and 7 for hematological malignancies (32 %). Fourteen (64 %) were industry sponsored. Since 2010, four centers have joined the Innovative Therapies For Children With Cancer, an international consortium whose aim is developing novel therapies for pediatric cancers. A substantial number of studies have opened in these 5 years, improving the portfolio of trials for children. Results of recently closed trials show the contribution of Spanish investigators, the introduction of molecularly targeted agents and their benefits. Clinical trials are the way to evaluate new drugs, avoiding the use of off-label drugs that carry significant risks. The Spanish pediatric oncology community through the SEHOP is committed to develop and participate in collaborative academic trials, to favor the advancement and optimization of existing therapies in pediatric cancer.

  17. Prediction of Dengue Disease Severity among Pediatric Thai Patients Using Early Clinical Laboratory Indicators

    PubMed Central

    Potts, James A.; Gibbons, Robert V.; Rothman, Alan L.; Srikiatkhachorn, Anon; Thomas, Stephen J.; Supradish, Pra-on; Lemon, Stephenie C.; Libraty, Daniel H.; Green, Sharone; Kalayanarooj, Siripen

    2010-01-01

    Background Dengue virus is endemic in tropical and sub-tropical resource-poor countries. Dengue illness can range from a nonspecific febrile illness to a severe disease, Dengue Shock Syndrome (DSS), in which patients develop circulatory failure. Earlier diagnosis of severe dengue illnesses would have a substantial impact on the allocation of health resources in endemic countries. Methods and Findings We compared clinical laboratory findings collected within 72 hours of fever onset from a prospective cohort children presenting to one of two hospitals (one urban and one rural) in Thailand. Classification and regression tree analysis was used to develop diagnostic algorithms using different categories of dengue disease severity to distinguish between patients at elevated risk of developing a severe dengue illness and those at low risk. A diagnostic algorithm using WBC count, percent monocytes, platelet count, and hematocrit achieved 97% sensitivity to identify patients who went on to develop DSS while correctly excluding 48% of non-severe cases. Addition of an indicator of severe plasma leakage to the WHO definition led to 99% sensitivity using WBC count, percent neutrophils, AST, platelet count, and age. Conclusions This study identified two easily applicable diagnostic algorithms using early clinical indicators obtained within the first 72 hours of illness onset. The algorithms have high sensitivity to distinguish patients at elevated risk of developing severe dengue illness from patients at low risk, which included patients with mild dengue and other non-dengue febrile illnesses. Although these algorithms need to be validated in other populations, this study highlights the potential usefulness of specific clinical indicators early in illness. PMID:20689812

  18. Origins and early development of human body knowledge.

    PubMed

    Slaughter, Virginia; Heron, Michelle

    2004-01-01

    As a knowable object, the human body is highly complex. Evidence from several converging lines of research, including psychological studies, neuroimaging and clinical neuropsychology, indicates that human body knowledge is widely distributed in the adult brain, and is instantiated in at least three partially independent levels of representation. Sensorimotor body knowledge is responsible for on-line control and movement of one's own body and may also contribute to the perception of others' moving bodies; visuo-spatial body knowledge specifies detailed structural descriptions of the spatial attributes of the human body; and lexical-semantic body knowledge contains language-based knowledge about the human body. In the first chapter of this Monograph, we outline the evidence for these three hypothesized levels of human body knowledge, then review relevant literature on infants' and young children's human body knowledge in terms of the three-level framework. In Chapters II and III, we report two complimentary series of studies that specifically investigate the emergence of visuo-spatial body knowledge in infancy. Our technique is to compare infants'responses to typical and scrambled human bodies, in order to evaluate when and how infants acquire knowledge about the canonical spatial layout of the human body. Data from a series of visual habituation studies indicate that infants first discriminate scrambled from typical human body picture sat 15 to 18 months of age. Data from object examination studies similarly indicate that infants are sensitive to violations of three-dimensional human body stimuli starting at 15-18 months of age. The overall pattern of data supports several conclusions about the early development of human body knowledge: (a) detailed visuo-spatial knowledge about the human body is first evident in the second year of life, (b) visuo-spatial knowledge of human faces and human bodies are at least partially independent in infancy and (c) infants' initial

  19. Promoting equity through integrated early child development and nutrition interventions.

    PubMed

    Black, Maureen M; Dewey, Kathryn G

    2014-01-01

    Sustainable development, a foundation of the post-2015 global agenda, depends on healthy and productive citizens. The origins of adult health begin early in life, stemming from genetic-environmental interactions that include adequate nutrition and opportunities for responsive learning. Inequities associated with inadequate nutrition and early learning opportunities can undermine children's health and development, thereby compromising their productivity and societal contributions. Transactional theory serves as a useful framework for examining the associations that link early child development and nutrition because it emphasizes the interplay that occurs between children and the environment, mediated through caregiver interactions. Although single interventions targeting early child development or nutrition can be effective, there is limited evidence on the development, implementation, evaluation, and scaling up of integrated interventions. This manuscript introduces a special edition of papers on six topics central to integrated child development/nutrition interventions: (1) review of integrated interventions; (2) methods and topics in designing integrated interventions; (3) economic considerations related to integrated interventions; (4) capacity-building considerations; (5) examples of integrated interventions; and (6) policy implications of integrated interventions. Ensuring the health and development of infants and young children through integrated child development/nutrition interventions promotes equity, a critical component of sustainable development.

  20. Seeing, Making, Doing: Creative Development in Early Years Settings. Early Education Support Series.

    ERIC Educational Resources Information Center

    Orley, Ray

    Part of a series for early years teachers in Scotland, this guide focuses on ways to provide creative opportunities that support and enhance child development. The guide discusses how to respect children's creativity while observing and developing their skills and suggests practical and creative alternatives to the mass production of identical…

  1. Early Brain and Child Development: Connections to Early Education and Child Care

    ERIC Educational Resources Information Center

    Romano, Judith T.

    2013-01-01

    The vast majority of young children spend time in settings outside of the home, and the nature of those settings directly impacts the child's health and development. The ecobiodevelopmental framework of early brain and child development serve as the backdrop for establishing quality. This article describes the use of quality rating systems,…

  2. Getting an Early Start on Early Child Development. Education Notes. 30194

    ERIC Educational Resources Information Center

    Young, Mary Eming; Dunkelberg, Erika

    2004-01-01

    The children born this year--2004--will be eleven years old in 2015--the age of primary school completion in most countries. This is the MDG (Millennium Development Goal) generation--for whom the international community has pledged that by 2015, all children will be able to complete primary schooling. Ensuring good early child development is the…

  3. Early Brain and Child Development: Connections to Early Education and Child Care

    ERIC Educational Resources Information Center

    Romano, Judith T.

    2013-01-01

    The vast majority of young children spend time in settings outside of the home, and the nature of those settings directly impacts the child's health and development. The ecobiodevelopmental framework of early brain and child development serve as the backdrop for establishing quality. This article describes the use of quality rating systems,…

  4. Integrated and Early Childhood Education: Preparation for Social Development. Theme A: Relevant Provision for Early Childhood.

    ERIC Educational Resources Information Center

    Axton, J. H. M.

    Factors which influence child development are listed and briefly discussed. These factors are (1) mother's childhood, (2) mother's age, (3) care during pregnancy and delivery, (4) early neonatal factors, (5) birth interval, (6) effect of repeated infection and malnutrition on brain growth and intellectual development, and (7) home environment. The…

  5. Getting an Early Start on Early Child Development. Education Notes. 30194

    ERIC Educational Resources Information Center

    Young, Mary Eming; Dunkelberg, Erika

    2004-01-01

    The children born this year--2004--will be eleven years old in 2015--the age of primary school completion in most countries. This is the MDG (Millennium Development Goal) generation--for whom the international community has pledged that by 2015, all children will be able to complete primary schooling. Ensuring good early child development is the…

  6. Improving early clinical trial phase identification of promising therapeutics.

    PubMed

    Kent, Thomas A; Shah, Shreyansh D; Mandava, Pitchaiah

    2015-07-21

    This review addresses decision-making underlying the frequent failure to confirm early-phase positive trial results and how to prioritize which early agents to transition to late phase. While unexpected toxicity is sometimes responsible for late-phase failures, lack of efficacy is also frequently found. In stroke as in other conditions, early trials often demonstrate imbalances in factors influencing outcome. Other issues complicate early trial analysis, including unequally distributed noise inherent in outcome measures and variations in natural history among studies. We contend that statistical approaches to correct for imbalances and noise, while likely valid for homogeneous conditions, appear unable to accommodate disease complexity and have failed to correctly identify effective agents. While blinding and randomization are important to reduce selection bias, these methods appear insufficient to insure valid conclusions. We found potential sources of analytical errors in nearly 90% of a sample of early stroke trials. To address these issues, we recommend changes in early-phase analysis and reporting: (1) restrict use of statistical correction to studies where the underlying assumptions are validated, (2) select dichotomous over continuous outcomes for small samples, (3) consider pooled samples to model natural history to detect early therapeutic signals and increase the likelihood of replication in larger samples, (4) report subgroup baseline conditions, (5) consider post hoc methods to restrict analysis to subjects with an appropriate match, and (6) increase the strength of effect threshold given these cumulative sources of noise and potential errors. More attention to these issues should lead to better decision-making regarding selection of agents to proceed to pivotal trials.

  7. Pancreatic cancer early detection: expanding higher-risk group with clinical and metabolomics parameters.

    PubMed

    Urayama, Shiro

    2015-02-14

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth and fifth leading cause of cancer death for each gender in developed countries. With lack of effective treatment and screening scheme available for the general population, the mortality rate is expected to increase over the next several decades in contrast to the other major malignancies such as lung, breast, prostate and colorectal cancers. Endoscopic ultrasound, with its highest level of detection capacity of smaller pancreatic lesions, is the commonly employed and preferred clinical imaging-based PDAC detection method. Various molecular biomarkers have been investigated for characterization of the disease, but none are shown to be useful or validated for clinical utilization for early detection. As seen from studies of a small subset of familial or genetically high-risk PDAC groups, the higher yield and utility of imaging-based screening methods are demonstrated for these groups. Multiple recent studies on the unique cancer metabolism including PDAC, demonstrate the potential for utility of the metabolites as the discriminant markers for this disease. In order to generate an early PDAC detection screening strategy available for a wider population, we propose to expand the population of higher risk PDAC group with combination clinical and metabolomics parameters.

  8. The Educational Impact of Exposure to Clinical Psychiatry Early in an Undergraduate Medical Curriculum.

    PubMed

    Brown, Menna; Barnes, Jacob; Silver, Katie; Williams, Nicholas; Newton, Philip M

    2016-04-01

    The medical school at Swansea University provides compulsory early exposure to clinical education through short learning opportunities in the clinical setting (LOCS). These are 3-4-h sessions chosen by students from a list of over 900. Students are required to complete ten LOCS in each of their first 2 years of medical school, with at least one per year being in psychiatry. The objective of this study was to evaluate the educational experience of students undertaking LOCS in psychiatry, in part to understand whether this experience affects student understanding of psychiatry and the likelihood that they will pursue it as a career. A mixed methods approach was used. Qualitative focus group discussions were conducted with medical students to explore perceptions of psychiatry and experiences of psychiatry LOCS. Findings informed the development of a structured quantitative survey aimed at a larger sample of students. Six qualitative themes emerged: (1) limited exposure to psychiatry, (2) organizational issues, (3) positive LOCS experiences, (4) stigma, (5) anticipated emotional burden, (6) psychiatry at odds with current understanding of medicine. Questionnaire data showed that psychiatry is not a popular future career choice when compared to other specialties. Psychiatry LOCS are extremely popular with students and have a positive effect on their understanding of the specialty but did little to influence their stated likelihood of pursuing psychiatry as a career. Early exposure to clinical psychiatry through LOCS gives students positive experiences, which improve understanding and awareness of psychiatry. They do not, however, affect stated career intentions for psychiatry as a profession.

  9. Incorporating an Early Detection System Into Routine Clinical Practice in Two Community Hospitals.

    PubMed

    Dummett, B Alex; Adams, Carmen; Scruth, Elizabeth; Liu, Vincent; Guo, Margaret; Escobar, Gabriel J

    2016-11-01

    Efforts to improve outcomes of patients who deteriorate outside the intensive care unit have included the use of rapid response teams (RRTs) as well as manual and automated prognostic scores. Although automated early warning systems (EWSs) are starting to enter clinical practice, there are few reports describing implementation and the processes required to integrate early warning approaches into hospitalists' workflows. We describe the implementation process at 2 community hospitals that deployed an EWS. We employed the Institute for Healthcare Improvement's iterative Plan-Do-Study-Act approach. Our basic workflow, which relies on having an RRT nurse and the EWS's 12-hour outcome time frame, has been accepted by clinicians and has not been associated with patient complaints. Whereas our main objective was to develop a set of workflows for integrating the electronic medical record EWS into clinical practice, we also uncovered issues that must be addressed prior to disseminating this intervention to other hospitals. One problematic area is that of documentation following an alert. Other areas that must be addressed prior to disseminating the intervention include the need for educating clinicians on the rationale for deploying the EWS, careful consideration of interdepartment service agreements, clear definition of clinician responsibilities, pragmatic documentation standards, and how to communicate with patients. In addition to the deployment of the EWS to other hospitals, a future direction for our teams will be to characterize process-outcomes relationships in the clinical response itself. Journal of Hospital Medicine 2016;11:S25-S31. © 2016 Society of Hospital Medicine.

  10. Development of pattern vision following early and extended blindness

    PubMed Central

    Kalia, Amy; Lesmes, Luis Andres; Dorr, Michael; Gandhi, Tapan; Chatterjee, Garga; Ganesh, Suma; Bex, Peter J.; Sinha, Pawan

    2014-01-01

    Visual plasticity peaks during early critical periods of normal visual development. Studies in animals and humans provide converging evidence that gains in visual function are minimal and deficits are most severe when visual deprivation persists beyond the critical period. Here we demonstrate visual development in a unique sample of patients who experienced extended early-onset blindness (beginning before 1 y of age and lasting 8–17 y) before removal of bilateral cataracts. These patients show surprising improvements in contrast sensitivity, an assay of basic spatial vision. We find that contrast sensitivity development is independent of the age of sight onset and that individual rates of improvement can exceed those exhibited by normally developing infants. These results reveal that the visual system can retain considerable plasticity, even after early blindness that extends beyond critical periods. PMID:24449865

  11. The effectiveness of early childhood development programs. A systematic review.

    PubMed

    Anderson, Laurie M; Shinn, Carolynne; Fullilove, Mindy T; Scrimshaw, Susan C; Fielding, Jonathan E; Normand, Jacques; Carande-Kulis, Vilma G

    2003-04-01

    Early childhood development is influenced by characteristics of the child, the family, and the broader social environment. Physical health, cognition, language, and social and emotional development underpin school readiness. Publicly funded, center-based, comprehensive early childhood development programs are a community resource that promotes the well-being of young children. Programs such as Head Start are designed to close the gap in readiness to learn between poor children and their more economically advantaged peers. Systematic reviews of the scientific literature demonstrate effectiveness of these programs in preventing developmental delay, as assessed by reductions in retention in grade and placement in special education.

  12. Professional Development Needs and Interests of Early Childhood Education Trainers

    ERIC Educational Resources Information Center

    Byington, Teresa A.; Tannock, Michelle T.

    2011-01-01

    An online survey of early childhood education (ECE) trainers was conducted to assess their professional development needs and determine any differences between new and experienced trainers. Trainers identified teaching techniques and resources commonly used. The survey information is guiding the development of ECE trainer criteria in a…

  13. Understanding Emotional Development: Helping Early Childhood Providers Better Support Families

    ERIC Educational Resources Information Center

    Edwards, Nicole Megan

    2012-01-01

    This article is intended to provide early childhood providers with a concise overview of emerging emotional development in young children (birth-5), the important role of primary caregivers, and the link between parenting, emotional development, and behavior. Specific suggestions that have been shared with urban Head Start mothers are offered,…

  14. Culture and Early Language Development: Implications for Assessment and Intervention

    ERIC Educational Resources Information Center

    Parada, Patricia M.

    2013-01-01

    The purpose of this qualitative study--"Culture and Early Language Development: Implications for Assessment and Intervention"--was to explore and describe the perceptions and beliefs of Salvadoran mothers of low socioeconomic status regarding the language development of their young children in order to identify cultural variations in…

  15. Symbolic Play and Early Language Development in Normal Children.

    ERIC Educational Resources Information Center

    Ogura, Tamiko

    Examined in a longitudinal study of children were correspondences and correlations between early language development on the one hand, and the manipulation of objects and play development on the other. There were developmental correspondences between the onset of five language landmarks (the emergence of first word, referential word, demonstrative…

  16. Culture and Early Language Development: Implications for Assessment and Intervention

    ERIC Educational Resources Information Center

    Parada, Patricia M.

    2013-01-01

    The purpose of this qualitative study--"Culture and Early Language Development: Implications for Assessment and Intervention"--was to explore and describe the perceptions and beliefs of Salvadoran mothers of low socioeconomic status regarding the language development of their young children in order to identify cultural variations in…

  17. Early Markers of Vulnerable Language Skill Development in Galactosaemia

    ERIC Educational Resources Information Center

    Lewis, Fiona M.; Coman, David J.; Syrmis, Maryanne

    2014-01-01

    There are no known biomedical or genetic markers to identify which infants with galactosaemia (GAL) are most at risk of poor language skill development, yet pre-linguistic communicative "red flag" behaviours are recognised as early identifiers of heightened vulnerability to impaired language development. We report on pre-linguistic…

  18. Helping Families Connect Early Literacy with Social-Emotional Development

    ERIC Educational Resources Information Center

    Santos, Rosa Milagros; Fettig, Angel; Shaffer, LaShorage

    2012-01-01

    Early childhood educators know that home is a child's first learning environment. From birth, children are comforted by hearing and listening to their caregivers' voices. The language used by families supports young children's development of oral language skills. Exposure to print materials in the home also supports literacy development. Literacy…

  19. Early Learning and Development: Cultural-Historical Concepts in Play

    ERIC Educational Resources Information Center

    Fleer, Marilyn

    2010-01-01

    "Early Learning and Development" provides a unique synthesis of cultural-historical theory from Vygotsky, Elkonin and Leontiev in the 20th century to the ground-breaking research of scholars such as Siraj-Blatchford, Kratsova and Hedegaard today. It demonstrates how development and learning are culturally embedded and institutionally defined, and…

  20. Professional development session for early career scientists at SITC 2012

    PubMed Central

    2013-01-01

    The Society for Immunotherapy of Cancer (SITC) 2012 Professional Development Session was held as part of the SITC 27th Annual Meeting, Washington, DC, on October 24, 2012. The session was designed as a new opportunity for early career investigators to learn about relevant career development topics in a didactic setting. PMID:25742323

  1. Early Markers of Vulnerable Language Skill Development in Galactosaemia

    ERIC Educational Resources Information Center

    Lewis, Fiona M.; Coman, David J.; Syrmis, Maryanne

    2014-01-01

    There are no known biomedical or genetic markers to identify which infants with galactosaemia (GAL) are most at risk of poor language skill development, yet pre-linguistic communicative "red flag" behaviours are recognised as early identifiers of heightened vulnerability to impaired language development. We report on pre-linguistic…

  2. Child Development, Early Childhood Education and Family Life: A Bibliography.

    ERIC Educational Resources Information Center

    Reardon, Beverly, Comp.

    This bibliographical listing of approximately 2500 books on child development, early childhood education and family life was compiled as a resource for parents and students. Books are listed alphabetically by author and are grouped according to the following categories: child development; observation of children; adolescence; language…

  3. Child Development, Early Childhood Education and Family Life: A Bibliography.

    ERIC Educational Resources Information Center

    Reardon, Beverly, Comp.

    This bibliographical listing of approximately 2500 books on child development, early childhood education and family life was compiled as a resource for parents and students. Books are listed alphabetically by author and are grouped according to the following categories: child development; observation of children; adolescence; language…

  4. Predictors of Early Termination in a University Counseling Training Clinic

    ERIC Educational Resources Information Center

    Lampropoulos, Georgios K.; Schneider, Mercedes K.; Spengler, Paul M.

    2009-01-01

    Despite the existence of counseling dropout research, there are limited predictive data for counseling in training clinics. Potential predictor variables were investigated in this archival study of 380 client files in a university counseling training clinic. Multinomial logistic regression, predictive discriminant analysis, and classification and…

  5. Predictors of Early Termination in a University Counseling Training Clinic

    ERIC Educational Resources Information Center

    Lampropoulos, Georgios K.; Schneider, Mercedes K.; Spengler, Paul M.

    2009-01-01

    Despite the existence of counseling dropout research, there are limited predictive data for counseling in training clinics. Potential predictor variables were investigated in this archival study of 380 client files in a university counseling training clinic. Multinomial logistic regression, predictive discriminant analysis, and classification and…

  6. Clinical utility of cerebrospinal fluid biomarkers in the diagnosis of early Alzheimer’s disease

    PubMed Central

    Blennow, Kaj; Dubois, Bruno; Fagan, Anne M.; Lewczuk, Piotr; de Leon, Mony J.; Hampel, Harald

    2015-01-01

    Several potential disease-modifying drugs for Alzheimer’s disease (AD) have failed to show any effect on disease progression in clinical trials, conceivably because the AD subjects are already too advanced to derive clinical benefit from treatment and because diagnosis based on clinical criteria alone introduces a high misdiagnosis rate. Thus, well-validated biomarkers for early detection and accurate diagnosis are crucial. Low cerebrospinal fluid (CSF) concentrations of the amyloid-β (Aβ1-42) peptide, in combination with high total tau and phosphorylated tau, are sensitive and specific biomarkers highly predictive of progression to AD dementia in patients with mild cognitive impairment. However, interlaboratory variations in the results seen with currently available immunoassays are of concern. Recent worldwide standardization efforts and quality control programs include standard operating procedures for both preanalytical (e.g., lumbar puncture and sample handling) and analytical (e.g., preparation of calibration curve) procedures. Efforts are also ongoing to develop highly reproducible assays on fully automated instruments. These global standardization and harmonization measures will provide the basis for the generalized international application of CSF bio-markers for both clinical trials and routine clinical diagnosis of AD. PMID:24795085

  7. [Early clinical trials in paediatric oncology in Spain: a nationwide perspective].

    PubMed

    Bautista, Francisco; Gallego, Soledad; Cañete, Adela; Mora, Jaume; Díaz de Heredia, Cristina; Cruz, Ofelia; Fernández, José María; Rives, Susana; Berlanga, Pablo; Hladun, Raquel; Juan Ribelles, Antonio; Madero, Luis; Ramírez, Manuel; Fernández Delgado, Rafael; Pérez-Martínez, Antonio; Mata, Cristina; Llort, Anna; Martín Broto, Javier; Cela, María Elena; Ramírez, Gema; Sábado, Constantino; Acha, Tomás; Astigarraga, Itziar; Sastre, Ana; Muñoz, Ascensión; Guibelalde, Mercedes; Moreno, Lucas

    2017-09-01

    Cancer is the leading cause of death between the first year of life and adolescence, and some types of diseases are still a major challenge in terms of cure. There is, therefore, a major need for new drugs. Recent findings in cancer biology open the door to the development of targeted therapies against individual molecular changes, as well as immunotherapy. Promising results in adult anti-cancer drug development have not yet been translated into paediatric clinical practice. A report is presented on the activity in early paediatric oncology trials (phase I-II) in Spain. All members of the Spanish Society of Paediatric Haematology Oncology (SEHOP) were contacted in order to identify early clinical trials in paediatric cancer opened between 2005 and 2015. A total of 30 trials had been opened in this period: 21 (70%) in solid tumours, and 9 (30%) in malignant haemopathies. A total of 212 patients have been enrolled. The majority was industry sponsored (53%). Since 2010, four centres have joined the international consortium of Innovative Therapies for Children with Cancer (ITCC), which has as its aim to develop novel therapies for paediatric tumours. A significant number of new studies have opened since 2010, improving the treatment opportunities for our children. Results of recently closed trials show the contribution of Spanish investigators, the introduction of molecularly targeted agents, and their benefits. The activity in clinical trials has increased in the years analysed. The SEHOP is committed to develop and participate in collaborative academic trials, in order to help in the advancement and optimisation of existing therapies in paediatric cancer. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Development of Early Measures of Comprehension: Innovation in Individual Growth and Development Indicators

    ERIC Educational Resources Information Center

    Wackerle-Hollman, Alisha K.; Rodriguez, Megan I.; Bradfield, Tracy A.; Rodriguez, Michael C.; McConnell, Scott R.

    2015-01-01

    Early comprehension is an important, but not well-understood, contribution to early literacy and language development. Specifically, research regarding the nature of skills representative of early comprehension, including how they contribute to later reading success, is needed to support best practices to adequately prepare students. This article…

  9. Development of Early Measures of Comprehension: Innovation in Individual Growth and Development Indicators

    ERIC Educational Resources Information Center

    Wackerle-Hollman, Alisha K.; Rodriguez, Megan I.; Bradfield, Tracy A.; Rodriguez, Michael C.; McConnell, Scott R.

    2015-01-01

    Early comprehension is an important, but not well-understood, contribution to early literacy and language development. Specifically, research regarding the nature of skills representative of early comprehension, including how they contribute to later reading success, is needed to support best practices to adequately prepare students. This article…

  10. Developing Early Literacy: Report of the National Early Literacy Panel. A Scientific Synthesis of Early Literacy Development and Implications for Intervention

    ERIC Educational Resources Information Center

    National Institute for Literacy, 2008

    2008-01-01

    The National Early Literacy Panel (NELP) was appointed in 2002 and carried out its work under the auspices of the National Center for Family Literacy (NCFL). NELP's primary goal was to identify interventions, parenting activities, and instructional practices that promote the development of children's early literacy skills. The National Institute…

  11. New Developments in Clinical Bacteriology Laboratories.

    PubMed

    Patel, Robin

    2016-10-01

    There are a number of changes underway in modern clinical bacteriology laboratories. Panel-based molecular diagnostics are now available for numerous applications, including, but not limited to, detection of bacteria and select antibacterial resistance markers in positive blood culture bottles, detection of acute gastroenteritis pathogens in stool, and detection of selected causes of acute meningitis and encephalitis in the cerebrospinal fluid. Today, rapid point-of-care nucleic acid amplification tests are bringing the accuracy of sophisticated molecular diagnostics closer to patients. A proteomic technology, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, is enabling rapid, accurate, and cost-effective identification of bacteria, as well as fungi, recovered in cultures. Laboratory automation, common in chemistry laboratories, is now available for clinical bacteriology laboratories. Finally, there are several technologies under development, such as rapid phenotypic antimicrobial susceptibility testing, whole-genome sequencing, and metagenomic analysis for the detection of bacteria in clinical specimens. It is helpful for clinicians to be aware of the pace of new development in their bacteriology laboratory to enable appropriate test ordering, to enable test interpretation, and to work with their laboratories and antimicrobial stewardship programs to ensure that new technology is implemented to optimally improve patient care.

  12. Emerging Use of Early Health Technology Assessment in Medical Product Development: A Scoping Review of the Literature.

    PubMed

    IJzerman, Maarten J; Koffijberg, Hendrik; Fenwick, Elisabeth; Krahn, Murray

    2017-07-01

    Early health technology assessment is increasingly being used to support health economic evidence development during early stages of clinical research. Such early models can be used to inform research and development about the design and management of new medical technologies to mitigate the risks, perceived by industry and the public sector, associated with market access and reimbursement. Over the past 25 years it has been suggested that health economic evaluation in the early stages may benefit the development and diffusion of medical products. Early health technology assessment has been suggested in the context of iterative economic evaluation alongside phase I and II clinical research to inform clinical trial design, market access, and pricing. In addition, performing early health technology assessment was also proposed at an even earlier stage for managing technology portfolios. This scoping review suggests a generally accepted definition of early health technology assessment to be "all methods used to inform industry and other stakeholders about the potential value of new medical products in development, including methods to quantify and manage uncertainty". The present review also aimed to identify recent published empirical studies employing an early-stage assessment of a medical product. With most included studies carried out to support a market launch, the dominant methodology was early health economic modeling. Further methodological development is required, in particular, by combining systems engineering and health economics to manage uncertainty in medical product portfolios.

  13. Clinical development and current status: Europe.

    PubMed

    Wirz, Dieter; Daniels, A U; Göpfert, Beat; Morscher, Erwin W

    2005-01-01

    This article reviews the development and current status of cemented fixation in total hip replacement in Europe. Key points include the wide country-to-country variation in use of cemented vs. non-cemented fixation and the largely overlooked importance of the choice of bone cement as a factor highly correlated with clinical outcome. Laboratory studies by the authors are also reviewed. Results suggest that the type of acrylic bone cement used affects wear phenomena at the implant/cement interface. Further studies by microcalorimetry suggest that certain aspects of acrylic starting materials (low molecular weight and use of radiation sterilization) affect long-term physico-chemical stability and may thus influence clinical outcomes.

  14. [Concepts boosting the clinical impact in early neurological rehabilitation].

    PubMed

    Gilart de Keranflec'h, Charlotte; Décaillet, François

    2016-10-01

    Vaudois university hospital in Lausanne, Switzerland, has an acute neurological rehabilitation unit. An interdisciplinary team cares for patients with brain injuries after their transfer from intensive care. In this context, nurses base their practice on different concepts and techniques for introducing early neurological rehabilitation into each care procedure. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  15. Development and Clinical Outcomes of a Dialectical Behavior Therapy Clinic

    ERIC Educational Resources Information Center

    Lajoie, Travis; Sonkiss, Joshua; Rich, Anne

    2011-01-01

    Objective: The authors describe the first 6 months of a dialectical behavior therapy (DBT) clinic operated by trainees in a general adult psychiatry residency program. The purpose of this report is to provide a model for the creation and maintenance of a formalized resident DBT clinic. Methods: Residents participated in the DBT clinic, attended a…

  16. Development and Clinical Outcomes of a Dialectical Behavior Therapy Clinic

    ERIC Educational Resources Information Center

    Lajoie, Travis; Sonkiss, Joshua; Rich, Anne

    2011-01-01

    Objective: The authors describe the first 6 months of a dialectical behavior therapy (DBT) clinic operated by trainees in a general adult psychiatry residency program. The purpose of this report is to provide a model for the creation and maintenance of a formalized resident DBT clinic. Methods: Residents participated in the DBT clinic, attended a…

  17. The development of self-regulation across early childhood.

    PubMed

    Montroy, Janelle J; Bowles, Ryan P; Skibbe, Lori E; McClelland, Megan M; Morrison, Frederick J

    2016-11-01

    The development of early childhood self-regulation is often considered an early life marker for later life successes. Yet little longitudinal research has evaluated whether there are different trajectories of self-regulation development across children. This study investigates the development of behavioral self-regulation between the ages of 3 and 7 years, with a direct focus on possible heterogeneity in the developmental trajectories, and a set of potential indicators that distinguish unique behavioral self-regulation trajectories. Across 3 diverse samples, 1,386 children were assessed on behavioral self-regulation from preschool through first grade. Results indicated that majority of children develop self-regulation rapidly during early childhood, and that children follow 3 distinct developmental patterns of growth. These 3 trajectories were distinguishable based on timing of rapid gains, as well as child gender, early language skills, and maternal education levels. Findings highlight early developmental differences in how self-regulation unfolds, with implications for offering individualized support across children. (PsycINFO Database Record

  18. Early determinants of development: a lipid perspective1234

    PubMed Central

    Carlson, Susan E

    2009-01-01

    This article results from an International Life Sciences Institute workshop on early nutritional determinants of health and development. The presentation on lipids focused mainly on the longer-chain products of the essential fatty acids, particularly docosahexaenoic acid (22:6n–3), and cognitive development as among the most studied lipids and outcomes, respectively, in early human nutrition. Because there have been several recent reviews on this topic, the present review takes a broader perspective with respect to both early development and lipids: an expanded research agenda is plausible on the basis of observations from some human studies and from animal studies. Other lipids known to be provided in variable amounts to infants through human milk are cholesterol and gangliosides. Short sections address the current state of knowledge and some questions that could be pursued. PMID:19321568

  19. Fertilization and early embryonic development in the porcine fallopian tube.

    PubMed

    Brüssow, K-P; Rátky, J; Rodriguez-Martinez, H

    2008-07-01

    Fertilization and early embryo development relies on a complex interplay between the Fallopian tube and the gametes before and after fertilization. Thereby the oviduct, as a dynamic reproductive organ, enables reception, transport and maturation of male and female gametes, their fusion, and supports early embryo development. This paper reviews current knowledge regarding physiological processes behind the transport of boar spermatozoa, their storage in and release from the functional sperm reservoir (SR), and of the interactions that newly ovulated oocytes play within the tube during their transport to the site of fertilization. Experimental evidence of an ovarian control on sperm release from the SR is highlighted. Furthermore, the impact of oviductal secretion on sperm capacitation, oocyte maturation, fertilization and early embryo development is stressed.

  20. Collaborative lymphoedema management: developing a clinical protocol.

    PubMed

    Thomson, Mary; Walker, Jackie

    2011-05-01

    Lymphoedema is a very distressing chronic condition prevalent in some metastatic cancers. Conservative treatment of lymphoedema in palliative care involves complete/complex decongestive therapy (CDT) using manual lymphatic drainage (MLD), compression therapy (bandaging and/or garments), skincare, and remedial exercises, adapted to the needs of the patient. The aim of this service development project was to identify current practice in a hospice palliative care service, develop new assessment tools, and implement a collaborative clinical protocol to improve access to lymphoedema management for patients in the hospice. Two audits provided new evidence about patient profiles, patient assessment, and treatment outcomes for cancer- and non-cancer-related lymphoedema. This project had a quality-improvement effect on service delivery and developed an effective partnership approach to lymphoedema management between local district nursing services and the specialist lymphoedema physiotherapist.

  1. New developments in multimodal clinical multiphoton tomography

    NASA Astrophysics Data System (ADS)

    König, Karsten

    2011-03-01

    80 years ago, the PhD student Maria Goeppert predicted in her thesis in Goettingen, Germany, two-photon effects. It took 30 years to prove her theory, and another three decades to realize the first two-photon microscope. With the beginning of this millennium, first clinical multiphoton tomographs started operation in research institutions, hospitals, and in the cosmetic industry. The multiphoton tomograph MPTflexTM with its miniaturized flexible scan head became the Prism-Award 2010 winner in the category Life Sciences. Multiphoton tomographs with its superior submicron spatial resolution can be upgraded to 5D imaging tools by adding spectral time-correlated single photon counting units. Furthermore, multimodal hybrid tomographs provide chemical fingerprinting and fast wide-field imaging. The world's first clinical CARS studies have been performed with a hybrid multimodal multiphoton tomograph in spring 2010. In particular, nonfluorescent lipids and water as well as mitochondrial fluorescent NAD(P)H, fluorescent elastin, keratin, and melanin as well as SHG-active collagen have been imaged in patients with dermatological disorders. Further multimodal approaches include the combination of multiphoton tomographs with low-resolution imaging tools such as ultrasound, optoacoustic, OCT, and dermoscopy systems. Multiphoton tomographs are currently employed in Australia, Japan, the US, and in several European countries for early diagnosis of skin cancer (malignant melanoma), optimization of treatment strategies (wound healing, dermatitis), and cosmetic research including long-term biosafety tests of ZnO sunscreen nanoparticles and the measurement of the stimulated biosynthesis of collagen by anti-ageing products.

  2. Photoacoustic Imaging in Oncology: Translational Preclinical and Early Clinical Experience

    PubMed Central

    Valluru, Keerthi S.; Wilson, Katheryne E.

    2016-01-01

    Photoacoustic imaging has evolved into a clinically translatable platform with the potential to complement existing imaging techniques for the management of cancer, including detection, characterization, prognosis, and treatment monitoring. In photoacoustic imaging, tissue is optically excited to produce ultrasonographic images that represent a spatial map of optical absorption of endogenous constituents such as hemoglobin, fat, melanin, and water or exogenous contrast agents such as dyes and nanoparticles. It can therefore provide functional and molecular information that allows noninvasive soft-tissue characterization. Photoacoustic imaging has matured over the years and is currently being translated into the clinic with various clinical studies underway. In this review, the current state of photoacoustic imaging is presented, including techniques and instrumentation, followed by a discussion of potential clinical applications of this technique for the detection and management of cancer. © RSNA, 2016 PMID:27429141

  3. The Alberta Stroke Program Early CT Score in clinical practice: what have we learned?

    PubMed

    Puetz, V; Dzialowski, I; Hill, M D; Demchuk, A M

    2009-10-01

    The introduction of brain imaging with computed tomography revolutionised the treatment of patients with acute ischaemic stroke. With the visual differentiation of haemorrhagic stroke from ischaemic stroke, thrombolytic therapy became feasible. The Alberta Stroke Program Early CT Score was devised to quantify the extent of early ischaemic changes in the middle cerebral artery territory on noncontrast computed tomography. With its systematic approach, the score is simple and reliable. However, the assessment of early ischaemic changes and Alberta Stroke Program Early CT scoring require training. The Alberta Stroke Program Early CT Score is a strong predictor of functional outcome. Furthermore, the effectiveness of intraarterial thrombolysis in patients with middle cerebral artery occlusion shows effect modification by the Alberta Stroke Program Early CT Score. This review summarises the Alberta Stroke Program Early CT Score methodology. We illustrate current knowledge regarding Alberta Stroke Program Early CT Score applied to clinical trials and comment on how Alberta Stroke Program Early CT Score may facilitate clinical treatment decision making and future trial design. Moreover, we introduce a modification of the Alberta Stroke Program Early CT Score methodology that disregards isolated cortical swelling, i.e. focal brain swelling without associated parenchymal hypoattenuation, as early ischaemic changes in the Alberta Stroke Program Early CT Score system.

  4. Early cardiac development: a view from stem cells to embryos

    PubMed Central

    Van Vliet, Patrick; Wu, Sean M.; Zaffran, Stéphane; Pucéat, Michel

    2012-01-01

    From the 1920s, early cardiac development has been studied in chick and, later, in mouse embryos in order to understand the first cell fate decisions that drive specification and determination of the endocardium, myocardium, and epicardium. More recently, mouse and human embryonic stem cells (ESCs) have demonstrated faithful recapitulation of early cardiogenesis and have contributed significantly to this research over the past few decades. Derived almost 15 years ago, human ESCs have provided a unique developmental model for understanding the genetic and epigenetic regulation of early human cardiogenesis. Here, we review the biological concepts underlying cell fate decisions during early cardiogenesis in model organisms and ESCs. We draw upon both pioneering and recent studies and highlight the continued role for in vitro stem cells in cardiac developmental biology. PMID:22893679

  5. Preclinical and clinical development of DNA vaccines for prostate cancer.

    PubMed

    Colluru, V T; Johnson, Laura E; Olson, Brian M; McNeel, Douglas G

    2016-04-01

    Prostate cancer is the most commonly diagnosed cancer in the United States. It is also the second leading cause of cancer-related death in men, making it one of the largest public health concerns today. Prostate cancer is an ideal disease for immunotherapies because of the generally slow progression, the dispensability of the target organ in the patient population, and the availability of several tissue-specific antigens. As such, several therapeutic vaccines have entered clinical trials, with one autologous cellular vaccine (sipuleucel-T) recently gaining Food and Drug Administration approval after demonstrating overall survival benefit in randomized phase III clinical trials. DNA-based vaccines are safe, economical, alternative "off-the-shelf" approaches that have undergone extensive evaluation in preclinical models. In fact, the first vaccine approved in the United States for the treatment of cancer was a DNA vaccine for canine melanoma. Several prostate cancer-specific DNA vaccines have been developed in the last decade and have shown promising results in early phase clinical trials. This review summarizes anticancer human DNA vaccine trials, with a focus on those conducted for prostate cancer. We conclude with an outline of special considerations important for the development and successful translation of DNA vaccines from the laboratory to the clinic.

  6. Non-clinical development of CER-001

    PubMed Central

    Barbaras, Ronald

    2015-01-01

    Cardiovascular disease remains the most pressing healthcare issue for the developed world and is becoming so for developing countries. There are no currently approved therapies that can rapidly reduce the burden of unstable, inflamed plaque in the overall coronary vascular bed. High-density lipoprotein (HDL) has multiple actions that could lead to plaque stabilization, such as rapid removal of large quantities of cholesterol from the vasculature through the process of reverse lipid transport, improvement in endothelial function, protection against oxidative damage, and reduction in inflammation. Short-term infusion of HDL-mimetics in animal models as well as in humans has shown promising effects on the plaque size and morphology. Cerenis Therapeutics has developed CER-001, a negatively charged lipoprotein complex consisting of phospholipid and recombinant human apoA-I that mimics the structure and function of natural HDL. Three clinical trials using CER-001 infusions have demonstrated improvements in the carotid wall thickness of patients with familial hypercholesterolaemia and in patients with hypo-alphalipoproteinaemia, as well as an impact on coronary plaque burden measured by intravascular ultrasonography at the lowest tested dose (3 mg/kg) in post-ACS patients. Here, we reviewed the non-clinical data leading to the demonstration that CER-001 is a full HDL mimetic. PMID:26500552

  7. Essential role for Max in early embryonic growth and development

    PubMed Central

    Shen-Li, Hong; O'Hagan, Rónán C.; Hou, Harry; Horner, James W.; Lee, Han-Woong; DePinho, Ronald A.

    2000-01-01

    Loss of Max function in the mouse resulted in generalized developmental arrest of both embryonic and extraembryonic tissues at early postimplantation (∼E5.5–6.5), coincident with loss or dilution of maternal Max stores in the expanding embryo in vivo and in blastocyst outgrowths in vitro. Developmentally arrested embryos were reduced in size and exhibited widespread cytological degeneration and feeble BrdU incorporation. Max and, by extension, the Myc superfamily, serve essential roles in early mammalian development and a maternal reservoir of Max exists in sufficient amount to sustain Myc superfamily function through preimplantation stages of development. PMID:10640271

  8. Early feeding practices and development of food allergies.

    PubMed

    Lack, Gideon; Penagos, Martin

    2011-01-01

    Despite increasing efforts to prevent food allergies in children, IgE-mediated food allergies continue to rise in westernized countries. Previous preventive strategies such as prolonged exclusive breastfeeding and delayed weaning onto solid foods have more recently been called into question. The present review discusses possible risk factors and theories for the development of food allergy. An alternative hypothesis is proposed, suggesting that early cutaneous exposure to food protein through a disrupted skin barrier leads to allergic sensitization and that early oral exposure of food allergen induces tolerance. Novel interventional strategies to prevent the development of food allergies are also discussed.

  9. Early childhood growth and development in rural Guatemala.

    PubMed

    Kuklina, Elena V; Ramakrishnan, Usha; Stein, Aryeh D; Barnhart, Huiman H; Martorell, Reynaldo

    2006-07-01

    Small size at birth and in early childhood has been associated with impaired neurodevelopment in studies from developing countries, but few have examined associations with growth. The objective of this study was to assess the relationship between growth and neurodevelopment during early childhood (birth-36 months). Multivariate regression models were used to analyze the data collected in the course of a study of pregnancy outcomes and early childhood growth and development carried out in rural Guatemala in 1991-1999. Motor and mental development scores were based on the Psychomotor and Mental Development Indices, respectively, derived from the administration of an adapted version of the Bayley Scales of Infant Development (Second Edition, 1993) at 6, 24 and 36 months. Z-scores for height-for-age (HAZ), weight-for-age (WAZ), and head circumference-for-age (HCZ) were used as indicators of attained size; changes in these Z-scores over time represent growth. Birth size was significantly associated with child development at 6 and 24 months. Gains in length and weight during the first 24 months were positively associated with child development, whereas growth from 24 to 36 months age was not associated with child development at 36 months. Motor development was more strongly and consistently related to child growth than was mental development. Head circumference gain after 6 months was not a significant predictor of child development at 24 and 36 months. Small size at birth and poor physical growth during the first 24 months are related to neurodevelopmental delays. More evidence from developing countries will help explain the underlying mechanisms and identify appropriate interventions to prevent neurodevelopmental delay in early childhood.

  10. Biophoton emission in synchronously developing population of early Drosophila embryos

    NASA Astrophysics Data System (ADS)

    Zhou, Yu-Ming; Ho, Mae-Wan; Bolton, John P.; Milani, Marziale; Costato, Michele; Musumeci, Francesco

    1996-11-01

    Ultraweak biophoton emission has been recorded in synchronously developing populations of early Drosophila embryos. On being stimulated briefly with white light within the first 40 minutes of development, a new kind of luminescence is observed in the form of superdelayed, intense flashes. We assume that the initial light stimulation sets up some kind of coherent interaction inside the system and develop a phenomenological number-phase-angle model to give a general interpretation of the superdelayed radiation patterns.

  11. Early dialogue between the developers of new technologies and pricing and reimbursement agencies: a pilot study.

    PubMed

    Backhouse, Martin E; Wonder, Michael; Hornby, Edward; Kilburg, Anne; Drummond, Michael; Mayer, Friedrich Karl

    2011-06-01

    It is common practice for developers of new health care technologies to engage in early dialogue with the major regulatory agencies; such discussions frequently center around the proposed clinical trial designs to support the registration of new interventions and suggestions on their improvement. Pricing and reimbursement agencies are increasingly using the results from health technology assessments to inform their decision making for new technologies. Such assessments are invariably underpinned by the phase 3 clinical trial evidence which may not provide answers to the key questions. Technology developers are beginning to realize that direct, early dialogue on the evidence requirements of the major pricing and reimbursement agencies, before phase 3 clinical trial designs for their key development compounds have been finalized, may be beneficial. This article reports on the pioneering efforts of one technology developer in seeking early dialogue with seven pricing and reimbursement agencies in five countries globally in 2007-2008 on their likely evidence requirements for a new oral treatment for patients with chronic plaque psoriasis. The pilot project demonstrated that a feasible process of early dialogue could be established, through a face-to-face meeting with prior circulation of a briefing book. Although there was some variation in the advice the similarities far outweighed the differences. More experience of early dialogue needs to be accumulated, involving a wider range of pricing and reimbursement agencies and compounds. The conclusion of this study, however, was that early dialogue can be a worthwhile process for all parties and can lead to a common understanding about evidence development for market access.

  12. Clinical development of demethylating agents in hematology

    PubMed Central

    Navada, Shyamala C.; Steinmann, Juliane; Lübbert, Michael; Silverman, Lewis R.

    2014-01-01

    The term epigenetics refers to the heritable changes in gene expression that are not associated with a change in the actual DNA sequence. Epigenetic dysregulation is linked to the pathogenesis of a number of malignancies and has been studied extensively in myelodysplastic syndromes and acute myeloid leukemia. DNA methylation is frequently altered in cancerous cells and likely results in transcriptional silencing of tumor suppressor genes. Re-expression of these genes by inhibition of the DNA methyltransferases has been successful in the treatment of benign and malignant disease. In this Review, we discuss the clinical development of demethylating agents in hematology, with a focus on azacitidine and decitabine. PMID:24382388

  13. Guidelines for Clinical Research in Developing Countries.

    PubMed

    Vray, Muriel; Simon, François; Bompart, François

    2007-01-01

    On the basis of a review of current clinical research conditions in developing countries, guidelines have been formulated to ensure scientific validity as well as adherence to universal ethical principles. The main recommendation is that projects should be reviewed by two Institutional Review Boards, one in the country where the Study Sponsor is based, and another in the country where the study is being carried out. In addition, an independent Data Safety Monitoring Board should be set up and systems established to ensure the effective reporting of Serious Adverse Events and to specify the Sponsor's obligations after the end of the Study.

  14. A Novel Way to Measure and Predict Development: A Heuristic Approach to Facilitate the Early Detection of Neurodevelopmental Disorders.

    PubMed

    Marschik, Peter B; Pokorny, Florian B; Peharz, Robert; Zhang, Dajie; O'Muircheartaigh, Jonathan; Roeyers, Herbert; Bölte, Sven; Spittle, Alicia J; Urlesberger, Berndt; Schuller, Björn; Poustka, Luise; Ozonoff, Sally; Pernkopf, Franz; Pock, Thomas; Tammimies, Kristiina; Enzinger, Christian; Krieber, Magdalena; Tomantschger, Iris; Bartl-Pokorny, Katrin D; Sigafoos, Jeff; Roche, Laura; Esposito, Gianluca; Gugatschka, Markus; Nielsen-Saines, Karin; Einspieler, Christa; Kaufmann, Walter E

    2017-05-01

    Substantial research exists focusing on the various aspects and domains of early human development. However, there is a clear blind spot in early postnatal development when dealing with neurodevelopmental disorders, especially those that manifest themselves clinically only in late infancy or even in childhood. This early developmental period may represent an important timeframe to study these disorders but has historically received far less research attention. We believe that only a comprehensive interdisciplinary approach will enable us to detect and delineate specific parameters for specific neurodevelopmental disorders at a very early age to improve early detection/diagnosis, enable prospective studies and eventually facilitate randomised trials of early intervention. In this article, we propose a dynamic framework for characterising neurofunctional biomarkers associated with specific disorders in the development of infants and children. We have named this automated detection 'Fingerprint Model', suggesting one possible approach to accurately and early identify neurodevelopmental disorders.

  15. Temperament, Executive Control, and ADHD across Early Development

    PubMed Central

    Rabinovitz, Beth B.; O’Neill, Sarah; Rajendran, Khushmand; Halperin, Jeffrey M.

    2015-01-01

    Research examining factors linking early temperament and later ADHD is limited by cross-sectional approaches and having the same informant rate both temperament and psychopathology. We used multi-informant/multi-method longitudinal data to test the hypothesis that negative emotionality during preschool is positively associated with ADHD symptom severity in middle childhood, but developing executive control mediates this relation. Children (N=161) with and without ADHD were evaluated three times: Parent and teacher temperament ratings and NEPSY Visual Attention at ages 3–4 years; WISC-IV Working Memory Index and NEPSY Response Set at age 6 years; and ADHD symptoms using the Kiddie-SADS at age 7 years. Parent and teacher ratings of preschoolers’ temperament were combined to form an Anger/Frustration composite. Similarly, an Executive Functioning composite was derived from age 6 measures. Bootstrapping was used to determine whether age 6 Executive Functioning mediated the relation between early Anger/Frustration and later ADHD symptom severity, while controlling for early executive functioning. Preschoolers’ Anger/Frustration was significantly associated with later ADHD symptoms, with this relation partially mediated by age 6 Executive Functioning. Developing executive control mediates the relation between early Anger/Frustration and later ADHD symptom severity, suggesting that Anger/Frustration influences ADHD symptom severity through its impact on developing executive control. Early interventions targeting the harmful influences of negative emotionality or enhancing executive functioning may diminish later ADHD severity. PMID:26854505

  16. Clinical prediction and diagnosis of neurosyphilis in HIV-infected patients with early Syphilis.

    PubMed

    Dumaresq, Jeannot; Langevin, Stéphanie; Gagnon, Simon; Serhir, Bouchra; Deligne, Benoît; Tremblay, Cécile; Tsang, Raymond S W; Fortin, Claude; Coutlée, François; Roger, Michel

    2013-12-01

    The diagnosis of neurosyphilis (NS) is a challenge, especially in HIV-infected patients, and the criteria for deciding when to perform a lumbar puncture (LP) in HIV-infected patients with syphilis are controversial. We retrospectively reviewed demographic, clinical, and laboratory data from 122 cases of HIV-infected patients with documented early syphilis who underwent an LP to rule out NS, and we evaluated 3 laboratory-developed validated real-time PCR assays, the Treponema pallidum particle agglutination (TPPA) assay, the fluorescent treponemal antibody absorption (FTA-ABS) assay, and the line immunoassay INNO-LIA Syphilis, for the diagnosis of NS from cerebrospinal fluid (CSF) samples of these patients. NS was defined by a reactive CSF-VDRL test result and/or a CSF white blood cell (WBC) count of >20 cells/μl. Thirty of the 122 patients (24.6%) had early NS. Headache, visual symptoms, a CD4 cell count of <500 cells/μl, and viremia, as defined by an HIV-1 RNA count of ≥50 copies/ml, were associated with NS in multivariate analysis (P = <0.001 for each factor). Blood serum rapid plasma reagin (RPR) titers were not associated with early NS (P = 0.575). For the diagnosis of NS, the PCR, FTA-ABS, TPPA, and INNO-LIA assays had sensitivities of 58%, 100%, 68%, and 100%, specificities of 67%, 12%, 49%, and 13%, and negative predictive values of 85%, 100%, 84%, and 100%, respectively. Visual disturbances, headache, uncontrolled HIV-1 viremia, and a CD4 cell count of <500 cells/μl were predictors of NS in HIV-infected patients with early syphilis, while blood serum RPR titers were not; therefore, RPR titers should not be used as the sole criterion for deciding whether to perform an LP in early syphilis. When applied to CSF samples, the INNO-LIA Syphilis assay easily helped rule out NS.

  17. Early clinical outcome and complications related to balloon kyphoplasty.

    PubMed

    Bergmann, Martin; Oberkircher, Ludwig; Bliemel, Christopher; Frangen, Thomas Manfred; Ruchholtz, Steffen; Krüger, Antonio

    2012-05-09

    The treatment of painful osteoporotic vertebral compression fractures using transpedicular cement augmentation has grown significantly over the last two decades. The benefits of balloon kyphoplasty compared to conservative treatment remain controversial and are discussed in the literature. The complication rates of vertebroplasty and kyphoplasty are considered to be low. The focus of this study was the analysis of acute and clinically relevant complications related to this procedure. In our department, all patients treated between February 2002 and February 2011 with percutaneous cement augmentation (372 patients, 522 augmented vertebral bodies) were prospectively recorded. Demographic data, comorbidities, fracture types, intraoperative data and all complications were documented. The pre- and postoperative pain-level and neurological status (Frankel-Score) were evaluated. All patients underwent a standardized surgical procedure. Two hundred and ninety-seven patients were treated solely by balloon kyphoplasty; 216 females (72.7%) and 81 males (27.3%). Average patient age was 76.21 years (±10.71, range 35-98 years). Average American Society Anestesiologists score was 3.02. According to the Orthopedic Trauma Association classification, there were 69 A 1.1 fractures, 177 A 1.2 fractures, 178 A 3.1.1 fractures and 3 A 3.1.3 fractures. Complications were divided into preoperative, intraoperative and postoperative events. There were 4 preoperative complications: 3 patients experienced persistent pain after the procedure. In one case, the pedicles could not be visualized during the procedure and the surgery was terminated. One hundred and twenty-nine (40.06%) of the patients showed intraoperative cement leaking outside the vertebras, one severe hypotension and tachycardia as reaction to the inflation of the balloons, and there was one cardiac arrest during surgery. Postoperative subcutaneous hematomas were observed in 3 cases, 13 patients developed a urinary tract

  18. Developing antitussives: the ideal clinical trial.

    PubMed

    Birring, Surinder S

    2009-04-01

    Antitussive drugs are amongst the most widely used medications worldwide; however no new class of drugs have been introduced into the market for many years. Trials showing patient benefit are scarce and have been hampered by the lack of objective and validated outcome measures. Recent improvements in the assessment of cough will facilitate better trials and aid the development of antitussive drugs. When conducting a trial, patient selection is of paramount importance. Patients with unexplained chronic cough and sub-acute cough following upper respiratory tract infection are ideal because they represent an unmet clinical need and an untapped market for pharmaceutical companies. Patients with asthma and chronic obstructive pulmonary disease are less suitable since cough suppression is not always desirable and the findings of trials may not be generalisable to all patients with cough. Randomized, placebo-controlled, double-blind clinical trials are obviously the gold standard. The choice of placebo, whether inert or active, depends on the incidence and severity of drug side-effects. The primary outcome measure should be objective and cough monitors are the ideal tool. Subjective outcome measures should be used to assess symptoms and health related quality of life. Properly conducted clinical trials are an opportunity to evaluate the benefits of currently available therapies and aid advances in the antitussive drug market.

  19. HIV-1 Entry Inhibitors: Recent Development and Clinical Use

    PubMed Central

    Henrich, Timothy J.; Kuritzkes, Daniel R.

    2014-01-01

    Purpose of review This review provides an overview of HIV-1 entry inhibitors, with a focus on drugs in the later stages of clinical development. Recent findings Entry of HIV-1 into target cells involves viral attachment, co-receptor binding and fusion. Antiretroviral drugs that interact with each step in the entry process have been developed, but only two are currently approved for clinical use. The small molecule attachment inhibitor BMS-663068 has shown potent antiviral activity in early phase studies, and phase 2b trials are currently underway. The post-attachment inhibitor ibalizumab has shown antiviral activity in phase 1 and 2 trials; further studies, including subcutaneous delivery of drug to healthy individuals, are anticipated. The CCR5 antagonist maraviroc is approved for use in treatment-naïve and treatment-experienced patients. Cenicriviroc, a small-molecule CCR5 antagonist that also has activity as a CCR2 antagonist, has entered phase 2b studies. No CXCR4 antagonists are currently in clinical trials, but once daily, next-generation injectable peptide fusion inhibitors have entered human trials. Both maraviroc and ibalizumab are being studied for prevention of HIV-1 transmission and/or for use in nucleoside reverse transcriptase inhibitor-sparing antiretroviral regimens. Summary Inhibition of HIV-1 entry continues to be a promising target for antiretroviral drug development. PMID:23290628

  20. Does preterm period sleep development predict early childhood growth trajectories?

    PubMed

    Winkler, M R; Park, J; Pan, W; Brandon, D H; Scher, M; Holditch-Davis, D

    2017-09-01

    The current study examined the relationship between sleep state development across the preterm and early post-term periods and subsequent growth trajectories from 1 to 27 months corrected age. Retrospective analysis of data collected prospectively from 111 preterm infants (⩽34 weeks gestation) who participated in a multi-site longitudinal study. Separate longitudinal parallel process models were calculated for each sleep state (active and quiet sleep) and growth (weight, length and body mass index (BMI) Z-scores) variable to estimate the associations between their developmental trajectories. Significant associations were identified between the trajectories of quiet sleep and weight, active sleep and weight, quiet sleep and BMI, and active sleep and BMI. No statistically meaningful associations were identified between the trajectories of early childhood length and the preterm sleep states. Faster preterm period sleep development appears to predict more favorable early childhood growth trajectories, particularly for weight, indicating preterm sleep may be an important biomarker for subsequent growth outcomes.

  1. Early childhood obesity is associated with compromised cerebellar development.

    PubMed

    Miller, Jennifer L; Couch, Jessica; Schwenk, Krista; Long, Michelle; Towler, Stephen; Theriaque, Douglas W; He, Guojun; Liu, Yijun; Driscoll, Daniel J; Leonard, Christiana M

    2009-01-01

    As part of a study investigating commonalities between Prader-Willi syndrome (PWS-a genetic imprinting disorder) and early-onset obesity of unknown etiology (EMO) we measured total cerebral and cerebellar volume on volumetric magnetic resonance imaging (MRI) images. Individuals with PWS (N = 16) and EMO (N = 12) had smaller cerebellar volumes than a control group of 15 siblings (p = .02 control vs. EMO; p = .0005 control vs. PWS), although there was no difference among the groups in cerebral volume. Individuals with PWS and EMO also had impaired cognitive function: general intellectual ability (GIA): PWS 65 +/- 25; EMO 81 +/- 19; and Controls 112 +/- 13 (p < .0001 controls vs. PWS and controls vs. EMO). As both conditions are characterized by early-onset obesity and slowed cognitive development, these results raise the possibility that early childhood obesity retards both cerebellar and cognitive development.

  2. Early Childhood Obesity is Associated with Compromised Cerebellar Development

    PubMed Central

    Miller, Jennifer L; Couch, Jessica; Schwenk, Krista; Long, Michelle; Towler, Stephen; Theriaque, Douglas W; He, Guojun; Liu, Yijun; Driscoll, Daniel J; Leonard, Christiana M

    2009-01-01

    As part of a study investigating commonalities between Prader-Willi syndrome (PWS — a genetic imprinting disorder) and early-onset obesity of unknown etiology (EMO) we measured total cerebral and cerebellar volume on volumetric MRI images. Individuals with PWS (n=16) and EMO (n=12) had smaller cerebellar volumes than a control group of 15 siblings (p=0.02 control vs. EMO; p=0.0005 control vs. PWS), although there was no difference among the groups in cerebral volume. Individuals with PWS and EMO also had impaired cognitive function: general intellectual ability (GIA): PWS 65 ± 25; EMO 81 ± 19; and Controls 112 ± 13 (p<0.0001 controls vs. PWS and controls vs. EMO). As both conditions are characterized by early-onset obesity and slowed cognitive development, these results raise the possibility that early childhood obesity retards both cerebellar and cognitive development. PMID:19437203

  3. Embedded Professional Development and Classroom-Based Early Reading Intervention: Early Diagnostic Reading Intervention through Coaching

    ERIC Educational Resources Information Center

    Amendum, Steven J.

    2014-01-01

    The purpose of the current mixed-methods study was to investigate a model of professional development and classroom-based early reading intervention implemented by the 1st-grade teaching team in a large urban/suburban school district in the southeastern United States. The intervention provided teachers with ongoing embedded professional…

  4. Social Contexts of Early Development in Education. Advances in Early Education and Day Care.

    ERIC Educational Resources Information Center

    Reifel, Stuart, Ed.

    This volume reflects some of the disciplinary and interdisciplinary diversity found in the study of programs for young children, and its chapters cover a number of matters central to early childhood development and practice, including preparation for practice. The book has 11 chapters divided into 4 parts that cover family and community, adults…

  5. The Australian Early Development Index: Reshaping Family-Child Relationships in Early Childhood Education

    ERIC Educational Resources Information Center

    Peers, Chris

    2011-01-01

    This article addresses the cultural significance of the Australian Early Development Index (AEDI) and discusses changes that the discourse of this instrument makes to the way in which the child is conceptualised. It analyses the technological function of the AEDI to examine how it makes the child a universal resource for human capital. The article…

  6. The Australian Early Development Index: Reshaping Family-Child Relationships in Early Childhood Education

    ERIC Educational Resources Information Center

    Peers, Chris

    2011-01-01

    This article addresses the cultural significance of the Australian Early Development Index (AEDI) and discusses changes that the discourse of this instrument makes to the way in which the child is conceptualised. It analyses the technological function of the AEDI to examine how it makes the child a universal resource for human capital. The article…

  7. Embedded Professional Development and Classroom-Based Early Reading Intervention: Early Diagnostic Reading Intervention through Coaching

    ERIC Educational Resources Information Center

    Amendum, Steven J.

    2014-01-01

    The purpose of the current mixed-methods study was to investigate a model of professional development and classroom-based early reading intervention implemented by the 1st-grade teaching team in a large urban/suburban school district in the southeastern United States. The intervention provided teachers with ongoing embedded professional…

  8. Early Learning Foundations. Indiana's Early Learning Development Framework Aligned to the Indiana Academic Standards, 2014

    ERIC Educational Resources Information Center

    Indiana Department of Education, 2015

    2015-01-01

    The "Foundations" (English/language arts, mathematics, social emotional skills, approaches to play and learning, science, social studies, creative arts, and physical health and growth) are Indiana's early learning development framework and are aligned to the 2014 Indiana Academic Standards. This framework provides core elements that…

  9. 77 FR 9947 - Guidance for Industry: Early Clinical Trials With Live Biotherapeutic Products: Chemistry...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-21

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry: Early Clinical Trials With Live Biotherapeutic Products: Chemistry, Manufacturing, and Control Information; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the...

  10. Early Career Boot Camp: a novel mechanism for enhancing early career development for psychologists in academic healthcare.

    PubMed

    Foran-Tuller, Kelly; Robiner, William N; Breland-Noble, Alfiee; Otey-Scott, Stacie; Wryobeck, John; King, Cheryl; Sanders, Kathryn

    2012-03-01

    The purpose of this article is to describe a pilot mentoring program for Early Career Psychologists (ECPs) working in Academic Health Centers (AHCs) and synthesize the lessons learned to contribute to future ECP and AHC career development training programs. The authors describe an early career development model, named the Early Career Boot Camp. This intensive experience was conducted as a workshop meant to build a supportive network and to provide mentorship and survival tools for working in AHCs. Four major components were addressed: professional effectiveness, clinical supervision, strategic career planning, and academic research. Nineteen attendees who were currently less than 5 years post completion of doctoral graduate programs in psychology participated in the program. The majority of boot camp components were rated as good to excellent, with no component receiving below average ratings. Of the components offered within the boot camp, mentoring and research activities were rated the strongest, followed by educational activities, challenges in AHCS, and promotion and tenure. The article describes the purpose, development, implementation, and assessment of the program in detail in an effort to provide an established outline for future organizations to utilize when mentoring ECPs.

  11. Implementation Of A Digital Multiple Viewing Station And Early Clinical Experience

    NASA Astrophysics Data System (ADS)

    Huang, H. K.; Mankovich, Nicholas J.; Taira, Ricky K.; Kangarloo, Hooshang

    1986-06-01

    The Clinical Radiology Imaging System (CRIS) developed in the UCLA Image Processing Laboratory (IPL) is designed to allow radiologists, clinicians, and technologists to review and manipulate radiological images in digital form on a multiple viewing station (MVS). The system is composed of a multiple viewing station located at a clinical site and a centralized computer system consisting of a VAX-11/750 minicomputer, a Gould/DeAnza IP8500 image processor, and optical and magnetic disk storage. A broadband network allows video and digital communication between the remote clinical site and the IPL research laboratory. The station allows the real-time presentation of six 512x512x8 bit images from any combination of CT, MRI, DF, ultrasound, and digitized radiographs. The user interacts with the system by way of menus, icons, and a trackball. The CRIS system has been implemented in the Pediatric Radiology Section of the UCLA Medical Center. This paper describes the hardware and software architecture of the system and some early clinical experience.

  12. Evidence-based medicine in pre-clinical years: a study of early introduction and usefulness

    PubMed Central

    ACHARYA, YOGESH; RAGHAVENDRA RAO, M.V.; ARJA, SATEESH

    2017-01-01

    Introduction: Evidence Based Medicine (EBM) has established itself as a strong predictor of future medical practice by medical students. The purpose of this study was to determine the effectiveness of EBM in pre-clinical years and reflect on self-assessment skill of 4th semester medical students regarding the understanding of EBM and its various determinants. Methods: All of the 4th semester (MD4) medical students at the Avalon University of Medical School, Curacao who had completed their EBM curriculum were asked to voluntarily participate in a cross sectional student survey containing qualitative and quantitative questionnaires in a 10-point scale. The students’ responses were analyzed statistically and the results reported. Results: Twenty-three students participated in the survey. 91% of them reported that EBM had helped them to better understand research process and 95% believed that EBM was necessary to develop clinical skills in the future. 78% of the students agreed that they were provided with enough resources for effective implementation of EBM in the university. All participants (100%) self reported that they could appraise the research articles effectively (mean score 8.26, S.D-1.45). Conclusions: EBM is an integrative and comprehensive way to successfully adopt concepts of acquired medical knowledge for effective medical practice. Early introduction of EBM in preclinical years proved favorable in students and better equipped them with the ability to critically apprehend and appraise new research and innovations in medicine for optimal learning experience. There is a definitive need for scientific and systematic design of the curriculum for early introduction of EBM in pre-clinical years, best suited for the students. The principles should be directed towards further research for the effective implementation of EBM to enhance clinical skills. PMID:28761882

  13. Development of tolerogenic strategies in the clinic.

    PubMed

    Knechtle, Stuart J

    2005-09-29

    The study of tolerance in the clinic can be divided into three areas: (i) focused evaluation of existing tolerant transplant recipients as to their mechanism of tolerance; (ii) prospective tolerance trials, such as combined bone marrow and kidney transplantation as well as T cell depletion followed by subsequent weaning of immunosuppression; and (iii) immunologic assays to assess the likelihood of rejection or tolerance. Frankly, a very small number of patients have been transplanted with the intention of removing all immunosuppressive therapy, but several clinical trials with this aim are currently in progress, largely sponsored by the Immune Tolerance Network, a joint venture between the National Institutes of Health and the Juvenile Diabetes Research Foundation. Similarly, a reliable assay to assess tolerance has not yet been developed but a variety of approaches towards assessing rejection, and in some cases tolerance, are being developed. It would be accurate to state that many of the experimental and preclinical approaches to the induction of tolerance have resulted in better immunosuppression for human transplantation, but reliable tolerance strategies in humans have not yet been achieved. Combined bone marrow and kidney transplantation may be considered as one exception to this, but such a strategy is not generally applicable to the vast majority of solid organ transplant recipients. This review will summarize efforts to date, particularly focusing on kidney transplantation.

  14. Development of early treatment strategies for high-risk myeloma precursor disease in the future.

    PubMed

    Landgren, Ola; Rajkumar, S Vincent

    2011-01-01

    Smoldering myeloma (SMM) is a precursor state of multiple myeloma. It is defined by an M-protein concentration ≥3 g/dL and/or ≥10% clonal bone marrow plasma cells, in the absence of end-organ damage. Based on clinical observations, the natural history of SMM varies greatly, from stable, monoclonal gammopathy of undetermined significance (MGUS)-like disease to highly progressive disease. Using conventional clinical markers, SMM patients can be stratified into clinical risk groups. However, due to considerable molecular heterogeneity, we currently lack reliable markers to predict prognosis for individual SMM patients. Based on the International Myeloma Working Group 2010 guidelines, patients diagnosed with MGUS and SMM should not be treated outside of clinical trials. Overall, treatment trials for MGUS patients are complicated, as these individuals are relatively healthy and the majority has a low life-time risk of progression, especially when other causes of death are taken into account. In contrast to MGUS, early treatment strategies for SMM are particularly attractive, as the rate of progression to multiple myeloma is substantially higher. Until recently, potent drugs with reasonable toxicity profiles have not been available for the development of early multiple myeloma treatment strategies. This review discusses how the integration of novel biological markers and clinical monitoring of SMM could facilitate the development of early treatment strategies for high-risk SMM patients in the future. Copyright © 2011. Published by Elsevier Inc.

  15. Innovative approaches to clinical development and trial design.

    PubMed

    Orloff, John J; Stanski, Donald

    2011-01-01

    Pharmaceutical innovation is increasingly risky, costly and at times inefficient, which has led to a decline in industry productivity. Despite the increased investment in R&D by the industry, the number of new molecular entities achieving marketing authorization is not increasing. Novel approaches to clinical development and trial design could have a key role in overcoming some of these challenges by improving efficiency and reducing attrition rates. The effectiveness of clinical development can be improved by adopting a more integrated model that increases flexibility and maximizes the use of accumulated knowledge. Central to this model of drug development are novel tools, including modelling and simulation, Bayesian methodologies, and adaptive designs, such as seamless adaptive designs and sample-size re-estimation methods. Applications of these methodologies to early- and late-stage drug development are described with some specific examples, along with advantages, challenges, and barriers to implementation. Because they are so flexible, these new trial designs require significant statistical analyses, simulations and logistical considerations to verify their operating characteristics, and therefore tend to require more time for the planning and protocol development phase. Greater awareness of the distinct advantages of innovative designs by regulators and sponsors are crucial to increasing the adoption of these modern tools.

  16. Rethinking the Food and Drug Administration's 2013 guidance on developing drugs for early-stage Alzheimer's disease.

    PubMed

    Schneider, Lon S

    2014-03-01

    The February 2013 Food and Drug Administration (FDA) draft guidance for developing drugs for early-stage Alzheimer's disease (AD) creates certain challenges as they guide toward the use of one cognitive outcome to gain accelerated marketing approval for preclinical AD drugs, and a composite clinical scale - the Clinical Dementia Rating Scale in particular - for the primary outcome for prodromal AD clinical trials. In light of the developing knowledge regarding early stage diagnoses and clinical trials outcomes, we recommend that FDA describe its requirements for validating preclinical AD diagnoses for drug development purposes, maintain the principle for requiring coprimary outcomes, and encourage the advancement of outcomes for early stage AD trials. The principles for drug development for early stage AD should not differ from those for clinical AD, especially as the diagnoses of prodromal and early AD impinge on each other. The FDA should not recommend that a composite scale be used as a sole primary efficacy outcome to support a marketing claim unless it requires that the cognitive and functional components of such a scale are demonstrated to be individually meaningful. The current draft guidelines may inadvertently constrain efforts to better assess the clinical effects of new drugs and inhibit innovation in an area where evidence-based clinical research practices are still evolving. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  17. [CLINICAL SIGNIFICANCE OF BIOMARKERS OF OSTEOCHONDRAL LESIONS IN EARLY RHEUMATOID ARTHRITIS].

    PubMed

    Rekalov, D

    2016-10-01

    The aim of the research was to study biomarkers of osteochondral lesions on early stages of rheumatoid arthritis (RA). The data showed the prognostic value of indicators of the erosive and destructive changes of joints in early and in the advanced stage of RA. Indicators that determine how directly, inflammatory process activity and markers associated with the speed and staging damage of articular surfaces is analyzed. That can adequately justify individualized clinical strategy in patients with early RA.

  18. The Impact of Early Clinical Training in Medical Education: A Multi-Institutional Assessment.

    ERIC Educational Resources Information Center

    Carney, Patricia A.; Bar-on, Miriam E.; Grayson, Martha S.; Klein, Martin; Cochran, Nan; Eliassen, M. Scottie; Gambert, Steven R.; Gupta, Krishan L.; Labrecque, Mary C.; Munson, Paul J.; Nierenberg, David W.; O'Donnell, Joseph F.; Whitehurst-Cook, Michelle; Willett, Rita M.

    1999-01-01

    Funded by the Generalist Physician Initiative, Dartmouth Medical School (New Hampshire), Virginia Commonwealth University, and New York Medical College adopted early community-based training models for longitudinal clinical experiences. The three programs, the methods used to evaluate an aspect of the program, lessons learned about early clinical…

  19. What are the clinical determinants of early energy expenditure in critically injured adults?

    PubMed

    Boulanger, B R; Nayman, R; McLean, R F; Phillips, E; Rizoli, S B

    1994-12-01

    The clinical determinants of energy expenditure in critically injured adults require definition. Among adult blunt trauma victims who required mechanical ventilation, the resting energy expenditure was calculated with the Harris-Benedict equation (HBEE) and the early (< or = 5 days postinjury) energy expenditure was measured by indirect calorimetry (MEE) (n = 115). The MEE was 2052 +/- 531 kcal/day and MEE/HBEE ("stress factor") was 1.24 +/- 0.2. The MEE was correlated with HBEE, age, height, weight, sex, temperature, and paralytic agents (p < 0.01). However, MEE did not correlate with ISS, admission GCS score, admission base deficit, initial systolic blood pressure, or the number of units of packed red blood cells transfused in the first 24 hours after injury (p = NS). Temperature and paralysis correlated with MEE/HBEE (p < 0.01). A regression model of MEE was developed with the clinical variables HBEE, temperature, and the presence or absence of paralytic agents (r2 = 0.62; p < 0.001): MEE (kcal/d) = 1.4(HBEE) + 71.4(temperature) + 274(paralytics; + = 1, - = 2) - 3485. In mechanically ventilated trauma victims, both the early energy expenditure and the stress factor are determined by host factors but are independent of the severity of the anatomic and physiologic insult. The degree of hypermetabolism observed in this population was less than previously reported.

  20. Changing the Perspective on Early Development of Rett Syndrome

    ERIC Educational Resources Information Center

    Marschik, Peter B.; Kaufmann, Walter E.; Sigafoos, Jeff; Wolin, Thomas; Zhang, Dajie; Bartl-Pokorny, Katrin D.; Pini, Giorgio; Zappella, Michele; Tager-Flusberg, Helen; Einspieler, Christa; Johnston, Michael V.

    2013-01-01

    We delineated the achievement of early speech-language milestones in 15 young children with Rett syndrome ("MECP2" positive) in the first two years of life using retrospective video analysis. By contrast to the commonly accepted concept that these children are normal in the pre-regression period, we found markedly atypical development of…

  1. Rethinking Early Learning and Development Standards in the Ugandan Context

    ERIC Educational Resources Information Center

    Ejuu, Godfrey

    2013-01-01

    Concerns that the African child is being tailored to be a "global child," alongside other homogenizing and dominating projections, such as early learning and development standards (ELDS), have increased. African communities need to be assured that global standards and global indicators will not further homogenize nations and thereby risk…

  2. More Alike than Different: Early Childhood Professional Development in Guatemala

    ERIC Educational Resources Information Center

    Hardin, Belinda J.; Vardell, Rosemarie; de Castaneda, Albertina

    2008-01-01

    This article describes an early childhood professional development project that took place in the summer of 2005 in Guatemala City. Located in Central America, Guatemala has a population of approximately 12.3 million people, including more than two million children under the age of 5 (UNESCO Institute for Statistics, 2007; UNICEF, 2004). Events…

  3. Career Planning and Development for Early-Career Scientists

    EPA Science Inventory

    Early career development can be looked at as being of two major phases. The first phase is the formal educational process leading to an awarded degree, postdoctoral training, and potentially formal certification in a scientific discipline. The second phase is the informal educa...

  4. Early Childhood Education for Sustainability: Recommendations for Development

    ERIC Educational Resources Information Center

    Daries, Julie; Engdahl, Ingrid; Otieno, Lorraine; Pramling-Samuelson, Ingrid; Siraj-Blatchford, John; Vallabh, Priya

    2009-01-01

    The following recommendations for "Education for Sustainable Development (ESD)" in Early Childhood Education were the product of an extended international collaboration that was supported by a number of bodies including the Centre for Environment and Sustainability in Gothenburg, the Swedish Ministry of Education and Research, the…

  5. HIV Infection: Transmission, Effects on Early Development, and Interventions.

    ERIC Educational Resources Information Center

    Lowenthal, Barbara

    1997-01-01

    Describes the modes of transmission of HIV and the course of the disease in infants and toddlers. Information is provided on its effects on early development, medical screening and treatments, therapies, psychosocial assistance, and interventions, including nutritional therapy, occupational and physical therapies, and speech and language therapy.…

  6. MAMMARY GLAND DEVELOPMENT: EARLY LIFE EFFECTS FROM THE ENVIRONMENT

    EPA Science Inventory

    Mammary Gland Development: Early Life Effects from the Environment

    S.E. Fenton. Reproductive Toxicology Division, National Health and Environmental Effects Laboratory, ORD, U.S. EPA, Research Triangle Park, NC 27711.

    As signs of precocious puberty in girls reach ...

  7. Regionalism and Development in Early Nineteenth Century Spanish America.

    ERIC Educational Resources Information Center

    Friedman, Douglas

    An understanding of regionalism in early 19th century Spanish America is crucial to any understanding of this region's economic development. Regionalism became the barrier to the kind of integrated national economy that some writers claim could have been implemented had it not been for the imposition of dependency by external forces. This…

  8. MAMMARY GLAND DEVELOPMENT: EARLY LIFE EFFECTS FROM THE ENVIRONMENT

    EPA Science Inventory

    Mammary Gland Development: Early Life Effects from the Environment

    S.E. Fenton. Reproductive Toxicology Division, National Health and Environmental Effects Laboratory, ORD, U.S. EPA, Research Triangle Park, NC 27711.

    As signs of precocious puberty in girls reach ...

  9. Early Journals and Their Influences on the Development of Gerontology

    ERIC Educational Resources Information Center

    Mercer, Lorraine; Carter, Lorraine

    2012-01-01

    This examination of early gerontology journals identifies the multidisciplinary backgrounds of contributors, methods of investigation, nascent theory development, and formative themes and controversies. Through use of content, thematic, and critical analyses of second year issues of "The Gerontologist," "Educational Gerontology," "Research on…

  10. Teacher Efficacy in an Early Childhood Professional Development School

    ERIC Educational Resources Information Center

    Epstein, Ann; Willhite, Gary L.

    2015-01-01

    Teacher efficacy is the belief teachers have in their ability to impact student learning. Efficacy includes teacher confidence in instructional, management and collaboration skills. The following study addresses teacher efficacy in an Early Childhood Professional Development School (PDS). The PDS experience provides an opportunity for mentor…

  11. Changing the Perspective on Early Development of Rett Syndrome

    ERIC Educational Resources Information Center

    Marschik, Peter B.; Kaufmann, Walter E.; Sigafoos, Jeff; Wolin, Thomas; Zhang, Dajie; Bartl-Pokorny, Katrin D.; Pini, Giorgio; Zappella, Michele; Tager-Flusberg, Helen; Einspieler, Christa; Johnston, Michael V.

    2013-01-01

    We delineated the achievement of early speech-language milestones in 15 young children with Rett syndrome ("MECP2" positive) in the first two years of life using retrospective video analysis. By contrast to the commonly accepted concept that these children are normal in the pre-regression period, we found markedly atypical development of…

  12. Early Intervention and Its Effects on Maternal and Child Development.

    ERIC Educational Resources Information Center

    Slaughter, Diana T.

    1983-01-01

    The longitudinal study reported used an intervention strategy to test the thesis that sociocultural background, mediated by maternal attitudes and behaviors, influences Black children's early development in educationally significant ways. Two models of parent education were contrasted: the Levenstein toy demonstration program and the…

  13. Early Childhood Development Program, 1986-87. Interim Evaluation Report.

    ERIC Educational Resources Information Center

    Rachal, Janella

    This interim evaluation of Louisiana's 1986-87 Early Childhood Development Program focuses primarily on ongoing second and third year projects, but also provides some descriptive information about the general characteristics and implementation strategies of first year projects. The purpose of the evaluation was to provide information to decision…

  14. Developing Early Undergraduate Research at a Two-Year College

    ERIC Educational Resources Information Center

    Sibbernsen, Kendra

    2013-01-01

    Two-year college (TYC) physics teachers are not often required to provide student research experiences as a part of their contracted duties. However, some TYC physics faculty members are interested in developing research opportunities for their freshman- and sophomore-level students, often called "early undergraduate research" (EUR).…

  15. State Guide to Developing Successful Early Childhood Data Systems

    ERIC Educational Resources Information Center

    ICF International (NJ1), 2012

    2012-01-01

    Early education leaders--inside and outside of government--are looking for new ways to improve quality, accountability, and efficiency across many different programs serving young children and their families, and they see investment in data systems as a pivotal part of that effort. However, it can be challenging to develop and implement effective…

  16. Investigating the Validity of the Australian Early Development Index

    ERIC Educational Resources Information Center

    Brinkman, Sally A.; Silburn, Sven; Lawrence, David; Goldfeld, Sharon; Sayers, Mary; Oberklaid, Frank

    2007-01-01

    This article aims to contribute to the ongoing evaluation of the Australian Early Development Index (AEDI) by investigating its construct and concurrent validity with a subsample of 642 children aged 4 to 5 years drawn from the Longitudinal Study of Australian Children (LSAC). Construct validity was examined by considering the theoretical…

  17. Career Planning and Development for Early-Career Scientists

    EPA Science Inventory

    Early career development can be looked at as being of two major phases. The first phase is the formal educational process leading to an awarded degree, postdoctoral training, and potentially formal certification in a scientific discipline. The second phase is the informal educa...

  18. The Use of Electrophysiology in the Study of Early Development

    ERIC Educational Resources Information Center

    Szucs, Denes

    2005-01-01

    Electrophysiology is a timely and important tool in the study of early cognitive development. This commentary polishes the definition of event-related potential (ERP) components; often interpreted as expressions of mental processes. Further, attention is drawn to time-frequency analysis of the electroencephalogram (EEG) which conveys much more…

  19. Identification of the Social Development in Early Childhood in Pakistan

    ERIC Educational Resources Information Center

    Malik, Asif; Sarwar, Muhammad; Khan, Naeemullah

    2010-01-01

    This study was conducted to identify the social development in early childhood years. It was delimited to eight private schools of Lahore City from the area of Faisal Town and Shadman. Forty students (male and female) were randomly selected as the sample. Five students from Nursery, Prep and grade one were selected from each school. A checklist…

  20. Landing Profile Development During the Early Shuttle Program

    NASA Technical Reports Server (NTRS)

    Bobko, Karol Joseph

    2012-01-01

    I was asked to speak about my experiences as an astronaut during the early Shuttle program. There were many challenging and exciting things that I participated in during the Shuttle program but the item I believe is most appropriate for this audience is the development of the landing trajectory for both manual and automatic landings of the Space Shuttle.