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Sample records for early clinical development

  1. The use of clinical utility assessments in early clinical development.

    PubMed

    Khan, Anis A; Perlstein, Itay; Krishna, Rajesh

    2009-03-01

    A quickly realizable benefit of model-based drug development is in reducing uncertainty in risk/benefit, comprising individually of safety and effectiveness, two key attributes of a product evaluated for regulatory approval, marketing, and use. In this review, we investigate gaps and opportunities in using fundamental decision analytic principles in drug development and present a quantitative clinical pharmacology framework for the application of such aids for early clinical development decision making. We anticipate that implementation of such emerging tools will enable sufficient scientific understanding of the two attributes to facilitate the early termination of compounds with less than desirable risk/benefit profiles and continuance of compounds with acceptable risk/benefit profiles. PMID:19145490

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

    PubMed

    Andrew, Nicola

    2013-05-01

    The literature recognises a relationship between clinical experience and a successful undergraduate experience in nursing; however what constitutes an effective approach remains the subject of debate, particularly in relation to first year of learning. There is evidence from a biological standpoint that early experience impacts on the behavioural development of animals, described by Konrad Lorenz (1903-1989) as 'imprinting'. The concept of imprinting has resonance for nursing. In this article the importance of 'getting it right at the beginning' is explored and what, if anything, Lorenz's theory tells us about the impact of early clinical learning on subsequent professional development. PMID:22975293

  3. 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…

  4. Early gait development in human infants: Plasticity and clinical applications.

    PubMed

    Teulier, Caroline; Lee, Do Kyeong; Ulrich, Beverly D

    2015-05-01

    In this paper we focus on how a developmental perspective on plasticity in the control of human movement can promote early therapy and improve gait acquisition in infants with developmental disabilities. Current knowledge about stepping development in healthy infants across the first year of life highlights strong plasticity, both in behavioral outcome and in underlying neuro-muscular activation. These data show that stepping, like other motor skills, emerges from the interaction between infant's maturation and the environment. This view is reinforced by showing that infants with different internal resources (like genetic disorder or neural tube defect) show unique developmental trajectories when supported on a treadmill, yet do respond. Moreover, we will show that their behavior can be improved by context manipulations (mostly sensory stimulation) or practice. Overall, plasticity in the neural, skeletal, and muscle tissues create new opportunities for optimizing early intervention by creatively tapping into the same developmental processes experienced by healthy infants. PMID:25782975

  5. 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. PMID:23949724

  6. Clinical trials in Huntington's disease: Interventions in early clinical development and newer methodological approaches.

    PubMed

    Sampaio, Cristina; Borowsky, Beth; Reilmann, Ralf

    2014-09-15

    Since the identification of the Huntington's disease (HD) gene, knowledge has accumulated about mechanisms directly or indirectly affected by the mutated Huntingtin protein. Transgenic and knock-in animal models of HD facilitate the preclinical evaluation of these targets. Several treatment approaches with varying, but growing, preclinical evidence have been translated into clinical trials. We review major landmarks in clinical development and report on the main clinical trials that are ongoing or have been recently completed. We also review clinical trial settings and designs that influence drug-development decisions, particularly given that HD is an orphan disease. In addition, we provide a critical analysis of the evolution of the methodology of HD clinical trials to identify trends toward new processes and endpoints. Biomarker studies, such as TRACK-HD and PREDICT-HD, have generated evidence for the potential usefulness of novel outcome measures for HD clinical trials, such as volumetric imaging, quantitative motor (Q-Motor) measures, and novel cognitive endpoints. All of these endpoints are currently applied in ongoing clinical trials, which will provide insight into their reliability, sensitivity, and validity, and their use may expedite proof-of-concept studies. We also outline the specific opportunities that could provide a framework for a successful avenue toward identifying and efficiently testing and translating novel mechanisms of action in the HD field. PMID:25216371

  7. [Responsibilities of clinical pharmacology in the early phase of drug development].

    PubMed

    Kuhlmann, J

    2000-05-01

    The path of a new drug from the idea to the product may be divided into 2 phases, namely drug discovery and drug development. Due to the scientific progress new and simple methods could be developed to determine the biological efficacy of a large number of compounds. During the first part of drug development necessary requirements for the first use in man are met by performing preclinical pharmacological, toxicological and pharmacokinetic investigations in the animal and in in-vitro testing. After a first clinical-pharmacological profile of the new substance has been established during phase I on the basis of which a decision for the continuation of the clinical trial is made, the aim of phases II and III is now to answer the important questions of the therapeutic efficacy and tolerability in a large number of patients with the target indication. Due to the continuously increasing time and costs of drug development, drug development should be streamlined combining preclinical and early clinical phases as an exploratory stage and later clinical development as a confirmatory stage. The development and appropriate use of surrogates and models may be helpful to determine drug actions in human and to assist in dose selection as the main requirement for a successful large clinical trial in the confirmatory stage. Identifying the genes responsible for the huge variations in how different patients respond to a drug, in terms of both the product's effectiveness and its side effects, and genotyping patients before including in large clinical trials may prevent selecting the wrong patient population and avoid expensive repetition of these studies. Taking responsibility as the link between research and development gives clinical pharmacology a major opportunity to assume a pivotal role in drug development. To reach this goal, clinical pharmacology must be fully integrated in the whole process of drug development from the candidate selection until the approval. PMID:10851846

  8. [Responsibilities of clinical pharmacology in the early phase of drug development].

    PubMed

    Kuhlmann, J

    1999-05-15

    The path of a new drug from the idea to the product may be divided into 2 phases, namely drug discovery and drug development. Due to the scientific progress new and simple methods could be developed to determine the biological efficacy of a large number of compounds. During the first part of drug development necessary requirements for the first use in man are met by performing preclinical pharmacological, toxicological and pharmacokinetic investigations in the animal and in in-vitro testing. After a first clinical-pharmacological profile of the new substance has been established during phase I on the basis of which a decision for the continuation of the clinical trial is made, the aim of phases II and III is now to answer the important questions of the therapeutic efficacy and tolerability in a large number of patients with the target indication. Due to the continuously increasing time and costs of drug development, drug development should be streamlined combining preclinical and early clinical phases as an exploratory stage and later clinical development as a confirmatory stage. The development and appropriate use of surrogates and models may be helpful to determine drug actions in human and to assist in dose selection as the main requirement for a successful large clinical trial in the confirmatory stage. Identifying the genes responsible for the huge variations in how different patients respond to a drug, in terms of both the product's effectiveness and its side effects, and genotyping patients before including in large clinical trials may prevent selecting the wrong patient population and avoid expensive repetition of these studies. Taking responsibility as the link between research and development gives clinical pharmacology a major opportunity to assume a pivotal role in drug development. To reach this goal, clinical pharmacology must be fully integrated in the whole process of drug development from the candidate selection until the approval. PMID:10408193

  9. The impact of early human data on clinical development: there is time to win.

    PubMed

    Swart, Piet; Lozac'h, Frederic; Simon, Marjorie; van Duijn, Esther; Vaes, Wouter H J

    2016-06-01

    Modern accelerator mass spectrometry (AMS) methods enable the routine application of this technology in drug development. By the administration of a (14)C-labelled microdose or microtrace, pharmacokinetic (PK) data, such as mass balance, metabolite profiling, and absolute bioavailability (AB) data, can be generated easier, faster, and at lower costs. Here, we emphasize the advances and impact of this technology for pharmaceutical companies. The availability of accurate intravenous (iv) PK and human absorption, distribution, metabolism, and excretion (ADME) information, even before or during Phase I trials, can improve the clinical development plan. Moreover, applying the microtrace approach during early clinical development might impact the number of clinical pharmacology and preclinical safety pharmacology studies required, and shorten the overall drug discovery program. PMID:27046542

  10. Development of a Simple Clinical Risk Score for Early Prediction of Severe Dengue in Adult Patients

    PubMed Central

    Lee, Ing-Kit; Liu, Jien-Wei; Chen, Yen-Hsu; Chen, Yi-Chun; Tsai, Ching-Yen; Huang, Shi-Yu; Lin, Chun-Yu; Huang, Chung-Hao

    2016-01-01

    We aimed to develop and validate a risk score to aid in the early identification of laboratory-confirmed dengue patients at high risk of severe dengue (SD) (i.e. severe plasma leakage with shock or respiratory distress, or severe bleeding or organ impairment). We retrospectively analyzed data of 1184 non-SD patients at hospital presentation and 69 SD patients before SD onset. We fit a logistic regression model using 85% of the population and converted the model coefficients to a numeric risk score. Subsequently, we validated the score using the remaining 15% of patients. Using the derivation cohort, two scoring algorithms for predicting SD were developed: models 1 (dengue illness ≤4 days) and 2 (dengue illness >4 days). In model 1, we identified four variables: age ≥65 years, minor gastrointestinal bleeding, leukocytosis, and platelet count ≥100×109 cells/L. Model 1 (ranging from −2 to +6 points) showed good discrimination between SD and non-SD, with an area under the receiver operating characteristic curve (AUC) of 0.848 (95% confidence interval [CI], 0.771–0.924). The optimal cutoff value for model 1 was 1 point, with a sensitivity and specificity for predicting SD of 70.3% and 90.6%, respectively. In model 2 (ranging from 0 to +3 points), significant predictors were age ≥65 years and leukocytosis. Model 2 showed an AUC of 0.859 (95% CI, 0.756–0.963), with an optimal cutoff value of 1 point (sensitivity, 80.3%; specificity, 85.8%). The median interval from hospital presentation to SD was 1 day. This finding underscores the importance of close monitoring, timely resuscitation of shock including intravenous fluid adjustment and early correction of dengue-related complications to prevent the progressive dengue severity. In the validation data, AUCs of 0.904 (95% CI, 0.825–0.983) and 0.917 (95% CI, 0.833–1.0) in models 1 and 2, respectively, were achieved. The observed SD rates (in both cohorts) were <3% for patients with a score <1 point, but >50

  11. Development of a Simple Clinical Risk Score for Early Prediction of Severe Dengue in Adult Patients.

    PubMed

    Lee, Ing-Kit; Liu, Jien-Wei; Chen, Yen-Hsu; Chen, Yi-Chun; Tsai, Ching-Yen; Huang, Shi-Yu; Lin, Chun-Yu; Huang, Chung-Hao

    2016-01-01

    We aimed to develop and validate a risk score to aid in the early identification of laboratory-confirmed dengue patients at high risk of severe dengue (SD) (i.e. severe plasma leakage with shock or respiratory distress, or severe bleeding or organ impairment). We retrospectively analyzed data of 1184 non-SD patients at hospital presentation and 69 SD patients before SD onset. We fit a logistic regression model using 85% of the population and converted the model coefficients to a numeric risk score. Subsequently, we validated the score using the remaining 15% of patients. Using the derivation cohort, two scoring algorithms for predicting SD were developed: models 1 (dengue illness ≤4 days) and 2 (dengue illness >4 days). In model 1, we identified four variables: age ≥65 years, minor gastrointestinal bleeding, leukocytosis, and platelet count ≥100×109 cells/L. Model 1 (ranging from -2 to +6 points) showed good discrimination between SD and non-SD, with an area under the receiver operating characteristic curve (AUC) of 0.848 (95% confidence interval [CI], 0.771-0.924). The optimal cutoff value for model 1 was 1 point, with a sensitivity and specificity for predicting SD of 70.3% and 90.6%, respectively. In model 2 (ranging from 0 to +3 points), significant predictors were age ≥65 years and leukocytosis. Model 2 showed an AUC of 0.859 (95% CI, 0.756-0.963), with an optimal cutoff value of 1 point (sensitivity, 80.3%; specificity, 85.8%). The median interval from hospital presentation to SD was 1 day. This finding underscores the importance of close monitoring, timely resuscitation of shock including intravenous fluid adjustment and early correction of dengue-related complications to prevent the progressive dengue severity. In the validation data, AUCs of 0.904 (95% CI, 0.825-0.983) and 0.917 (95% CI, 0.833-1.0) in models 1 and 2, respectively, were achieved. The observed SD rates (in both cohorts) were <3% for patients with a score <1 point, but >50% for those

  12. Development of dietary phytochemical chemopreventive agents: biomarkers and choice of dose for early clinical trials.

    PubMed

    Scott, Edwina N; Gescher, Andreas J; Steward, William P; Brown, Karen

    2009-06-01

    In view of safety concerns surrounding the use of pharmaceuticals such as nonsteroidal anti-inflammatory drugs and tamoxifen as cancer chemopreventive agents, potentially innocuous phytochemicals derived from the diet are considered attractive alternatives. However, results from cancer chemoprevention trials of dietary agents have been disappointing to date, as promising activities observed in rodent models and cells in vitro have not translated into clinical success. This may be partly due to the development process for these agents, which is complex for a number of reasons; the definitive end point, inhibition of carcinogenesis, requires large numbers of individuals followed-up over many years. Furthermore, whereas biomarkers are frequently used as surrogate efficacy end points to expedite the process, biomarker assessment and validation has proven difficult because dietary agents exert multiple actions with an unknown hierarchy of biological importance. These factors have made determining the dose for clinical investigation extremely challenging, and at present, there are no defined strategies for rationally identifying the most appropriate doses. In this commentary, the complexities involved in the development of dietary chemoprevention agents are discussed, and a tentative route towards selection of the optimal clinical dose is proposed. The approach highlights the need to conduct long-term preclinical studies with realistic concentrations that are achievable in human tissues and the importance of efficacy biomarkers that are intrinsically linked to the key mechanisms of action. A more logical design of studies should increase the likelihood that the encouraging preclinical results observed for many phytochemicals translate into tangible clinical benefit. PMID:19470784

  13. Accountable to whom, for what? An exploration of the early development of Clinical Commissioning Groups in the English NHS

    PubMed Central

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

    2013-01-01

    Objective One of the key goals of the current reforms in the English National Health Service (NHS) under the Health and Social Care Act, 2012, is to increase the accountability of those responsible for commissioning care for patients (clinical commissioning groups (CCGs)), while at the same time allowing them a greater autonomy. This study was set out to explore CCG's developing accountability relationships. Design We carried out detailed case studies in eight CCGs, using interviews, observation and documentary analysis to explore their multiple accountabilities. Setting/participants We interviewed 91 people, including general practitioners, managers and governing body members in developing CCGs, and undertook 439 h of observation in a wide variety of meetings. Results CCGs are subject to a managerial, sanction-backed accountability to NHS England (the highest tier in the new organisational hierarchy), alongside a number of other external accountabilities to the public and to some of the other new organisations created by the reforms. In addition, unlike their predecessor commissioning organisations, they are subject to complex internal accountabilities to their members. Conclusions The accountability regime to which CCGs are subject to is considerably more complex than that which applied their predecessor organisations. It remains to be seen whether the twin aspirations of increased autonomy and increased accountability can be realised in practice. However, this early study raises some important issues and concerns, including the risk that the different bodies to whom CCGs are accountable will have differing (or conflicting) agendas, and the lack of clarity over the operation of sanction regimes. PMID:24327362

  14. 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

  15. Early Developments, 2001.

    ERIC Educational Resources Information Center

    Buysee, Virginia, Ed.; Winton, Pam, Ed.

    2001-01-01

    This document consists of the single 2001 issue of a journal reporting new research in early childhood development conducted by the Frank Porter Graham Child Development Center at the University of North Carolina at Chapel Hill. The issue focuses on pre-kindergarten programs, highlighting a recent assessment of the skills of entering…

  16. 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…

  17. 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…

  18. Factors in the development of clinical informatics competence in early career health sciences professionals in Australia: a qualitative study.

    PubMed

    Gray, Kathleen; Sim, Jenny

    2011-03-01

    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 university education and during workplace learning and training. This study is based on a broad review of the literature on clinical informatics education and training; its findings support international analyses and suggest that new strategic efforts among stakeholders in the healthcare system are required to make progress in building workforce capacity in this field, in Australia and elsewhere. PMID:20544387

  19. Early Childhood Development.

    ERIC Educational Resources Information Center

    Koh, Edgar, Ed.

    1989-01-01

    Focused on early childhood development, this "UNICEF Intercom" asserts that developmental programs should aim to give children a fair chance at growth beyond survival. First presented are moral, scientific, social equity, economic, population, and programatic arguments for looking beyond the fundamental objective of saving young lives.…

  20. 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,…

  1. Early clinical development of artemether-lumefantrine dispersible tablet: palatability of three flavours and bioavailability in healthy subjects

    PubMed Central

    2010-01-01

    Background Efforts to ease administration and enhance acceptability of the oral anti-malarial artemether-lumefantrine (A-L) crushed tablet to infants and children triggered the development of a novel dispersible tablet of A-L. During early development of this new formulation, two studies were performed in healthy subjects, one to evaluate the palatability of three flavours of A-L, and a second one to compare the bioavailability of active principles between the dispersible tablet and the tablet (administered crushed and intact). Methods Study 1 was performed in 48 healthy schoolchildren in Tanzania. Within 1 day, all subjects tasted a strawberry-, orange- and cherry-flavoured oral A-L suspension for 10 seconds (without swallowing) in a randomized, single-blind, crossover fashion. The palatability of each formulation was rated using a visual analogue scale (VAS). Study 2 was an open, randomized crossover trial in 48 healthy adults given single doses of A-L (80 mg artemether + 480 mg lumefantrine) with food. The objectives were to compare the bioavailability of artemether, dihydroartemisinin (DHA) and lumefantrine between the dispersible tablet and the tablet administered crushed (primary objective) and intact (secondary objective). Results Study 1 showed no statistically significant difference in VAS scores between the three flavours but cherry had the highest score in several ratings (particularly for overall liking). Study 2 demonstrated that the dispersible and crushed tablets delivered bioequivalent artemether, DHA and lumefantrine systemic exposure (area under the curve [AUC]); mean ± SD AUC0-tlast were 208 ± 113 vs 195 ± 93 h.ng/ml for artemether, 206 ± 81 vs 199 ± 84 h.ng/ml for DHA and 262 ± 107 vs 291 ± 106 h.μg/ml for lumefantrine. Bioequivalence was also shown for peak plasma concentrations (Cmax) of DHA and lumefantrine. Compared with the intact tablet, the dispersible tablet resulted in bioequivalent lumefantrine exposure, but AUC and Cmax values

  2. 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

  3. Adenosine A2A receptor antagonists in Parkinson's disease: progress in clinical trials from the newly approved istradefylline to drugs in early development and those already discontinued.

    PubMed

    Pinna, Annalisa

    2014-05-01

    Neurotransmitters other than dopamine, such as norepinephrine, 5-hydroxytryptamine, glutamate, adenosine and acetylcholine, are involved in Parkinson's disease (PD) and contribute to its symptomatology. Thus, the progress of non-dopaminergic therapies for PD has attracted much interest in recent years. Among new classes of drugs, adenosine A2A antagonists have emerged as promising candidates. The development of new highly selective adenosine A2A receptor antagonists, and their encouraging anti-parkinsonian responses in animal models of PD, has provided a rationale for clinical trials to evaluate the therapeutic potential and the safety of these agents in patients with PD. To date, the clinical research regarding A2A antagonists and their potential utilization in PD therapy continues to evolve between drugs just or previously discontinued (preladenant and vipadenant), new derivatives in development (tozadenant, PBF-509, ST1535, ST4206 and V81444) and the relatively old drug istradefylline, which has finally been licensed as an anti-parkinsonian drug in Japan. All these compounds have been shown to have a good safety profile and be well tolerated. Moreover, results from phase II and III trials also demonstrate that A2A antagonists are effective in reducing off-time, without worsening troublesome dyskinesia, and in increasing on-time with a mild increase of non-troublesome dyskinesia, in patients at an advanced stage of PD treated with L-DOPA. In addition, early findings suggest that A2A antagonists might also be efficacious as monotherapy in patients at an early stage of PD. This review summarizes pharmacological and clinical data available on istradefylline, tozadenant, PBF-509, ST1535, ST4206, V81444, preladenant and vipadenant. PMID:24687255

  4. Design and conduct of early clinical studies of two or more targeted anticancer therapies: recommendations from the task force on Methodology for the Development of Innovative Cancer Therapies.

    PubMed

    Seymour, Lesley K; Calvert, A Hilary; Lobbezoo, Marinus W; Eisenhauer, Elizabeth A; Giaccone, Giuseppe

    2013-05-01

    The Methodology for the Development of Innovative Cancer Therapies (MDICT) task force considered aspects of the design and conduct of early (phase I and II) studies of combinations of molecular targeted agents during their 2012 meeting. The task force defined necessary non-clinical data, such as evidence of additive or synergistic effects in multiple molecularly credentialed and validated models, and appropriate pharmacodynamic marker development. A robust hypothesis was considered critical while non-clinical pharmacokinetic studies were also considered valuable. Clinical trials should include clear objectives that will prove or disprove the hypothesis. Predictive biomarkers/classifiers should be explored in phase I studies, rather than used to select patients. Trial design should be efficient and flexible rather than based on a strict progression from phase I to II to III; researchers could consider phase I studies with an expansion cohort, Phase I/II designs or phase II studies with a safety run in. Pharmacokinetics are recommended when interactions or overlapping toxicity is expected. Pharmacodynamic evaluations should be considered especially in a subset of patients closest to the recommended dose; an attempt should be made to validate surrogate tissues to enable inclusion for all patients. Schedule and or dose should be formally explored for e.g. with a randomised or an adaptive design. Data and knowledge sharing was strongly recommended, including the creation of formal or informal consortia of laboratories with individual expertise in pathway or target based models, collaboration between companies to ensure that agents which are 'best in class' are combined, and the development of databases which will be able to inform the development of future recommendations/guidelines. PMID:23428669

  5. Development of clinical sites.

    PubMed

    O'Brien, Mary

    2015-02-01

    Clinical experiences are vital to all types of healthcare educational programs. Supervised clinical experiences provide the opportunity for the learner to apply didactic knowledge and theory to real world situations and hone skills necessary for entry into practice. Nurse anesthesia programs utilize a wide variety of clinical sites to expose student registered nurse anesthetists to experiences that will prepare them clinically, academically and professionally to enter practice as a Certified Registered Nurse Anesthetist. This article describes the process of developing a clinical site. A thorough evaluation will determine the types of experiences meant to be offered at the site, the resources available to house and educate the students, and how to evaluate the effectiveness of the clinical site. Open communication between the clinical coordinator and the program director or designee is essential to ensure success of the clinical site. The Council on Accreditation of Nurse Anesthesia Educational Programs has resources available to guide those interested in becoming a clinical site, as well as for program administrators who seek to add new experiences to their programs. PMID:25842629

  6. Neurobiology of early life stress: clinical studies.

    PubMed

    Heim, Christine; Nemeroff, Charles B

    2002-04-01

    A burgeoning number of clinical studies have evaluated the immediate and long-term neurobiological effects of early developmental stress, eg, child abuse and neglect or parental loss, in the past years. This review summarizes and discusses the available findings from neuroendocrine (hypothalamic-pituitary-adrenal axis, other neuroendocrine axes), neurochemical (catecholamines, serotonin, other neurotransmitters), psychophysiological (autonomic function, startle reactivity, brain electrical activity) and neuroimaging studies (brain structure, function) conducted in children or adults with a history of early life stress, with or without psychiatric disorders. Early developmental stress in humans appears to be associated with neurobiological alterations that are similar to many findings in animal models of early life stress, and likely represent the biological basis of an enhanced risk for psychopathology. Clinical studies are now beginning to explore potentially differential neurobiological effects of different types of early life stress and the existence of critical developmental periods, which may be sensitive to the neurobiological effects of specific stressors. In addition, the role of a multitude of moderating and mediating factors in the determination of individual vulnerability or resilience to the neurobiological effects of early life stress should be addressed. Findings from such studies may ultimately help to prevent the deleterious neurobiological and psychopathological consequences in the unacceptably high number of children exposed to early life stress in modern society. PMID:11953939

  7. 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)

  8. 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

  9. CRITICAL READING DEVELOPS EARLY.

    ERIC Educational Resources Information Center

    LEE, DORRIS; AND OTHERS

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

  10. Clinical development of siltuximab.

    PubMed

    Davis, Christine C; Shah, Katherine S; Lechowicz, Mary Jo

    2015-07-01

    Siltuximab is a chimeric monoclonal antibody targeting interleukin-6 (IL-6), which in the fall of 2014 became the first FDA-approved treatment of the rare disease idiopathic multicentric Castleman's disease (MCD). MCD is a non-clonal lymphoproliferative disorder in which common symptoms include fever, night sweats, weight loss, and fatigue. Symptoms are driven by an overall hypercytokinemia, predominantly IL-6. While under clinical development, siltuximab was studied in several other disease states including multiple myeloma, non-Hodgkin lymphomas, and several solid tumors in which it did not demonstrate significant benefit. The efficacy of siltuximab in MCD is mainly confined to systemic symptomatic response and quality of life benefits with minimal complete responses and approximately 30 % partial responses, by radiographic criteria. Siltuximab treatment therefore is important in the overall treatment of this rare disease state. This review focuses on the clinical development and pharmaceutical approval of siltuximab. PMID:25986720

  11. [Early Diagnosis of Osteoarthritis: Clinical Reality and Promising Experimental Techniques].

    PubMed

    Arnscheidt, C; Meder, A; Rolauffs, B

    2016-06-01

    It is considered that the structural damage in early osteoarthritis (OA) is potentially reversible. It is therefore particularly important for orthopaedic and trauma surgery to develop strategies and technologies for diagnosing early OA processes. This review presents 3 case reports to illustrate the current clinical diagnostic procedure for OA. Experimental techniques with translational character are discussed in the context of the detection of early degenerative processes relevant to OA. Non-invasive imaging methods such as quantitative MRI, ultrasound, optical coherence tomography (OCT), scintigraphy and diffraction-enhanced synchrotron imaging (DEI), as well as biochemical methods and proteomics, are considered. Early detection of OA is reviewed with minimally invasive techniques, such as arthroscopy, as well as the combination of arthroscopic techniques with indentation, spectrometry, and multiphoton microscopy. In addition, a brief summary of macroscopic and histologic scores is presented. Finally, the spatial organisation of joint surface chondrocytes as an image-based biomarker is used to illustrate an early OA detection strategy that focusses on early changes in tissue architecture potentially prior to damage. In summary, multiple translational techniques are able to detect early OA processes but we do not know whether they truly represent the initial events. Moreover, at this point it is difficult to judge the future clinical relevance of these procedures and to compare their efficacy, as there have been comparative studies. However, the expected gain in knowledge will hopefully help us top attain a more comprehensive understanding of early OA and to develop novel methods for its early diagnosis, therapy, and prevention. Overall, the clinical diagnosis of early OA remains one of the greatest challenges of our field. We still face uncharted territory. PMID:26894867

  12. 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.

  13. Percutaneous endoscopic lumbar discectomy - early clinical experience.

    PubMed

    Hirano, Yoshitaka; Mizuno, Junichi; Takeda, Masaaki; Itoh, Yasunobu; Matsuoka, Hidenori; Watanabe, Kazuo

    2012-01-01

    We report our early clinical experience with percutaneous endoscopic lumbar discectomy (PELD) for herniated nucleus pulposus (HNP) in the lumbar spine. We introduced PELD to our clinical practice in June 2009. A total of 311 patients with degenerative lumbar spine disease were treated in our hospital up to August 2011. Thirty-seven patients with lumbar HNP were treated by PELD. PELD was carried out under local anesthesia, and the endoscope was continuously irrigated with saline. Twenty-eight patients were treated through the transforaminal approach, 5 were treated through the interlaminar approach, and 4 were treated through the extraforaminal approach. Surgery was discontinued due to uncontrollable intraoperative pain or anatomical inaccessibility in one case of the interlaminar approach and 2 cases of the extraforaminal approach. In the other 34 patients, the elapsed time of surgery was 34 to 103 minutes (mean 62.4 minutes). Extracorporeal blood loss was insignificant. Immediate symptom relief was achieved in all patients, and postoperative magnetic resonance imaging revealed sufficient removal of the HNP. The length of the postoperative hospital stay was 1 or 2 days in all patients. The surgical method of PELD is completely different from percutaneous nucleotomy, and the aim is to directly remove the HNP with minimum damage to the musculoskeletal structure. Although this study is based on our early clinical outcomes, PELD seemed to be a promising minimally invasive surgery for HNP in the lumbar spine. PMID:23006872

  14. Early experiences of accredited clinical informatics fellowships.

    PubMed

    Longhurst, Christopher A; Pageler, Natalie M; Palma, Jonathan P; Finnell, John T; Levy, Bruce P; Yackel, Thomas R; Mohan, Vishnu; Hersh, William R

    2016-07-01

    Since the launch of the clinical informatics subspecialty for physicians in 2013, over 1100 physicians have used the practice and education pathways to become board-certified in clinical informatics. Starting in 2018, only physicians who have completed a 2-year clinical informatics fellowship program accredited by the Accreditation Council on Graduate Medical Education will be eligible to take the board exam. The purpose of this viewpoint piece is to describe the collective experience of the first four programs accredited by the Accreditation Council on Graduate Medical Education and to share lessons learned in developing new fellowship programs in this novel medical subspecialty. PMID:27206458

  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. [Early Development under Microgravity Conditions].

    PubMed

    Ogneva, I V

    2015-01-01

    The review is devoted to various aspects of early development under the space flight conditions. The different possible cell mechanosensors are considered. Structural and functional changes in the cells, predominantly, in non-muscle ones, were discussed. The results of the different experiments with the embryos of fish, amphibians, birds and mammals under microgravity conditions are shown discussing possible reasons for the development of morphological changes. PMID:26591615

  17. Clinical benefits of early triptan therapy for migraine.

    PubMed

    Láinez, Mja

    2004-01-01

    The introduction of the triptans brought advances in achieving complete and sustained pain resolution in migraine patients, compared with non-migraine-specific treatments. However, sustained pain-free rates for triptans recorded in many clinical trials are still relatively low. This may be due to study participants being treated late into the attack, when pain is already moderate or severe. Studies with almotriptan have shown that efficacy is enhanced when treatment is given early in a migraine attack while pain is still mild, compared with later administration when pain intensity is greater. Developments in our understanding of migraine pathophysiology provide a rationale for this phenomenon, with improved efficacy seen when abortive treatment is administered before central sensitization develops. A limited window of therapeutic opportunity exists early in an attack to improve the outcome of triptan treatment. Early intervention is recommended to avoid the significant pain and disability commonly associated with moderate or severe migraine. PMID:15595991

  18. 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

  19. Quality-of-care standards for early arthritis clinics.

    PubMed

    Ivorra, José Andrés Román; Martínez, Juan Antonio; Lázaro, Pablo; Navarro, Federico; Fernandez-Nebro, Antonio; de Miguel, Eugenio; Loza, Estibaliz; Carmona, Loreto

    2013-10-01

    The diagnosis and treatment of early arthritis is associated with improved patient outcomes. One way to achieve this is by organising early arthritis clinics (EACs). The objective of this project was to develop standards of quality for EACs. The standards were developed using the two-round Delphi method. The questionnaire, developed using the best-available scientific evidence, includes potentially relevant items describing the dimensions of quality of care in the EAC. The questionnaire was completed by 26 experts (physicians responsible for the EACs in Spain and chiefs of the rheumatology service in Spanish hospitals). Two hundred and forty-four items (standards) describing the quality of the EAC were developed, grouped by the following dimensions: (1) patient referral to the EAC; (2) standards of structure for an EAC; (3) standards of process; (4) relation between primary care physicians and the EAC; (5) diagnosis and assessment of early arthritis; (6) patient treatment and follow-up in the EAC; (7) research and training in an EAC; and (8) quality of care perceived by the patient. An operational definition of early arthritis was also developed based on eight criteria. The standards developed can be used to measure/establish the requirements, resources, and processes that EACs have or should have to carry out their treatment, research, and educational activities. These standards may be useful to health professionals, patient associations, and health authorities. PMID:23568381

  20. 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

  1. Challenges assessing clinical endpoints in early Huntington disease.

    PubMed

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

    2010-11-15

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

  2. Sleep and Early Cortical Development

    PubMed Central

    Olini, Nadja; Huber, Reto; LeBourgeois, Monique

    2016-01-01

    Sleep is increasingly recognized as a key process in neurodevelopment. Animal data show that sleep is essential for the maturation of fundamental brain functions, and growing epidemiological findings indicate that children with early sleep disturbance suffer from later cognitive, attentional, and psychosocial problems. Still, major gaps exist in understanding processes underlying links between sleep and neurodevelopment. One challenge is to translate findings from animal research to humans. In this review, we describe parallels and differences in sleep and development of the cortex in humans and animals and discuss emerging questions. PMID:26807347

  3. Early drug development of inhibitors of the insulin-like growth factor-I receptor pathway: Lessons from the first clinical trials

    PubMed Central

    Rodon, Jordi; DeSantos, Victoria; Ferry, Robert Jean; Kurzrock, Razelle

    2011-01-01

    The insulin-like growth factor-I receptor (IGF-IR) was first cloned in 1986. Since then, intense work has defined classic phosphorelays activated via the IGF-IR, which regulate cell proliferation, apoptosis, motility, and fate. The understanding of the roles of hormones in cancer and the growth hormone–IGF–IGF-binding protein axis specifically has yield to a second wave of development: the design of specific inhibitors that interrupt the signaling associated with this axis. The ability to manipulate these pathways holds not only significant therapeutic implications but also increase the chance of deeper insight about the role of the axis in carcinogenesis and metastasis. Nowadays, >25 molecules with the same goal are at different stages of development. Here, we review the clinical and preclinical experience with the two most-investigated strategies, tyrosine kinase inhibitors and monoclonal antibodies, and the advantages and disadvantages of each strategy, as well as other alternatives and possible drug combinations. We also review the bio-markers explored in the first clinical trials, the strategies that have been explored thus far, and the clinical trials that are going to explore their role in cancer treatment. PMID:18790742

  4. Cognitive Development in Early Readers.

    ERIC Educational Resources Information Center

    Briggs, Chari; Elkind, David

    Some studies of early readers are discussed. It is pointed out that study of early readers has relevance for practical and theoretical issues in psychology and education. Of interest in this document are the following questions: (1) Are there any special talents or traits distinguishing early from non-early readers? (2) Do children who read early…

  5. [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. PMID:26580942

  6. Early Clinical Signs and Symptoms of HIV Infection

    PubMed Central

    Miedzinski, Lil J.

    1992-01-01

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

  7. Early flower development in Arabidopsis.

    PubMed Central

    Smyth, D R; Bowman, J L; Meyerowitz, E M

    1990-01-01

    The early development of the flower of Arabidopsis thaliana is described from initiation until the opening of the bud. The morphogenesis, growth rate, and surface structure of floral organs were recorded in detail using scanning electron microscopy. Flower development has been divided into 12 stages using a series of landmark events. Stage 1 begins with the initiation of a floral buttress on the flank of the apical meristem. Stage 2 commences when the flower primordium becomes separate from the meristem. Sepal primordia then arise (stage 3) and grow to overlie the primordium (stage 4). Petal and stamen primordia appear next (stage 5) and are soon enclosed by the sepals (stage 6). During stage 6, petal primordia grow slowly, whereas stamen primordia enlarge more rapidly. Stage 7 begins when the medial stamens become stalked. These soon develop locules (stage 8). A long stage 9 then commences with the petal primordia becoming stalked. During this stage all organs lengthen rapidly. This includes the gynoecium, which commences growth as an open-ended tube during stage 6. When the petals reach the length of the lateral stamens, stage 10 begins. Stigmatic papillae appear soon after (stage 11), and the petals rapidly reach the height of the medial stamens (stage 12). This final stage ends when the 1-millimeter-long bud opens. Under our growing conditions 1.9 buds were initiated per day on average, and they took 13.25 days to progress through the 12 stages from initiation until opening. PMID:2152125

  8. 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.

  9. Medical students’ attitudes towards early clinical exposure in Iran

    PubMed Central

    Khabaz Mafinejad, Mahboobeh; Peiman, Soheil; Khajavirad, Nasim; Mirabdolhagh Hazaveh, Mojgan; Edalatifard, Maryam; Allameh, Seyed-Farshad; Naderi, Neda; Foroumandi, Morteza; Afshari, Ali; Asghari, Fariba

    2016-01-01

    Objectives This study was carried out to investigate the medical students’ attitudes towards early clinical exposure at Tehran University of Medical Sciences. Methods A cross-sectional study was conducted during 2012-2015. A convenience sample of 298 first- and second-year students, enrolled in the undergraduate medical curriculum, participated in an early clinical exposure program. To collect data from medical students, a questionnaire consisting of open-ended questions and structured questions, rated on a five-point Likert scale, was used to investigate students’ attitudes toward early clinical exposure. Results Of the 298 medical students, 216 (72%) completed the questionnaires. The results demonstrated that medical students had a positive attitude toward early clinical exposure. Most students (80.1%) stated that early clinical exposure could familiarize them with the role of basic sciences knowledge in medicine and how to apply this knowledge in clinical settings. Moreover, 84.5% of them believed that early clinical exposure increased their interest in medicine and encouraged them to read more. Furthermore, content analysis of the students’ responses uncovered three main themes of early clinical exposure, were considered helpful to improve learning: “integration of theory and practice”, “interaction with others and professional development” and “desire and motivation for learning medicine”. Conclusions Medical students found their first experience with clinical setting valuable. Providing clinical exposure in the initial years of medical curricula and teaching the application of basic sciences knowledge in clinical practice can enhance students’ understanding of the role they will play in the future as a physician. PMID:27318794

  10. Taiwanese Early Childhood Educators' Professional Development

    ERIC Educational Resources Information Center

    Hsu, Ching-Yun

    2008-01-01

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

  11. Strategies for Supporting Early Literacy Development

    ERIC Educational Resources Information Center

    Dennis, Lindsay R.; Horn, Eva

    2011-01-01

    The development of early literacy skills is critical to children's later success in reading and reading-related activities; therefore, understanding how teachers can support early literacy development is equally important. In this article, the authors provide information on how early childhood teachers can use specific strategies and techniques as…

  12. Clinical development of Ebola vaccines.

    PubMed

    Sridhar, Saranya

    2015-09-01

    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

  13. 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

  14. Early hematopoiesis and macrophage development.

    PubMed

    McGrath, Kathleen E; Frame, Jenna M; Palis, James

    2015-12-01

    The paradigm that all blood cells are derived from hematopoietic stem cells (HSCs) has been challenged by two findings. First, there are tissue-resident hematopoietic cells, including subsets of macrophages that are not replenished by adult HSCs, but instead are maintained by self-renewal of fetal-derived cells. Second, during embryogenesis, there is a conserved program of HSC-independent hematopoiesis that precedes HSC function and is required for embryonic survival. The presence of waves of HSC-independent hematopoiesis as well as fetal HSCs raises questions about the origin of fetal-derived adult tissue-resident macrophages. In the murine embryo, historical examination of embryonic macrophage and monocyte populations combined with recent reports utilizing genetic lineage-tracing approaches has led to a model of macrophage ontogeny that can be integrated with existing models of hematopoietic ontogeny. The first wave of hematopoiesis contains primitive erythroid, megakaryocyte and macrophage progenitors that arise in the yolk sac, and these macrophage progenitors are the source of early macrophages throughout the embryo, including the liver. A second wave of multipotential erythro-myeloid progenitors (EMPs) also arises in the yolk sac. EMPs colonize the fetal liver, initiating myelopoiesis and forming macrophages. Lineage tracing indicates that this second wave of macrophages are distributed in most fetal tissues, although not appreciably in the brain. Thus, fetal-derived adult tissue-resident macrophages, other than microglia, appear to predominately derive from EMPs. While HSCs emerge at midgestation and colonize the fetal liver, the relative contribution of fetal HSCs to tissue macrophages at later stages of development is unclear. The inclusion of macrophage potential in multiple waves of hematopoiesis is consistent with reports of their functional roles throughout development in innate immunity, phagocytosis, and tissue morphogenesis and remodeling

  15. Early experience with tedizolid: clinical efficacy, pharmacodynamics, and resistance.

    PubMed

    Rybak, Jeffrey M; Marx, Kayleigh; Martin, Craig A

    2014-11-01

    Antimicrobial resistance among gram-positive organisms such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) continues to limit therapeutic options. The oxazolidinones are a synthetic class of agents now commonly relied on for the treatment of serious MRSA and VRE infections. With increasing utilization of linezolid, resistant pathogens have once again begun to emerge. Tedizolid, a next-generation oxazolidinone, possesses a spectrum of activity including MRSA and VRE, with significantly enhanced potency also against linezolid-resistant strains. Preclinical and early clinical studies have reported positive results, demonstrating a favorable pharmacokinetic profile in combination with key potential safety advantages. In two phase III clinical trials, tedizolid was found noninferior to linezolid in the treatment of acute bacterial skin and skin structure infections. Investigations for treatment of ventilator-acquired and health care-associated pneumonia are currently underway. Tedizolid has been subjected to pharmacodynamics studies throughout its development that have highlighted properties unique to this agent. Considerable accumulations in epithelial lining fluid and antimicrobial activity greatly augmented by the presence of granulocytes suggest that slow but bactericidal activity may be possible in some clinical scenarios. Structural distinctions between tedizolid and linezolid suggest that tedizolid has decreased vulnerability to oxazolidinone resistance mechanisms. Tedizolid minimum inhibitory concentrations are essentially unchanged in organisms possessing the chloramphenicol-florfenicol resistance gene, a horizontally transferable linezolid resistance mechanism. Although the clinical experience with tedizolid remains limited, early data suggest a potential role in the treatment of serious infections due to multidrug-resistant gram-positive pathogens. PMID:25266820

  16. 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

  17. Prostaglandins: a report on early clinical studies

    PubMed Central

    Hinman, J. W.

    1970-01-01

    The prostaglandins are a unique group of pharmacologically active lipids which are widely distributed in mammalian tissues and body fluids. The chemistry of this family of compounds has been established in elegant detail. Research quantities of these highly active natural compounds were obtained by enzymatic bioconversion of essential fatty acids and now studies devoted to the elucidation of their physiological roles and their clinical potential are progressing rapidly. Fields of greatest current interest in clinical medicine include renal-cardiovascular research, induction of labour and therapeutic abortion, control of the reproductive cycle (including fertility control), bronchodilation, enhancement of nasal patency and antisecretory activity. Results available to date are too preliminary for many conclusions to be drawn, but are sufficiently encouraging to assure continued and expanding efforts in several fields. PMID:4098885

  18. Early Childhood Educators' Knowledge of Early Literacy Development

    ERIC Educational Resources Information Center

    Crim, Courtney; Hawkins, Jacqueline; Thornton, Jenifer; Rosof, Holly Boon; Copley, Juanita; Thomas, Emily

    2008-01-01

    The foundation of all learning is rooted in the development of language and literacy abilities. Literacy development begins well before children enter school and can accelerate in an early childhood classroom setting. Teacher educators often hear about the importance of literacy development. In particular, the significance of phonological…

  19. 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

  20. Supporting Mathematical Development in the Early Years

    ERIC Educational Resources Information Center

    Pound, Linda

    2006-01-01

    This book provides practical guidance for parents, teachers, and other early years workers who want to give children a good start in mathematical development. Showing how competent children are as mathematicians from an early age, the book offers an overview of young children's mathematical behaviour at home and in early years settings. This book…

  1. 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…

  2. 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…

  3. Early clinical outcomes following laparoscopic inguinal hernia repair.

    PubMed

    Tolver, Mette Astrup

    2013-07-01

    Laparoscopic inguinal hernia repair (TAPP) has gained increasing popularity because of less post-operative pain and a shorter duration of convalescence compared with open hernia repair technique (Lichtenstein). However, investigation of duration of convalescence with non-restrictive recommendations, and a procedure-specific characterization of the early clinical outcomes after TAPP was lacking. Furthermore, optimization of the post-operative period with fibrin sealant versus tacks for fixation of mesh, and the glucocorticoid dexamethasone versus placebo needed to be investigated in randomized clinical trials. The objective of this PhD thesis was to characterize the early clinical outcomes after TAPP and optimize the post-operative period. The four studies included in this thesis have investigated duration of convalescence and procedure-specific post-operative pain and other early clinical outcomes after TAPP. Furthermore, it has been shown that fibrin sealant can improve the early post-operative period compared with tacks, while dexamethasone showed no advantages apart from reduced use of antiemetics compared with placebo. Based on these findings, and the existing knowledge, 3-5 days of convalescence should be expected when 1 day of convalescence is recommended and future studies should focus on reducing intraabdominal pain after TAPP. Fibrin sealant can optimize the early clinical outcomes but the risk of hernia recurrence and chronic pain needs to be evaluated. Dexamethasone should be investigated in higher doses. PMID:23809977

  4. 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…

  5. Challenges in Developing Clinical Workstation

    SciTech Connect

    Narayanan, Venkatesh; Vedula, Venumadhav

    2008-09-26

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

  6. [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. PMID:26847235

  7. 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

  8. 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.

  9. Clinical features associated with an early onset in chronic tic disorders.

    PubMed

    Richer, Francois; Daghfal, Roula; Rouleau, Guy A; Lespérance, Paul; Chouinard, Sylvain

    2015-12-30

    In chronic tic disorders such as Tourette syndrome (TS), tics often appear between 4 and 8 years but they can also appear in early childhood, a period in which symptom expression may be affected by early brain development. The present study examined whether symptom expression in early-onset TS was distinct from that observed in TS with a later onset. We compared the clinical characteristics in children with TS who developed tics before age 4 or after age 6. Early-onset TS was significantly associated with an increased rate of stuttering and other speech disfluencies as well as an increased rate of oppositional defiant disorder, symptoms that often appear before age 4. Early-onset TS was also linked to maternal transmission of tics. Early-onset TS was not significantly associated with tic severity, obsessive-compulsive behavior or attention-deficit hyperactivity disorder. The results suggest that an early onset affects symptom expression in tic disorders. PMID:26596364

  10. Systems, Development, and Early Intervention.

    ERIC Educational Resources Information Center

    Sameroff, Arnold J.

    1992-01-01

    This commentary on the study reported in this monograph focuses on three topics raised by the study: (1) social systems, or individuals in the context of institutions; (2) the study of development through the use of disabled populations as experiments in human growth; and (3) the ability of intervention programs to manipulate development. (BC)

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

    PubMed Central

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

    2016-01-01

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

  12. 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

  13. Online Early Childhood Professional Development: Selected Experiences

    ERIC Educational Resources Information Center

    Olsen, Heather

    2010-01-01

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

  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. The Early Development of Precocity.

    ERIC Educational Resources Information Center

    Robinson, Nancy M.

    1987-01-01

    The limited research on precocity in infants and preschool children is reviewed, examining specifically the problems of: describing young gifted children, predicting their future development, determining the origins of high achievement motivation and commitment, and nurturing the talent at home and/or in the preschool. (Author/JDD)

  16. Assessment of Early Child Development.

    ERIC Educational Resources Information Center

    Flapan, Dorothy

    This is a short assessment outline for use by non-clinicians in evaluating the development of young children. It usually requires 20-30 minutes to assess one child. It may be used periodically to evaluate changes, as a year-end summary, or as a means of communicating with others who have contacts with the child. Sections of the assessment deal…

  17. 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

  18. 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. PMID:7845413

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

    PubMed

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

    2012-03-01

    If diseases of food-producing animals or zoonoses (re-)emerge, early clinical decision making is of major importance. In this particular condition, it is difficult to apply a classic evidence-based veterinary medicine process, because of a lack of available published data. A method based on the partition of field clinical observations (evidences) could be developed as an interesting alternative approach. The classification and regression tree (CART) analysis was used to improve the early clinical detection in two cases of emerging diseases: bovine spongiform encephalopathy (mad cow disease) and bluetongue due to the serotype 8-virus in cattle. PMID:22374122

  20. 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

  1. Measuring time during early embryonic development.

    PubMed

    Ferree, Patrick L; Deneke, Victoria E; Di Talia, Stefano

    2016-07-01

    In most metazoans, embryonic development is orchestrated by a precise series of cellular behaviors. Understanding how such events are regulated to achieve a stereotypical temporal progression is a fundamental problem in developmental biology. In this review, we argue that studying the regulation of the cell cycle in early embryonic development will reveal novel principles of how embryos accurately measure time. We will discuss the strategies that have emerged from studying early development of Drosophila embryos. By comparing the development of flies to that of other metazoans, we will highlight both conserved and alternative mechanisms to generate precision during embryonic development. PMID:26994526

  2. Contraceptive development and clinical trials.

    PubMed

    Fraser, I S

    1986-02-01

    This article provides an overview of the contraceptive development process, with particular emphasis on the importance of clinical trials. Development of a new contraceptive drug begins with chemical synthesis of a large number of substances that may have antifertility effects. Before human trials are considered, drugs must undergo a complex process of animal toxicology testing. Such studies assess acute, subacute, and chronic toxicity. Once a drug has passed the initial screening process, human testing must follow a logical sequence of clinical trials: phase I, pharmacology testing; phase II, initial assessment of efficacy, safety, acceptability, and ease of use; phase III, acurate assessment of efficacy, side effects, and reasons for discontinuation under controlled conditions; and phase IV, evaluation of effectiveness under field conditions. When these have been satisfactorily completed, a detailed marketing application must be submitted to the drug regulatory agency in each country. The process of assessment of the application often takes as long as 2 years. Once marketing approval has been received, there is still a need for postmarketing surveillance of the performance of the new contraceptive method. In many cases, a careful program of training is required. Among the research and recording strategies for postmarketing surveillance are voluntary recording of possible adverse reactions, longterm prospective cohort studies, retrospective case-control studies, and registered release. As controls on the safety and performance of new contraceptive methods are being tightened, the time scale and costs of development are increasing. The time from the 1st synthesis of a drug to marketing approval often takes 13-14 years and costs US$25-50 million. Since the patent life of a new substance is limited to 17 years in most countries, pharmaceutical companies have little time to recoup development costs, which has caused fewer new methods to be developed. PMID:3708511

  3. 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. PMID:23801434

  4. Epidemiological, clinical, and genetic characteristics of early-onset parkinsonism.

    PubMed

    Schrag, Anette; Schott, Jonathan M

    2006-04-01

    In this review we discuss the epidemiological, clinical, and genetic characteristics of early-onset parkinsonism, defined as parkinsonism starting before age 40 (sometimes 50) years. Juvenile parkinsonism is very rare and is the result of various secondary or genetic causes. In patients with onset at or above age 21 years, secondary causes require exclusion but are rare; most cases with a fairly pure parkinsonian syndrome (eg, young-onset Parkinson's disease; YOPD) are due to typical Lewy-body Parkinson's disease or, less commonly, genetic causes. In comparison with patients with late-onset disease, most patients with YOPD progress more slowly in terms of motor features and have a longer disease course with preservation of cognitive function, but typically develop motor fluctuations and dyskinesias earlier. Patients with YOPD generally experience a greater effect in their lives than those with late onset, with poorer social adjustment, higher rates of depression, and lower quality of life. Management of YOPD must therefore aim to maintain occupational, social, and daily functioning, while delaying or ameliorating motor complications of treatment, providing psychological support, and, where possible, preventing psychiatric complications including depression. PMID:16545752

  5. Tremelimumab: research and clinical development

    PubMed Central

    Comin-Anduix, Begoña; Escuin-Ordinas, Helena; Ibarrondo, Francisco Javier

    2016-01-01

    The immune checkpoint therapy is a relatively recent strategy that aims to tweak the immune system to effectively attack cancer cells. The understanding of the immune responses and their regulation at the intracellular level and the development of fully humanized monoclonal antibodies are the pillars of an approach that could elicit durable clinical responses and even remission in some patients with cancer. Most of the immune checkpoints that regulate the T-cell responses (activation and inhibition) operate through proteins present on the cytoplasmic membrane of the immune cells. Therefore, specific antibodies capable of blocking the inhibitory signals should lead to unrestrained immune responses that supersede the inhibitory mechanisms, which are naturally present in the tumor microenviroment. The best-known and most successful targets for immune checkpoint therapy are the cytotoxic T-lymphocyte antigen-4 and programmed cell death-1 coreceptors. Tremelimumab (CP-675,206) is a fully humanized monoclonal antibody specific for cytotoxic T-lymphocyte antigen-4, which has been successfully used to treat patients with metastatic melanoma and some other cancers. Although still a work in progress, the use of tremelimumab as an immune checkpoint therapeutic agent is a promising approach alone or in combination with other anticancer drugs. Here, we review the use of this antibody in a number of clinical trials against solid tumors. PMID:27042127

  6. Developing clinical trials for biosimilars.

    PubMed

    Bui, Lynne A; Taylor, Carrie

    2014-02-01

    Biosimilars offer the prospect of providing efficacious and safe treatment options for many diseases, including cancer, while potentially increasing accessibility with greater affordability relative to biologics. Because biologics are large, complex molecules that cannot be exactly duplicated, biosimilars cannot be considered "generic" versions of biologic drugs. This review will examine important considerations for biosimilar clinical trials. Since the aim of biosimilar manufacturing is to produce a molecule highly similar to the reference biologic, a comparability exercise is needed to demonstrate similarity with the reference biologic product based on physicochemical characterization. In vitro analytical studies and in vivo studies as well as pharmacokinetic/pharmacodynamic (PK/PD) assessments also are conducted. Lastly, because it may not be possible to fully characterize a biosimilar in relation to its reference biologic, robust pharmacovigilance strategies are utilized to ensure that any matters in regard to safety can be monitored. Other key topics will be discussed, including regulatory guidance for the evaluation of biosimilars, clinical trial design considerations, and whether data submitted for the approval of a biosimilar for one indication can be extrapolated to other indications for which the reference biologic is approved. European and Canadian experiences in biosimilar development will be reviewed. PMID:24560024

  7. Ganetespib: research and clinical development

    PubMed Central

    Jhaveri, Komal; Modi, Shanu

    2015-01-01

    Under stressful conditions, the heat shock protein 90 (HSP90) molecular chaperone protects cellular proteins (client proteins) from degradation via the ubiquitin-proteasome pathway. HSP90 expression is upregulated in cancers, and this contributes to the malignant phenotype of increased proliferation and decreased apoptosis and maintenance of metastatic potential via conservation of its client proteins, including human epidermal growth factor receptor 2, anaplastic lymphoma kinase, androgen receptor, estrogen receptor, Akt, Raf-1, cell cycle proteins, and B-cell lymphoma 2 among others. Hence, inhibition of HSP90 leads to the simultaneous degradation of its many clients, thereby disrupting multiple oncogenic signaling cascades. This has sparked tremendous interest in the development of HSP90 inhibitors as an innovative anticancer strategy. Based on the wealth of compelling data from preclinical studies, a number of HSP90 inhibitors have entered into clinical testing. However, despite enormous promise and anticancer activity reported to date, none of the HSP90 inhibitors in development has been approved for cancer therapy, and the full potential of this class of agents is yet to be realized. This article provides a review on ganetespib, a small molecule HSP90 inhibitor that is currently under evaluation in a broad range of cancer types in combination with other therapeutic agents with the hope of further enhancing its efficacy and overcoming drug resistance. Based on our current understanding of the complex HSP90 machinery combined with the emerging data from these key clinical trials, ganetespib has the potential to be the first-in-class HSP90 inhibitor to be approved as a new anticancer therapy. PMID:26244021

  8. 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…

  9. 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…

  10. Transcriptome Encyclopedia of Early Human Development.

    PubMed

    Sahakyan, Anna; Plath, Kathrin

    2016-05-01

    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. PMID:27153491

  11. 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,…

  12. Patterns of Early Lexical and Phonological Development.

    ERIC Educational Resources Information Center

    Stoel-Gammon, Carol; Cooper, Judith A.

    1984-01-01

    Analyzes early lexical and phonological development in three children from late babbling through the acquisition of 50 conventional words. Focuses on (1) the relationship between prelinguistic and linguistic vocalizations, (2) phonological development after the onset of speech, (3) patterns of lexical selection, (4) rate of lexical acquisition,…

  13. 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. PMID:17152748

  14. 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. PMID:23184588

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

    ERIC Educational Resources Information Center

    Guhn, Martin; Goelman, Hillel

    2011-01-01

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

  16. 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…

  17. 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

  18. 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.…

  19. Operating Principles and Early Lexical Development.

    ERIC Educational Resources Information Center

    Mervis, Carolyn B.

    Two types of operating principles thought to play an important role in early lexical development are discussed. The principles are those concerned with: (1) assignment of reference or meaning to words; and (2) formation and evolution of categories. Discussion also addresses related issues, such as the developmentally important relationship between…

  20. 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;…

  1. Cross-Cultural Perspectives on Early Development.

    ERIC Educational Resources Information Center

    Kagan, Jerome

    The popular view among American psychologists has been that there is a continuity of psychological structure that is shaped by early experience. Data gathered in studies of Guatemalan villages imply serious discontinuities in the development of particular cognitive competencies and capacities for affect through preadolescence. The first two years…

  2. EARLY CRANIOFACIAL DEVELOPMENT: LIFE AMONG THE SIGNALS

    EPA Science Inventory

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

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

  3. 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,…

  4. 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 that age of…

  5. Measuring in support of early childhood development

    PubMed Central

    Hertzman, Clyde; Clinton, Jean; Lynk, Andrew

    2011-01-01

    A child’s early experiences and environments have a significant, measurable effect on later life trajectories of health and well-being. Each child’s own world, especially parents and other caregivers, literally sculpts the brain and impacts stress pathways. Effective early childhood interventions exist that can improve adult and societal outcomes. In this statement, the Canadian Paediatric Society calls on federal and provincial/territorial governments to measure and monitor the developmental progress of children in Canada, which can vary widely among communities and demographic groups. The statement explores the objectives for collecting quality information about early child development, its determinants and long-term outcomes. It also examines four approaches to collecting population-based, person-specific and longitudinal data, both in young children and later in life. A key outcome of monitoring development is timely intervention. Linking individual data to the home and community levels is a critical step, so that communities and governments can monitor and take actions that support early child development. PMID:23204908

  6. New players unveiled in early anther development

    PubMed Central

    Salinas, María

    2011-01-01

    Anther development is an important process for the successful sexual reproduction in plants. Whereas the regulation of the late stages of anther development is quite well described in A. thaliana, little is known about the regulation of the early stages of this process. Two novel groups of factors involved in these early stages have recently been described, namely ROXYs, members of the Glutaredoxin (GRX) family of small and ubiquitous oxidoreductases involved in various cellular and stress-related responses, and SBP-box Genes. ROXYs belong to the CC-type of GRXs with a CCXC active motif and are specific for higher plants. SBP-box genes encode for SQUAMOSA PROMOTER BINDING PROTEIN transcription factors, many of which are targeted by miR156 and miR157. Strikingly, both the enzymes and the transcription factors represent evolutionary conserved gene families and loss-of-function of these genes exhibits similar anther phenotypes, e.g. arresting sporogenous cell formation and missing pollen sacs. This mini-review gives an overview of how these factors affect early anther development and discusses a possible relationship between these factors and other known early anther genes. PMID:21633200

  7. Measuring in support of early childhood development.

    PubMed

    Hertzman, Clyde; Clinton, Jean; Lynk, Andrew

    2011-12-01

    A child's early experiences and environments have a significant, measurable effect on later life trajectories of health and well-being. Each child's own world, especially parents and other caregivers, literally sculpts the brain and impacts stress pathways. Effective early childhood interventions exist that can improve adult and societal outcomes. In this statement, the Canadian Paediatric Society calls on federal and provincial/territorial governments to measure and monitor the developmental progress of children in Canada, which can vary widely among communities and demographic groups. The statement explores the objectives for collecting quality information about early child development, its determinants and long-term outcomes. It also examines four approaches to collecting population-based, person-specific and longitudinal data, both in young children and later in life. A key outcome of monitoring development is timely intervention. Linking individual data to the home and community levels is a critical step, so that communities and governments can monitor and take actions that support early child development. PMID:23204908

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

    PubMed Central

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

    2014-01-01

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

  9. 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. PMID:25754419

  10. 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.

  11. 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. PMID:25572407

  12. Clinical Psychology: A Research and Development Model.

    ERIC Educational Resources Information Center

    Broskowski, Anthony

    The purpose of this paper is to present a clinical research and development (R and D) model along with the rationale for its implementation and a sample training program for clinical psychologists. Although it may be possible to correct some problems by a clearer restatement of the scientist-professional model, a new model of clinical R and D has…

  13. 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

  14. Early development of Silvetia babingtonii (Fucales, Phaeophyceae)

    NASA Astrophysics Data System (ADS)

    Wang, Gaoge; Wei, Xiaojiao; Shuai, Limei; Lu, Bojun; Wang, Shasha; Kang, Dongdong

    2014-08-01

    Silvetia babingtonii is a potentially economic brown alga for sources of food and high-value added utilization. So far, sporeling nursery and field cultivation has not been successful. The lack of knowledge on development and life cycle of this alga hinder the development of techniques for the sporeings and cultivation. In this study, internal structure of oogonium and antherium of S. babingtonii was observed with hematoxylin and eosin staining and through microscope. Meanwhile, early development from zygotes to juvenile sporelings was studied at 20°C under 60-100 μmol photons m-2s-1. Zygotes germinated and divided into thallus and rhizoid cells. The larger thallus cells further divided and developed into juvenile sporelings; while the smaller rhizoid cells divided and elongated into rhizoid hairs. These findings documented the life cycle of S. babingtonii and provided fundamental knowledge for sporeling nursery in the near future.

  15. 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. PMID:27107972

  16. 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

  17. [Clinical relevance of the early detection of arthrosis].

    PubMed

    Willauschus, W; Herrmann, J; Wirtz, P; Weseloh, G

    1995-01-01

    In the years 1989 to 1992 615 local persons underwent yearly examinations for analysis of osteoarthrosis of the hip and knee by means of comprehensive documentation of orthopaedic health history and clinical findings. Of special interest in our investigation were the Altman ACR criteria for osteoarthrosis of the hip and knee over the years. We can show, that finding the diagnosis is as accurate with the ACR criteria as well as the far more extensive Lequesne and Tegner-Lysholm score. Analysis of the investigations over the years revealed clearly different results in the frequency of osteoarthrosis. The reason is the nature of osteoarthrosis changing between silent and active phases especially during time of onset. Our investigations show, that valuable criteria exists for detection of early osteoarthrosis, however apparent are deficits for observing its course. PMID:8571651

  18. 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. PMID:23743210

  19. Clinical Impact of Vaccine Development.

    PubMed

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

    2016-01-01

    The discovery and development of immunization has been a singular improvement in the health of mankind. This chapter reviews currently available vaccines, their historical development, and impact on public health. Specific mention is made in regard to the challenges and pursuit of a vaccine for the human immunodeficiency virus as well as the unfounded link between autism and measles vaccination. PMID:27076123

  20. 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

  1. 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.

  2. 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.

  3. Moral Development in Early Adolescence: Perspective on a Perplexing Issue.

    ERIC Educational Resources Information Center

    Grinder, Robert E.; Nelsen, Edward A.

    1980-01-01

    The authors focus on the moral development of the early adolescent (ages 10 to 15). The ways in which early adolescents develop morally, social influences on such development, and the expression of morality behaviorally are discussed. (Editor/KC)

  4. 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…

  5. 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. PMID:27037326

  6. 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

  7. Astronewt: early development of newt in space

    NASA Astrophysics Data System (ADS)

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

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

  8. Disciplined approach to drug discovery and early development.

    PubMed

    Plenge, Robert M

    2016-07-27

    Our modern health care system demands therapeutic interventions that improve the lives of patients. Unfortunately, decreased productivity in therapeutics research and development (R&D) has driven drug costs up while delivering insufficient value to patients. Here, I discuss a model of translational medicine that connects four components of the early R&D pipeline-causal human biology, therapeutic modality, biomarkers of target modulation, and proof-of-concept clinical trials. Whereas the individual components of this model are not new, technological advances and a disciplined approach to integrating all four areas offer hope for improving R&D productivity. PMID:27464747

  9. 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

  10. 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.

  11. White matter tractography in early psychosis: clinical and neurocognitive associations

    PubMed Central

    Hatton, Sean N.; Lagopoulos, Jim; Hermens, Daniel F.; Hickie, Ian B.; Scott, Elizabeth; Bennett, Maxwell R.

    2014-01-01

    Background While many diffusion tensor imaging (DTI) investigations have noted disruptions to white matter integrity in individuals with chronic psychotic disorders, fewer studies have been conducted in young people at the early stages of disease onset. Using whole tract reconstruction techniques, the aim of this study was to identify the white matter pathology associated with the common clinical symptoms and executive function impairments observed in young people with psychosis. Methods We obtained MRI scans from young people with psychosis and healthy controls. Eighteen major white matter tracts were reconstructed to determine group differences in fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD) and then were subsequently correlated with symptomatology and neurocognitive performance. Results Our study included 42 young people with psychosis (mean age 23 yr) and 45 healthy controls (mean age 25 yr). Compared with the control group, the psychosis group had reduced FA and AD in the left inferior longitudinal fasciculus (ILF) and forceps major indicative of axonal disorganization, reduction and/or loss. These changes were associated with worse overall psychiatric symptom severity, increases in positive and negative symptoms, and worse current levels of depression. The psychosis group also showed FA reductions in the left superior longitudinal fasciculus that were associated with impaired neurocognitive performance in attention and semantic fluency. Limitations Our analysis grouped 4 subcategories of psychosis together, and a larger follow-up study comparing affective and nonaffective psychoses is warranted. Conclusion Our findings suggest that impaired axonal coherence in the left ILF and forceps major underpin psychiatric symptoms in young people in the early stages of psychosis. PMID:25111788

  12. 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)

  13. 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

  14. Clinical skill development for community pharmacists.

    PubMed

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

    1996-09-01

    The importance of establishing clinical pharmacy services in the community cannot be understated in light of current challenges to the traditional dispensing role as the primary service of the community pharmacist. Advancements in automated dispensing technology and declining prescription fee reimbursement are rapidly forcing pharmacists to seek alternative sources of revenue. Providing pharmaceutical care is a viable option to increase customer loyalty job satisfaction, and reimbursement. To support the development of clinical services, academic institutions are forming partnerships with individual community practitioners to overcome perceived educational and training barriers. The authors describe the design and development of two unique clinical skill development programs at the University of Illinois at Chicago. This paper also outlines the patient focused services that the participants have established upon completing the training. These programs successfully enhanced participants' therapeutic knowledge base and facilitated development of the clinical skills necessary for direct patient care. PMID:8824077

  15. 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.

  16. Early lymphoid lesions: conceptual, diagnostic and clinical challenges

    PubMed Central

    Ganapathi, Karthik A.; Pittaluga, Stefania; Odejide, Oreofe O.; Freedman, Arnold S.; Jaffe, Elaine S.

    2014-01-01

    There are no “benign lymphomas”, a fact due to the nature of lymphoid cells to circulate and home as part of their normal function. Thus, benign clonal expansions of lymphocytes are only rarely recognized when localized. Recent studies have identified a number of lymphoid proliferations that lie at the interface between benign and malignant. Some of these are clonal proliferations that carry many of the molecular hallmarks of their malignant counterparts, such as BCL2/IGH and CCND1/IGH translocations associated with the in situ forms of follicular lymphoma and mantle cell lymphoma, respectively. There are other clonal B-cell proliferations with low risk of progression; these include the pediatric variants of follicular lymphoma and marginal zone lymphoma. Historically, early or incipient forms of T/NK-cell neoplasia also have been identified, such as lymphomatoid papulosis and refractory celiac disease. More recently an indolent form of T-cell lymphoproliferative disease affecting the gastrointestinal tract has been described. Usually, CD8+, the clonal cells are confined to the mucosa. The clinical course is chronic, but non-progressive. NK-cell enteropathy is a clinically similar condition, composed of cytologically atypical NK-cells that may involve the stomach, small bowel or colon. Breast implant-associated anaplastic large cell lymphoma is a cytologically alarming lesion that is self-limited if confined to the seroma cavity. Atypical lymphoid proliferations that lie at the border of benign and malignant can serve as instructive models of lymphomagenesis. It is also critical that they be correctly diagnosed to avoid unnecessary and potentially harmful therapy. PMID:25176983

  17. Neuroimaging biomarkers for early drug development in schizophrenia.

    PubMed

    Tregellas, Jason R

    2014-07-15

    Given the relative inability of currently available antipsychotic treatments to adequately provide sustained recovery and improve quality of life for patients with schizophrenia, new treatment strategies are urgently needed. One way to improve the therapeutic development process may be an increased use of biomarkers in early clinical trials. Reliable biomarkers that reflect aspects of disease pathophysiology can be used to determine if potential treatment strategies are engaging their desired biological targets. This review evaluates three potential neuroimaging biomarkers: hippocampal hyperactivity, gamma-band deficits, and default network abnormalities. These deficits have been widely replicated in the illness, correlate with measures of positive symptoms, are consistent with models of disease pathology, and have shown initial promise as biomarkers of biological response in early studies of potential treatment strategies. Two key features of these deficits, and a guiding rationale for the focus of this review, are that the deficits are not dependent upon patients' performance of specific cognitive tasks and they have analogues in animal models of schizophrenia, greatly increasing their appeal for use as biomarkers. Using neuroimaging biomarkers such as those proposed here to establish early in the therapeutic development process if treatment strategies are having their intended biological effect in humans may facilitate development of new treatments for schizophrenia. PMID:24094513

  18. Neuroimaging Biomarkers for Early Drug Development in Schizophrenia

    PubMed Central

    Tregellas, Jason R.

    2013-01-01

    Given the relative inability of currently available antipsychotic treatments to adequately provide sustained recovery and improve quality of life for patients with schizophrenia, new treatment strategies are urgently needed. One way to improve the therapeutic development process may be an increased use of biomarkers in early clinical trials. Reliable biomarkers that reflect aspects of disease pathophysiology can be used to determine if potential treatment strategies are engaging their desired biological targets. This review evaluates three potential neuroimaging biomarkers: hippocampal hyperactivity, gamma-band deficits and default network abnormalities. These deficits have been widely replicated in the illness, correlate with measures of positive symptoms, are consistent with models of disease pathology, and have shown initial promise as biomarkers of biological response in early studies of potential treatment strategies. Two key features of these deficits, and a guiding rational for the focus of this review, is that the deficits are not dependent upon patients' performance of specific cognitive tasks, and have analogues in animal models of schizophrenia, greatly increasing their appeal for use as biomarkers. Using neuroimaging biomarkers such as those proposed here to establish early in the therapeutic development process if treatment strategies are having their intended biological effect in humans may facilitate development of new treatments for schizophrenia. PMID:24094513

  19. Perception of Medical Faculties towards Early Clinical Exposure and MCI Vision 2015 Documents in Western Maharashtra

    PubMed Central

    Latti, Ramchandra G

    2015-01-01

    Introduction The Medical Council of India (MCI) has advocated early clinical exposure for students in medical colleges. In its ‘Vision-2015’ document for further reforms in undergraduate medical education, the MCI underlined the need for clinical teaching from first year onwards in medical colleges. Aim Our aim was to collect and analyse perception of medical faculties towards early clinical exposure and MCI Vision 2015 and to study the awareness, depth and interest among medical faculties towards these changes. Materials and Methods We used 10-item self developed survey questionnaires, which was validated from experts in medical education. 10–item questionnaire was based on awareness, depth and interest among medical faculties towards early clinical exposure and MCI Vision 2015 documents released by MCI in 2011. Qualitative data was assessed using percentage scale. We were approached to 182 preclinical medical faculties, however responses were received from 127 medical faculties from first year medical course subjects from six different college’s viz. two from Deemed University, two from Government sector and two from private sector but affiliated to Maharashtra University of Health sciences, Nasik, India. Results A 94.48% faculty members were aware regarding MCI Vision 2015 documents released by MCI in 2011. Average 12% faculties could answer specific approach MCQs based on MCI Vision 2015 documents. However, 82.67% faculties agreed early clinical exposure will be definitely helpful if implemented in curriculum. Conclusion The present work underlines need of special coaching and attention towards this important issue in medical education. PMID:26816885

  20. 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. PMID:12317893

  1. Clinical features of early erythema migrans disease and related disorders.

    PubMed

    Weber, K; Neubert, U

    1986-12-01

    104 patients with erythema migrans disease (EMD), 7 patients with borrelia lymphocytoma (BL), and 21 patients with acrodermatitis chronica atrophicans (ACA) were prospectively followed for a median of 20, 14, and 12 months, respectively. 99 patients with EMD and 6 with BL were treated with antibiotics early for their illness. 72 patients with EMD had 1 to 10 constitutional symptoms besides the erythema migrans, 32 had erythema migrans alone, and a child with BL had urticaria. Out of 39 patients with EMD, 23 acquired arthralgia, 18 signs and symptoms consistent with neurologic manifestations and 8 with cardiac involvement before or after therapy. 4 patients with EMD and 1 with BL had up to 10 multiple erythema migrans lesions. 3 patients with EMD experienced a reinfection and 1 with ACA a relapse. Several patients with ACA developed signs and symptoms consistent with neurologic, cardiac and joint involvement, and 2 had a history of EMD. Elevated antibody titers against Borrelia burgdorferi were present in 48% of 69 patients with EMD, 5 with BL and 11 with ACA, and in 93% of another group with EMD, 2 with BL and 10 with ACA, when tested against other borreliae. Increased values of the ESR, IgG, IgA and IgM were found in more patients with ACA than with EMD. The median of IgA and IgM was significantly higher in ACA than in EMD. Borreliae were found in brain and liver of a newborn. Early EMD appears to be quite similar to early Lyme disease. PMID:3577481

  2. Clinical review: early patient mobilization in the ICU.

    PubMed

    Hodgson, Carol L; Berney, Sue; Harrold, Megan; Saxena, Manoj; Bellomo, Rinaldo

    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

  3. Early clinical studies of novel therapies for thyroid cancers.

    PubMed

    Sherman, Steven I

    2008-06-01

    Historically, systemic therapies for advanced, metastatic thyroid carcinomas have been poorly effective. However, as a result of a confluence of increasing knowledge of the biologic basis for thyroid cancer development and progression, identification of therapeutic agents that could target these biologic abnormalities, and enthusiasm for research by both funding agencies as well as patients, multiple clinical trials have been initiated and successfully completed during the past several years. This article focuses on findings from key studies that reflect the new paradigms for treatment. PMID:18502340

  4. Economic deprivation and early childhood development.

    PubMed

    Duncan, G J; Brooks-Gunn, J; Klebanov, P K

    1994-04-01

    We consider 3 questions regarding the effects of economic deprivation on child development. First, how are developmental outcomes in childhood affected by poverty and such poverty correlates as single parenthood, ethnicity, and maternal education? Second, what are the developmental consequences of the duration and timing of family economic deprivation? And, third, what is the comparative influence of economic deprivation at the family and neighborhood level? We investigate these issues with longitudinal data from the Infant Health and Development Program. We find that family income and poverty status are powerful correlates of the cognitive development and behavior of children, even after accounting for other differences--in particular family structure and maternal schooling--between low- and high-income families. While the duration of poverty matters, its timing in early childhood does not. Age-5 IQs are found to be higher in neighborhoods with greater concentrations of affluent neighbors, while the prevalence of low-income neighbors appears to increase the incidence of externalizing behavior problems. PMID:7516849

  5. Third-generation neuroimaging in early schizophrenia: translating research evidence into clinical utility.

    PubMed

    Borgwardt, Stefan; Fusar-Poli, Paolo

    2012-04-01

    Psychiatric imaging needs to move away from simple investigations of the neurobiology underlying the early phases of schizophrenia to translate imaging findings in the clinical field, targeting clinical outcomes including transition, remission and response to preventive interventions. PMID:22474231

  6. 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

  7. 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. PMID:8300774

  8. Ibrutinib and novel BTK inhibitors in clinical development.

    PubMed

    Akinleye, Akintunde; Chen, Yamei; Mukhi, Nikhil; Song, Yongping; Liu, Delong

    2013-01-01

    Small molecule inhibitors targeting dysregulated pathways (RAS/RAF/MEK, PI3K/AKT/mTOR, JAK/STAT) have significantly improved clinical outcomes in cancer patients. Recently Bruton's tyrosine kinase (BTK), a crucial terminal kinase enzyme in the B-cell antigen receptor (BCR) signaling pathway, has emerged as an attractive target for therapeutic intervention in human malignancies and autoimmune disorders. Ibrutinib, a novel first-in-human BTK-inhibitor, has demonstrated clinical effectiveness and tolerability in early clinical trials and has progressed into phase III trials. However, additional research is necessary to identify the optimal dosing schedule, as well as patients most likely to benefit from BTK inhibition. This review summarizes preclinical and clinical development of ibrutinib and other novel BTK inhibitors (GDC-0834, CGI-560, CGI-1746, HM-71224, CC-292, and ONO-4059, CNX-774, LFM-A13) in the treatment of B-cell malignancies and autoimmune disorders. PMID:23958373

  9. Ibrutinib and novel BTK inhibitors in clinical development

    PubMed Central

    2013-01-01

    Small molecule inhibitors targeting dysregulated pathways (RAS/RAF/MEK, PI3K/AKT/mTOR, JAK/STAT) have significantly improved clinical outcomes in cancer patients. Recently Bruton’s tyrosine kinase (BTK), a crucial terminal kinase enzyme in the B-cell antigen receptor (BCR) signaling pathway, has emerged as an attractive target for therapeutic intervention in human malignancies and autoimmune disorders. Ibrutinib, a novel first-in-human BTK-inhibitor, has demonstrated clinical effectiveness and tolerability in early clinical trials and has progressed into phase III trials. However, additional research is necessary to identify the optimal dosing schedule, as well as patients most likely to benefit from BTK inhibition. This review summarizes preclinical and clinical development of ibrutinib and other novel BTK inhibitors (GDC-0834, CGI-560, CGI-1746, HM-71224, CC-292, and ONO-4059, CNX-774, LFM-A13) in the treatment of B-cell malignancies and autoimmune disorders. PMID:23958373

  10. QIN. Early experiences in establishing a regional quantitative imaging network for PET/CT clinical trials

    PubMed Central

    Doot, Robert K.; Thompson, Tove; Greer, Benjamin E.; Allberg, Keith C.; Linden, Hannah M.; Mankoff, David A.; Kinahan, Paul E.

    2012-01-01

    The Seattle Cancer Care Alliance (SCCA) is a Pacific Northwest regional network that enables patients from community cancer centers to participate in multicenter oncology clinical trials where patients can receive some trial-related procedures at their local center. Results of positron emission tomography (PET) scans performed at community cancer centers are not currently used in SCCA Network trials since clinical trials customarily accept results from only trial-accredited PET imaging centers located at academic and large hospitals. Oncologists would prefer the option of using standard clinical PET scans from Network sites in multicenter clinical trials to increase accrual of patients for whom additional travel requirements for imaging is a barrier to recruitment. In an effort to increase accrual of rural and other underserved populations to Network trials, researchers and clinicians at the University of Washington, SCCA and its Network are assessing feasibility of using PET scans from all Network sites in their oncology clinical trials. A feasibility study is required because the reproducibility of multicenter PET measurements ranges from approximately 3% to 40% at national academic centers. Early experiences from both national and local PET phantom imaging trials are discussed and next steps are proposed for including patient PET scans from the emerging regional quantitative imaging network in clinical trials. There are feasible methods to determine and characterize PET quantitation errors and improve data quality by either prospective scanner calibration or retrospective post hoc corrections. These methods should be developed and implemented in multicenter clinical trials employing quantitative PET imaging of patients. PMID:22795929

  11. 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…

  12. Clinical update: recognising brain tumours early in children.

    PubMed

    Paul, Siba Prosad; Debono, Rachel; Walker, David

    2013-04-01

    Brain tumour accounts for a quarter of all childhood cancers and is the leading cause of cancer related deaths in children. Initial symptoms can be misleading and is often misinterpreted as being caused by a less serious childhood illness. Available statistics show that it takes almost three times longer for the brain tumour in children to get diagnosed in the United Kingdom in comparison to other developed countries. Head Smart campaign was launched in the UK in 2011 with an aim to decrease the time from the onset of symptoms to diagnosis; initial results have been highly encouraging. Community practitioners play an important role in not only identifying symptoms (by following Head Smart symptom card) and selecting patients for reassurance, review or early referral but also by providing valuable support to the family post diagnosis in the community. PMID:23646820

  13. 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

  14. Early development of Brycon orthotaenia (Pisces: Characidae).

    PubMed

    Gomes, Rafael Zeferino; Sato, Yoshimi; Rizzo, Elizete; Bazzoli, Nilo

    2013-02-01

    Brycon orthotaenia is an important fish for commercial and sport fishing and may reach 7 kg in body weight; it is endangered in some regions of Brazil's São Francisco River Basin. Breeders were subjected to spawning induction to analyse the early development; oocytes and semen were obtained by manual extrusion and fertilization was carried out using the dry method. After fertilization, eggs were kept in incubators at 24°C. Egg samples were collected every 10 min until hatching in order to monitor embryonic development and were analysed and photographed. Larvae samples were collected daily until the seventh day to analyse the larvae development; larvae were fixed in Bouin's fluid and subjected to routine histological and histochemical techniques for glycoprotein and glyco-conjugated detection. Oocyte extrusion occurred 6 h after the second hormone dose at 26°C. The recently extruded oocytes were spherical, dark green and non-adhesive, with a diameter of 1479.67 ± 53.18 and 3094.60 ± 80.34 μm after hydration. The blastopore closure occurred within 7 h 30 min of fertilization and the fertilization rate was 50.0 ± 5.5 % at 24°C. Embryonic development was completed within 21 h 30 min of fertilization. Complete yolk sac resorption and mouth opening occurred on the third day after hatching, at which time an adhesive organ with mucosubstances was observed. On the third day, an olfactory chamber with cilia and intense cannibalism amongst the larvae was observed. The complete differentiation of the digestive system occurred on the fifth day and the nervous and sensorial systems differentiation occurred on the sixth to seventh days. PMID:21733293

  15. Clinical engineering strategies for career development.

    PubMed

    Boxerman, S B; Gribbins, R E

    1982-01-01

    In the continuing development of clinical engineering, new problem areas are beginning to emerge. Issues related to career development are gaining prominence, and job satisfaction, career advancement, and "burnout" are becoming increasingly important. To address these issues, clinical engineers must assume personal responsibility for their own careers. They must broaden their perception of clinical engineering to include a managerial perspective. The extent to which they assume managerial responsibilities is a function of their personal interests and talents. This involvement can range from a consultative role in decisions involving high technology to a position in the institution's top management staff. This broader definition will significantly benefit not only the field of clinical engineering but individual practitioners as well. PMID:10255250

  16. Alternative strategies in drug development: clinical pharmacological aspects.

    PubMed

    Kuhlmann, J

    1999-12-01

    Due to the continuous increase in time and cost of drug development and the considerable amount of resources required by the traditional approach, companies can no longer afford to continue to late phase 3 with drugs which are unlikely to be therapeutically effective. The future challenge must be for the pharmaceutical industry to slash its research and development costs by achieving a significant cut in the attrition rate for drugs entering preclinical and clinical development, and to reduce the development time and to increase the probability of success in later clinical trials by streamlining the development processes. In the 100 years to 1995, the pharmaceutical industry worked on about 500 targets with a limited number of compounds, whereas now, using new technologies like genomics, high throughput screening and combinatorial chemistry, drug companies will see an explosion in the number of targets and leads it can explore. Therefore, a tough selection process for picking candidate compounds out of research and a quick kill process for the candidate, which does not measure up in advanced trials, is mandatory to avoid wasting time, energy and money. To improve the transition from research to development it is necessary to validate new targets, define success criteria for research, integrate bioinformation at every stage in drug discovery, define prerequisites for development, identify the "losers" and select the "winners" early and concentrate efforts on them, and to automate the research and development (R&D) process to optimize resource requirements versus time lines and to ensure effective flow of information from drug discovery to late phase of development. In drug development a deeper understanding of a drugs' action is necessary from animal models and phase I, IIa studies prior to taking the drug further in development. Instead of moving from discovery thorough development phases in sequential steps, drug development should be streamlined combining

  17. Practical Guidance for Implementing Predictive Biomarkers into Early Phase Clinical Studies

    PubMed Central

    Marton, Matthew J.; Weiner, Russell

    2013-01-01

    The recent U.S. Food and Drug Administration (FDA) coapprovals of several therapeutic compounds and their companion diagnostic devices (FDA News Release, 2011, 2013) to identify patients who would benefit from treatment have led to considerable interest in incorporating predictive biomarkers in clinical studies. Yet, the translation of predictive biomarkers poses unique technical, logistic, and regulatory challenges that need to be addressed by a multidisciplinary team including discovery scientists, clinicians, biomarker experts, regulatory personnel, and assay developers. These issues can be placed into four broad categories: sample collection, assay validation, sample analysis, and regulatory requirements. In this paper, we provide a primer for drug development teams who are eager to implement a predictive patient segmentation marker into an early clinical trial in a way that facilitates subsequent development of a companion diagnostic. Using examples of nucleic acid-based assays, we briefly review common issues encountered when translating a biomarker to the clinic but focus primarily on key practical issues that should be considered by clinical teams when planning to use a biomarker to balance arms of a study or to determine eligibility for a clinical study. PMID:24236296

  18. Development of a clinical data architecture.

    PubMed Central

    Beeler, G. W.; Gibbons, P. S.; Chute, C. G.

    1992-01-01

    This paper presents a methodology for developing a data architecture for clinical medicine. The methodology uses an object-oriented analysis approach that takes advantage of the domain expertise of practicing physicians. The resulting high-level data model combines a structured, event-based model of clinical information with the process-oriented structures usually associated with problem lists and practice protocols. PMID:1482875

  19. 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…

  20. Early Parental Depression and Child Language Development

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  1. 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).…

  2. 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. PMID:25096861

  3. Early practical experience and the social responsiveness of clinical education: systematic review

    PubMed Central

    Littlewood, Sonia; Ypinazar, Valmae; Margolis, Stephen A; Scherpbier, Albert; Spencer, John; Dornan, Tim

    2005-01-01

    Objectives To find how early experience in clinical and community settings (“early experience”) affects medical education, and identify strengths and limitations of the available evidence. Design A systematic review rating, by consensus, the strength and importance of outcomes reported in the decade 1992-2001. Data sources Bibliographical databases and journals were searched for publications on the topic, reviewed under the auspices of the recently formed Best Evidence Medical Education (BEME) collaboration. Selection of studies All empirical studies (verifiable, observational data) were included, whatever their design, method, or language of publication. Results Early experience was most commonly provided in community settings, aiming to recruit primary care practitioners for underserved populations. It increased the popularity of primary care residencies, albeit among self selected students. It fostered self awareness and empathic attitudes towards ill people, boosted students' confidence, motivated them, gave them satisfaction, and helped them develop a professional identity. By helping develop interpersonal skills, it made entering clerkships a less stressful experience. Early experience helped students learn about professional roles and responsibilities, healthcare systems, and health needs of a population. It made biomedical, behavioural, and social sciences more relevant and easier to learn. It motivated and rewarded teachers and patients and enriched curriculums. In some countries, junior students provided preventive health care directly to underserved populations. Conclusion Early experience helps medical students learn, helps them develop appropriate attitudes towards their studies and future practice, and orientates medical curriculums towards society's needs. Experimental evidence of its benefit is unlikely to be forthcoming and yet more medical schools are likely to provide it. Effort could usefully be concentrated on evaluating the methods and

  4. 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. PMID:22640946

  5. Development of autophagy inducers in clinical medicine

    PubMed Central

    Levine, Beth; Packer, Milton; Codogno, Patrice

    2015-01-01

    Defects in autophagy have been linked to a wide range of medical illnesses, including cancer as well as infectious, neurodegenerative, inflammatory, and metabolic diseases. These observations have led to the hypothesis that autophagy inducers may prevent or treat certain clinical conditions. Lifestyle and nutritional factors, such as exercise and caloric restriction, may exert their known health benefits through the autophagy pathway. Several currently available FDA-approved drugs have been shown to enhance autophagy, and this autophagy-enhancing action may be repurposed for use in novel clinical indications. The development of new drugs that are designed to be more selective inducers of autophagy function in target organs is expected to maximize clinical benefits while minimizing toxicity. This Review summarizes the rationale and current approaches for developing autophagy inducers in medicine, the factors to be considered in defining disease targets for such therapy, and the potential benefits of such treatment for human health. PMID:25654546

  6. A historical perspective concerning population-based and clinical studies of early arthritis and early rheumatoid arthritis.

    PubMed

    Sokka, T; Pincus, T

    2003-01-01

    Research concerning early arthritis and early rheumatoid arthritis (RA) may be considered to have begun with population-based studies in the United Kingdom, the United States and Scandinavia, from the late 1950s to the late 1960s. These studies indicated that the majority of people with clinical findings of RA had no evidence of disease 3-5 years later, and that only about 25% to 30% of people in a population who met the criteria for RA had rheumatoid factor. These findings may have contributed to an underestimation of RA until the severity of long-term outcomes of clinical RA were recognized in the 1980s on the basis of clinical cohorts. The first major early RA clinical cohort was established in 1957-1963 in Bath, England. Although results at 3 and even 11 years were not overly unfavorable, by 15 and 20 years most patients had severe outcomes of functional declines and premature mortality. The Middle-sex (UK) early RA cohort established in 1966-1971 indicated that radiographic abnormalities were observed in about 70% of patients by 2 years of disease, and were seen in most patients initially in the feet. The Memphis (Tennessee, USA) early RA cohort established in 1967-1971 suggested that a progressive course of RA is predicted by a higher number of involved joints at baseline. The Lund (Sweden) early RA cohort established in 1985-1989 indicated rather severe long-term outcomes in patients treated according to traditional conservative approaches to use of disease modifying anti-rheumatic drugs (DMARDs). The early RA study (ERAS) involving nine National Health Service trusts in the UK was established in 1987-93, and showed associations of education level and socioeconomic status with clinical status. The movement towards early arthritis clinics was given great impetus following the work by Emery in the early 1990s. These studies and others described elsewhere in this supplement have contributed to the foundations for the clinical approach to early arthritis in the

  7. Clinical Characteristics and Outcomes Associated with the Natural History of Early Repolarization in a Young, Biracial Cohort Followed to Middle Age: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

    PubMed Central

    Ilkhanoff, Leonard; Soliman, Elsayed Z.; Prineas, Ronald J.; Walsh, Joseph A.; Ning, Hongyan; Liu, Kiang; Carr, J. Jeffrey; Jacobs, David R.; Lloyd-Jones, Donald M.

    2014-01-01

    Background Early repolarization (ER), a common electrocardiographic phenotype, has been associated with increased mortality risk in middle-aged adults. Data are sparse on long-term follow-up and outcomes associated with ER in younger adults. Methods and Results We prospectively examined 5,039 participants (mean age 25 years at baseline, 40% black) from the CARDIA cohort over 23 years. Twelve-lead electrocardiograms were recorded and analyzed at Years 0, 7 and 20 and coded as definite or probable ER using a standardized algorithm. Cox regression was used, and models were adjusted for important baseline and clinical covariates. Kaplan-Meier curves were created for presence of ER and total mortality and cardiovascular (CV) mortality. Participants with ER were more likely to be black, male, smoke, have higher systolic blood pressure, lower heart rate, and BMI, and also higher exercise duration, and longer PR, QRS and QT intervals. ER was associated with total mortality (HR1.77, 1.38–2.28, p<0.01), and CV mortality (HR 1.59, 1.01–2.50, p=0.04) in unadjusted analyses, but adjustment for age, sex, and race attenuated associations almost completely. Sex-race stratified analyses showed no significant associations between ER and outcome for any of the subgroups except blacks. Conclusions The presence of ER at any time point over 23 years of follow-up was not associated with adverse outcomes. Black race and male sex confound the unadjusted association of ER and outcomes, with no race-sex interactions noted. Further studies are necessary to understand the factors associated with heightened risk of death in those who maintain ER into and beyond middle age. PMID:24759868

  8. Clinical results of early stage prostatic cancer treated by pelvic lymphadenectomy and /sup 125/I implants

    SciTech Connect

    Kandzari, S.J.; Belis, J.A.; Kim, J.C.; Gnepp, D.R.; Riley, R.S.

    1982-05-01

    Eighty patients with clinically early stage adenocarcinoma of the prostate were treated with pelvic lymphadenectomy and interstitial implantation of /sup 125/I seeds. A new applicator that permits greater accuracy in spacing the seeds has been developed. Postoperative complications were minimal, with urinary irritability being the most common. Multiple transrectal needle biopsies were performed 12 and 18 months after treatment in 46 patients. The prostatic biopsies were negative for carcinoma in 61 per cent and positive in 39 per cent of the patients. Long-term followup is needed to correlate post-treatment biopsies with survival and to determine if patients with positive biopsies should receive further treatment.

  9. New and emerging therapeutic options for malignant pleural mesothelioma: review of early clinical trials

    PubMed Central

    Kotova, Svetlana; Wong, Raymond M; Cameron, Robert B

    2015-01-01

    Malignant pleural mesothelioma (MPM) is a rare tumor that is challenging to control. Despite some benefit from using the multimodality-approach (surgery, combination chemotherapy and radiation), survival remains poor. However, current research produced a list of potential therapies. Here, we summarize significant new preclinical and early clinical developments in treatment of MPM, which include mesothelin specific antibody and toxin therapies, interleukin-4 (IL-4) receptor toxins, dendritic cell vaccines, immune checkpoint inhibitors, and gene-based therapies. In addition, several local modalities such as photodynamic therapy, postoperative lavage using betadine, and cryotherapy for local recurrence, have also shown to be effective for local control of disease. PMID:25670913

  10. Multi-regional clinical trials and global drug development.

    PubMed

    Shenoy, Premnath

    2016-01-01

    Drug development has been globalized, and multi-regional clinical trial (MRCT) for regulatory submission has widely been conducted by many discovery based global pharmaceutical companies with the objective of reducing the time lag of launch in key markets and improve patient access to new and innovative treatments. Sponsors are facing several challenges while conducting multiregional clinical trials. Challenges under the heads statistics, clinical, regulatory operational, and ethics have been discussed. Regulators in different countries such as USA, EU-Japan, and China have issued guidance documents in respect of MRCT's. Lack of harmonization in the design and planning of MRCT is perceived to create a difficult situation to sponsors adversely affecting progressing MRCT in more and more discoveries. International conference on hormonisation (ICH) has initiated the process for having a harmonized guidance document on MRCT. This document is likely to be issued in early 2017. PMID:27141471

  11. Multi-regional clinical trials and global drug development

    PubMed Central

    Shenoy, Premnath

    2016-01-01

    Drug development has been globalized, and multi-regional clinical trial (MRCT) for regulatory submission has widely been conducted by many discovery based global pharmaceutical companies with the objective of reducing the time lag of launch in key markets and improve patient access to new and innovative treatments. Sponsors are facing several challenges while conducting multiregional clinical trials. Challenges under the heads statistics, clinical, regulatory operational, and ethics have been discussed. Regulators in different countries such as USA, EU-Japan, and China have issued guidance documents in respect of MRCT's. Lack of harmonization in the design and planning of MRCT is perceived to create a difficult situation to sponsors adversely affecting progressing MRCT in more and more discoveries. International conference on hormonisation (ICH) has initiated the process for having a harmonized guidance document on MRCT. This document is likely to be issued in early 2017. PMID:27141471

  12. Contemporary Trends and Developments in Early Childhood Education in China

    ERIC Educational Resources Information Center

    Zhu, Jiaxiong; Zhang, Jie

    2008-01-01

    Early childhood education in China has gone through a century-long development process and has made great progress in the past two decades. Contemporary early childhood education is becoming diverse in its forms and educational approaches, and is aligning itself with the increasingly open and diversified society. It is clear that early childhood…

  13. Desired professional development pathways for clinical pharmacists.

    PubMed

    Shord, Stacy S; Schwinghammer, Terry L; Badowski, Melissa; Banderas, Julie; Burton, Michael E; Chapleau, Christopher A; Gallagher, Jason C; Matsuura, Gregory; Parli, Sara E; Yunker, Nancy

    2013-04-01

    The 2012 American College of Clinical Pharmacy (ACCP) Certification Affairs Committee was charged with developing guidelines for the desired professional development pathways for clinical pharmacists. This document summarizes recommendations for postgraduate education and training for graduates of U.S. schools and colleges of pharmacy and describes the preferred pathways for achieving, demonstrating, and maintaining competence as clinical pharmacists. After initial licensure within the state or jurisdiction in which the pharmacist intends to practice, completion of an accredited PGY1 pharmacy residency is recommended to further develop the knowledge and skills needed to optimize medication therapy outcomes. An accredited PGY2 pharmacy residency should be completed if a pharmacist wishes to seek employment in a specific therapeutic area or practice setting, if such a residency exists. Clinical pharmacists intending to conduct advanced research that is competitive for federal funding are encouraged to complete a fellowship or graduate education. Initial certification by the Board of Pharmacy Specialties (BPS) or other appropriate sponsoring organizations should be completed in the desired primary therapeutic area or practice setting within 2 years after accepting a position within the desired specific therapeutic area or practice setting. Clinical pharmacists subsequently will need to meet the requirements to maintain pharmacist licensure and board certification. Traineeships, practice-based activities, and certificate programs can be used to obtain additional knowledge and skills that support professional growth. Pharmacists are strongly encouraged to adopt a lifelong, systematic process for professional development and work with ACCP and other professional organizations to facilitate the development and implementation of innovative strategies to assess core practice competencies. PMID:23401084

  14. 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

  15. Clinical utility of cerebrospinal fluid biomarkers in the diagnosis of early Alzheimer's disease.

    PubMed

    Blennow, Kaj; Dubois, Bruno; Fagan, Anne M; Lewczuk, Piotr; de Leon, Mony J; Hampel, Harald

    2015-01-01

    Several potential disease-modifying drugs for Alzheimer's disease (AD) have failed to show any effect on disease progression in clinical trials, conceivably because the AD subjects are already too advanced to derive clinical benefit from treatment and because diagnosis based on clinical criteria alone introduces a high misdiagnosis rate. Thus, well-validated biomarkers for early detection and accurate diagnosis are crucial. Low cerebrospinal fluid (CSF) concentrations of the amyloid-β (Aβ1-42) peptide, in combination with high total tau and phosphorylated tau, are sensitive and specific biomarkers highly predictive of progression to AD dementia in patients with mild cognitive impairment. However, interlaboratory variations in the results seen with currently available immunoassays are of concern. Recent worldwide standardization efforts and quality control programs include standard operating procedures for both preanalytical (e.g., lumbar puncture and sample handling) and analytical (e.g., preparation of calibration curve) procedures. Efforts are also ongoing to develop highly reproducible assays on fully automated instruments. These global standardization and harmonization measures will provide the basis for the generalized international application of CSF biomarkers for both clinical trials and routine clinical diagnosis of AD. PMID:24795085

  16. Clinical utility of cerebrospinal fluid biomarkers in the diagnosis of early Alzheimer’s disease

    PubMed Central

    Blennow, Kaj; Dubois, Bruno; Fagan, Anne M.; Lewczuk, Piotr; de Leon, Mony J.; Hampel, Harald

    2015-01-01

    Several potential disease-modifying drugs for Alzheimer’s disease (AD) have failed to show any effect on disease progression in clinical trials, conceivably because the AD subjects are already too advanced to derive clinical benefit from treatment and because diagnosis based on clinical criteria alone introduces a high misdiagnosis rate. Thus, well-validated biomarkers for early detection and accurate diagnosis are crucial. Low cerebrospinal fluid (CSF) concentrations of the amyloid-β (Aβ1-42) peptide, in combination with high total tau and phosphorylated tau, are sensitive and specific biomarkers highly predictive of progression to AD dementia in patients with mild cognitive impairment. However, interlaboratory variations in the results seen with currently available immunoassays are of concern. Recent worldwide standardization efforts and quality control programs include standard operating procedures for both preanalytical (e.g., lumbar puncture and sample handling) and analytical (e.g., preparation of calibration curve) procedures. Efforts are also ongoing to develop highly reproducible assays on fully automated instruments. These global standardization and harmonization measures will provide the basis for the generalized international application of CSF bio-markers for both clinical trials and routine clinical diagnosis of AD. PMID:24795085

  17. 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…

  18. 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…

  19. 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…

  20. 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…

  1. Pancreatic cancer early detection: Expanding higher-risk group with clinical and metabolomics parameters

    PubMed Central

    Urayama, Shiro

    2015-01-01

    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. PMID:25684935

  2. Clinical development of oncolytic viruses in China.

    PubMed

    Liang, Min

    2012-07-01

    The oncolytic virus, being a promising new therapeutic strategy for cancer, has inspired a wave of recent clinical research and development in China. The first commercialized oncolytic virus, Oncorine, was approved by Chinese SFDA in November 2005 for nasopharyngeal carcinoma combined with chemotherapy. Since then, a number of oncolytic viruses have been moved into clinical trials. Among these are the armed oncolytic adenoviruses such as H103 (expressing the heat shock protein) currently has finished phase I trial, and KH901 (expressing GM-CSF) now launched in phase II trial In this review, we will discuss the current status of ongoing oncolytic virus projects being conducted at various clinical stages in China, including the preliminary market response for Oncorine after it was launched into the Chinese market in 2006. PMID:21740357

  3. Lexically Based Learning and Early Grammatical Development.

    ERIC Educational Resources Information Center

    Lieven, Elena V. M.

    1997-01-01

    Tests Pine & Lieven's (1993) suggestion that a lexically-based positional analysis can account for the structure of a considerable proportion of children's early multiword corpora. Results reveal that the positional analysis accounts for 60% of the children's multiword utterances and that most other utterances are defined as frozen. (33…

  4. 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…

  5. Early Adolescence: A Critical Development Transition?

    ERIC Educational Resources Information Center

    Petersen, Anne C.

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

  6. Early literacy and early numeracy: the value of including early literacy skills in the prediction of numeracy development.

    PubMed

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

    2011-12-01

    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 year later on the PENS test and on the Applied Problems and Calculation subtests of the Woodcock-Johnson III Tests of Achievement. Three mixed effect regressions were conducted using Time 2 PENS, Applied Problems, and Calculation as the dependent variables. Print Knowledge and Vocabulary accounted for unique variance in the prediction of Time 2 numeracy scores. Phonological Awareness did not uniquely predict any of the mathematics domains. The findings of this study identify an important link between early literacy and early numeracy development. PMID:21831396

  7. Adjuvant bisphosphonates in early breast cancer: consensus guidance for clinical practice from a European Panel.

    PubMed

    Hadji, P; Coleman, R E; Wilson, C; Powles, T J; Clézardin, P; Aapro, M; Costa, L; Body, J-J; Markopoulos, C; Santini, D; Diel, I; Di Leo, A; Cameron, D; Dodwell, D; Smith, I; Gnant, M; Gray, R; Harbeck, N; Thurlimann, B; Untch, M; Cortes, J; Martin, M; Albert, U-S; Conte, P-F; Ejlertsen, B; Bergh, J; Kaufmann, M; Holen, I

    2016-03-01

    Bisphosphonates have been studied in randomised trials in early breast cancer to investigate their ability to prevent cancer treatment-induced bone loss (CTIBL) and reduce the risk of disease recurrence and metastasis. Treatment benefits have been reported but bisphosphonates do not currently have regulatory approval for either of these potential indications. This consensus paper provides a review of the evidence and offers guidance to breast cancer clinicians on the use of bisphosphonates in early breast cancer. Using the nominal group methodology for consensus, a systematic review of the literature was augmented by a workshop held in October 2014 for breast cancer and bone specialists to present and debate the available pre-clinical and clinical evidence for the use of adjuvant bisphosphonates. This was followed by a questionnaire to all members of the writing committee to identify areas of consensus. The panel recommended that bisphosphonates should be considered as part of routine clinical practice for the prevention of CTIBL in all patients with a T score of <-2.0 or ≥2 clinical risk factors for fracture. Compelling evidence from a meta-analysis of trial data of >18,000 patients supports clinically significant benefits of bisphosphonates on the development of bone metastases and breast cancer mortality in post-menopausal women or those receiving ovarian suppression therapy. Therefore, the panel recommends that bisphosphonates (either intravenous zoledronic acid or oral clodronate) are considered as part of the adjuvant breast cancer treatment in this population and the potential benefits and risks discussed with relevant patients. PMID:26681681

  8. 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. PMID:26868802

  9. Photoacoustic Imaging in Oncology: Translational Preclinical and Early Clinical Experience.

    PubMed

    Valluru, Keerthi S; Wilson, Katheryne E; Willmann, Jürgen K

    2016-08-01

    Photoacoustic imaging has evolved into a clinically translatable platform with the potential to complement existing imaging techniques for the management of cancer, including detection, characterization, prognosis, and treatment monitoring. In photoacoustic imaging, tissue is optically excited to produce ultrasonographic images that represent a spatial map of optical absorption of endogenous constituents such as hemoglobin, fat, melanin, and water or exogenous contrast agents such as dyes and nanoparticles. It can therefore provide functional and molecular information that allows noninvasive soft-tissue characterization. Photoacoustic imaging has matured over the years and is currently being translated into the clinic with various clinical studies underway. In this review, the current state of photoacoustic imaging is presented, including techniques and instrumentation, followed by a discussion of potential clinical applications of this technique for the detection and management of cancer. (©) RSNA, 2016. PMID:27429141

  10. Early experiences in establishing a regional quantitative imaging network for PET/CT clinical trials.

    PubMed

    Doot, Robert K; Thompson, Tove; Greer, Benjamin E; Allberg, Keith C; Linden, Hannah M; Mankoff, David A; Kinahan, Paul E

    2012-11-01

    The Seattle Cancer Care Alliance (SCCA) is a Pacific Northwest regional network that enables patients from community cancer centers to participate in multicenter oncology clinical trials where patients can receive some trial-related procedures at their local center. Results of positron emission tomography (PET) scans performed at community cancer centers are not currently used in SCCA Network trials since clinical trials customarily accept results from only trial-accredited PET imaging centers located at academic and large hospitals. Oncologists would prefer the option of using standard clinical PET scans from Network sites in multicenter clinical trials to increase accrual of patients for whom additional travel requirements for imaging are a barrier to recruitment. In an effort to increase accrual of rural and other underserved populations to Network trials, researchers and clinicians at the University of Washington, SCCA and its Network are assessing the feasibility of using PET scans from all Network sites in their oncology clinical trials. A feasibility study is required because the reproducibility of multicenter PET measurements ranges from approximately 3% to 40% at national academic centers. Early experiences from both national and local PET phantom imaging trials are discussed, and next steps are proposed for including patient PET scans from the emerging regional quantitative imaging network in clinical trials. There are feasible methods to determine and characterize PET quantitation errors and improve data quality by either prospective scanner calibration or retrospective post hoc corrections. These methods should be developed and implemented in multicenter clinical trials employing quantitative PET imaging of patients. PMID:22795929

  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. 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. PMID:25922995

  13. Lessons Learned for Collaborative Clinical Content Development

    PubMed Central

    Collins, S.A.; Bavuso, K.; Zuccotti, G.; Rocha, R.A.

    2013-01-01

    Background Site-specific content configuration of vendor-based Electronic Health Records (EHRs) is a vital step in the development of standardized and interoperable content that can be used for clinical decision-support, reporting, care coordination, and information exchange. The multi-site, multi-stakeholder Acute Care Documentation (ACD) project at Partners Healthcare Systems (PHS) aimed to develop highly structured clinical content with adequate breadth and depth to meet the needs of all types of acute care clinicians at two academic medical centers. The Knowledge Management (KM) team at PHS led the informatics and knowledge management effort for the project. Objectives We aimed to evaluate the role, governance, and project management processes and resources for the KM team’s effort as part of the standardized clinical content creation. Methods We employed the Center for Disease Control’s six step Program Evaluation Framework to guide our evaluation steps. We administered a forty-four question, open-ended, semi-structured voluntary survey to gather focused, credible evidence from members of the KM team. Qualitative open-coding was performed to identify themes for lessons learned and concluding recommendations. Results Six surveys were completed. Qualitative data analysis informed five lessons learned and thirty specific recommendations associated with the lessons learned. The five lessons learned are: 1) Assess and meet knowledge needs and set expectations at the start of the project; 2) Define an accountable decision-making process; 3) Increase team meeting moderation skills; 4) Ensure adequate resources and competency training with online asynchronous collaboration tools; 5) Develop focused, goal-oriented teams and supportive, consultative service based teams. Conclusions Knowledge management requirements for the development of standardized clinical content within a vendor-based EHR among multi-stakeholder teams and sites include: 1) assessing and meeting

  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. Early responses in randomized clinical trials of triptans in acute migraine treatment. Are they clinically relevant? A comment.

    PubMed

    Tfelt-Hansen, Peer

    2010-07-01

    One can question the clinical relevance of early headache responses after oral and intranasal triptans. Thus, for pain-free the early responses were significant but in absolute values they were only a few percentages: the therapeutic gains (TGs) were 1.8% (95% CI = 0.3-3%) for oral almotriptan 12.5 after 30 minutes and 1.0% (95% CI = 0-2%) after intranasal zolmitriptan 5 mg after 15 minutes. These results are compared with subcutaneous sumatriptan 6 mg which has TGs of 11% (95% CI = 7-15%) to 14% (95% CI = 11-17%) for pain-free after 30 minutes. Subcutaneous sumatriptan has a 2 times higher response rate than intranasal zolmitriptan and is 5 times more effective than oral almotriptan at these early time points. It is concluded that if a very early and clinically relevant effect is desired then the migraine patient should use the subcutaneous administration form of sumatriptan. PMID:19178578

  16. Studying Children's Early Literacy Development: Confirmatory Multidimensional Scaling Growth Modeling

    ERIC Educational Resources Information Center

    Ding, Cody

    2012-01-01

    There has been considerable debate over the ways in which children's early literacy skills develop over time. Using confirmatory multidimensional scaling (MDS) growth analysis, this paper directly tested the hypothesis of a cumulative trajectory versus a compensatory trajectory of development in early literacy skills among a group of 1233…

  17. 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…

  18. 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…

  19. Supporting Early Childhood Educators through Professional Development Partnerships

    ERIC Educational Resources Information Center

    Mraz, Maryann

    2011-01-01

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

  20. 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…

  1. Achievement Gap. Early Developments. Volume 11, Number 2, Fall 2007

    ERIC Educational Resources Information Center

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

    2007-01-01

    Research has identified a host of factors that likely contribute to the disparity in achievement, negating the possibility that a one-size-fits-all answer exists. Therefore, the initiatives highlighted in this issue of "Early Developments" address a variety of approaches. This issue of "Early Developments" includes the following articles: (1) The…

  2. 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…

  3. The Young Black Child: His Early Education and Development.

    ERIC Educational Resources Information Center

    Ward, Evangeline H.

    The early education and development of the black child must involve his sense of who he is as a basic component of any services designed for him. This is most effectively achieved by those who care most, are most knowledgeable about his culture, are willing to learn about early human development, and are devoted to adapting all of these to each…

  4. Program Evaluation. Early Developments. Volume 8, Number 3, Fall 2004

    ERIC Educational Resources Information Center

    Manuel, John

    2004-01-01

    This issue of "Early Developments" is devoted to program evaluation, a type of work that many at FPG are engaged in, either conducting evaluations or helping agencies and states conduct evaluations. Many readers know FPG for its research in prevention, early intervention, child care, and child and family development, but in the past several years,…

  5. 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…

  6. A Randomized Clinical Trial of Foster Care as an Intervention for Early Institutionalization: Long Term Improvements in White Matter Microstructure

    PubMed Central

    Bick, Johanna; Zhu, Tong; Stamoulis, Catherine; Fox, Nathan A.; Zeanah, Charles

    2015-01-01

    Importance Severe early life neglect is associated with compromises in brain development and associated behavioral functioning. Although early intervention has been shown to support more normative trajectories of brain development, specific improvements in white matter pathways that underlie emotional and cognitive development are unknown. Objective To examine associations between early life neglect, early intervention, and microstructural integrity of white matter pathways in middle childhood. Design, setting, and participants The Bucharest Early Intervention Project is a randomized clinical trial of high quality foster care as an intervention for institutionally reared children in Bucharest, Romania. During infancy, children were randomly selected to remain in an institution or to be placed into foster care. Developmental trajectories of these children were compared to a group of socio-demographically matched children reared in biological families at baseline and several points throughout development. At around eight years of age, 69 of the original 136 children underwent structural MRI scans. Intervention(s) for Clinical Trials Institutionally reared children were randomized into high quality foster homes in Bucharest, Romania. Main Outcome Measure(s) Four estimates of white matter integrity (Fractional Anisotropy, and Mean, Radial, and Axial Diffusivity) for 48 white matter tracts throughout the brain were obtained through Diffusion Tensor Imaging. Results Significant associations emerged between early life neglect and microstructural integrity of the body of the corpus callosum and tracts involved in limbic circuitry (fornix crus, cingulum), fronto-striatal circuitry (anterior and superior corona radiata, external capsule) and sensory processing (medial lemniscus, retrolenticular internal capsule). Follow up analyses revealed that early intervention promoted more normative white matter development among previously neglected children who entered foster care

  7. 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…

  8. Biologic perspective on early erotic development.

    PubMed

    Yates, Alayne

    2004-07-01

    Neurobiologic researchers can understand children's sexuality in less moral and more biologic terms. Genetically programmed levels of neurotransmitters and hormones establish a baseline trajectory of erotic interest and activity across the lifespan. Environmental influences also contribute. Intense early stimulation can affect the brain and create a condition of hyper eroticism, whereas too little stimulation can limit the ability to bond and impair the sexual response. Children who are erotically challenged or challenging are viewed correctly as having a brain imbalance, rather than as victims or as being morally deficient. This should pave the way for more humane, objective, and effective interventions. PMID:15183369

  9. Early history of electroencephalography and establishment of the American Clinical Neurophysiology Society.

    PubMed

    Stone, James L; Hughes, John R

    2013-02-01

    The field of electroencephalography (EEG) had its origin with the discovery of recordable electrical potentials from activated nerves and muscles of animals and in the last quarter of the 19th century from the cerebral cortex of animals. By the 1920s, Hans Berger, a neuropsychiatrist from Germany, recorded potentials from the scalp of patients with skull defects and, a few years later, with more sensitive equipment from intact subjects. Concurrently, the introduction of electronic vacuum tube amplification and the cathode ray oscilloscope was made by American physiologists or "axonologists," interested in peripheral nerve recordings. Berger's findings were independently confirmed in early 1934 by Lord Adrian in England and by Hallowell Davis at Harvard, in the United States. In the United States, the earliest contributions to human EEG were made by Hallowell Davis, Herbert H. Jasper, Frederic A. Gibbs, William Lennox, and Alfred L. Loomis. Remarkable progress in the development of EEG as a useful clinical tool followed the 1935 report by the Harvard group on the electrographic and clinical correlations in patients with absence (petit mal) seizures and altered states of consciousness. Technical aspects of the EEG and additional clinical EEG correlations were elucidated by the above investigators and a number of others. Further study led to gatherings of the EEG pioneers at Loomis' laboratory in New York (1935-1939), Regional EEG society formation, and the American Clinical Neurophysiology Society in 1946. PMID:23377440

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

    MedlinePlus

    ... health, behavior, school performance and other indicators of development in infancy, early childhood, middle childhood and middle adolescence. SECCYD is the most comprehensive study of children and the many environments in which they develop. The NICHD supported the ...

  11. Comparative transcriptomics of early dipteran development

    PubMed Central

    2013-01-01

    Background Modern sequencing technologies have massively increased the amount of data available for comparative genomics. Whole-transcriptome shotgun sequencing (RNA-seq) provides a powerful basis for comparative studies. In particular, this approach holds great promise for emerging model species in fields such as evolutionary developmental biology (evo-devo). Results We have sequenced early embryonic transcriptomes of two non-drosophilid dipteran species: the moth midge Clogmia albipunctata, and the scuttle fly Megaselia abdita. Our analysis includes a third, published, transcriptome for the hoverfly Episyrphus balteatus. These emerging models for comparative developmental studies close an important phylogenetic gap between Drosophila melanogaster and other insect model systems. In this paper, we provide a comparative analysis of early embryonic transcriptomes across species, and use our data for a phylogenomic re-evaluation of dipteran phylogenetic relationships. Conclusions We show how comparative transcriptomics can be used to create useful resources for evo-devo, and to investigate phylogenetic relationships. Our results demonstrate that de novo assembly of short (Illumina) reads yields high-quality, high-coverage transcriptomic data sets. We use these data to investigate deep dipteran phylogenetic relationships. Our results, based on a concatenation of 160 orthologous genes, provide support for the traditional view of Clogmia being the sister group of Brachycera (Megaselia, Episyrphus, Drosophila), rather than that of Culicomorpha (which includes mosquitoes and blackflies). PMID:23432914

  12. Clinical Development of Immune Checkpoint Inhibitors.

    PubMed

    Ito, Ayumu; Kondo, Shunsuke; Tada, Kohei; Kitano, Shigehisa

    2015-01-01

    Recent progress in cancer immunotherapy has been remarkable. Most striking are the clinical development and approval of immunomodulators, also known as immune checkpoint inhibitors. These monoclonal antibodies (mAb) are directed to immune checkpoint molecules, which are expressed on immune cells and mediate signals to attenuate excessive immune reactions. Although mAbs targeting tumor associated antigens, such as anti-CD20 mAb and anti-Her2 mAb, directly recognize tumor cells and induce cell death, immune checkpoint inhibitors restore and augment the antitumor immune activities of cytotoxic T cells by blocking immune checkpoint molecules on T cells or their ligands on antigen presenting and tumor cells. Based on preclinical data, many clinical trials have demonstrated the acceptable safety profiles and efficacies of immune checkpoint inhibitors in a variety of cancers. The first in class approved immune checkpoint inhibitor is ipilimumab, an anti-CTLA-4 (cytotoxic T lymphocyte antigen-4) mAb. Two pivotal phase III randomized controlled trials demonstrated a survival benefit in patients with metastatic melanoma. In 2011, the US Food and Drug Administration (FDA) approved ipilimumab for metastatic melanoma. Several clinical trials have since investigated new agents, alone and in combination, for various cancers. In this review, we discuss the current development status of and future challenges in utilizing immune checkpoint inhibitors. PMID:26161407

  13. Clinical Development of Immune Checkpoint Inhibitors

    PubMed Central

    Ito, Ayumu; Kondo, Shunsuke; Tada, Kohei; Kitano, Shigehisa

    2015-01-01

    Recent progress in cancer immunotherapy has been remarkable. Most striking are the clinical development and approval of immunomodulators, also known as immune checkpoint inhibitors. These monoclonal antibodies (mAb) are directed to immune checkpoint molecules, which are expressed on immune cells and mediate signals to attenuate excessive immune reactions. Although mAbs targeting tumor associated antigens, such as anti-CD20 mAb and anti-Her2 mAb, directly recognize tumor cells and induce cell death, immune checkpoint inhibitors restore and augment the antitumor immune activities of cytotoxic T cells by blocking immune checkpoint molecules on T cells or their ligands on antigen presenting and tumor cells. Based on preclinical data, many clinical trials have demonstrated the acceptable safety profiles and efficacies of immune checkpoint inhibitors in a variety of cancers. The first in class approved immune checkpoint inhibitor is ipilimumab, an anti-CTLA-4 (cytotoxic T lymphocyte antigen-4) mAb. Two pivotal phase III randomized controlled trials demonstrated a survival benefit in patients with metastatic melanoma. In 2011, the US Food and Drug Administration (FDA) approved ipilimumab for metastatic melanoma. Several clinical trials have since investigated new agents, alone and in combination, for various cancers. In this review, we discuss the current development status of and future challenges in utilizing immune checkpoint inhibitors. PMID:26161407

  14. Clinical correlates of raphe serotonergic dysfunction in early Parkinson's disease.

    PubMed

    Qamhawi, Zahi; Towey, David; Shah, Bina; Pagano, Gennaro; Seibyl, John; Marek, Kenneth; Borghammer, Per; Brooks, David James; Pavese, Nicola

    2015-10-01

    Post-mortem and neuroimaging studies suggest that the serotonergic system, which originates from the brainstem raphe nuclei, is disrupted in Parkinson's disease. This could contribute to the occurrence of non-motor symptoms and tremor, which are only partially explained by dopamine loss. However, the level of involvement of the serotonergic raphe nuclei in early Parkinson's disease is still debated. (123)I-FP-CIT single photon emission computed tomography is a marker of dopamine and serotonin transporter availability. While (123)I-FP-CIT binds primarily to dopamine transporters in the striatum, its binding in the brainstem raphe nuclei reflects serotonin transporter availability. We interrogated baseline single photon emission computed tomography scans of subjects recruited by the Parkinson's Progression Markers Initiative to determine: (i) the integrity of the brainstem raphe nuclei in early Parkinson's disease; and (ii) whether raphe serotonin transporter levels correlate with severity of tremor and symptoms of fatigue, depression, and sleep disturbance. Three hundred and forty-five patients with early drug-naïve Parkinson's disease, 185 healthy controls, and 56 subjects with possible Parkinson's disease without evidence of dopaminergic deficit were included. In the Parkinson's disease cohort, 37 patients had a tremulous, 106 patients had a pure akinetic-rigid, and 202 had a mixed phenotype. Patients with Parkinson's disease had significantly lower serotonin transporter availability in the brainstem raphe nuclei compared to controls (P < 0.01) and subjects without evidence of dopaminergic deficit (P < 0.05). However, only 13% of patients with Parkinson's disease individually had reduced signals. Raphe serotonin transporter availability over the entire Parkinson's disease cohort were associated with rest tremor amplitude (β = -0.106, P < 0.05), rest tremor constancy (β = -0.109, P < 0.05), and index of rest tremor severity (β = -0.104, P < 0.05). The tremulous

  15. Developing a section labeler for clinical documents.

    PubMed

    Haug, Peter J; Wu, Xinzi; Ferraro, Jeffery P; Savova, Guergana K; Huff, Stanley M; Chute, Christopher G

    2014-01-01

    Natural language processing (NLP) technologies provide an opportunity to extract key patient data from free text documents within the electronic health record (EHR). We are developing a series of components from which to construct NLP pipelines. These pipelines typically begin with a component whose goal is to label sections within medical documents with codes indicating the anticipated semantics of their content. This Clinical Section Labeler prepares the document for further, focused information extraction. Below we describe the evaluation of six algorithms designed for use in a Clinical Section Labeler. These algorithms are trained with N-gram-based feature sets extracted from document sections and the document types. In the evaluation, 6 different Bayesian models were trained and used to assign one of 27 different topics to each section. A tree-augmented Bayesian network using the document type and N-grams derived from section headers proved most accurate in assigning individual sections appropriate section topics. PMID:25954369

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

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-01

    ...The Food and Drug Administration (FDA) is announcing the availability of the guidance entitled ``Investigational Device Exemptions (IDEs) for Early Feasibility Medical Device Clinical Studies, Including Certain First in Human (FIH) Studies.'' Through the approaches announced in this guidance, FDA intends to facilitate early feasibility studies of medical devices, using appropriate risk......

  18. The Impact of Early Clinical Training in Medical Education: A Multi-Institutional Assessment.

    ERIC Educational Resources Information Center

    Carney, Patricia A.; Bar-on, Miriam E.; Grayson, Martha S.; Klein, Martin; Cochran, Nan; Eliassen, M. Scottie; Gambert, Steven R.; Gupta, Krishan L.; Labrecque, Mary C.; Munson, Paul J.; Nierenberg, David W.; O'Donnell, Joseph F.; Whitehurst-Cook, Michelle; Willett, Rita M.

    1999-01-01

    Funded by the Generalist Physician Initiative, Dartmouth Medical School (New Hampshire), Virginia Commonwealth University, and New York Medical College adopted early community-based training models for longitudinal clinical experiences. The three programs, the methods used to evaluate an aspect of the program, lessons learned about early clinical…

  19. Dual language exposure and early bilingual development*

    PubMed Central

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

    2015-01-01

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

  20. 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.

  1. Early Numeracy Assessment: The Development of the Preschool Early Numeracy Scales

    ERIC Educational Resources Information Center

    Purpura, David J.; Lonigan, Christopher J.

    2015-01-01

    Research Findings: The focus of this study was to construct and validate 12 brief early numeracy assessment tasks that measure the skills and concepts identified as key to early mathematics development by the National Council of Teachers of Mathematics (2006) and the National Mathematics Advisory Panel (2008)-as well as critical developmental…

  2. 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. PMID:24705660

  3. 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. PMID:26857973

  4. 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

  5. Economic Deprivation and Early-Childhood Development.

    ERIC Educational Resources Information Center

    Duncan, Greg J.; And Others

    This study used longitudinal data from the Infant Health and Development Program (IHDP) to examine three issues regarding effects of economic deprivation on child development: (1) the effects on children's developmental outcomes of poverty and such poverty correlates as single parenthood, ethnicity, and maternal education; (2) the developmental…

  6. 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…

  7. 76 FR 9583 - Draft Guidance for Industry on Clinical Pharmacogenomics: Premarketing Evaluation in Early Phase...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-18

    ..., metabolism, and excretion), and pharmacodynamics (i.e., all of the effects of the drug on various physiologic... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Clinical Pharmacogenomics: Premarketing Evaluation in Early Phase Clinical Studies; Availability AGENCY: Food and Drug Administration,...

  8. 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,…

  9. Alberta Learning: Early Development Instrument Pilot Project Evaluation.

    ERIC Educational Resources Information Center

    Meaney, Wanda; Harris-Lorenze, Elayne

    The Early Development Instrument (EDI) was designed by McMaster University to measure the outcomes of childrens early years as they influence their readiness to learn at school. The EDI was piloted in several Canadian cities in recent years through two national initiatives. Building on these initiatives, Alberta Learning piloted the EDI as a…

  10. 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…

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

    ERIC Educational Resources Information Center

    Bain, Julie; James, Deborah; Harrison, Mary

    2015-01-01

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

  12. 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…

  13. Framing Early Childhood Development: Strategic Communications and Public Preferences

    ERIC Educational Resources Information Center

    Gilliam, Franklin D.; Bales, Susan Nall

    2004-01-01

    This brief focuses on the potential role that strategic communications can play in helping state (Maternal Child Health) MCH programs and their collaborating partners frame their message to enhance the public's understanding of the importance of early child development and the need for a comprehensive and integrated early childhood system. The…

  14. Online Professional Development: Choices for Early Childhood Educators

    ERIC Educational Resources Information Center

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

    2010-01-01

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

  15. The Influence of Early Stimulation on Language Development.

    ERIC Educational Resources Information Center

    Fowler, William; Swenson, Amy

    This longitudinal study explored the effects of early language stimulation upon norms of the language development of three infants. When the infants were 4-5 months old, a long-term program of intensified early language stimulation was implemented by weekly home tutoring sessions with the parents. The tutor stimulation program consisted of an…

  16. 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.…

  17. Education for Sustainable Development in Early Childhood Education in Finland

    ERIC Educational Resources Information Center

    Reunamo, Jyrki; Suomela, Liisa

    2013-01-01

    In the Finnish early childhood education and care (ECEC) curriculum, there is no specific content for education for sustainable development (ESD). Thus, it is not possible to get direct guidelines on how to conduct ESD in ECEC from the curriculum. We seek to look at the preferences of Finnish early childhood educators through the model of extended…

  18. Developing Prosocial Behaviors in Early Adolescence with Reactive Aggression

    ERIC Educational Resources Information Center

    Fung, Annis L. C.

    2008-01-01

    Despite the alarming rise of early adolescence aggression in Hong Kong, it is the pioneer evidence-based outcome study on Anger Coping Training (ACT) program for early adolescence with reactive aggression to develop their prosocial behaviors. This research program involved experimental and control groups with pre- and post-comparison using a …

  19. 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…

  20. The Play of Disabled Children in Early Development.

    ERIC Educational Resources Information Center

    Pirila, Silja; And Others

    Play is a central facilitating element of early development. As a child plays, he or she practices spontaneously cognitive, emotional, and motor abilities. This research project, part of a larger project on early intervention with young disabled children, investigated the play of children with a motor handicap. The sample consisted of 61 disabled…

  1. 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…

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

    ERIC Educational Resources Information Center

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

    2014-01-01

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

  3. 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. PMID:26828547

  4. 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.

  5. 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.

  6. History and clinical significance of early repolarization syndrome.

    PubMed

    Mahida, Saagar; Derval, Nicolas; Sacher, Frederic; Berte, Benjamin; Yamashita, Seigo; Hooks, Darren A; Denis, Arnaud; Lim, Han; Amraoui, Sana; Aljefairi, Nora; Hocini, Meleze; Jais, Pierre; Haissaguerre, Michel

    2015-01-01

    The early repolarization (ER) pattern has historically been regarded as a benign ECG variant. However, in recent years this view has been challenged based on multiple reports linking the ER pattern with an increased risk of sudden cardiac death. The mechanistic basis of ventricular arrhythmogenesis in ER syndrome is presently incompletely understood. Furthermore, strategies for risk stratification and therapy for ER syndrome remain suboptimal. The recent emergence of novel mapping techniques for cardiac arrhythmia has ushered a new era of research into the mechanistic basis of ER syndrome. This review provides an overview of current evidence relating to ER and risk of ventricular arrhythmias and discusses potential future areas of research to elucidate the mechanisms of ventricular arrhythmogenesis. PMID:25257090

  7. Social anxiety disorder: etiology and early clinical presentation.

    PubMed

    Beidel, D C

    1998-01-01

    Behavioral and biological theories addressing the etiology of social anxiety disorder are discussed. Although not often diagnosed until adolescence or adulthood, social anxiety disorder can have its onset during childhood. Early recognition and treatment of this condition may prevent both immediate and long-term detrimental outcomes and, possibly, the onset of comorbid conditions. However, special considerations are required for the diagnosis and treatment of childhood social anxiety disorder. Therapists face special challenges when treating youth with social anxiety disorder, including patient and parent considerations. Although not documented specifically for children with social anxiety disorders, data from families with anxious children suggest that familial factors may play a role in treatment outcome. PMID:9811427

  8. ECR-MAPK regulation in liver early development.

    PubMed

    Zhao, Xiu-Ju; Zhuo, Hexian

    2014-01-01

    Early growth is connected to a key link between embryonic development and aging. In this paper, liver gene expression profiles were assayed at postnatal day 22 and week 16 of age. Meanwhile another independent animal experiment and cell culture were carried out for validation. Significance analysis of microarrays, qPCR verification, drug induction/inhibition assays, and metabonomics indicated that alpha-2u globulin (extracellular region)-socs2 (-SH2-containing signals/receptor tyrosine kinases)-ppp2r2a/pik3c3 (MAPK signaling)-hsd3b5/cav2 (metabolism/organization) plays a vital role in early development. Taken together, early development of male rats is ECR and MAPK-mediated coordination of cancer-like growth and negative regulations. Our data represent the first comprehensive description of early individual development, which could be a valuable basis for understanding the functioning of the gene interaction network of infant development. PMID:25580437

  9. 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

    ... clinical trial design, including product characteristics, manufacturing considerations and preclinical... document provides recommendations with respect to these products as to clinical trial design, including... of Early-Phase Clinical Trials of Cellular and Gene Therapy Products; Availability AGENCY: Food...

  10. Nature's experiment? Handedness and early childhood development.

    PubMed

    Johnston, David W; Nicholls, Michael E R; Shah, Manisha; Shields, Michael A

    2009-05-01

    In recent years, a large body of research has investigated the various factors affecting child development and the consequent impact of child development on future educational and labor market outcomes. In this article, we contribute to this literature by investigating the effect of handedness on child development. This is an important issue given that around 10% of the world's population is left-handed and given recent research demonstrating that child development strongly affects adult outcomes. Using a large, nationally representative sample of young children, we find that the probability of a child being left-handed is not significantly related to child health at birth, family composition, parental employment, or household income. We also find robust evidence that left-handed (and mixed-handed) children perform significantly worse in nearly all measures of development than right-handed children, with the relative disadvantage being larger for boys than girls. Importantly, these differentials cannot be explained by different socioeconomic characteristics of the household, parental attitudes, or investments in learning resources. PMID:21305394

  11. Catumaxomab: clinical development and future directions.

    PubMed

    Linke, Rolf; Klein, Anke; Seimetz, Diane

    2010-01-01

    Catumaxomab, a monoclonal bispecific trifunctional antibody, was approved in the European Union in April 2009 for the intraperitoneal treatment of patients with malignant ascites. The marketing authorization holder Fresenius Biotech GmbH developed catumaxomab (Removab(®)) together with its partner TRION Pharma GmbH, Germany. It is the first substance worldwide with a regulatory label for the treatment of malignant ascites due to epithelial carcinomas. Since the peritoneum is of mesothelial origin and therefore lacks EpCAM expression, the intraperitoneal administration of catumaxomab is an attractive targeted immunotherapeutic approach. Catumaxomab is able to destroy EpCAM positive tumor cells in the peritoneal cavity known as the main cause of malignant ascites. In addition, catumaxomab is a potential therapeutic option for several primary tumors since the EpCAM molecule is expressed on the majority of epithelial carcinomas. This review focuses on the clinical development of catumaxomab and indicates future directions. PMID:20190561

  12. Early physical and motor development of mouse offspring exposed to valproic acid throughout intrauterine development.

    PubMed

    Podgorac, Jelena; Pešić, Vesna; Pavković, Željko; Martać, Ljiljana; Kanazir, Selma; Filipović, Ljupka; Sekulić, Slobodan

    2016-09-15

    Clinical research has identified developmental delay and physical malformations in children prenatally exposed to the antiepileptic drug (AED) valproic acid (VPA). However, the early signs of neurodevelopmental deficits, their evolution during postnatal development and growth, and the dose effects of VPA are not well understood. The present study aimed to examine the influence of maternal exposure to a wide dose range (50, 100, 200 and 400mg/kg/day) of VPA during breeding and gestation on early physical and neuromotor development in mice offspring. Body weight gain, eye opening, the surface righting reflex (SRR) and tail suspension test (TST) were examined in the offspring at postnatal days 5, 10 and 15. We observed that: (1) all tested doses of VPA reduced the body weight of the offspring and the timing of eye opening; (2) offspring exposed to VPA displayed immature forms of righting and required more time to complete the SRR; (3) latency for the first immobilization in the TST is shorter in offspring exposed to higher doses of VPA; however, mice in all groups exposed to VPA exhibited atypical changes in this parameter during the examined period of maturation; (4) irregularities in swinging and curling activities were observed in animals exposed to higher doses of VPA. This study points to delayed somatic development and postponed maturation of the motor system in all of the offspring prenatally exposed to VPA, with stronger effects observed at higher doses. The results implicate that the strategy of continuous monitoring of general health and achievements in motor milestones during the early postnatal development in prenatally VPA-exposed offspring, irrespectively of the dose applied, could help to recognize early developmental irregularities. PMID:27188530

  13. Global health and development in early childhood.

    PubMed

    Aboud, Frances E; Yousafzai, Aisha K

    2015-01-01

    Health and nutritional risks co-occur in the lives of children under the age of 2 years who live in developing countries. We review evidence showing how these risks, in addition to inadequate psychosocial stimulation, prevent children from developing expected cognitive and language abilities. A systematic review and meta-analysis of 21 interventions aimed at enhancing stimulation and 18 interventions that provided better nutrition--all conducted since 2000--revealed that stimulation had a medium effect size of 0.42 and 0.47 on cognitive and language development, respectively, whereas nutrition by itself had a small effect size of 0.09. The implementation processes of these interventions are described and compared. A number of unresolved issues are outlined and discussed, including ways to maximize parental health behavior change, assess mediators that account for intervention effects, and expand the assessment of young children's brain functions that underlie language and cognition and are affected by nutrition and stimulation. PMID:25196276

  14. Preventing the development of SLE: identifying risk factors and proposing pathways for clinical care.

    PubMed

    Choi, M Y; Barber, M R W; Barber, C E H; Clarke, A E; Fritzler, M J

    2016-07-01

    Although challenging, developing evidence-based approaches to an early and accurate diagnosis of systemic lupus erythematosus is a key approach to preventing disease and lupus-associated morbidity and mortality. Advances in our understanding of preclinical and incomplete lupus erythematosus have enabled the identification of risk factors that may predict disease and the development of potential strategies aimed at primary prevention. Emerging data support the notion that there is a temporal disease progression from initial asymptomatic autoimmunity (preclinical lupus) through early clinical features of the disease (incomplete lupus erythematosus) to finally becoming fully classifiable systemic lupus erythematosus (complete lupus erythematosus). Here, we review the demographic, clinical, biomarker as well as genetic and environmental features that are reported to increase the risk of disease progression. Based on these risk factors, we propose a clinical care pathway for patients with early disease. We envisage that such a pathway, through early identification of disease, may improve patient outcomes, while reducing health care costs. PMID:27252260

  15. Developing Microcomputer Programs for Early Literacy.

    ERIC Educational Resources Information Center

    Moxley, Roy A.; Barry, Pamela J.

    Through an adaptation of a language experience approach, microcomputer programs were designed to develop the literacy skills of four 4-year-old nursery school children. In order to document the design process, the intervention procedures, and their effects, case studies were made. Instruction was based on a highly interactive strategy with short,…

  16. Early developments in solar cooling equipment

    NASA Technical Reports Server (NTRS)

    Price, J. M.

    1978-01-01

    A brief description of a development program to design, fabricate and field test a series of solar operated or driven cooling devices, undertaken by the Marshall Space Flight Center in the context of the Solar Heating and Cooling Demonstration Act of 1974, is presented. Attention is given to two basic design concepts: the Rankine cycle principle and the use of a dessicant for cooling.

  17. 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…

  18. On Class Differences and Early Development.

    ERIC Educational Resources Information Center

    Kagan, Jerome

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

  19. Reading Development Subtypes and Their Early Characteristics

    ERIC Educational Resources Information Center

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

    2007-01-01

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

  20. Maternal DNA Methylation Regulates Early Trophoblast Development

    PubMed Central

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

    2016-01-01

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

  1. 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…

  2. 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…

  3. How education changes clinical documentation in early pregnancy.

    PubMed

    Ali, Fida; Higgins, Mary F

    2016-05-01

    The aim of this audit was to record medical history taking in the records of women attending with early pregnancy issues in order to assess the effect of training in this area. The medical education intervention comprised of a 30-min interactive tutorial. Retrospective chart review at three time points: pre education (July 2013, n = 45), immediately post-education (August 2013, n = 45) and longer term post-intervention (October 2013, n = 20). Pre-education, medical history was missing in 77.8% of charts compared to 13.4% immediately post-intervention and 10% long-term post-intervention (p < 0.05). Similar findings were noted with regard to documentation of age, surgical history, medications, allergies and last menstrual period (LMP). While there was a high rate of ultrasound investigations, the documentation of these (by placing an image in the chart) improved after the intervention. Education in requirements for medical history taking can improve documentation. PMID:26789554

  4. Early clinical experience with the POEM procedure for achalasia

    PubMed Central

    Hong, Dennis; Pescarus, Radu; Khan, Rana; Ambrosini, Luciano; Anvari, Mehran; Cadeddu, Margherita

    2015-01-01

    Background Per oral endoscopic myotomy (POEM) is a viable alternative to standard Heller myotomy for surgical treatment of achalasia. Outcomes from the United States, Europe and Asia have been reported. We sought to report data after the initiation of POEM in a Canadian centre. Methods We enrolled patients with achalasia in a research ethics board–approved pilot study. Surgeons learned the POEM procedure in a systematic manner that included visiting experts in POEM, practice in an animal laboratory and mentoring from POEM experts. Preoperative evaluation included manometry, 24-hour pH, barium swallow, endoscopy and Eckhardt Symptom Score. All patients underwent gastrograffin swallow on postoperative day 1. Patients were re-evaluated using the Eckhardt score on postoperative day 14. Results Ten patients underwent POEM. Seven patients had previous endoscopic treatments: 6 had balloon dilatation and 1 had botulinum toxin injection. Mean preoperative Eckhardt score was 8.1 ± 2.4. Mean preoperative lower esophageal sphincter resting and residual pressure was 32.3 ± 9.2 and 20.8 ± 5.3, respectively. Mean duration of surgery was 141.3 ± 43.7 minutes. Mean length of hospital stay was 1 day. No major perioperative complications occurred. On postoperative day 14, the mean Eckhardt score was 1 ± 1.2. Conclusion Our approach to POEM introduction was systematic and deliberate. The procedure is safe, feasible and has good perioperative outcomes. Our early results are consistent with current literature. PMID:26574830

  5. Percutaneous coronary angioscopy with a new steerable microangioscope: experimental and early clinical results

    NASA Astrophysics Data System (ADS)

    Ramee, Stephen R.; White, Christopher J.; Mesa, Juan E.; Murgo, Joseph P.; Doyle, Andrew T.; McQueen, Colleen L.

    1990-07-01

    We have developed a new, steerable microangioscope for performing percutaneous coronary angioscopy. The angioscopic catheter is made of polyethylene, contains a distal balloon for occlusion of blood flow during imaging, fits through an 8 Fr percutaneous coronary angioplasty (PTCA) guiding catheter and is steerable by means of a guidewire. Initial feasibility was demonstrated in animal studies involving both peripheral and coronary arteries. Angioscopic findings in normal vessels included normal endothelial surface, collateral blood flow, and side branches. Angioscopy was also performed after balloon denudation of the arteries, laser- assisted balloon angioplasty, and stent implantation. In early human clinical trials we have performed percutaneous angioscopy in six patients undergoing percutaneous coronary angioplasty without complications. Findings in these patients include atherosclerotic plaque, thrombus, and dissection. This new device has great potential for use in the research, diagnosis, and treatment of coronary atherosclerosis.

  6. Branch Mode Selection during Early Lung Development

    PubMed Central

    Menshykau, Denis; Kraemer, Conradin; Iber, Dagmar

    2012-01-01

    Many organs of higher organisms, such as the vascular system, lung, kidney, pancreas, liver and glands, are heavily branched structures. The branching process during lung development has been studied in great detail and is remarkably stereotyped. The branched tree is generated by the sequential, non-random use of three geometrically simple modes of branching (domain branching, planar and orthogonal bifurcation). While many regulatory components and local interactions have been defined an integrated understanding of the regulatory network that controls the branching process is lacking. We have developed a deterministic, spatio-temporal differential-equation based model of the core signaling network that governs lung branching morphogenesis. The model focuses on the two key signaling factors that have been identified in experiments, fibroblast growth factor (FGF10) and sonic hedgehog (SHH) as well as the SHH receptor patched (Ptc). We show that the reported biochemical interactions give rise to a Schnakenberg-type Turing patterning mechanisms that allows us to reproduce experimental observations in wildtype and mutant mice. The kinetic parameters as well as the domain shape are based on experimental data where available. The developed model is robust to small absolute and large relative changes in the parameter values. At the same time there is a strong regulatory potential in that the switching between branching modes can be achieved by targeted changes in the parameter values. We note that the sequence of different branching events may also be the result of different growth speeds: fast growth triggers lateral branching while slow growth favours bifurcations in our model. We conclude that the FGF10-SHH-Ptc1 module is sufficient to generate pattern that correspond to the observed branching modes. PMID:22359491

  7. Branch mode selection during early lung development.

    PubMed

    Menshykau, Denis; Kraemer, Conradin; Iber, Dagmar

    2012-01-01

    Many organs of higher organisms, such as the vascular system, lung, kidney, pancreas, liver and glands, are heavily branched structures. The branching process during lung development has been studied in great detail and is remarkably stereotyped. The branched tree is generated by the sequential, non-random use of three geometrically simple modes of branching (domain branching, planar and orthogonal bifurcation). While many regulatory components and local interactions have been defined an integrated understanding of the regulatory network that controls the branching process is lacking. We have developed a deterministic, spatio-temporal differential-equation based model of the core signaling network that governs lung branching morphogenesis. The model focuses on the two key signaling factors that have been identified in experiments, fibroblast growth factor (FGF10) and sonic hedgehog (SHH) as well as the SHH receptor patched (Ptc). We show that the reported biochemical interactions give rise to a Schnakenberg-type Turing patterning mechanisms that allows us to reproduce experimental observations in wildtype and mutant mice. The kinetic parameters as well as the domain shape are based on experimental data where available. The developed model is robust to small absolute and large relative changes in the parameter values. At the same time there is a strong regulatory potential in that the switching between branching modes can be achieved by targeted changes in the parameter values. We note that the sequence of different branching events may also be the result of different growth speeds: fast growth triggers lateral branching while slow growth favours bifurcations in our model. We conclude that the FGF10-SHH-Ptc1 module is sufficient to generate pattern that correspond to the observed branching modes. PMID:22359491

  8. Lineage determinants in early endocrine development

    PubMed Central

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

    2013-01-01

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

  9. Pattern formation during early floral development.

    PubMed

    Vaddepalli, Prasad; Scholz, Sebastian; Schneitz, Kay

    2015-06-01

    Flowers are central to sexual reproduction in plants. The study of floral development proved tremendously successful in obtaining key insight into processes, such as fate determination, pattern formation, and growth regulation. Recent advances relate to the complex mechanisms underlying the crosstalk between phytohormone signaling, cell and tissue mechanics, and regulatory gene networks that positions floral buds at the apex and directs floral specification, initiation and outgrowth. Furthermore, progress has been made in elucidating the intercellular communication and temporal coordination necessary to organize the behavior of the various functional subdomains within the young flower. PMID:25687790

  10. Inside information: Financial conflicts of interest for research subjects in early phase clinical trials.

    PubMed

    Helft, Paul R; Ratain, Mark J; Epstein, Richard A; Siegler, Mark

    2004-05-01

    In recent years, several research subjects have told us that they had bought or intended to buy stock in the companies sponsoring the clinical trials in which they were enrolled. This situation has led us to ask what, if any, are physician-investigators' scientific, ethical, and legal responsibilities concerning research subjects who choose to buy stock in the companies sponsoring the clinical trials in which they are participating. Although the scope of this problem is unknown and is likely to be small, this commentary examines the scientific, ethical, and legal concerns raised by such activities on the part of research subjects enrolled in early phase clinical trials. In addition, this commentary also outlines the basis for our opinion that research subjects involved in an early phase clinical trial should avoid the financial conflicts of interest created by trading stock in the company sponsoring the clinical trial. PMID:15126602

  11. 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.

  12. Epigenetic Control of Early Mouse Development.

    PubMed

    Lim, C Y; Knowles, B B; Solter, D; Messerschmidt, D M

    2016-01-01

    Although the genes sequentially transcribed in the mammalian embryo prior to implantation have been identified, understanding of the molecular processes ensuring this transcription is still in development. The genomes of the sperm and egg are hypermethylated, hence transcriptionally silent. Their union, in the prepared environment of the egg, initiates their epigenetic genomic reprogramming into a totipotent zygote, in which the genome gradually becomes transcriptionally activated. During gametogenesis, sex-specific processes result in sperm and eggs with disparate epigenomes, both of which require drastic reprogramming to establish the totipotent genome of the zygote and the pluripotent inner cell mass of the blastocyst. Herein, we describe the factors, DNA and histone modifications, activation and repression of retrotransposons, and cytoplasmic localizations, known to influence the activation of the mammalian genome at the initiation of new life. PMID:27475856

  13. 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. PMID:25910905

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

    ERIC Educational Resources Information Center

    Australian Institute of Health and Welfare, 2011

    2011-01-01

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

  15. 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…

  16. Translation and Clinical Development of Antithrombotic Aptamers.

    PubMed

    Nimjee, Shahid M; Povsic, Thomas J; Sullenger, Bruce A; Becker, Richard C

    2016-06-01

    Thrombosis is a necessary physiological process to protect the body from uncontrolled bleeding. Pathological thrombus formation can lead to devastating clinical events including heart attack, stroke, deep vein thrombosis, pulmonary embolism, and disseminated intravascular coagulation. Numerous drugs have been developed to inhibit thrombosis. These have been targeted to coagulation factors along with proteins and receptors that activate platelets. While these drugs are effective at preventing blood clotting, their major side effect is inadvertent hemorrhage that can result in significant morbidity and mortality. There exists a need for anticoagulants that are not only effective at preventing thrombosis but can also be readily reversed. Aptamers offer a potential solution, representing a new class of drug agents that can be isolated to any protein and where antidote oligonucleotides can be designed based on the sequence of the aptamer. We present a summary of the anticoagulant and antithrombotic aptamers that have been identified and their stage of development and comment on the future of aptamer-based drug development to treat thrombosis. PMID:26882082

  17. Case studies in clinical practice development.

    PubMed

    Chopra, Romi; Lipman, John; Murphy, Timothy P

    2005-03-01

    By asking identical questions of several successful practitioners of clinical interventional radiology, a snapshot of the current and future status of interventional radiology as a clinical discipline is presented. PMID:21326672

  18. Origins and early development of human body knowledge.

    PubMed

    Slaughter, Virginia; Heron, Michelle

    2004-01-01

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

  19. Distinguishing malaria and influenza: Early clinical features in controlled human experimental infection studies☆

    PubMed Central

    Lillie, Patrick J.; Duncan, Christopher J.A.; Sheehy, Susanne H.; Meyer, Joel; O'Hara, Geraldine A.; Gilbert, Sarah C.; Hill, Adrian V.S.

    2012-01-01

    Summary During the H1N1 influenza pandemic (pH1N1/09) diagnostic algorithms were developed to guide antiviral provision. However febrile illnesses are notoriously difficult to distinguish clinically. Recent evidence highlights the importance of incorporating travel history into diagnostic algorithms to prevent the catastrophic misdiagnosis of life-threatening infections such as malaria. We applied retrospectively the UK pH1N1/09 case definition to a unique cohort of healthy adult volunteers exposed to Plasmodium falciparum malaria or influenza to assess the predictive value of this case definition, and to explore the distinguishing clinical features of early phase infection with these pathogens under experimental conditions. For influenza exposure the positive predictive value of the pH1N1/09 case definition was only 0.38 (95% CI: 0.06–0.60), with a negative predictive value of 0.27 (95% CI: 0.02–0.51). Interestingly, 8/11 symptomatic malaria-infected adults would have been inappropriately classified with influenza by the pH1N1/09 case definition, while 5/8 symptomatic influenza-exposed volunteers would have been classified without influenza (P = 0.18 Fisher's exact). Cough (P = 0.005) and nasal symptoms (P = 0.001) were the only clinical features that distinguished influenza-exposed from malaria-exposed volunteers. An open mind regarding the clinical cause of undifferentiated febrile illness, particularly in the absence of upper respiratory tract symptoms, remains important even during influenza pandemic settings. These data support incorporating travel history into pandemic algorithms. PMID:22531678

  20. 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,…

  1. Developing a Critical Practice of Clinical Supervision.

    ERIC Educational Resources Information Center

    Smyth, W. John

    1985-01-01

    The etymology of the term "clinical supervision" is discussed. How clinical supervision can be used with teachers as an active force toward reform and change is then examined. Through clinical supervision teachers can assist each other to gain control over their own professional lives and destinies. (RM)

  2. 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. PMID:21335698

  3. Changes of MR and DTI appearance in early human brain development

    NASA Astrophysics Data System (ADS)

    Marc, Cassian; Vachet, Clement; Gerig, Guido; Blocher, Joseph; Gilmore, John; Styner, Martin

    2010-03-01

    Understanding myelination in early brain development is of clinical importance, as many neurological disorders have their origin in early cerebral organization and maturation. The goal of this work is to study a large neonate database acquired with standard MR imagery to illuminate effects of early development in MRI. 90 neonates were selected from a study of healthy brain development. Subjects were imaged via MRI postnatally. MR acquisition included high-resolution structural and diffusion tensor images. Unbiased atlases for structural and DTI data were generated and co-registered into a single coordinate frame for voxel-wise comparison of MR and DTI appearance across time. All original datasets were mapped into this frame and structural image data was additionally intensity normalized. In addition, myelinated white matter probabilistic segmentations from our neonate tissue segmentation were mapped into the same space to study how our segmentation results were affected by the changing intensity characteristics in early development Linear regression maps and p-value maps were computed and visualized. The resulting visualization of voxelswise corresponding maps of all MR and DTI properties captures early development information in MR imagery. Surprisingly, we encountered regions of seemingly decreased myelinated WM probability over time even though we expected a confident increase for all of the brain. The intensity changes in the MR images in those regions help explain this counterintuitive result. The regressional results indicate that this is an effect of intensity changes due not solely to myelination processes but also likely brain dehydration processes in early postnatal development.

  4. 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…

  5. 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. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26526165

  6. Skeletal adverse effects with aromatase inhibitors in early breast cancer: evidence to date and clinical guidance

    PubMed Central

    Servitja, Sonia; Martos, Tamara; Rodriguez Sanz, Maria; Garcia-Giralt, Natalia; Prieto-Alhambra, Daniel; Garrigos, Laia; Nogues, Xavier

    2015-01-01

    Aromatase inhibitors (AIs) are routinely used in the adjuvant treatment of women with hormone receptor-positive early breast cancer. Patients who receive AIs have an increased risk of bone loss and arthralgia compared with those treated with tamoxifen. In addition to the effects of AIs, the population of women with early breast cancer has a high prevalence of 25-hydroxyvitamin D (25(OH)D) insufficiency. In our experience 88% of patients had concentrations lower than 30 ng/ml. Vitamin D supplementation should be adapted to the baseline concentration. Another relevant finding in our research program was the close relationship between 25(OH)D levels and intensity of AI-related arthralgia (AIrA). A target concentration of 40 ng/ml 25(OH)D may prevent development of AIrA. We also demonstrate that AIrA is genetically determined: single nucleotide polymorphisms located in genes encoding key factors for the metabolism of estrogens and vitamin D (CYP17A1, VDR, and CYP27B1) are associated with self-reported arthralgia during AI therapy. We recommend establishing an individualized protocol of bone-health surveillance based on baseline and evolutionary clinical variables. PMID:26327926

  7. Early warning and clinical outcome prediction of acute-on-chronic hepatitis B liver failure

    PubMed Central

    Chen, En-Qiang; Zeng, Fan; Zhou, Ling-Yun; Tang, Hong

    2015-01-01

    Hepatitis B virus (HBV) associated acute-on-chronic liver failure (ACLF) is an increasingly recognized fatal liver disease encompassing a severe acute exacerbation of liver function in patients with chronic hepatitis B (CHB). Despite the introduction of an artificial liver support system and antiviral therapy, the short-term prognosis of HBV-ACLF is still extremely poor unless emergency liver transplantation is performed. In such a situation, stopping or slowing the progression of CHB to ACLF at an early stage is the most effective way of reducing the morbidity and mortality of HBV-ACLF. It is well-known that the occurrence and progression of HBV-ACLF is associated with many factors, and the outcomes of HBV-ACLF patients can be significantly improved if timely and appropriate interventions are provided. In this review, we highlight recent developments in early warning and clinical outcome prediction in patients with HBV-ACLF and provide an outlook for future research in this field. PMID:26576085

  8. Evaluation of a clinical tool for early etiology identification in status epilepticus

    PubMed Central

    Alvarez, Vincent; Westover, M. Brandon; Drislane, Frank W.; Dworetzky, Barbara A.; Curley, David

    2016-01-01

    Summary Objectives Because early etiologic identification is critical to select appropriate specific status epilepticus (SE) management, we aim to validate a clinical tool we developed that uses history and readily available investigations to guide prompt etiologic assessment. Methods This prospective multicenter study included all adult patients treated for SE of all but anoxic causes from four academic centers. The proposed tool is designed as a checklist covering frequent precipitating factors for SE. The study team completed the checklist at the time the patient was identified by electroencephalography (EEG) request. Only information available in the emergency department or at the time of in-hospital SE identification was used. Concordance between the etiology indicated by the tool and the determined etiology at hospital discharge was analyzed, together with interrater agreement. Results Two hundred twelve patients were included. Concordance between the etiology hypothesis generated using the tool and the finally determined etiology was 88.7% (95% confidence interval (CI) 86.4–89.8) (κ = 0.88). Interrater agreement was 83.3% (95% CI 80.4–96) (κ = 0.81). Significance This tool is valid and reliable for identification early the etiology of an SE. Physicians managing patients in SE may benefit from using it to identify promptly the underlying etiology, thus facilitating selection of the appropriate treatment. PMID:25385281

  9. 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. PMID:24698029

  10. Ramucirumab Clinical Development: an Emerging Role in Gastrointestinal Tumors.

    PubMed

    Sanchez-Gastaldo, Amparo; Gonzalez-Exposito, Reyes; Garcia-Carbonero, Rocío

    2016-08-01

    Ramucirumab (IMC-1121B, LY3009806) is a fully human G1 monoclonal antibody that specifically targets vascular endotelial growth factor receptor 2 (VEGFR-2) with a substantially greater binding affinity than that of its natural ligands. Early clinical trials in patients with advanced solid tumors demonstrated that biologically relevant blood target concentrations are achievable with tolerable doses, and also showed some preliminary evidence of clinical activity. Several pivotal phase III trials have now been concluded and have led regulatory agencies to grant marketing authorization to ramucirumab for use as second line therapy in patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma (as single agent or in combination with paclitaxel), in patients with advanced colorectal carcinoma (CRC) (in combination with infusional fluorouracil and irinotecan (FOLFIRI regimen)) and in patients with advanced non-small cell lung cancer (NSCLC) (in combination with docetaxel). In contrast, ramucirumab failed to significantly improve survival versus placebo as second line therapy in patients with advanced hepatocellular carcinoma (HCC). The aim of this review is to summarize the clinical development and emerging role of ramucirumab in gastrointestinal (GI) tumors, including relevant aspects of its mechanism of action, pharmacology, safety profile, and antitumor activity in gastric, HCC, and CRC carcinomas. PMID:26887374

  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. Clinical Characteristics and Prognostic Factors in Early-Onset Alopecia Totalis and Alopecia Universalis

    PubMed Central

    Cho, Hyun Hee; Jo, Seong Jin; Paik, Seung Hwan; Jeon, Hye Chan; Kim, Kyu Han; Eun, Hee Chul

    2012-01-01

    Alopecia totalis (AT) and alopecia universalis (AU), severe forms of alopecia areata (AA), show distinguishable clinical characteristics from those of patch AA. In this study, we investigated the clinical characteristics of AT/AU according to the onset age. Based on the onset age around adolescence (< or ≥ 13 yr), 108 patients were classified in an early-onset group and the other 179 patients in a late-onset group. We found that more patients in the early-onset group had a family history of AA, nail dystrophy, and history of atopic dermatitis than those in the late-onset group. These clinical differences were more prominent in patients with AU than in those with AT. In addition, significantly more patients with concomitant medical disorders, especially allergic diseases were found in the early-onset group (45.8%) than in the late-onset group (31.2%). All treatment modalities failed to show any association with the present hair condition of patients. In the early-onset group, patients with AU or a family history of AA showed worse prognosis, whereas this trend was not observed in the late-onset group. Systemic evaluations might be needed in early-onset patients due to the higher incidence of comorbid diseases. It is suggested that patients with AU or family history of AA make worse progress in the early-onset group than in the late-onset group. PMID:22787378

  13. Children with disorders of sex development: A qualitative study of early parental experience

    PubMed Central

    2011-01-01

    Background Clinical research on psychological aspects of disorders of sex development (DSD) has focused on psychosexual differentiation with relatively little attention directed toward parents' experiences of early clinical management and their influence on patient and family psychosocial adaptation. Objectives To characterize parental experiences in the early clinical care of children born with DSD. Study Design Content analysis of interviews with parents (n = 41) of 28 children, newborn to 6 years, with DSD. Results Four major domains emerged as salient to parents: (1) the gender assignment process, (2) decisions regarding genital surgery, (3) disclosing information about their child's DSD, and (4) interacting with healthcare providers. Findings suggested discordance between scientific and parental understandings of the determinants of "sex" and "gender." Parents' expectations regarding the benefits of genital surgery appear largely met; however, parents still had concerns about their child's future physical, social and sexual development. Two areas experienced by many parents as particularly stressful were: (1) uncertainties regarding diagnosis and optimal management, and (2) conflicts between maintaining privacy versus disclosing the condition to access social support. Conclusions Parents' experiences and gaps in understanding can be used to inform the clinical care of patients with DSD and their families. Improving communication between parents and providers (and between parents and their support providers) throughout the early clinical management process may be important in decreasing stress and improving outcomes for families of children with DSD. PMID:21992519

  14. Rad6 is a Potential Early Marker of Melanoma Development

    PubMed Central

    Rosner, Karli; Adsule, Shreelekha; Haynes, Brittany; Kirou, Evangelia; Kato, Ikuko; Mehregan, Darius R.; Shekhar, Malathy P.V.

    2014-01-01

    Melanoma is the leading cause of death from skin cancer in industrialized countries. Several melanoma-related biomarkers and signaling pathways have been identified; however, their relevance to melanoma development/progression or to clinical outcome remains to be established. Aberrant activation of Wnt/β-catenin pathway is implicated in various cancers including melanoma. We have previously demonstrated Rad6, an ubiquitin-conjugating enzyme, as an important mediator of β-catenin stability in breast cancer cells. Similar to breast cancer, β-catenin-activating mutations are rare in melanomas, and since β-catenin signaling is implicated in melanoma, we examined the relationship between β-catenin levels/activity and expression of β-catenin transcriptional targets Rad6 and microphthalmia-associated transcription factor-M (Mitf-M) in melanoma cell models, and expression of Rad6, β-catenin, and Melan-A in nevi and cutaneous melanoma tissue specimens. Our data show that Rad6 is only weakly expressed in normal human melanocytes but is overexpressed in melanoma lines. Unlike Mitf-M, Rad6 overexpression in melanoma lines is positively associated with high molecular weight β-catenin protein levels and β-catenin transcriptional activity. Double-immunofluorescence staining of Rad6 and Melan-A in melanoma tissue microarray showed that histological diagnosis of melanoma is significantly associated with Rad6/Melan-A dual positivity in the melanoma group compared to the nevi group (P = .0029). In contrast to strong β-catenin expression in normal and tumor areas of superficial spreading malignant melanoma (SSMM), Rad6 expression is undetectable in normal areas and Rad6 expression increases coincide with increased Melan-A in the transformed regions of SSMM. These data suggest a role for Rad6 in melanoma pathogenesis and that Rad6 expression status may serve as an early marker for melanoma development. PMID:24831578

  15. Rad6 is a Potential Early Marker of Melanoma Development.

    PubMed

    Rosner, Karli; Adsule, Shreelekha; Haynes, Brittany; Kirou, Evangelia; Kato, Ikuko; Mehregan, Darius R; Shekhar, Malathy P V

    2014-05-12

    Melanoma is the leading cause of death from skin cancer in industrialized countries. Several melanoma-related biomarkers and signaling pathways have been identified; however, their relevance to melanoma development/progression or to clinical outcome remains to be established. Aberrant activation of Wnt/β-catenin pathway is implicated in various cancers including melanoma. We have previously demonstrated Rad6, an ubiquitin-conjugating enzyme, as an important mediator of β-catenin stability in breast cancer cells. Similar to breast cancer, β-catenin-activating mutations are rare in melanomas, and since β-catenin signaling is implicated in melanoma, we examined the relationship between β-catenin levels/activity and expression of β-catenin transcriptional targets Rad6 and microphthalmia-associated transcription factor-M (Mitf-M) in melanoma cell models, and expression of Rad6, β-catenin, and Melan-A in nevi and cutaneous melanoma tissue specimens. Our data show that Rad6 is only weakly expressed in normal human melanocytes but is overexpressed in melanoma lines. Unlike Mitf-M, Rad6 overexpression in melanoma lines is positively associated with high molecular weight β-catenin protein levels and β-catenin transcriptional activity. Double-immunofluorescence staining of Rad6 and Melan-A in melanoma tissue microarray showed that histological diagnosis of melanoma is significantly associated with Rad6/Melan-A dual positivity in the melanoma group compared to the nevi group (P=.0029). In contrast to strong β-catenin expression in normal and tumor areas of superficial spreading malignant melanoma (SSMM), Rad6 expression is undetectable in normal areas and Rad6 expression increases coincide with increased Melan-A in the transformed regions of SSMM. These data suggest a role for Rad6 in melanoma pathogenesis and that Rad6 expression status may serve as an early marker for melanoma development. PMID:24831578

  16. Development of pattern vision following early and extended blindness

    PubMed Central

    Kalia, Amy; Lesmes, Luis Andres; Dorr, Michael; Gandhi, Tapan; Chatterjee, Garga; Ganesh, Suma; Bex, Peter J.; Sinha, Pawan

    2014-01-01

    Visual plasticity peaks during early critical periods of normal visual development. Studies in animals and humans provide converging evidence that gains in visual function are minimal and deficits are most severe when visual deprivation persists beyond the critical period. Here we demonstrate visual development in a unique sample of patients who experienced extended early-onset blindness (beginning before 1 y of age and lasting 8–17 y) before removal of bilateral cataracts. These patients show surprising improvements in contrast sensitivity, an assay of basic spatial vision. We find that contrast sensitivity development is independent of the age of sight onset and that individual rates of improvement can exceed those exhibited by normally developing infants. These results reveal that the visual system can retain considerable plasticity, even after early blindness that extends beyond critical periods. PMID:24449865

  17. 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

  18. Developing Early Literacy: Report of the National Early Literacy Panel. A Scientific Synthesis of Early Literacy Development and Implications for Intervention

    ERIC Educational Resources Information Center

    National Institute for Literacy, 2008

    2008-01-01

    The National Early Literacy Panel (NELP) was appointed in 2002 and carried out its work under the auspices of the National Center for Family Literacy (NCFL). NELP's primary goal was to identify interventions, parenting activities, and instructional practices that promote the development of children's early literacy skills. The National Institute…

  19. 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…

  20. 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…

  1. Professional Development for Early Childhood Education: A National Perspective

    ERIC Educational Resources Information Center

    Shore, Rebecca Ann

    2012-01-01

    The article introduces the reader to a special issue of "NHSA Dialog" that focuses on the professional development (PD) of early childhood educators. The article opens with a perspective from a historical lens, namely that of PD in K-12 education and the evolution of Learning Forward, formerly the National Staff Development Council. The recently…

  2. 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…

  3. 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…

  4. Salinity on survival and early development of biofuel feedstock crops

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plant survival, growth and development can be influenced by irrigation water salinity level. Affects of salinity on early development of biofuel feedstock crops need to be clarified. The biofuel feedstock crops canola (Brassica napus L.), sorghum [Sorghum bicolor (L.) Moench], and sunflower (Helia...

  5. 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…

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

    PubMed

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

    2016-07-01

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

  7. 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

  8. Early Intervention in Conduct Problems in Children. Clinical Approaches to Early Intervention in Child and Adolescent Mental Health, Volume 3.

    ERIC Educational Resources Information Center

    Sanders, Matthew R.; Gooley, Shylaja; Nicholson, Jan

    Conduct problems represent a complex set of symptoms and can have a range of negative effects in many areas of a child's life, including ongoing development; family functioning; peer relationships; and learning. These problems generally appear during the preschool years and early identification and intervention are critical to their treatment.…

  9. Regulation of maternal mRNAs in early development.

    PubMed

    Farley, Brian M; Ryder, Sean P

    2008-01-01

    Most sexually reproducing metazoans are anisogamous, meaning that the two gametes that combine during fertilization differ greatly in size. By convention, the larger gametes are considered female and are called ova, while the smaller gametes are male and are called sperm. In most cases, both gametes contribute similarly to the chromosomal content of the new organism. In contrast, the maternal gamete contributes nearly all of the cytoplasm. This cytoplasmic contribution is crucial to patterning early development; it contains the maternal proteins and transcripts that guide the early steps of development prior to the activation of zygotic transcription. This review compares and contrasts early development in common laboratory model organisms in order to highlight the similarities and differences in the regulation of maternal factors. We will focus on the production and reversible silencing of maternal mRNAs during oogenesis, their asymmetric activation after fertilization, and their subsequent clearance at the midblastula transition. Where possible, insights from mechanistic studies are presented. PMID:18365862

  10. 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

  11. 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.…

  12. 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…

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

    ERIC Educational Resources Information Center

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

    2005-01-01

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

  14. 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.

  15. 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…

  16. 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

  17. 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

  18. New Hampshire Early Childhood Professional Development System: Guide to Early Childhood Careers.

    ERIC Educational Resources Information Center

    McDonnell, Tessa, Ed.

    The community of child care providers in New Hampshire has adopted the Early Childhood Professional Development System as an initial step toward assuring quality care and education for children. This guide describes the components of that system and is presented in eight sections. Section 1 of the guide introduces the system based on a set of two…

  19. Social Contexts of Early Development in Education. Advances in Early Education and Day Care.

    ERIC Educational Resources Information Center

    Reifel, Stuart, Ed.

    This volume reflects some of the disciplinary and interdisciplinary diversity found in the study of programs for young children, and its chapters cover a number of matters central to early childhood development and practice, including preparation for practice. The book has 11 chapters divided into 4 parts that cover family and community, adults…

  20. 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…

  1. 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

  2. Clinical implications of the development of the person.

    PubMed

    Suess, Gerhard J; Sroufe, June

    2005-12-01

    The Minnesota longitudinal study of parents and children from birth to adulthood provides both a theoretical framework and a host of empirical findings that can serve to bridge the gap between research and clinical application. Key among these findings are: (a) the ongoing impact of early relationship experiences throughout the years, even with later experience and circumstances controlled; (b) the cumulative nature of experience and its continual impact with current context; (c) the important role of adult partner relationships; (d) the increasingly active role of the persons themselves in their own development; and (e) the interplay between experience, representation, and ongoing adaptation. These findings, and the theoretical structure underlying them, suggest the need for complex, comprehensive intervention that begins early, with a focus on altering the quality of parent - child relationships. At the same time, additional components, including couples therapy and efforts to alter the child's inner constructions of experience, are clearly suggested. One must attend to forces maintaining children on maladaptive developmental pathways once established, as well as understanding the factors that initiated such pathways. PMID:16332582

  3. Early Childhood Obesity is Associated with Compromised Cerebellar Development

    PubMed Central

    Miller, Jennifer L; Couch, Jessica; Schwenk, Krista; Long, Michelle; Towler, Stephen; Theriaque, Douglas W; He, Guojun; Liu, Yijun; Driscoll, Daniel J; Leonard, Christiana M

    2009-01-01

    As part of a study investigating commonalities between Prader-Willi syndrome (PWS — a genetic imprinting disorder) and early-onset obesity of unknown etiology (EMO) we measured total cerebral and cerebellar volume on volumetric MRI images. Individuals with PWS (n=16) and EMO (n=12) had smaller cerebellar volumes than a control group of 15 siblings (p=0.02 control vs. EMO; p=0.0005 control vs. PWS), although there was no difference among the groups in cerebral volume. Individuals with PWS and EMO also had impaired cognitive function: general intellectual ability (GIA): PWS 65 ± 25; EMO 81 ± 19; and Controls 112 ± 13 (p<0.0001 controls vs. PWS and controls vs. EMO). As both conditions are characterized by early-onset obesity and slowed cognitive development, these results raise the possibility that early childhood obesity retards both cerebellar and cognitive development. PMID:19437203

  4. A comparison of ultrasound and clinical examination in the detection of flexor tenosynovitis in early arthritis

    PubMed Central

    2011-01-01

    Background Tenosynovitis is widely accepted to be common in rheumatoid arthritis (RA) and postulated to be the first manifestation of RA, but its true prevalence in early disease and in particular the hand has not been firmly established. The aims of this study were first to investigate the frequency and distribution of finger flexor tenosynovitis using ultrasound in early arthritis, second to compare clinical examination with ultrasound (US) using the latter as the gold standard. Methods 33 consecutive patients who had who were initially diagnosed with polyarthritis and suspected of polyarthritis and clinical suspicion of inflammatory arthritis of the hands and wrists were assessed during consecutive, routine presentations to the rheumatology outpatient clinic. We scanned a total of 165 finger tendons and subsequent comparisons were made using clinical examination. Results Flexor tenosynovitis was found in 17 patients (51.5%) on ultrasound compared with 16 (48.4%) of all patients on clinical examination. Most commonly damaged joint involved on US was the second finger followed by the third, fifth, and fourth. Both modalities demonstrated more pathology on the second and third metacarpophalangeal (MCP) compared with the fourth and fifth MCP. A joint-by-joint comparison of US and clinical examination demonstrated that although the sensitivity, specificities and positive predictive values of clinical examination were relatively high, negative predictive value of clinical examination was low (0.23). Conclusions Our study suggest that clinical examination can be a valuable tool for detecting flexor disease in view of its high specificity and positive predictive values, but a negative clinical examination does not exclude inflammation and an US should be considered. Further work is recommended to standardize definitions and image acquisition for peritendinous inflammation for ultrasound. PMID:21549008

  5. 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

  6. 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.

  7. Clinical patterns and outcome of early-onset inflammatory bowel disease.

    PubMed

    Ledder, Oren; Catto-Smith, Anthony G; Oliver, Mark R; Alex, George; Cameron, Donald J S; Hardikar, Winita

    2014-11-01

    We sought to determine whether extremely-early-onset childhood inflammatory bowel disease (age <6 years; 20 ulcerative colitis [UC], 8 Crohn disease [CD], 2 indeterminate, sequentially diagnosed) was clinically more severe than in older children (6-17 years; 19 UC, 39 CD, 2 indeterminate). Early-onset UC was marked by less abdominal pain at presentation, but an aggressive course with a significant reduction in weight-for-age, increased use of immunosuppressants, and more surgery. Children with early-onset CD were more likely to have bloody stools at presentation and an isolated colitis. This study supports the suggestion that inflammatory bowel disease phenotype differs in early-onset disease. PMID:24979317

  8. Clinical development of intramuscular electroporation: providing a "boost" for DNA vaccines.

    PubMed

    Khan, Amir S; Broderick, Kate E; Sardesai, Niranjan Y

    2014-01-01

    The development of effective vaccines has helped to eradicate or control the spread of numerous infectious diseases. However, there are many more diseases that have proved more difficult to eliminate using conventional vaccines. The recent innovation of DNA vaccines may provide a "boost" to the development efforts. While the early efforts of DNA vaccines in the clinic were disappointing, the use of in vivo electroporation has helped to provide some basis for optimism. Now, there are several ongoing clinical studies of vaccines against such diseases as malaria, HIV, hepatitis C, and even various types of cancer. This review will highlight three recently published clinical studies using intramuscular DNA administration with electroporation. PMID:24510832

  9. 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

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

    PubMed

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

    2016-05-13

    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 44weeks, 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

  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. Illumina Spin-off to Develop Early-Detection Test.

    PubMed

    Colwell, Janet

    2016-04-01

    DNA-sequencing giant Illumina has formed a new company, called Grail, to develop liquid biopsies capable of spotting cancer before symptoms arise. The start-up is working on a low-cost "pan-cancer" test that can detect multiple cancer types early, which it hopes to introduce by 2019. PMID:26873346

  13. 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…

  14. Participation as a Basis for Developing Early Intervention Outcomes

    ERIC Educational Resources Information Center

    Wilcox, M. Jeanne; Woods, Juliann

    2011-01-01

    Purpose: This article describes how participation in activities/routines can be used as a basis for understanding children's communication and language skills and how that knowledge can be extended to collaborate with families and caregivers to develop meaningful early intervention outcomes. Method: The approach is centered on children's use of…

  15. 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…

  16. 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…

  17. 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 ...

  18. Formative Evaluation of the Early Development Instrument: Progress and Prospects

    ERIC Educational Resources Information Center

    Keating, Daniel P.

    2007-01-01

    This article is a commentary for the special issue on the Early Development Instrument (EDI), a community tool to assess children's school readiness and developmental outcomes at a group level. The EDI is administered by kindergarten teachers, who assess their kindergarten students on 5 developmental domains: physical health and well-being, social…

  19. 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...

  20. 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…

  1. 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…

  2. Socio-Emotional Development and Early Schooling: Experimental Research

    ERIC Educational Resources Information Center

    Lamb, Michael E.

    2004-01-01

    Since the 1960s, researchers, legislators, advocacy groups, and social partners have examined, analysed, and written articles on the effects of early childhood care outside the family context on children's development and capacity for adaptation. Since the availability of non-parental care for children is often considered essential for women…

  3. The Benefits of Early Child Development Programs: An Economic Analysis.

    ERIC Educational Resources Information Center

    van der Gaag, Jacques; Tan, Jee-Peng

    This paper provides a framework for estimating the economic benefits of early child development (ECD) programs and applies the framework to preliminary data from the Bolivian ECD program (known as the PIDI Project). The evaluation quantifies the benefits of increased lifetime productivity as a result of ECD enrollment. The evaluation also takes…

  4. 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…

  5. 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…

  6. Early Childhood Education for Sustainability: Recommendations for Development

    ERIC Educational Resources Information Center

    Daries, Julie; Engdahl, Ingrid; Otieno, Lorraine; Pramling-Samuelson, Ingrid; Siraj-Blatchford, John; Vallabh, Priya

    2009-01-01

    The following recommendations for "Education for Sustainable Development (ESD)" in Early Childhood Education were the product of an extended international collaboration that was supported by a number of bodies including the Centre for Environment and Sustainability in Gothenburg, the Swedish Ministry of Education and Research, the Swedish National…

  7. Characterizing Key Features of the Early Childhood Professional Development Literature

    ERIC Educational Resources Information Center

    Snyder, Patricia; Hemmeter, Mary Louise; Meeker, Kathleen Artman; Kinder, Kiersten; Pasia, Cathleen; McLaughlin, Tara

    2012-01-01

    Professional development (PD) has been defined as facilitated teaching and learning experiences designed to enhance practitioners' knowledge, skills, and dispositions as well as their capacity to provide high-quality early learning experiences for young children. The purpose of this study was to use a framework from the National Professional…

  8. The Ecology of Early Reading Development for Children in Poverty

    ERIC Educational Resources Information Center

    Kainz, Kirsten; Vernon-Feagans, Lynne

    2007-01-01

    In this study we investigated reading development from kindergarten to third grade for 1,913 economically disadvantaged children from the Early Childhood Longitudinal Study-Kindergarten Cohort. Characteristics of the child, the family, classroom instruction, and school composition were used to model influences from multiple levels of children's…

  9. Early Journals and Their Influences on the Development of Gerontology

    ERIC Educational Resources Information Center

    Mercer, Lorraine; Carter, Lorraine

    2012-01-01

    This examination of early gerontology journals identifies the multidisciplinary backgrounds of contributors, methods of investigation, nascent theory development, and formative themes and controversies. Through use of content, thematic, and critical analyses of second year issues of "The Gerontologist," "Educational Gerontology," "Research on…

  10. Development of an Early Hebrew Oral Reading Fluency Measure

    ERIC Educational Resources Information Center

    Goldberg, Scott J.; Weinberger, Elana R.; Goodman, Nina E.; Ross, Shoshana

    2010-01-01

    Currently, there are no Hebrew (L2) reading assessments that have been tested to obtain evidence for reliability and validity on which to base decisions about Hebrew instruction. The authors developed a Hebrew benchmark assessment tool for first grade students modeled after Dynamic Indicators of Basic Early Literacy Skills, a standardized test of…

  11. 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…

  12. 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.…

  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. Teaching Parents How to Facilitate Social Development during Early Childhood

    ERIC Educational Resources Information Center

    Progar, Michelle

    2011-01-01

    Social competency gained in early childhood influences numerous domains of a child's life throughout the lifespan. Since the preschool years are a time when children begin forming friendships with peers and may be exposed to a classroom setting for the first time, developing social competency is imperative for functioning well with the many people…

  15. 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…

  16. A Productive System of Early Years Professional Development

    ERIC Educational Resources Information Center

    Hordern, Jim

    2013-01-01

    This paper uses the concept of the productive system to identify some of the tensions between the stages of professional development of early years practitioners and the relationships between the various actors within the system of professional formation in England. In the context of the recommendations of the Nutbrown Review a series of…

  17. Teacher Efficacy in an Early Childhood Professional Development School

    ERIC Educational Resources Information Center

    Epstein, Ann; Willhite, Gary L.

    2015-01-01

    Teacher efficacy is the belief teachers have in their ability to impact student learning. Efficacy includes teacher confidence in instructional, management and collaboration skills. The following study addresses teacher efficacy in an Early Childhood Professional Development School (PDS). The PDS experience provides an opportunity for mentor…

  18. 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

  19. Child Development Associate. Administration for Early Childhood Programs.

    ERIC Educational Resources Information Center

    Oscar Rose Junior Coll., Midwest City, OK.

    The purpose of this Child Development Associate (CDA) training module, one in a series of 18, is to provide the CDA intern with the knowledge and skills necessary for the administration of early childhood programs. The module stipulates competency-based objectives and provides essential information, suggestions, examples and learning activities on…

  20. Changing the Perspective on Early Development of Rett Syndrome

    ERIC Educational Resources Information Center

    Marschik, Peter B.; Kaufmann, Walter E.; Sigafoos, Jeff; Wolin, Thomas; Zhang, Dajie; Bartl-Pokorny, Katrin D.; Pini, Giorgio; Zappella, Michele; Tager-Flusberg, Helen; Einspieler, Christa; Johnston, Michael V.

    2013-01-01

    We delineated the achievement of early speech-language milestones in 15 young children with Rett syndrome ("MECP2" positive) in the first two years of life using retrospective video analysis. By contrast to the commonly accepted concept that these children are normal in the pre-regression period, we found markedly atypical development of…

  1. Approaches to Developing Health in Early Years Settings

    ERIC Educational Resources Information Center

    Mooney, Ann; Boddy, Janet; Statham, June; Warwick, Ian

    2008-01-01

    Purpose: The purpose of the paper is to consider the opportunities and difficulties in developing health-promotion work in early years settings in the UK. Design/methodology/approach: As the first study of its kind conducted in the UK, a multi-method approach was adopted involving: an overview of health-related guidance and of effective…

  2. Visual and Auditory Temporal Processing and Early Reading Development

    ERIC Educational Resources Information Center

    Hood, Michelle; Conlon, Elizabeth

    2004-01-01

    This study investigated the ability of temporal processing measures obtained before school entry to predict early reading development in an unselected sample of 125 children (68 males, 57 females). Visual and auditory temporal order judgment (TOJ) tasks measured at Preschool (mean age 5.36 years) significantly predicted letter and word…

  3. Early Language Development After Peri-natal Stroke

    PubMed Central

    Trauner, Doris A.; Eshagh, Karin; Ballantyne, Angela O.; Bates, Elizabeth

    2013-01-01

    Early unilateral brain damage has different implications for language development than does similar damage in adults, given the plasticity of the developing brain. The goal of this study was to examine early markers of language and gesture at 12 and 24 months in children who had peri-natal right hemisphere (RH) or left hemisphere (LH) stroke (n = 71), compared with typically developing controls (n = 126). Parents completed the MacArthur-Bates Communicative Development Inventory (CDI): Words & Gestures (12 month data point), or the CDI: Words & Sentences (24 month data point). Statistical analyses were performed on percentile scores using analysis of variance techniques. At 12 months, there were no differences among groups for Words Understood, Phrases Understood or Words Produced. At 24 months, both lesion groups scored significantly lower than controls on Word Production, Irregular Words, and Mean Length of Sentences, but lesion groups did not differ from each other. In longitudinal subset of participants, expressive vocabulary failed to progress as expected from 12 to 24 months in the stroke group, with no differences based on lesion side. Gesture and word production were dissociated in the left hemisphere subjects. Findings suggest that early language development after peri-natal stroke takes a different course from that of typical language development, perhaps reflecting brain reorganization secondary to plasticity in the developing brain. PMID:23711573

  4. 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

  5. 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.

  6. 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

  7. Early development of multiple epithelial neoplasms in Netherton syndrome.

    PubMed

    Krasagakis, K; Ioannidou, D J; Stephanidou, M; Manios, A; Panayiotides, J G; Tosca, A D

    2003-01-01

    We report a case of Netherton syndrome manifested as congenital ichthyosiform erythroderma, trichorrhexis invaginata and atopy, who in early adulthood developed multiple, aggressive epithelial neoplasms in sun-exposed areas of the skin, in areas with papillomatous skin hyperplasia and at the left parotid region. The occurrence of cutaneous neoplasia has been reported in syndromes with congenital ichthyosis and suggests that the underlying genetic defects may cause the development of cancer in prone patients. PMID:12920370

  8. Developing Early Undergraduate Research at a Two-Year College

    NASA Astrophysics Data System (ADS)

    Sibbernsen, Kendra

    2013-11-01

    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). Here are some suggestions if you are interested in developing and managing EUR at your TYC.

  9. 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

  10. Linking Early Brain and Biological Development to Psychiatry: Introduction and Symposia Review

    PubMed Central

    Attridge, Mark; Ghali, Laura

    2011-01-01

    Objective: This paper introduces the special issue of the Journal of the Canadian Academy of Child and Adolescent Psychiatry on the theme of how multiple factors in early brain and biological development can influence a variety of outcomes in mental health and addictions in childhood, adolescence and adulthood. Method: In Part 1, we preview three papers in this issue. In Part 2, we highlight two recent innovative knowledge-transfer symposia featuring the application of the science in early development and addictions. Results: The papers focus on the subtopics of brain plasticity, mood disorders, and comparative research with monkeys on gene-environment interactions and parent-child attachment. In addition, the research presented at the Early Brain and Biological Development Symposium and the Recovery from Addiction Symposium is also reviewed. Held in 2010 in Banff, Alberta, each five-day program was intended to bridge the gap between scientific and clinical experts and those in the province responsible for policy, programs, and services. Conclusions: The science now links common neurobiological maturation processes, adverse early childhood experiences, and key aspects of the social environment with risks for mental health disorders and addictions later in life. The final paper in this issue examines the clinical and policy implications of this research knowledge. PMID:22114607

  11. Effects of early life stress on amygdala and striatal development.

    PubMed

    Fareri, Dominic S; Tottenham, Nim

    2016-06-01

    Species-expected caregiving early in life is critical for the normative development and regulation of emotional behavior, the ability to effectively evaluate affective stimuli in the environment, and the ability to sustain social relationships. Severe psychosocial stressors early in life (early life stress; ELS) in the form of the absence of species expected caregiving (i.e., caregiver deprivation), can drastically impact one's social and emotional success, leading to the onset of internalizing illness later in life. Development of the amygdala and striatum, two key regions supporting affective valuation and learning, is significantly affected by ELS, and their altered developmental trajectories have important implications for cognitive, behavioral and socioemotional development. However, an understanding of the impact of ELS on the development of functional interactions between these regions and subsequent behavioral effects is lacking. In this review, we highlight the roles of the amygdala and striatum in affective valuation and learning in maturity and across development. We discuss their function separately as well as their interaction. We highlight evidence across species characterizing how ELS induced changes in the development of the amygdala and striatum mediate subsequent behavioral changes associated with internalizing illness, positing a particular import of the effect of ELS on their interaction. PMID:27174149

  12. Major developments in clinical chemical instrumentation.

    PubMed

    Caraway, W T

    1981-07-01

    The introduction of instrumentation into the clinical chemistry laboratory is reviewed for the period extending from about 1890 to 1960. Topics covered, from a historical point of view, include the microscope, analytical balance, and centrifuge, colorimetry and spectrophotometry, flame photometry, gasometric analysis, pH, electrophoresis, chromatography, radioisotopes, and automation. PMID:7035606

  13. Atrophy Patterns in Early Clinical Stages Across Distinct Phenotypes of Alzheimer’s Disease

    PubMed Central

    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.

    2015-01-01

    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. PMID:26260856

  14. Clinical observations of early and late normal tissue injury in patients receiving fast neutron irradiation

    SciTech Connect

    Ornitz, R.D.; Bradley, E.W.; Mossman, K.L.; Fender, F.M.; Schell, M.C.; Rogers, C.C.

    1980-03-01

    This communication describes early and late normal tissue effects in 177 patients treated totally or in part by 15 MeV neutrons from the Naval Research Laboratory Cyclotron in Washington, D.C. between October 1973 and December 1976. Late normal tissue reactions were found to be greater than would be expected from careful observation of the early clinical responses to neutron treatment. Neutron prescriptions must be written based on the late effect tolerance level experience which is being accumulated at several neutron therapy facilities.

  15. 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…

  16. Nurses’ Clinical Judgment Development: A Qualitative Research in Iran

    PubMed Central

    Seidi, Jamal; Alhani, Fatemeh; Salsali, Mahvash

    2015-01-01

    Background: Clinical judgment development is necessary because it leads to appropriate nursing diagnoses, clinical decision-making and health promotion. Objectives: In this study we explored the process of Iranian nurses’ development in clinical judgment. Patients and Methods: This qualitative study was conducted in 2013 at hospitals of Kurdistan University of Medical Sciences, located in the Sanandaj city of Iran. The data were collected based on semi-structured interviews and the study included 24 participants. Data analysis was carried out concurrently with data collection using the grounded theory method. Results: The study participants’ main concern was ‘being non-professional in clinical judgment’. In response to this concern, they were struggling for gaining professional autonomy, striving for integrating clinical judgment skills, scrambling to make effective educational interventions and striving for professional and inter professional collaboration in clinical judgment. The core category was ‘struggling for becoming professional in clinical judgment development’. When nurses were supported professionally, they were able to develop their professional clinical judgment. Conclusions: The findings of this study provided critical information about nurses’ professionalization in clinical judgment. Accordingly, the participants adopted different strategies to develop their clinical judgment ability. Integrating these strategies into nursing theory and clinical education can improve nurses’ clinical judgment ability. PMID:26473075

  17. 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 ...

  18. Externalizing the Critical Thinking in Knowledge Development and Clinical Judgment.

    ERIC Educational Resources Information Center

    Facione, Noreen C.; Facione, Peter A.

    1996-01-01

    Translates the American Philosophical Association's profile of a critical thinker into teaching and assessment strategies that can be used in nursing education to develop competent clinical judgment. (SK)

  19. Identification of early vascular calcification with (18)F-sodium fluoride: potential clinical application.

    PubMed

    Doris, Mhairi K; Newby, David E

    2016-06-01

    Vascular calcification plays a prominent role in cardiovascular disease. Once considered to be a passive consequence of aging, this pathological process is now accepted to be dynamic and tightly regulated, its onset triggered by inflammation and necrosis and its progression bearing key similarities to osteogenesis. A major potential advance in our ability to understand the natural history and clinical implications of vascular calcification is the detection of its early and dynamic stages through the use of the positron-emitting radiotracer, (18)F-sodium fluoride. Alongside anatomical information gained from computed tomography, hybrid positron emission and computed tomography (PET/CT) imaging with (18)F-sodium fluoride has, for the first time, enabled the non-invasive detection of microcalcification within the aortic valve, great vessels, and vulnerable coronary plaque. This has raised promise that exploring this process may allow improved risk prediction, better application of current therapies and ultimately the development of novel treatments to target this widespread pathology. PMID:26854119

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

    PubMed

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

    2010-08-01

    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

  1. 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. PMID:25555255

  2. Telomerase Activity is Downregulated Early During Human Brain Development.

    PubMed

    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

  3. 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

  4. 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.

  5. Peanut Allergy: New Developments and Clinical Implications.

    PubMed

    Commins, Scott P; Kim, Edwin H; Orgel, Kelly; Kulis, Mike

    2016-05-01

    Food allergies have increased in prevalence over the past 20 years, now becoming an important public health concern. Although there are no therapies currently available for routine clinical care, recent reports have indicated that immunotherapies targeting the mucosal immune system may be effective. Oral immunotherapy is conducted by administering small, increasing amounts of food allergen; it has shown promise for desensitizing individuals with peanut, egg, or milk allergies. Sublingual immunotherapy also desensitizes allergic patients to foods-two major studies have examined the effects of sublingual immunotherapy in subjects with peanut allergies. We review the complex nature of IgE-mediated food allergies and the therapies being evaluated in clinical trials. We focus on the diagnosis and management of food allergies and investigational therapies. PMID:27039393

  6. Developing a sleep apnoea clinic for prisoners.

    PubMed

    Reynolds, Sue

    People in prison may experience barriers in accessing health services. By exploring some of these barriers and how they have been overcome, this article describes how prisoners were made aware of obstructive sleep apnoea and the associated risks, and how a clinic was set up in a prison healthcare centre. It shows how access to a community service was made available to the prisoners, and details how the service was set up, how it operates and what the outcomes achieved. PMID:27396098

  7. [Further understanding on myocardial damage in the early stage post severe burn and its clinical significance].

    PubMed

    Huang, Y S

    2016-05-20

    A series of studies demonstrated that myocardial damage and cardiac dysfunction occurs immediately following severe burn, even before significant reduction in blood volume due to increased capillary permeability. Such myocardial damage and cardiac dysfunction leads to cardiac deficiency, and it is a precipitating factor for burn shock and ischemic/hypoxic injury. In recent years, many experimental and clinical studies elucidated the pathogenesis and confirmed the clinical importance of prevention and treatment of"shock heart"in the early stage post severe burn. PMID:27188482

  8. The dynamics of methionine supply and demand during early development.

    PubMed

    McBreairty, Laura E; Bertolo, Robert F

    2016-06-01

    Methionine is an indispensable amino acid that, when not incorporated into protein, is converted into the methyl donor S-adenosylmethionine as entry into the methionine cycle. Following transmethylation, homocysteine is either remethylated to reform methionine or irreversibly trans-sulfurated to form cysteine. Methionine flux to transmethylation and to protein synthesis are both high in the neonate and this review focuses on the dynamics of methionine supply and demand during early development, when growth requires expansion of pools of protein and transmethylation products such as creatine and phosphatidylcholine (PC). The nutrients folate and betaine (derived from choline) donate a methyl group during remethylation, providing an endogenous supply of methionine to meet the methionine demand. During early development, variability in the dietary supply of these methionine cycle-related nutrients can affect both the supply and the demand of methionine. For example, a greater need for creatine synthesis can limit methionine availability for protein and PC synthesis, whereas increased availability of remethylation nutrients can increase protein synthesis if dietary methionine is limiting. Moreover, changes to methyl group availability early in life can lead to permanent changes in epigenetic patterns of DNA methylation, which have been implicated in the early origins of adult disease phenomena. This review aims to summarize how changes in methyl supply and demand can affect the availability of methionine for various functions and highlights the importance of variability in methionine-related nutrients in the infant diet. PMID:27177124

  9. Radiofrequency ablation versus resection for Barcelona clinic liver cancer very early/early stage hepatocellular carcinoma: a systematic review

    PubMed Central

    He, Zhen-Xin; Xiang, Pu; Gong, Jian-Ping; Cheng, Nan-Sheng; Zhang, Wei

    2016-01-01

    Aim To compare the long-term survival outcomes of radiofrequency ablation and liver resection for single very early/early stage hepatocellular carcinoma (HCC). Methods The Cochrane Library (Issue 3, 2015), Embase (1974 to March 15, 2015), PubMed (1950 to March 15, 2015), Web of Science (1900 to March 15, 2015), and Chinese Biomedical Literature Database (1978 to March 15, 2015) were searched to identify relevant trials. Only trials that compared radiofrequency ablation and liver resection for single very early stage (≤2 cm) or early stage (≤3 cm) HCC according to the Barcelona clinic liver cancer (BCLC) staging system were considered for inclusion in this review. The primary outcomes that we analyzed were the 3-year and 5-year overall survival (OS) rates, and the secondary outcomes that we analyzed were the 3-year and 5-year disease-free survival (DFS) rates. Review Manager 5.3 was used to perform a cumulative meta-analysis. Possible publication bias was examined using a funnel plot. A random-effects model was applied to summarize the various outcomes. Results Six studies involving 947 patients were identified that compared radiofrequency ablation (n=528) to liver resection (n=419) for single BCLC very early HCC. In these six studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were significantly lower in the radiofrequency ablation group than in the liver resection group (risk ratio [RR] =0.90, 95% confidence interval [CI]: 0.83–0.98, P=0.01; RR =0.84, 95% CI: 0.75–0.95, P=0.004; RR =0.77, 95% CI: 0.60–0.98, P=0.04; and RR =0.70, 95% CI: 0.52–0.94, P=0.02, respectively). Ten studies involving 2,501 patients were identified that compared radiofrequency ablation (n=1,476) to liver resection (n=1,025) for single BCLC early HCC. In these ten studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were also significantly lower in the radiofrequency ablation group than in the liver resection group (RR =0.93, 95% CI: 0.88–0

  10. Complement Split Products in Amniotic Fluid in Pregnancies Subsequently Developing Early-Onset Preeclampsia

    PubMed Central

    Banadakoppa, Manu; Vidaeff, Alex C.; Yallampalli, Uma; Ramin, Susan M.; Belfort, Michael A.; Yallampalli, Chandra

    2015-01-01

    Objective. To determine the second-trimester amniotic fluid concentrations of complement split products in pregnancies subsequently affected by early-onset preeclampsia. Study Design. Cohort of 731 women with singleton pregnancies undergoing second-trimester genetic amniocentesis followed up to delivery and analyzed as a nested case-control study. Cases of preeclampsia developing before 34 weeks' gestation (n = 15) were compared with 47 uncomplicated term controls. Amniotic fluid collected at amniocentesis was tested for complement split products Bb, C4a, C3a, and C5a. Results. Women who developed early-onset preeclampsia as compared with the term pregnant controls had significantly higher (P = 0.04) median amniotic fluid C3a levels (318.7 ng/mL versus 254.5 ng/mL). Median amniotic fluid Bb levels were also significantly higher (P = 0.03) in preeclamptic women than in normal pregnant women (1127 ng/mL versus 749 ng/mL). Median levels of C4a and C5a were not significantly different between the groups. Conclusion. Our data suggest that complement activation in early pregnancy is associated with early-onset preeclampsia. We believe this to be the first prospective study to link complement activation in amniotic fluid in early pregnancy and later development of preeclampsia. Our findings provide evidence that immune dysregulation may precede the clinical manifestations of preeclampsia and that the alternative complement pathway is principally involved. PMID:26556948

  11. Early development of Chondrus ocellatus holm (Gigartinaceae, Rhodophyta)

    NASA Astrophysics Data System (ADS)

    Wang, Aihua; Wang, Jicheng; Duan, Delin

    2006-06-01

    Chondrus is an economically important red algae widely used for food and biochemical purpose. It early development is crucial for the culture and seedling propagation. We chose tetraspores and carpospores of Chondrus ocellatus as examples for experiment of the culture, induction and release in laboratory condition, aiming to understand early development of C. ocellatus and to apply in seedling production. Mature C. ocellatus were collected in Qingdao, China, from Nov. to Dec. 2004. After the gametophyte and tetrasporophyte were brushed and washed with sterilized seawater, the algal materials were treated in 1.5% KI for 20 min, then were dried for 1h to stimulate the releasing of spores. After the spores released overnight, it were cultured in PES medium, incubated at 18 °C, 10±2 μmol/(m2·s1) in 12∶12h (light: dark). The observation and recording under microscope were carried out. Continuous observation of the early development showed that both tetraspore and carpospore are similar to each other. In general, three stages of the early development were shown being division, discoid crust and seedling stages. To the division stage, the most obvious feature was the increasing of cell number; during the discoid crust stage, the discoid crust had a three-dimensional axis, and it began to differentiate into two types of cells: the basal cells and the apical cells; and to the seedling stage, several protuberances-like appeared on the discoid crusts and formed juvenile seedlings. Carpospores and tetraspores exhibited a similar development process that included division stage, discoid crust stage and seedling stage.

  12. Community mental health nursing and early intervention in dementia: developing practice through a single case history.

    PubMed

    Keady, John; Woods, Bob; Hahn, Sue; Hill, Jim

    2004-09-01

    People Nursing in association with Journal of Clinical Nursing 13, 6b, 57-67 Community mental health nursing and early intervention in dementia: developing practice through a single case history This paper reports on a single case history taken from the 'Dementia Action Research and Education' project, a 15-month primary care intervention study that was undertaken in North Wales in the early part of 2000. The study sought to address the meaning, context and diversity of early intervention in dementia care and employed a community mental health nurse and a psychiatric social worker to undertake early and psychosocial interventions with older people with dementia (aged 75 years and over) and their families. The workers tape-recorded, documented and analysed their interventions with 27 older people with dementia and their families over the 15-month duration of the study. Clinical supervision was also undertaken during the intervention phase. One case history is presented in this paper to illustrate the work of the community mental health nurse and to identify areas of practice development. Greater role transparency, collaborative working and improvement in educational preparation for practice are called for. PMID:15724820

  13. 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

  14. 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…

  15. Partnering industry to develop clinical information systems.

    PubMed

    Hughes, Victoria; Hamer, Susan

    2012-09-01

    Over the past six months, the nursing team from the Department of Health's Informatics Directorate has been working with colleagues in industry to promote and share learning and understanding of issues surrounding the nursing profession. Team members were asked among other things to identify key questions senior nursing colleagues and suppliers should ask one another when considering the implementation of a new system for recording clinical information and extracting pertinent data. This article aims to encourage collaborative working and understanding of the importance of senior nurse involvement in choosing and delivering the right system for staff and patients. PMID:23008903

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

    PubMed

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

    2016-04-01

    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

  17. 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

  18. Lexically-based learning and early grammatical development.

    PubMed

    Lieven, E V; Pine, J M; Baldwin, G

    1997-02-01

    Pine & Lieven (1993) suggest that a lexically-based positional analysis can account for the structure of a considerable proportion of children's early multiword corpora. The present study tests this claim on a second, larger sample of eleven children aged between 1;0 and 3;0 from a different social background, and extends the analysis to later in development. Results indicate that the positional analysis can account for a mean of 60% of all the children's multiword utterances and that the great majority of all other utterances are defined as frozen by the analysis. Alternative explanations of the data based on hypothesizing underlying syntactic or semantic relations are investigated through analyses of pronoun case marking and of verbs with prototypical agent-patient roles. Neither supports the view that the children's utterances are being produced on the basis of general underlying rules and categories. The implications of widespread distributional learning in early language development are discussed. PMID:9154014

  19. 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).

  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 comparison of two assays for rapid detection of cytomegalovirus early nuclear antigen.

    PubMed

    Woods, G L; Johnson, A M; Thiele, G M

    1990-03-01

    Three methods for detection of cytomegalovirus (CMV) in 218 clinical specimens were compared: (1) shell vial assay to detect the early nuclear antigen after incubation for 16 hours and 40 hours (Syva Company); (2) 24-well plate assay to detect the early nuclear antigen after incubation for 16 hours (DuPont); and (3) convention tissue cell culture. CMV was detected in 26 specimens (12%) by one or more of these methods. With the shell vial assay, 12 (46%) and 15 (58%) specimens were positive after incubation for 16 hours and 40 hours, respectively. CMV was detected in 17 specimens (65%) by the 24-well plate assay. There was no significant difference in the detection of CMV between these assays. CMV was identified by conventional tissue culture in 15 of 22 (68%) evaluable cultures after an average of 14.2 days. More specimens were positive by conventional culture than by the 16-hour shell vial assay (P = 0.035). For optimal detection of CMV in clinical specimens, both conventional tissue cell culture and an early antigen assay should be performed. The two early antigen assays evaluated in this study yielded comparable results. However, the 24-well plates are more easily manipulated, and the 24-well plate assay, as performed, was easier to interpret and more cost efficient. PMID:2155527

  2. 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

  3. The development of emotion regulation and dysregulation: a clinical perspective.

    PubMed

    Cole, P M; Michel, M K; Teti, L O

    1994-01-01

    the world of events and relationships. The emotional conditions of early childhood appear to be very important in optimizing or interfering with how the child's emotionality regulates his or her interpersonal and intrapsychic functioning and how the child learns to regulate emotion. The experiences that accrue around emotional events influence the stable aspects of the developing personality and become trait-like aspects of the person (Malatesta & Wilson, 1988). Dysregulation occurs when an emotional reaction loses breadth and flexibility. If a dysregulatory pattern becomes stabilized and part of the emotional repertoire, it is likely that this pattern is a symptom and supports other symptoms. When development and adaptation are compromised, the dysregulation has evolved into a form of psychopathology. The line between normative variations and clinical conditions is not clearly drawn.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:7984169

  4. Identification of Mytilus edulis genetic regulators during early development.

    PubMed

    Bassim, Sleiman; Tanguy, Arnaud; Genard, Bertrand; Moraga, Dario; Tremblay, Rejean

    2014-11-01

    Understanding the mechanisms that enable growth and survival of an organism while driving it to the full range of its adaptation is fundamental to the issues of biodiversity and evolution, particularly regarding global climatic changes. Here we report the Illumina RNA-sequencing (RNA-seq) and de novo assembly of the blue mussel Mytilus edulis transcriptome during early development. This study is based on high-throughput data, which associates genome-wide differentially expressed transcript (DET) patterns with early activation of developmental processes. Approximately 50,383 high-quality contigs were assembled. Over 8000 transcripts were associated with functional proteins from public databases. Coding and non-coding genes served to design customized microarrays targeting every developmental stage, which encompass major transitions in tissue organization. Consequently, multi-processing pattern exploration protocols applied to 3633 DETs helped discover 12 unique coordinated eigengenes supposedly implicated in various physiological and morphological changes that larvae undergo during early development. Moreover, dynamic Bayesian networks (DBNs) provided key insights to understand stage-specific molecular mechanisms activated throughout ontogeny. In addition, delayed and contemporaneous interactions between DETs were coerced with 16 relevant regulators that interrelated in non-random genetic regulatory networks (GRNs). Genes associated with mechanisms of neural and muscular development have been characterized and further included in dynamic networks necessary in growth and functional morphology. This is the first large-scale study being dedicated to M. edulis throughout early ontogeny. Integration between RNA-seq and microarray data enabled a high-throughput exploration of hidden processes essential in growth and survival of microscopic mussel larvae. Our integrative approach will support a holistic understanding of systems biology and will help establish new links

  5. The Development of Children's Early Numeracy through Key Stage 1

    ERIC Educational Resources Information Center

    Aubrey, Carol; Godfrey, Ray

    2003-01-01

    This paper describes a limited longitudinal study of young children's early numeracy development 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-of-age), located within the broader context of progress through to Key Stage 1 SAT…

  6. Reading Instruction Affects the Cognitive Skills Supporting Early Reading Development

    ERIC Educational Resources Information Center

    McGeown, Sarah P.; Johnston, Rhona S.; Medford, Emma

    2012-01-01

    This study examined the cognitive skills associated with early reading development when children were taught by different types of instruction. Seventy-nine children (mean age at pre-test 4;10 (0.22 S.D.) and post-test 5;03 (0.21 S.D.)) were taught to read either by an eclectic approach which included sight-word learning, guessing from context and…

  7. Dynamic Self-Organization and Early Lexical Development in Children

    ERIC Educational Resources Information Center

    Li, Ping; Zhao, Xiaowei; Whinney, Brian Mac

    2007-01-01

    In this study we present a self-organizing connectionist model of early lexical development. We call this model DevLex-II, based on the earlier DevLex model. DevLex-II can simulate a variety of empirical patterns in children's acquisition of words. These include a clear vocabulary spurt, effects of word frequency and length on age of acquisition,…

  8. Development of a Metabolic Biosignature for Detection of Early Lyme Disease

    PubMed Central

    Molins, Claudia R.; Ashton, Laura V.; Wormser, Gary P.; Hess, Ann M.; Delorey, Mark J.; Mahapatra, Sebabrata; Schriefer, Martin E.; Belisle, John T.

    2015-01-01

    Background. Early Lyme disease patients often present to the clinic prior to developing a detectable antibody response to Borrelia burgdorferi, the etiologic agent. Thus, existing 2-tier serology-based assays yield low sensitivities (29%–40%) for early infection. The lack of an accurate laboratory test for early Lyme disease contributes to misconceptions about diagnosis and treatment, and underscores the need for new diagnostic approaches. Methods. Retrospective serum samples from patients with early Lyme disease, other diseases, and healthy controls were analyzed for small molecule metabolites by liquid chromatography-mass spectrometry (LC-MS). A metabolomics data workflow was applied to select a biosignature for classifying early Lyme disease and non-Lyme disease patients. A statistical model of the biosignature was trained using the patients' LC-MS data, and subsequently applied as an experimental diagnostic tool with LC-MS data from additional patient sera. The accuracy of this method was compared with standard 2-tier serology. Results. Metabolic biosignature development selected 95 molecular features that distinguished early Lyme disease patients from healthy controls. Statistical modeling reduced the biosignature to 44 molecular features, and correctly classified early Lyme disease patients and healthy controls with a sensitivity of 88% (84%–95%), and a specificity of 95% (90%–100%). Importantly, the metabolic biosignature correctly classified 77%–95% of the of serology negative Lyme disease patients. Conclusions. The data provide proof-of-concept that metabolic profiling for early Lyme disease can achieve significantly greater (P < .0001) diagnostic sensitivity than current 2-tier serology, while retaining high specificity. PMID:25761869

  9. Early zebrafish development: It’s in the maternal genes

    PubMed Central

    Abrams, Elliott W.; Mullins, Mary C.

    2009-01-01

    Summary The earliest stages of embryonic development in all animals examined rely on maternal gene products that are generated during oogenesis and supplied to the egg. The period of maternal control of embryonic development varies among animals according to the onset of zygotic transcription and the persistence of maternal gene products. This maternal regulation has been little studied in vertebrates, due to the difficulty in manipulating maternal gene function and lack of basic molecular information. However, recent maternal-effect screens in the zebrafish have generated more than 40 unique mutants that are providing new molecular entry points to the maternal control of early vertebrate development. Here we discuss recent studies of 12 zebrafish mutant genes that illuminate the maternal molecular controls on embryonic development, including advances in the regulation of animal-vegetal polarity, egg activation, cleavage development, body plan formation, tissue morphogenesis, microRNA function and germ cell development. PMID:19608405

  10. Niemann-Pick disease type C clinical database: cognitive and coordination deficits are early disease indicators

    PubMed Central

    2013-01-01

    Background The neurodegenerative lysosomal storage disorder Niemann-Pick disease type C (NP-C) is characterized by a broad clinical variability involving neurological, psychiatric and systemic signs. Diverse patterns of disease manifestation and progression considerably delay its diagnosis. Here we introduce the NP-C clinical database (NPC-cdb) to systematically obtain, store and analyze diagnostic and clinical findings in patients with NP-C. We apply NPC-cdb to study NP-C temporal expression in a large German-Swiss patient cohort. Methods Current and past medical history was systematically acquired from 42 patients using tailored questionnaires. Manifestation of 72 distinct neuropsychiatric signs was modeled over the course of disease. The sequence of disease progression was re-constructed by a novel clinical outcome scale (NPC-cdb score). Results The efficiency of current clinical diagnostic standards negatively correlates with duration of disease (p<3.9x10-4), suggesting insufficient sensitivity in patients early in the disease process. Neurological signs considered as typical for NP-C were frequent (e.g., cognitive impairment 86%, ataxia 79%, vertical supranuclear gaze palsy 76%) and their presence co-occurred with accelerated diagnosis. However, less specific neuropsychiatric signs were reported to arise considerably more early in the disease process (e.g., clumsiness -4.9±1.1 y before diagnosis). Most patients showed a steady disease progression that correlated with age at neurological onset. However, a distinct subcohort (n=6) with initially steadily progressing disease later showed a 2.9-fold accelerated progression that was associated with the onset of seizures (p<7x10-4), suggesting seizures as predictive for a poor prognosis. Conclusions Considering early, but less specific neuropsychiatric signs may accelerate the path to diagnosing NP-C in a patient. PMID:23433426

  11. 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

  12. 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…

  13. Biased gene expression in early honeybee larval development

    PubMed Central

    2013-01-01

    Background Female larvae of the honeybee (Apis mellifera) develop into either queens or workers depending on nutrition. This nutritional stimulus triggers different developmental trajectories, resulting in adults that differ from each other in physiology, behaviour and life span. Results To understand how these trajectories are established we have generated a comprehensive atlas of gene expression throughout larval development. We found substantial differences in gene expression between worker and queen-destined larvae at 6 hours after hatching. Some of these early changes in gene expression are maintained throughout larval development, indicating that caste-specific developmental trajectories are established much earlier than previously thought. Within our gene expression data we identified processes that potentially underlie caste differentiation. Queen-destined larvae have higher expression of genes involved in transcription, translation and protein folding early in development with a later switch to genes involved in energy generation. Using RNA interference, we were able to demonstrate that one of these genes, hexamerin 70b, has a role in caste differentiation. Both queen and worker developmental trajectories are associated with the expression of genes that have alternative splice variants, although only a single variant of a gene tends to be differentially expressed in a given caste. Conclusions Our data, based on the biases in gene expression early in development together with published data, supports the idea that caste development in the honeybee consists of two phases; an initial biased phase of development, where larvae can still switch to the other caste by differential feeding, followed by commitment to a particular developmental trajectory. PMID:24350621

  14. 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…

  15. 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. PMID:27145214

  16. The Role of Androgen Hormones in Early Follicular Development

    PubMed Central

    Gervásio, Catiele Garcia; Bernuci, Marcelo Picinin; Silva-de-Sá, Marcos Felipe; Rosa-e-Silva, Ana Carolina Japur de Sá

    2014-01-01

    Background. Although chronic hyperandrogenism, a typical feature of polycystic ovary syndrome, is often associated with disturbed reproductive performance, androgens have been shown to promote ovarian follicle growth in shorter exposures. Here, we review the main effects of androgens on the regulation of early folliculogenesis and the potential of their application in improving follicular in vitro growth. Review. Androgens may affect folliculogenesis directly via androgen receptors (ARs) or indirectly through aromatization to estrogen. ARs are highly expressed in the granulosa and theca cells of early stage follicles and slightly expressed in mature follicles. Short-term androgen exposure augments FSH receptor expression in the granulosa cells of developing follicles and enhances the FSH-induced cAMP formation necessary for the transcription of genes involved in the control of follicular cell proliferation and differentiation. AR activation also increases insulin-like growth factor (IGF-1) and its receptor gene expression in the granulosa and theca cells of growing follicles and in the oocytes of primordial follicles, thus facilitating IGF-1 actions in both follicular recruitment and subsequent development. Conclusion. During the early and intermediate stages of follicular maturation, locally produced androgens facilitate the transition of follicles from the dormant to the growing pool as well as their further development. PMID:25006485

  17. Developing an empirical base for clinical nurse specialist education.

    PubMed

    Stahl, Arleen M; Nardi, Deena; Lewandowski, Margaret A

    2008-01-01

    This article reports on the design of a clinical nurse specialist (CNS) education program using National Association of Clinical Nurse Specialists (NACNS) CNS competencies to guide CNS program clinical competency expectations and curriculum outcomes. The purpose is to contribute to the development of an empirical base for education and credentialing of CNSs. The NACNS CNS core competencies and practice competencies in all 3 spheres of influence guided the creation of clinical competency grids for this university's practicum courses. This project describes the development, testing, and application of these clinical competency grids that link the program's CNS clinical courses with the NACNS CNS competencies. These documents guide identification, tracking, measurement, and evaluation of the competencies throughout the clinical practice portion of the CNS program. This ongoing project will continue to provide data necessary to the benchmarking of CNS practice competencies, which is needed to evaluate the effectiveness of direct practice performance and the currency of graduate nursing education. PMID:18438164

  18. Early Low Urinary CXCL9 and CXCL10 Might Predict Immunological Quiescence in Clinically and Histologically Stable Kidney Recipients.

    PubMed

    Rabant, M; Amrouche, L; Morin, L; Bonifay, R; Lebreton, X; Aouni, L; Benon, A; Sauvaget, V; Le Vaillant, L; Aulagnon, F; Sberro, R; Snanoudj, R; Mejean, A; Legendre, C; Terzi, F; Anglicheau, D

    2016-06-01

    We monitored the urinary C-X-C motif chemokine (CXCL)9 and CXCL10 levels in 1722 urine samples from 300 consecutive kidney recipients collected during the first posttransplantation year and assessed their predictive value for subsequent acute rejection (AR). The trajectories of urinary CXCL10 showed an early increase at 1 month (p = 0.0005) and 3 months (p = 0.0009) in patients who subsequently developed AR. At 1 year, the AR-free allograft survival rates were 90% and 54% in patients with CXCL10:creatinine (CXCL10:Cr) levels <2.79 ng/mmoL and >2.79 ng/mmoL at 1 month, respectively (p < 0.0001), and 88% and 56% in patients with CXCL10:Cr levels <5.32 ng/mmoL and >5.32 ng/mmoL at 3 months (p < 0.0001), respectively. CXCL9:Cr levels also associate, albeit less robustly, with AR-free allograft survival. Early CXCL10:Cr levels predicted clinical and subclinical rejection and both T cell- and antibody-mediated rejection. In 222 stable patients, CXCL10:Cr at 3 months predicted AR independent of concomitant protocol biopsy results (p = 0.009). Although its positive predictive value was low, a high negative predictive value suggests that early CXCL10:Cr might predict immunological quiescence on a triple-drug calcineurin inhibitor-based immunosuppressive regimen in the first posttransplantation year, even in clinically and histologically stable patients. The clinical utility of this test will need to be addressed by dedicated prospective clinical trials. PMID:26694099

  19. Genetic mutation analysis at early stages of cell line development using next generation sequencing.

    PubMed

    Wright, Chapman; Groot, Joost; Swahn, Samantha; McLaughlin, Helen; Liu, Mei; Xu, Chongfeng; Sun, Chao; Zheng, Eric; Estes, Scott

    2016-05-01

    A central goal for most biopharmaceutical companies is to reduce the development timeline to reach clinical proof of concept. This objective requires the development of tools that ensure the quality of biotherapeutic material destined for the clinic. Recent advances in high throughput protein analytics provide confidence in our ability to assess productivity and product quality attributes at early stages of cell line development. However, one quality attribute has, until recently, been absent from the standard battery of analytical tests facilitating informed choices early in cell line selection: genetic sequence confirmation. Techniques historically used for mutation analysis, such as detailed mass spectrometry, have limitations on the sample number and turnaround times making it less attractive at early stages. Thus, we explored the utility of Next-Generation Sequencing (NGS) as a solution to address these limitations. Amplicon sequencing is one such NGS technique that is robust, rapid, sensitive, and amenable to multiplexing, all of which are essential attributes for our purposes. Here we report a NGS method based upon amplicon sequencing that has been successfully incorporated into our cell line development workflow alongside other high-throughput protein analytical assays. The NGS method has demonstrated its value by identifying at least one Chinese hamster ovary (CHO) clone expressing a variant form of the biotherapeutic in each of the four clinical programs in which it has been utilized. We believe this sequence confirmation method is essential to safely accelerating the time to clinical proof of concept of biotherapeutics, and guard against delays related to sequence mutations. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:813-817, 2016. PMID:27004436

  20. Delayed perforation after endoscopic submucosal dissection for early gastric cancer: Clinical features and treatment

    PubMed Central

    Yano, Takafumi; Tanabe, Satoshi; Ishido, Kenji; Azuma, Mizutomo; Wada, Takuya; Suzuki, Mizuto; Kawanishi, Natsuko; Yamane, Sakiko; Sasaki, Tohru; Katada, Chikatoshi; Mikami, Tetsuo; Katada, Natsuya; Koizumi, Wasaburo

    2016-01-01

    Perforation is an important procedural complication of endoscopic submucosal dissection (ESD) for early gastric cancer. Although the incidence of delayed perforation after ESD is low, extreme caution is necessary because many cases require surgical intervention. Among 1984 lesions of early gastric cancer treated in our hospital by ESD in 1588 patients from September 2002 through March 2015, delayed perforation developed in 4 patients (4 lesions, 0.25%). A diagnosis of delayed perforation requires prompt action, including surgical intervention when required. PMID:27114751

  1. Plasticity of defensive behavior and fear in early development

    PubMed Central

    Wiedenmayer, Christoph P.

    2009-01-01

    Animals have the ability to respond to threatening situations with sets of defensive behaviors. This review demonstrates that defensive behaviors change during early life in mammals. First, unlearned responses are reorganized during early ontogeny and expressed in an age-specific way. Second, the expression of defensive responses is influenced by early experience prior to the first encounter with a threat. Third, once animals have been exposed to a threatening stimulus they subsequently modify their behavior. The neural bases of defensive behavior and the processes that alter them during development are discussed. Maturation of components and connections of the fear circuit seem to contribute to changes in unlearned fear responses. Early experience and learning modify these developmental processes and shape the expression of defensive behavior. Continuous reorganization of the neural substrate and defensive behavior during ontogeny seems to allow the animal to adjust to the conditions it encounters at a given age in a given environment. It is proposed that the developmental changes in defensive behavior can be conceptualized as phenotypic plasticity. PMID:19073211

  2. Early vancomycin-resistant enterococcus (VRE) bacteremia after allogeneic bone marrow transplantation is associated with a rapidly deteriorating clinical course.

    PubMed

    Avery, R; Kalaycio, M; Pohlman, B; Sobecks, R; Kuczkowski, E; Andresen, S; Mossad, S; Shamp, J; Curtis, J; Kosar, J; Sands, K; Serafin, M; Bolwell, B

    2005-03-01

    Vancomycin-resistant enterococcal (VRE) infection is a growing threat. We studied the incidence, risk factors, and clinical course of early-onset VRE bacteremia in allogeneic hematopoietic stem cell transplant recipients. We carried out a chart review of 281 allogeneic hematopoietic stem cell transplant recipients from 1997-2003, including preparative regimen, diagnosis, status of disease, graft-versus-host disease prophylaxis, antimicrobial therapy, and survival. VRE bacteremia developed in 12/281 (4.3%) recipients; 10 (3.6%) were within 21 days of transplant. Diagnoses were acute leukemia (7), NHL (2), and MDS (1). In all, 70% had refractory/relapsed disease; 30% were in remission. In total, 50% had circulating blasts. Nine of 10 had matched unrelated donors (7/9 with CD8+ T-cell depletion). The average time to positive VRE cultures was 15 days; average WBC was 0.05, and 80% had concomitant infections. Despite treatment, all patients died within 73 days of VRE bacteremia. Intra-abdominal complications were common. Causes of death included bacterial or fungal infection, multiorgan failure, VOD, ARDS, and relapse. A total of 60% of patients engrafted neutrophils, but none engrafted platelets. Early VRE bacteremia after allogeneic bone marrow transplant is associated with a rapidly deteriorating clinical course, although not always directly due to VRE. Early VRE may be a marker for the critical condition of these high-risk patients at the time of transplant. PMID:15640812

  3. Distinct Clinic-Pathological Features of Early Differentiated-Type Gastric Cancers after Helicobacter pylori Eradication.

    PubMed

    Horiguchi, Noriyuki; Tahara, Tomomitsu; Kawamura, Tomohiko; Okubo, Masaaki; Ishizuka, Takamitsu; Nakagawa, Yoshihito; Nagasaka, Mitsuo; Shibata, Tomoyuki; Ohmiya, Naoki

    2016-01-01

    Background. Gastric cancer is discovered even after successful eradication of H. pylori. We investigated clinic pathological features of early gastric cancers after H. pylori eradication. Methods. 51 early gastric cancers (EGCs) from 44 patients diagnosed after successful H. pylori eradication were included as eradication group. The clinic-pathological features were compared with that of 131 EGCs from 120 patients who did not have a history of H. pylori eradication (control group). Results. Compared with control group, clinic-pathological features of eradication group were characterized as depressed (p < 0.0001), reddish (p = 0.0001), and smaller (p = 0.0095) lesions, which was also confirmed in the comparison of six metachronous lesions diagnosed after initial ESD and subsequent successful H. pylori eradication. Prevalence of both SM2 (submucosal invasion greater than 500 μm) and unexpected SM2 cases tended to be higher in eradication group (p = 0.077, 0.0867, resp.). Prevalence of inconclusive diagnosis of gastric cancer during pretreatment biopsy was also higher in the same group (26.0% versus 1.6%, p < 0.0001). Conclusions. Informative clinic pathological features of EGC after H. pylori eradication are depressed, reddish appearances, which should be treated as a caution because histological diagnosis of cancerous tissue is sometimes difficult by endoscopic biopsy. PMID:27212944

  4. Distinct Clinic-Pathological Features of Early Differentiated-Type Gastric Cancers after Helicobacter pylori Eradication

    PubMed Central

    Horiguchi, Noriyuki; Tahara, Tomomitsu; Kawamura, Tomohiko; Okubo, Masaaki; Ishizuka, Takamitsu; Nakagawa, Yoshihito; Nagasaka, Mitsuo; Shibata, Tomoyuki; Ohmiya, Naoki

    2016-01-01

    Background. Gastric cancer is discovered even after successful eradication of H. pylori. We investigated clinic pathological features of early gastric cancers after H. pylori eradication. Methods. 51 early gastric cancers (EGCs) from 44 patients diagnosed after successful H. pylori eradication were included as eradication group. The clinic-pathological features were compared with that of 131 EGCs from 120 patients who did not have a history of H. pylori eradication (control group). Results. Compared with control group, clinic-pathological features of eradication group were characterized as depressed (p < 0.0001), reddish (p = 0.0001), and smaller (p = 0.0095) lesions, which was also confirmed in the comparison of six metachronous lesions diagnosed after initial ESD and subsequent successful H. pylori eradication. Prevalence of both SM2 (submucosal invasion greater than 500 μm) and unexpected SM2 cases tended to be higher in eradication group (p = 0.077, 0.0867, resp.). Prevalence of inconclusive diagnosis of gastric cancer during pretreatment biopsy was also higher in the same group (26.0% versus 1.6%, p < 0.0001). Conclusions. Informative clinic pathological features of EGC after H. pylori eradication are depressed, reddish appearances, which should be treated as a caution because histological diagnosis of cancerous tissue is sometimes difficult by endoscopic biopsy. PMID:27212944

  5. 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.

  6. 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

  7. 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

  8. 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. PMID:23691980

  9. [The development of a finger joint phantom for the optical simulation of early inflammatory rheumatic changes].

    PubMed

    Prapavat, V; Runge, W; Mans, J; Krause, A; Beuthan, J; Müller, G

    1997-11-01

    In the field of rheumatology, conventional diagnostic methods permit the detection only of advanced stages of the disease, which is at odds with the current clinical demand for the early diagnosis of inflammatory rheumatic diseases. Prompted by current needs, we developed a finger joint phantom that enables the optical and geometrical simulation of an early stage of rheumatoid arthritis (RA). The results presented here form the experimental basis for an evaluation of new RA diagnostic systems based on near infrared light. The early stage of RA is characterised mainly by a vigorous proliferation of the synovial membrane and clouding of the synovial fluid. Using a double-integrating-sphere technique, the absorption and scattering coefficients (mua, mus') are experimentally determined for healthy and pathologically altered synovial fluid and capsule tissue. Using a variable mixture of Intralipid Indian ink and water as a scattering/absorption medium, the optical properties of skin, synovial fluid or capsule can be selected individually. Since the optical and geometrical properties of bone tissue remain constant in early-stage RA, a solid material is used for its simulation. Using the finger joint phantom described herein, the optical properties of joint regions can be adjusted specifically, enabling an evaluation of their effects on an optical signal--for example, during fluorography--and the investigation of these effects for diagnostically useful information. The experimental foundation for the development of a new optical system for the early diagnosis of RA has now been laid. PMID:9490122

  10. 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.

  11. Early pregnancy metabolite profiling discovers a potential biomarker for the subsequent development of gestational diabetes mellitus.

    PubMed

    de Seymour, Jamie V; Conlon, Cathryn A; Sulek, Karolina; Villas Bôas, Silas G; McCowan, Lesley M E; Kenny, Louise C; Baker, Philip N

    2014-10-01

    Current early pregnancy screening tools to identify women at risk of developing gestational diabetes mellitus lack both specificity and sensitivity. As a result, the foetus and mother are often subjected to insult during disease progression, prior to diagnosis and treatment in later pregnancy. Metabolomics is an analytical approach, which allows for appraisal of small molecular mass compounds in a biofluid. The aim of this pilot study was to investigate the relationship between the early gestation serum metabolite profile and the subsequent development of gestational diabetes mellitus in the search for early pregnancy biomarkers and potential metabolic mechanisms. Our nested case-control study analysed maternal serum at 20 weeks' gestation, obtained from the New Zealand cohort of the Screening for Pregnancy Endpoints study. Metabolomic profiling was performed using gas chromatography coupled to mass spectrometry, and metabolites were identified using R software and an in-house mass spectral library. Statistical analysis was performed using SPSS version 21.0. Forty-eight metabolites were identified in the serum samples. Itaconic acid (P = 0.0003), with a false discovery rate of 0.012, was found to be significantly more abundant in women who subsequently developed gestational diabetes mellitus, when compared to controls with uncomplicated pregnancies. The current pilot study found that itaconic acid may have potential as a novel biomarker in early pregnancy to predict the subsequent development of gestational diabetes mellitus. However, the findings from this pilot study require validation with a larger, diverse population before translation into the clinical setting. PMID:25064235

  12. Clinically suspected acute myopericarditis with cardiac tamponade associated with peripheral blood eosinophilia presenting in early pregnancy: a case report

    PubMed Central

    2013-01-01

    Introduction The clinical presentation of eosinophilic myocarditis may vary from asymptomatic to the manifestation of severe symptoms, including cardiac tamponade and arrhythmias. In pregnant patients with this condition, drugs must be used cautiously up to approximately the 4th month of pregnancy because drug use should be limited during the period of fetal organogenesis. Case presentation A 30-year-old Asian woman at 14 weeks of pregnancy with progressive malaise was hospitalized. The electrocardiogram revealed ST elevation and low QRS voltage. Echocardiography revealed massive pericardial effusion and myocardial swelling. A laboratory examination revealed an increase in her white blood cell count, with a predominance of neutrophils. Pericardial drainage was performed for relief of the cardiac tamponade. The pericardial effusion revealed an abundance of eosinophils. Subsequently, the peripheral blood eosinophil count began to rise, and the patient was clinically diagnosed with eosinophilic myopericarditis. The patient’s condition improved rapidly following the initiation of prednisolone treatment, and she finally delivered a full-term normal infant. Conclusions A patient with clinically suspected myopericarditis in the early stage of pregnancy who improved rapidly with pericardial drainage and prednisolone therapy, and successfully delivered a normal full-term infant; the diagnosis was made in the early stage of the disease, based on the detection of an abundance of eosinophils in the pericardial effusion preceding the subsequent development of peripheral blood eosinophilia. PMID:23668918

  13. Where need meets opportunity: youth development programs for early teens.

    PubMed

    Quinn, J

    1999-01-01

    Early adolescence is a time of burgeoning independence, autonomy, and focus on peers. It is also a time when individual interests, skills, and preferences become salient to young people. Not surprisingly, out-of-school programs designed to capture the interest of early teens are diverse in focus and varied in structure, ranging from sports teams to drop-in recreation centers, from museum apprenticeships to mentoring relationships between an individual teen and an adult. This article describes the array of various organizations that offer programs and services for youths in their early teens. It explains the philosophy of positive youth development that has emerged as a unifying theme in this long-standing but newly self-conscious field. Principles of best practice are reviewed, as are five key implementation challenges: increasing participation by youths; expanding access to programs, especially in low-income communities; improving funding; evaluating program effectiveness; and coordination with other youth services. The article closes with a discussion anticipating the new opportunities that accompany the attention and funding now going toward positive youth development programs that enrich the lives of young people through informal learning. PMID:10646262

  14. Explaining the Early Development and Health of Teen Mothers’ Children*

    PubMed Central

    Mollborn, Stefanie; Dennis, Jeff A.

    2013-01-01

    The transmission of social disadvantage from teenage mothers to their children is well established, but when and why do these disparities emerge in the early life course? Using nationally representative data from the Early Childhood Longitudinal Study-Birth Cohort, this study investigated the relationship between teen childbearing and children’s cognition, behavior, and health from infancy through preschool. Developmental disparities between teenage mothers’ children and others were largely nonexistent at 9 months but accumulated with age. Having a teenage mother predicted compromised development across several domains by age 4½. Our conceptual model expected preexisting disadvantage, ongoing resource disadvantage, and compromised parenting quality to explain the association between teen childbearing and child outcomes. Preexisting social disadvantage accounted for much of this relationship. Financial, social, and material resources in the child’s household partially or fully explained each of the remaining significant relationships between teenage childbearing and child outcomes. Parenting quality explained a smaller proportion of these relationships than did resources, and these factors’ influences were largely independent. Because children of teenage mothers with a modest set of resources were not predicted to have compromised development, resources provided in early childhood may have the potential to reduce developmental disparities for teenage mothers’ children. PMID:23630407

  15. 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. PMID:24583922

  16. 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

  17. 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.

  18. Human memory development and its dysfunction after early hippocampal injury.

    PubMed

    de Haan, Michelle; Mishkin, Mortimer; Baldeweg, Torsten; Vargha-Khadem, Faraneh

    2006-07-01

    Cognitive memory involves long-term memories for facts (semantic memory) and personal experiences (episodic memory) that can be brought to mind. There is consensus that the hippocampus and related medial temporal lobe (MTL) structures are crucial for adult cognitive memory, but much less is known about their contribution to memory during infancy and childhood. We argue that the MTL is involved in memory from early in life, supporting recognition memory within the first postnatal months and recall memory within the first year. We propose that normal development involves a sequence in which a form of semantic-like memory emerges first, whereas the characteristics of episodic memory develop only later with progressive development of the hippocampus. Early bilateral injury to the hippocampus disrupts this normal pattern such that memory skills cannot develop beyond the stage of semantic memories. This review is part of the INMED/TINS special issue "Nature and nurture in brain development and neurological disorders", based on presentations at the annual INMED/TINS symposium (http://inmednet.com/). PMID:16750273

  19. 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.

  20. 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. PMID:23123839

  1. [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

  2. [Early lung cancer detection in an occupational asbestos exposed population: clinical impact of low-dose computed tomography screening].

    PubMed

    Pira, E; Coggiola, M; Bosio, D

    2010-01-01

    Lung cancer is the primary cause of cancer mortality in developed countries. Early detection and surgical resection is essential for the treatment of lung cancer. The introduction of low-dose spiral computed tomography (LDCT) is considered one of the most promising clinical research developments in early diagnosis of lung cancer. Our study is aimed at the evaluation of spiral CT in a cohort of subjects with a past occupational exposure to asbestos at high risk of developing lung cancer. 149 subjects were enrolled between 2007 and 2009 (the criteria for enrollment were date of birth between 1930-1961, no previous cancer and general good health, latency from the beginning of exposure > 10 years, exposure duration > 1 year, possibility to undergo to surgery). A helical low-dose CT (LDCT) of the chest was performed yearly and an evaluation protocol derived from IEO with a morphological analysis of nodules have been adopted. 13 nodules were diagnosed in the first CT, 7 in the second and 3 in the third but no invasive procedures have been taken and no lung cancer have been detected. Our early follow-up data aren't able yet to evaluate the effect of screening with LDCT on mortality but have do not confirm some of the literature initial results such as the Increase in cases of overdiagnosis (false positive) due to the high prevalence of benign lesions. PMID:21438306

  3. Clinical features and drug induced side effects in early versus late antidepressant responders.

    PubMed

    Fabbri, Chiara; Marsano, Agnese; Balestri, Martina; De Ronchi, Diana; Serretti, Alessandro

    2013-10-01

    Early antidepressant response (2nd week) has been reported as the result of a true antidepressant effect and a predictor of subsequent stable response. With the purpose to study the clinical profile of early response/remission (2nd week) compared to late response/remission (4th-6th weeks), two independent major depressive disorder (MDD) samples (the Sequenced Treatment Alternatives to Relieve Depression or STAR*D n=1922 and an Italian sample n=171) were investigated. Patients were treated with citalopram in the STAR*D while in a naturalistic setting in the Italian sample. Depressive symptomatology was assessed by the Hamilton Depressive Rating Scale weekly in the Italian sample and biweekly by the Quick Inventory of Depressive Symptomatology Clinician Rated in the STAR*D. Logistic regression was used to investigate possible predictors of early response and the Bonferroni correction was applied. In the STAR*D, higher levels of baseline core depressive symptoms (Bech subscale) were associated with early response (p=0.00017), as well as lower baseline insomnia (p=0.003) and higher work and social functioning (p=0.001). In the Italian sample none of these variables were associated with the phenotype, but a non significant trend of lower baseline quality of life (p=0.078) was observed in late remitters. In the STAR*D late responders reported higher levels of antidepressant induced side effects, especially difficulty in sleeping (p=5.68e-13), with a non significant trend in the same direction in the Italian sample (p=0.09). The identification of late versus early antidepressant responders at the beginning of the treatment may be useful to guide therapeutic choices in clinical settings. PMID:23800418

  4. 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.

  5. Clinical heterogeneity in patients with early-stage Parkinson's disease: a cluster analysis.

    PubMed

    Liu, Ping; Feng, Tao; Wang, Yong-jun; Zhang, Xuan; Chen, Biao

    2011-09-01

    The aim of this study was to investigate the clinical heterogeneity of Parkinson's disease (PD) among a cohort of Chinese patients in early stages. Clinical data on demographics, motor variables, motor phenotypes, disease progression, global cognitive function, depression, apathy, sleep quality, constipation, fatigue, and L-dopa complications were collected from 138 Chinese PD subjects in early stages (Hoehn and Yahr stages 1-3). The PD subject subtypes were classified using k-means cluster analysis according to the clinical data from five- to three-cluster consecutively. Kappa statistical analysis was performed to evaluate the consistency among different subtype solutions. The cluster analysis indicated four main subtypes: the non-tremor dominant subtype (NTD, n=28, 20.3%), rapid disease progression subtype (RDP, n=7, 5.1%), young-onset subtype (YO, n=50, 36.2%), and tremor dominant subtype (TD, n=53, 38.4%). Overall, 78.3% (108/138) of subjects were always classified between the same three groups (52 always in TD, 7 in RDP, and 49 in NTD), and 98.6% (136/138) between five- and four-cluster solutions. However, subjects classified as NTD in the four-cluster analysis were dispersed into different subtypes in the three-cluster analysis, with low concordance between four- and three-cluster solutions (kappa value=-0.139, P=0.001). This study defines clinical heterogeneity of PD patients in early stages using a data-driven approach. The subtypes generated by the four-cluster solution appear to exhibit ideal internal cohesion and external isolation. PMID:21887844

  6. 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…

  7. Very Early Detection of Alzheimer Neuropathology and the Role of Brain Reserve in Modifying Its Clinical Expression

    PubMed Central

    Mortimer, James A.; Borenstein, Amy R.; Gosche, Karen M.; Snowdon, David A.

    2005-01-01

    Numerous studies show that the pathology of Alzheimer's disease is present decades before a clinical diagnosis of dementia can be made. Given the likelihood that agents will become available that reliably delay onset and/or slow progression of Alzheimer's disease, it will be important to detect preclinical Alzheimer's disease as early as possible for maximal treatment effect. Detection of individuals by sensitive cognitive measures provides one way to identify people who are at high risk of developing clinical Alzheimer's disease. However, it is likely that those with considerable brain or cognitive reserve will be able to mask cognitive deficits until very close to the onset of the dementia, rendering such cognitive measures insensitive. Optimum biomarkers for Alzheimer's disease therefore need to target the severity of underlying brain pathology independently of brain reserve. Findings are presented showing the importance of higher education and larger brain size in masking the underlying disease pathology. PMID:16306243

  8. 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.

  9. Diffusion Tensor Imaging for Understanding Brain Development in Early Life

    PubMed Central

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

    2015-01-01

    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. PMID:25559117

  10. 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. PMID

  11. Implementation of new clinical programs in the VHA healthcare system: the importance of early collaboration between clinical leadership and research.

    PubMed

    Wu, R Ryanne; Kinsinger, Linda S; Provenzale, Dawn; King, Heather A; Akerly, Patricia; Barnes, Lottie K; Datta, Santanu K; Grubber, Janet M; Katich, Nicholas; McNeil, Rebecca B; Monte, Robert; Sperber, Nina R; Atkins, David; Jackson, George L

    2014-12-01

    Collaboration between policy, research, and clinical partners is crucial to achieving proven quality care. The Veterans Health Administration has expended great efforts towards fostering such collaborations. Through this, we have learned that an ideal collaboration involves partnership from the very beginning of a new clinical program, so that the program is designed in a way that ensures quality, validity, and puts into place the infrastructure necessary for a reliable evaluation. This paper will give an example of one such project, the Lung Cancer Screening Demonstration Project (LCSDP). We will outline the ways that clinical, policy, and research partners collaborated in design, planning, and implementation in order to create a sustainable model that could be rigorously evaluated for efficacy and fidelity. We will describe the use of the Donabedian quality matrix to determine the necessary characteristics of a quality program and the importance of the linkage with engineering, information technology, and clinical paradigms to connect the development of an on-the-ground clinical program with the evaluation goal of a learning healthcare organization. While the LCSDP is the example given here, these partnerships and suggestions are salient to any healthcare organization seeking to implement new scientifically proven care in a useful and reliable way. PMID:25355086

  12. 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

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

    PubMed

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

    2015-12-01

    Eye gaze is a key channel of non-verbal communication in humans. Eye contact with others is present from birth, and eye gaze processing is crucial for social learning and adult-infant communication. 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 and gaze following 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 and standardized tests of cognitive, motor, and linguistic development 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

  14. 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.

  15. 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

  16. 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

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

    PubMed

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

    2013-03-01

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

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

    PubMed Central

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

    2011-01-01

    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 children's exposure to a chronically chaotic household may be one critical experience that is related to poorer language, beyond the contribution of SES and other demographic variables. In addition, it is not clear whether parenting might mediate the relationship between chaos and language. The purpose of this study was to understand how multiple indicators of chaos over children's first three years of life, in a representative sample of children living in low wealth rural communities, were related to child expressive and receptive language at 36 months. Factor analysis of 10 chaos indicators over five time periods suggested two factors that were named household disorganization and instability. Results suggested that after accounting for thirteen covariates like maternal education and poverty, one of two chaos composites (household disorganization) accounted for significant variance in receptive and expressive language. Parenting partially mediated this relationship although household disorganization continued to account for unique variance in predicting early language. PMID:23049162

  19. Clinical monitoring of early caries lesions using cross polarization optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Fried, Daniel; Staninec, Michal; Darling, Cynthia L.; Chan, Kenneth H.; Pelzner, Roger B.

    New methods are needed for the nondestructive measurement of tooth demineralization and remineralization and to monitor the progression of incipient caries lesions (tooth decay) for effective nonsurgical intervention and to evaluate the performance of anti-caries treatments such as chemical treatments or laser irradiation. Studies have shown that optical coherence tomography (OCT) has great potential to fulfill this role, since it can be used to measure the depth and severity of early lesions with an axial resolution exceeding 10-μm. It is easy to apply in vivo and it can be used to image the convoluted topography of tooth occlusal surfaces. In this paper we present early results from two clinical studies underway to measure the effect of fluoride intervention on early lesions. CP-OCT was used to monitor early lesions on enamel and root surfaces before and after intervention with fluoride varnish. The lesion depth and internal structure were resolved for all the lesions examined and some lesions had well defined surface zones of lower reflectivity that may be indicative of arrested lesions. Changes were also noted in the structure of some of the lesions after fluoride intervention.

  20. Nursing students in clinical practice--developing a model for clinical supervision.

    PubMed

    Häggman-Laitila, Arja; Elina, Eriksson; Riitta, Meretoja; Kirsi, Sillanpää; Leena, Rekola

    2007-11-01

    The aim of this study was to develop a model for clinical supervision to promote the clinical practice of nursing students. The study was implemented in Finland and it was carried out in three phases. Firstly, data were collected by means of a literature review and focus group interviews. Secondly, the data were analysed and described in expert groups, and finally the model itself was evaluated by 23 nursing experts. The data of literature review and focus group interviews consisted of 27 studies and four groups from three organisations: nurses (n=7), managers (n=6), teachers (n=8) and students (n=6). The data were analysed by qualitative content analysis. The model devolved from the study includes the concepts describing prerequisites, content and influence of clinical supervision. The prerequisites are nursing skills, a holistic view of the nursing curriculum, pedagogical, organisational, development, cooperation and interaction competence and decision-making skills. The content of clinical supervision includes support of professional development, pedagogical competence, research and development activities and collaborative working. Clinical supervision has influence on students' professional and personal development and conception of the future of nursing profession, students' preparedness for career planning and the teacher's and preceptor's professional development. The model could unify the notions of all parties concerned of the prerequisites, content and influence of clinical supervision. Furthermore, the entire supervision process and its control could be clarified. The model may be utilised in selecting and educating preceptors and evaluating the quality of clinical supervision. PMID:17936544

  1. Miz1 Is Required for Early Embryonic Development during Gastrulation

    PubMed Central

    Adhikary, Sovana; Peukert, Karen; Karsunky, Holger; Beuger, Vincent; Lutz, Werner; Elsässer, Hans-Peter; Möröy, Tarik; Eilers, Martin

    2003-01-01

    Miz1 is a member of the POZ domain/zinc finger transcription factor family. In vivo, Miz1 forms a complex with the Myc oncoprotein and recruits Myc to core promoter elements. Myc represses transcription through Miz1 binding sites. We now show that the Miz1 gene is ubiquitously expressed during mouse embryogenesis. In order to elucidate the physiological function of Miz1, we have deleted the mouse Miz1 gene by homologous recombination. Miz1+/− mice are indistinguishable from wild-type animals; in contrast, Miz1−/− embryos are not viable. They are severely retarded in early embryonic development and do not undergo normal gastrulation. Expression of Goosecoid and Brachyury is detectable in Miz1−/− embryos, suggesting that Miz1 is not required for signal transduction by Nodal. Expression of p21Cip1, a target gene of Miz1 is unaltered; in contrast, expression of p57Kip2, another target gene of Miz1 is absent in Miz1−/− embryos. Miz1−/− embryos succumb to massive apoptosis of ectodermal cells around day 7.5 of embryonic development. Our results show that Miz1 is required for early embryonic development during gastrulation. PMID:14560010

  2. 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. PMID:24780627

  3. A Gene Expression Atlas of Early Craniofacial Development

    PubMed Central

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

    2014-01-01

    We present a gene expression atlas of early mouse craniofacial development. Laser capture microdissection (LCM) was used to isolate cells from the principal critical micro-regions, 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. PMID:24780627

  4. 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

  5. The Clinical Supervision Cycle: A Component of Staff Development Programs.

    ERIC Educational Resources Information Center

    Cramer, Susan R.; Koskela, Ruth A.

    Findings are reported from a statewide survey of middle and junior high schools in Wisconsin. The study had two major purposes: (1) to determine the extent to which the clinical supervision cycle was a component of staff development programs; and (2) to identify characteristics of existing clinical supervision practices within staff development…

  6. Very early onset and greater vulnerability in schizophrenia: A clinical and neuroimaging study

    PubMed Central

    Margari, Francesco; Presicci, Anna; Petruzzelli, Maria Giuseppina; Ventura, Patrizia; Di Cuonzo, Franca; Palma, Michele; Margari, Lucia

    2008-01-01

    Although schizophrenia has been diagnosed in children, this group of disorders has received too little attention in the clinical and research literature. Preliminary data suggest that early onset schizophrenia (EOS) and very early onset schizophrenia (VEOS) tend to have a worse outcome than adult onset schizophrenia, and seem to be related to a greater familial vulnerability, due to genetic, psychosocial, and environmental factors. Recently, advanced neuroimaging techniques have revealed structural and functional brain abnormalities in some cerebral areas. This paper reports on a case diagnosed as VEOS, with premorbid year-long psychopathological history. The patient showed atypical proton magnetic resonance spectroscopy findings, and normal brain and spine computer tomography and brain magnetic resonance images. PMID:19043525

  7. Biological and clinical developments in melanoma vaccines.

    PubMed

    Marchand, M; Brichard, V; van Baren, N; Coulie, P G

    2001-05-01

    The identification of antigens recognised on human tumours by autologous T-lymphocytes has opened the way for vaccination strategies involving defined tumour antigens. These vaccinations are therapeutic, i.e. they involve patients with detectable disease. Tumour regressions have been observed in a minority of melanoma patients in Phase I/II trials. Some of these regressions have been complete and long lasting. Improving the efficacy of therapeutic vaccines will critically depend on their capacity to trigger a robust immune response, on the development of appropriate methods to monitor these antitumour immune responses to vaccination and on a better understanding of the mechanisms used by tumours to escape immune attack. Finally, the initiation of large randomised Phase III trials will determine the impact of these vaccines on melanoma treatment. PMID:11727521

  8. Bridging the gap: facilities and technologies for development of early stage therapeutic mAb candidates.

    PubMed

    Munro, Trent P; Mahler, Stephen M; Huang, Edwin P; Chin, David Y; Gray, Peter P

    2011-01-01

    Therapeutic monoclonal antibodies (mAbs) currently dominate the biologics marketplace. Development of a new therapeutic mAb candidate is a complex, multistep process and early stages of development typically begin in an academic research environment. Recently, a number of facilities and initiatives have been launched to aid researchers along this difficult path and facilitate progression of the next mAb blockbuster. Complementing this, there has been a renewed interest from the pharmaceutical industry to reconnect with academia in order to boost dwindling pipelines and encourage innovation. In this review, we examine the steps required to take a therapeutic mAb from discovery through early stage preclinical development and toward becoming a feasible clinical candidate. Discussion of the technologies used for mAb discovery, production in mammalian cells and innovations in single-use bioprocessing is included. We also examine regulatory requirements for product quality and characterization that should be considered at the earliest stages of mAb development. We provide details on the facilities available to help researchers and small-biotech build value into early stage product development, and include examples from within our own facility of how technologies are utilized and an analysis of our client base. PMID:21822050

  9. A Sensor To Detect the Early Stages in the Development of Crystalline Proteus mirabilis Biofilm on Indwelling Bladder Catheters

    PubMed Central

    Stickler, D. J.; Jones, S. M.; Adusei, G. O.; Waters, M. G.

    2006-01-01

    A simple sensor has been developed to detect the early stages of urinary catheter encrustation and avoid the clinical crises induced by catheter blockage. In laboratory models of colonization by Proteus mirabilis, the sensor signaled encrustation at an average time of 43 h before catheters were blocked with crystalline biofilm. PMID:16597888

  10. 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…

  11. Clinical policy: Critical issues in the initial evaluation and management of patients presenting to the emergency department in early pregnancy.

    PubMed

    Hahn, Sigrid A; Lavonas, Eric J; Mace, Sharon E; Napoli, Anthony M; Fesmire, Francis M

    2012-09-01

    This clinical policy from the American College of Emergency Physicians is the revision of the 2003 Clinical Policy: Critical Issues in the Initial Evaluation and Management of Patients Presenting to the Emergency Department in Early Pregnancy.(1) A writing subcommittee reviewed the literature to derive evidence-based recommendations to help clinicians answer the following critical questions: (1) Should the emergency physician obtain a pelvic ultrasound in a clinically stable pregnant patient who presents to the emergency department (ED) with abdominal pain and/or vaginal bleeding and a beta human chorionic gonadotropin (β-hCG) level below a discriminatory threshold? (2) In patients who have an indeterminate transvaginal ultrasound, what is the diagnostic utility of β-hCG for predicting possible ectopic pregnancy? (3) In patients receiving methotrexate for confirmed or suspected ectopic pregnancy, what are the implications for ED management? Evidence was graded and recommendations were developed based on the strength of the available data in the medical literature. A literature search was also performed for a critical question from the 2003 clinical policy.(1) Is the administration of anti-D immunoglobulin indicated among Rh-negative women during the first trimester of pregnancy with threatened abortion, complete abortion, ectopic pregnancy, or minor abdominal trauma? Because no new, high-quality articles were found, the management recommendations from the previous policy are discussed in the introduction. PMID:22921048

  12. AMTA Monograph Series - Effective Clinical Practice in Music Therapy Early Childhood and School Age Educational Settings

    ERIC Educational Resources Information Center

    Humpal, Marcia Earl, Ed.; Colwell, Cynthia, Ed.

    2006-01-01

    Educators, families, and media in increasing numbers are recognizing the unique role music plays in young children's development. More and more daycare, preschool, and early intervention centers offer employment opportunities that reflect the needs and attitudes of our ever-changing society. Furthermore, Federal and state regulations, a changing…

  13. Clinical pharmacology: special safety considerations in drug development and pharmacovigilance.

    PubMed

    Atuah, Kwame N; Hughes, Dyfrig; Pirmohamed, Munir

    2004-01-01

    The dose of a drug is a major determinant of its safety, and establishing a safe dose of a novel drug is a prime objective during clinical development. The design of pre-marketing clinical trials precludes the representation of important subpopulations such as children, the elderly and people with co-morbidities. Therefore, postmarketing surveillance (PMS) activities are required to monitor the safety profile of drugs in real clinical practice. Furthermore, individual variations in pharmacogenetic profiles, the immune system, drug metabolic pathways and drug-drug interactions are also important factors in the occurrence of adverse drug reactions. Thus, the safety of a drug is a major clinical consideration before and after it is marketed. A multidisciplinary approach is required to enhance the safety profile of drugs at all stages of development, including PMS activities. Clinical pharmacology encompasses a range of disciplines and forms the backbone of drug safety consideration during clinical drug development. In this review we give an overview of the clinical drug development process and consider its limitations. We present a discussion of several aspects of clinical pharmacology and their application to enhancing drug safety. Pharmacokinetic-pharmacodynamic modelling provides a method of predicting a clinically safe dose; consideration of drug pharmacokinetics in special populations may enhance safe therapeutics in a wider spectrum of patients, while pharmacogenetics provides the possibility of genotype-specific therapeutics. Pharmacovigilance activities are also discussed. Given the complex nature and unpredictability of type B reactions, PMS activities are crucial in managing the risks drugs pose to the general population. The various aspects of clinical pharmacology discussed make a strong case for this field as the backbone of optimising and promoting safe development and use of drugs. PMID:15154826

  14. 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…

  15. Brugada Syndrome and Early Repolarisation: Distinct Clinical Entities or Different Phenotypes of the Same Genetic Disease?

    PubMed Central

    Caputo, Maria Luce; Regoli, François; Moccetti, Tiziano; Brugada, Pedro; Auricchio, Angelo

    2016-01-01

    Brugada and early repolarisation (ER) syndromes are currently considered two distinct inherited electrical disorders with overlapping clinical and electrocardiographic features. A considerable number of patients diagnosed with ER syndrome have a genetic mutation related to Brugada syndrome (BrS). Due to the high variable phenotypic manifestation, patients with BrS may present with inferolateral repolarisation abnormalities only, resembling the ER pattern. Moreover, the complex genotype–phenotype interaction in BrS can lead to the occurrence of mixed phenotypes with ER syndrome. The first part of this review focuses on specific clinical and electrocardiographic features of BrS and ER syndrome, highlighting the similarity shared by the two primary electrical disorders. The genetic background, with emphasis on the complexity of genotype–phenotype interaction, is explored in the second part of this review.

  16. A Clinical Algorithm for Early Identification and Intervention of Cervical Muscular Torticollis.

    PubMed

    Nichter, Stephanie

    2016-06-01

    Congenital muscular torticollis (CMT) is a common newborn pediatric muscular deformity of the neck. The purpose of this article is to suggest a clinical algorithm for pediatric clinicians to promote prompt identification and intervention for infants with CMT. Early intervention for a child with CMT at less than 1 month of age yields a 98% success rate by 2.5 months of age, with the infant achieving near normal range of motion. Intervention initiated at 6 months of age or later can require 9 to 10 months of therapy with less success in achieving full range of motion of the cervical musculature. The clinical algorithm proposed here incorporates the American Physical Therapy Association guideline for CMT to optimize outcomes for the child and reduce health care expenditures. Current evidence and guidelines demonstrate that primary care providers are the primary diagnostic clinicians, while physical therapists are the preferred provider for the treatment of CMT. PMID:26307184

  17. 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.

  18. [Development of Autogenic Training Clinical Effectiveness Scale (ATCES)].

    PubMed

    Ikezuki, Makoto; Miyauchi, Yuko; Yamaguchi, Hajime; Koshikawa, Fusako

    2002-02-01

    The purpose of the present study was to develop a scale measuring clinical effectiveness of autogenic training. In Study 1, 167 undergraduates completed a survey of items concerning physical and mental states, which were thought to vary in the course of autogenic training. With item and factor analyses, 20 items were selected, and the resulting scale (ATCES) had high discrimination and clear factor structure. In Study 2, reliability and concurrent and clinical validity of the scale were examined with three groups of respondents: 85 mentally healthy, 31 control, 13 clinical persons. The scale showed a high test-retest correlation (r = .83) and alpha coefficient (alpha = .86). ATCES had a Pearson correlation coefficient of r = .56 with General Health Questionnaire (GHQ-12), and r = .73 with trait anxiety (STAI-T). And ATCES successfully discriminated the mentally healthy and clinical groups in terms of clinical effectiveness. These results demonstrated high reliability and sufficient concurrent and clinical validity of the new scale. PMID:11977841

  19. 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.

  20. Early-life experience, epigenetics, and the developing brain.

    PubMed

    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

  1. 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

  2. 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

  3. 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

  4. Does bilingual experience affect early visual perceptual development?

    PubMed Central

    Schonberg, Christina; Sandhofer, Catherine M.; Tsang, Tawny; Johnson, Scott P.

    2014-01-01

    Visual attention and perception develop rapidly during the first few months after birth, and these behaviors are critical components in the development of language and cognitive abilities. Here we ask how early bilingual experiences might lead to differences in visual attention and perception. Experiments 1–3 investigated the looking behavior of monolingual and bilingual infants when presented with social (Experiment 1), mixed (Experiment 2), or non-social (Experiment 3) stimuli. In each of these experiments, infants' dwell times (DT) and number of fixations to areas of interest (AOIs) were analyzed, giving a sense of where the infants looked. To examine how the infants looked at the stimuli in a more global sense, Experiment 4 combined and analyzed the saccade data collected in Experiments 1–3. There were no significant differences between monolingual and bilingual infants' DTs, AOI fixations, or saccade characteristics (specifically, frequency, and amplitude) in any of the experiments. These results suggest that monolingual and bilingual infants process their visual environments similarly, supporting the idea that the substantial cognitive differences between monolinguals and bilinguals in early childhood are more related to active vocabulary production than perception of the environment. PMID:25566116

  5. 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. PMID:27060416

  6. Single cell dissection of early kidney development: multilineage priming.

    PubMed

    Brunskill, Eric W; Park, Joo-Seop; Chung, Eunah; Chen, Feng; Magella, Bliss; Potter, S Steven

    2014-08-01

    We used a single cell RNA-seq strategy to create an atlas of gene expression patterns in the developing kidney. At several stages of kidney development, histologically uniform populations of cells give rise to multiple distinct lineages. We performed single cell RNA-seq analysis of total mouse kidneys at E11.5 and E12.5, as well as the renal vesicles at P4. We define an early stage of progenitor cell induction driven primarily by gene repression. Surprising stochastic expression of marker genes associated with differentiated cell types was observed in E11.5 progenitors. We provide a global view of the polarized gene expression already present in the renal vesicle, the first epithelial precursor of the nephron. We show that Hox gene read-through transcripts can be spliced to produce intergenic homeobox swaps. We also identify a surprising number of genes with partially degraded noncoding RNA. Perhaps most interesting, at early developmental times single cells often expressed genes related to several developmental pathways. This provides powerful evidence that initial organogenesis involves a process of multilineage priming. This is followed by a combination of gene repression, which turns off the genes associated with most possible lineages, and the activation of increasing numbers of genes driving the chosen developmental direction. PMID:25053437

  7. Single cell dissection of early kidney development: multilineage priming

    PubMed Central

    Brunskill, Eric W.; Park, Joo-Seop; Chung, Eunah; Chen, Feng; Magella, Bliss; Potter, S. Steven

    2014-01-01

    We used a single cell RNA-seq strategy to create an atlas of gene expression patterns in the developing kidney. At several stages of kidney development, histologically uniform populations of cells give rise to multiple distinct lineages. We performed single cell RNA-seq analysis of total mouse kidneys at E11.5 and E12.5, as well as the renal vesicles at P4. We define an early stage of progenitor cell induction driven primarily by gene repression. Surprising stochastic expression of marker genes associated with differentiated cell types was observed in E11.5 progenitors. We provide a global view of the polarized gene expression already present in the renal vesicle, the first epithelial precursor of the nephron. We show that Hox gene read-through transcripts can be spliced to produce intergenic homeobox swaps. We also identify a surprising number of genes with partially degraded noncoding RNA. Perhaps most interesting, at early developmental times single cells often expressed genes related to several developmental pathways. This provides powerful evidence that initial organogenesis involves a process of multilineage priming. This is followed by a combination of gene repression, which turns off the genes associated with most possible lineages, and the activation of increasing numbers of genes driving the chosen developmental direction. PMID:25053437

  8. Design of clinical trials for therapeutic cancer vaccines development.

    PubMed

    Mackiewicz, Jacek; Mackiewicz, Andrzej

    2009-12-25

    Advances in molecular and cellular biology as well as biotechnology led to definition of a group of drugs referred to as medicinal products of advanced technologies. It includes gene therapy products, somatic cell therapeutics and tissue engineering. Therapeutic cancer vaccines including whole cell tumor cells vaccines or gene modified whole cells belong to somatic therapeutics and/or gene therapy products category. The drug development is a multistep complex process. It comprises of two phases: preclinical and clinical. Guidelines on preclinical testing of cell based immunotherapy medicinal products have been defined by regulatory agencies and are available. However, clinical testing of therapeutic cancer vaccines is still under debate. It presents a serious problem since recently clinical efficacy of the number of cancer vaccines has been demonstrated that focused a lot of public attention. In general clinical testing in the current form is very expensive, time consuming and poorly designed what may lead to overlooking of products clinically beneficial for patients. Accordingly regulatory authorities and researches including Cancer Vaccine Clinical Trial Working Group proposed three regulatory solutions to facilitate clinical development of cancer vaccines: cost-recovery program, conditional marketing authorization, and a new development paradigm. Paradigm includes a model in which cancer vaccines are investigated in two types of clinical trials: proof-of-principle and efficacy. The proof-of-principle trial objectives are: safety; dose selection and schedule of vaccination; and demonstration of proof-of-principle. Efficacy trials are randomized clinical trials with objectives of demonstrating clinical benefit either directly or through a surrogate. The clinical end points are still under debate. PMID:19835869

  9. 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.

  10. Studying MAP Kinase pathways during early development of Xenopus laevis.

    PubMed

    Keren, Aviad; Bengal, Eyal

    2010-01-01

    The following chapter describes several methods involved in the detection of MAPK activities and phosphorylated proteins during early development of Xenopus laevis. The Xenopus embryo provides a powerful platform for biochemical studies. We describe here basic methods of embryo manipulations such as egg fertilization, embryo growth and maintenance, microinjection of capped RNA and antisense morpholino oligonucleotides (AMOs), and isolation of explants. In addition, we describe methods to detect phosphorylated proteins, to analyze kinase activity, and to interfere with signaling pathways. Immunohistochemical staining performed on whole embryos or on tissue sections is an additional method for the detection of phosphorylated proteins in the developing embryo. Approaches to activate or inhibit MAPK activities including the ectopic expression of mutated isoforms of MAPK kinase, or the incubation of embryo explants with pharmacological inhibitors are described. Finally, we describe an in vitro kinase assay specifically designed for the Xenopus embryo. PMID:20811998

  11. 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.

  12. AstroNewt: early development of newt in space.

    PubMed

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

    1996-01-01

    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. PMID:11538624

  13. The effect of early, comprehensive genomic testing on clinical care in neonatal diabetes: an international cohort study

    PubMed Central

    De Franco, Elisa; Flanagan, Sarah E; Houghton, Jayne AL; Allen, Hana Lango; Mackay, Deborah JG; Temple, I Karen; Ellard, Sian; Hattersley, Andrew T

    2015-01-01

    Summary Background Traditional genetic testing focusses on analysis of one or a few genes according to clinical features; this approach is changing as improved sequencing methods enable simultaneous analysis of several genes. Neonatal diabetes is the presenting feature of many discrete clinical phenotypes defined by different genetic causes. Genetic subtype defines treatment, with improved glycaemic control on sulfonylurea treatment for most patients with potassium channel mutations. We investigated the effect of early, comprehensive testing of all known genetic causes of neonatal diabetes. Methods In this large, international, cohort study, we studied patients with neonatal diabetes diagnosed with diabetes before 6 months of age who were referred from 79 countries. We identified mutations by comprehensive genetic testing including Sanger sequencing, 6q24 methylation analysis, and targeted next-generation sequencing of all known neonatal diabetes genes. Findings Between January, 2000, and August, 2013, genetic testing was done in 1020 patients (571 boys, 449 girls). Mutations in the potassium channel genes were the most common cause (n=390) of neonatal diabetes, but were identified less frequently in consanguineous families (12% in consanguineous families vs 46% in non-consanguineous families; p<0·0001). Median duration of diabetes at the time of genetic testing decreased from more than 4 years before 2005 to less than 3 months after 2012. Earlier referral for genetic testing affected the clinical phenotype. In patients with genetically diagnosed Wolcott-Rallison syndrome, 23 (88%) of 26 patients tested within 3 months from diagnosis had isolated diabetes, compared with three (17%) of 18 patients referred later (>4 years; p<0·0001), in whom skeletal and liver involvement was common. Similarly, for patients with genetically diagnosed transient neonatal diabetes, the diabetes had remitted in only ten (10%) of 101 patients tested early (<3 months) compared with 60

  14. An Internet Portal for the Development of Clinical Practice Guidelines

    PubMed Central

    Höhne, W.J.; Karge, T.; Siegmund, B.; Preiss, J.; Hoffmann, J.C.; Zeitz, M.; Fölsch, U.R.

    2010-01-01

    Background The complexity and quality requirements for the development of clinical practice guidelines steadily increase. Internet technologies support this process by optimizing the development process. Objective The aim of this internet based solution was to facilitate the development of clinical practice guidelines. Methods An internet portal was developed allowing for a shared workplace to support clinical practice guideline authoring. It is based on a Content Management System and combines different tools for document handling and editing, communication as well as process and team steering. Results Until now, the internet portal has been successfully implicated in the development of six evidence- and consensus-based clinical practice guidelines. Additional German and European clinical practice guidelines are currently generated with support of the internet portal. The available tools allow for a flexible design of the scheduled workflow, depending on the requirements of the respective group. An additional strength of the platform is the advantage to transfer all data from a previous version of a guideline into the next ‘life-cycle’. Conclusion The application of the portal results in a considerable reduction of costs and development time of the resulting clinical practice guidelines. PMID:23616852

  15. 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

  16. 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

    2014-07-01

    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

  17. Clinical value of gadoxetic acid-enhanced magnetic resonance imaging in surgery for hepatocellular carcinoma - with a special emphasis on early hepatocellular carcinoma

    PubMed Central

    Matsuda, Masanori

    2015-01-01

    Gadoxetic acid- or gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) achieves excellent lesion detection and characterization for both hypervascular hepatocellular carcinoma (HCC) in arterial phase imaging and hypovascular early HCC (small well-differentiated HCC of the vaguely nodular type) in hepatobiliary phase imaging, and has become an indispensable imaging modality in the treatment of HCC. Early HCCs have been detected more frequently since the introduction of EOB-MRI into daily clinical practice. Early HCC is known to progress to conventional hypervascular HCC, and many risk factors have been identified for the hypervascularization of early HCC including the diameter of the tumor, presence of fat, and imaging findings of EOB-MRI. The rate of the development of hypervascular HCC was previously reported to be high in patients with chronic liver disease and early HCC. The presence of early HCC is regarded as a predictor for the recurrence of HCC following hepatic resection. On the other hand, although early HCC itself is currently not regarded as a target lesion for hepatic resection, early HCC at high risk of hypervascularity needs to be treated by local ablation therapy. If concomitant early HCC with progressed HCC is at high risk of hypervascularization and the functional liver reserve of a patient is sufficient, its simultaneous treatment at the time of hepatic resection for progressed HCC is recommended. Further studies on larger numbers of patients are needed before this strategy is adopted. PMID:26730272

  18. 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…

  19. 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…

  20. 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