Science.gov

Sample records for early clinical development

  1. 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

  2. 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…

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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…

  15. 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…

  16. 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,…

  17. 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.

  18. 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

  19. 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…

  20. 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.

  1. 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.

  2. 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,…

  3. 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.

  4. 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)

  5. 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

  6. 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…

  7. 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

  8. 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

  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. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. [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.

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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…

  5. 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

  6. 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.

  7. 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…

  8. 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,…

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. 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)

  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. 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

  19. 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].

  20. 78 FR 60291 - Investigational Device Exemptions for Early Feasibility Medical Device Clinical Studies...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-01

    ... ``Investigational Device Exemptions (IDEs) for Early Feasibility Medical Device Clinical Studies, Including Certain... facilitate early feasibility studies of medical devices, using appropriate risk mitigation strategies, under the IDE regulations. Early feasibility studies allow for limited early clinical evaluations of...

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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…

  8. 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…

  9. 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…

  10. 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,…

  11. [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.

  12. 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

  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. 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.

  15. 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

  16. 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

  17. 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…

  18. 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.

  19. 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…

  20. 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…

  1. 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;…

  2. 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…

  3. 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…

  4. 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,…

  5. 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...

  6. 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.…

  7. 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

  8. 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.

  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. 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

  11. [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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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…

  17. 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

  18. 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…

  19. 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).

  20. 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…

  1. 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.

  2. 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.

  3. 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.

  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. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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…

  10. 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.

  11. 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.

  12. 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

  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. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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)

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. Immunopathology of early and clinically silent lupus nephropathy.

    PubMed Central

    Cavallo, T.; Cameron, W. R.; Lapenas, D.

    1977-01-01

    Detailed immunopathologic studies of early or silent renal alterations in systemic lupus erythematosus have been sparse. The renal biopsies of 16 lupus patients with normal renal function, including 8 with hematuria and/or proteinuria of recent onset, and 8 without clinically detectable renal disease were investigated by light, immunofluorescence, and electron microscopy. Immunoglobulins, complement components, and electron-dense deposits were detected in glomeruli of all patients, regardless of morphologic appearance or lack of clinical evidence of renal involvement. Features of membranous glomerulonepritis were observed in 4 patients with substantial proteinuria. In the remaining 12 patients, including 3 with hematuria and 4 with slight proteinuria, either minimal glomerular alterations or features of mesangial proliferative glomerulonephritis were seen. Transformation of the original disease was demonstrated in 3 of 3 patients rebiopsied within 2 years. The significance of these findings is discussed in relation to a) the spectrum of clinical and immunopathologic alterations in lupus nephritis and b) transformation of the original disease. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:322502

  7. 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…

  8. 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

  9. 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.

  10. 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.

  11. 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…

  12. Why Children Matter: Investing in Early Childhood Care and Development.

    ERIC Educational Resources Information Center

    Cohn, Ruth; Chetley, Andrew

    This publication reflects the philosophy and support of the Bernard van Leer Foundation for early childhood care and development. It highlights different approaches to early childhood care and development and explains why the foundation believes that investing in early childhood is one of the best ways of building a brighter, better future. The…

  13. 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,…

  14. 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.

  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. 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…

  17. 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.

  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. 45 CFR 1304.21 - Education and early childhood development.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND... early childhood development. (a) Child development and education approach for all children. (1) In order... child development and education must: (i) Be developmentally and linguistically appropriate,...

  20. 45 CFR 1304.21 - Education and early childhood development.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND... early childhood development. (a) Child development and education approach for all children. (1) In order... child development and education must: (i) Be developmentally and linguistically appropriate,...

  1. 45 CFR 1304.21 - Education and early childhood development.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND... early childhood development. (a) Child development and education approach for all children. (1) In order... child development and education must: (i) Be developmentally and linguistically appropriate,...

  2. 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).…

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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…

  12. 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…

  13. 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…

  14. 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…

  15. 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.

  16. 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.

  17. 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…

  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. 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

  20. 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

  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. 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.

  3. 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…

  4. 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…

  5. 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…

  6. 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…

  7. 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 ...

  8. 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…

  9. 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…

  10. 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…

  11. 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

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. 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)

  17. 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.

  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. 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.

  1. 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

  2. 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.

  3. 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 ...

  4. 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.

  5. 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.

  6. Biomarkers for Early Detection of Clinically Relevant Prostate Cancer: A Multi-Institutional Validation Trial

    DTIC Science & Technology

    2015-10-01

    1 1 AWARD NUMBER: W81XWH-14-1-0596 TITLE: Biomarkers for Early Detection of Clinically Relevant Prostate Cancer. A Multi-Institutional...Validation Trial PRINCIPAL INVESTIGATOR: Jesse McKenney, MD CONTRACTING ORGANIZATION: Cleveland Clinic Foundation Cleveland, OH 44195 REPORT DATE...COVERED 30 Sep 2014 - 29 Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Biomarkers for Early Detection of Clinically Relevant Prostate Cancer. A

  7. 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.

  8. 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…

  9. 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.…

  10. 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…

  11. 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…

  12. 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…

  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. 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.

  16. Early Caregiving and Human Biobehavioral Development: A Comparative Physiology Approach

    PubMed Central

    Hane, Amie A.; Fox, Nathan A.

    2015-01-01

    A large and growing body of evidence demonstrates associations between quality of the early caregiving environment and risk for stress-related illness across the lifespan. The recent research examining associations between early caregiving environments and subsequent development is reviewed, with particular attention to early programming and subsequent malleability of systems underlying stress responsivity. A developmental comparative physiology model is suggested; one in which postnatal programming and phenotypic plasticity act in concert as mechanisms underlying the persisting effects of early care environments for biobehavioral outcomes. PMID:26753173

  17. 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.

  18. 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

  19. 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…

  20. 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…

  1. 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…

  2. 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…

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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)

  9. 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.

  10. 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…

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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…

  1. 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…

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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,…

  7. 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…

  8. 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…

  9. 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

  10. 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.

  11. 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…

  12. 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.

  13. 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.

  14. 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.

  15. 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…

  16. Is Early Clinical Evidence of Autonomic Shift Predictive of Infection Following Aneurysmal Subarachnoid Hemorrhage?

    PubMed Central

    Fletcher, Jeffrey J.; Rajajee, Venkatakrishna; Wilson, Thomas J.; Zahuranec, Darin B.

    2014-01-01

    Background Autonomic shift (AS), characterized by increased sympathetic nervous system activation, has been implicated in neurologically mediated cardiopulmonary dysfunction and immunodepression following stroke. We investigated the prevalence of AS defined by readily available clinical parameters and determined the association of AS with subsequent infection in a cohort of patients with aneurysmal SAH (aSAH). Methods Data were obtained from a single center cohort study of aSAH patients admitted January 1, 2007 through April 1, 2012. AS was defined as at least one early (<72 hours) routine clinical marker of neurologically mediated cardiopulmonary dysfunction based on electrocardiogram, echocardiogram, cardiac enzymes, or neurogenic pulmonary edema. Multivariable logistic regression models were developed to evaluate the association between AS and subsequent infection after adjusting for other covariates. Results A total 167 patients were included in the analysis (mean age 56, 27% male). AS was seen in 66/167 (40%; 95% CI, 32%–47%), and infection was seen in 80/167 (48%; 95% CI, 40%–55%). AS was associated with subsequent infection on unadjusted analysis (OR=2.11; 95% CI, 1.12–3.97); however, this association was no longer significant when adjusting for other predictors of infection (OR 1.36; 95% CI, 0.67–2.76). Age, clinical grade, and aneurysm location were all independent predictors of infection following aSAH. Conclusions We identified AS based on readily available clinical markers in 40% of patients with aSAH, though AS defined by these clinical criteria was not an independent predictor of infection. Additional studies may be warranted to determine the optimal definition of AS and the clinical significance of this finding. PMID:24189451

  17. 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.

  18. 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…

  19. 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…

  20. 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…

  1. 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…

  2. 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,…

  3. 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…

  4. 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

  5. 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…

  6. 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…

  7. 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.

  8. 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.

  9. 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.

  10. 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…

  11. 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

  12. Early evolution of the thermometer and application to clinical medicine.

    PubMed

    Wright, William F

    2016-02-01

    By the time of Hippocrates and Galen the notion of fevers and temperature were known. Through ensuing centuries, ancient Greek, Roman, and medieval savants and physicians made additional contributions to the understanding of fever, temperature, and thermometry. By the end of that era, there was a working definition of what constitutes a rationale temperature scale, the distinction between fever as a symptom and fever as a disease, an elaborate classification scheme for temperature, hypotheses as to the causes of fever, and methods for measuring fevers. Based on the definition of fever at that time, the 16th century scientist Galileo promulgated production of thermometric instruments hundreds of years before they were routinely used in the clinical setting. In this work we examine the history of fever and clinical thermometry in the ancient world through the end of the eighteenth century with descriptions of instruments for its measure and human relationship to fever.

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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

  19. Clinical characteristics of early- and late-onset gout: A cross-sectional observational study from a Chinese gout clinic.

    PubMed

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

    2016-11-01

    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.

  20. 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

  1. 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.

  2. 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

  3. Compilation and Clinical Applicability of an Early Auditory Processing Assessment Battery for Young Children.

    ERIC Educational Resources Information Center

    Fair, Lisl; Louw, Brenda; Hugo, Rene

    2001-01-01

    This study compiled a comprehensive early auditory processing skills assessment battery and evaluated the battery to toddlers with (n=8) and without (n=9) early recurrent otitis media. The assessment battery successfully distinguished between normal and deficient early auditory processing development in the subjects. The study also found parents…

  4. 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

  5. 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.

  6. Vasopressin in preeclampsia: a novel very early human pregnancy biomarker and clinically relevant mouse model.

    PubMed

    Santillan, Mark K; Santillan, Donna A; Scroggins, Sabrina M; Min, James Y; Sandgren, Jeremy A; Pearson, Nicole A; Leslie, Kimberly K; Hunter, Stephen K; Zamba, Gideon K D; Gibson-Corley, Katherine N; Grobe, Justin L

    2014-10-01

    Preeclampsia, a cardiovascular disorder of late pregnancy, is characterized as a low-renin hypertensive state relative to normotensive pregnancy. Because other nonpregnant low-renin hypertensive disorders often exhibit and are occasionally dependent on elevated arginine vasopressin (AVP) secretion, we hypothesized a possible use for plasma AVP measurements in the prediction of preeclampsia. Copeptin is an inert prosegment of AVP that is secreted in a 1:1 molar ratio and exhibits a substantially longer biological half-life compared with AVP, rendering it a clinically useful biomarker of AVP secretion. Copeptin was measured throughout pregnancy in maternal plasma from preeclamptic and control women. Maternal plasma copeptin was significantly higher throughout preeclamptic pregnancies versus control pregnancies. While controlling for clinically significant confounders (age, body mass index, chronic essential hypertension, twin gestation, diabetes mellitus, and history of preeclampsia) using multivariate regression, the association of higher copeptin concentration and the development of preeclampsia remained significant. Receiver operating characteristic analyses reveal that as early as the sixth week of gestation, elevated maternal plasma copeptin concentration is a highly significant predictor of preeclampsia throughout pregnancy. Finally, chronic infusion of AVP during pregnancy (24 ng per hour) is sufficient to phenocopy preeclampsia in C57BL/6J mice, causing pregnancy-specific hypertension, renal glomerular endotheliosis, proteinuria, and intrauterine growth restriction. These data implicate AVP release as a novel predictive biomarker for preeclampsia very early in pregnancy, identify chronic AVP infusion as a novel and clinically relevant model of preeclampsia in mice, and are consistent with a potential causative role for AVP in preeclampsia in humans.

  7. Mirrors in early clinical photography (1862-1882): a descriptive study.

    PubMed

    Horgmo, Øystein H

    2015-01-01

    In the mid-nineteenth century, photographers used mirrors to document different views of a patient in the same image. The first clinical photographs were taken by portrait photographers. As conventions for clinical photography were not yet established, early clinical photographs resemble contemporary portraits. The use of mirrors in clinical photography probably originated from the portrait studios, as several renowned photographers employed mirrors in their studio portraits. Clinical photographs taken for the US Army Medical Museum between 1862 and 1882 show different ways of employing this mirror technique.

  8. Clinical workout for the early detection of cognitive decline and dementia.

    PubMed

    Tsolaki, M

    2014-11-01

    Aging is the major risk factor for the development of human neurodegenerative maladies such as Alzheimer's, Huntington's and Parkinson's diseases (PDs) and prion disorders, all of which stem from toxic protein aggregation. All of these diseases are correlated with cognitive decline. Cognitive Decline is a dynamic state from normal cognition of aging to dementia. According to the original criteria for Alzheimer's Disease (AD) (1984), a clinical diagnosis was possible only when someone was already demented. The prevalence rates of Cognitive Decline (mild cognitive impairment plus dementia) are very high now and will be higher in future because of the increasing survival time of people. Many neurological and psychiatric diseases are correlated with cognitive decline. Diagnosis of cognitive decline is mostly clinical (clinical criteria), but there are multiple biomarkers that could help us mostly in research programs such as short or long, paper and pencil or computerized neuropsychological batteries for cognition, activities of daily living and behavior, electroencephalograph, event-related potentials, and imaging-structural magnetic resonance imaging (MRI) and functional (fMRI, Pittsburgh bound positron emission tomography, FDG-PET, single photon emission computerized tomography and imaging of tau pathology)-cerebrospinal fluid proteins (Abeta, tau and phospho-tau in AD and α-synuclein (αSyn) for PD). Blood biomarkers need more studies to confirm their usefulness. Genetic markers are also studied but until now are not used in clinical praxis. Finally, in everyday clinical praxis and in research workout for early detection of cognitive decline, the combination of biomarkers is useful.

  9. Paediatric early warning systems for detecting and responding to clinical deterioration in children: a systematic review

    PubMed Central

    Lambert, Veronica; Matthews, Anne; MacDonell, Rachel; Fitzsimons, John

    2017-01-01

    Objective To systematically review the available evidence on paediatric early warning systems (PEWS) for use in acute paediatric healthcare settings for the detection of, and timely response to, clinical deterioration in children. Method The electronic databases PubMed, MEDLINE, CINAHL, EMBASE and Cochrane were searched systematically from inception up to August 2016. Eligible studies had to refer to PEWS, inclusive of rapid response systems and teams. Outcomes had to be specific to the identification of and/or response to clinical deterioration in children (including neonates) in paediatric hospital settings (including emergency departments). 2 review authors independently completed the screening and selection process, the quality appraisal of the retrieved evidence and data extraction; with a third reviewer resolving any discrepancies, as required. Results were narratively synthesised. Results From a total screening of 2742 papers, 90 papers, of varied designs, were identified as eligible for inclusion in the review. Findings revealed that PEWS are extensively used internationally in paediatric inpatient hospital settings. However, robust empirical evidence on which PEWS is most effective was limited. The studies examined did however highlight some evidence of positive directional trends in improving clinical and process-based outcomes for clinically deteriorating children. Favourable outcomes were also identified for enhanced multidisciplinary team work, communication and confidence in recognising, reporting and making decisions about child clinical deterioration. Conclusions Despite many studies reporting on the complexity and multifaceted nature of PEWS, no evidence was sourced which examined PEWS as a complex healthcare intervention. Future research needs to investigate PEWS as a complex multifaceted sociotechnical system that is embedded in a wider safety culture influenced by many organisational and human factors. PEWS should be embraced as a part of a

  10. [Early clinical features of severe peripheral facial paralysis and acupuncture strategies].

    PubMed

    Wang, Sheng-Qiang; Li, Yun; Bai, Ya-Ping

    2010-05-01

    In order to have a good grasp of rules of acupuncture for severe peripheral facial paralysis, the early clinical features of severe peripheral facial paralysis (Bell's palsy) are studied and analyzed from the aspect of injury level, injury degrees, clinical syndromes and symptoms; consequently, the treatment strategies with acupuncture are proposed. The severe peripheral facial paralysis is an important research area in clinic trials which verifies the effectiveness of acupuncture treatment.

  11. 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…

  12. 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…

  13. 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…

  14. Bacterial DNA microarrays for clinical microbiology: the early logarithmic phase.

    PubMed

    Cassone, Marco; Giordano, Antonio; Pozzi, Gianni

    2007-01-01

    In this era of coexistence of high-throughput sequencing technologies and serious difficulties in the management of both common and novel infectious syndromes, new techniques which improve the study of micro-organisms is timely. In bacteriology, the most important subjects are bacterial pathogenicity, discovery of the genomic complexity of bacteria, and the epidemiology of antimicrobial resistance traits. From the clinical point of view, genetic testing is flanking phenotypic testing for the assessment of new, difficult to test antibiotic resistance traits, and for correlations with the microbial behaviour in vivo. The demand for faster, comprehensive and highly parallel microbial diagnostics is also cogent even at the basic laboratory level, where the ultimate objective is saving lives. In this setting, DNA microarrays offer a pivotal contribution by allowing performance of hybridization experiments in highly parallel formats, with an increasing reliability. Not only they are useful in deciphering host and microbial pathophysiology, they can also make the difference in the management of prognostic and therapeutic aspects of many diseases. Here, we provide an overview of the current use and the potential of DNA microarrays in clinical bacteriology, and several applications and technical solutions are discussed.

  15. Gaucher disease: clinical profile and therapeutic developments.

    PubMed

    Cox, Timothy M

    2010-12-06

    Gaucher disease is a rare inborn error of glycosphingolipid metabolism due to deficiency of lysosomal acid β-glucocerebrosidase; the condition has totemic significance for the development of orphan drugs. A designer therapy, which harnesses the mannose receptor to complement the functional defect in macrophages, ameliorates the principal clinical manifestations in hematopoietic bone marrow and viscera. While several aspects of Gaucher disease (particularly those affecting the skeleton and brain) are refractory to treatment, enzyme (replacement) therapy has become a pharmaceutical blockbuster. Human β-glucocerebrosidase was originally obtained from placenta and the Genzyme Corporation (Allston, MA) subsequently developed a recombinant product. After purification, the enzyme is modified to reveal terminal mannose residues which facilitate selective uptake of the protein, imiglucerase (Cerezyme(®)), in macrophage-rich tissues. The unprecedented success of Cerezyme has attracted fierce competition: two biosimilar agents, velaglucerase-alfa, VPRIV(®) (Shire Human Genetic Therapies, Dublin, Ireland) and taliglucerase-alfa (Protalix, Carmiel, Israel), are now approved or in late-phase clinical development as potential 'niche busters'. Oral treatments have advantages over biological agents for disorders requiring lifelong therapy and additional stratagems which utilize small, orally active molecules have been introduced; these include two chemically distinct compounds which inhibit uridine diphosphate glucose: N-acylsphingosine glucosyltransferase, the first step in the biosynthesis of glucosylceramide - a key molecular target in Gaucher disease and other glycosphingolipidoses. Academic and commercial enterprises in biotechnology have combined strategically to expand the therapeutic repertoire in Gaucher disease. The innovative potential of orphan drug legislation has been realized - with prodigious rewards for companies embracing its humanitarian precepts. In the era

  16. Early development of synchrony in cortical activations in the human

    PubMed Central

    Koolen, N.; Dereymaeker, A.; Räsänen, O.; Jansen, K.; Vervisch, J.; Matic, V.; Naulaers, G.; De Vos, M.; Van Huffel, S.; Vanhatalo, S.

    2016-01-01

    Early intermittent cortical activity is thought to play a crucial role in the growth of neuronal network development, and large scale brain networks are known to provide the basis for higher brain functions. Yet, the early development of the large scale synchrony in cortical activations is unknown. Here, we tested the hypothesis that the early intermittent cortical activations seen in the human scalp EEG show a clear developmental course during the last trimester of pregnancy, the period of intensive growth of cortico-cortical connections. We recorded scalp EEG from altogether 22 premature infants at post-menstrual age between 30 and 44 weeks, and the early cortical synchrony was quantified using recently introduced activation synchrony index (ASI). The developmental correlations of ASI were computed for individual EEG signals as well as anatomically and mathematically defined spatial subgroups. We report two main findings. First, we observed a robust and statistically significant increase in ASI in all cortical areas. Second, there were significant spatial gradients in the synchrony in fronto-occipital and left-to-right directions. These findings provide evidence that early cortical activity is increasingly synchronized across the neocortex. The ASI-based metrics introduced in our work allow direct translational comparison to in vivo animal models, as well as hold promise for implementation as a functional developmental biomarker in future research on human neonates. PMID:26876605

  17. 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…

  18. Development and Implementation of an Effective Early Childhood Handicapped Program.

    ERIC Educational Resources Information Center

    Condon, Kathryn; Dahlstrom, Mark

    The paper describes the Early Childhood Handicapped Program of Kenosha (WI). The program focuses on receptive and expressive language, fine and gross motor skills, self-help skills, cognitive skills, perceptual skills, and social/emotional skills development. For admission into the program, children must exhibit significant delays in two or more…

  19. Reflecting on Early Literacy Development in the Context of Vanuatu

    ERIC Educational Resources Information Center

    Hughes, Desma

    2004-01-01

    A low level of literacy development plagues many parts of the Pacific region despite the fact that parents are very keen for their children to become literate in order to embrace the modern world. Issues concerning early education and the attainment of literacy are still a challenge in the Pacific. In order to understand the reasons for the low…

  20. 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…

  1. 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.

  2. 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…

  3. Brain Development & Early Childhood: An Arkansas Kids Count Special Report.

    ERIC Educational Resources Information Center

    Rule, J. Chris

    Using recent economic data on state spending and information about childhood brain development, this Kids Count mini-report offers a snapshot of where Arkansas stands on early education and spending on such programs. The report examines the next steps, challenging conventional wisdom in order to explore the best path for improving child outcomes…

  4. An Analysis of Early Childhood Education Research and Development.

    ERIC Educational Resources Information Center

    Scott, Myrtle; And Others

    This volume organizes information on research and development in early childhood education. Goals and objectives of the 77 programs reviewed are described, and the strategies for implementing the programs are discussed. Organizational factors and the problems encountered in the programs and projects are considered. There is a short discussion of…

  5. Predictors of Early versus Later Spelling Development in Danish

    ERIC Educational Resources Information Center

    Nielsen, Anne-Mette Veber; Juul, Holger

    2016-01-01

    The present study examined phoneme awareness, phonological short term memory, letter knowledge, rapid automatized naming (RAN), and visual-verbal paired associate learning (PAL) as longitudinal predictors of spelling skills in an early phase (Grade 2) and a later phase (Grade 5) of development in a sample of 140 children learning to spell in the…

  6. Cognitive and Cultural Determinants of Early IE Development.

    ERIC Educational Resources Information Center

    Stephens, Mark W.

    Results of several studies of cognitive and cultural correlates and determinants of early IE development are discussed, and some implications of the findings are pointed out. In studies of correlations between IE and intelligence test scores, results show that the scores increase regularly with age, from age 4 through 8, and there are fairly…

  7. 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...

  8. Promoting and Investing in Early Childhood Development Projects.

    ERIC Educational Resources Information Center

    Seng, Seok Hoon

    This paper describes the impact of three early childhood education research programs in Australia, Singapore, and Malaysia, and funded by the Bernard van Leer Foundation. The Mount Druitt Project in Australia has implemented institution- and home-based educational programs, which also monitor children's physical development and work closely with…

  9. 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…

  10. 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…

  11. 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).…

  12. 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…

  13. Starting Smart: How Early Experiences Affect Brain Development. Second Edition.

    ERIC Educational Resources Information Center

    Hawley, Theresa

    Based on recent research, it is now believed that brain growth is highly dependent upon children's early experiences. Neurons allow communication and coordinated functioning among various brain areas. Brain development after birth consists of an ongoing process of wiring and rewiring the connections among neurons. The forming and breaking of…

  14. 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 ...

  15. 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…

  16. 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…

  17. 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.…

  18. 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…

  19. 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…

  20. Applying cognitive training to target executive functions during early development

    PubMed Central

    Wass, Sam V.

    2015-01-01

    Developmental psychopathology is increasingly recognizing the importance of distinguishing causal processes (i.e., the mechanisms that cause a disease) from developmental outcomes (i.e., the symptoms of the disorder as it is eventually diagnosed). Targeting causal processes early in disordered development may be more effective than waiting until outcomes are established and then trying to reverse the pathogenic process. In this review, I evaluate evidence suggesting that neural and behavioral plasticity may be greatest at very early stages of development. I also describe correlational evidence suggesting that, across a number of conditions, early emerging individual differences in attentional control and working memory may play a role in mediating later-developing differences in academic and other forms of learning. I review the currently small number of studies that applied direct and indirect cognitive training targeted at young individuals and discuss methodological challenges associated with targeting this age group. I also discuss a number of ways in which early, targeted cognitive training may be used to help us understand the developmental mechanisms subserving typical and atypical cognitive development. PMID:24511910

  1. Early Childhood Traumatic Brain Injuries: Effects on Development and Interventions.

    ERIC Educational Resources Information Center

    Lowenthal, Barbara

    1998-01-01

    Describes the variety of possible effects of traumatic brain injuries (TBI) on early childhood development in the cognitive, language, social-emotional, motor, and adaptive domains. Suggests interventions which can assist young survivors and their families. Suggests that more long-term, intensive studies be conducted on the short- and long-term…

  2. Early Retinoic acid deprivation in developing zebrafish results in microphthalmia

    PubMed Central

    Le, Hong-Gam T.; Dowling, John E.; Cameron, D. Joshua

    2013-01-01

    Vitamin A deficiency causes impaired vision and blindness in millions of children around the world. Previous studies in zebrafish have demonstrated that retinoic acid (RA), the acid form of vitamin A, plays a vital role in early eye development. The objective of this study was to describe the effects of early RA deficiency by treating zebrafish with diethylaminobenzaldehyde (DEAB), a potent inhibitor of the enzyme retinaldehyde dehydrogenase (Raldh) that converts retinal to RA. Zebrafish embryos were treated for 2 hours beginning at 9 hours post-fertilization (hpf). Gross morphology and retinal development were examined at regular intervals for 5 days after treatment. The optokinetic reflex (OKR) test, visual background adaptation (VBA) test, and the electroretinogram (ERG) were performed to assess visual function and behavior. Early treatment of zebrafish embryos with 100 μM DEAB (9hr) resulted in reduced eye size and this microphthalmia persisted through larval development. Retinal histology revealed that DEAB eyes, had significant developmental abnormalities but had relatively normal retinal lamination by 5.5 days post-fertilization (dpf). However, the fish showed neither, an OKR or VBA response. Further, the retina did not respond to light as measured by the ERG. We conclude that early deficiency of RA during eye development causes microphthalmia as well as other visual defects, and that timing of the RA deficiency is critical to the developmental outcome. PMID:23013828

  3. Learning Workers: Young New Zealanders and Early Career Development

    ERIC Educational Resources Information Center

    Vaughan, Karen

    2010-01-01

    Young adults' early career development is an increasingly important field of inquiry. With the complexity of modern transitions from school and the lifelong learning demands of emerging knowledge societies, governments are concerned to improve learning pathways into, and through, tertiary education and work. Young adults are exploring new learning…

  4. Family Concepts in Early Learning and Development Standards

    ERIC Educational Resources Information Center

    Walsh, Bridget A.; Sanchez, Claudia; Lee, Angela M.; Casillas, Nicole; Hansen, Caitlynn

    2016-01-01

    This exploratory study investigated the use of concepts related to families, parents, and the home in 51 state-level early learning and development standards documents. Guidelines from six national family involvement, engagement, and school-partnership models were used to create the Family Involvement Models Analysis Chart (FIMAC), which served as…

  5. Translational and Early Phase Strategies for Treatment Development: Report of ISCTM Autumn 2013 Symposium

    PubMed Central

    Young, Jared W.; Potter, William Z.; Riley, Steve; Groeneveld, Geert J.; Kinon, Bruce J.; Egan, Mike F.; Feltner, Douglas E.

    2015-01-01

    For decades, there has been a distinct disconnect translating a compound’s effects from basic neuroscience into clinical efficacy. This disconnect has not only been in terms of generating approved compounds, but also in rejecting targets. During the drug discovery process there are key points to be adhered to that would strengthen the likelihood of a compound being translated to the clinic. These points include 1) the importance of translational pharmacology whereby preclinical pharmacological data should predict clinical efficacy; 2) rigorous early phase drug evaluation to enhance early go/no-go decisionmaking; 3) using exposure response modeling to predict drug efficacy during proof-of-concept trials; 4) designing and conducting the appropriate proof-of-concept study; and 5) optimizing Phase II studies to set the stage for success in Phase III trials. These topics were covered in The International Society for CNS Clinical Trials and Methodology (ISCTM) Autumn 2013 meeting on the topic of translational and early development strategies and tools led by Drs. Potter and Feltner. This report comprises a review of those proceedings with a concluding summary to advance future clinical trials. PMID:25977839

  6. Translational and Early Phase Strategies for Treatment Development: Report of ISCTM Autumn 2013 Symposium.

    PubMed

    Young, Jared W; Potter, William Z; Riley, Steve; Groeneveld, Geert J; Kinon, Bruce J; Egan, Mike F; Feltner, Douglas E

    2015-01-01

    For decades, there has been a distinct disconnect translating a compound's effects from basic neuroscience into clinical efficacy. This disconnect has not only been in terms of generating approved compounds, but also in rejecting targets. During the drug discovery process there are key points to be adhered to that would strengthen the likelihood of a compound being translated to the clinic. These points include 1) the importance of translational pharmacology whereby preclinical pharmacological data should predict clinical efficacy; 2) rigorous early phase drug evaluation to enhance early go/no-go decisionmaking; 3) using exposure response modeling to predict drug efficacy during proof-of-concept trials; 4) designing and conducting the appropriate proof-of-concept study; and 5) optimizing Phase II studies to set the stage for success in Phase III trials. These topics were covered in The International Society for CNS Clinical Trials and Methodology (ISCTM) Autumn 2013 meeting on the topic of translational and early development strategies and tools led by Drs. Potter and Feltner. This report comprises a review of those proceedings with a concluding summary to advance future clinical trials.

  7. Photodynamic therapy for locally advanced pancreatic cancer: early clinical results

    NASA Astrophysics Data System (ADS)

    Sandanayake, N. S.; Huggett, M. T.; Bown, S. G.; Pogue, B. W.; Hasan, T.; Pereira, S. P.

    2010-02-01

    Pancreatic adenocarcinoma ranks as the fourth most common cause of cancer death in the USA. Patients usually present late with advanced disease, limiting attempted curative surgery to 10% of cases. Overall prognosis is poor with one-year survival rates of less than 10% with palliative chemotherapy and/or radiotherapy. Given these dismal results, a minimally invasive treatment capable of local destruction of tumor tissue with low morbidity may have a place in the treatment of this disease. In this paper we review the preclinical photodynamic therapy (PDT) studies which have shown that it is possible to achieve a zone of necrosis in normal pancreas and implanted tumour tissue. Side effects of treatment and evidence of a potential survival advantage are discussed. We describe the only published clinical study of pancreatic interstitial PDT, which was carried out by our group (Bown et al Gut 2002), in 16 patients with unresectable locally advanced pancreatic adenocarcinoma. All patients had evidence of tumor necrosis on follow-up imaging, with a median survival from diagnosis of 12.5 months. Finally, we outline a phase I dose-escalation study of verteporfin single fibre PDT followed by standard gemcitabine chemotherapy which our group is currently undertaking in patients with locally advanced pancreatic cancer. Randomized controlled studies are also planned.

  8. Early development of Xenopus embryos is affected by simulated gravity

    NASA Technical Reports Server (NTRS)

    Yokota, Hiroki; Neff, Anton W.; Malacinski, George M.

    1994-01-01

    Early amphibian (Xenopus laevis) development under clinostat-simulated weightlessness and centrifuge-simulated hypergravity was studied. The results revealed significant effects on (i) 'morphological patterning' such as the cleavage furrow pattern in the vegetal hemisphere at the eight-cell stage and the shape of the dorsal lip in early gastrulae and (ii) 'the timing of embryonic events' such as the third cleavage furrow completion and the dorsal lip appearance. Substantial variations in sensitivity to simulated force fields were observed, which should be considered in interpreting spaceflight data.

  9. Developing International Collaborations for Early Career Researchers in Psychology

    PubMed Central

    Flanagan, Julianne C.; Barrett, Emma L.; Crome, Erica; Forbes, Miriam

    2015-01-01

    International collaboration is becoming increasingly vital as the emphasis on unmet need for mental health across cultures and nations grows. Opportunities exist for early career researchers to engage in international collaboration. However, little information is provided about such opportunities in most current psychology training models. The authors are early career researchers in psychology from U.S. and Australia who have developed a collaborative relationship over the past two years. Our goal is to increase awareness of funding opportunities to support international research and to highlight the benefits and challenges associated with international collaboration based on our experience. PMID:27453624

  10. Teachers' Perceptions of Their Mentoring Role in Three Different Clinical Settings: Student Teaching, Early Field Experiences, and Entry Year Teaching

    ERIC Educational Resources Information Center

    Gut, Dianne M.; Beam, Pamela C.; Henning, John E.; Cochran, Deborah C.; Knight, Rhonda Talford

    2014-01-01

    The purpose of this study was to determine the differences in mentoring across three different clinical settings: student teaching, early field experiences, and entry year teachers. Eighteen teachers with mentoring experience in all three clinical settings were selected and interviewed. The teachers' expectations for teacher development,…

  11. Germination and early plant development of ten plant species ...

    EPA Pesticide Factsheets

    Ten agronomic plant species were exposed to different concentrations of nano titanium dioxide (nTiO2) or nano cerium oxide (nCeO2) (0, 250, 500 and 1000 mg/L) to examine potential effects on germination and early seedling development. We modified a standard test protocol developed for soluble chemicals (OPPTS 850.4200) to determine if such an approach might be useful for screening engineered nanomaterials (ENMs) and whether there were differences in response across a range of commercially important plant species to two common metal oxide ENMs. Eight of 10 species responded to nTiO2, and 5 species responded to nCeO2. Overall, it appeared that early root growth may be a more sensitive indicator of potential effects from ENM exposure than germination. The observed effects did not always relate to the exposure concentration, indicating that mass-based concentration may not fully explain developmental effects of these two ENMs. The results suggest that nTiO2 and nCeO2 have different effects on early plant growth of agronomic species, which may alter the timing of specific developmental events during their life cycle. In addition, standard germination tests, which are commonly used for toxicity screening of new materials, may not detect the subtle but potentially more important changes associated with early growth and development in terrestrial plants. Engineered nanoparticles (ENMs) have been recognized as valuable components of new technologies and are current

  12. Early postoperative tumor progression predicts clinical outcome in glioblastoma-implication for clinical trials.

    PubMed

    Merkel, Andreas; Soeldner, Dorothea; Wendl, Christina; Urkan, Dilek; Kuramatsu, Joji B; Seliger, Corinna; Proescholdt, Martin; Eyupoglu, Ilker Y; Hau, Peter; Uhl, Martin

    2017-01-18

    Molecular markers define the diagnosis of glioblastoma in the new WHO classification of 2016, challenging neuro-oncology centers to provide timely treatment initiation. The aim of this study was to determine whether a time delay to treatment initiation was accompanied by signs of early tumor progression in an MRI before the start of radiotherapy, and, if so, whether this influences the survival of glioblastoma patients. Images from 61 patients with early post-surgery MRI and a second MRI just before the start of radiotherapy were examined retrospectively for signs of early tumor progression. Survival information was analyzed using the Kaplan-Meier method, and a Cox multivariate analysis was performed to identify independent variables for survival prediction. 59 percent of patients showed signs of early tumor progression after a mean time of 24.1 days from the early post-surgery MRI to the start of radiotherapy. Compared to the group without signs of early tumor progression, which had a mean time of 23.3 days (p = 0.685, Student's t test), progression free survival was reduced from 320 to 185 days (HR 2.3; CI 95% 1.3-4.0; p = 0.0042, log-rank test) and overall survival from 778 to 329 days (HR 2.9; CI 95% 1.6-5.1; p = 0.0005). A multivariate Cox regression analysis revealed that the Karnofsky performance score, O-6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, and signs of early tumor progression are prognostic markers of overall survival. Early tumor progression at the start of radiotherapy is associated with a worse prognosis for glioblastoma patients. A standardized baseline MRI might allow for better patient stratification.

  13. Research and Clinical Center for Child Development Annual Report, 1990-1991, No. 14.

    ERIC Educational Resources Information Center

    Wakai, Kunio, Ed.

    This annual report by the Research and Clinical Center for Child Development at Hokkaido University in Sapporo, Japan contains 10 articles by Japanese and American researchers on various aspects of children's cognitive and affective development. The following articles are presented: (1) "Making the Cut: Early Schooling and Cognitive…

  14. Alternatives to the fish early life-stage test: Developing a conceptual model for early fish development

    EPA Science Inventory

    Chronic fish toxicity is a key parameter for hazard classification and environmental risk assessment of chemicals, and the OECD 210 fish early life-stage (FELS) test is the primary guideline test used for various international regulatory programs. There exists a need to develop ...

  15. Optimal adaptive two-stage designs for early phase II clinical trials.

    PubMed

    Shan, Guogen; Wilding, Gregory E; Hutson, Alan D; Gerstenberger, Shawn

    2016-04-15

    Simon's optimal two-stage design has been widely used in early phase clinical trials for Oncology and AIDS studies with binary endpoints. With this approach, the second-stage sample size is fixed when the trial passes the first stage with sufficient activity. Adaptive designs, such as those due to Banerjee and Tsiatis (2006) and Englert and Kieser (2013), are flexible in the sense that the second-stage sample size depends on the response from the first stage, and these designs are often seen to reduce the expected sample size under the null hypothesis as compared with Simon's approach. An unappealing trait of the existing designs is that they are not associated with a second-stage sample size, which is a non-increasing function of the first-stage response rate. In this paper, an efficient intelligent process, the branch-and-bound algorithm, is used in extensively searching for the optimal adaptive design with the smallest expected sample size under the null, while the type I and II error rates are maintained and the aforementioned monotonicity characteristic is respected. The proposed optimal design is observed to have smaller expected sample sizes compared to Simon's optimal design, and the maximum total sample size of the proposed adaptive design is very close to that from Simon's method. The proposed optimal adaptive two-stage design is recommended for use in practice to improve the flexibility and efficiency of early phase therapeutic development.

  16. Gross Motor Development, Movement Abnormalities, and Early Identification of Autism

    PubMed Central

    Young, Gregory S.; Goldring, Stacy; Greiss-Hess, Laura; Herrera, Adriana M.; Steele, Joel; Macari, Suzanne; Hepburn, Susan; Rogers, Sally J.

    2015-01-01

    Gross motor development (supine, prone, rolling, sitting, crawling, walking) and movement abnormalities were examined in the home videos of infants later diagnosed with autism (regression and no regression subgroups), developmental delays (DD), or typical development. Group differences in maturity were found for walking, prone, and supine, with the DD and Autism-No Regression groups both showing later developing motor maturity than typical children. The only statistically significant differences in movement abnormalities were in the DD group; the two autism groups did not differ from the typical group in rates of movement abnormalities or lack of protective responses. These findings do not replicate previous investigations suggesting that early motor abnormalities seen on home video can assist in early identification of autism. PMID:17805956

  17. c-Myb is essential for early T cell development

    PubMed Central

    Allen, Robert D.; Bender, Timothy P.; Siu, Gerald

    1999-01-01

    The c-Myb transcription factor is important for fetal hematopoiesis and has been proposed to mediate later stages of lymphocyte development. Using homozygous null c-Myb/Rag1 chimeric mice, we have determined that c-Myb plays an important role in the differentiation of macrophages and lymphocytes from precursor stem cells. We also determine that deletion of c-Myb leads to a complete block in early T cell development just before the oligopotent thymocyte matures into the definitive T cell precursor. These data indicate that c-Myb plays an important role at multiple stages of hematopoiesis and is required at an early stage of T cell development. PMID:10323859

  18. Early stress and human behavioral development: emerging evolutionary perspectives.

    PubMed

    Del Giudice, M

    2014-08-01

    Stress experienced early in life exerts a powerful, lasting influence on development. Converging empirical findings show that stressful experiences become deeply embedded in the child's neurobiology, with an astonishing range of long-term effects on cognition, emotion, and behavior. In contrast with the prevailing view that such effects are the maladaptive outcomes of 'toxic' stress, adaptive models regard them as manifestations of evolved developmental plasticity. In this paper, I offer a brief introduction to adaptive models of early stress and human behavioral development, with emphasis on recent theoretical contributions and emerging concepts in the field. I begin by contrasting dysregulation models of early stress with their adaptive counterparts; I then introduce life history theory as a unifying framework, and review recent work on predictive adaptive responses (PARs) in human life history development. In particular, I discuss the distinction between forecasting the future state of the environment (external prediction) and forecasting the future state of the organism (internal prediction). Next, I present the adaptive calibration model, an integrative model of individual differences in stress responsivity based on life history concepts. I conclude by examining how maternal-fetal conflict may shape the physiology of prenatal stress and its adaptive and maladaptive effects on postnatal development. In total, I aim to show how theoretical work from evolutionary biology is reshaping the way we think about the role of stress in human development, and provide researchers with an up-to-date conceptual map of this fascinating and rapidly evolving field.

  19. Early Childhood WIC Participation, Cognitive Development and Academic Achievement

    PubMed Central

    Jackson, Margot I.

    2015-01-01

    For the half of American children who live in or near poverty, nutritional policy is part of the safety net against hunger and its negative effects on children’s development. The Special Supplemental Nutrition Program for Women, Infants and Children (WIC) provides steadily available food from the food groups essential for physical and cognitive development. The effects of WIC on dietary quality among participating women and children are strong and positive. Furthermore, there is a strong influence of nutrition on cognitive development and socioeconomic inequality. Yet, research on the non-health effects of U.S. child nutritional policy is scarce, despite the ultimate goal of health policies directed at children—to enable productive functioning across multiple social institutions over the life course. Using two nationally representative, longitudinal surveys of children—the Early Childhood Longitudinal Study, Birth Cohort (ECLS-B) and the Child Development Supplement (CDS) of the Panel Study of Income Dynamics—I examine how prenatal and early childhood exposure to WIC is associated in the short-term with cognitive development, and in the longer-term with reading and math learning. Results suggest that early WIC participation is associated with both cognitive and academic benefits. These findings suggest that WIC meaningfully contributes to children’s educational prospects. PMID:25555255

  20. Telomerase Activity is Downregulated Early During Human Brain Development

    PubMed Central

    Ishaq, Abbas; Hanson, Peter S.; Morris, Christopher M.; Saretzki, Gabriele

    2016-01-01

    Changes in hTERT splice variant expression have been proposed to facilitate the decrease of telomerase activity during fetal development in various human tissues. Here, we analyzed the expression of telomerase RNA (hTR), wild type and α-spliced hTERT in developing human fetal brain (post conception weeks, pcw, 6–19) and in young and old cortices using qPCR and correlated it to telomerase activity measured by TRAP assay. Decrease of telomerase activity occurred early during brain development and correlated strongest to decreased hTR expression. The expression of α-spliced hTERT increased between pcw 10 and 19, while that of wild type hTERT remained unchanged. Lack of expression differences between young and old cortices suggests that most changes seem to occur early during human brain development. Using in vitro differentiation of neural precursor stem cells (NPSCs) derived at pcw 6 we found a decrease in telomerase activity but no major expression changes in telomerase associated genes. Thus, they do not seem to model the mechanisms for the decrease in telomerase activity in fetal brains. Our results suggest that decreased hTR levels, as well as transient increase in α-spliced hTERT, might both contribute to downregulation of telomerase activity during early human brain development between 6 and 17 pcw. PMID:27322326

  1. Early childhood service development and intersectoral collaboration in rural Australia.

    PubMed

    Johns, Susan

    2010-01-01

    There is a paucity of research into the development of intersectoral collaborations designed to support early childhood development in rural communities. Drawing on findings from a qualitative study conducted in three small rural communities in Tasmania, this paper will examine community-based intersectoral collaborations involving government and non-government organisations from the health and allied health, education and community service sectors. The paper analyses the process of developing intersectoral collaborations from the perspective of early childhood health and wellbeing. The specific focus is on collaborations that build family and community capacity. Findings indicate that three groups of factors operate interdependently to influence collaborations: social capital, leadership and environmental factors. Each community has different leadership sources, structures and processes, shaped by levels of community social capital, and by environmental factors such as policy and resources. Effective models of early childhood development require strong local and external leadership. Rural communities that are able to identify and harness the skills, knowledge and resources of internal and external leaders are well positioned to take greater ownership of their own health and wellbeing. The paper provides guidelines for developing and enhancing the capacity of rural communities at different stages of collaborative readiness.

  2. Early engineering approaches to improve peptide developability and manufacturability.

    PubMed

    Furman, Jennifer L; Chiu, Mark; Hunter, Michael J

    2015-01-01

    Downstream success in Pharmaceutical Development requires thoughtful molecule design early in the lifetime of any potential therapeutic. Most therapeutic monoclonal antibodies are quite similar with respect to their developability properties. However, the properties of therapeutic peptides tend to be as diverse as the molecules themselves. Analysis of the primary sequence reveals sites of potential adverse posttranslational modifications including asparagine deamidation, aspartic acid isomerization, methionine, tryptophan, and cysteine oxidation and, potentially, chemical and proteolytic degradation liabilities that can impact the developability and manufacturability of a potential therapeutic peptide. Assessing these liabilities, both biophysically and functionally, early in a molecule's lifetime can drive a more effective path forward in the drug discovery process. In addition to these potential liabilities, more complex peptides that contain multiple disulfide bonds can pose particular challenges with respect to production and manufacturability. Approaches to reducing the disulfide bond complexity of these peptides are often explored with mixed success. Proteolytic degradation is a major contributor to decreased half-life and efficacy. Addressing this aspect of peptide stability early in the discovery process increases downstream success. We will address aspects of peptide sequence analysis, molecule complexity, developability analysis, and manufacturing routes that drive the decision making processes during peptide therapeutic development.

  3. Early childhood WIC participation, cognitive development and academic achievement.

    PubMed

    Jackson, Margot I

    2015-02-01

    For the 22% of American children who live below the federal poverty line, and the additional 23% who live below twice that level, nutritional policy is part of the safety net against hunger and its negative effects on children's development. The Special Supplemental Nutrition Program for Women, Infants and Children (WIC) provides steadily available food from the food groups essential for physical and cognitive development. The effects of WIC on dietary quality among participating women and children are strong and positive. Furthermore, there is a strong influence of nutrition on cognitive development and socioeconomic inequality. Yet, research on the non-health effects of U.S. child nutritional policy is scarce, despite the ultimate goal of health policies directed at children-to enable productive functioning across multiple social institutions over the life course. Using two nationally representative, longitudinal surveys of children-the Early Childhood Longitudinal Study, Birth Cohort (ECLS-B) and the Child Development Supplement (CDS) of the Panel Study of Income Dynamics-I examine how prenatal and early childhood exposure to WIC is associated in the short-term with cognitive development, and in the longer-term with reading and math learning. Results show that early WIC participation is associated with both cognitive and academic benefits. These findings suggest that WIC meaningfully contributes to children's educational prospects.

  4. Amnestic Mild Cognitive Impairment and Early Alzheimer's Disease in an Asian Memory Clinic – Evidence for a Clinical Spectrum

    PubMed Central

    Chan, M.; Tay, L.; Chong, M.S.

    2011-01-01

    Objectives To determine if mild cognitive impairment (MCI) represents a continuum of cognitive and functional deficits. Methods Clinical data of 164 subjects with no dementia (ND, n = 52), uncertain dementia (n = 69), and mild probable Alzheimer's disease (AD, n = 43) were reviewed. Uncertain dementia patients were classified as pre-MCI (n = 11), early amnestic MCI (e-aMCI, n = 15) and late amnestic MCI (l-aMCI, n = 15). Cognitive assessments [Chinese Mini-Mental State Examination (CMMSE) and a validated neuropsychological battery], functional assessments (Lawton's scale for instrumental activities of daily living) and neuroimaging (ischemic lesions and medial temporal lobe atrophy) were reviewed. Results ND, aMCI and mild AD subjects demonstrated a significant trend for worsening performance for all cognitive and functional measures (ANOVA, p < 0.05). Pre-MCI subjects performed significantly better than aMCI subjects in all verbal memory domains (p < 0.001), while l-aMCI had worse functional performance (p = 0.007), a trend towards greater depressive symptoms (p = 0.05) and higher medial temporal lobe atrophy scores (p = 0.06). l-aMCI subjects were more likely than either pre-MCI or e-aMCI to progress to dementia over a mean follow-up period of 2.5 years (46.7 vs. 9.1 and 20.0%, respectively). Conclusions Clinical delineation of aMCI allows the differentiation of those likely to progress for better correlation to biomarker development. PMID:22163238

  5. Early Psychosis and Trauma-Related Disorders: Clinical Practice Guidelines and Future Directions

    PubMed Central

    Cragin, Casey A.; Straus, Martha B.; Blacker, Dawn; Tully, Laura M.; Niendam, Tara A.

    2017-01-01

    Despite high rates of trauma-related disorders among individuals with early psychosis, no clinical practice guidelines for the treatment of comorbid early psychosis and trauma-related disorders exist to date. Indeed, the routine exclusion of individuals with past and current psychosis from participation in trauma research and practice has limited the accumulation of research that could support such clinical practice guidelines. While preliminary research evidence suggests that traditional, evidence-based treatments for trauma-related disorders can be safely and effectively employed to reduce symptoms of posttraumatic stress and chronic psychosis, it remains unclear whether such treatments are appropriate for individuals in the early stages of psychotic illness. Clinical experts (N = 118) representing 121 early psychosis programs across 28 states were surveyed using the expert consensus method. Forty-nine clinical experts responded and reached consensus on 46 of 49 expert consensus items related to the treatment of comorbid early psychosis and trauma-related disorders. Conjoint or family therapy and individual therapy were rated as treatment approaches of choice. Anxiety or stress management and psychoeducation were rated as treatment interventions of choice for addressing both trauma symptoms and psychotic symptoms. In addition, case management was rated as a treatment intervention of choice for addressing psychotic symptoms. No consensus was reached on expert consensus items regarding the appropriateness of a parallel treatment approach exposure interventions for addressing psychotic symptoms, or sensorimotor or movement interventions for addressing trauma symptoms. In areas where expert consensus exists and is supported by current research, preliminary clinical practice guidelines for the treatment of comorbid early psychosis and trauma-related disorders are offered. In areas where expert consensus does not exist, recommendations for future research are

  6. Clinical development of phosphatidylinositol 3-kinase inhibitors for cancer treatment

    PubMed Central

    2012-01-01

    The phosphatidylinositol 3-kinase (PI3K) pathway is commonly deregulated in cancer. In recent years, the results of the first phase I clinical trials with PI3K inhibitors have become available. In comparison to other targeted agents such v-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitors in melanoma or crizotinib in anaplastic lymphoma receptor tyrosine kinase (ALK) translocated tumors, the number of objective responses to PI3K inhibitors is less dramatic. In this review we propose possible strategies to optimize the clinical development of PI3K inhibitors: by exploring the potential role of PI3K isoform-specific inhibitors in improving the therapeutic index, molecular characterization as a basis for patient selection, and the relevance of performing serial tumor biopsies to understand the associated mechanisms of drug resistance. The main focus of this review will be on PI3K isoform-specific inhibitors by describing the functions of different PI3K isoforms, the preclinical activity of selective PI3K isoform-specific inhibitors and the early clinical data of these compounds. PMID:23232172

  7. Exceptional dinosaur fossils show ontogenetic development of early feathers.

    PubMed

    Xu, Xing; Zheng, Xiaoting; You, Hailu

    2010-04-29

    Recent discoveries of feathered dinosaur specimens have greatly improved our understanding of the origin and early evolution of feathers, but little information is available on the ontogenetic development of early feathers. Here we describe an early-juvenile specimen and a late-juvenile specimen, both referable to the oviraptorosaur Similicaudipteryx, recovered from the Lower Cretaceous Yixian Formation of western Liaoning, China. The two specimens have strikingly different remiges and rectrices, suggesting that a radical morphological change occurred during feather development, as is the case for modern feathers. However, both the remiges and the rectrices are proximally ribbon-like in the younger specimen but fully pennaceous in the older specimen, a pattern not known in any modern bird. In combination with the wide distribution of proximally ribbon-like pennaceous feathers and elongate broad filamentous feathers among extinct theropods, this find suggests that early feathers were developmentally more diverse than modern ones and that some developmental features, and the resultant morphotypes, have been lost in feather evolution.

  8. Socioeconomic status and functional brain development - associations in early infancy.

    PubMed

    Tomalski, Przemyslaw; Moore, Derek G; Ribeiro, Helena; Axelsson, Emma L; Murphy, Elizabeth; Karmiloff-Smith, Annette; Johnson, Mark H; Kushnerenko, Elena

    2013-09-01

    Socioeconomic status (SES) impacts on both structural and functional brain development in childhood, but how early its effects can be demonstrated is unknown. In this study we measured resting baseline EEG activity in the gamma frequency range in awake 6-9-month-olds from areas of East London with high socioeconomic deprivation. Between-subject comparisons of infants from low- and high-income families revealed significantly lower frontal gamma power in infants from low-income homes. Similar power differences were found when comparing infants according to maternal occupation, with lower occupational status groups yielding lower power. Infant sleep, maternal education, length of gestation, and birth weight, as well as smoke exposure and bilingualism, did not explain these differences. Our results show that the effects of socioeconomic disparities on brain activity can already be detected in early infancy, potentially pointing to very early risk for language and attention difficulties. This is the first study to reveal region-selective differences in functional brain development associated with early infancy in low-income families.

  9. Conditions on Early Mars Might Have Fostered Rapid and Early Development of Life

    NASA Technical Reports Server (NTRS)

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

    2007-01-01

    The exploration of Mars during the past decades has begun to unveil the history of the planet. The combinations of remote sensing, in situ geochemical compositional measurements and photographic observations from both above and on the surface have shown Mars to have a dynamic and active geologic evolution. Mars geologic evolution clearly had conditions that were suitable for supporting life. For a planet to be able to be habitable, it must have water, carbon sources, energy sources and 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-carved canyons and oceans or lakes with the early presence of near surface water shown by precipitated carbonates in ALH84001 well-dated at approx.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, early active volcanism continuing throughout Martian history, and, and continuing impact processes, (iii) Carbon and water from possibly extensive volcanic outgassing (i.e. H2O, CO2, CH4, CO, O2, N2, H2S, SO2, etc.) and (iv) some crustal tectonics as revealed by faulting and possible plate movement reflected by the magnetic pattern in the crust. The question arises: "Why would life not evolve from these favorable conditions on early Mars in its first 600 My?" During this period, it seems likely that 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 all favor the formation of early life. Even if life developed elsewhere (on Earth, Venus, or on other solar systems) and was transported to Mars, the surface conditions were likely very hospitable for that introduced life to multiply and evolve.

  10. Early Clinical Implications of Microalbuminuria in Patients with Acute Ischaemic Stroke

    PubMed Central

    Pais, Christopher C.

    2016-01-01

    Introduction Cardiovascular and cerebrovascular diseases are leading causes of morbidity and mortality worldwide. Stroke accounts for the second leading cause of death, about 11.13% of total deaths worldwide. Microalbuminuria is known to be associated with increased risk of mortality in ischaemic stroke patients. But there have been no studies to assess whether microalbuminuria affects the early clinical outcome of patients with acute ischaemic stroke. Aim This study aims to investigate whether microalbuminuria affects the early clinical outcome of patients with acute ischaemic stroke. Materials and Methods This is a prospective study of patients with ischaemic stroke (who presented within 24 hours of symptom onset) who were consecutively admitted in three tertiary care centres during the time period from November 2013 to June 2015. Early clinical outcomes in patients were assessed by investigating the presence of Early Neurological Deterioration (END) using the National Institute of Health Stroke Scale. Urine albumin creatinine ratio was divided into two categories – Normal (less than 30mg/g of creatinine) or Urine Microalbuminuria (30-300 mg/g of creatinine). Results Total 42 out of 70 patients (60%) were found to have microalbuminuria. In multivariate logistic regression analysis, microalbuminuria was found to be independently associated with END in patients with acute ischaemic stroke (p=0.044). Conclusion In the early periods following acute ischaemic stroke, patients with microalbuminuria have worse clinical outcome. PMID:27790489

  11. Subsets of a Large Cognitive Battery Better Power Clinical Trials on Early Stage Alzheimer Disease

    PubMed Central

    Xiong, Chengjie; Weng, Hua; Bennett, David A.; Boyle, Patricia A.; Shah, Raj C.; Fague, Scot; Hall, Charles B.; Lipton, Richard B.; Morris, John C.

    2014-01-01

    Background/Aims Cognitive batteries routinely used by the Alzheimer disease (AD) research community may contain items uninformative for tracking disease progression to power clinical trials on early stage AD. We aim to identify subsets of the most informative items from an existing cognitive battery for better powering clinical trials on early AD. Methods Longitudinal change in item scores from the battery was associated with the onset of Mild Cognitive Impairment (MCI) in 1513 elderly individuals. Items whose longitudinal changes were correlated with the onset of MCI were selected as informative for tracking the early cognitive progression. Results 226 items in the battery were annually assessed over a follow-up of up to 13 years. Changes of item scores over time from 187 items were significantly correlated with the onset of MCI. For clinical trials on preclinical AD and on MCI, informative items permit smaller or similar sample sizes as compared to the entire battery, whereas uninformative items require much larger sample sizes. Conclusions Longitudinal changes in item scores from about 17% of items in the cognitive battery are uninformative for tracking early disease progression. Clinical trials on early AD can be better powered using informative items rather than the entire battery. PMID:25376544

  12. Type II diabetes of early onset: a distinct clinical and genetic syndrome?

    PubMed Central

    O'Rahilly, S; Spivey, R S; Holman, R R; Nugent, Z; Clark, A; Turner, R C

    1987-01-01

    The inheritance of non-insulin-dependent (type II) diabetes was studied by a continuous infusion of glucose test in all available first degree relatives of 48 diabetic probands of various ages and with differing severity of disease. In an initial study of 38 type II diabetic subjects and their first degree relatives six islet cell antibody negative patients with early onset disease (aged 25-40 at diagnosis) were found to have a particularly high familial prevalence of diabetes or glucose intolerance. Nine of 10 parents available for study either had type II diabetes or were glucose intolerant. A high prevalence of diabetes or glucose intolerance was also found in their siblings (11/16;69%). In a second study of the families of a further 10 young diabetic probands (presenting age 25-40) whose islet cell antibody state was unknown a similar high prevalence of diabetes or glucose intolerance was found among parents of the five islet cell antibody negative probands (8/9; 89%) but not among parents of the five islet cell antibody positive probands (3/8;38%). Islet cell antibody negative diabetics with early onset type II disease may have inherited a diabetogenic gene or genes from both parents. They commonly need insulin to maintain adequate glycaemic control and may develop severe diabetic complications. Early onset type II diabetes may represent a syndrome in which characteristic pedigrees, clinical severity, and absence of islet autoimmunity make it distinct from either type I diabetes, maturity onset diabetes of the young, or late onset type II diabetes. PMID:3107658

  13. Comparison of clinical evaluation and neurosensory testing in the early diagnosis of superimposed entrapment neuropathy in diabetic patients.

    PubMed

    Siemionow, Maria; Zielinski, Maciej; Sari, Alper

    2006-07-01

    Diabetic patients are more susceptible to the development of entrapment neuropathy than nondiabetics. Since these patients suffer from a slowly progressing diabetic polyneuropathy, standard neurosensory and motor tests of nerve function are not sufficient in the diagnosis of superimposed nerve compression. This is most evident in the early stages of compression when quantitative diagnosis is important for making decisions on surgical decompression. We evaluated the validity of computer-assisted pressure-specified sensory device (PSSD) testing in the early detection of superimposed entrapment in diabetic neuropathy in comparison with standard clinical tests. Twenty-five diabetic patients with complaints of peripheral nerve dysfunction were evaluated by clinical tests and PSSD. Out of those, nerve entrapment was detected in 15 patients (60%) (9 in late and 6 in early stage) by neurosensory PSSD testing. Standard clinical tests were confirmative in 33.3% of these cases (44% of late and 16.7% of early stage). Out of 144 evaluated nerves, 50 were diagnosed with entrapment (24 in late and 26 in early stage) using PSSD. Clinically, diagnosis was confirmed in 16% of entrapped nerves (20.8% of late and 11.5% of early stage). Average diabetes duration in patients with entrapment diagnosed using PSSD was significantly shorter than for those diagnosed clinically (4.14 +/- 2.04 vs. 7.2 +/- 1.3, respectively; P = 0.005). Among evaluated factors, mean age and diabetes duration were found to be significantly shorter in patients with entrapment than in those with advanced diffused changes (54.47 +/- 13.07 vs. 67.10 +/- 14.2; P = 0.019 and 5.33 +/- 3.74 vs.14.22 +/- 8.17; P = 0.006; respectively). Our results revealed higher sensitivity of PSSD in comparison with standard clinical tests in the detection of early-stage entrapment in patients with diabetes. To assess accuracy of PSSD in the proper patients' qualification for surgery, further prospective, postoperative studies are

  14. Intraoperative radiation therapy in malignant glioma: early clinical results.

    PubMed

    Ortiz de Urbina, D; Santos, M; Garcia-Berrocal, I; Bustos, J C; Samblas, J; Gutierrez-Diaz, J A; Delgado, J M; Donckaster, G; Calvo, F A

    1995-08-01

    Intraoperative radiation therapy (IORT) with high energy electron beams is a treatment modality that has been included in multimodal programs in oncology to improve local tumor control. From August 1991 to December 1993, 17 patients with primary (8) or recurrent (9) high grade malignant gliomas, anaplastic astrocytoma (4), anaplastic oligodendroglioma (6) and glioblastoma multiforme (7), underwent surgical resection and a single dose of 10-20 Gy intraoperative radiation therapy was delivered in tumor bed. Fourteen patients received either pre-operative (8) or post-operative (6) external beam radiation therapy. Primary gliomas: 18-months actuarial survival rate has been 56% (range: 1-21+ months) and the median survival time has not yet been achieved. Four patients developed tumor progression (median time to tumor progression: 9 months). Recurrent gliomas: 18-months actuarial survival rate and median survival time has been 47% and 13 months (range: 6-32+ months) respectively. The median time to tumor progression was 11 months. No IORT related mortality has been observed. IORT is an attractive, tolerable and feasible treatment modality as antitumoral intensification procedure in high grade malignant gliomas.

  15. Trimodal detection of early childhood caries using laser light scanning and fluorescence spectroscopy: clinical prototype

    PubMed Central

    Kim, Amy S.; Ridge, Jeremy S.; Nelson, Leonard Y.; Berg, Joel H.; Seibel, Eric J.

    2013-01-01

    Abstract. There is currently a need for a safe and effective way to detect and diagnose early stages of childhood caries. A multimodal optical clinical prototype for diagnosing caries demineralization in vivo has been developed. The device can be used to quickly image and screen for any signs of demineralized enamel by obtaining high-resolution and high-contrast surface images using a 405-nm laser as the illumination source, as well as obtaining autofluorescence and bacterial fluorescence images. When a suspicious region of demineralization is located, the device also performs dual laser fluorescence spectroscopy using 405- and 532-nm laser excitation. An autofluorescence ratio of the two excitation lasers is computed and used to quantitatively diagnose enamel health. The device was tested on five patients in vivo as well as on 28 extracted teeth with clinically diagnosed carious lesions. The device was able to provide detailed images that highlighted the lesions identified by the clinicians. The autofluorescence spectroscopic ratios obtained from the extracted teeth successfully quantitatively discriminated between sound and demineralized enamel. PMID:23986369

  16. Behavioural and psychological symptoms of dementia in Down syndrome: Early indicators of clinical Alzheimer's disease?

    PubMed

    Dekker, Alain D; Strydom, André; Coppus, Antonia M W; Nizetic, Dean; Vermeiren, Yannick; Naudé, Petrus J W; Van Dam, Debby; Potier, Marie-Claude; Fortea, Juan; De Deyn, Peter P

    2015-12-01

    Behavioural and Psychological Symptoms of Dementia (BPSD) are a core symptom of dementia and are associated with suffering, earlier institutionalization and accelerated cognitive decline for patients and increased caregiver burden. Despite the extremely high risk for Down syndrome (DS) individuals to develop dementia due to Alzheimer's disease (AD), BPSD have not been comprehensively assessed in the DS population. Due to the great variety of DS cohorts, diagnostic methodologies, sub-optimal scales, covariates and outcome measures, it is questionable whether BPSD have always been accurately assessed. However, accurate recognition of BPSD may increase awareness and understanding of these behavioural aberrations, thus enabling adaptive caregiving and, importantly, allowing for therapeutic interventions. Particular BPSD can be observed (long) before the clinical dementia diagnosis and could therefore serve as early indicators of those at risk, and provide a new, non-invasive way to monitor, or at least give an indication of, the complex progression to dementia in DS. Therefore, this review summarizes and evaluates the rather limited knowledge on BPSD in DS and highlights its importance and potential for daily clinical practice.

  17. Multiple sclerosis presented as clinically isolated syndrome: the need for early diagnosis and treatment

    PubMed Central

    Pelidou, Sigliti-Henrietta; Giannopoulos, Sotirios; Tzavidi, Sotiria; Lagos, Georgios; Kyritsis, Athanassios P

    2008-01-01

    Objective To aid in the timely diagnosis of patients who present with clinically isolated syndrome (CIS). Patients and methods We studied 25 patients (18 women, 7 men), originally presented in our clinic with a CIS suggestive of multiple sclerosis (MS). All patients underwent the full investigation procedure including routine tests, serology, cerebrospinal fluid (CSF) examinations, evoked potentials (EPs), and magnetic resonance imaging (MRI) of brain and cervical spinal cord. Patients were imaged at baseline, and every three months thereafter up to a year. Results The CIS was consisted of optic neuritis in 12 cases, incomplete transverse myelitis (ITM) in 7 cases, Lhermitte sign in 2 cases, internuclear ophthalmoplegia (INO) in 2 cases, mild brainstem syndrome in 1 case, and tonic-clonic seizures in 1 case. Using the baseline and three-month scans 18/25 (72%) patients developed definite MS in one year of follow up while 7 (28%) had no further findings during this observation period. Immunomodulatory treatments were applied to all definite MS patients. Conclusion In light of new treatments available, MRIs at 3 month intervals are helpful to obtain the definite diagnosis of MS as early as possible. PMID:18827858

  18. [Effect of zuoguiwan on early embryonic development of mice].

    PubMed

    Feng, Q J; Feng, M L; Wang, Y L

    1996-11-01

    Effects of Zuoguiwan (ZGW, a prescription for reinforcing Kidney Yin) on early embryonic development were observed by using embryonic developmental retardation model of mice formed by alcohol. Drug was given in three ways: add ZGW into cultural medium directly (group A), add the serum of mice received ZGW (group B) and cultured the embryo taken from ZGW treated mice (group C). The result was compared with that treated with Bazhen decoction (BZD, a prescription for supplementing Qi and blood). Results showed that the in vitro developmental rate of embryo from 2-cell stage to blastula stage in group B and C, which approached to normal control group, was higher than that in untreated model obviously. While in BZW group, it was higher than in normal control group only in certain stage. However, adding ZGW directly into culture medium didn't reveal marked effect on early embryonic development.

  19. [Plasticity of neuroendocrine and immune systems in early development].

    PubMed

    Zakharova, L A

    2014-01-01

    This article provides an analysis of our own and published data on the reciprocal morphogenetic influence of the neiuroendocriie and imnimune systems on their formation and function in mammals. It is substantiated that, in early ontogeny, neurohormones regulate the growth and differentiation of various tissues in the body, including the lymphoid tissue. Thymicpeptides, in turn, affect the development of the hypothalamic-pitiitary-adrenal and gonadal-systems. Various adverse factors and changes in the physiological concentrations of hormones in the critical periods of development of these systems change their functions, and the plasticity of physiological systems in early ontogeny allows the body to adapt to new conditions. Disturbances in the interaction of the neuroendocrineand immune systems in the perinatal period induce apredisposition to various diseases in progeny.

  20. Studies Toward Birth and Early Mammalian Development in Space

    NASA Technical Reports Server (NTRS)

    Ronca, April E.; Dalton, Bonnie (Technical Monitor)

    2002-01-01

    Successful reproduction is the hallmark of a species' ability to adapt to its environment and must be realized to sustain life beyond Earth. Before taking this immense step, we need to understand the effects of altered gravity on critical phases of mammalian reproduction, viz., those events surrounding pregnancy, birth and the early development of offspring. No mammal has yet undergone birth in space. however studies spanning the gravity continuum from 0 to 2-g are revealing insights into how birth and early postnatal development will proceed in space. In this presentation, I will report the results of behavioral studies of rat mothers and offspring exposed from mid- to late pregnancy to either hypogravity (0-g) or hypergravity (1.5 or 2-g).

  1. Clinical features of HIV disease in developing countries.

    PubMed

    Grant, A

    2002-06-01

    HIV disease progresses from an asymptomatic period of variable duration, through mild symptoms, to severe disease characteristic of cellular immunodeficiency. The rate of progression from infection to severe disease is probably similar world-wide. However, individuals in developing countries have more symptomatic disease, in keeping with the high incidence of morbidity in the general population, and poor survival with advanced disease. The clinical manifestations of severe HIV-related immunosuppression vary with geographical region. Tuberculosis (TB) is the most important severe opportunistic disease in developing countries: the clinical presentation may differ from TB in the immunocompetent. Bacterial infections, particularly due to Streptococcus pneumoniae and non-typhoid Salmonella spp., are also important causes of morbidity and mortality. Fungal diseases such as Pneumocystis carinii pneumonia (PCP), cryptococcosis, histoplasmosis and penicilliosis vary in prevalence in different geographical regions. A high index of suspicion of HIV infection and knowledge of the local spectrum of HIV disease are important for early diagnosis and appropriate management of HIV-related disease.

  2. Developing an Early Childhood Teacher Workforce Development Strategy for Rural and Remote Communities

    ERIC Educational Resources Information Center

    Price, Anne; Jackson-Barrett, Elizabeth

    2009-01-01

    The North West Early Childhood and Primary Teacher Workforce Development Strategy offers students in the Pilbara and Kimberley the opportunity to enrol in a Western Australian University's fully accredited Bachelor of Education (Early Childhood and Primary) part time and externally--so they can continue to live and work in their communities. The…

  3. Early development and replacement of the stickleback dentition

    PubMed Central

    Ellis, Nicholas A.; Donde, Nikunj N.; Miller, Craig T.

    2017-01-01

    Teeth have long served as a model system to study basic questions about vertebrate organogenesis, morphogenesis, and evolution. In non-mammalian vertebrates, teeth typically regenerate throughout adult life. Fish have evolved a tremendous diversity in dental patterning in both their oral and pharyngeal dentitions, offering numerous opportunities to study how morphology develops, regenerates, and evolves in different lineages. Threespine stickleback fish (Gasterosteus aculeatus) have emerged as a new system to study how morphology evolves, and provide a particularly powerful system to study the development and evolution of dental morphology. Here we describe the oral and pharyngeal dentitions of stickleback fish, providing additional morphological, histological, and molecular evidence for homology of oral and pharyngeal teeth. Focusing on the ventral pharyngeal dentition in a dense developmental time course of lab-reared fish, we describe the temporal and spatial consensus sequence of early tooth formation. Early in development, this sequence is highly stereotypical and consists of seventeen primary teeth forming the early tooth field, followed by the first tooth replacement event. Comparing this detailed morphological and ontogenetic sequence to that described in other fish reveals that major changes to how dental morphology arises and regenerates have evolved across different fish lineages. PMID:27145214

  4. Early development and replacement of the stickleback dentition.

    PubMed

    Ellis, Nicholas A; Donde, Nikunj N; Miller, Craig T

    2016-08-01

    Teeth have long served as a model system to study basic questions about vertebrate organogenesis, morphogenesis, and evolution. In nonmammalian vertebrates, teeth typically regenerate throughout adult life. Fish have evolved a tremendous diversity in dental patterning in both their oral and pharyngeal dentitions, offering numerous opportunities to study how morphology develops, regenerates, and evolves in different lineages. Threespine stickleback fish (Gasterosteus aculeatus) have emerged as a new system to study how morphology evolves, and provide a particularly powerful system to study the development and evolution of dental morphology. Here, we describe the oral and pharyngeal dentitions of stickleback fish, providing additional morphological, histological, and molecular evidence for homology of oral and pharyngeal teeth. Focusing on the ventral pharyngeal dentition in a dense developmental time course of lab-reared fish, we describe the temporal and spatial consensus sequence of early tooth formation. Early in development, this sequence is highly stereotypical and consists of seventeen primary teeth forming the early tooth field, followed by the first tooth replacement event. Comparing this detailed morphological and ontogenetic sequence to that described in other fish reveals that major changes to how dental morphology arises and regenerates have evolved across different fish lineages. J. Morphol. 277:1072-1083, 2016. © 2016 Wiley Periodicals, Inc.

  5. Developing Self-Esteem in the Early Years

    ERIC Educational Resources Information Center

    Pawl, Jeree

    2012-01-01

    Jeree Pawl, PhD, former clinical professor, Department of Psychiatry, University of California at San Francisco and past director of the Infant-Parent Program located at San Francisco General Hospital responds to questions about how parents and caregivers can support the development of self-esteem in very young children. Contrary to the idea that…

  6. Early mathematics development and later achievement: Further evidence

    NASA Astrophysics Data System (ADS)

    Aubrey, Carol; Godfrey, Ray; Dahl, Sarah

    2006-05-01

    There is a growing international recognition of the importance of the early years of schooling as well as an interest being shown in the relationship of early education to later achievement. This article focuses on a cohort of English pupils who have been tracked through primary school during the first five years of the new National Numeracy Strategy. It reports a limited longitudinal study of young children's early mathematical development, initially within three testing cycles: at the mid-point and towards the end of their reception year (at five years-of-age) and again at the mid-point of Year 1 (at six years-ofage). These cycles were located within the broader context of progress through to the end of Key Stage 1 (at seven years) and Key Stage 2 (at eleven years) on the basis of national standardised assessment tests (SATs). Results showed that children who bring into school early mathematical knowledge do appear to be advantaged in terms of their mathematical progress through primary school. Numerical attainment increases in importance across the primary years and practical problem solving remains an important element of this. This finding is significant given the current emphasis on numerical calculation in the English curriculum. It is concluded that without active intervention, it is likely that children with little mathematical knowledge at the beginning of formal schooling will remain low achievers throughout their primary years and, probably, beyond.

  7. Regulatory pathways coordinating cell cycle progression in early Xenopus development.

    PubMed

    Gotoh, Tetsuya; Villa, Linda M; Capelluto, Daniel G S; Finkielstein, Carla V

    2011-01-01

    The African clawed frog, Xenopus laevis, is used extensively as a model organism for studying both cell development and cell cycle regulation. For over 20 years now, this model organism has contributed to answering fundamental questions concerning the mechanisms that underlie cell cycle transitions--the cellular components that synthesize, modify, repair, and degrade nucleic acids and proteins, the signaling pathways that allow cells to communicate, and the regulatory pathways that lead to selective expression of subsets of genes. In addition, the remarkable simplicity of the Xenopus early cell cycle allows for tractable manipulation and dissection of the basic components driving each transition. In this organism, early cell divisions are characterized by rapid cycles alternating phases of DNA synthesis and division. The post-blastula stages incorporate gap phases, lengthening progression, and allowing more time for DNA repair. Various cyclin/Cdk complexes are differentially expressed during the early cycles with orderly progression being driven by both the combined action of cyclin synthesis and degradation and the appropriate selection of specific substrates by their Cdk components. Like other multicellular organisms, chief developmental events in early Xenopus embryogenesis coincide with profound remodeling of the cell cycle, suggesting that cell proliferation and differentiation events are linked and coordinated through crosstalk mechanisms acting on signaling pathways involving the expression of cell cycle control genes.

  8. Professional behaviors, sense of belonging, and professional socialization of early career clinical laboratory scientists

    NASA Astrophysics Data System (ADS)

    Schill, Janna Marie

    Professional socialization is a process that individuals experience as members of a profession and consists of the knowledge, attitudes, and experiences that influence and shape their professional identity. The process of professional socialization has not been studied in the clinical laboratory science profession. Clinical laboratory science is an allied health profession that is faced by a workforce shortage that has been caused by a decrease in new graduates, decreased retention of qualified professionals, and increased retirements. Other allied health professions such as nursing, athletic training, and pharmacy have studied professional socialization as a way to identify factors that may influence the retention of early career professionals. This mixed method study, which quantitatively used Hall's Professionalism Scale (1968) in addition to qualitative focus group interviews, sought to identify the professional attitudes and behaviors, sense of belonging, and professional socialization of early career clinical laboratory scientists. Early career clinical laboratory scientists were divided into two groups based upon the amount of work experience they had; new clinical laboratory science graduates have had less than one year of work experience and novice clinical laboratory scientists had between one and three years of work experience. This study found that early career clinical laboratory scientists have established professional identities and view themselves as members of the clinical laboratory science field within four proposed stages of professional socialization consisting of pre-arrival, encounter, adaptation, and commitment. New CLS graduates and novice clinical laboratory scientists were found to be at different stages of the professional stage process. New CLS graduates, who had less than one year of work experience, were found to be in the encounter stage. Novice clinical laboratory scientists, with one to three years of work experience, were found to

  9. Development of tsunami early warning systems and future challenges

    NASA Astrophysics Data System (ADS)

    Wächter, J.; Babeyko, A.; Fleischer, J.; Häner, R.; Hammitzsch, M.; Kloth, A.; Lendholt, M.

    2012-06-01

    Fostered by and embedded in the general development of information and communications technology (ICT), the evolution of tsunami warning systems (TWS) shows a significant development from seismic-centred to multi-sensor system architectures using additional sensors (e.g. tide gauges and buoys) for the detection of tsunami waves in the ocean. Currently, the beginning implementation of regional tsunami warning infrastructures indicates a new phase in the development of TWS. A new generation of TWS should not only be able to realise multi-sensor monitoring for tsunami detection. Moreover, these systems have to be capable to form a collaborative communication infrastructure of distributed tsunami warning systems in order to implement regional, ocean-wide monitoring and warning strategies. In the context of the development of the German Indonesian Tsunami Early Warning System (GITEWS) and in the EU-funded FP6 project Distant Early Warning System (DEWS), a service platform for both sensor integration and warning dissemination has been newly developed and demonstrated. In particular, standards of the Open Geospatial Consortium (OGC) and the Organization for the Advancement of Structured Information Standards (OASIS) have been successfully incorporated. In the FP7 project Collaborative, Complex and Critical Decision-Support in Evolving Crises (TRIDEC), new developments in ICT (e.g. complex event processing (CEP) and event-driven architecture (EDA)) are used to extend the existing platform to realise a component-based technology framework for building distributed tsunami warning systems.

  10. Resistance, Reproduction, Both, or Neither: Exploring the Influence of Early Childhood Professional Development Specialists on the Field of Early Childhood

    ERIC Educational Resources Information Center

    Gomez, Rebecca E.

    2012-01-01

    This article details the findings from a qualitative study that explored the ways individuals who work with early childhood education (ECE) practitioners in professional development settings influenced those practitioners' understandings of early childhood policy and early childhood systems. Defined as individuals who work in the professional…

  11. Long-term prognosis of clinically early IgA nephropathy is not always favorable

    PubMed Central

    2014-01-01

    Background The long-term prognosis of clinically early IgA nephropathy (IgAN) patients remains to be clarified. We investigated the long-term outcomes of IgAN patients with an apparently benign presentation and evaluated prognostic factors for renal survival. Methods We included patients with biopsy-proven IgAN who had estimated glomerular filtration rates (eGFR) ≥60 mL/min/1.73 m2, normal blood pressure, and proteinuria <0.5 g/day at the time of biopsy. The primary outcome was progression to end-stage renal disease (ESRD). The secondary outcome was a 50% increase in serum creatinine level or an increase in proteinuria to >1 g/day. Results The analysis included 153 patients who met the inclusion criteria. At diagnosis, their median systolic blood pressure was 120 (110–130) mmHg, eGFR was 85.9 (74.9–100.1) mL/min/1.73 m2, and proteinuria was 0.25 (0.13–0.38) g/day. Of these, 4 patients died and 6 reached ESRD. The 30-year renal survival rate was 85.5%. Three patients had increased serum creatinine levels and 11 developed proteinuria. Remission was observed in 35 (22.9%) patients. A moderate or severe degree of interstitial fibrosis (adjusted odd ratio [OR] 5.93, 95% confidence interval [CI] 1.44–24.45, P = 0.014) and hypoalbuminemia (adjusted OR 6.18, 95% CI 1.20–31.79, P = 0.029) were independent predictors of the secondary outcome. Conclusions This study showed that the prognosis of early IgAN was not always favorable, even resulting in progression to ESRD in some cases. Hypoalbuminemia and interstitial fibrosis should also be considered important prognostic factors in clinically early IgAN patients. PMID:24946688

  12. The ESSENCE in child psychiatry: Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations.

    PubMed

    Gillberg, Christopher

    2010-01-01

    Co-existence of disorders--including attention-deficit/hyperactivity disorder, oppositional defiant disorder, tic disorder, developmental coordination disorder, and autism spectrum disorder--and sharing of symptoms across disorders (sometimes referred to as comorbidity) is the rule rather than the exception in child psychiatry and developmental medicine. The acronym ESSENCE refers to Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations. It is a term I have coined to refer to the reality of children (and their parents) presenting in clinical settings with impairing child symptoms before age 3 (-5) years in the fields of (a) general development, (b) communication and language, (c) social inter-relatedness, (d) motor coordination, (e) attention, (f) activity, (g) behaviour, (h) mood, and/or (i) sleep. Children with major difficulties in one or more (usually several) of these fields, will be referred to and seen by health visitors, nurses, social workers, education specialists, pediatricians, GPs, speech and language therapists, child neurologists, child psychiatrists, psychologists, neurophysiologists, dentists, clinical geneticists, occupational therapists and physiotherapists, but, usually they will be seen only by one of these specialists, when they would have needed the input of two or more of the experts referred to. Major problems in at least one ESSENCE domain before age 5 years often signals major problems in the same or overlapping domains years later. There is no time to wait; something needs to be done, and that something is unlikely to be just in the area of speech and language, just in the area of autism or just in special education.

  13. Proteomic profiling change during the early development of silicosis disease

    PubMed Central

    Miao, Rongming; Ding, Bangmei; Zhang, Yingyi; Xia, Qian; Li, Yong

    2016-01-01

    Background Silicosis is one of several severe occupational diseases for which effective diagnostic tools during early development are currently unavailable. In this study we focused on proteomic profiling during the early stages of silicosis to investigate the pathophysiology and identify the proteins involved. Methods Two-dimensional (2D) gel electrophoresis and MALDI-TOF-MS were used to assess the proteomic differences between healthy individuals (HI), dust-exposed workers without silicosis (DEW) and silicosis patients (SP). Proteins abundances that differed by a factor of two-fold or greater were subjected to more detailed analysis, and enzyme linked to immunosorbent assay (ELISA) was employed to correlate with protein expression data. Results Compared with HI, 42 proteins were more abundant and 8 were less abundant in DEW, and these were also differentially accumulated in SP. Closer inspection revealed that serine protease granzyme A, alpha-1-B-glycoprotein (A1BG) and the T4 surface glycoprotein precursor (TSGP) were among the up-regulated proteins in DEW and SP. Significant changes in serine proteases, glycoproteins and proto-oncogenes may be associated with the response to cytotoxicity and infectious pathogens by activation of T cells, positive regulation of extracellular matrix structural constituents and immune response, and fibroblast proliferation. Up-regulation of cytokines included TNFs, interferon beta precursor, interleukin 6, atypical chemokine receptor 2, TNFR13BV, and mutant IL-17F may be involved in the increased and persistent immune response and fibrosis that occurred during silicosis development. Conclusions Granzymes, glycoproteins, cytokines and immune factors were dramatically involved in the immune response, metabolism, signal regulation and fibrosis during the early development of silicosis. Proteomic profiling has expanded our understanding of the pathogenesis of silicosis, and identified a number of targets that may be potential

  14. The role of early auditory development in attachment and communication.

    PubMed

    Moon, Christine

    2011-12-01

    Auditory perception and learning take place during the third trimester of gestation. Fetuses and newborns who lack typical auditory experience can go on to develop typical socioemotional attachment and language, given a supportive environment. For hospitalized preterm infants in developmentally sensitive neonatal intensive care units, detrimental effects of deviant early auditory experience may be remediated by later experience, but much is unknown about the causes of language deficits of prematurity. Prenatal auditory stimulation programs that incorporate audio speakers against the maternal belly should be discouraged because of possible overstimulation effects on the developing auditory system and sleep/wake state organization.

  15. Development of an assisting detection system for early infarct diagnosis

    SciTech Connect

    Sim, K. S.; Nia, M. E.; Ee, C. S.

    2015-04-24

    In this paper, a detection assisting system for early infarct detection is developed. This new developed method is used to assist the medical practitioners to diagnose infarct from computed tomography images of brain. Using this assisting system, the infarct could be diagnosed at earlier stages. The non-contrast computed tomography (NCCT) brain images are the data set used for this system. Detection module extracts the pixel data from NCCT brain images, and produces the colourized version of images. The proposed method showed great potential in detecting infarct, and helps medical practitioners to make earlier and better diagnoses.

  16. Early child development and developmental delay in indigenous communities.

    PubMed

    Cappiello, Matthew M; Gahagan, Sheila

    2009-12-01

    Developmental delay is common and often responds to early intervention. As with other health outcomes, the prevalence of developmental delay may be socially determined. Children in many Indigenous communities experience increased risk for developmental delay. This article highlights special conditions in Indigenous communities related to child development. It addresses the challenges of screening and evaluation for developmental delay in the context of Indigenous cultures, and in settings where resources are often inadequate. It is clear that careful research on child development in Indigenous settings is urgently needed. Intervention strategies tied to cultural traditions could enhance interest, acceptability, and ultimately developmental outcomes in children at risk.

  17. Methodological choices for the clinical development of medical devices.

    PubMed

    Bernard, Alain; Vaneau, Michel; Fournel, Isabelle; Galmiche, Hubert; Nony, Patrice; Dubernard, Jean Michel

    2014-01-01

    Clinical evidence available for the assessment of medical devices (MDs) is frequently insufficient. New MDs should be subjected to high quality clinical studies to demonstrate their benefit to patients. The randomized controlled trial (RCT) is the study design reaching the highest level of evidence in order to demonstrate the efficacy of a new MD. However, the clinical context of some MDs makes it difficult to carry out a conventional RCT. The objectives of this review are to present problems related to conducting conventional RCTs and to identify other experimental designs, their limitations, and their applications. A systematic literature search was conducted for the period January 2000 to July 2012 by searching medical bibliographic databases. Problems related to conducting conventional RCTs of MDs were identified: timing the assessment, eligible population and recruitment, acceptability, blinding, choice of comparator group, and learning curve. Other types of experimental designs have been described. Zelen's design trials and randomized consent design trials facilitate the recruitment of patients, but can cause ethical problems to arise. Expertise-based RCTs involve randomization to a team that specializes in a given intervention. Sometimes, the feasibility of an expertise-based randomized trial may be greater than that of a conventional trial. Cross-over trials reduce the number of patients, but are not applicable when a learning curve is required. Sequential trials have the advantage of allowing a trial to be stopped early depending on the results of first inclusions, but they require an independent committee. Bayesian methods combine existing information with information from the ongoing trial. These methods are particularly useful in situations where the number of subjects is small. The disadvantage is the risk of including erroneous prior information. Other types of experimental designs exist when conventional trials cannot always be applied to the

  18. Gene Expression Changes and Early Events in Cotton Fibre Development

    PubMed Central

    Lee, Jinsuk J.; Woodward, Andrew W.; Chen, Z. Jeffrey

    2007-01-01

    Background Cotton is the dominant source of natural textile fibre and a significant oil crop. Cotton fibres, produced by certain species in the genus Gossypium, are seed trichomes derived from individual cells of the epidermal layer of the seed coat. Cotton fibre development is delineated into four distinct and overlapping developmental stages: fibre initiation, elongation, secondary wall biosynthesis and maturation. Scope Recent advances in gene expression studies are beginning to provide new insights into a better understanding of early events in cotton fibre development. Fibre cell development is a complex process involving many pathways, including various signal transduction and transcriptional regulation components. Several analyses using expressed sequence tags and microarray have identified transcripts that preferentially accumulate during fibre development. These studies, as well as complementation and overexpression experiments using cotton genes in arabidopsis and tobacco, indicate some similar molecular events between trichome development from the leaf epidermis and fibre development from the ovule epidermis. Specifically, MYB transcription factors regulate leaf trichome development in arabidopsis and may regulate seed trichome development in cotton. In addition, transcript profiling and ovule culture experiments both indicate that several phytohormones and other signalling pathways mediate cotton fibre development. Auxin and gibberellins promote early stages of fibre initiation; ethylene- and brassinosteroid-related genes are up-regulated during the fibre elongation phase; and genes associated with calmodulin and calmodulin-binding proteins are up-regulated in fibre initials. Additional genomic data, mutant and functional analyses, and genome mapping studies promise to reveal the critical factors mediating cotton fibre cell development. PMID:17905721

  19. Utilizing Existing Clinical and Population Biospecimen Resources for Discovery or Validation of Markers for Early Cancer Detection

    Cancer.gov

    Utilizing Existing Clinical and Population Biospecimen Resources for Discovery or Validation of Markers for Early Cancer Detection, a 2013 workshop sponsored by the Epidemiology and Genomics Research Program.

  20. Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS): Demographic and Clinical Characteristics

    ERIC Educational Resources Information Center

    Frazier, Jean A.; McClellan, Jon; Findling, Robert L.; Vitiello, Benedetto; Anderson, Robert; Zablotsky, Benjamin; Williams, Emily; McNamara, Nora K.; Jackson, Joseph A.; Ritz, Louise; Hlastala, Stefanie A.; Pierson, Leslie; Varley, Jennifer A.; Puglia, Madeline; Maloney, Ann E.; Ambler, Denisse; Hunt-Harrison, Tyehimba; Hamer, Robert M.; Noyes, Nancy; Lieberman, Jeffrey A.; Sikich, Linmarie

    2007-01-01

    Objective: We examined baseline demographic and clinical profiles of youths enrolled from 2001 to 2006 in the publicly funded multicenter, randomized controlled trial Treatment of Early-Onset Schizophrenia Spectrum Disorders. Method: Youths (8-19 years) with schizophrenia (SZ) and schizoaffective disorder were recruited at four academic sites.…

  1. Preparation of Clinical Nurse Specialists for Family-Centered Early Intervention.

    ERIC Educational Resources Information Center

    Brandt, Patricia A.; Magyary, Diane L.

    1989-01-01

    Nursing specialists are prepared at the master's level to function as members of interdisciplinary and family-centered early intervention teams for disabled children. A specialty program of study emphasizes advanced and specialized clinical practice; education of clients, families, staff, and professionals; consultation; research use; evaluation…

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

    ERIC Educational Resources Information Center

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

    2005-01-01

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

  3. Recognizing Business Issues in Professional Psychology for Clinical PsyD Trainees and Early Career Psychologists

    ERIC Educational Resources Information Center

    Maciel, Michelle

    2012-01-01

    The largest number of licensed psychologists are centralized in California. More PsyD than PhD degrees in clinical psychology are now awarded, and California houses 16 of the 59 APA-accredited programs. Post-millennia Early Career Psychologists (ECPs) typically accumulate over $120,000 in education debt, and may be concerned with the cost-benefit…

  4. Incidence of and risk factors for cognitive impairment in an early Parkinson disease clinical trial cohort

    PubMed Central

    Uc, E Y.; McDermott, M P.; Marder, K S.; Anderson, S W.; Litvan, I; Como, P G.; Auinger, P; Chou, K L.; Growdon, J C.

    2009-01-01

    Objective: To investigate the incidence of and risk factors for cognitive impairment in a large, well-defined clinical trial cohort of patients with early Parkinson disease (PD). Methods: The Mini-Mental State Examination (MMSE) was administered periodically over a median follow-up period of 6.5 years to participants in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism trial and its extension studies. Cognitive impairment was defined as scoring 2 standard deviations below age- and education-adjusted MMSE norms. Results: Cumulative incidence of cognitive impairment in the 740 participants with clinically confirmed PD (baseline age 61.0 ± 9.6 years, Hoehn-Yahr stage 1–2.5) was 2.4% (95% confidence interval: 1.2%–3.5%) at 2 years and 5.8% (3.7%–7.7%) at 5 years. Subjects who developed cognitive impairment (n = 46) showed significant progressive decline on neuropsychological tests measuring verbal learning and memory, visuospatial working memory, visuomotor speed, and attention, while the performance of the nonimpaired subjects (n = 694) stayed stable. Cognitive impairment was associated with older age, hallucinations, male gender, increased symmetry of parkinsonism, increased severity of motor impairment (except for tremor), speech and swallowing impairments, dexterity loss, and presence of gastroenterologic/urologic disorders at baseline. Conclusions: The relatively low incidence of cognitive impairment in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism study may reflect recruitment bias inherent to clinical trial volunteers (e.g., younger age) or limitations of the Mini-Mental State Examination–based criterion. Besides confirming known risk factors for cognitive impairment, we identified potentially novel predictors such as bulbar dysfunction and gastroenterologic/urologic disorders (suggestive of autonomic dysfunction) early in the course of the disease. GLOSSARY CI = confidence interval; COWA = Controlled Word Association

  5. Assessing Clinical Reasoning (ASCLIRE): Instrument Development and Validation

    ERIC Educational Resources Information Center

    Kunina-Habenicht, Olga; Hautz, Wolf E.; Knigge, Michel; Spies, Claudia; Ahlers, Olaf

    2015-01-01

    Clinical reasoning is an essential competency in medical education. This study aimed at developing and validating a test to assess diagnostic accuracy, collected information, and diagnostic decision time in clinical reasoning. A norm-referenced computer-based test for the assessment of clinical reasoning (ASCLIRE) was developed, integrating the…

  6. Understanding early-stage dune development: morphodynamics of aeolian protodunes

    NASA Astrophysics Data System (ADS)

    Baddock, Matthew; Wiggs, Giles; Nield, Joanna

    2016-04-01

    For such a fundamental aspect of bedform development, the initiation and early-stage growth of sand dunes remain poorly understood. Protodunes are bedforms within the continuum of early-stage depositional aeolian features that exist between flat sand patches and small dunes. As transitory bedforms with the potential to develop into dunes, the detailed study of protodune morphodynamics can provide significant insights into nascent dune development. As part of a multi-annual study investigating bedform change through repeat morphological surveys of bedforms with differing maturity, measurements of near-surface airflow and sand transport were conducted over a protodune in a small Namibian barchan dune field. The protodune was approximately 85 m in length and 1 m high, and was without a slipface. Data show that over the course of a week, patterns of airflow and transport flux variation were linked with accretion at the crest, and erosion of the leeside edge showing an increase in protodune height, and providing evidence of the dune's vertical development. Surveys reveal the longer term evolution of the protodune, in the context of changes exhibited by nearby, fully developed barchan dunes, and long term monitoring of wind regime at the site.

  7. Ca2+ signalling and early embryonic patterning during zebrafish development.

    PubMed

    Webb, Sarah E; Miller, Andrew L

    2007-09-01

    1. It has been proposed that Ca2+ signalling, in the form of pulses, waves and steady gradients, may play a crucial role in key pattern-forming events during early vertebrate development. 2. With reference to the embryo of the zebrafish (Danio rerio), herein we review the Ca2+ transients reported from the cleavage to segmentation periods. This time-window includes most of the major pattern-forming events of early development, which transform a single-cell zygote into a complex multicellular embryo with established primary germ layers and body axes. 3. Data are presented to support our proposal that intracellular Ca2+ waves are an essential feature of embryonic cytokinesis and that propagating intercellular Ca2+ waves (both long and short range) may play a crucial role in: (i) the establishment of the embryonic periderm and the coordination of cell movements during epiboly, convergence and extension; (ii) the establishment of the basic embryonic axes and germ layers; and (iii) definition of the morphological boundaries of specific tissue domains and embryonic structures, including future organ anlagen. 4. The potential downstream targets of these Ca2+ transients are also discussed, as well as how they may integrate with other pattern-forming signalling pathways known to modulate early developmental events.

  8. TRPM Channels and Magnesium in Early Embryonic Development

    PubMed Central

    Komiya, Yuko; Runnels, Loren W.

    2015-01-01

    Magnesium (Mg2+) is the second most abundant cellular cation and is essential for all stages of life, from the early embryo to adult. Mg2+ deficiency causes or contributes to many human diseases, including migraine headaches, Parkinson’s disease, Alzheimer’s disease, hypotension, type 2 diabetes mellitus and cardiac arrhythmias. Although the concentration of Mg2+ in the extracellular environment can vary significantly, the total intracellular Mg2+ concentration is actively maintained within a relatively narrow range (14 – 20 mM) via tight, yet poorly understood, regulation of intracellular Mg2+ by Mg2+ transporters and Mg2+-permeant ion channels. Recent studies have continued to add to the growing number of Mg2+ transporters and ion channels involved in Mg2+ homeostasis, including TRPM6 and TRPM7, members of the transient receptor potential (TRP) ion channel family. Mutations in TRPM6, including amino acid substitutions that prevent its heterooligomerization with TRPM7, occur in the rare autosomal-recessive disease hypomagnesemia with secondary hypocalcemia (HSH). However, is the fact that genetic ablation of either gene in mice results in early embryonic lethality that has raised the question of whether these channels’ capacity to mediate Mg2+ influx plays an important role in embryonic development. Here we review what is known of the function of Mg2+ in early development and summarize recent findings regarding the function of the TRPM6 and TRPM7 ion channels during embryogenesis. PMID:26679946

  9. An Embodied Account of Early Executive-Function Development

    PubMed Central

    Gottwald, Janna M.; Achermann, Sheila; Marciszko, Carin; Lindskog, Marcus; Gredebäck, Gustaf

    2016-01-01

    The importance of executive functioning for later life outcomes, along with its potential to be positively affected by intervention programs, motivates the need to find early markers of executive functioning. In this study, 18-month-olds performed three executive-function tasks—involving simple inhibition, working memory, and more complex inhibition—and a motion-capture task assessing prospective motor control during reaching. We demonstrated that prospective motor control, as measured by the peak velocity of the first movement unit, is related to infants’ performance on simple-inhibition and working memory tasks. The current study provides evidence that motor control and executive functioning are intertwined early in life, which suggests an embodied perspective on executive-functioning development. We argue that executive functions and prospective motor control develop from a common source and a single motive: to control action. This is the first demonstration that low-level movement planning is related to higher-order executive control early in life. PMID:27765900

  10. Hormonal regulation of early follicle development in the rat ovary.

    PubMed

    Hsueh, A J; McGee, E A; Hayashi, M; Hsu, S Y

    2000-05-25

    Although earlier studies focused on the hormonal regulation of antral and preovulatory follicles, recent studies indicate the importance of the hormonal control mechanism for preantral follicles. The endocrine hormone FSH is not only a survival factor for early antral follicles but also a potent growth and differentiation factor for preantral follicles. In addition, KGF secreted by theca cells and c-kit ligand secreted by granulosa cells play paracrine roles in the regulation of preantral follicle growth and development. Furthermore oocyte-derived GDF-9 promotes the growth and differentiation of early follicles by acting on somatic cells in the follicle. It is likely that the genetic makeup of an oocyte could determine the secretion of oocyte hormones which would, in turn, regulate the growth and differentiation of the surrounding somatic cells of that follicle. A better understanding of the hormonal mechanisms underlying early follicle development could provide a refined culture system for the in vitro maturation of fertilizable oocytes and future design of fertility and contraceptive agents.

  11. Gestural development and its relation to a child's early vocabulary.

    PubMed

    Kraljević, Jelena Kuvač; Cepanec, Maja; Simleša, Sanja

    2014-05-01

    Gesture and language are tightly connected during the development of a child's communication skills. Gestures mostly precede and define the way of language development; even opposite direction has been found. Few recent studies have focused on the relationship between specific gestures and specific word categories, emphasising that the onset of one gesture type predicts the onset of certain word categories or of the earliest word combinations. The aim of this study was to analyse predicative roles of different gesture types on the onset of first word categories in a child's early expressive vocabulary. Our data show that different types of gestures predict different types of word production. Object gestures predict open-class words from the age of 13 months, and gestural routines predict closed-class words and social terms from 8 months. Receptive vocabulary has a strong mediating role for all linguistically defined categories (open- and closed-class words) but not for social terms, which are the largest word category in a child's early expressive vocabulary. Accordingly, main contribution of this study is to define the impact of different gesture types on early expressive vocabulary and to determine the role of receptive vocabulary in gesture-expressive vocabulary relation in the Croatian language.

  12. Developing urinary metabolomic signatures as early bladder cancer diagnostic markers.

    PubMed

    Shen, Chong; Sun, Zeyu; Chen, Deying; Su, Xiaoling; Jiang, Jing; Li, Gonghui; Lin, Biaoyang; Yan, Jiajun

    2015-01-01

    Early detection is vital to improve the overall survival rate of bladder cancer (BCa) patients, yet there is a lack of a reliable urine-based assay for early detection of BCa. Urine metabolites represented a potential rich source of biomarkers for BCa. This study aimed to develop a metabolomics approach for high coverage discovery and identification of metabolites in urine samples. Urine samples from 23 early stage BCa patients and 21 healthy volunteers with minimum sample preparations were analyzed by a short 30 min UPLC-HRMS method. We detected and quantified over 9000 unique UPLC-HRMS features, which is more than four times than about 2000 features detected in previous urine metabolomic studies. Furthermore, multivariate OPLS-DA classification models were established to differentiate urine samples from bladder cancer cohort and normal health cohort. We identified three BCa-upregulated metabolites: nicotinuric acid, trehalose, AspAspGlyTrp, and three BCa-downregulated metabolites: inosinic acid, ureidosuccinic acid, GlyCysAlaLys. Finally, analysis of six post-surgery BCa urine samples showed that these BCa-metabolomic features reverted to normal state after tumor removal, suggesting that they reflected metabolomic features associated with BCa. ROC analyses using two linear regression models to combine the identified markers showed a high diagnostic performance for detecting BCa with AUC (area under the ROC curve) values of 0.919 to 0.934. In summary, we developed a high coverage metabolomic approach that has potential for biomarker discovery in cancers.

  13. Clinical mutation assay of tumors: new developments.

    PubMed

    Starostik, Petr

    2017-01-01

    Mutation detection in tumors started with classical cytogenetics as the method of choice more than 50 years ago. Karyotyping proved to be sensitive enough to detect deletions or duplications of large chromosome segments, and translocations. Over time, new techniques were developed to detect mutations that are much smaller in scope. The availability of Sanger sequencing and the invention of the PCR improved the discriminatory power of mutation detection to just one base change in the genomic DNA sequence. Techniques derived from PCR (allele-specific PCR, qPCR) and improved or modified sequencing methods (capillary electrophoresis, pyrosequencing) considerably increased the efficiency and sample throughput of mutation detection assays. With the advent of massive parallel sequencing [also called next-generation sequencing (NGS)] in the past decade, a major shift to even higher sample throughput and a significant decrease in cost per sequenced base occurred. The application of the new technology provided a whole slew of novel biomarkers and potential therapy targets to improve diagnosis and treatment. It even led to changes in cancer classification as new information on the mutation profile of tumors became available that characterizes some disease entities better than morphology. NGS, which usually interrogates multiple genes at once and is a prime example of a multianalyte assay, started to replace older single analyte assays focused on analysis of one target, one gene. However, the transition to these extremely complex NGS-based assays is associated with multiple challenges. There are issues with adequate tissue source of nucleic acids, sequencing library preparation, bioinformatics, government regulations and oversight, reimbursement, and electronic medical records that need to be resolved to successfully implement the new technology in a clinical laboratory.

  14. The Psl economy in early P. aeruginosa biofilm development

    NASA Astrophysics Data System (ADS)

    Zhao, Kun; Tseng, Boo Shan; Jin, Fan; Gibiansky, Max; Harrison, Joe; Parsek, Matthew; Wong, Gerard

    2012-02-01

    Psl from P. aeruginosa (PAO1) is a mannose- and galactose-rich exopolysaccharide (EPS). It has been shown that Psl plays an important role in bacterial surface adhesion. Here, we examine role of Psl in controlling motility and microcolony formation during early biofilm development, by translating video microscopy movies into searchable databases of bacterial trajectories. We use a massively-parallel cell tracking algorithm to extract the full motility history of every cell in a large community. We find that at early stages of growth, P. aeruginosa motility is guided by Psl and self-organize in a manner analogous to a capitalist economic system, resulting in a power law bacterial distribution where a small number of bacteria are extremely ``rich'' in communally produced Psl. By comparing overproducers and underproducers of Psl, we find that local Psl levels determine post-division cell fates: High local Psl levels drive the formation of sessile microcolonies that grow exponentially.

  15. Early Clinical Experiences for Second-Year Student Pharmacists at an Academic Medical Center

    PubMed Central

    Amerine, Lindsey B.; Chen, Sheh-Li; Luter, David N.; Arnall, Justin; Smith, Shayna; Roth, Mary T.; Rodgers, Philip T.; Williams, Dennis M.; Pinelli, Nicole R.

    2015-01-01

    Objective. To examine student outcomes associated with the Student Medication and Reconciliation Team (SMART) program, which was designed to provide second-year student pharmacists at the University of North Carolina (UNC) Eshelman School of Pharmacy direct patient care experience at UNC Medical Center. Design. Twenty-two second-year student pharmacists were randomly selected from volunteers, given program training, and scheduled for three 5-hour evening shifts in 2013-2014. Pre/post surveys and reflection statements were collected from 19 students. Data were analyzed with a mixed methods approach. Assessment. Survey results revealed an increase in student self-efficacy (p<0.05) and positive perceptions of SMART. Qualitative findings suggest the program provided opportunities for students to develop strategies for practice, promoted an appreciation for the various roles pharmacists play in health care, and fostered an appreciation for the complexity of real-world practice. Conclusion. Early clinical experiences can enhance student learning and development while fostering an appreciation for pharmacy practice. PMID:26839428

  16. Regulation of bone morphogenetic proteins in early embryonic development

    NASA Astrophysics Data System (ADS)

    Yamamoto, Yukiyo; Oelgeschläger, Michael

    2004-11-01

    Bone morphogenetic proteins (BMPs), a large subgroup of the TGF-β family of secreted growth factors, control fundamental events in early embryonic development, organogenesis and adult tissue homeostasis. The plethora of dose-dependent cellular processes regulated by BMP signalling demand a tight regulation of BMP activity. Over the last decade, a number of proteins have been identified that bind BMPs in the extracellular space and regulate the interaction of BMPs with their cognate receptors, including the secreted BMP antagonist Chordin. In the early vertebrate embryo, the localized secretion of BMP antagonists from the dorsal blastopore lip establishes a functional BMP signalling gradient that is required for the determination of the dorsoventral or back to belly body axis. In particular, inhibition of BMP activity is essential for the formation of neural tissue in the development of vertebrate and invertebrate embryos. Here we review recent studies that have provided new insight into the regulation of BMP signalling in the extracellular space. In particular, we discuss the recently identified Twisted gastrulation protein that modulates, in concert with metalloproteinases of the Tolloid family, the interaction of Chordin with BMP and a family of proteins that share structural similarities with Chordin in the respective BMP binding domains. In addition, genetic and functional studies in zebrafish and frog provide compelling evidence that the secreted protein Sizzled functionally interacts with the Chd BMP pathway, despite being expressed ventrally in the early gastrula-stage embryo. These intriguing discoveries may have important implications, not only for our current concept of early embryonic patterning, but also for the regulation of BMP activity at later developmental stages and tissue homeostasis in the adult.

  17. Diffusion tensor imaging for understanding brain development in early life.

    PubMed

    Qiu, Anqi; Mori, Susumu; Miller, Michael I

    2015-01-03

    The human brain rapidly develops during the final weeks of gestation and in the first two years following birth. Diffusion tensor imaging (DTI) is a unique in vivo imaging technique that allows three-dimensional visualization of the white matter anatomy in the brain. It has been considered to be a valuable tool for studying brain development in early life. In this review, we first introduce the DTI technique. We then review DTI findings on white matter development at the fetal stage and in infancy as well as DTI applications for understanding neurocognitive development and brain abnormalities in preterm infants. Finally, we discuss limitations of DTI and potential valuable imaging techniques for studying white matter myelination.

  18. On the evolution of early development in the Nematoda.

    PubMed Central

    Goldstein, B

    2001-01-01

    The phylum Nematoda serves as an excellent model system for exploring how development evolves, using a comparative approach to developmental genetics. More than 100 laboratories are studying developmental mechanisms in the nematode Caenorhabditis elegans, and many of the methods that have been developed for C. elegans can be applied to other nematodes. This review summarizes what is known so far about steps in early development that have evolved in the nematodes, and proposes potential experiments that could make use of these data to further our understanding of how development evolves. The promise of such a comparative approach to developmental genetics is to fill a wide gap in our understanding of evolution--a gap spanning from mutations in developmental genes through to their phenotypic results, on which natural selection may act. PMID:11604120

  19. Illinois Early Learning Project Tip Sheets: Physical Development and Health.

    ERIC Educational Resources Information Center

    2003

    The Illinois Early Learning Project (IEL) is funded by the Illinois State Board of Education to provide information resources on early learning and training related to implementing the Illinois Early Learning Standards for parents and for early childhood personnel in all settings. The IEL tip sheets offer suggestions to parents and early childhood…

  20. [Historic Development of Clinical Biology Laboratories in Luxembourg].

    PubMed

    Wennig R; Humbel R-L

    2014-01-01

    After a short overview on the development of diagnostic tools in clinical biology at an international level from Antiquity towards today, a history of the clinical biology including public and private institutions in Luxembourg will be outlined.

  1. The Early Use of Blinding in Therapeutic Clinical Research of Neurological Disorders

    PubMed Central

    Jensen, Matthew B.; Janik, Erika L.; Waclawik, Andrew J.

    2016-01-01

    We sought to identify early uses of blinding in therapeutic clinical trials of neurological disorders by multiple search methods. A 1784 report by Benjamin Franklin and others described the evaluation of the use of Mesmerism to treat neurological and other syndromes including headache and epilepsy, using blindfolds and screens. This report demonstrated the usefulness of blinding to reduce bias in clinical research, yet despite this early discovery, blinding was not widely accepted or routinely used until the 20th century. Blinded clinical trials began to be used for various neurological syndromes in the 1950s, sporadically at first and then increasing in frequency in subsequent years. The reason for this delay is unclear, but we propose several hypotheses. PMID:27617324

  2. Low level lead exposure in the prenatal and early preschool periods: early preschool development.

    PubMed

    Ernhart, C B; Morrow-Tlucak, M; Marler, M R; Wolf, A W

    1987-01-01

    The hypothesis that low level lead exposure in the fetal and early preschool years is related to neuropsychological deficit was examined in a prospective study of child development. We also tested the hypothesis of reverse causality, i.e., that lead level is a function of prior developmental status. Fetal lead exposure was measured in maternal and cord blood while preschool lead level was measured in venous blood samples at ages six months, two years and three years. These blood lead measures (PbB) were related to concurrent and ensuing scores on developmental measures at six months, one year, two years, and three years. With statistical control of covariate measures (age, sex, race, birth weight, birth order, gestational exposure to other toxic substances, maternal intelligence, and several indicators of the quality of the caretaking environment) as well as potentially confounding risk factors (gestational exposure to alcohol and other toxic substances), most statistically significant associations of PbB with concurrent and later development were completely attenuated. Effects of lead exposure, significant or not, were not consistent in direction. In reverse-causality analyses, PbB was not related significantly to prior measures of developmental retardation or acceleration. It was concluded that the relationship of lead level and measures of development in these early years was primarily a function of the dependence of each on the quality of the caretaking environment.

  3. Early somatosensory processing in individuals at risk for developing psychoses

    PubMed Central

    Hagenmuller, Florence; Heekeren, Karsten; Theodoridou, Anastasia; Walitza, Susanne; Haker, Helene; Rössler, Wulf; Kawohl, Wolfram

    2014-01-01

    Human cortical somatosensory evoked potentials (SEPs) allow an accurate investigation of thalamocortical and early cortical processing. SEPs reveal a burst of superimposed early (N20) high-frequency oscillations around 600 Hz. Previous studies reported alterations of SEPs in patients with schizophrenia. This study addresses the question whether those alterations are also observable in populations at risk for developing schizophrenia or bipolar disorders. To our knowledge to date, this is the first study investigating SEPs in a population at risk for developing psychoses. Median nerve SEPs were investigated using multichannel EEG in individuals at risk for developing bipolar disorders (n = 25), individuals with high-risk status (n = 59) and ultra-high-risk status for schizophrenia (n = 73) and a gender and age-matched control group (n = 45). Strengths and latencies of low- and high-frequency components as estimated by dipole source analysis were compared between groups. Low- and high-frequency source activity was reduced in both groups at risk for schizophrenia, in comparison to the group at risk for bipolar disorders. HFO amplitudes were also significant reduced in subjects with high-risk status for schizophrenia compared to healthy controls. These differences were accentuated among cannabis non-users. Reduced N20 source strengths were related to higher positive symptom load. These results suggest that the risk for schizophrenia, in contrast to bipolar disorders, may involve an impairment of early cerebral somatosensory processing. Neurophysiologic alterations in schizophrenia precede the onset of initial psychotic episode and may serve as indicator of vulnerability for developing schizophrenia. PMID:25309363

  4. Early Social Experience Affects the Development of Eye Gaze Processing

    PubMed Central

    Senju, Atsushi; Vernetti, Angélina; Ganea, Natasa; Hudry, Kristelle; Tucker, Leslie; Charman, Tony; Johnson, Mark H.

    2015-01-01

    Summary Eye gaze is a key channel of non-verbal communication in humans [1, 2, 3]. Eye contact with others is present from birth [4], and eye gaze processing is crucial for social learning and adult-infant communication [5, 6, 7]. However, little is known about the effect of selectively different experience of eye contact and gaze communication on early social and communicative development. To directly address this question, we assessed 14 sighted infants of blind parents (SIBPs) longitudinally at 6–10 and 12–16 months. Face scanning [8] and gaze following [7, 9] were assessed using eye tracking. In addition, naturalistic observations were made when the infants were interacting with their blind parent and with an unfamiliar sighted adult. Established measures of emergent autistic-like behaviors [10] and standardized tests of cognitive, motor, and linguistic development [11] were also collected. These data were then compared with those obtained from a group of infants of sighted parents. Despite showing typical social skills development overall, infants of blind parents allocated less attention to adult eye movements and gaze direction, an effect that increased between 6–10 and 12–16 months of age. The results suggest that infants adjust their use of adults’ eye gaze depending on gaze communication experience from early in life. The results highlight that human functional brain development shows selective experience-dependent plasticity adaptive to the individual’s specific social environment. PMID:26752077

  5. Studies toward birth and early mammalian development in space.

    PubMed

    Ronca, April E

    2003-01-01

    Sustaining life beyond Earth on either space stations or other planets will require a clear understanding of how the space environment affects key phases of mammalian reproduction and development. Pregnancy, parturition (birth) and the early development of offspring are complex processes essential for successful reproduction and the proliferation of mammalian species. While no mammal has yet undergone birth within the space environment, studies spanning the gravity continuum from 0- to 2-g are revealing startling insights into how reproduction and development may proceed under gravitational conditions deviating from those typically experienced on Earth. In this report, I review studies of pregnant Norway rats and their offspring flown in microgravity onboard the NASA Space Shuttle throughout the period corresponding to mid- to late gestation, and analogous studies of pregnant rats exposed to hypergravity (hg) onboard the NASA Ames Research Center 24-ft centrifuge. Studies of postnatal rats flown in space or exposed to centrifugation are reviewed. Although many important questions remain unanswered, the available data suggest that numerous aspects of pregnancy, birth and early mammalian development can proceed under altered gravity conditions.

  6. Studies toward birth and early mammalian development in space

    NASA Astrophysics Data System (ADS)

    Ronca, April E.

    2003-10-01

    Sustaining life beyond Earth on either space stations or other planets will require a clear understanding of how the space environment affects key phases of mammalian reproduction and development. Pregnancy, parturition (birth) and the early development of offspring are complex processes essential for successful reproduction and the proliferation of mammalian species. While no mammal has yet undergone birth within the space environment, studies spanning the gravity continuum from 0- to 2-g are revealing startling insights into how reproduction and development may proceed under gravitational conditions deviating from those typically experienced on Earth. In this report, I review studies of pregnant Norway rats and their offspring flown in microgravity (μg) onboard the NASA Space Shuttle throughout the period corresponding to mid- to late gestation, and analogous studies of pregnant rats exposed to hypergravity ( ht) onboard the NASA Ames Research Center 24-ft centrifuge. Studies of postnatal rats flown in space or exposed to centrifugation are reviewed. Although many important questions remain unanswered, the available data suggest that numerous aspects of pregnancy, birth and early mammalian development can proceed under altered gravity conditions. Published by Elsevier Ltd on behalf of COSPAR.

  7. Practical Applications for Clinical Breast Examination (CBE) and Breast Self-Examination (BSE) in Screening and Early Detection of Breast Cancer*

    PubMed Central

    Miller, Anthony B.

    2008-01-01

    Summary The background and preliminary results in terms of stage distribution are given for a trial of Clinical Breast Examination and the teaching of Breast Self-Examination in Cairo, Egypt. A stage shift towards early diagnosis appears to have been achieved. This has encouraged the development of similar projects in other middle income developing countries. PMID:20824015

  8. Clinical features of early onset, familial Alzheimer`s disease linked to chromosome 14

    SciTech Connect

    Mullan, M.; Bennett, C.; Figueredo, C.; Crawford, F.

    1995-02-27

    Early onset familial Alzheimer`s disease (AD) has an autosomal dominant mode of inheritance. Two genes are responsible for the majority of cases of this subtype of AD. Mutations in the {beta}-amyloid precursor protein ({beta}APP) gene on chromosome 21 have been shown to completely cosegregate with the disease. We and others have previously described the clinical features of families with {beta}APP mutations at the codon 717 locus in an attempt to define the phenotype associated with a valine to isoleucine (Val {r_arrow} Ile) or a valine to glycine (Val {r_arrow} Gly) change. More recently, a second locus for very early onset disease has been localized to chromosome 14. The results of linkage studies in some families suggesting linkage to both chromosomes have been explained by the suggestion of a second (centromeric) locus on chromosome 21. Here we report the clinical features and genetic analysis of a British pedigree (F74) with early onset AD in which neither the {beta}APP locus nor any other chromosome 21 locus segregates with the disease, but in which good evidence is seen for linkage on the long arm of chromosome 14. In particular we report marker data suggesting that the chromosome 14 disease locus is close to D14S43 and D14S77. Given the likelihood that F74 represents a chromosome 14 linked family, we describe the clinical features and make a limited clinical comparison with the {beta}APP717 Val {r_arrow} Ile and {beta}APP717 Val {r_arrow} Gly encoded families that have been previously described. We conclude that although several previously reported clinical features occur to excess in early onset familial AD, no single clinical feature demarcates either the chromosome 14 or {beta}APP codon 717 mutated families except mean age of onset. 52 refs., 2 figs., 5 tabs.

  9. Effects of low-intensity pulsed electromagnetic fields on the early development of sea urchins

    SciTech Connect

    Falugi, C.; Grattarola, M.; Prestipino, G.

    1987-06-01

    The effects of weak electromagnetic signals on the early development of the sea urchin Paracentrotus lividus have been studied. The duration and repetition of the pulses were similar to those used for bone healing in clinical practice. A sequence of pulses, applied for a time ranging from 2 to 4 h, accelerates the cleavages of sea urchin embryo cells. This effect can be quantitatively assessed by determining the time shifts induced by the applied electromagnetic field on the completion of the first and second cleavages in a population of fertilized eggs. The exposed embryos were allowed to develop up to the pluteus stage, showing no abnormalities.

  10. Fathers’ Sensitive Parenting and the Development of Early Executive Functioning

    PubMed Central

    Towe-Goodman, Nissa R.; Willoughby, Michael; Blair, Clancy; Gustafsson, Hanna C.; Mills-Koonce, W. Roger; Cox, Martha J.

    2014-01-01

    Using data from a diverse sample of 620 families residing in rural, predominately low-income communities, this study examined longitudinal links between fathers’ sensitive parenting in infancy and toddlerhood and children’s early executive functioning, as well as the contribution of maternal sensitive parenting. After accounting for the quality of concurrent and prior parental care, children’s early cognitive ability, and other child and family factors, fathers’ and mothers’ sensitive and supportive parenting during play at 24-months predicted children’s executive functioning at 3-years of age. In contrast, paternal parenting quality during play at 7-months did not make an independent contribution above that of maternal care, but the links between maternal sensitive and supportive parenting and executive functioning seemed to operate in similar ways during infancy and toddlerhood. These findings add to prior work on early experience and children’s executive functioning, suggesting that both fathers and mothers play a distinct and complementary role in the development of these self-regulatory skills. PMID:25347539

  11. Early growth and development of later life metabolic disorders.

    PubMed

    Foo, Joo-Pin; Mantzoros, Christos

    2013-01-01

    Growth is effected via a complex interaction of genetic, nutritional, environmental and growth factors. Hormonal factors such as the growth hormone (GH) and insulin-like growth factor (IGF) signaling system, the human placental lactogen, and insulin play an integral role in early growth. Genetic factors affecting the GH-IGF system and insulin secretion and actions, and epigenetic mechanisms including DNA methylation have been further implicated as contributory factors. These hormonal systems, on a background of genetic susceptibility, together with other factors including maternal nutrition, placental and environmental factors, regulate not only early growth but also development. These interactions may impact on later health consequences in adult life. Accumulating data in the last few decades on developmental programming and later life metabolic disorders has provided a novel perspective on the possible pathogenesis of metabolic dysregulation. Despite postulations put forward to elucidate the mechanism underlying the association between early growth and later life metabolic disorders, it remains unclear what the dominant factor(s) would be, how any underlying mechanisms interact, or whether these mechanisms are truly causal.

  12. The role of ADME pharmacogenomics in early clinical trials: perspective of the Industry Pharmacogenomics Working Group (I-PWG).

    PubMed

    Tremaine, Larry; Brian, William; DelMonte, Terrye; Francke, Stephan; Groenen, Peter; Johnson, Keith; Li, Lei; Pearson, Kimberly; Marshall, Jean-Claude

    2015-12-01

    Genetic polymorphisms in metabolizing enzymes and drug transporters have been shown to significantly impact the exposure of drugs having a high dependence on a single mechanism for their absorption, distribution or clearance, such that genotyping can lead to actionable steps in disease treatment. Recently, global regulatory agencies have provided guidance for assessment of pharmacogenomics during early stages of drug development, both in the form of formal guidance and perspectives published in scientific journals. The Industry Pharmacogenomics Working Group (I-PWG), conducted a survey among member companies to assess the practices relating to absorption, distribution, metabolism, excretion pharmacogenomics) during early stages of clinical development, to assess the impact of the recent Regulatory Guidance issued by the US FDA and EMA on Industry practices.

  13. Early anther ablation triggers parthenocarpic fruit development in tomato.

    PubMed

    Medina, Mónica; Roque, Edelín; Pineda, Benito; Cañas, Luis; Rodriguez-Concepción, Manuel; Beltrán, José Pío; Gómez-Mena, Concepción

    2013-08-01

    Fruit set and fruit development in tomato is largely affected by changes in environmental conditions, therefore autonomous fruit set independent of fertilization is a highly desirable trait in tomato. Here, we report the production and characterization of male-sterile transgenic plants that produce parthenocarpic fruits in two tomato cultivars (Micro-Tom and Moneymaker). We generated male-sterility using the cytotoxic gene barnase targeted to the anthers with the PsEND1 anther-specific promoter. The ovaries of these plants grew in the absence of fertilization producing seedless, parthenocarpic fruits. Early anther ablation is essential to trigger the developing of the transgenic ovaries into fruits, in the absence of the signals usually generated during pollination and fertilization. Ovaries are fully functional and can be manually pollinated to obtain seeds. The transgenic plants obtained in the commercial cultivar Moneymaker show that the parthenocarpic development of the fruit does not have negative consequences in fruit quality. Throughout metabolomic analyses of the tomato fruits, we have identified two elite lines which showed increased levels of several health promoting metabolites and volatile compounds. Thus, early anther ablation can be considered a useful tool to promote fruit set and to obtain seedless and good quality fruits in tomato plants. These plants are also useful parental lines to be used in hybrid breeding approaches.

  14. A gene expression atlas of early craniofacial development.

    PubMed

    Brunskill, Eric W; Potter, Andrew S; Distasio, Andrew; Dexheimer, Phillip; Plassard, Andrew; Aronow, Bruce J; Potter, S Steven

    2014-07-15

    We present a gene expression atlas of early mouse craniofacial development. Laser capture microdissection (LCM) was used to isolate cells from the principal critical microregions, whose development, differentiation and signaling interactions are responsible for the construction of the mammalian face. At E8.5, as migrating neural crest cells begin to exit the neural fold/epidermal ectoderm boundary, we examined the cranial mesenchyme, composed of mixed neural crest and paraxial mesoderm cells, as well as cells from adjacent neuroepithelium. At E9.5 cells from the cranial mesenchyme, overlying olfactory placode/epidermal ectoderm, and underlying neuroepithelium, as well as the emerging mandibular and maxillary arches were sampled. At E10.5, as the facial prominences form, cells from the medial and lateral prominences, the olfactory pit, multiple discrete regions of underlying neuroepithelium, the mandibular and maxillary arches, including both their mesenchymal and ectodermal components, as well as Rathke's pouch, were similarly sampled and profiled using both microarray and RNA-seq technologies. Further, we performed single cell studies to better define the gene expression states of the early E8.5 pioneer neural crest cells and paraxial mesoderm. Taken together, and analyzable by a variety of biological network approaches, these data provide a complementing and cross validating resource capable of fueling discovery of novel compartment specific markers and signatures whose combinatorial interactions of transcription factors and growth factors/receptors are responsible for providing the master genetic blueprint for craniofacial development.

  15. Proteomic analysis of early seed development in Pinus massoniana L.

    PubMed

    Zhen, Yan; Zhao, Zhen-Zhou; Zheng, Ren-Hua; Shi, Jisen

    2012-05-01

    Understanding seed development is important for large-scale propagation and germplasm conservation for the Masson pine. We undertook a proteomic analysis of Masson pine seeds during the early stages of embryogenesis. Two-dimensional difference gel electrophoresis (2D DIGE) was used to quantify the differences in protein expression during early seed development. Using electrospray ionization mass spectrometry/mass spectrometry, we identified proteins from 43 gel spots that had been excised from preparative "pick" gels. Proteins involved in carbon metabolism were identified and were predominantly expressed at higher levels during the cleavage polyembryony and columnar embryo stages. Functional annotation of one seed protein revealed it involvement in programmed cell death and translation of selective mRNAs, which may play an important role in subordinate embryo elimination and suspensor degeneration in polyembryonic seed gymnosperms. Other identified proteins were associated with protein folding, nitrogen metabolism, disease/defense response, and protein storage, synthesis and stabilization. The comprehensive protein expression profiles generated by this study will provide new insights into the complex developmental process of seed development in Masson pine.

  16. Apoptosis in early development of the sea urchin, Strongylocentrotus purpuratus.

    PubMed

    Vega Thurber, Rebecca; Epel, David

    2007-03-01

    Apoptosis provides metazoans remarkable developmental flexibility by (1) eliminating damaged undifferentiated cells early in development and then (2) sculpting, patterning, and restructuring tissues during successive stages thereafter. We show here that apoptotic programmed cell death is infrequent and not obligatory during early embryogenesis of the purple sea urchin, Strongylocentrotus purpuratus. During the first 30 h of urchin development, fewer than 20% of embryos exhibit any cell death. Cell death during the cleavage stages consists of necrotic or pathological cell death, while cell death during the blastula and gastrula stages is random and predominantly caspase-mediated apoptosis. Apoptosis remains infrequent during the late blastula stage followed by a gradual increase in frequency during gastrulation. Even after prolonged exposure during the cleavage period to chemical stress, apoptosis occurs in less than 50% of embryos and always around the pre-hatching stage. Embryonic suppression of apoptosis through caspase inhibition leads to functionally normal larvae that can survive to metamorphosis, but in the presence of inducers of apoptosis, caspase inhibition leads to deformed larvae and reduced survival. Remarkably, however, pharmacological induction of apoptosis, while reducing overall survival, also significantly accelerates development of the survivors such that metamorphosis occurs up to a week before controls.

  17. Novel oral anticoagulants and reversal agents: Considerations for clinical development.

    PubMed

    Sarich, Troy C; Seltzer, Jonathan H; Berkowitz, Scott D; Costin', James; Curnutte, John T; Gibson, C Michael; Hoffman, Maureane; Kaminskas, Edvardas; Krucoff, Mitchell W; Levy, Jerrold H; Mintz, Paul D; Reilly, Paul A; Sager, Philip T; Singer, Daniel E; Stockbridge, Norman; Weitz, Jeffrey I; Kowey, Peter R

    2015-06-01

    This white paper provides a summary of presentations and discussions that were held at an Anticoagulant-Induced Bleeding and Reversal Agents Think Tank co-sponsored by the Cardiac Safety Research Consortium and the US Food and Drug Administration (FDA) at the FDA's White Oak Headquarters on April 22, 2014. Attention focused on a development pathway for reversal agents for the novel oral anticoagulants (NOACs). This is important because anticoagulation is still widely underused for stroke prevention in patients with atrial fibrillation. Undertreatment persists, although NOACs, in general, overcome some of the difficulties associated with anticoagulation provided by vitamin K antagonists. One reason for the lack of a wider uptake is the absence of NOAC reversal agents. As there are neither widely accepted academic and industry standards nor a definitive regulatory policy on the development of such reversal agents, this meeting provided a forum for leaders in the fields of cardiovascular clinical trials and cardiovascular safety to discuss the issues and develop recommendations. Attendees included representatives from pharmaceutical companies; regulatory agencies; end point adjudication specialist groups; contract research organizations; and active, academically based physicians. There was wide and solid consensus that NOACs overall offer improvements in convenience, efficacy, and safety compared with warfarin, even without reversal agents. Still, it was broadly accepted that it would be helpful to have reversal agents available for clinicians to use. Because it is not feasible to do definitive outcomes studies demonstrating a reversal agent's clinical benefits, it was felt that these agents could be approved for use in life-threatening bleeding situations if the molecules were well characterized preclinically, their pharmacodynamic and pharmacokinetic profiles were well understood, and showed no harmful adverse events in early human testing. There was also consensus

  18. Skill Learning Through Early Clinical Exposure: An Experience of Indian Medical School

    PubMed Central

    Jagzape, Arunita; Srivastava, Tripti; Gotarkar, Shashank

    2016-01-01

    Introduction Indian Medical curriculum being discipline based, there is a line of demarcation between preclinical and clinical subjects. The challenges in medical education include the methods that would enhance the clinical education quality; one such method been Early Clinical Exposure (ECE). ECE can help to instill the skill component of medical education in the first year students helping to minimize the line of demarcation. Hence this study was undertaken to assess the skill learning of students through early clinical exposure and to collate the perception of them. Materials and Methods: In the present study, students of 1st MBBS were exposed to ECE as an adjunct teaching method with preset modules. They were evaluated by Objectively Structured Clinical Examination (OSCE). Feedback was obtained from 1st MBBS and also from the same students after passing the 1st MBBS in 4th semester. Results Significant differences in pre and post OSCE scores were noted (p<0.0001). Seventy six percent students rated ECE as an excellent tool. Second year students also perceived ECE held in 1st year was helpful to correlate topics and increasing confidence. Conclusion ECE had an effective influence on learning as manifested in skills gained by the students and their perceptions of ECE being helpful prospectively in their routine clinical posting. PMID:26894088

  19. APECS: A Network for Polar Early Career Scientist Professional Development

    NASA Astrophysics Data System (ADS)

    Enderlin, E. M.

    2014-12-01

    The Association of Polar Early Career Researchers (APECS) is an international and interdisciplinary organization for undergraduate and graduate students, postdoctoral researchers, early faculty members, educators and others with interests in the polar regions, alpine regions and the wider Cryosphere. APECS is a scientific, non-profit organization with free individual membership that aims to stimulate research collaborations and develop effective future leaders in polar research, education, and outreach. APECS grew out of the 4th International Polar Year (2007-08), which emphasized the need to stimulate and nurture the next generation of scientists in order to improve the understanding and communication of the polar regions and its global connections. The APECS organizational structure includes a Council and an elected Executive Committee that are supported by a Directorate. These positions are open to all individual members through a democratic process. The APECS Directorate is funded by the Norwegian Research Council, the University of Tromsø and the Norwegian Polar Institute and is hosted by the University of Tromsø. Early career scientists benefit from a range of activities hosted/organized by APECS. Every year, numerous activities are run with partner organizations and in conjunction with major polar conferences and meetings. In-person and online panels and workshops focus on a range of topics, from developing field skills to applying for a job after graduate school. Career development webinars are hosted each fall and topical research webinars are hosted throughout the year and archived online (http://www.apecs.is). The APECS website also contains abundant information on polar news, upcoming conferences and meetings, and job postings for early career scientists. To better respond to members' needs, APECS has national/regional committees that are linked to the international overarching organization. Many of these committees organize regional meetings or

  20. Use of Child Development Assessment in Early Childhood Education: Early Childhood Practitioner and Student Attitudes toward Formal and Informal Testing

    ERIC Educational Resources Information Center

    Brown, Jacqueline; Rolfe, Sharne A.

    2005-01-01

    Twenty early childhood practitioners (ECPs) and final-year Bachelor of Early Childhood Studies students completed a questionnaire about their use (or planned use) of formal and informal child development assessment instruments, their choice of specific instruments, and factors influencing decisions to conduct child development assessments within…

  1. ADDME – Avoiding Drug Development Mistakes Early: central nervous system drug discovery perspective

    PubMed Central

    Tsaioun, Katya; Bottlaender, Michel; Mabondzo, Aloise

    2009-01-01

    The advent of early absorption, distribution, metabolism, excretion, and toxicity (ADMET) screening has increased the attrition rate of weak drug candidates early in the drug-discovery process, and decreased the proportion of compounds failing in clinical trials for ADMET reasons. This paper reviews the history of ADMET screening and its place in pharmaceutical development, and central nervous system drug discovery in particular. Assays that have been developed in response to specific needs and improvements in technology that result in higher throughput and greater accuracy of prediction of human mechanisms of absorption and toxicity are discussed. The paper concludes with the authors' forecast of new models that will better predict human efficacy and toxicity. PMID:19534730

  2. Atrophy patterns in early clinical stages across distinct phenotypes of Alzheimer's disease.

    PubMed

    Ossenkoppele, Rik; Cohn-Sheehy, Brendan I; La Joie, Renaud; Vogel, Jacob W; Möller, Christiane; Lehmann, Manja; van Berckel, Bart N M; Seeley, William W; Pijnenburg, Yolande A; Gorno-Tempini, Maria L; Kramer, Joel H; Barkhof, Frederik; Rosen, Howard J; van der Flier, Wiesje M; Jagust, William J; Miller, Bruce L; Scheltens, Philip; Rabinovici, Gil D

    2015-11-01

    Alzheimer's disease (AD) can present with distinct clinical variants. Identifying the earliest neurodegenerative changes associated with each variant has implications for early diagnosis, and for understanding the mechanisms that underlie regional vulnerability and disease progression in AD. We performed voxel-based morphometry to detect atrophy patterns in early clinical stages of four AD phenotypes: Posterior cortical atrophy (PCA, "visual variant," n=93), logopenic variant primary progressive aphasia (lvPPA, "language variant," n=74), and memory-predominant AD categorized as early age-of-onset (EOAD, <65 years, n=114) and late age-of-onset (LOAD, >65 years, n=114). Patients with each syndrome were stratified based on: (1) degree of functional impairment, as measured by the clinical dementia rating (CDR) scale, and (2) overall extent of brain atrophy, as measured by a neuroimaging approach that sums the number of brain voxels showing significantly lower gray matter volume than cognitively normal controls (n=80). Even at the earliest clinical stage (CDR=0.5 or bottom quartile of overall atrophy), patients with each syndrome showed both common and variant-specific atrophy. Common atrophy across variants was found in temporoparietal regions that comprise the posterior default mode network (DMN). Early syndrome-specific atrophy mirrored functional brain networks underlying functions that are uniquely affected in each variant: Language network in lvPPA, posterior cingulate cortex-hippocampal circuit in amnestic EOAD and LOAD, and visual networks in PCA. At more advanced stages, atrophy patterns largely converged across AD variants. These findings support a model in which neurodegeneration selectively targets both the DMN and syndrome-specific vulnerable networks at the earliest clinical stages of AD.

  3. Accident Sequence Precursor Program Large Early Release Frequency Model Development

    SciTech Connect

    Brown, T.D.; Brownson, D.A.; Duran, F.A.; Gregory, J.J.; Rodrick, E.G.

    1999-01-04

    The objectives for the ASP large early release frequency (LERF) model development work is to build a Level 2 containment response model that would capture all of the events necessary to define LERF as outlined in Regulatory Guide 1.174, can be directly interfaced with the existing Level 1 models, is technically correct, can be readily modified to incorporate new information or to represent another plant, and can be executed in SAPHIRE. The ASP LERF models being developed will meet these objectives while providing the NRC with the capability to independently assess the risk impact of plant-specific changes proposed by the utilities that change the nuclear power plants' licensing basis. Together with the ASP Level 1 models, the ASP LERF models provide the NRC with the capability of performing equipment and event assessments to determine their impact on a plant's LERF for internal events during power operation. In addition, the ASP LERF models are capable of being updated to reflect changes in information regarding the system operations and phenomenological events, and of being updated to assess the potential for early fatalities for each LERF sequence. As the ASP Level 1 models evolve to include more analysis capabilities, the LERF models will also be refined to reflect the appropriate level of detail needed to demonstrate the new capabilities. An approach was formulated for the development of detailed LERF models using the NUREG-1150 APET models as a guide. The modifications to the SAPHIRE computer code have allowed the development of these detailed models and the ability to analyze these models in a reasonable time. Ten reference LERF plant models, including six PWR models and four BWR models, which cover a wide variety of containment and nuclear steam supply systems designs, will be complete in 1999. These reference models will be used as the starting point for developing the LERF models for the remaining nuclear power plants.

  4. 78 FR 39736 - Draft Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-02

    ... of Early-Phase Clinical Trials of Cellular and Gene Therapy Products; Availability AGENCY: Food and... Design of Early-Phase Clinical Trials of Cellular and Gene Therapy Products'' dated July 2013. The draft... (CT) and gene therapy (GT) products (referred to collectively as CGT products) with recommendations...

  5. Influence of early neurological complications on clinical outcome following lung transplant

    PubMed Central

    Salvado, Maria; Martinez-de La Ossa, Alejandro; Deu, Maria; Romero, Laura; Roman, Antonio; Sacanell, Judith; Laborda, Cesar; Rochera, Isabel; Nadal, Miriam; Carmona, Francesc; Santamarina, Estevo; Raguer, Nuria; Canela, Merce; Solé, Joan

    2017-01-01

    Background Neurological complications after lung transplantation are common. The full spectrum of neurological complications and their impact on clinical outcomes has not been extensively studied. Methods We investigated the neurological incidence of complications, categorized according to whether they affected the central, peripheral or autonomic nervous systems, in a series of 109 patients undergoing lung transplantation at our center between January 1 2013 and December 31 2014. Results Fifty-one patients (46.8%) presented at least one neurological complication. Critical illness polyneuropathy-myopathy (31 cases) and phrenic nerve injury (26 cases) were the two most prevalent complications. These two neuromuscular complications lengthened hospital stays by a median period of 35.5 and 32.5 days respectively. However, neurological complications did not affect patients’ survival. Conclusions The real incidence of neurological complications among lung transplant recipients is probably underestimated. They usually appear in the first two months after surgery. Despite not affecting mortality, they do affect the mean length of hospital stay, and especially the time spent in the Intensive Care Unit. We found no risk factor for neurological complications except for long operating times, ischemic time and need for transfusion. It is necessary to develop programs for the prevention and early recognition of these complications, and the prevention of their precipitant and risk factors. PMID:28301586

  6. Early Breast Cancer Precursor Lesions: Lessons Learned from Molecular and Clinical Studies

    PubMed Central

    Sinn, Hans-Peter; Elsawaf, Zeinab; Helmchen, Birgit; Aulmann, Sebastian

    2010-01-01

    Atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), and lobular neoplasia (LN) form a group of early precursor lesions that are part of the low-grade pathway in breast cancer development. This concept implies that the neoplastic disease process begins at a stage much earlier than in situ carcinoma. We have performed a review of the published literature for the upgrade risk to ductal carcinoma in situ or invasive carcinoma in open biopsy after a diagnosis of ADH, FEA, or LN in core needle biopsy. This has revealed the highest upgrade risk for ADH (28.2% after open biopsy), followed by LN (14.9%), and FEA (10.2%). With LN, the pleomorphic subtype is believed to confer a higher risk than classical LN. With all types of precursor lesions, careful attention must be paid to the clinicopathological correlation for the guidance of the clinical management. Follow-up biopsies are generally indicated in ADH, and if there is any radiological-pathological discrepancy, also in LN or FEA. PMID:22590441

  7. Early Requestive Development in Consecutive Third Language Learning

    ERIC Educational Resources Information Center

    Safont-Jorda, Maria-Pilar

    2011-01-01

    While research on early simultaneous bilingual acquisition is well-documented, studies on multiple language acquisition in early childhood are still needed. Existing studies have mainly focused on early simultaneous acquisition of three or more languages. Some attention has already been paid to early pragmatic differentiation and cross-linguistic…

  8. Development of Multimedia Computer Applications for Clinical Pharmacy Training.

    ERIC Educational Resources Information Center

    Schlict, John R.; Livengood, Bruce; Shepherd, John

    1997-01-01

    Computer simulations in clinical pharmacy education help expose students to clinical patient management earlier and enable training of large numbers of students outside conventional clinical practice sites. Multimedia instruction and its application to pharmacy training are described, the general process for developing multimedia presentations is…

  9. NEP Early Flight program: System performance and development considerations

    NASA Technical Reports Server (NTRS)

    Doherty, Michael P.; George, Jeffrey A.

    1993-01-01

    A mission/system study of Nuclear Electric Propulsion (NEP) for early robotic planetary science mission applications has been conducted. Subject missions considered included a Mars orbiter with a Phobos and Deimos Rendezvous; a Comet Kopff Rendezvous; a Multiple Mainbelt Asteroid Rendezvous (MMBAR); an Asteroid (Vesta) Sample Return; a Trojan Asteroid (Odysseus) Rendezvous; and a Jupiter mini Grand Tour. The purpose of the study was to determine if 'near-term' NEP technology could be used on an early NEP flight to demonstrate the technologies while conducting a useful science mission. The analysis shows that, depending upon technology readiness date, the missions could be performed with low power NEP. The technology and system development costs associated with vehicle/stage development for a candidate mission are presented. The study assumed relatively mature space electric power and space electric propulsion technologies (more advanced technologies have been already shown by others to be enabling for many outer planetary missions). Thus, a very important first step in using NEP would be taken, which would contribute valuable solar system science, as well as reduce the risks associated with using NEP for more demanding outer planetary science mission applications.

  10. Early Development of the Gut Microbiota and Immune Health

    PubMed Central

    Francino, M. Pilar

    2014-01-01

    In recent years, the increase in human microbiome research brought about by the rapidly evolving “omic” technologies has established that the balance among the microbial groups present in the human gut, and their multipronged interactions with the host, are crucial for health. On the other hand, epidemiological and experimental support has also grown for the ‘early programming hypothesis’, according to which factors that act in utero and early in life program the risks for adverse health outcomes later on. The microbiota of the gut develops during infancy, in close interaction with immune development, and with extensive variability across individuals. It follows that the specific process of gut colonization and the microbe-host interactions established in an individual during this period have the potential to represent main determinants of life-long propensity to immune disease. Although much remains to be learnt on the progression of events by which the gut microbiota becomes established and initiates its intimate relationships with the host, and on the long-term repercussions of this process, recent works have advanced significatively in this direction. PMID:25438024

  11. Liriodenine alkaloid in Annona diversifolia during early development.

    PubMed

    de la Cruz Chacón, I; González-Esquinca, A R

    2012-01-01

    Plants of the Annonaceae family produce a series of alkaloids, including liriodenine oxoaporphine. Its distribution in these primitive angiosperms suggests that it plays an important role, but very little is known about which plant organs it accumulates in, or in which developmental stages it is synthesised. Accordingly, liriodenine production was studied during the early stages of germination and seedling development in Annona diversifolia Saff. Liriodenine samples were obtained from the roots and were characterised on the basis of spectroscopic data. Quantification was done by HPLC in the organs and tissues of newly collected seeds, seeds following 1-, 2-, 5- and 10-day imbibitions, upon emergence of the radicle and at the seedling stage. According to our results, liriodenine could not have originated from the parent plant, nor during embryogenesis because it appears for the first time in the endosperm approximately 5 days after the start of imbibition. Therefore, its synthesis does not depend directly on photosynthesis. During the seedling stage it is found in the root and the stem but it is absent from the cotyledonary leaves and the first true leaves. Liriodenine biosynthesis begins during the early stages of development in the endosperm and seed radicles.

  12. Little chameleons: The development of social mimicry during early childhood.

    PubMed

    van Schaik, Johanna E; Hunnius, Sabine

    2016-07-01

    Adults use behavioral mimicry to blend in with (or stand out from) their social environment. Adopting another's mannerisms and behaviors, or "mimicking", communicates liking and similarity between interaction partners and has been shown to serve as an implicit affiliation mechanism. Given this important social function, it is surprising that so little is known about the development of mimicry. In two studies, we investigated mimicry and its social sensitivity during early childhood. Children of 4 to 6years (Study 1) and 3years (Study 2) first chose a novel group based on their color preference. Following a baseline phase, children observed videos of in-group and out-group models performing behaviors that are typically mimicked in adults. Importantly, the children received neither instructions nor encouragement to copy the behaviors. Both 3-year-olds and 4- to 6-year-olds displayed behavioral mimicry. Furthermore, 4- to 6-year-olds mimicked the in-group model more than the out-group model, and this in-group bias was also evident in their explicit group preferences. Together, these studies present the first evidence for behavioral mimicry and its social sensitivity during early childhood. Placed in the context of social development, the findings provide a necessary contribution to current developmental and psychological theories on mimicry and behavior copying.

  13. Early-Life Experience, Epigenetics, and the Developing Brain

    PubMed Central

    Kundakovic, Marija; Champagne, Frances A

    2015-01-01

    Development is a dynamic process that involves interplay between genes and the environment. In mammals, the quality of the postnatal environment is shaped by parent–offspring interactions that promote growth and survival and can lead to divergent developmental trajectories with implications for later-life neurobiological and behavioral characteristics. Emerging evidence suggests that epigenetic factors (ie, DNA methylation, posttranslational histone modifications, and small non-coding RNAs) may have a critical role in these parental care effects. Although this evidence is drawn primarily from rodent studies, there is increasing support for these effects in humans. Through these molecular mechanisms, variation in risk of psychopathology may emerge, particularly as a consequence of early-life neglect and abuse. Here we will highlight evidence of dynamic epigenetic changes in the developing brain in response to variation in the quality of postnatal parent–offspring interactions. The recruitment of epigenetic pathways for the biological embedding of early-life experience may also have transgenerational consequences and we will describe and contrast two routes through which this transmission can occur: experience dependent vs germline inheritance. Finally, we will speculate regarding the future directions of epigenetic research and how it can help us gain a better understanding of the developmental origins of psychiatric dysfunction. PMID:24917200

  14. ESE-1 in Early Development: Approaches for the Future

    PubMed Central

    Lee, Chan Mi; Wu, Jing; Xia, Yi; Hu, Jim

    2016-01-01

    E26 transformation-specific (Ets) family of transcription factors are characterized by the presence of Ets-DNA binding domain and have been found to be highly involved in hematopoiesis and various tissue differentiation. ESE-1, or Elf3 in mice, is a member of epithelium-specific Ets sub-family which is most prominently expressed in epithelial tissues such as the gut, mammary gland, and lung. The role of ESE-1 during embryogenesis had long been alluded from 30% fetal lethality in homozygous knockout mice and its high expression in preimplantation mouse embryos, but there has been no in-depth of analysis of ESE-1 function in early development. With improved proteomics, gene editing tools and increasing knowledge of ESE-1 function in adult tissues, we hereby propose future research directions for the study of ESE-1 in embryogenesis, including studying its regulation at the protein level and at the protein family level, as well as better defining the developmental phase under investigation. Understanding the role of ESE-1 in early development will provide new insights into its involvement in tissue regeneration and cancer, as well as how it functions with other Ets factors as a protein family. PMID:27446923

  15. Early Neurobehavioral Development of Mice Lacking Endogenous PACAP.

    PubMed

    Farkas, Jozsef; Sandor, Balazs; Tamas, Andrea; Kiss, Peter; Hashimoto, Hitoshi; Nagy, Andras D; Fulop, Balazs D; Juhasz, Tamas; Manavalan, Sridharan; Reglodi, Dora

    2017-04-01

    Pituitary adenylate cyclase activating polypeptide (PACAP) is a multifunctional neuropeptide. In addition to its diverse physiological roles, PACAP has important functions in the embryonic development of various tissues, and it is also considered as a trophic factor during development and in the case of neuronal injuries. Data suggest that the development of the nervous system is severely affected by the lack of endogenous PACAP. Short-term neurofunctional outcome correlates with long-term functional deficits; however, the early neurobehavioral development of PACAP-deficient mice has not yet been evaluated. Therefore, the aim of the present study was to describe the postnatal development of physical signs and neurological reflexes in mice partially or completely lacking PACAP. We examined developmental hallmarks during the first 3 weeks of the postnatal period, during which period most neurological reflexes and motor coordination show most intensive development, and we describe the neurobehavioral development using a complex battery of tests. In the present study, we found that PACAP-deficient mice had slower weight gain throughout the observation period. Interestingly, mice partially lacking PACAP weighed significantly less than homozygous mice. There was no difference between male and female mice during the first 3 weeks. Some other signs were also more severely affected in the heterozygous mice than in the homozygous mice, such as air righting, grasp, and gait initiation reflexes. Interestingly, incisor teeth erupted earlier in mice lacking PACAP. Motor coordination, shown by the number of foot-faults on an elevated grid, was also less developed in PACAP-deficient mice. In summary, our results show that mice lacking endogenous PACAP have slower weight gain during the first weeks of development and slower neurobehavioral development regarding a few developmental hallmarks.

  16. Altered Gravity and Early Heart Development in Culture

    NASA Technical Reports Server (NTRS)

    Wiens, Darrell J.; Lwigale, P.; Denning, J.

    1996-01-01

    The macromolecules comprising the cytoskeleton and extracellular matrix of cells may be sensitive to gravitation. Since early development of organs depends on dynamic interactions across cell surfaces, altered gravity may disturb development. We investigated this possibility for heart development. Previous studies showed that the extracellular matrix glycoprotein fibronectin (Fn) is necessary for normal heart development. We cultured precardiac tissue explants in a high aspect ratio bioreactor vessel (HARV) to simulate microgravity. We observed tissue morphology, contraction, and Fn distribution by immunolocalization in HARV rotated and control (lxg) explants, cultured 18 hr. We also measured Fn amount by immunoassay. Explants in HARV were rotated at 6 rpm to achieve continuous freefall. Thirty-five of 37 control, but only 1 of 37 matched rotated explants exhibited contractions. Tissue architecture was identical. Immunolocalization of Fn showed remarkable differences which may be related to the development of contractions. The Fn staining in the HARV explants was less intense in all areas. Areas of linear staining along epithelia were present but shorter, and there was less intercellular staining in both mesenchymal tissue and myocardium. Initial immunoassay results of 5 matched pairs of explants showed a 22% reduction in total tissue Fn in the HARV rotated samples. Our results indicate that altered gravity in the HARV reduced the amount and distribution of Fn, as assessed by two independent criteria. This was correlated with a reduction in the development of contractile activity.

  17. Language, bilingualism, and executive functioning in early development.

    PubMed

    Morton, J Bruce

    2010-12-01

    Okanda, et al. (2010) reported new evidence concerning associations between language ability, bilingualism, and executive functioning early in development. The paper adds to a growing body of literature suggesting that bilingualism is associated with advantages in executive functioning generally, and the Dimensional Change Card Sort task in particular. However, as with all findings that hinge on between-group comparisons, there is a need to exercise caution before drawing firm conclusions about the effects of bilingualism on the development of executive control. Several lines of recent evidence are outlined that challenge key assumptions underlying the standard account of the bilingual advantage. Okanda, et al.'s findings are discussed in light of this evidence.

  18. Early development and function of the Xenopus tadpole retinotectal circuit.

    PubMed

    Liu, Zhenyu; Hamodi, Ali S; Pratt, Kara G

    2016-12-01

    The retinotectal circuit is the major component of the amphibian visual system. It is comprised of the retinal ganglion cells (RGCs) in the eye, which project their axons to the optic tectum and form synapses onto postsynaptic tectal neurons. The retinotectal circuit is relatively simple, and develops quickly: Xenopus tadpoles begin displaying retinotectal-dependent visual avoidance behaviors by approximately 7-8 days post-fertilization, early larval stage. In this review we first provide a summary of the dynamic development of the retinotectal circuit, including the microcircuitry formed by local tectal-tectal connections within the tectum. Second, we discuss the basic visual avoidance behavior generated specifically by this circuit, and how this behavior is being used as an assay to test visual system function.

  19. Metabolic Remodeling in early development and cardiomyocyte maturation

    PubMed Central

    Kreipke, Rebecca; Wang, Yuliang; Miklas, Jason Wayne; Mathieu, Julie; Ruohola-Baker, Hannele

    2016-01-01

    Aberrations in metabolism contribute to a large number of diseases, such as diabetes, obesity, cancer, and cardiovascular diseases, that have a substantial impact on the mortality rates and quality of life worldwide. However, the mechanisms leading to these changes in metabolic state – and whether they are conserved between diseases – is not well understood. Changes in metabolism similar to those seen in pathological conditions are observed during normal development in a number of different cell types. This provides hope that understanding the mechanism of these metabolic switches in normal development may provide useful insight in correcting them in pathological cases. Here, we focus on the metabolic remodeling observed both in early stage embryonic stem cells and during the maturation of cardiomyocytes. PMID:26912118

  20. Modeling and managing risk early in software development

    NASA Technical Reports Server (NTRS)

    Briand, Lionel C.; Thomas, William M.; Hetmanski, Christopher J.

    1993-01-01

    In order to improve the quality of the software development process, we need to be able to build empirical multivariate models based on data collectable early in the software process. These models need to be both useful for prediction and easy to interpret, so that remedial actions may be taken in order to control and optimize the development process. We present an automated modeling technique which can be used as an alternative to regression techniques. We show how it can be used to facilitate the identification and aid the interpretation of the significant trends which characterize 'high risk' components in several Ada systems. Finally, we evaluate the effectiveness of our technique based on a comparison with logistic regression based models.

  1. Preclinical and clinical development of siRNA-based therapeutics

    PubMed Central

    Ozcan, Gulnihal; Ozpolat, Bulent; Coleman, Robert L.; Sood, Anil K.; Lopez-Berestein, Gabriel

    2015-01-01

    Discovery of RNA interference, first in plants and C. elegans and later in mammalian cells, led to the emergence of a transformative view in biomedical research. Knowledge of the multiple actions of non-coding RNAs has truly allowed viewing DNA, RNA and proteins in novel ways. Small interfering RNAs (siRNAs) can be used as tools to study single gene function both in vitro and in vivo and are an attractive new class of therapeutics, especially against undruggable targets for the treatment of cancer and other diseases. Despite the potential of siRNAs in cancer therapy, many challenges remain, including rapid degradation, poor cellular uptake and off-target effects. Rational design strategies, selection algorithms, chemical modifications and nanocarriers offer significant opportunities to overcome these challenges. Here, we review the development of siRNAs as therapeutic agents from early design to clinical trial, with special emphasis on the development of EphA2-targeting siRNAs for ovarian cancer treatment. PMID:25666164

  2. Multilevel analysis of air pollution and early childhood neurobehavioral development.

    PubMed

    Lin, Ching-Chun; Yang, Shih-Kuan; Lin, Kuan-Chia; Ho, Wen-Chao; Hsieh, Wu-Shiun; Shu, Bih-Ching; Chen, Pau-Chung

    2014-07-02

    To investigate the association between the ambient air pollution levels during the prenatal and postnatal stages and early childhood neurobehavioral development, our study recruited 533 mother-infant pairs from 11 towns in Taiwan. All study subjects were asked to complete childhood neurobehavioral development scales and questionnaires at 6 and 18 months. Air pollution, including particulate matter ≤10 μm (PM10), carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), and hydrocarbons, was measured at air quality monitoring stations in the towns where the subjects lived. Multilevel analyses were applied to assess the association between air pollution and childhood neurobehavioral development during pregnancy and when the children were 0 to 6 months, 7 to 12 months, and 13 to 18 months old. At 18 months, poor subclinical neurodevelopment in early childhood is associated with the average SO2 exposure of prenatal, during all trimesters of pregnancy and at postnatal ages up to 12 months (first trimester β = -0.083, se = 0.030; second and third trimester β = -0.114, se = 0.045; from birth to 12 months of age β = -0.091, se = 0.034). Furthermore, adverse gross motor below average scores at six months of age were associated with increased average non-methane hydrocarbon, (NMHC) levels during the second and third trimesters (β = -8.742, se = 3.512). Low-level SO2 exposure prenatally and up to twelve months postnatal could cause adverse neurobehavioral effects at 18 months of age. Maternal NMHC exposure during the 2nd and 3rd trimesters of pregnancy would be also associated with poor gross motor development in their children at 6 months of age.

  3. Multilevel Analysis of Air Pollution and Early Childhood Neurobehavioral Development

    PubMed Central

    Lin, Ching-Chun; Yang, Shih-Kuan; Lin, Kuan-Chia; Ho, Wen-Chao; Hsieh, Wu-Shiun; Shu, Bih-Ching; Chen, Pau-Chung

    2014-01-01

    To investigate the association between the ambient air pollution levels during the prenatal and postnatal stages and early childhood neurobehavioral development, our study recruited 533 mother-infant pairs from 11 towns in Taiwan. All study subjects were asked to complete childhood neurobehavioral development scales and questionnaires at 6 and 18 months. Air pollution, including particulate matter ≤10 μm (PM10), carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), and hydrocarbons, was measured at air quality monitoring stations in the towns where the subjects lived. Multilevel analyses were applied to assess the association between air pollution and childhood neurobehavioral development during pregnancy and when the children were 0 to 6 months, 7 to 12 months, and 13 to 18 months old. At 18 months, poor subclinical neurodevelopment in early childhood is associated with the average SO2 exposure of prenatal, during all trimesters of pregnancy and at postnatal ages up to 12 months (first trimester β = −0.083, se = 0.030; second and third trimester β = −0.114, se = 0.045; from birth to 12 months of age β = −0.091, se = 0.034). Furthermore, adverse gross motor below average scores at six months of age were associated with increased average non-methane hydrocarbon, (NMHC) levels during the second and third trimesters (β = −8.742, se = 3.512). Low-level SO2 exposure prenatally and up to twelve months postnatal could cause adverse neurobehavioral effects at 18 months of age. Maternal NMHC exposure during the 2nd and 3rd trimesters of pregnancy would be also associated with poor gross motor development in their children at 6 months of age. PMID:24992486

  4. Coaching in the Context of Social-Emotional Development: Implications for Targeted Early Childhood Professional Development

    ERIC Educational Resources Information Center

    Harkins, Diane M.

    2013-01-01

    This study was designed to inform professional development in early childhood education (ECE) by examining the use of coaching to improve teacher performance in the classroom. Professional development programs that include coaching, a relationship-based method of enhancing application of newly acquired knowledge and skills, have received…

  5. Brain Development and Early Learning: Research on Brain Development. Quality Matters. Volume 1, Winter 2007

    ERIC Educational Resources Information Center

    Edie, David; Schmid, Deborah

    2007-01-01

    For decades researchers have been aware of the extraordinary development of a child's brain during the first five years of life. Recent advances in neuroscience have helped crystallize earlier findings, bringing new clarity and understanding to the field of early childhood brain development. Children are born ready to learn. They cultivate 85…

  6. Development of a clinical preceptor model.

    PubMed

    Blum, Cynthia Ann

    2009-01-01

    To reflect contemporary nursing care, the practicing nurse is in an ideal position to shape the clinical experience for student nurses. Although nurse preceptors are frequently used to assist in practice education of nursing students, their contribution to the creation of these programs has not been explored. The author discusses the results of a participatory action research study with the aim of creating a preceptor-guided practice education model for use throughout an undergraduate bachelor of science in nursing curriculum.

  7. Mechanisms and clinical significance of early recurrences of atrial arrhythmias after catheter ablation for atrial fibrillation

    PubMed Central

    Liang, Jackson J; Dixit, Sanjay; Santangeli, Pasquale

    2016-01-01

    Early recurrence of atrial arrhythmias (ERAA) after ablation is common and strongly predicts late recurrences and ablation failure. However, since arrhythmia may eventually resolve in up to half of patients with ERAA, guidelines do not recommend immediate reintervention for ERAA episodes occurring during a 3-mo post-ablation blanking period. Certain clinical demographic, electrophysiologic, procedural, and ERAA-related characteristics may predict a higher likelihood of long-term ablation failure. In this review, we aim to discuss potential mechanisms of ERAA, and to summarize the clinical significance, prognostic implications, and treatment options for ERAA. PMID:27957250

  8. Deuterostome evolution: early development in the enteropneust hemichordate, Ptychodera flava

    NASA Technical Reports Server (NTRS)

    Henry, J. Q.; Tagawa, K.; Martindale, M. Q.

    2001-01-01

    Molecular and morphological comparisons indicate that the Echinodermata and Hemichordata represent closely related sister-phyla within the Deuterostomia. Much less is known about the development of the hemichordates compared to other deuterostomes. For the first time, cell lineage analyses have been carried out for an indirect-developing representative of the enteropneust hemichordates, Ptychodera flava. Single blastomeres were iontophoretically labeled with Dil at the 2- through 16-cell stages, and their fates followed through development to the tornaria larval stage. The early cleavage pattern of P. flava is similar to that of the direct-developing hemichordate, Saccoglossus kowalevskii, as well as that displayed by indirect-developing echinoids. The 16-celled embryo contains eight animal "mesomeres," four slightly larger "macromeres," and four somewhat smaller vegetal "micromeres." The first cleavage plane was not found to bear one specific relationship relative to the larval dorsoventral axis. Although individual blastomeres generate discrete clones of cells, the appearance and exact locations of these clones are variable with respect to the embryonic dorsoventral and bilateral axes. The eight animal mesomeres generate anterior (animal) ectoderm of the larva, which includes the apical organ; however, contributions to the apical organ were found to be variable as only a subset of the animal blastomeres end up contributing to its formation and this varies from embryo to embryo. The macromeres generate posterior larval ectoderm, and the vegetal micromeres form all the internal, endomesodermal tissues. These blastomere contributions are similar to those found during development of the only other hemichordate studied, the direct-developing enteropneust, S. kowalevskii. Finally, isolated blastomeres prepared at either the two- or the four-cell stage are capable of forming normal-appearing, miniature tornaria larvae. These findings indicate that the fates of these

  9. Deuterostome evolution: early development in the enteropneust hemichordate, Ptychodera flava.

    PubMed

    Henry, J Q; Tagawa, K; Martindale, M Q

    2001-01-01

    Molecular and morphological comparisons indicate that the Echinodermata and Hemichordata represent closely related sister-phyla within the Deuterostomia. Much less is known about the development of the hemichordates compared to other deuterostomes. For the first time, cell lineage analyses have been carried out for an indirect-developing representative of the enteropneust hemichordates, Ptychodera flava. Single blastomeres were iontophoretically labeled with Dil at the 2- through 16-cell stages, and their fates followed through development to the tornaria larval stage. The early cleavage pattern of P. flava is similar to that of the direct-developing hemichordate, Saccoglossus kowalevskii, as well as that displayed by indirect-developing echinoids. The 16-celled embryo contains eight animal "mesomeres," four slightly larger "macromeres," and four somewhat smaller vegetal "micromeres." The first cleavage plane was not found to bear one specific relationship relative to the larval dorsoventral axis. Although individual blastomeres generate discrete clones of cells, the appearance and exact locations of these clones are variable with respect to the embryonic dorsoventral and bilateral axes. The eight animal mesomeres generate anterior (animal) ectoderm of the larva, which includes the apical organ; however, contributions to the apical organ were found to be variable as only a subset of the animal blastomeres end up contributing to its formation and this varies from embryo to embryo. The macromeres generate posterior larval ectoderm, and the vegetal micromeres form all the internal, endomesodermal tissues. These blastomere contributions are similar to those found during development of the only other hemichordate studied, the direct-developing enteropneust, S. kowalevskii. Finally, isolated blastomeres prepared at either the two- or the four-cell stage are capable of forming normal-appearing, miniature tornaria larvae. These findings indicate that the fates of these

  10. Dual effects of fluoxetine on mouse early embryonic development

    SciTech Connect

    Kim, Chang-Woon; Choe, Changyong; Kim, Eun-Jin; Lee, Jae-Ik; Yoon, Sook-Young; Cho, Young-Woo; Han, Sunkyu; Tak, Hyun-Min; Han, Jaehee; Kang, Dawon

    2012-11-15

    Fluoxetine, a selective serotonin reuptake inhibitor, regulates a variety of physiological processes, such as cell proliferation and apoptosis, in mammalian cells. Little is known about the role of fluoxetine in early embryonic development. This study was undertaken to investigate the effect of fluoxetine during mouse early embryonic development. Late two-cell stage embryos (2-cells) were cultured in the presence of various concentrations of fluoxetine (1 to 50 μM) for different durations. When late 2-cells were incubated with 5 μM fluoxetine for 6 h, the percentage that developed into blastocysts increased compared to the control value. However, late 2-cells exposed to fluoxetine (5 μM) over 24 h showed a reduction in blastocyst formation. The addition of fluoxetine (5 μM) together with KN93 or KN62 (calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitors) failed to increase blastocyst formation. Fluoxetine treatment inhibited TREK-1 and TREK-2, members of the two-pore domain K{sup +} channel family expressed in mouse embryos, activities, indicating that fluoxetine-induced membrane depolarization in late 2-cells might have resulted from TREK inhibition. In addition, long-term exposure to fluoxetine altered the TREK mRNA expression levels. Furthermore, injection of siRNA targeting TREKs significantly decreased blastocyst formation by ∼ 30% compared to injection of scrambled siRNA. Long-term exposure of fluoxetine had no effect on blastocyst formation of TREK deficient embryos. These results indicate that low-dose and short-term exposures of late 2-cells to fluoxetine probably increase blastocyst formation through activation of CaMKII-dependent signal transduction pathways, whereas long-term exposure decreases mouse early embryonic development through inhibition of TREK channel gating. Highlights: ► Short-term exposure of 2-cells to fluoxetine enhances mouse blastocyst formation. ► The enhancive effect of fluoxetine is resulted from Ca

  11. Long-Term Maternal Effects of Early Childhood Intervention: Findings from the Infant Health and Development Program (IHDP)

    ERIC Educational Resources Information Center

    Martin, Anne; Brooks-Gunn, Jeanne; Klebanov, Pamela; Buka, Stephen L.; McCormick, Marie C.

    2008-01-01

    The Infant Health and Development Program (IHDP) was a randomized clinical trial of early intervention services for low birth weight, premature infants. Mothers and infants received services for 3 years beginning at neonatal discharge. At the intervention's conclusion, mothers in the intervention group who had lighter (less than 2001 g) birth…

  12. Early Decision-Making in Drug Development: The Potential Role of Pharmaco-EEG and Pharmaco-Sleep.

    PubMed

    Wilson, Frederick J; Danjou, Philippe

    2015-01-01

    The pharmaceutical industry has been suffering from low clinical success rates of new drugs for some time with particularly high attrition in early clinical development, especially for drugs aimed at central targets. Both pharmaco-electroencephalography (EEG) and pharmaco-sleep, along with other biomarker techniques, have significant potential to assist with this problem by enabling early decisions to be made about the likelihood of a compound proving successful in the clinic. This paper discusses the role and points of application of biomarker techniques in early drug development. It proposes a framework for the use of pharmaco-EEG and pharmaco-sleep in drug development that (i) relies on the combination of preclinical data and an understanding of translatability to generate robust hypotheses for testing in early clinical studies and (ii) is backed up by a clear decision-making process. The areas that need further development before this framework can be put fully into practice are discussed, along with some possible routes by which this could be achieved through precompetitive co-operation within the industry.

  13. 78 FR 9396 - Draft Guidance for Industry on Alzheimer's Disease: Developing Drugs for the Treatment of Early...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-08

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Alzheimer's Disease... a draft guidance for industry entitled ``Alzheimer's Disease: Developing Drugs for the Treatment of... demonstrate efficacy in clinical trials in patients in the early stages of Alzheimer's disease that...

  14. Biomarkers for Early Detection of Clinically Relevant Prostate Cancer: A Multi-Institutional Validation Trial

    DTIC Science & Technology

    2015-10-01

    diagnosed with early stage prostate cancer a critical need exists for molecular assays that accurately distinguish aggressive prostate cancer from those...their ability to distinguish aggressive cancers from indolent cancers. We have established agreements with three commercial companies to analyze their...in clinical practice to predict aggressive disease. The accuracy of each biomarker for predicting short- and long-term progression will be

  15. Outcomes of laparoscopic fertility-sparing surgery in clinically early-stage epithelial ovarian cancer

    PubMed Central

    Park, Jin-Young; Lee, Yoo-Young; Kim, Tae-Joong; Kim, Byoung-Gie; Bae, Duk-Soo

    2016-01-01

    Objective Fertility-sparing surgery (FSS) is becoming an important technique in the surgical management of young women with early-stage epithelial ovarian cancer (EOC). We retrospectively evaluated the outcome of laparoscopic FSS in presumed clinically early-stage EOC. Methods We retrospectively searched databases of patients who received laparoscopic FSS for EOC between January 1999 and December 2012 at Samsung Medical Center. Women aged ≤40 years were included. The perioperative, oncological, and obstetric outcomes of these patients were evaluated. Results A total of 18 patients was evaluated. The median age of the patients was 33.5 years (range, 14 to 40 years). The number of patients with clinically stage IA and IC was 6 (33.3%) and 12 (66.7%), respectively. There were 7 (38.9%), 5 (27.8%), 3 (16.7%), and 3 patients (16.7%) with mucinous, endometrioid, clear cell, and serous tumor types, respectively. Complete surgical staging to preserve the uterus and one ovary with adnexa was performed in 4 patients (22.2%). Two out of them were upstaged to The International Federation of Gynecology and Obstetrics stage IIIA1. During the median follow-up of 47.3 months (range, 11.5 to 195.3 months), there were no perioperative or long term surgical complications. Four women (22.2%) conceived after their respective ovarian cancer treatments. Three (16.7%) of them completed full-term delivery and one is expecting a baby. One patient had disease recurrence. No patient died of the disease. Conclusion FSS in young patients with presumed clinically early-stage EOC is a challenging and cautious procedure. Further studies are urgent to determine the safety and feasibility of laparoscopic FSS in young patients with presumed clinically early-stage EOC. PMID:26768783

  16. Early intestinal Bacteroides fragilis colonisation and development of asthma

    PubMed Central

    Vael, Carl; Nelen, Vera; Verhulst, Stijn L; Goossens, Herman; Desager, Kristine N

    2008-01-01

    Background The 'hygiene hypothesis' suggests that early exposure to microbes can be protective against atopic disease. The intestinal microbial flora could operate as an important postnatal regulator of the Th1/Th2 balance. The aim of the study was to investigate the association between early intestinal colonisation and the development of asthma in the first 3 years of life. Methods In a prospective birth cohort, 117 children were classified according to the Asthma Predictive Index. A positive index included wheezing during the first three years of life combined with eczema in the child in the first years of life or with a parental history of asthma. A faecal sample was taken at the age of 3 weeks and cultured on selective media. Results Asthma Predictive Index was positive in 26/117 (22%) of the children. The prevalence of colonisation with Bacteroides fragilis was higher at 3 weeks in index+ compared to index- children (64% vs. 34% p < 0,05). Bacteroides fragilis and Total Anaerobes counts at 3 weeks were significantly higher in children with a positive index as compared with those without. After adjusting for confounders a positive association was found between Bacteroides fragilis colonisation and Asthma Predictive Index (odds ratio: 4,4; confidence interval: 1,7 – 11,8). Conclusion Bacteroides fragilis colonisation at age 3 weeks is an early indicator of possible asthma later in life. This study could provide the means for more accurate targeting of treatment and prevention and thus more effective and better controlled modulation of the microbial milieu. PMID:18822123

  17. Metabolic gene profile in early human fetal heart development.

    PubMed

    Iruretagoyena, J I; Davis, W; Bird, C; Olsen, J; Radue, R; Teo Broman, A; Kendziorski, C; Splinter BonDurant, S; Golos, T; Bird, I; Shah, D

    2014-07-01

    The primitive cardiac tube starts beating 6-8 weeks post fertilization in the developing embryo. In order to describe normal cardiac development during late first and early second trimester in human fetuses this study used microarray and pathways analysis and created a corresponding 'normal' database. Fourteen fetal hearts from human fetuses between 10 and 18 weeks of gestational age (GA) were prospectively collected at the time of elective termination of pregnancy. RNA from recovered tissues was used for transcriptome analysis with Affymetrix 1.0 ST microarray chip. From the amassed data we investigated differences in cardiac development within the 10-18 GA period dividing the sample by GA in three groups: 10-12 (H1), 13-15 (H2) and 16-18 (H3) weeks. A fold change of 2 or above adjusted for a false discovery rate of 5% was used as initial cutoff to determine differential gene expression for individual genes. Test for enrichment to identify functional groups was carried out using the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Array analysis correctly identified the cardiac specific genes, and transcripts reported to be differentially expressed were confirmed by qRT-PCR. Single transcript and Ontology analysis showed first trimester heart expression of myosin-related genes to be up-regulated >5-fold compared with second trimester heart. In contrast the second trimester hearts showed further gestation-related increases in many genes involved in energy production and cardiac remodeling. In conclusion, fetal heart development during the first trimester was dominated by heart-specific genes coding for myocardial development and differentiation. During the second trimester, transcripts related to energy generation and cardiomyocyte communication for contractile coordination/proliferation were more dominant. Transcripts related to fatty acid metabolism can be seen as early as 10 weeks and clearly increase as the heart matures. Retinol

  18. Mining Disease Risk Patterns from Nationwide Clinical Databases for the Assessment of Early Rheumatoid Arthritis Risk

    PubMed Central

    Chin, Chu Yu; Weng, Meng Yu; Lin, Tzu Chieh; Cheng, Shyr Yuan; Yang, Yea Huei Kao; Tseng, Vincent S.

    2015-01-01

    Rheumatoid arthritis (RA) is a chronic autoimmune rheumatic disease that can cause painful swelling in the joint lining, morning stiffness, and joint deformation/destruction. These symptoms decrease both quality of life and life expectancy. However, if RA can be diagnosed in the early stages, it can be controlled with pharmacotherapy. Although many studies have examined the possibility of early assessment and diagnosis, few have considered the relationship between significant risk factors and the early assessment of RA. In this paper, we present a novel framework for early RA assessment that utilizes data preprocessing, risk pattern mining, validation, and analysis. Under our proposed framework, two risk patterns can be discovered. Type I refers to well-known risk patterns that have been identified by existing studies, whereas Type II denotes unknown relationship risk patterns that have rarely or never been reported in the literature. These Type II patterns are very valuable in supporting novel hypotheses in clinical trials of RA, and constitute the main contribution of this work. To ensure the robustness of our experimental evaluation, we use a nationwide clinical database containing information on 1,314 RA-diagnosed patients over a 12-year follow-up period (1997–2008) and 965,279 non-RA patients. Our proposed framework is employed on this large-scale population-based dataset, and is shown to effectively discover rich RA risk patterns. These patterns may assist physicians in patient assessment, and enhance opportunities for early detection of RA. The proposed framework is broadly applicable to the mining of risk patterns for major disease assessments. This enables the identification of early risk patterns that are significantly associated with a target disease. PMID:25875441

  19. Mining disease risk patterns from nationwide clinical databases for the assessment of early rheumatoid arthritis risk.

    PubMed

    Chin, Chu Yu; Weng, Meng Yu; Lin, Tzu Chieh; Cheng, Shyr Yuan; Yang, Yea Huei Kao; Tseng, Vincent S

    2015-01-01

    Rheumatoid arthritis (RA) is a chronic autoimmune rheumatic disease that can cause painful swelling in the joint lining, morning stiffness, and joint deformation/destruction. These symptoms decrease both quality of life and life expectancy. However, if RA can be diagnosed in the early stages, it can be controlled with pharmacotherapy. Although many studies have examined the possibility of early assessment and diagnosis, few have considered the relationship between significant risk factors and the early assessment of RA. In this paper, we present a novel framework for early RA assessment that utilizes data preprocessing, risk pattern mining, validation, and analysis. Under our proposed framework, two risk patterns can be discovered. Type I refers to well-known risk patterns that have been identified by existing studies, whereas Type II denotes unknown relationship risk patterns that have rarely or never been reported in the literature. These Type II patterns are very valuable in supporting novel hypotheses in clinical trials of RA, and constitute the main contribution of this work. To ensure the robustness of our experimental evaluation, we use a nationwide clinical database containing information on 1,314 RA-diagnosed patients over a 12-year follow-up period (1997-2008) and 965,279 non-RA patients. Our proposed framework is employed on this large-scale population-based dataset, and is shown to effectively discover rich RA risk patterns. These patterns may assist physicians in patient assessment, and enhance opportunities for early detection of RA. The proposed framework is broadly applicable to the mining of risk patterns for major disease assessments. This enables the identification of early risk patterns that are significantly associated with a target disease.

  20. Clinical efficacy of early loading versus conventional loading of dental implants

    PubMed Central

    Zhu, Yanfei; Zheng, Xinyi; Zeng, Guanqi; Xu, Yi; Qu, Xinhua; Zhu, Min; Lu, Eryi

    2015-01-01

    The aim of this study was to determine the clinical differences between early and conventional loading protocols for dental implants. A comprehensive search of the Medline, Embase, and OVID databases for studies published through January 10, 2015 was conducted. Fourteen studies were included in our analysis. We found that early loading imposed a significantly higher risk of implant failure than did conventional loading (risk ratio = 2.09, 95% confidence interval [CI] [1.18, 3.69], P = 0.01), while no significant differences between the methods were found with regards to the marginal bone loss (weighted mean differences [WMD] = 0.11, 95% CI [−0.07, 0.28], P = 0.23), periotest value (WMD = 0.02, 95% CI [−0.83, 0.87], P = 0.96), or implant stability quotient (WMD = 0.79, 95% CI [−0.03, 1.62], P = 0.06). As for the health status of the peri-implant tissue, conventionally loaded implants demonstrated better performance than did early loaded implants. Subgroup analyses demonstrated that the sample size, time of publication, loading definition, implant position, extent, and restoration type influenced the results. Although early implant loading is convenient and comfortable for patients, this method still cannot achieve the same clinical outcomes as the conventional loading method. PMID:26542097

  1. Clinical teaching improvement: past and future for faculty development.

    PubMed

    Skeff, K M; Stratos, G A; Mygdal, W K; DeWitt, T G; Manfred, L M; Quirk, M E; Roberts, K B; Greenberg, L W

    1997-04-01

    Faculty development programs have focused on the improvement of clinical teaching for several decades, resulting in a wide variety of programs for clinical teachers. With the current constraints on medical education, faculty developers must reexamine prior work and decide on future directions. This article discusses 1) the rationale for providing faculty development for clinical teachers, 2) the competencies needed by clinical teachers, 3) the available programs to assist faculty to master those competencies, and 4) the evaluation methods that have been used to assess these programs. Given this background, we discuss possible future directions to advance the field.

  2. Factors in Dry Period Associated with Intramammary Infection and Subsequent Clinical Mastitis in Early Postpartum Cows

    PubMed Central

    Leelahapongsathon, Kansuda; Piroon, Tipapun; Chaisri, Wasana; Suriyasathaporn, Witaya

    2016-01-01

    The objective of this study was to determine cow characteristics and farm management factors during the dry period associated with early postparturient intramammary infection (IMI) and subsequent clinical mastitis (CM). Data were collected three times: before drying off (P1), during the dry period (P2), and 5 to 14 days after calving (P3), using questionnaires and farm investigation. Milk samples were aseptically collected for bacterial identification at P1 and P3. Factors associated with IMI and CM were analyzed using multiple logistic regression models. The final model showed that IMI in early postpartum was significantly associated with full insertion of dry cow antibiotic, dry cows in barns with a combination of tie and free stalls, body condition score (BCS) in dry period and after calving, and milk yield before drying off. For IMI cows, factors significantly associated with clinical expression of mastitis were having daily barn cleaning, teat disinfected with alcohol before administration of dry cow therapy, BCS before drying off, milk yield before drying off, and days in milk at drying off. In conclusion, both cow and farm management factors are associated with the IMI rate and subsequent expression of clinical signs of mastitis in early postpartum cows. PMID:26949960

  3. Heterogeneity of Parkinson's disease in the early clinical stages using a data driven approach

    PubMed Central

    Lewis, S; Foltynie, T; Blackwell, A; Robbins, T; Owen, A; Barker, R

    2005-01-01

    Objective: To investigate the heterogeneity of idiopathic Parkinson's disease (PD) in a data driven manner among a cohort of patients in the early clinical stages of the disease meeting established diagnostic criteria. Methods: Data on demographic, motor, mood, and cognitive measures were collected from 120 consecutive patients in the early stages of PD (Hoehn and Yahr I–III) attending a specialist PD research clinic. Statistical cluster analysis of the data allowed the existence of the patient subgroups generated to be explored. Results: The analysis revealed four main subgroups: (a) patients with a younger disease onset; (b) a tremor dominant subgroup of patients; (c) a non-tremor dominant subgroup with significant levels of cognitive impairment and mild depression; and (d) a subgroup with rapid disease progression but no cognitive impairment. Conclusions: This study complements and extends previous research by using a data driven approach to define the clinical heterogeneity of early PD. The approach adopted in this study for the identification of subgroups of patients within Parkinson's disease has important implications for generating testable hypotheses on defining the heterogeneity of this common condition and its aetiopathological basis and thus its treatment. PMID:15716523

  4. [Xenotransplantation: recent developments and futur clinical applications].

    PubMed

    Sgroi, A; Morel, P; Bühler, L

    2012-06-20

    The aim of xenotransplantation is to allow the transplantation of animal organs or cells to humans. This approach would immediately eliminate the human organ shortage that is responsible for a significant mortality of patients on the waiting list for transplantation of organs. The immune differences between pig and human induce an immediate rejection of porcine tissues by humans. This rejection has recently been partially controlled by genetic engineering of pigs, the use of new immunosuppressive drugs and encapsulation of isolated cells. However, due to the risk of transmission of animal infectious agents to humans, the WHO recommends that clinical application of xenotransplantation only takes place if adequate regulations are in place.

  5. Increased Screen Time: Implications for Early Childhood Development and Behavior.

    PubMed

    Radesky, Jenny S; Christakis, Dimitri A

    2016-10-01

    The authors review trends in adoption of new digital technologies (eg, mobile and interactive media) by families with young children (ages 0-8 years), continued use of television and video games, and the evidence for learning from digital versus hands-on play. The authors also discuss continued concerns about health and developmental/behavioral risks of excessive media use for child cognitive, language, literacy, and social-emotional development. This evidence is then applied to clinical care in terms of the screening questions providers can use, tools available to providers and parents, and changes in anticipatory guidance.

  6. Effectiveness of early clinical exposure in learning respiratory physiology among the newly entrant MBBS students

    PubMed Central

    DAS, PIYALI; BISWAS, SUBHRADEV; SINGH, RAMJI; MUKHERJEE, SANHITA; GHOSHAL, SHARMISTHA; PRAMANIK, DEBASIS

    2017-01-01

    Introduction: Early Clinical Exposure has been conceptualized to orient medical students towards actual clinical scenario and help them correlate their theoretical knowledge with real life situations in early years of MBBS courses. In the present study we explored the outcome of early clinical exposure in the context of basic science topics (Physiology) in fresh MBBS entrants and compared their performance with a conventionally taught control group. Methods: One hundred fifty voluntary students of 1st year MBBS (2015-16) batch consisted the sample of this study. They were divided into two groups through the simple random method (using computer generated random number table with roll numbers of the students). They were evaluated by MCQ (Multiple Choice Question) and OSCE (Objective Structured Clinical Examination) before and after being taught a basic Physiology topic (respiratory system) theoretically. The study group underwent clinical exposure before the post-test while the control group did not. Performance of the students was compared between the two groups by unpaired student’s t-test whereas marks of pre and post-test within the same group were compared by paired Student’s t-test. Everywhere p<0.05 was considered to be significant. Results: The marks of each group in the pre and post-tests differed significantly (P<0.05 in each case). Post-test marks were significantly greater in each group though the level of improvement was strikingly higher in the study group (p=0.01). Though there was no significant difference in pre-test marks of both groups (P=0.73), post-test marks were significantly higher in the study group (P=0.04). Among the exposed students, majority (92%) opined that ECE was a better technique being practically oriented and more interesting while some (8%) found it to be more time and energy-consuming, suitable for selective portions of basic science topics. Conclusion: Early clinical exposure may be an effective technique to supplement the

  7. Sex Differences in Clinical Features of Early, Treated Parkinson’s Disease

    PubMed Central

    Augustine, Erika F.; Pérez, Adriana; Dhall, Rohit; Umeh, Chizoba C.; Videnovic, Aleksandar; Cambi, Franca; Wills, Anne-Marie A.; Elm, Jordan J.; Zweig, Richard M.; Shulman, Lisa M.; Nance, Martha A.; Bainbridge, Jacquelyn; Suchowersky, Oksana

    2015-01-01

    Introduction To improve our understanding of sex differences in the clinical characteristics of Parkinson’s Disease, we sought to examine differences in the clinical features and disease severity of men and women with early treated Parkinson’s Disease (PD) enrolled in a large-scale clinical trial. Methods Analysis was performed of baseline data from the National Institutes of Health Exploratory Trials in Parkinson’s Disease (NET-PD) Long-term Study-1, a randomized, multi-center, double-blind, placebo-controlled study of 10 grams of oral creatine/day in individuals with early, treated PD. We compared mean age at symptom onset, age at PD diagnosis, and age at randomization between men and women using t-test statistics. Sex differences in clinical features were evaluated, including: symptoms at diagnosis (motor) and symptoms at randomization (motor, non-motor, and daily functioning). Results 1,741 participants were enrolled (62.5% male). No differences were detected in mean age at PD onset, age at PD diagnosis, age at randomization, motor symptoms, or daily functioning between men and women. Differences in non-motor symptoms were observed, with women demonstrating better performance compared to men on SCOPA-COG (Z = 5.064, p<0.0001) and Symbol Digit Modality measures (Z = 5.221, p<0.0001). Conclusions Overall, men and women did not demonstrate differences in clinical motor features early in the course of PD. However, the differences observed in non-motor cognitive symptoms suggests further assessment of the influence of sex on non-motor symptoms in later stages of PD is warranted. PMID:26171861

  8. Windows in early mammary development: critical or not?

    PubMed

    Knight, C H; Sorensen, A

    2001-09-01

    Two critical windows in mammary development have been proposed. The first arises from observations in rodents that nutrition during fetal and neonatal periods can affect mammary ductular outgrowth, subsequent proliferative activity and, eventually, tumorigenesis, that is, potentially it could have a long-term effect on pathological outcome (breast cancer) in women. The second similarly involves early diet, but in this case the outcome is phenotypic, in that dairy heifers reared too quickly during the peripubertal period subsequently show impaired udder development and reduced milk yield persisting throughout life. Most mammary development occurs during pregnancy, but this period is usually thought of only in terms of the immediate outcome for the subsequent lactation; it is not believed to be a critical window, at least in terms of lifetime mammary productivity. This review examines the evidence underlying these various claims and attempts to define the mechanisms involved, and also considers whether derangements occurring earlier in life (prenatally) could also have long-term consequences for physiological or pathological mammary development.

  9. Longitudinal development of prefrontal function during early childhood.

    PubMed

    Moriguchi, Yusuke; Hiraki, Kazuo

    2011-04-01

    This is a longitudinal study on development of prefrontal function in young children. Prefrontal areas have been observed to develop dramatically during early childhood. To elucidate this development, we gave children cognitive shifting tasks related to prefrontal function at 3 years of age (Time 1) and 4 years of age (Time 2). We then monitored developmental changes in behavioral performance and examined prefrontal activation using near infrared spectroscopy. We found that children showed better behavioral performance and significantly stronger inferior prefrontal activation at Time 2 than they did at Time 1. Moreover, we demonstrated individual differences in prefrontal activation for the same behavioral tasks. Children who performed better in tasks at Time 1 showed significant activation of the right inferior prefrontal regions at Time 1 and significant activation of the bilateral inferior prefrontal regions at Time 2. Children who showed poorer performance at Time 1 exhibited no significant inferior prefrontal activation at Time 1 but significant left inferior prefrontal activation at Time 2. These results indicate the importance of the longitudinal method to address the link between cognitive and neural development.

  10. Mechanical origins of rightward torsion in early chick brain development

    NASA Astrophysics Data System (ADS)

    Chen, Zi; Guo, Qiaohang; Dai, Eric; Taber, Larry

    2015-03-01

    During early development, the neural tube of the chick embryo undergoes a combination of progressive ventral bending and rightward torsion. This torsional deformation is one of the major organ-level left-right asymmetry events in development. Previous studies suggested that bending is mainly due to differential growth, however, the mechanism for torsion remains poorly understood. Since the heart almost always loops rightwards that the brain twists, researchers have speculated that heart looping affects the direction of brain torsion. However, direct evidence is lacking, nor is the mechanical origin of such torsion understood. In our study, experimental perturbations show that the bending and torsional deformations in the brain are coupled and that the vitelline membrane applies an external load necessary for torsion to occur. Moreover, the asymmetry of the looping heart gives rise to the chirality of the twisted brain. A computational model and a 3D printed physical model are employed to help interpret these findings. Our work clarifies the mechanical origins of brain torsion and the associated left-right asymmetry, and further reveals that the asymmetric development in one organ can induce the asymmetry of another developing organ through mechanics, reminiscent of D'Arcy Thompson's view of biological form as ``diagram of forces''. Z.C. is supported by the Society in Science - Branco Weiss fellowship, administered by ETH Zurich. L.A.T acknowledges the support from NIH Grants R01 GM075200 and R01 NS070918.

  11. Early structural development of the Okavango rift zone, NW Botswana

    NASA Astrophysics Data System (ADS)

    Kinabo, B. D.; Atekwana, E. A.; Hogan, J. P.; Modisi, M. P.; Wheaton, D. D.; Kampunzu, A. B.

    2007-06-01

    Aeromagnetic and gravity data collected across the Okavango rift zone, northwest Botswana are used to map the distribution of faults, provide insights into the two-dimensional shallow subsurface geometry of the rift, and evaluate models for basin formation as well as the role of pre-existing basement fabric on the development of this nascent continental rift. The structural fabric (fold axes and foliation) of the Proterozoic basement terrane is clearly imaged on both gravity and magnetic maps. The strike of rift-related faults (030-050° in the north and 060-070° in the south) parallels fold axes and the prominent foliation directions of the basement rocks. These pre-existing fabrics and structures represent a significant strength anisotropy that controlled the orientation of younger brittle faults within the stress regime present during initiation of this rift. Northwest dipping faults consistently exhibit greater displacements than southeast dipping faults, suggesting a developing half-graben geometry for this rift zone. However, the absence of fully developed half-grabens along this rift zone suggests that the border fault system is not fully developed consistent with the infancy of rifting. Three en-echelon northeast trending depocenters coincide with structural grabens that define the Okavango rift zone. Along the southeastern boundary of the rift, developing border faults define a 50 km wide zone of subsidence within a larger 150 km wide zone of extension forming a rift-in-rift structure. We infer from this observation that the localization of strain resulting from extension is occurring mostly along the southeastern boundary where the border fault system is being initiated, underscoring the important role of border faults in accommodating strain even during this early stage of rift development. We conclude that incipient rift zones may provide critical insights into the development of rift basins during the earliest stages of continental rifting.

  12. [Clinical nursing manpower: development and future prospects].

    PubMed

    Lin, Chiou-Fen; Kao, Ching-Chiu

    2014-04-01

    The significant changes in nursing manpower utilization in Taiwan over the past two decades are due in large part to the implementation of the National Health Insurance program and the rising need for long-term care. The changes have impacted clinical nursing manpower utilization in two important ways. Firstly, there has been a substantial increase in overall demand for nursing manpower. In particular, the need for clinical nurses has nearly quadrupled during this time period. Secondly, the level of difficulty involved in patient care has risen dramatically, with factors including increased disease severity and increased care quality expectations, among others. These changes, coupled with demands on nursing manpower imposed from other sectors, underpin and further exacerbate the problem of nursing manpower shortages throughout the healthcare system. To raise the quality of the nursing work environment, the Ministry of Health and Welfare (MOHW) brought together Taiwan's key professional nursing organizations to promote 10 care-reform strategies, establish the nursing-aid manpower system, and create the nursing classification system as an approach to effectively attract nurses to take positions in the medical system.

  13. Teaching Skills to Promote Clinical Reasoning in Early Basic Science Courses

    ERIC Educational Resources Information Center

    Elizondo-Omana, Rodrigo Enrique; Morales-Gomez, Jesus Alberto; Morquecho-Espinoza, Orlando; Hinojosa-Amaya, Jose Miguel; Villarreal-Silva, Eliud Enrique; Garcia-Rodriguez, Maria de los Angeles; Guzman-Lopez, Santos

    2010-01-01

    Basic and superior reasoning skills are woven into the clinical reasoning process just as they are used to solve any problem. As clinical reasoning is the central competence of medical education, development of these reasoning skills should occur throughout the undergraduate medical curriculum. The authors describe here a method of teaching…

  14. Investing in the foundation of sustainable development: pathways to scale up for early childhood development.

    PubMed

    Richter, Linda M; Daelmans, Bernadette; Lombardi, Joan; Heymann, Jody; Boo, Florencia Lopez; Behrman, Jere R; Lu, Chunling; Lucas, Jane E; Perez-Escamilla, Rafael; Dua, Tarun; Bhutta, Zulfiqar A; Stenberg, Karin; Gertler, Paul; Darmstadt, Gary L

    2017-01-07

    Building on long-term benefits of early intervention (Paper 2 of this Series) and increasing commitment to early childhood development (Paper 1 of this Series), scaled up support for the youngest children is essential to improving health, human capital, and wellbeing across the life course. In this third paper, new analyses show that the burden of poor development is higher than estimated, taking into account additional risk factors. National programmes are needed. Greater political prioritisation is core to scale-up, as are policies that afford families time and financial resources to provide nurturing care for young children. Effective and feasible programmes to support early child development are now available. All sectors, particularly education, and social and child protection, must play a role to meet the holistic needs of young children. However, health provides a critical starting point for scaling up, given its reach to pregnant women, families, and young children. Starting at conception, interventions to promote nurturing care can feasibly build on existing health and nutrition services at limited additional cost. Failure to scale up has severe personal and social consequences. Children at elevated risk for compromised development due to stunting and poverty are likely to forgo about a quarter of average adult income per year, and the cost of inaction to gross domestic product can be double what some countries currently spend on health. Services and interventions to support early childhood development are essential to realising the vision of the Sustainable Development Goals.

  15. Late Cretaceous-Early Palaeogene tectonic development of SE Asia

    NASA Astrophysics Data System (ADS)

    Morley, C. K.

    2012-10-01

    The Late Cretaceous-Early Palaeogene history of the continental core of SE Asia (Sundaland) marks the time prior to collision of India with Asia when SE Asia, from the Tethys in the west to the Palaeo-Pacific in the east, lay in the upper plate of subduction zones. In Myanmar and Sumatra, subduction was interrupted in the Aptian-Albian by a phase of arc accretion (Woyla and Mawgyi arcs) and in Java, eastern Borneo and Western Sulawesi by collision of continental fragments rifted from northern Australia. Subsequent resumption of subduction in the Myanmar-Thailand sector explains: 1) early creation of oceanic crust in the Andaman Sea in a supra-subduction zone setting ~ 95 Ma, 2) the belt of granite plutons of Late Cretaceous-Early Palaeogene age (starting ~ 88 Ma) in western Thailand and central Myanmar, and 3) amphibolite grade metamorphism between 70 and 80 Ma seen in gneissic outcrops in western and central Thailand, and 4) accretionary prism development in the Western Belt of Myanmar, until glancing collision with the NE corner of Greater India promoted ophiolite obduction, deformation and exhumation of marine sediments in the early Palaeogene. The Ranong strike-slip fault and other less well documented faults, were episodically active during the Late Cretaceous-Palaeogene time. N to NW directed subduction of the Palaeo-Pacific ocean below Southern China, Vietnam and Borneo created a major magmatic arc, associated with rift basins, metamorphic core complexes and strike-slip deformation which continued into the Late Cretaceous. The origin and timing of termination of subduction has recently been explained by collision of a large Luconia continental fragment either during the Late Cretaceous or Palaeogene. Evidence for such a collision is absent from the South China Sea well and seismic reflection record and here collision is discounted. Instead relocation of the subducting margin further west, possibly in response of back-arc extension (which created the Proto

  16. Improving Latino Children's Early Language and Literacy Development: Key Features of Early Childhood Education within Family Literacy Programmes

    ERIC Educational Resources Information Center

    Jung, Youngok; Zuniga, Stephen; Howes, Carollee; Jeon, Hyun-Joo; Parrish, Deborah; Quick, Heather; Manship, Karen; Hauser, Alison

    2016-01-01

    Noting the lack of research on how early childhood education (ECE) programmes within family literacy programmes influence Latino children's early language and literacy development, this study examined key features of ECE programmes, specifically teacher-child interactions and child engagement in language and literacy activities and how these…

  17. Exploring Parental Involvement in Early Years Education in China: Development and Validation of the Chinese Early Parental Involvement Scale (CEPIS)

    ERIC Educational Resources Information Center

    Lau, Eva Yi Hung; Li, Hui; Rao, Nirmala

    2012-01-01

    This study developed and validated an instrument, the Chinese Early Parental Involvement Scale (CEPIS), that can be widely used in both local and international contexts to assess Chinese parental involvement in early childhood education. The study was carried out in two stages: (1) focus group interviews were conducted with 41 teachers and 35…

  18. Ethnic Group Differences in Early Head Start Parents Parenting Beliefs and Practices and Links to Children's Early Cognitive Development

    ERIC Educational Resources Information Center

    Keels, Micere

    2009-01-01

    Data from the Early Head Start Research and Evaluation study were used to examine the extent to which several factors mediate between- and within-ethnic-group differences in parenting beliefs and behaviors, and children's early cognitive development (analysis sample of 1198 families). The findings indicate that Hispanic-, European-, and…

  19. Documenting with Early Childhood Education Teachers: Pedagogical Documentation as a Tool for Developing Early Childhood Pedagogy and Practises

    ERIC Educational Resources Information Center

    Rintakorpi, Kati

    2016-01-01

    The Finnish social pedagogical curriculum for early childhood education directs early childhood teachers to use documentation to assess and develop pedagogy and practise. This empirical study examines the challenges and benefits a group of Finnish preschool teachers experienced when they learned to document their work. Although the idea of…

  20. Nuclear lamins during gametogenesis, fertilization and early development

    NASA Technical Reports Server (NTRS)

    Maul, G. G.; Schatten, G.

    1986-01-01

    The distribution of lamins (described by Gerace, 1978, as major proteins of nuclear envelope) during gametogenesis, fertilization, and early development was investigated in germ cells of a mouse (Mus musculus), an echinoderm (Lytechinus variegatus), and the surf clam (Spisula solidissima) was investigated in order to determine whether the differences detected could be correlated with differences in the function of cells in these stages of the germ cells. In order to monitor the behavior of lamins, the gametes and embryos were labeled with antibodies to lamins A, C, and B extracted from autoimmune sera of patients with scleroderma and Lupus erythematosus. Results indicated that lamin B could be identified in nuclear envelopes on only those nuclei where chromatin is attached and where RNA synthesis takes place.

  1. Early development of ceramic fiber insulation for the Space Shuttle

    NASA Technical Reports Server (NTRS)

    Buckley, J. D.; Strouhal, G.; Gangler, J. J.

    1981-01-01

    The evolution of reusable surface insulation is described, with attention to the mullite and other aluminosilicates, zirconia, and silicon carbide-coated carbon compositions experimented with in the late 1960s and early 1970s. Evaluation and development concentrated in this period on such aspects of design and material properties as cold soak performance, attachment, shock impingement, surface coating cracks, and tile gap design and heating. In addressing the central problem of heat-shield thermal conductivity, it was found that for a given density, silica fibers had a lower conductivity than those of mullite. This was due to the one-micron, as opposed to 4.7-micron, diameter of the silica fibers, which resulted in smaller pores and therefore less convective and radiative heat transfer. Attention is also given to tile coating materials and the high-temperature processes by which they were applied.

  2. Roles of Pel and Psl in very early biofilm development

    NASA Astrophysics Data System (ADS)

    Cooley, B. J.; Thatcher, Travis; L'Her, Guillaume; Reed, Erin; Stuart, Jamie; Kissinger, April; Gordon, Vernita

    2012-02-01

    Biofilms are dynamic, multicellular communities of unicellular organisms. Biofilms cause many chronic infections; an important case is the opportunistic human pathogen Pseudomonas aeruginosa. Bacteria in biofilms produce an extracellular matrix that binds bacteria to each other and to a surface. The two primary extracellular matrix components produced by P. aeruginosa are the polysaccharides Pel and Psl. Here we examine the roles of Pel and Psl in the very early stages of biofilm development, just after initial surface attachment. We use high-throughput automated tracking and analysis to compare wild-type bacteria with mutants incapable of producing Pel, Psl, or both. We examine motion on a surface as well as inter-bacterial interactions. These results quantify the unique roles played by Pel and Psl and show an unexpected relationship between Pel expression and adhesion to a surface.

  3. Early stopping in clinical trials and epidemiologic studies for "futility": conditional power versus sequential analysis.

    PubMed

    van der Tweel, Ingeborg; van Noord, Paulus A H

    2003-07-01

    Early stopping of a clinical trial is well accepted when there is enough evidence for a significant effect. However, during the course of a trial, there can be reasons to consider early termination for "futility." In epidemiologic studies, costly or destructive laboratory tests or slow case accrual can make it desirable to stop a study early for reasons of efficiency. Estimation of the conditional power (CP) is proposed as a decision tool to stop a study early or to continue it. We consider the disadvantages of this method. We propose (group) sequential continuation of the trial or study as a less arbitrary strategy. We re-analyzed two data sets from the literature to illustrate the advantages of a sequential approach. We conclude that (group) sequential analyses have several advantages over CP. More studies should consider a sequential design and analysis to enable early stopping when enough evidence has accumulated to conclude a lack of the expected effect. Such a strategy can save valuable resources for more promising hypotheses.

  4. Clinical, pathologic, and molecular features of early-onset colorectal carcinoma.

    PubMed

    Yantiss, Rhonda K; Goodarzi, Mahmoud; Zhou, Xi K; Rennert, Hanna; Pirog, Edyta C; Banner, Barbara F; Chen, Yao-Tseng

    2009-04-01

    The incidence of colorectal carcinoma has increased among patients <40 years of age for unclear reasons. In this study, we describe the clinical, pathologic, and molecular features of colorectal carcinomas that developed in young patients. We compiled a study group of 24 patients <40 years of age with colorectal carcinoma, and 45 patients > or =40 years of age served as controls. Cases were evaluated for clinical risk factors of malignancy and pathologic features predictive of outcome. The tumors were immunohistochemically stained for O6-methylguanine methyltransferase, MLH-1, MSH-2, MSH-6, beta-catenin, chemokine (C-X-C motif) receptor 4, epidermal growth factor receptor, TP53, p16, survivin, and alpha-methylacyl-CoA racemase; assessed for microsatellite instability and mutations in beta-catenin, APC, EGFR, PIK3CA, KRAS, and BRAF; evaluated for micro-RNA expression (miR-21, miR-20a, miR-183, miR-192, miR-145, miR-106a, miR-181b, and miR-203); and examined for evidence of human papillomavirus infection. One study patient each had ulcerative colitis and hereditary nonpolyposis colorectal cancer. Ninety-two percent of tumors from young patients occurred in the distal colon (P=0.006), particularly the rectum (58%, P=0.02), and 75% were stage III or IV. Tumors from young patients showed more frequent lymphovascular (81%, P=0.03) and/or venous (48%, P=0.003) invasion, an infiltrative growth pattern (81%, P=0.03), and alpha-methylacyl-CoA racemase expression (83%, P=0.02) compared with controls. Carcinomas in this group showed significantly increased expression of miR-21, miR-20a, miR-145, miR-181b, and miR-203 (P< or =0.005 for all comparisons with controls). These results indicate that early-onset carcinomas commonly show pathologic features associated with aggressive behavior. Posttranslational regulation of mRNA and subsequent protein expression may be particularly important to the development of colorectal carcinomas in young patients.

  5. Diversity. Early Developments. Volume 8, Number 1, Spring 2004

    ERIC Educational Resources Information Center

    Manuel, John

    2004-01-01

    What is it about cultural diversity that challenges early childhood programs? One factor is that children enter early childhood and early intervention programs from families with a wide range of values and cultural experiences. Sometimes those values and experiences differ from those of the teachers and caregivers in those programs. Another factor…

  6. Effective Early Learning: Mapping Diversity and Tracking Development.

    ERIC Educational Resources Information Center

    Pascal, Christine

    This paper describes and reviews the Effective Early Learning (EEL) Research Project's approach to quality evaluation and improvement in early childhood settings in the United Kingdom which focuses primarily on enhancing the effectiveness of the early learning experiences of young children. The project began work in May 1993 and is completing its…

  7. Development of an operational coastal flooding early warning system

    NASA Astrophysics Data System (ADS)

    Doong, D.-J.; Chuang, L. Z.-H.; Wu, L.-C.; Fan, Y.-M.; Kao, C. C.; Wang, J.-H.

    2012-02-01

    Coastal floods are a consistent threat to oceanfront countries, causing major human suffering and substantial economic losses. Climate change is exacerbating the problem. An early warning system is essential to mitigate the loss of life and property from coastal flooding. The purpose of this study is to develop a coastal flooding early warning system (CoFEWs) by integrating existing sea-state monitoring technology, numerical ocean forecasting models, historical database and experiences, as well as computer science. The proposed system has capability of offering data for the past, information for the present and future. The system was developed for the Taiwanese coast due to its frequent threat by typhoons. An operational system without any manual work is the basic requirement of the system. Integration of various data sources is the system kernel. Numerical ocean models play an important role within the system because they provide data for assessment of possible flooding. The regional wave model (SWAN) that nested with the large domain wave model (NWW III) is operationally set up for coastal wave forecasting, in addition to the storm surge predicted by a POM model. Data assimilation technology is incorporated for enhanced accuracy. A warning signal is presented when the storm water level that accumulated from astronomical tide, storm surge, and wave-induced run-up exceeds the alarm sea level. This warning system has been in practical use for coastal flooding damage mitigation in Taiwan for years. An example of the system operation during the Typhoon Haitung which struck Taiwan in 2005 is illustrated in this study.

  8. Production and clinical development of nanoparticles for gene delivery

    PubMed Central

    Chen, Jie; Guo, Zhaopei; Tian, Huayu; Chen, Xuesi

    2016-01-01

    Gene therapy is a promising strategy for specific treatment of numerous gene-associated human diseases by intentionally altering the gene expression in pathological cells. A successful clinical application of gene-based therapy depends on an efficient gene delivery system. Many efforts have been attempted to improve the safety and efficiency of gene-based therapies. Nanoparticles have been proved to be the most promising vehicles for clinical gene therapy due to their tunable size, shape, surface, and biological behaviors. In this review, the clinical development of nanoparticles for gene delivery will be particularly highlighted. Several promising candidates, which are closest to clinical applications, will be briefly reviewed. Then, the recent developments of nanoparticles for clinical gene therapy will be identified and summarized. Finally, the development of nanoparticles for clinical gene delivery in future will be prospected. PMID:27088105

  9. Early descriptions of acromegaly and gigantism and their historical evolution as clinical entities.

    PubMed

    Mammis, Antonios; Eloy, Jean Anderson; Liu, James K

    2010-10-01

    Giants have been a subject of fascination throughout history. Whereas descriptions of giants have existed in the lay literature for millennia, the first attempt at a medical description was published by Johannes Wier in 1567. However, it was Pierre Marie, in 1886, who established the term "acromegaly" for the first time and established a distinct clinical diagnosis with clear clinical descriptions in 2 patients with the characteristic presentation. Multiple autopsy findings revealed a consistent correlation between acromegaly and pituitary enlargement. In 1909, Harvey Cushing postulated a “hormone of growth" as the underlying pathophysiological trigger involved in pituitary hypersecretion in patients with acromegaly. This theory was supported by his observations of clinical remission in patients with acromegaly in whom he had performed hypophysectomy. In this paper, the authors present some of the early accounts of acromegaly and gigantism, and describe its historical evolution as a medical and surgical entity.

  10. Effectiveness of the Lidcombe Program for early stuttering in Australian community clinics.

    PubMed

    O'Brian, Sue; Iverach, Lisa; Jones, Mark; Onslow, Mark; Packman, Ann; Menzies, Ross

    2013-12-01

    This study explored the effectiveness of the Lidcombe Program for early stuttering in community clinics. Participants were 31 speech-language pathologists (SLPs) using the Lidcombe Program in clinics across Australia, and 57 of their young stuttering clients. Percentage of syllables stuttered (%SS) was collected 9 months after beginning treatment along with information about variables likely to influence outcomes. The mean %SS for the 57 children 9 months after starting treatment was 1.7. The most significant predictor of outcome was Lidcombe Program Trainers Consortium (LPTC) training. The children of trained SLPs (n = 19), compared to the children of untrained SLPs, took 76% more sessions to complete stage 1, but achieved 54% lower %SS scores, 9 months after starting treatment. Results suggest that outcomes for the Lidcombe Program in the general community may be comparable to those obtained in clinical trials when SLPs receive formal training and support.

  11. The SCL gene specifies haemangioblast development from early mesoderm.

    PubMed Central

    Gering, M; Rodaway, A R; Göttgens, B; Patient, R K; Green, A R

    1998-01-01

    The SCL gene encodes a basic helix-loop-helix (bHLH) transcription factor that is essential for the development of all haematopoietic lineages. SCL is also expressed in endothelial cells, but its function is not essential for specification of endothelial progenitors and the role of SCL in endothelial development is obscure. We isolated the zebrafish SCL homologue and show that it was co-expressed in early mesoderm with markers of haematopoietic, endothelial and pronephric progenitors. Ectopic expression of SCL mRNA in zebrafish embryos resulted in overproduction of common haematopoietic and endothelial precursors, perturbation of vasculogenesis and concomitant loss of pronephric duct and somitic tissue. Notochord and neural tube formation were unaffected. These results provide the first evidence that SCL specifies formation of haemangioblasts, the proposed common precursor of blood and endothelial lineages. Our data also underline the striking similarities between the role of SCL in haematopoiesis/vasculogenesis and the function of other bHLH proteins in muscle and neural development. PMID:9670018

  12. Nitric oxide (NO) and phytohormones crosstalk during early plant development.

    PubMed

    Sanz, Luis; Albertos, Pablo; Mateos, Isabel; Sánchez-Vicente, Inmaculada; Lechón, Tamara; Fernández-Marcos, María; Lorenzo, Oscar

    2015-05-01

    During the past two decades, nitric oxide (NO) has evolved from a mere gaseous free radical to become a new messenger in plant biology with an important role in a plethora of physiological processes. This molecule is involved in the regulation of plant growth and development, pathogen defence and abiotic stress responses, and in most cases this is achieved through its interaction with phytohormones. Understanding the role of plant growth regulators is essential to elucidate how plants activate the appropriate set of responses to a particular developmental stage or a particular stress. The first task to achieve this goal is the identification of molecular targets, especially those involved in the regulation of the crosstalk. The nature of NO targets in these growth and development processes and stress responses remains poorly described. Currently, the molecular mechanisms underlying the effects of NO in these processes and their interaction with other plant hormones are beginning to unravel. In this review, we made a compilation of the described interactions between NO and phytohormones during early plant developmental processes (i.e. seed dormancy and germination, hypocotyl elongation and root development).

  13. Napping facilitates word learning in early lexical development.

    PubMed

    Horváth, Klára; Myers, Kyle; Foster, Russell; Plunkett, Kim

    2015-10-01

    Little is known about the role that night-time sleep and daytime naps play in early cognitive development. Our aim was to investigate how napping affects word learning in 16-month-olds. Thirty-four typically developing infants were assigned randomly to nap and wake groups. After teaching two novel object-word pairs to infants, we tested their initial performance with an intermodal preferential looking task in which infants are expected to increase their target looking time compared to a distracter after hearing its auditory label. A second test session followed after approximately a 2-h delay. The delay contained sleep for the nap group or no sleep for the wake group. Looking behaviour was measured with an automatic eye-tracker. Vocabulary size was assessed using the Oxford Communicative Development Inventory. A significant interaction between group and session was found in preferential looking towards the target picture. The performance of the nap group increased after the nap, whereas that of the wake group did not change. The gain in performance correlated positively with the expressive vocabulary size in the nap group. These results indicate that daytime napping helps consolidate word learning in infancy.

  14. Early influences and childhood development. Does helicobacter play a role?

    PubMed

    Lee, Adrian

    2007-11-01

    In the late 1960s, Rene Dubos showed that a variety of nutritional stress in utero or in early infancy could have dramatic impact on childhood development that was irreversible. This included detectable changes in the brain. Since that time, iron deficiency anemia (IDA) has been identified as one of the major nutritional stresses that leads to permanent behavioral changes in both experimental animals and humans resulting in poorer cognitive, motor, and social-emotional function. It has been proposed that these changes play an important part in the inter-generational transmission of poverty. More recently, it is becoming clear that Helicobacter pylori causes IDA in populations on an iron-limiting diet. The main thesis of this article is that H. pylori infection may indeed have an impact on childhood development and that much more research is needed in this area as intervention via immunization or antimicrobial therapy in populations in the developing world may have major positive benefits via cure of IDA and prevention of brain damage in the young.

  15. Smart Boards to Chalkboards: Professional Development for Early Childhood Teachers in Rural East Africa

    ERIC Educational Resources Information Center

    Williams, Jeanne

    2012-01-01

    The purpose of this study was to examine the teaching strategies of early childhood development teachers in rural East Africa. Teams of early childhood educators from the United States presented professional development conferences for East African Early Childhood Development teachers during the summers of 2007 and 2008. The conferences introduced…

  16. Early changes in emotional processing as a marker of clinical response to SSRI treatment in depression.

    PubMed

    Godlewska, B R; Browning, M; Norbury, R; Cowen, P J; Harmer, C J

    2016-11-22

    Antidepressant treatment reduces behavioural and neural markers of negative emotional bias early in treatment and has been proposed as a mechanism of antidepressant drug action. Here, we provide a critical test of this hypothesis by assessing whether neural markers of early emotional processing changes predict later clinical response in depression. Thirty-five unmedicated patients with major depression took the selective serotonin re-uptake inhibitor (SSRI), escitalopram (10 mg), over 6 weeks, and were classified as responders (22 patients) versus non-responders (13 patients), based on at least a 50% reduction in symptoms by the end of treatment. The neural response to fearful and happy emotional facial expressions was assessed before and after 7 days of treatment using functional magnetic resonance imaging. Changes in the neural response to these facial cues after 7 days of escitalopram were compared in patients as a function of later clinical response. A sample of healthy controls was also assessed. At baseline, depressed patients showed greater activation to fear versus happy faces than controls in the insula and dorsal anterior cingulate. Depressed patients who went on to respond to the SSRI had a greater reduction in neural activity to fearful versus happy facial expressions after just 7 days of escitalopram across a network of regions including the anterior cingulate, insula, amygdala and thalamus. Mediation analysis confirmed that the direct effect of neural change on symptom response was not mediated by initial changes in depressive symptoms. These results support the hypothesis that early changes in emotional processing with antidepressant treatment are the basis of later clinical improvement. As such, early correction of negative bias may be a key mechanism of antidepressant drug action and a potentially useful predictor of therapeutic response.

  17. Early changes in emotional processing as a marker of clinical response to SSRI treatment in depression

    PubMed Central

    Godlewska, B R; Browning, M; Norbury, R; Cowen, P J; Harmer, C J

    2016-01-01

    Antidepressant treatment reduces behavioural and neural markers of negative emotional bias early in treatment and has been proposed as a mechanism of antidepressant drug action. Here, we provide a critical test of this hypothesis by assessing whether neural markers of early emotional processing changes predict later clinical response in depression. Thirty-five unmedicated patients with major depression took the selective serotonin re-uptake inhibitor (SSRI), escitalopram (10 mg), over 6 weeks, and were classified as responders (22 patients) versus non-responders (13 patients), based on at least a 50% reduction in symptoms by the end of treatment. The neural response to fearful and happy emotional facial expressions was assessed before and after 7 days of treatment using functional magnetic resonance imaging. Changes in the neural response to these facial cues after 7 days of escitalopram were compared in patients as a function of later clinical response. A sample of healthy controls was also assessed. At baseline, depressed patients showed greater activation to fear versus happy faces than controls in the insula and dorsal anterior cingulate. Depressed patients who went on to respond to the SSRI had a greater reduction in neural activity to fearful versus happy facial expressions after just 7 days of escitalopram across a network of regions including the anterior cingulate, insula, amygdala and thalamus. Mediation analysis confirmed that the direct effect of neural change on symptom response was not mediated by initial changes in depressive symptoms. These results support the hypothesis that early changes in emotional processing with antidepressant treatment are the basis of later clinical improvement. As such, early correction of negative bias may be a key mechanism of antidepressant drug action and a potentially useful predictor of therapeutic response. PMID:27874847

  18. Clinical benefits and impact of early use of long‐acting injectable antipsychotics for schizophrenia

    PubMed Central

    Dawson, Gail; Zummo, Jacqueline

    2015-01-01

    Abstract Aim Results from clinical trials support the use of oral antipsychotics for treatment of early or first‐episode psychosis in patients with schizophrenia. This paper will review literature on the advantages of early initiation of treatment for schizophrenia and the clinical benefits of early use of long‐acting injectable antipsychotics (LAIs). Method A comprehensive literature review was conducted to identify published literature on the use of LAIs early in the treatment of schizophrenia. Results Although there is a higher response rate to initial antipsychotic treatment for a first‐episode of schizophrenia than with subsequent antipsychotic treatment, we have not effectively addressed this issue. Poor adherence to treatment is a primary cause of relapse and rehospitalization in subsequent years and was associated with higher relapse rates resulting in devastating effects and substantial economic burden. The costs of nonadherence were estimated to be $1.48 billion. Thus, a major challenge with the treatment of schizophrenia is changing poor adherence to persistence with antipsychotic therapy. LAIs are known to be at least as effective as oral antipsychotics for treating schizophrenia, and yet are underutilized. Further, LAIs address many of the problems associated with adherence to oral therapy. Recent evidence suggests that LAIs are effective for treating first‐episode psychosis and for early initiation of treatment for schizophrenia. Conclusion Although consistent antipsychotic treatment represents a critical part of treatment, a person‐centred approach to treating schizophrenia is essential for all aspects of care, including establishing and maintaining a therapeutic alliance, strengthening shared decision‐making and adherence, and achieving long‐lasting recovery. PMID:26403538

  19. Understanding developmental pharmacodynamics: importance for drug development and clinical practice.

    PubMed

    Mulla, Hussain

    2010-08-01

    Developmental pharmacodynamics is the study of age-related maturation of the structure and function of biologic systems and how this affects response to pharmacotherapy. This may manifest as a change in the potency, efficacy, or therapeutic range of a drug. The paucity of studies exploring developmental pharmacodynamics reflects the lack of suitable juvenile animal models and the ethical and practical constraints of conducting studies in children. However, where data from animal models are available, valuable insight has been gained into how response to therapy can change through the course of development. For example, animal neurodevelopmental models have revealed that temporal differences in the maturation of norepinephrine and serotonin neurotransmitter systems may explain the lack of efficacy of some antidepressants in children. GABA(A) receptors that switch from an excitatory to inhibitory mode during early development help to explain paradoxical seizures experienced by infants after exposure to benzodiazepines. The increased sensitivity of neonates to morphine may be due to increased postnatal expression of the mu opioid receptor. An age dependency to the pharmacokinetic-pharmacodynamic relationship has also been found in some clinical studies. For example, immunosuppressive effects of ciclosporin (cyclosporine) revealed markedly enhanced sensitivity in infants compared with older children and adults. A study of sotalol in the treatment of children with supraventricular tachycardia showed that neonates exhibited a higher sensitivity towards QTc interval prolongation compared with older children. However, the data are limited and efforts to increase and establish data on developmental pharmacodynamics are necessary to achieve optimal drug therapy in children and to ensure long-term success of pediatric drug development. This requires a dual 'bottom up' (ontogeny knowledge driven) and 'top down' (pediatric pharmacokinetic-pharmacodynamic studies) approach.

  20. Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline

    PubMed Central

    Harris, Lyndsay N.; McShane, Lisa M.; Andre, Fabrice; Collyar, Deborah E.; Gonzalez-Angulo, Ana M.; Hammond, Elizabeth H.; Kuderer, Nicole M.; Liu, Minetta C.; Mennel, Robert G.; Van Poznak, Catherine; Bast, Robert C.; Hayes, Daniel F.

    2016-01-01

    Purpose To provide recommendations on appropriate use of breast tumor biomarker assay results to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer. Methods A literature search and prospectively defined study selection sought systematic reviews, meta-analyses, randomized controlled trials, prospective-retrospective studies, and prospective comparative observational studies published from 2006 through 2014. Outcomes of interest included overall survival and disease-free or recurrence-free survival. Expert panel members used informal consensus to develop evidence-based guideline recommendations. Results The literature search identified 50 relevant studies. One randomized clinical trial and 18 prospective-retrospective studies were found to have evaluated the clinical utility, as defined by the guideline, of specific biomarkers for guiding decisions on the need for adjuvant systemic therapy. No studies that met guideline criteria for clinical utility were found to guide choice of specific treatments or regimens. Recommendations In addition to estrogen and progesterone receptors and human epidermal growth factor receptor 2, the panel found sufficient evidence of clinical utility for the biomarker assays Oncotype DX, EndoPredict, PAM50, Breast Cancer Index, and urokinase plasminogen activator and plasminogen activator inhibitor type 1 in specific subgroups of breast cancer. No biomarker except for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 was found to guide choices of specific treatment regimens. Treatment decisions should also consider disease stage, comorbidities, and patient preferences. PMID:26858339

  1. Development of a clinical data warehouse from an intensive care clinical information system.

    PubMed

    de Mul, Marleen; Alons, Peter; van der Velde, Peter; Konings, Ilse; Bakker, Jan; Hazelzet, Jan

    2012-01-01

    There are relatively few institutions that have developed clinical data warehouses, containing patient data from the point of care. Because of the various care practices, data types and definitions, and the perceived incompleteness of clinical information systems, the development of a clinical data warehouse is a challenge. In order to deal with managerial and clinical information needs, as well as educational and research aims that are important in the setting of a university hospital, Erasmus Medical Center Rotterdam, The Netherlands, developed a data warehouse incrementally. In this paper we report on the in-house development of an integral part of the data warehouse specifically for the intensive care units (ICU-DWH). It was modeled using Atos Origin Metadata Frame method. The paper describes the methodology, the development process and the content of the ICU-DWH, and discusses the need for (clinical) data warehouses in intensive care.

  2. Evaluation systems for clinical governance development: a comparative study.

    PubMed

    Hooshmand, Elaheh; Tourani, Sogand; Ravaghi, Hamid; Ebrahimipour, Hossein

    2014-01-01

    Lack of scientific and confirmed researches and expert knowledge about evaluation systems for clinical governance development in Iran have made studies on different evaluation systems for clinical governance development a necessity. These studies must provide applied strategies to design criteria of implementing clinical governance for hospital's accreditation. This is a descriptive and comparative study on development of clinical governance models all over the world. Data have been gathered by reviewing related articles. Models have been studied in comprehensive review method. The evaluated models of clinical governance development were Australian, NHS, SPOCK and OPTIGOV. The final aspects extracted from these models were Responsiveness, Policies and Strategies, Organizational Structure, Allocating Resources, Education and Occupational Development, Performance Evaluation, External Evaluation, Patient Oriented Approach, Risk Management, Personnel's Participation, Information Technology, Human Resources, Research and Development, Evidence Based Medicine, Clinical Audit, Health Technology Assessment and Quality. These results are applicable for completing the present criteria which evaluating clinical governance application and provide practical framework to evaluate country's hospital on the basis of clinical governance elements.

  3. The Children Are Waiting. The Report of the Early Childhood Development Task Force.

    ERIC Educational Resources Information Center

    Early Childhood Development Task Force, New York, NY.

    The Task Force on Early Childhood Development for New York City examined early childhood services and explored the feasibility of establishing an office for early childhood services. This report assesses the effectiveness of early childhood services in meeting the needs of children and their parents and recommends changes in the quantity and…

  4. Early Implementation of QbD in Biopharmaceutical Development: A Practical Example

    PubMed Central

    Zurdo, Jesús; Arnell, Andreas; Obrezanova, Olga; Smith, Noel; Gómez de la Cuesta, Ramón; Gallagher, Thomas R. A.; Michael, Rebecca; Stallwood, Yvette; Ekblad, Caroline; Abrahmsén, Lars; Höidén-Guthenberg, Ingmarie

    2015-01-01

    In drug development, the “onus” of the low R&D efficiency has been put traditionally onto the drug discovery process (i.e., finding the right target or “binding” functionality). Here, we show that manufacturing is not only a central component of product success, but also that, by integrating manufacturing and discovery activities in a “holistic” interpretation of QbD methodologies, we could expect to increase the efficiency of the drug discovery process as a whole. In this new context, early risk assessment, using developability methodologies and computational methods in particular, can assist in reducing risks during development in a cost-effective way. We define specific areas of risk and how they can impact product quality in a broad sense, including essential aspects such as product efficacy and patient safety. Emerging industry practices around developability are introduced, including some specific examples of applications to biotherapeutics. Furthermore, we suggest some potential workflows to illustrate how developability strategies can be introduced in practical terms during early drug development in order to mitigate risks, reduce drug attrition and ultimately increase the robustness of the biopharmaceutical supply chain. Finally, we also discuss how the implementation of such methodologies could accelerate the access of new therapeutic treatments to patients in the clinic. PMID:26075248

  5. Development of clinical assessment criteria for postgraduate nursing students.

    PubMed

    Tolhurst, B G; Bonner, A

    2000-04-01

    This paper explores the development and implementation of specific criteria to determine the level of clinical performance of postgraduate nursing students during the first year of a Master of Nursing course. The authors describe two commonly used clinical skill assessment tools and identify limitations of these tools for postgraduate nursing students. As a result of these limitations, Clinical Assessment Criteria (CAC) utilising the framework of Benner (1984) was developed. Inherent within the CAC is four levels of clinical nursing performance, which enable the nurse teacher and student to monitor the progression from novice to proficient levels of practice within a specialty area. Following a successful pilot study, the CAC was incorporated into clinical assessments in nine specialty postgraduate courses. Furthermore, the framework developed for the CAC can also be integrated into a variety of professional development domains.

  6. On developing a clinical sense of self.

    PubMed

    Lerner, Paul M

    2005-02-01

    It was Donald Winnicott who first described the mutual impact of mother and infant on each one's developing sense of self. It is my experience that something of the same occurs in the patient-clinician relationship. As the patient's sense of self evolves in the therapeutic relationship, the therapist's professional sense of self also develops in the context of this relationship. Herein, I describe a case in which I both assessed and treated a patient and recognized later the deep impact the experience had on my professional sense of self.

  7. Developing a clinical academic career pathway for nursing.

    PubMed

    Coombs, Maureen; Latter, Sue; Richardson, Alison

    Since the publication of the UK Clinical Research Collaboration's (UKRC, 2007) recommendations on careers in clinical research, interest has grown in the concept of clinical academic nursing careers, with increased debate on how such roles might be developed and sustained (Department of Health, 2012). To embed clinical academic nursing roles in the NHS and universities, a clear understanding and appreciation of the contribution that such posts might make to organisational objectives and outcomes must be developed. This paper outlines an initiative to define the potential practice and research contribution of clinical academic roles through setting out role descriptors. This exercise was based on our experience of a clinical academic career initiative at the University of Southampton run in partnership with NHS organisations. Role descriptors were developed by a group of service providers, academics and two clinical academic award-holders from the local programme. This paper outlines clinical academic roles from novice to professor and describes examples of role descriptors at the different levels of a career pathway. These descriptors are informed by clinical academic posts in place at Southampton as well as others at the planning stage. Understanding the nature of clinical academic posts and the contribution that these roles can make to healthcare will enable them to become embedded into organisational structures and career pathways.

  8. The Development of Emotional and Behavioral Control in Early Childhood: Heterotypic Continuity and Relations to Early School Adjustment

    PubMed Central

    Chang, Hyein; Shaw, Daniel S; Cheong, JeeWon

    2015-01-01

    We examined heterotypic continuity of emotional and behavioral control (EBC) across early childhood and related early manifestations of EBC to children’s school adjustment in 310 low-income, ethnically diverse boys. Multiple informants and methods were used to measure different indicators of EBC at 18, 24, 42, and 60 months, which were chosen to reflect salient regulatory challenges children face across development. Teachers rated boys’ externalizing and internalizing behaviors, and social skills at 72 months. Results indicated a modest degree of heterotypic continuity of EBC, with different constructs of EBC associated between adjacent time points and, in some instances, across more distant time points. Further, children who had struggled with early EBC demonstrated higher externalizing problems and lower social skills in school. Findings suggest that early deficits in EBC may be a target for early identification and prevention, as they may forecast continued difficulty in later-developing EBC skills and socioemotional problems. PMID:26550611

  9. Preschoolers Know, but How Do They Know? Developing a Framework for Early Epistemology Development

    ERIC Educational Resources Information Center

    Winsor, Denise L.; Blake, Sally

    2009-01-01

    Two areas that are lacking for the purpose of training high-quality preschool teachers; and constructing developmentally appropriate learning standards and curriculum for preschool children are awareness of early epistemic development (beliefs about knowledge and knowing) and understanding preschoolers' cognitive processes during epistemic…

  10. Androgen Receptor Expression in Early Triple-Negative Breast Cancer: Clinical Significance and Prognostic Associations

    PubMed Central

    Pistelli, Mirco; Caramanti, Miriam; Biscotti, Tommasina; Santinelli, Alfredo; Pagliacci, Alessandra; De Lisa, Mariagrazia; Ballatore, Zelmira; Ridolfi, Francesca; Maccaroni, Elena; Bracci, Raffaella; Berardi, Rossana; Battelli, Nicola; Cascinu, Stefano

    2014-01-01

    Background: Triple-negative breast cancers (TNBC) are characterized by aggressive tumour biology resulting in a poor prognosis. Androgen receptor (AR) is one of newly emerging biomarker in TNBC. In recent years, ARs have been demonstrated to play an important role in the genesis and in the development of breast cancer, although their prognostic role is still debated. In the present study, we explored the correlation of AR expression with clinical, pathological and molecular features and its impact on prognosis in early TNBC. Patients and Methods: ARs were considered positive in case of tumors with >10% nuclear-stained. Survival distribution was estimated by the Kaplan Meier method. The univariate and multivariate analyses were performed. The difference among variables were calculated by chi-square test. Results: 81 TNBC patients diagnosed between January 2006 and December 2011 were included in the analysis. Slides were stained immunohistochemically for estrogen and progesterone receptors, HER-2, Ki-67, ALDH1, e-cadherin and AR. Of the 81 TNBC samples, 18.8% showed positive immunostaining for AR, 23.5% and 44.4% of patients were negative for e-cadherin and ALDH1, respectively. Positive AR immunostaining was inversely correlated with a higher Ki-67 (p < 0.0001) and a lympho-vascular invasion (p = 0.01), but no other variables. Univariate survival analysis revealed that AR expression was not associated with disease-free survival (p = 0.72) or overall survival (p = 0.93). Conclusions: The expression of AR is associated with some biological features of TNBC, such as Ki-67 and lympho-vascular invasion; nevertheless the prognostic significance of AR was not documented in our analysis. However, since ARs are expressed in a significant number of TNBC, prospective studies in order to determine the biological mechanisms and their potential role as novel treatment target. PMID:24978437

  11. Developing an Early Warning System for Machu Picchu Pueblo, Peru.

    NASA Astrophysics Data System (ADS)

    Bulmer, Mark; Farquhar, Tony

    2010-05-01

    The town of Machu Picchu, Peru, is linked to Ollantaytambo and Cusco by rail and serves as the main station for the 400,000+ tourists visiting Machu Picchu. Due to the tourist industry the town grown threefold in population in the past two decades. Today, due to the limited availability of low-lying ground, construction is occurring higher up on the unstable valley slopes. The town is located at 2000 m asl while the surrounding peaks rise to over 4000 m asl. Slopes range from < 10° on the valley floor to > 70° in the surrounding granite mountains. The town has grown on the downstream right bank of the Vilcanota River, at the confluence of the Alcamayo and the Aguas Calientes Rivers. Broadly, a dry winter season runs from May to August with a rainy summer season running from October to March. The rainy months provide around 80% of the annual rainfall average, which ranges from 1,600 to 2,300 mm. Seasonal temperature variations are considered modest. An assessment of the geohazards in and around the town has been undertaken. Those of particular concern to the town are 1) large rocks falling onto the town and/or the rail line, 2) flash flooding by any one of its three rivers, and 3) mudflows and landslides. To improve the existing municipal warning system a prototype early warning system incorporating suitable technologies that could monitor weather, river flow and slope satability was installed along the Aguas Calientes River in 2009. This has a distributed modular construction allowing most components to be installed, maintained, swapped, salvaged, repaired and/or replaced by local technicians. A diverse set of candidate power, communication and sensor technologies was deployed and evaluated. Most of the candidate technologies had never been deployed in similar terrain, altitude or weather. The successful deployment of the prototype proved that it is technically feasible to develop early warning capacity in the town.

  12. Impact of Early Postnatal Androgen Exposure on Voice Development

    PubMed Central

    Grisa, Leila; Leonel, Maria L.; Gonçalves, Maria I. R.; Pletsch, Francisco; Sade, Elis R.; Custódio, Gislaine; Zagonel, Ivete P. S.; Longui, Carlos A.; Figueiredo, Bonald C.

    2012-01-01

    Background The impact of early postnatal androgen exposure on female laryngeal tissue may depend on certain characteristics of this exposure. We assessed the impact of the dose, duration, and timing of early androgen exposure on the vocal development of female subjects who had been treated for adrenocortical tumor (ACT) in childhood. Methods The long-term effects of androgen exposure on the fundamental vocal frequency (F0), vocal pitch, and final height and the presence of virilizing signs were examined in 9 adult (age, 18.4 to 33.5 years) and 10 adolescent (13.6 to 17.8 years) female ACT patients. We also compared the current values with values obtained 0.9 years to 7.4 years after these subjects had undergone ACT surgery, a period during which they had shown normal androgen levels. Results Of the 19 subjects, 17 (89%) had been diagnosed with ACT before 4 years of age, 1 (5%) at 8.16 years, and 1 (5%) at 10.75 years. Androgen exposure (2 to 30 months) was sufficiently strong to cause pubic hair growth in all subjects and clitoromegaly in 74% (14/19) of the subjects, but did not reduce their height from the target value. Although androgen exposure induced a remarkable reduction in F0 (132 Hz) and moderate pitch virilization in 1 subject and partial F0 virilization, resulting in F0 of 165 and 169 Hz, in 2 subjects, the majority had normal F0 ranging from 189 to 245 Hz. Conclusions Female laryngeal tissue is less sensitive to androgen exposure between birth and adrenarche than during other periods. Differential larynx sensitivity to androgen exposure in childhood and F0 irreversibility in adulthood are age-, concentration-, duration-, and timing-dependent events that may also be affected by exposure to inhibitory or stimulatory hormones. Further studies are required to better characterize each of these factors. PMID:23284635

  13. [Clinical-pharmacological aspects to accelerate the development process from the preclinical to the clinical phase/1st communication: The contribution of clinical pharmacology].

    PubMed

    Kuhlmann, Jochen

    2004-01-01

    To improve the transition from research to development a critical evaluation of the individual project by research and disease area teams is required to include input from pharmacology, toxicology, pharmacokinetics, galenics, clinical pharmacology, clinical as well as regulatory experts and marketing. Decisions on the individual development strategy should be made prior to the start of development and all projects should be reviewed at predefined stages throughout the product development life cycle. This ensures consistency of decision-making not only during the development of individual products but throughout the entire development pipeline. Studies in the exploratory stage of drug development should be designed for decision making in contrast to later clinical trials in the confirmatory stage that require power for proof-of-safety and proof-of-efficacy. The more thorough and profound studies have been carried out during this exploratory stage of drug development, the earlier a decision can be made on the continuation or discontinuation of further development, thus saving development time and money and assessing and considerably reducing the risk for the patients and increasing the success rate of the project in the later confirmatory effectiveness trial with an adequate number of subjects receiving the new therapy under typical conditions of use. Strategies which may be helpful to improve the quality of decisions in drug discovery and drug development are: discovery experiments should be done to critically evaluate the compound, the "killer" experiments should be done as early as possible, continuous effort on preclinical disease models is necessary to improve predictability of efficacy in patients ("humanized" research): genomic technology should be used to identify novel, disease-related targets and to characterise preclinical test systems, improvement of knowledge and experience concerning the relevance of new technologies for the clinical picture; genotyping

  14. Hypothesis: atorvastatin has pleiotropic effects that translate into early clinical benefits on cardiovascular disease.

    PubMed

    Novela, Cristina; Hennekens, Charles H

    2004-03-01

    The results of numerous long-term, randomized trials show that statins significantly decrease the risks of myocardial infarction, stroke, and vascular death as well as total mortality. The benefits of statins on cardiovascular disease in patients who are not experiencing acute coronary syndromes generally become apparent only after about 2 years. In contrast, atorvastatin conferred an early clinical benefit in the lipid-lowering arm of the long-term Anglo Scandinavian Cardiac Outcomes Trial as well as early benefit on progression of atherosclerosis in the Reversal of Atherosclerosis with Aggressive Lipid Lowering trial. An unexpected finding at baseline in the prospective Interaction of Atorvastatin and Clopidogrel Study was that patients on atorvastatin had significantly decreased platelet activity compared with either patients on other statins or those taking no statins. Atorvastatin has protective effects against membrane lipid peroxidation at pharmacologic concentrations. These and other considerations contribute to the hypothesis that atorvastatin has pleiotropic effects that translate into early clinical benefits on cardiovascular disease.

  15. Targeting apoptosis: preclinical and early clinical experience with mapatumumab, an agonist monoclonal antibody targeting TRAIL-R1.

    PubMed

    Moretto, Patricia; Hotte, Sébastien J

    2009-03-01

    In spite of the advances in survival with chemotherapy and radiotherapy, many cancer patients continue to experience failure with treatments. Advances in molecular oncology and the development of numerous targeted therapies, used by themselves or in combination with at present available treatments such as chemotherapy and radiation, will hopefully improve the fate of these patients. It has been well understood for many years now that deregulation of apoptosis is a major hallmark of cancer cells. Mapatumumab, a fully human agonistic monoclonal antibody to TNF-related apoptosis-inducing ligand receptor 1, has been developed to induce apoptosis in cancer cells although having minimal effects on normal cells. This paper reviews the preclinical and early clinical data of this exciting new agent and discusses options for future development of mapatumumab, mostly in combinations with other therapies.

  16. Involvement of Notch signaling in early chick ovarian follicle development.

    PubMed

    Li, Jun; Zhao, Dan; Guo, Changquan; Li, Jian; Mi, Yuling; Zhang, Caiqiao

    2016-01-01

    The formation of primordial follicles is a crucial process in the establishment of follicle pools required for the female's reproductive life span. For laying hens, ample follicles are a prerequisite for high laying performance. Notch signaling plays critical roles in germ cell cysts breakdown and in the formation of primordial follicles. Here, we investigated the role of Notch signaling in the ovarian development of post-hatch chicks. Results showed that around post-hatch day 4 (H4), the germ cell cysts broke apart, oocytes became surrounded by squamous pregranulosa cells, and the primordial follicles were then formed. Subsequently, we detected the expression of Notch signaling-related genes including Notch receptors (Notch1, 2), ligands (Jag1, 2 and Dll1, 4), and target genes (Hes1, Hey1). These genes all showed expression at H4 and some of these genes were up-regulated during primordial follicle formation. To evaluate the Notch signaling requirement for early follicular development, we adopted an in vitro ovary culture system. Suppression of Notch signaling by γ-secretase inhibitor induced a decrease of primordial follicles and an increase of germ cells in cysts. Attenuating Notch signaling also inhibited the phosphatidylinositol 3-kinase/protein kinase B pathways and suppressed cadherin expression. These results suggest that Notch signaling is endowed with an indispensable role in primordial follicle formation in post-hatch chicks.

  17. Probing early heart development to instruct stem cell differentiation strategies.

    PubMed

    Calderon, Damelys; Bardot, Evan; Dubois, Nicole

    2016-12-01

    Scientists have studied organs and their development for centuries and, along that path, described models and mechanisms explaining the developmental principles of organogenesis. In particular, with respect to the heart, new fundamental discoveries are reported continuously that keep changing the way we think about early cardiac development. These discoveries are driven by the need to answer long-standing questions regarding the origin of the earliest cells specified to the cardiac lineage, the differentiation potential of distinct cardiac progenitor cells, and, very importantly, the molecular mechanisms underlying these specification events. As evidenced by numerous examples, the wealth of developmental knowledge collected over the years has had an invaluable impact on establishing efficient strategies to generate cardiovascular cell types ex vivo, from either pluripotent stem cells or via direct reprogramming approaches. The ability to generate functional cardiovascular cells in an efficient and reliable manner will contribute to therapeutic strategies aimed at alleviating the increasing burden of cardiovascular disease and morbidity. Here we will discuss the recent discoveries in the field of cardiac progenitor biology and their translation to the pluripotent stem cell model to illustrate how developmental concepts have instructed regenerative model systems in the past and promise to do so in the future. Developmental Dynamics 245:1130-1144, 2016. © 2016 Wiley Periodicals, Inc.

  18. Controls on development and diversity of Early Archean stromatolites.

    PubMed

    Allwood, Abigail C; Grotzinger, John P; Knoll, Andrew H; Burch, Ian W; Anderson, Mark S; Coleman, Max L; Kanik, Isik

    2009-06-16

    The approximately 3,450-million-year-old Strelley Pool Formation in Western Australia contains a reef-like assembly of laminated sedimentary accretion structures (stromatolites) that have macroscale characteristics suggestive of biological influence. However, direct microscale evidence of biology--namely, organic microbial remains or biosedimentary fabrics--has to date eluded discovery in the extensively-recrystallized rocks. Recently-identified outcrops with relatively good textural preservation record microscale evidence of primary sedimentary processes, including some that indicate probable microbial mat formation. Furthermore, we find relict fabrics and organic layers that covary with stromatolite morphology, linking morphologic diversity to changes in sedimentation, seafloor mineral precipitation, and inferred microbial mat development. Thus, the most direct and compelling signatures of life in the Strelley Pool Formation are those observed at the microscopic scale. By examining spatiotemporal changes in microscale characteristics it is possible not only to recognize the presence of probable microbial mats during stromatolite development, but also to infer aspects of the biological inputs to stromatolite morphogenesis. The persistence of an inferred biological signal through changing environmental circumstances and stromatolite types indicates that benthic microbial populations adapted to shifting environmental conditions in early oceans.

  19. Controls on development and diversity of Early Archean stromatolites

    PubMed Central

    Allwood, Abigail C.; Grotzinger, John P.; Knoll, Andrew H.; Burch, Ian W.; Anderson, Mark S.; Coleman, Max L.; Kanik, Isik

    2009-01-01

    The ≈3,450-million-year-old Strelley Pool Formation in Western Australia contains a reef-like assembly of laminated sedimentary accretion structures (stromatolites) that have macroscale characteristics suggestive of biological influence. However, direct microscale evidence of biology—namely, organic microbial remains or biosedimentary fabrics—has to date eluded discovery in the extensively-recrystallized rocks. Recently-identified outcrops with relatively good textural preservation record microscale evidence of primary sedimentary processes, including some that indicate probable microbial mat formation. Furthermore, we find relict fabrics and organic layers that covary with stromatolite morphology, linking morphologic diversity to changes in sedimentation, seafloor mineral precipitation, and inferred microbial mat development. Thus, the most direct and compelling signatures of life in the Strelley Pool Formation are those observed at the microscopic scale. By examining spatiotemporal changes in microscale characteristics it is possible not only to recognize the presence of probable microbial mats during stromatolite development, but also to infer aspects of the biological inputs to stromatolite morphogenesis. The persistence of an inferred biological signal through changing environmental circumstances and stromatolite types indicates that benthic microbial populations adapted to shifting environmental conditions in early oceans. PMID:19515817

  20. Management of organic impurities in small molecule medicinal products: Deriving safe limits for use in early development.

    PubMed

    Harvey, James; Fleetwood, Andrew; Ogilvie, Ron; Teasdale, Andrew; Wilcox, Phil; Spanhaak, Steven

    2017-03-01

    Management of organic non-mutagenic impurities (NMIs) in medicinal products is regulated by the ICH Q3A, B and C guidelines that are applicable at late stages of clinical development (Phase III onwards) and as a consequence there is no guidance for the assessment and control of NMIs in early clinical trials. An analysis of several key in vivo toxicology databases supports the ICH Q3A defined concept that a lifetime dose to 1 mg/day of a NMI would not represent a safety concern to patients. In conjunction with routine (Q)SAR approaches, this 1 mg/day value could be used as a universal qualification threshold for a NMI during any stage of clinical development. This analysis also proposes that modification of this 1 mg/day dose using an established methodology (i.e. Modified Haber's Law) could support 5 mg/day or 0.7% (whichever is lower) as an acceptable limit for a NMI in a drug substance or product in early clinical studies (<6 months). Given the controlled nature of clinical development and the knowledge that most toxicities are dose and duration dependent, these proposed NMI limits provide assurance of patient safety throughout clinical development, without the requirement to commission dedicated in vivo toxicology impurity qualification studies.