Transcription-dependent induction of G1 phase during the zebra fish midblastula transition.

PubMed

Zamir, E; Kam, Z; Yarden, A

1997-02-01

The early development of the zebra fish (Danio rerio) embryo is characterized by a series of rapid and synchronous cell cycles with no detectable transcription. This period is followed by the midblastula transition (MBT), during which the cell cycle gradually lengthens, cell synchrony is lost, and zygotic transcription is initially detected. In this work, we examined the changes in the pattern of the cell cycle during MBT in zebra fish and whether these changes are dependent on the initiation of zygotic transcription. To characterize the pattern of the early zebra fish cell cycles, the embryonic DNA content was determined by flow cytometric analysis. We found that G1 phase is below detection levels during the first 10 cleavages and can be initially detected at the onset of MBT. Inhibition of zygotic transcription, by microinjection of actinomycin D, abolished the appearance of G1 phase at MBT. Premature activation of zygotic transcription, by microinjection of nonspecific DNA, induced G1 phase before the onset of MBT, while coinjection of actinomycin D and nonspecific DNA abolished this early appearance of G1 phase. We therefore suggest that during the early development of the zebra fish embryo, G1 phase appears at the onset of MBT and that the activation of transcription at MBT is essential and sufficient for the G1-phase induction.

Failures in Phase III: Causes and Consequences.

PubMed

Seruga, Bostjan; Ocana, Alberto; Amir, Eitan; Tannock, Ian F

2015-10-15

Phase III randomized controlled trials (RCT) in oncology fail to lead to registration of new therapies more often than RCTs in other medical disciplines. Most RCTs are sponsored by the pharmaceutical industry, which reflects industry's increasing responsibility in cancer drug development. Many preclinical models are unreliable for evaluation of new anticancer agents, and stronger evidence of biologic effect should be required before a new agent enters the clinical development pathway. Whenever possible, early-phase clinical trials should include pharmacodynamic studies to demonstrate that new agents inhibit their molecular targets and demonstrate substantial antitumor activity at tolerated doses in an enriched population of patients. Here, we review recent RCTs and found that these conditions were not met for most of the targeted anticancer agents, which failed in recent RCTs. Many recent phase III RCTs were initiated without sufficient evidence of activity from early-phase clinical trials. Because patients treated within such trials can be harmed, they should not be undertaken. The bar should also be raised when making decisions to proceed from phase II to III and from phase III to marketing approval. Many approved agents showed only better progression-free survival than standard treatment in phase III trials and were not shown to improve survival or its quality. Introduction of value-based pricing of new anticancer agents would dissuade the continued development of agents with borderline activity in early-phase clinical trials. When collaborating with industry, oncologists should be more critical and better advocates for cancer patients. ©2015 American Association for Cancer Research.

Phase 0/I/II Cancer Prevention Clinical Trials Program (Consortia) | Division of Cancer Prevention

Cancer.gov

Five cancer research centers lead multiple collaborative networks to assess potential cancer preventive agents and to conduct early clinical development of promising preventive agents. Also called the Consortia for Early Phase Prevention Trials, the studies require extensive biomarker analysis, investigation of the biologic effects of the cancer preventive agents on their

Masks as Self-Study. Challenging and Sustaining Teachers' Personal and Professional Personae in Early-Mid Career Life Phases

ERIC Educational Resources Information Center

Leitch, Ruth

2010-01-01

Drawing on previous research identifying how teachers' capacities to sustain their effectiveness in different phases of their professional lives are affected positively and/or negatively by their sense of identity, this paper illuminates three early-mid career teachers' self-study inquiries, centring on mask work. The creative development of…

Development of the Sri Lankan early teenagers' violence inventory: an instrument to measure peer violence in schools.

PubMed

Wijeratne, Monika; Seneviratne, Rohini; Gunawardena, Nalika; Østbye, Truls; Lynch, Catherine; Sandøy, Ingvild Fossgard

2014-01-01

This study was designed to develop an inventory to measure peer violence among early teens (13-15 years of age) in schools in Sri Lanka. Development of SLETVI was carried out in two phases. In phase I, development of an operational definition for peer violence, identification, and finalizing violent acts for inventory was done by a combination of qualitative methods: a comprehensive literature review, focus group discussions among 13-15-year-old adolescents, their teachers and parents, and consultative meetings with experts in the field. Inventory was then pretested. In phase II, elaboration of SLETVI was carried out by administering it to a sample of 1700 adolescents (13-15 years old). Exploratory factor analysis using principal component analysis was performed separately for experiences of victimization and perpetration. Test-retest reliability of SLETVI was assessed. SLETVI included 37 items in three factors: "less severe violence," "severe physical," and "severe relational" violence. Combined use of qualitative and quantitative methods enabled development of a culturally valid and reliable operational inventory to assess early teenagers' peer violence in Sri Lankan and other South Asian schools.

The Cost of Inequality: The Importance of Investing in High Quality Early Childhood Education Programs

ERIC Educational Resources Information Center

Keith, Rebecca S.

2017-01-01

The focus of this dissertation was to explore the importance of high quality early education in later secondary education development, quantifying quality in early childhood education programs, and examining how teacher education contributes to quality of early childhood education programs. For phase I, early childhood education positively…

Defining multiple, distinct, and shared spatiotemporal patterns of DNA replication and endoreduplication from 3D image analysis of developing maize (Zea mays L.) root tip nuclei.

PubMed

Bass, Hank W; Hoffman, Gregg G; Lee, Tae-Jin; Wear, Emily E; Joseph, Stacey R; Allen, George C; Hanley-Bowdoin, Linda; Thompson, William F

2015-11-01

Spatiotemporal patterns of DNA replication have been described for yeast and many types of cultured animal cells, frequently after cell cycle arrest to aid in synchronization. However, patterns of DNA replication in nuclei from plants or naturally developing organs remain largely uncharacterized. Here we report findings from 3D quantitative analysis of DNA replication and endoreduplication in nuclei from pulse-labeled developing maize root tips. In both early and middle S phase nuclei, flow-sorted on the basis of DNA content, replicative labeling was widely distributed across euchromatic regions of the nucleoplasm. We did not observe the perinuclear or perinucleolar replicative labeling patterns characteristic of middle S phase in mammals. Instead, the early versus middle S phase patterns in maize could be distinguished cytologically by correlating two quantitative, continuous variables, replicative labeling and DAPI staining. Early S nuclei exhibited widely distributed euchromatic labeling preferentially localized to regions with weak DAPI signals. Middle S nuclei also exhibited widely distributed euchromatic labeling, but the label was preferentially localized to regions with strong DAPI signals. Highly condensed heterochromatin, including knobs, replicated during late S phase as previously reported. Similar spatiotemporal replication patterns were observed for both mitotic and endocycling maize nuclei. These results revealed that maize euchromatin exists as an intermingled mixture of two components distinguished by their condensation state and replication timing. These different patterns might reflect a previously described genome organization pattern, with "gene islands" mostly replicating during early S phase followed by most of the intergenic repetitive regions replicating during middle S phase.

Comparative transcriptome analysis during early fruit development between three seedy citrus genotypes and their seedless mutants

USDA-ARS?s Scientific Manuscript database

Identification of genes with differential transcript abundance (GDTA) in seedless mutants may enhance understanding of seedless citrus development. Transcriptome analysis was conducted at three time points during early fruit development (Phase 1) of three seedy citrus genotypes: Fallglo [Bower citru...

Challenges and perspective of drug repurposing strategies in early phase clinical trials.

PubMed

Kato, Shumei; Moulder, Stacy L; Ueno, Naoto T; Wheler, Jennifer J; Meric-Bernstam, Funda; Kurzrock, Razelle; Janku, Filip

2015-01-01

Despite significant investments in the development of new agents only 5% of cancer drugs entering Phase I clinical trials are ultimately approved for routine clinical cancer care. Drug repurposing strategies using novel combinations of previously tested anticancer agents could reduce the cost and improve treatment outcomes. At MD Anderson Cancer Center, early phase clinical trials with drug repurposing strategies demonstrated promising outcomes in patients with both rare and common treatment refractory advanced cancers. Despite clinical efficacy advancing drug repurposing strategies in the clinical trial trajectory beyond early phase studies has been challenging mainly due to lack of funding and interest from the pharmaceutical industry. In this review, we delineate our experience and challenges with drug repurposing strategies.

Changes in neural circuitry associated with depression at pre-clinical, pre-motor and early motor phases of Parkinson's disease.

PubMed

Borgonovo, Janina; Allende-Castro, Camilo; Laliena, Almudena; Guerrero, Néstor; Silva, Hernán; Concha, Miguel L

2017-02-01

Although Parkinson's Disease (PD) is mostly considered a motor disorder, it can present at early stages as a non-motor pathology. Among the non-motor clinical manifestations, depression shows a high prevalence and can be one of the first clinical signs to appear, even a decade before the onset of motor symptoms. Here, we review the evidence of early dysfunction in neural circuitry associated with depression in the context of PD, focusing on pre-clinical, pre-motor and early motor phases of the disease. In the pre-clinical phase, structural and functional changes in the substantia nigra, basal ganglia and limbic structures are already observed. Some of these changes are linked to motor compensation mechanisms while others correspond to pathological processes common to PD and depression and thus could underlie the appearance of depressive symptoms during the pre-motor phase. Studies of the early motor phase (less than five years post diagnosis) reveal an association between the extent of damage in different monoaminergic systems and the appearance of emotional disorders. We propose that the limbic loop of the basal ganglia and the lateral habenula play key roles in the early genesis of depression in PD. Alterations in the neural circuitry linked with emotional control might be sensitive markers of the ongoing neurodegenerative process and thus may serve to facilitate an early diagnosis of this disease. To take advantage of this, we need to improve the clinical criteria and develop biomarkers to identify depression, which could be used to determine individuals at risk to develop PD. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Effect of immune modulation on immunogenic and protective activity of a live plague vaccine].

PubMed

Karal'nik, B V; Ponomareva, T S; Deriabin, P N; Denisova, T G; Mel'nikova, N N; Tugambaev, T I; Atshabar, B B; Zakarian, S B

2014-01-01

Comparative evaluation of the effect of polyoxidonium and betaleukin on immunogenic and protective activity of a live plague vaccine in model animal experiments. Plague vaccine EV, polyoxidonium, betaleukin, erythrocytic antigenic diagnosticum for determination of F1 antibodies and immune reagents for detection of lymphocytes with F1 receptors (LFR) in adhesive test developed by the authors were used. The experiments were carried out in 12 rabbits and 169 guinea pigs. Immune modulation accelerated the appearance and disappearance of LFR (early phase) and ensured a more rapid and intensive antibody formation (effector phase). Activation by betaleukin is more pronounced than by polyoxidonium. The more rapid and intensive was the development of early phase, the more effective was antibody response to the vaccine. Immune modulation in the experiment with guinea pigs significantly increased protective activity of the vaccine. The use of immune modulators increased immunogenic (in both early and effector phases of antigen-specific response) and protective activity of the EV vaccine. A connection between the acceleration of the first phase of antigen-specific response and general intensity of effector phase of immune response to the EV vaccine was detected. ,

Examination of a modified cell cycle synchronization method and bovine nuclear transfer using synchronized early G1 phase fibroblast cells.

PubMed

Urakawa, Manami; Ideta, Atsushi; Sawada, Tokihiko; Aoyagi, Yoshito

2004-08-01

Somatic cell nuclear transfer has a low success rate, due to a high incidence of fetal loss and increased perinatal morbidity/mortality. One factor that may affect the successful development of nuclear transfer embryos is the cell cycle stage of the donor cell. In order to establish a cell cycle synchronization method that can consistently produce cloned embryos and offspring, we examined the effects of different combinations of three cell treatments on the recovery rate of mitotic phase cells using bovine fetal fibroblasts. In the first experiment, we examined the recovery rate of mitotic phase cells by a combination of treatment with a metaphase arrestant (1 microM 2-methoxyestradiol), shaking the plate and selecting cells with a diameter of 20 microns. As a result, 99% of mitotic phase cells were recovered by repeating the combined treatment of metaphase arrestant and shaking, and collection of cells with a specific diameter. In the second experiment, nuclear transfer was carried out using early G1 phase cells by choosing pairs of bridged cells derived from mitotic phase cells recovered by the combined treatment of 1 microM 2-methoxyestradiol and shaking, and collection of cells with a diameter of 20 microns. The reconstructed embryos were transferred to recipient heifers to determine post-implantation development. Development of embryos reconstructed from early G1 phase cells from the >/=6 cells stage on Day 3 to the morula-blastocyst stage on Day 6 was 100%. Ten blastocysts constructed from two cell lines were transferred into 10 recipient heifers. Nine of the 10 recipients delivered single live calves. In conclusion, mitotic phase bovine fibroblast cells were easily recovered by the combined treatments of 1 microM 2-methoxyestradiol, shaking, and selecting cells of the appropriate diameter. Furthermore, nuclear transfer using cells in the early G1 phase as donor cells gave a high rate of offspring production.

The Development of Attention and Response Inhibition in Early Childhood

ERIC Educational Resources Information Center

Bartgis, Jami; Thomas, David G.; Lefler, Elizabeth K.; Hartung, Cynthia M.

2008-01-01

The goal of this study was to examine the development of attention and response inhibition from ages 5 to 7. Forty children (20 5-year-olds and 20 7-year-olds) completed four counterbalanced phases of a continuous performance task. Phase 1 was designed to measure attention without distraction, Phase 2 was designed to measure attention with…

Definition of technology development missions for early space stations. Large space structures, phase 2, midterm review

NASA Technical Reports Server (NTRS)

1984-01-01

The large space structures technology development missions to be performed on an early manned space station was studied and defined and the resources needed and the design implications to an early space station to carry out these large space structures technology development missions were determined. Emphasis is being placed on more detail in mission designs and space station resource requirements.

About the Chemopreventive Agent Development Research Group | Division of Cancer Prevention

Cancer.gov

The Chemopreventive Agent Development Research Group promotes and supports research on early chemopreventive agent development, from preclinical studies to phase I clinical trials. The group’s projects aim to identify and develop prevention agents with the potential to block, reverse, or delay the early stages of cancer. The overarching goal is to determine positive and

Extension of quality-by-design concept to the early development phase of pharmaceutical R&D processes.

PubMed

Csóka, Ildikó; Pallagi, Edina; Paál, Tamás L

2018-03-27

Here, we propose the extension of the quality-by-design (QbD) concept to also fit the early development phases of pharmaceuticals by adding elements that are currently widely applied, but not yet included in the QbD model in a structured way. These are the introduction of a 'zero' preformulation phase (i.e., selection of drug substance, possible dosage forms and administration routes based on the evaluated therapeutic need); building in stakeholders' (industry, patient, and regulatory) requirements into the quality target product profile (QTTP); and the use of modern quality management tools during the composition and process design phase [collecting critical quality attributes (CQAs) and selection of CPPs) for (still laboratory-scale) design space (DS) development. Moreover, during industrial scale-up, CQAs (as well as critical process parameters; CPPs) can be changed; however, we recommend that the existing QbD elements are reconsidered and updated after this phase. Copyright © 2018 Elsevier Ltd. All rights reserved.

Nonlinear development of shocklike structure in the solar wind.

PubMed

Lee, E; Parks, G K; Wilber, M; Lin, N

2009-07-17

We report first in situ multispacecraft observations of nonlinear steepening of compressional pulses in the solar wind upstream of Earth's bow shock. The magnetic field of a compressional pulse formed at the upstream edge of density holes is shown to suddenly break and steepen into a shocklike structure. During the early phase of development thermalization of ions is insignificant. Substantial thermalization of ions occurs as gyrating ions are observed at the steepened edge. These observations indicate that the mechanisms causing the dissipation of magnetic fields (currents) and ions are different in the early phase of shock development.

Developing Adaptive Systems at Early Stages of Children's Foreign Language Development

ERIC Educational Resources Information Center

Espada, Ana Belen Cumbreno; Garcia, Mercedes Rico; Fuentes, Alejandro Curado; Gomez, Eva Ma Dominguez

2006-01-01

This paper describes the integration of hypermedia adaptive systems for foreign language learners at an early age. Our research project is concerned with exploring the relationship between language learning and information technology according to six different phases: a preliminary study of the plausible adaptive system; the development of lessons…

Three steps to writing adaptive study protocols in the early phase clinical development of new medicines

PubMed Central

2014-01-01

This article attempts to define terminology and to describe a process for writing adaptive, early phase study protocols which are transparent, self-intuitive and uniform. It provides a step by step guide, giving templates from projects which received regulatory authorisation and were successfully performed in the UK. During adaptive studies evolving data is used to modify the trial design and conduct within the protocol-defined remit. Adaptations within that remit are documented using non-substantial protocol amendments which do not require regulatory or ethical review. This concept is efficient in gathering relevant data in exploratory early phase studies, ethical and time- and cost-effective. PMID:24980283

The influence of gravity on the process of development of animal systems

NASA Technical Reports Server (NTRS)

Malacinski, G. M.; Neff, A. W.

1984-01-01

The development of animal systems is described in terms of a series of overlapping phases: pattern specification; differentiation; growth; and aging. The extent to which altered (micro) gravity (g) affects those phases is briefly reviewed for several animal systems. As a model, amphibian egg/early embryo is described. Recent data derived from clinostat protocols indicates that microgravity simulation alters early pattern specification (dorsal/ventral polarity) but does not adversely influence subsequent morphogenesis. Possible explanations for the absence of catastrophic microgravity effects on amphibian embryogenesis are discussed.

Development of the Sri Lankan Early Teenagers' Violence Inventory: An Instrument to Measure Peer Violence in Schools

PubMed Central

Seneviratne, Rohini; Østbye, Truls; Lynch, Catherine; Sandøy, Ingvild Fossgard

2014-01-01

This study was designed to develop an inventory to measure peer violence among early teens (13–15 years of age) in schools in Sri Lanka. Development of SLETVI was carried out in two phases. In phase I, development of an operational definition for peer violence, identification, and finalizing violent acts for inventory was done by a combination of qualitative methods: a comprehensive literature review, focus group discussions among 13–15-year-old adolescents, their teachers and parents, and consultative meetings with experts in the field. Inventory was then pretested. In phase II, elaboration of SLETVI was carried out by administering it to a sample of 1700 adolescents (13–15 years old). Exploratory factor analysis using principal component analysis was performed separately for experiences of victimization and perpetration. Test-retest reliability of SLETVI was assessed. SLETVI included 37 items in three factors: “less severe violence,” “severe physical,” and “severe relational” violence. Combined use of qualitative and quantitative methods enabled development of a culturally valid and reliable operational inventory to assess early teenagers' peer violence in Sri Lankan and other South Asian schools. PMID:25061607

A psychological approach to providing self-management education for people with type 2 diabetes: the Diabetes Manual

PubMed Central

Sturt, Jackie; Taylor, Hafrun; Docherty, Andrea; Dale, Jeremy; Louise, Taylor

2006-01-01

Background The objectives of this study were twofold (i) to develop the Diabetes Manual, a self-management educational intervention aimed at improving biomedical and psychosocial outcomes (ii) to produce early phase evidence relating to validity and clinical feasibility to inform future research and systematic reviews. Methods Using the UK Medical Research Council's complex intervention framework, the Diabetes Manual and associated self management interventions were developed through pre-clinical, and phase I evaluation phases guided by adult-learning and self-efficacy theories, clinical feasibility and health policy protocols. A qualitative needs assessment and an RCT contributed data to the pre-clinical phase. Phase I incorporated intervention development informed by the pre-clinical phase and a feasibility survey. Results The pre-clinical and phase I studies resulted in the production in the Diabetes Manual programme for trial evaluation as delivered within routine primary care consultations. Conclusion This complex intervention shows early feasibility and face validity for both diabetes health professionals and people with diabetes. Randomised trial will determine effectiveness against clinical and psychological outcomes. Further study of some component parts, delivered in alternative combinations, is recommended. PMID:17129376

A cross-sectional pilot study of the Scottish early development instrument: a tool for addressing inequality

PubMed Central

2013-01-01

Background Early childhood is recognised as a key developmental phase with implications for social, academic, health and wellbeing outcomes in later childhood and indeed throughout the adult lifespan. Community level data on inequalities in early child development are therefore required to establish the impact of government early years’ policies and programmes on children’s strengths and vulnerabilities at local and national level. This would allow local leaders to target tailored interventions according to community needs to improve children’s readiness for the transition to school. The challenge is collecting valid data on sufficient samples of children entering school to derive robust inferences about each local birth cohort’s developmental status. This information needs to be presented in a way that allows community stakeholders to understand the results, expediting the improvement of preschool programming to improve future cohorts’ development in the early years. The aim of the study was to carry out a pilot to test the feasibility and ease of use in Scotland of the 104-item teacher-administered Early Development Instrument, an internationally validated measure of children’s global development at school entry developed in Canada. Methods Phase 1 was piloted in an education district with 14 Primary 1 teachers assessing a cohort of 154 children, following which the instrument was adapted for the Scottish context (Scottish Early Development Instrument: SEDI). Phase 2 was then carried out using the SEDI. Data were analysed from a larger sample of 1090 participants, comprising all Primary 1 children within this school district, evaluated by 68 teachers. Results The SEDI displayed adequate psychometric and discriminatory properties and is appropriate for use across Scotland without any further modifications. Children in the lowest socioeconomic status quintiles were 2–3 times more likely than children in the most affluent quintile to score low in at least one developmental domain. Even in the most affluent quintile though, 17% of children were ‘developmentally vulnerable’, suggesting that those in need cannot be identified by socioeconomic status alone. Conclusions The SEDI offers a feasible means of providing communities with a holistic overview of school readiness for targeting early years’ interventions. PMID:24341526

Development and application of a biorelevant dissolution method using USP apparatus 4 in early phase formulation development.

PubMed

Fang, Jiang B; Robertson, Vivian K; Rawat, Archana; Flick, Tawnya; Tang, Zhe J; Cauchon, Nina S; McElvain, James S

2010-10-04

Dissolution testing is frequently used to determine the rate and extent at which a drug is released from a dosage form, and it plays many important roles throughout drug product development. However, the traditional dissolution approach often emphasizes its application in quality control testing and usually strives to obtain 100% drug release. As a result, dissolution methods are not necessarily biorelevant and meaningful application of traditional dissolution methods in the early phases of drug product development can be very limited. This article will describe the development of a biorelevant in vitro dissolution method using USP apparatus 4, biorelevant media, and real-time online UV analysis. Several case studies in the areas of formulation selection, lot-to-lot variability, and food effect will be presented to demonstrate the application of this method in early phase formulation development. This biorelevant dissolution method using USP apparatus 4 provides a valuable tool to predict certain aspects of the in vivo drug release. It can be used to facilitate the formulation development/selection for pharmacokinetic (PK) and clinical studies. It may also potentially be used to minimize the number of PK studies, and to aid in the design of more efficient PK and clinical studies.

Optimization of Primary Drying in Lyophilization during Early Phase Drug Development using a Definitive Screening Design with Formulation and Process Factors.

PubMed

Goldman, Johnathan M; More, Haresh T; Yee, Olga; Borgeson, Elizabeth; Remy, Brenda; Rowe, Jasmine; Sadineni, Vikram

2018-06-08

Development of optimal drug product lyophilization cycles is typically accomplished via multiple engineering runs to determine appropriate process parameters. These runs require significant time and product investments, which are especially costly during early phase development when the drug product formulation and lyophilization process are often defined simultaneously. Even small changes in the formulation may require a new set of engineering runs to define lyophilization process parameters. In order to overcome these development difficulties, an eight factor definitive screening design (DSD), including both formulation and process parameters, was executed on a fully human monoclonal antibody (mAb) drug product. The DSD enables evaluation of several interdependent factors to define critical parameters that affect primary drying time and product temperature. From these parameters, a lyophilization development model is defined where near optimal process parameters can be derived for many different drug product formulations. This concept is demonstrated on a mAb drug product where statistically predicted cycle responses agree well with those measured experimentally. This design of experiments (DoE) approach for early phase lyophilization cycle development offers a workflow that significantly decreases the development time of clinically and potentially commercially viable lyophilization cycles for a platform formulation that still has variable range of compositions. Copyright © 2018. Published by Elsevier Inc.

Differential Response Pattern of Oropharyngeal Pressure by Bolus and Dry Swallows.

PubMed

Hasegawa, Mana; Kurose, Masayuki; Okamoto, Keiichiro; Yamada, Yoshiaki; Tsujimura, Takanori; Inoue, Makoto; Sato, Taisuke; Narumi, Takatsune; Fujii, Noritaka; Yamamura, Kensuke

2018-02-01

The aim of this study was to determine if bolus and dry swallow showed similar pressure changes in the oropharynx using our newly developed device. A unique character of it includes that baropressure can be measured with the sensor being placed in the balloon and can assess the swallowing mechanics in terms of pressure changes in the oropharynx with less influences of direct contacts of boluses and oropharyngeal structures during swallow indirectly. Fifteen healthy subjects swallowed saliva (dry), 15 ml of water, 45 ml of water, and 15 ml of two different types of food in terms of viscosity (potage soup-type and mayonnaise-type foods). Suprahyoid muscle activity was recorded simultaneously. Three parameters, area under the curve (AUC), peak amplitude, and duration of pressure, were analyzed from each swallow. Almost all of the bolus swallowing events had biphasic baropressure responses consisting of an early phase and late phase (99%), whereas 90% of the saliva swallowing events had a single phase. AUC, peak, and duration displayed greater effects during the late phase than during the early phase. Baropressure of the early phase, but not of the late phase, significantly increased with increasing volume; however, small but significant viscosity effects on pressure were seen during both phases. Peak pressure of the late phase was preceded by maximum muscle activity, whereas that of the early phase was seen when muscle activity displayed a peak response. These findings indicated that our device with the ability to measure baropressure has the potential to provide additional parameter to assess the swallow physiology, and biphasic baropressure responses in the early and late phases could reflect functional aspects of the swallowing reflexes.

Developmental Changes in Sensory-Evoked Optical Intrinsic Signals in the Rat Barrel Cortex.

PubMed

Sintsov, Mikhail; Suchkov, Dmitrii; Khazipov, Rustem; Minlebaev, Marat

2017-01-01

Optical Intrinsic Signal imaging (OISi) is a powerful technique for optical brain studies. OIS mainly reflects the hemodynamic response (HR) and metabolism, but it may also involve changes in tissue light scattering (LS) caused by transient cellular swelling in the active tissue. Here, we explored the developmental features of sensory-evoked OIS in the rat barrel cortex during the first 3 months after birth. Multispectral OISi revealed that two temporally distinct components contribute to the neonatal OIS: an early phase of LS followed by a late phase of HR. The contribution of LS to the early response was also evidenced by an increase in light transmission through the active barrel. The early OIS phase correlated in time and amplitude with the sensory-evoked electrophysiological response. Application of the Modified Beer-Lambert Law (MBLL) to the OIS data revealed that HR during the early phase involved only a slight decrease in blood oxygenation without any change in blood volume. In contrast, HR during the late phase manifested an adult-like increase in blood volume and oxygenation. During development, the peak time of the delayed HR progressively shortened with age, nearly reaching the stimulus onset and overlapping with the early LS phase by the fourth postnatal week. Thus, LS contributes to the sensory-evoked OIS in the barrel cortex of rats at all ages, and it dominates the early OIS phase in neonatal rats due to delayed HR. Our results are also consistent with the delayed blood oxygen level dependent (BOLD) signal in human preterm infants.

Developmental Changes in Sensory-Evoked Optical Intrinsic Signals in the Rat Barrel Cortex

PubMed Central

Sintsov, Mikhail; Suchkov, Dmitrii; Khazipov, Rustem; Minlebaev, Marat

2017-01-01

Optical Intrinsic Signal imaging (OISi) is a powerful technique for optical brain studies. OIS mainly reflects the hemodynamic response (HR) and metabolism, but it may also involve changes in tissue light scattering (LS) caused by transient cellular swelling in the active tissue. Here, we explored the developmental features of sensory-evoked OIS in the rat barrel cortex during the first 3 months after birth. Multispectral OISi revealed that two temporally distinct components contribute to the neonatal OIS: an early phase of LS followed by a late phase of HR. The contribution of LS to the early response was also evidenced by an increase in light transmission through the active barrel. The early OIS phase correlated in time and amplitude with the sensory-evoked electrophysiological response. Application of the Modified Beer-Lambert Law (MBLL) to the OIS data revealed that HR during the early phase involved only a slight decrease in blood oxygenation without any change in blood volume. In contrast, HR during the late phase manifested an adult-like increase in blood volume and oxygenation. During development, the peak time of the delayed HR progressively shortened with age, nearly reaching the stimulus onset and overlapping with the early LS phase by the fourth postnatal week. Thus, LS contributes to the sensory-evoked OIS in the barrel cortex of rats at all ages, and it dominates the early OIS phase in neonatal rats due to delayed HR. Our results are also consistent with the delayed blood oxygen level dependent (BOLD) signal in human preterm infants. PMID:29311827

The Development of Case Studies to Evaluate the Usefulness of Teaching Interactions in One-to-One Teaching of Early Number

ERIC Educational Resources Information Center

Ewing, Bronwyn

2016-01-01

This research paper reports on phase two of an Australian study that examined video-recorded intensive one-to-one teaching interactions with 6-7-year-old students who were in their second year of schooling and identified by the their class teacher as low attaining in early number. The two-phased study from which this paper emerges was originally…

Design Tools for Cost-Effective Implementation of Planetary Protection Requirements

NASA Technical Reports Server (NTRS)

Hamlin, Louise; Belz, Andrea; Evans, Michael; Kastner, Jason; Satter, Celeste; Spry, Andy

2006-01-01

Since the Viking missions to Mars in the 1970s, accounting for the costs associated with planetary protection implementation has not been done systematically during early project formulation phases, leading to unanticipated costs during subsequent implementation phases of flight projects. The simultaneous development of more stringent planetary protection requirements, resulting from new knowledge about the limits of life on Earth, together with current plans to conduct life-detection experiments on a number of different solar system target bodies motivates a systematic approach to integrating planetary protection requirements and mission design. A current development effort at NASA's Jet Propulsion Laboratory is aimed at integrating planetary protection requirements more fully into the early phases of mission architecture formulation and at developing tools to more rigorously predict associated cost and schedule impacts of architecture options chosen to meet planetary protection requirements.

Diverse roles of actin in C. elegans early embryogenesis

PubMed Central

Velarde, Nathalie; Gunsalus, Kristin C; Piano, Fabio

2007-01-01

Background The actin cytoskeleton plays critical roles in early development in Caenorhabditis elegans. To further understand the complex roles of actin in early embryogenesis we use RNAi and in vivo imaging of filamentous actin (F-actin) dynamics. Results Using RNAi, we found processes that are differentially sensitive to levels of actin during early embryogenesis. Mild actin depletion shows defects in cortical ruffling, pseudocleavage, and establishment of polarity, while more severe depletion shows defects in polar body extrusion, cytokinesis, chromosome segregation, and eventually, egg production. These defects indicate that actin is required for proper oocyte development, fertilization, and a wide range of important events during early embryogenesis, including proper chromosome segregation. In vivo visualization of the cortical actin cytoskeleton shows dynamics that parallel but are distinct from the previously described myosin dynamics. Two distinct types of actin organization are observed at the cortex. During asymmetric polarization to the anterior, or the establishment phase (Phase I), actin forms a meshwork of microfilaments and focal accumulations throughout the cortex, while during the anterior maintenance phase (Phase II) it undergoes a morphological transition to asymmetrically localized puncta. The proper asymmetric redistribution is dependent on the PAR proteins, while both asymmetric redistribution and morphological transitions are dependent upon PFN-1 and NMY-2. Just before cytokinesis, actin disappears from most of the cortex and is only found around the presumptive cytokinetic furrow. Finally, we describe dynamic actin-enriched comets in the early embryo. Conclusion During early C. elegans embryogenesis actin plays more roles and its organization is more dynamic than previously described. Morphological transitions of F-actin, from meshwork to puncta, as well as asymmetric redistribution, are regulated by the PAR proteins. Results from this study indicate new insights into the cellular and developmental roles of the actin cytoskeleton. PMID:18157918

Development of the Play Experience Model to Enhance Desirable Qualifications of Early Childhood

ERIC Educational Resources Information Center

Panpum, Watchara; Soonthornrojana, Wimonrat; Nakunsong, Thatsanee

2015-01-01

The objectives of this research were to develop the play experience model and to study the effect of usage in play experience model for enhancing the early childhood's desirable qualification. There were 3 phases of research: 1) the document and context in experience management were studied, 2) the play experience model was developed, and 3) the…

Goals and Strategies for the Human Lunar Reference Architecture

NASA Technical Reports Server (NTRS)

Seaman, Calvin H.

2010-01-01

The presentation examines common goals for human lunar exploration and strategic guidance. Three major sections include illustrative example goals, introduction to the GPoD campaign, and GPoD overview. The first section includes slides about strategic view of partnerships, the moon as a stepping stone and a uniquely preserved record, human-robotic partnership, innovative engagement, strategic considerations, and evaluation of campaigns against common goals. The second section examines campaigns considered, the philosophy of GPoD, GPoD campaign phase definitions, and GPoD design decision points. The third section examines lunar exploration capabilities, extended stay-relocation exploration mode, notional campaign destinations for GPoD, early robotics phase, development of the GPoD early robotics phase, polar exploration/system validation phase, polar relocatability phase, non-polar relocatability phase, long duration phase, and return to evaluation of campaigns.

Molindone and hepatotoxicity.

PubMed

Bhatia, S C; Banta, L E; Ehrlich, D W

1985-10-01

An adolescent male with chronic schizophrenic disorder, paranoid type, was treated with molindone. He developed hepatotoxicity in the early treatment phase as evidenced by flu-like symptoms and laboratory abnormalities of liver functions. These symptoms and his hepatic functions improved on discontinuing molindone. Similar liver function trends were seen on reintroduction and subsequent withdrawal of the drug. Hepatic hypersensitivity has not been reported previously with the use of this drug. It is suggested that clinicians should be aware of this association and should assess hepatic functions in patients who develop a prodromal flu-like syndrome with this drug, especially in the early treatment phase.

Phase III Early Restoration Public Meetings | NOAA Gulf Spill Restoration

Science.gov Websites

Archive Home Phase III Early Restoration Public Meetings Phase III Early Restoration Public Meetings share Posted on December 6, 2013 | Assessment and Early Restoration Restoration Area Title: Phase III Early on the draft plan for the third phase of Early Restoration, which proposes more than $625 million in

Early phase clinical trials with human immunodeficiency virus-1 and malaria vectored vaccines in The Gambia: frontline challenges in study design and implementation.

PubMed

Afolabi, Muhammed O; Adetifa, Jane U; Imoukhuede, Egeruan B; Viebig, Nicola K; Kampmann, Beate; Bojang, Kalifa

2014-05-01

Human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and malaria are among the most important infectious diseases in developing countries. Existing control strategies are unlikely to curtail these diseases in the absence of efficacious vaccines. Testing of HIV and malaria vaccines candidates start with early phase trials that are increasingly being conducted in developing countries where the burden of the diseases is high. Unique challenges, which affect planning and implementation of vaccine trials according to internationally accepted standards have thus been identified. In this review, we highlight specific challenges encountered during two early phase trials of novel HIV-1 and malaria vectored vaccine candidates conducted in The Gambia and how some of these issues were pragmatically addressed. We hope our experience will be useful for key study personnel involved in day-to-day running of similar clinical trials. It may also guide future design and implementation of vaccine trials in resource-constrained settings.

CD101, a Novel Echinocandin, Possesses Potent Antibiofilm Activity against Early and Mature Candida albicans Biofilms.

PubMed

Chandra, Jyotsna; Ghannoum, Mahmoud A

2018-02-01

Currently available echinocandins are generally effective against Candida biofilms, but the recent emergence of resistance has underscored the importance of developing new antifungal agents that are effective against biofilms. CD101 is a long-acting novel echinocandin with distinctive pharmacokinetic properties and improved stability and safety relative to other drugs in the same class. CD101 is currently being evaluated as a once-weekly intravenous (i.v.) infusion for the treatment of candidemia and invasive candidiasis. In this study, we determined (i) the effect of CD101 against early and mature phase biofilms formed by C. albicans in vitro and (ii) the temporal effect of CD101 on the formation of biofilms using time-lapse microscopy (TLM). Early- or mature-phase biofilms were formed on silicone elastomer discs and were exposed to the test compounds for 24 h and quantified by measuring their metabolic activity. Separate batches were observed under a confocal microscope or used to capture TLM images from 0 to 16 h. Measurements of their metabolic activity showed that CD101 (0.25 or 1 μg/ml) significantly prevented adhesion-phase cells from developing into mature biofilms ( P = 0.0062 or 0.0064, respectively) and eradicated preformed mature biofilms ( P = 0.04 or 0.01, respectively) compared to those of untreated controls. Confocal microscopy showed significant reductions in biofilm thicknesses for both early and mature phases ( P < 0.05). TLM showed that CD101 stopped the growth of adhesion- and early-phase biofilms within minutes. CD101-treated hyphae failed to grow into mature biofilms. These results suggest that CD101 may be effective in the prevention and treatment of biofilm-associated nosocomial infections. Copyright © 2018 Chandra and Ghannoum.

Gene expression profiles of Vibrio parahaemolyticus in the early stationary phase.

PubMed

Meng, L; Alter, T; Aho, T; Huehn, S

2015-09-01

Vibrio (V.) parahaemolyticus is an aquatic bacterium capable of causing foodborne gastroenteritis. In the environment or the food chain, V. parahaemolyticus cells are usually forced into the stationary phase, the common phase for bacterial survival in the environment. So far, little is known about whole genomic expression of V. parahaemolyticus in the early stationary phase compared with the exponential growth phase. We performed whole transcriptomic profiling of V. parahaemolyticus cells in both phases (exponential and early stationary phase). Our data showed in total that 172 genes were induced in early stationary phase, while 61 genes were repressed in early stationary phase compared with the exponential phase. Three functional categories showed stable gene expression in the early stationary phase. Eleven functional categories showed that up-regulation of genes was dominant over down-regulation in the early stationary phase. Although genes related to endogenous metabolism were repressed in the early stationary phase, massive regulation of gene expression occurred in the early stationary phase, indicating the expressed gene set of V. parahaemolyticus in the early stationary phase impacts environmental survival. Vibrio (V.) parahaemolyticus is one of the main bacterial causes of foodborne intestinal infections. This bacterium usually is forced into stationary phase in the environment, which includes, e.g. seafood. When bacteria are in stationary phase, physiological changes can lead to a resistance to many stresses, including physical and chemical challenges during food processing. To the best of our knowledge, highlighting the whole genome expression changes in the early stationary phase compared with exponential phase, as well as the investigation of physiological changes of V. parahaemolyticus such as the survival mechanism in the stationary phase has been the very first study in this field. © 2015 The Society for Applied Microbiology.

Insights into intermediate phases of human intestinal fluids visualized by atomic force microscopy and cryo-transmission electron microscopy ex vivo.

PubMed

Müllertz, Anette; Fatouros, Dimitrios G; Smith, James R; Vertzoni, Maria; Reppas, Christos

2012-02-06

The current work aims to study at the ultrastructural level the morphological development of colloidal intermediate phases of human intestinal fluids (HIFs) produced during lipid digestion. HIFs were aspirated near the ligament of Treitz early (30 min), Aspirate(early), and 1 h, Aspirate(1h)(ave,comp), after the administration of a heterogeneous liquid meal into the antrum. The composition of the sample aspirated 1 h after meal administration was similar to the average lumenal composition 1 h after meal administration (Aspirate(1h)(ave,comp)). The colloidal structures of individual aspirates and supernatants of aspirates after ultracentrifugation (micellar phase) were characterized by means of atomic force microscopy (AFM) and cryogenic transmission electron microscopy (Cryo-TEM). AFM revealed domain-like structures in Aspirate(early) and both vesicles and large aggregates Aspirate(1h)(ave,comp). Rough surfaces and domains varying in size were frequently present in the micellar phase of both Aspirate(early) and Aspirate(1h)(ave,comp). Cryo-TEM revealed an abundance of spherical micelles and occasionally presented worm-like micelles coexisting with faceted and less defined vesicles in Aspirate(early) and Aspirate(1h)(ave,comp). In Aspirate(1h)(ave,comp) oil droplets were visualized with bilayers closely located to their surface suggesting lipolytic product phases accumulated on the surface of the oil droplet. In the micellar phase of Aspirate(early), Cryo-TEM revealed the presence of spherical micelles, small vesicles, membrane fragments, oil droplets and plate-like structures. In the micellar phase of Aspirate(1h)(ave,comp) the only difference was the absence of oil droplets. Visualization studies previously performed with biorelevant media revealed structural features with many similarities as presented in the current investigation. The impression of the complexity and diversion of these phases has been reinforced with the excessive variation of structural features visualized ex vivo in the current study offering insights at the ultrastuctural level of intermediate phases which impact drug solubilization.

Socio-Economic Status and Early Childhood Cognitive Skills: A Mediation Analysis Using the Young Lives Panel

ERIC Educational Resources Information Center

Lopez Boo, Florencia

2016-01-01

This article documents differences in cognitive development, as measured by the Peabody Picture Vocabulary Test (PPVT), between children from households with high and low socioeconomic status (SES) in two different phases of early childhood in four developing countries. A large number of potential mediators, such as urban residence, preschool…

Development of decision-making support tools for early right-of-way acquisitions.

DOT National Transportation Integrated Search

2010-01-01

This report documents the work performed during phase two of Project 0-5534, Asset Management Texas : Style. This phase included gathering historical Texas Department of Transportation (TxDOT) right-of-way : acquisition information, analyzi...

Phase III of Early Restoration | NOAA Gulf Spill Restoration

Science.gov Websites

information about this phase of Early Restoration, including fact sheets on each project. The final Phase III 44 projects are documented in a final Record of Decision. Information about Phase III of Early Archive Home Phase III of Early Restoration Phase III of Early Restoration Beach habitat would be restored

The History of the Development of the Rectenna. [solar power satellites

NASA Technical Reports Server (NTRS)

Brown, W. C.

1980-01-01

The history of the development of the rectenna is reviewed through its early conceptual developmental phases. Some selective aspects of the current solar power satellite rectenna development are examined.

The practical application of adaptive study design in early phase clinical trials: a retrospective analysis of time savings.

PubMed

Lorch, U; Berelowitz, K; Ozen, C; Naseem, A; Akuffo, E; Taubel, J

2012-05-01

The interest in adaptive study design is evident from the growing amount of clinical research employing this model in the mid to later stages of medicines development. Little has been published on the practical application and merits of adaptive study design in early phase clinical research. This paper describes a retrospective analysis performed on a sample of 29 industry lead adaptive early phase studies commencing between 1 January 2006 and 31 December 2010 in a clinical trials unit in London, England. All studies containing at least one adaptive feature in the original protocol were included in the analysis. The scope of the analysis was to assess whether the use of adaptive study designs provided tangible benefits over the use of conventional study designs using time savings as the main measure. We conclude that the use of adaptive study design saves time in early phase research programs. This is achieved by abolishing the need for substantial amendments or by mitigating their impact on timelines and by using adaptive scheduling efficiencies.

‘Much clearer with pictures’: using community-based participatory research to design and test a Picture Option Grid for underserved patients with breast cancer

PubMed Central

Durand, Marie-Anne; Alam, Shama; Grande, Stuart W; Elwyn, Glyn

2016-01-01

Objective Women of low socioeconomic status (SES) diagnosed with early stage breast cancer experience decision-making, treatment and outcome disparities. Evidence suggests that decision aids can benefit underserved patients, when tailored to their needs. Our aim was to develop and test the usability, acceptability and accessibility of a pictorial encounter decision aid targeted at women of low SES diagnosed with early stage breast cancer. Design Community-based participatory research (CBPR) using think-aloud protocols (phases 1 and 2) and semistructured interviews (phase 3). Setting Underserved community settings (eg, knitting groups, bingo halls, senior centres) and breast clinics. Participants In phase 1, we recruited a convenience sample of clinicians and academics. In phase 2, we targeted women over 40 years of age, of low SES, regardless of breast cancer history, and in phase 3, women of low SES, recently diagnosed with breast cancer. Intervention The pictorial encounter decision aid was derived from an evidence-based table comparing treatment options for breast cancer (http://www.optiongrid.org). Outcome measures We assessed the usability, acceptability and accessibility of the pictorial decision aid prototypes using the think-aloud protocol and semistructured interviews. Results After initial testing of the first prototype with 18 academics and health professionals, new versions were developed and tested with 53 lay individuals in community settings. Usability was high. In response to feedback indicating that the use of cartoon characters was considered insensitive, a picture-only version was developed and tested with 23 lay people in phase 2, and 10 target users in phase 3. Conclusions and relevance Using CBPR methods and iterative user testing cycles improved usability and accessibility, and led to the development of the Picture Option Grid, entirely guided by multiple stakeholder feedback. All women of low SES recently diagnosed with early stage breast cancer found the Picture Option Grid usable, acceptable and accessible. PMID:26839014

Modular space station phase B extension integrated ground operations

NASA Technical Reports Server (NTRS)

Selegue, D. F.

1971-01-01

Requirements for development test, manufacturing, facilities, GSE, training, logistics support, and launch operations are described. The prime integrating requirement is the early establishment of a common data base and its use throughout the design, development, and operational life of the station. The common data base is defined, and the concept of its use is presented. Development requirements for the station modules and subsystems are outlined along with a master development phasing chart.

NCI–RTOG Translational Program Strategic Guidelines for the Early-Stage Development of Radiosensitizers

PubMed Central

2013-01-01

The addition of chemotherapeutic agents to ionizing radiation has improved survival in many malignancies. Cure rates may be further improved by adding novel targeted agents to current radiotherapy or radiochemotherapy regimens. Despite promising laboratory data, progress in the clinical development of new drugs with radiation has been limited. To define and address the problems involved, a collaborative effort between individuals within the translational research program of the Radiation Oncology Therapy Group and the National Cancer Institute was established. We discerned challenges to drug development with radiation including: 1) the limited relevance of preclinical work, 2) the pharmaceutical industry’s diminished interest, and 3) the important individual skills and institutional commitments required to ensure a successful program. The differences between early-phase trial designs with and without radiation are noted as substantial. The traditional endpoints for early-phase clinical trials—acute toxicity and maximum-tolerated dose—are of limited value when combining targeted agents with radiation. Furthermore, response rate is not a useful surrogate marker of activity in radiation combination trials.Consequently, a risk-stratified model for drug-dose escalation with radiation is proposed, based upon the known and estimated adverse effects. The guidelines discuss new clinical trial designs, such as the time-to-event continual reassessment method design for phase I trials, randomized phase II “screening” trials, and the use of surrogate endpoints, such as pathological response. It is hoped that by providing a clear pathway, this article will accelerate the rate of drug development with radiation. PMID:23231975

Watching, Creating and Achieving: Creative Technologies as a Conduit for Learning in the Early Years

ERIC Educational Resources Information Center

McDonald, Susan; Howell, Jennifer

2012-01-01

This paper describes the use of robotics in an Early Years classroom as a tool to aid the development of technological skills in a creative environment rich with literacy and numeracy opportunities. The pilot project illustrates how a three-phase process can result in the development of: (1) emergent literacy and numeracy, (2) digital access for…

The Influence of Maternal Early to Mid-Gestation Nutrient Restriction of Long Chain Polyunsaturated Fatty Acids in Fetal Sheep

USDA-ARS?s Scientific Manuscript database

The early to mid-gestational period (days 28-78) in sheep is the period of most rapid placental development. Maternal nutrient restriction (MNR) in this phase has negative consequences on fetal growth and development, predisposing the fetus to disease in adult life. The influence of MNR on fetal tis...

Early dialogue between the developers of new technologies and pricing and reimbursement agencies: a pilot study.

PubMed

Backhouse, Martin E; Wonder, Michael; Hornby, Edward; Kilburg, Anne; Drummond, Michael; Mayer, Friedrich Karl

2011-06-01

It is common practice for developers of new health care technologies to engage in early dialogue with the major regulatory agencies; such discussions frequently center around the proposed clinical trial designs to support the registration of new interventions and suggestions on their improvement. Pricing and reimbursement agencies are increasingly using the results from health technology assessments to inform their decision making for new technologies. Such assessments are invariably underpinned by the phase 3 clinical trial evidence which may not provide answers to the key questions. Technology developers are beginning to realize that direct, early dialogue on the evidence requirements of the major pricing and reimbursement agencies, before phase 3 clinical trial designs for their key development compounds have been finalized, may be beneficial. This article reports on the pioneering efforts of one technology developer in seeking early dialogue with seven pricing and reimbursement agencies in five countries globally in 2007-2008 on their likely evidence requirements for a new oral treatment for patients with chronic plaque psoriasis. The pilot project demonstrated that a feasible process of early dialogue could be established, through a face-to-face meeting with prior circulation of a briefing book. Although there was some variation in the advice the similarities far outweighed the differences. More experience of early dialogue needs to be accumulated, involving a wider range of pricing and reimbursement agencies and compounds. The conclusion of this study, however, was that early dialogue can be a worthwhile process for all parties and can lead to a common understanding about evidence development for market access. Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Early stages of styrene-isoprene copolymerization in gas phase clusters probed by resonance enhanced multiphoton ionization.

PubMed

Mahmoud, Hatem; Germanenko, Igor N; El-Shall, M Samy

2006-04-06

We present direct evidence for the formation of the covalent bonded styrene (isoprene)(2) oligomer and the isoprene dimer ions following resonance ionization of the gas phase styrene-isoprene binary clusters. The application of resonance ionization to study polymerization reactions in clusters provides new information on the structure and mechanism of formation of the early stages of polymerization and holds considerable promise for the discovery of new initiation mechanisms and for the development of novel materials with unique properties.

SAD phasing: History, current impact and future opportunities.

PubMed

Rose, John P; Wang, Bi-Cheng

2016-07-15

Single wavelength anomalous diffraction (SAD) can trace its beginnings to the early 1950s. Researchers at the time recognized that SAD offers some unique features that might be advantageous for crystallographic phasing, despite the fact that at that time recording accurate SAD data was problematic. In this review we will follow the trail from those early days, highlighting key advances in the field and interpreting them in terms on how they stimulated continued phasing development that produced the theoretical foundation for the routine macromolecular structure determination by SAD today. The technological advances over the past three decades in both hardware and software, which played a significant role in making SAD phasing a 'first choice method', will also be described. Copyright © 2016 Elsevier Inc. All rights reserved.

Cell wall structures leading to cultivar differences in softening rates develop early during apple (Malus x domestica) fruit growth.

PubMed

Ng, Jovyn K T; Schröder, Roswitha; Sutherland, Paul W; Hallett, Ian C; Hall, Miriam I; Prakash, Roneel; Smith, Bronwen G; Melton, Laurence D; Johnston, Jason W

2013-11-19

There is a paucity of information regarding development of fruit tissue microstructure and changes in the cell walls during fruit growth, and how these developmental processes differ between cultivars with contrasting softening behaviour. In this study we compare two apple cultivars that show different softening rates during fruit development and ripening. We investigate whether these different softening behaviours manifest themselves late during ethylene-induced softening in the ripening phase, or early during fruit expansion and maturation. 'Scifresh' (slow softening) and 'Royal Gala' (rapid softening) apples show differences in cortical microstructure and cell adhesion as early as the cell expansion phase. 'Scifresh' apples showed reduced loss of firmness and greater dry matter accumulation compared with 'Royal Gala' during early fruit development, suggesting differences in resource allocation that influence tissue structural properties. Tricellular junctions in 'Scifresh' were rich in highly-esterified pectin, contributing to stronger cell adhesion and an increased resistance to the development of large airspaces during cell expansion. Consequently, mature fruit of 'Scifresh' showed larger, more angular shaped cells than 'Royal Gala', with less airspaces and denser tissue. Stronger cell adhesion in ripe 'Scifresh' resulted in tissue fracture by cell rupture rather than by cell-to-cell-separation as seen in 'Royal Gala'. CDTA-soluble pectin differed in both cultivars during development, implicating its involvement in cell adhesion. Low pectin methylesterase activity during early stages of fruit development coupled with the lack of immuno-detectable PG was associated with increased cell adhesion in 'Scifresh'. Our results indicate that cell wall structures leading to differences in softening rates of apple fruit develop early during fruit growth and well before the induction of the ripening process.

Cell wall structures leading to cultivar differences in softening rates develop early during apple (Malus x domestica) fruit growth

PubMed Central

2013-01-01

Background There is a paucity of information regarding development of fruit tissue microstructure and changes in the cell walls during fruit growth, and how these developmental processes differ between cultivars with contrasting softening behaviour. In this study we compare two apple cultivars that show different softening rates during fruit development and ripening. We investigate whether these different softening behaviours manifest themselves late during ethylene-induced softening in the ripening phase, or early during fruit expansion and maturation. Results ‘Scifresh’ (slow softening) and ‘Royal Gala’ (rapid softening) apples show differences in cortical microstructure and cell adhesion as early as the cell expansion phase. ‘Scifresh’ apples showed reduced loss of firmness and greater dry matter accumulation compared with ‘Royal Gala’ during early fruit development, suggesting differences in resource allocation that influence tissue structural properties. Tricellular junctions in ‘Scifresh’ were rich in highly-esterified pectin, contributing to stronger cell adhesion and an increased resistance to the development of large airspaces during cell expansion. Consequently, mature fruit of ‘Scifresh’ showed larger, more angular shaped cells than ‘Royal Gala’, with less airspaces and denser tissue. Stronger cell adhesion in ripe ‘Scifresh’ resulted in tissue fracture by cell rupture rather than by cell-to-cell-separation as seen in ‘Royal Gala’. CDTA-soluble pectin differed in both cultivars during development, implicating its involvement in cell adhesion. Low pectin methylesterase activity during early stages of fruit development coupled with the lack of immuno-detectable PG was associated with increased cell adhesion in ‘Scifresh’. Conclusions Our results indicate that cell wall structures leading to differences in softening rates of apple fruit develop early during fruit growth and well before the induction of the ripening process. PMID:24252512

The Kuznets process in Malaysia.

PubMed

Randolph, S

1990-10-01

This study looks at how the Kuznets process, the structural determinants of the aggregate inequality trend during the course of economic development, is transpiring in Malaysia. A time-series test of Kuznets's hypothesis concerning the trend in participation income in the course of economic growth and its underlying structural components is conducted using data from the Malaysian Family Life Survey. The study covers the period 1968-76 during which the equalizing phase of growth was expected to take hold. Analysis determined that while many of the underlying processes which Kuznets speculated combined to generate the aggregate trend in participation income are at work in Malaysia, others are either absent or their phasing has been altered. The equalizing phase in the course of development has been delayed in arriving. Inequality in the nonagricultural sector exceeded that in the agricultural sector, and the wage gap which opened during the early phase of development declined with further development. These findings conform with Kuznets's expectations. Available time-series evidence from other currently developing countries suggests that inequality is typically higher in the nonagricultural sector during the early phase of development and that an increasing and subsequently decreasing between-sector wage gap is a broadly shared experience. This study's findings also support Kuznets's expectation that inequality within the agricultural sector can worsen in the face of dualistic agricultural development. Finally, Malaysia's trend in inequality within the nonagricultural sector exerted the greatest influence upon the aggregate trend in inequality per Kuznets's hypothesis.

White matter changes in early phase schizophrenia and cannabis use: an update and systematic review of diffusion tensor imaging studies.

PubMed

Cookey, Jacob; Bernier, Denise; Tibbo, Philip G

2014-07-01

The impact of cannabis use on the brain tissue is still unclear, both in the healthy developing brain and in people with schizophrenia. The focus of this review is on white matter, the primary connective infrastructure of the brain. We systematically reviewed diffusion tensor imaging (DTI) studies of early phase schizophrenia (illness effect), of cannabis use in otherwise healthy brains (drug effect), and of early phase schizophrenia with cannabis use (combined effects). Studies had to include a healthy, non-cannabis using, control group as well as report on fractional anisotropy as it is the most commonly used DTI index. We excluded cohorts with heavy alcohol or illicit drug use and studies with a sample size of less than 20 in the clinical group. We retained 17 studies of early phase schizophrenia, which together indicate deficits in white matter integrity observed in all fiber tract families, but most frequently in association, callosal and projection fibers. In otherwise healthy cannabis users (2 studies), deficits in white matter tracts were reported mainly in callosal fibers, but also in projection and limbic fibers. In cannabis users with early phase schizophrenia (1 study), deficits in white matter integrity were also observed in all fiber tract families, except for limbic fibers. The current literature points to several families of white matter tracts being differentially affected in early phase schizophrenia. Further work is required to reveal the impact of cannabis use in otherwise healthy people as well as those with schizophrenia. Paucity of available studies as well as restricting analysis to FA values represent the main limitations of this review. Copyright © 2014 Elsevier B.V. All rights reserved.

Advanced Stirling Convertor Update

NASA Astrophysics Data System (ADS)

Wood, J. Gary; Carroll, Cliff; Matejczyk, Dan; Penswick, L. B.; Soendker, E.

2006-01-01

This paper reports on the 88 We Advanced Stirling Convertor (ASC) currently being developed under Phase II of a NASA NRA program for possible use in advanced high specific power radioisotope space power systems. An early developmental unit, the Frequency Test Bed (FTB) which was built and tested in Phase I demonstrated 36% efficiency. The ASC-1 currently being developed under Phase II, uses a high temperature heater head to allow for operation at 850 °C and is expected to have an efficiency approaching 40% (based on AC electrical out) at a temperature ratio of 3.1. The final lightweight ASC-2 convertor to be developed in Phase III is expected to have a mass of approximately 1 kg. The implementation of the ASC would allow for much higher specific power radioisotope power systems, requiring significantly less radioisotope fuel than current systems. The first run of the ASC-1 occurred in September 2005, and full temperature operation was achieved in early October 2005. Presented is an update on progress on the ASC program as well as the plans for future development. Also presented are efforts being performed to ensure the ASC has the required long life already demonstrated in free-piston Stirling cryocoolers.

Low temperatures are required to induce the development of fertile flowers in transgenic male and female early flowering poplar (Populus tremula L.)

PubMed Central

Hoenicka, Hans; Lehnhardt, Denise; Briones, Valentina; Nilsson, Ove; Fladung, Matthias

2016-01-01

Until now, artificial early flowering poplar systems have mostly led to the development of sterile flowers. In this study, several strategies aimed at inducting fertile flowers in pHSP::AtFT transgenic poplar were evaluated, in particular the influence of temperature and photoperiod. Our results provide evidence that temperature, and not photoperiod, is the key factor required for the development of fertile flowers in early flowering poplar. Fertile flowers were only obtained when a cold treatment phase of several weeks was used after the heat treatment phase. Heat treatments induced AtFT gene activity through activation of the heat-shock promoter (pHSP). Photoperiod did not show a similar influence on flower fertility as pollen grains were obtained under both long- and short-day conditions. Fertility was confirmed in flowers of both male and female plants. For the first time, crosses were successfully performed with transgenic female early flowering poplar. All mature flowers obtained after 8 weeks of inductive treatments were fertile. Gene expression studies also confirmed that cold temperatures influenced expression of poplar genes homologous to ‘pollen development genes’ from Arabidopsis thaliana (L.) Heynh. Homology and expression patterns suggested a role for PtTDF1, PtBAM1, PtSERK1/2 and PtMS1 on anther and pollen development in poplar flowers. The system developed in this study allows a fast and very reliable induction of fertile poplar flowers in a very short period of time. The non-reproductive phase, usually 7–10 years, can now be shortened to 6–10 months, and fertile flowers can be obtained independently of the season. This system is a reliable tool for breeding purposes (high-speed breeding technology), genomics and biosafety research. PMID:27052434

Phase V of Early Restoration | NOAA Gulf Spill Restoration

Science.gov Websites

Phase V Early Restoration Plan and Environmental Assessment. The project will acquire land along Florida million. Phase V Early Restoration Plan and Environmental Assessment (pdf, 10 MB) Draft Phase V Early Restoration Plan and Environmental Assessment (Executive Summary) (2 MB) Phase V Fact Sheet (pdf, 2 MB) Gulf

Assessing Risk/Benefit for Trials Using Preclinical Evidence: A Proposal

PubMed Central

Kimmelman, Jonathan; Henderson, Valerie C.

2015-01-01

Abstract Moral evaluation of risk/benefit in early phase studies requires assessing the clinical promise of a candidate intervention using preclinical evidence. Yet there is little to guide ethics committees, investigators, sponsors or other stakeholders morally charged with making these assessments (“evaluators”). In what follows, we draw on published guidelines for preclinical study design to develop a structured process for assessing the clinical promise of new interventions. In the first step, evaluators gather all relevant preclinical studies, assess the magnitude of treatment effects, and determine clinical promise in light of various threats to valid clinical inference. In the second step, evaluators adjust assessments of clinical promise from preclinical studies by examining how other agents in the same reference class-and supported by similar evidence- have fared in clinical development. Assessments of clinical promise can then be fed into moral evaluation of risk and benefit in early phase trials. Though our approach has limitations, it offers a systematic and transparent method for assessing risk/benefit in early phase trials of novel interventions. PMID:26463620

Child neurology: Past, present, and future: part 1: history.

PubMed

Millichap, John J; Millichap, J Gordon

2009-08-18

The founding period of child neurology occurred in 3 phases: 1) early individual contributory phase, 2) organized training phase, and 3) expansion phase. In the late 19th and early 20th centuries, individuals in pediatrics, neurology, and psychiatry established clinics and made important contributions to the literature on childhood epilepsy, cerebral palsy, and pediatric neurology. The latter half of the 20th century saw the organization of training programs in pediatric neurology, with fellowships supported by the NIH. This development was followed by a rapid expansion in the number of trainees certified in child neurology and their appointment to divisions of neurology in children's hospitals. In recent years, referrals of children with neurologic disorders have increased, and disorders previously managed by pediatricians are often seen in neurology clinics. The era of subspecialization is embraced by the practicing physician. The present day status of pediatric neurology and suggestions for the future development of the specialty are subjects for further discussion.

Phytochrome-mediated germination and early development in spores of Dryopteris filix-mas L.: phase-specific and non phase-specific inhibition by staurosporine

NASA Technical Reports Server (NTRS)

Haas, C. J.; Scheuerlein, R.; Roux, S. J.

1991-01-01

The alkaloid staurosporine, currently known as the most potent inhibitor of protein kinase C, PKC, was tested for its ability to inhibit phytochrome-mediated spore germination in Dryopteris filix-mas L., evaluated by the induction of chlorophyll synthesis. Approximately half-maximal inhibition was obtained at a concentration of 10(-5) M. This effect of staurosporine was phase-specific and was found during the same period in which the presence of extracellular calcium is necessary for realization of the light signal. Furthermore, the ability of staurosporine to prevent progression of a germinated spore into early gametophyte development, evaluated by the accumulation of chlorophyll, was examined. Again, staurosporine (10(-5) M) significantly diminished chlorophyll accumulation, determined quantitatively in vivo by single-cell measurements, in a non-phase specific way. The fact that the phase-specific inhibitory effect of staurosporine in preventing germination was coincident with the phase-specific requirement of Ca2+ suggests that both Ca2+ and staurosporine affect the same step in the signal-transduction chain. A phosphorylation event catalysed by PKC or any Ca2+ -dependent protein kinase is proposed as the target of staurosporine and Ca2+.

A Science Data System Approach for the SMAP Mission

NASA Technical Reports Server (NTRS)

Woollard, David; Kwoun, Oh-ig; Bicknell, Tom; West, Richard; Leung, Kon

2009-01-01

Though Science Data System (SDS) development has not traditionally been part of the mission concept phase, lessons learned and study of past Earth science missions indicate that SDS functionality can greatly benefit algorithm developers in all mission phases. We have proposed a SDS approach for the SMAP Mission that incorporates early support for an algorithm testbed, allowing scientists to develop codes and seamlessly integrate them into the operational SDS. This approach will greatly reduce both the costs and risks involved in algorithm transitioning and SDS development.

Space Station - An integrated approach to operational logistics support

NASA Technical Reports Server (NTRS)

Hosmer, G. J.

1986-01-01

Development of an efficient and cost effective operational logistics system for the Space Station will require logistics planning early in the program's design and development phase. This paper will focus on Integrated Logistics Support (ILS) Program techniques and their application to the Space Station program design, production and deployment phases to assure the development of an effective and cost efficient operational logistics system. The paper will provide the methodology and time-phased programmatic steps required to establish a Space Station ILS Program that will provide an operational logistics system based on planned Space Station program logistics support.

What Are the Types and Phases of Rett Syndrome?

MedlinePlus

... Snapshot of Pregnancy & Infant Development Advances Snapshot of Child Development Advances Snapshot of Adult & Family Health Advances NICHD ... fact, these infants show problems with very early development. In one study, ... . The child loses skills (regresses) quickly. Purposeful hand movements and ...

Label-free proteome profiling reveals developmental-dependent patterns in young barley grains.

PubMed

Kaspar-Schoenefeld, Stephanie; Merx, Kathleen; Jozefowicz, Anna Maria; Hartmann, Anja; Seiffert, Udo; Weschke, Winfriede; Matros, Andrea; Mock, Hans-Peter

2016-06-30

Due to its importance as a cereal crop worldwide, high interest in the determination of factors influencing barley grain quality exists. This study focusses on the elucidation of protein networks affecting early grain developmental processes. NanoLC-based separation coupled to label-free MS detection was applied to gain insights into biochemical processes during five different grain developmental phases (pre-storage until storage phase, 3days to 16days after flowering). Multivariate statistics revealed two distinct developmental patterns during the analysed grain developmental phases: proteins showed either highest abundance in the middle phase of development - in the transition phase - or at later developmental stages - within the storage phase. Verification of developmental patterns observed by proteomic analysis was done by applying hypothesis-driven approaches, namely Western Blot analysis and enzyme assays. High general metabolic activity of the grain with regard to protein synthesis, cell cycle regulation, defence against oxidative stress, and energy production via photosynthesis was observed in the transition phase. Proteins upregulated in the storage phase are related towards storage protein accumulation, and interestingly to the defence of storage reserves against pathogens. A mixed regulatory pattern for most enzymes detected in our study points to regulatory mechanisms at the level of protein isoforms. In-depth understanding of early grain developmental processes of cereal caryopses is of high importance as they influence final grain weight and quality. Our knowledge about these processes is still limited, especially on proteome level. To identify key mechanisms in early barley grain development, a label-free data-independent proteomics acquisition approach has been applied. Our data clearly show, that proteins either exhibit highest expression during cellularization and the switch to the storage phase (transition phase, 5-7 DAF), or during storage product accumulation (10-16 DAF). The results highlight versatile cellular metabolic activity in the transition phase and strong convergence towards storage product accumulation in the storage phase. Notably, both phases are characterized by particular protective mechanism, such as scavenging of oxidative stress and defence against pathogens, during the transition and the storage phase, respectively. Copyright © 2016 Elsevier B.V. All rights reserved.

The Impact of Early Design Phase Risk Identification Biases on Space System Project Performance

NASA Technical Reports Server (NTRS)

Reeves, John D., Jr.; Eveleigh, Tim; Holzer, Thomas; Sarkani, Shahryar

2012-01-01

Risk identification during the early design phases of complex systems is commonly implemented but often fails to result in the identification of events and circumstances that truly challenge project performance. Inefficiencies in cost and schedule estimation are usually held accountable for cost and schedule overruns, but the true root cause is often the realization of programmatic risks. A deeper understanding of frequent risk identification trends and biases pervasive during space system design and development is needed, for it would lead to improved execution of existing identification processes and methods.

Early Program Development

NASA Image and Video Library

1969-01-01

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

Maturational effect on Functional Movement Screen™ score in adolescent soccer players.

PubMed

Portas, Matthew David; Parkin, Guy; Roberts, James; Batterham, Alan Mark

2016-10-01

The effect of maturity on Functional Movement Screen (FMS) scores in elite, adolescent soccer players was examined. A cross-sectional observational study was completed. Participants were 1163 male English Football League soccer players (age 8-18 years). Players were mid-foundation phase (MF) (U9); late foundation phase (LF) (U10 and U11); early youth development phase (EYD) (U12 and U13); mid-youth development (MYD) phase (U14-U15); Late Youth Development Phase (LYD) (U16) and early professional development phase (EPD) (U18). Age from peak height velocity was estimated and players were categorized as pre- or post-peak height velocity (PHV). To analyse where differences in FMStotal score existed we separated the screen into FMSmove (3 movement tests); FMSflex (2 mobility tests) and FMSstab (2 stability tests). FMStotal median score ranged from 11 at MF to 14 for EPD. There was a substantial increase (10%) in those able to achieve a score of ≥14 on FMStotal in those who were post-PHV compared to pre-PHV. This was explained by a substantial increase in those achieving a score of ≥4 on FMSstab (21%). There was a substantial increase in the proportion of players who achieved the FMStotal threshold of ≥14 with an increase of 47.5 (41.4-53.6)% from the MF phase to the EPD phase due to improvements in FMSmove and FMSstab. PHV and maturity have substantial effects on FMS performance. FMS assessment appears to be invalid for very young players. Findings are relevant to those analyzing movement in soccer players. Copyright © 2015 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Phase IV of Early Restoration | NOAA Gulf Spill Restoration

Science.gov Websites

Trustees published the Final Phase IV Early Restoration Plan and Environmental Assessments. The plan habitats. Useful Links: Final Phase IV Early Restoration Plan and Environmental Assessments (pdf, 4.8 MB ) Final Phase IV Early Restoration Plan and Environmental Assessments Executive Summary (pdf, 729 KB

Early Restoration | NOAA Gulf Spill Restoration

Science.gov Websites

Early Restoration Plan. On April 20, 2011 we reached an agreement with BP to start restoration planning draft plan for the third phase of early restoration in December 2013. We are considering your comments : All Phase III information and documents Phase II Useful Links: Phase II Early Restoration Plan &

Developing an inventor support service which performs early stage market and manufacturing evaluations. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1991-10-01

American businesses are learning the difficult high cost lesson of ignoring production and market factors (producibility, unit product cost (UPC), marketability, etc) during the engineering design phase of product development. Studies have shown that the Japanese spend three times as long as Americans in the design feasibility and decision process of new product introductions and one third the amount of time in the implementation of those products. There is a 20 to 1 cost benefit on effort applied in the design phase versus the production phase of the product life cycle. The number one goal of this project was tomore » establish an organization that has, as one of its purposes, the providing of services responsive to the needs of independent inventors. The number two goal was to demonstrate the value of providing marketing and manufacturing counsel at an early stage in the product development process. The first study goal was met by providing the materials and information necessary to establish an evaluation team and an organization to handle such evaluations. The second study goal was met by demonstrating the impact of early market analysis and manufacturing considerations on product design and therefore on the description of the invention for four different inventions. These inventions were selected at various stages of development. Regardless of stage of development, the marketing and manufacturing reviews resulted in significant changes in design and/or market positioning.« less

Developing an inventor support service which performs early stage market and manufacturing evaluations. [Final Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1991-10-01

American businesses are learning the difficult high cost lesson of ignoring production and market factors (producibility, unit product cost (UPC), marketability, etc) during the engineering design phase of product development. Studies have shown that the Japanese spend three times as long as Americans in the design feasibility and decision process of new product introductions and one third the amount of time in the implementation of those products. There is a 20 to 1 cost benefit on effort applied in the design phase versus the production phase of the product life cycle. The number one goal of this project was tomore » establish an organization that has, as one of its purposes, the providing of services responsive to the needs of independent inventors. The number two goal was to demonstrate the value of providing marketing and manufacturing counsel at an early stage in the product development process. The first study goal was met by providing the materials and information necessary to establish an evaluation team and an organization to handle such evaluations. The second study goal was met by demonstrating the impact of early market analysis and manufacturing considerations on product design and therefore on the description of the invention for four different inventions. These inventions were selected at various stages of development. Regardless of stage of development, the marketing and manufacturing reviews resulted in significant changes in design and/or market positioning.« less

Early Origins of Child Obesity: Bridging Disciplines and Phases of Development - September 30–October 1, 2010

PubMed Central

Christoffel, Katherine Kaufer; Wang, Xiaobin; Binns, Helen J.

2012-01-01

This report summarizes a conference: “Early Origins of Child Obesity: Bridging Disciplines and Phases of Development”, held in Chicago on September 30–October 1, 2010. The conference was funded in part by the National Institutes of Health and the Williams Heart Foundation, to achieve the conference objective: forging a next-step research agenda related to the early origins of childhood obesity. This research agenda was to include working with an array of factors (from genetic determinants to societal ones) along a continuum from prenatal life to age 7, with an emphasis on how the developing child deals with the challenges presented by his/her environment (prenatal, parental, nutritional, etc.). The conference offered a unique opportunity to facilitate communication and planning of future work among a variety of researchers whose work separately addresses different periods in early life. Over the span of two days, speakers addressed existing, critical research topics within each of the most-studied age ranges. On the final day, workshops fostered the discussion needed to identify the highest priority research topics related to linking varied early factor domains. These are presented for use in planning future research and research funding. PMID:23443002

A Framework for Performing V&V within Reuse-Based Software Engineering

NASA Technical Reports Server (NTRS)

Addy, Edward A.

1996-01-01

Verification and validation (V&V) is performed during application development for many systems, especially safety-critical and mission-critical systems. The V&V process is intended to discover errors, especially errors related to critical processing, as early as possible during the development process. Early discovery is important in order to minimize the cost and other impacts of correcting these errors. In order to provide early detection of errors, V&V is conducted in parallel with system development, often beginning with the concept phase. In reuse-based software engineering, however, decisions on the requirements, design and even implementation of domain assets can be made prior to beginning development of a specific system. In this case, V&V must be performed during domain engineering in order to have an impact on system development. This paper describes a framework for performing V&V within architecture-centric, reuse-based software engineering. This framework includes the activities of traditional application-level V&V, and extends these activities into domain engineering and into the transition between domain engineering and application engineering. The framework includes descriptions of the types of activities to be performed during each of the life-cycle phases, and provides motivation for the activities.

Antitopoisomerase antibody positivity predates nailfold capillaroscopy abnormalities in scleroderma. Postulated classification of 'prescleroderma'.

PubMed

Englert, H; Champion, D; Wu, J C; Giallussi, J; McGrath, M; Manolios, N

2011-02-01

In a patient with early topoisomerase antibody-positive scleroderma, antinuclear antibody positivity was fortuitously observed to predate nailfold capillaroscopy changes. Using this case as a template, the prediagnostic phase of the presumed multifactorial disease may be divided into 5 temporal phases--phase 1 representing conception and intrauterine environment, phase 2 representing the extrauterine environment predating environmental exposure; phase 3 representing the early post-environmental exposure interval with no detectable perturbed body status; phase 4 representing the post-environmental exposure interval characterized by autoantibody production and microvascular changes, and phase 5, the symptomatic clinical prediagnostic interval (Raynaud's, skin, musculoskeletal, gastrointestinal, cardiorespiratory) prompting scleroderma diagnosis. Temporal classification of prescleroderma aids in both the understanding and definition of scleroderma 'onset'. If altered nailfold capillaries and autoantibodies develop at comparable rates, and if the findings from this case--that autoantibody changes precede microvascular changes--are truly representative of the preclinical disease phase, then these findings argue that the evolution of the disease is from within the vessel outwards, rather than vice versa. © 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.

Accumulation of unsaturated lipids in monocytes during early phase pyrogen tolerance.

PubMed

Szewczenko-Pawlikowski, M; Kozak, W

2000-04-12

This paper presents data that inspired a new explanation for the mechanism of early phase endotoxin tolerance. Rabbits injected intravenously with LPS from Salmonella abortus developed a two-phase fever (6 h) and monophasic hyperlipidemia of very low density lipoproteins (two consecutive days). If during these days rabbits were injected with the same dose of LPS at 24-h intervals, the second phase of fever disappeared, i.e. early phase pyrogenic tolerance was obtained. This was correlated with a decrease of lipoprotein hyperlipidemia (measured 1.5 h after LPS injection) and an accumulation of lipids rich in double bonds in monocytes (measured 3.5 h after LPS injection). Results showed that the degree of unsaturation of acyl chains (AC) in monocytes (AC/DB, DB=double bonds) is negatively correlated (r=-0.72) with fever response (fever index). The authors maintain that a gradual increase in monocyte membrane fluidity is an adaptation to repeated exposure of monocytes to lipid A and is responsible for the progressive desensitization of monocytes to endotoxin. It is suggested that disorders of this mechanism lead to an accumulation of abnormal quantities of saturated lipids and cholesterol within macrophages, which, as foam cells, are the starting point for atherosclerosis pathology.

Cathodoluminescence investigations on quartz cement in the sandstones of Khabour Formation from Iraqi Kurdistan Region, Northern Iraq

NASA Astrophysics Data System (ADS)

Omer, Muhamed F.; Friis, Henrik

2014-03-01

The Ordovician deltaic to shallow marine Khabour Formation in Northern Iraq consists mainly of sandstone with minor siltstone and interbedded shale. The sandstones are pervasively cemented by quartz that resulted in very little preserved primary porosity. Cathodoluminescence and petrographic studies showed that the silica cementation occurred in five successive phases which can be distinguished by their luminescence pattern. The precipitations of two phases have predated the major compaction process while the other phases are younger. The successive phases represent a sequence of changes in silica supply which were classified as very early and early, derived from dissolved biogenic silica that precipitated as opal/microquartz, possibly pre-compactional and of non-luminescent quartz overgrowth type. This was followed by phases whose silica supply derived from pressure solution of quartz, dissolution of feldspar, and hydrothermal fluids related to major thrust fault event. These successive quartz cement phases showed an increase in luminescence and the development of complicated zonation pattern in late-stage quartz cementation.

Biomarkers for Cystic Fibrosis Drug Development

PubMed Central

Muhlebach, Marianne S.; Clancy, JP; Heltshe, Sonya L.; Ziady, Assem; Kelley, Tom; Accurso, Frank; Pilewski, Joseph; Mayer-Hamblett, Nicole; Joseloff, Elizabeth; Sagel, Scott D.

2016-01-01

Purpose To provide a review of the status of biomarkers in cystic fibrosis drug development, including regulatory definitions and considerations, a summary of biomarkers in current use with supportive data, current gaps, and future needs. Methods Biomarkers are considered across several areas of CF drug development, including cystic fibrosis transmembrane conductance regulator modulation, infection, and inflammation. Results Sweat chloride, nasal potential difference, and intestinal current measurements have been standardized and examined in the context of multicenter trials to quantify CFTR function. Detection and quantification of pathogenic bacteria in CF respiratory cultures (e.g.: Pseudomonas aeruginosa) is commonly used in early phase antimicrobial clinical trials, and to monitor safety of therapeutic interventions. Sputum (e.g.: neutrophil elastase, myeloperoxidase, calprotectin) and blood biomarkers (e.g.: C reactive protein, calprotectin, serum amyloid A) have had variable success in detecting response to inflammatory treatments. Conclusions Biomarkers are used throughout the drug development process in CF, and many have been used in early phase clinical trials to provide proof of concept, detect drug bioactivity, and inform dosing for later-phase studies. Advances in the precision of current biomarkers, and the identification of new biomarkers with ‘omics-based technologies, are needed to accelerate CF drug development. PMID:28215711

Operational Features of the Kamehameha Early Education Project. Technical Report #4.

ERIC Educational Resources Information Center

Gallimore, Ronald; And Others

This report summarizes the operational features of the initial phases of the Kamehameha Early Education Project (KEEP). The rationale for KEEP's focus on conducting research on programs similar to those in the public schools rather than on developing radically innovative educational programs is discussed. Start up procedures such as recruitment of…

Early Childhood Program: Summary of Context Analysis Phase.

ERIC Educational Resources Information Center

Southwest Educational Development Lab., Austin, TX.

Progress made in the field of early childhood development during the past decade is examined to provide the background and rationale for tree programs funded by the National Institute of Education (NIE) in 1974: a parenting information center, a multimedia child care training package, and television spots related to child rearing principles. The…

Towards Risk Based Design for NASA's Missions

NASA Technical Reports Server (NTRS)

Tumer, Irem Y.; Barrientos, Francesca; Meshkat, Leila

2004-01-01

This paper describes the concept of Risk Based Design in the context of NASA s low volume, high cost missions. The concept of accounting for risk in the design lifecycle has been discussed and proposed under several research topics, including reliability, risk analysis, optimization, uncertainty, decision-based design, and robust design. This work aims to identify and develop methods to enable and automate a means to characterize and optimize risk, and use risk as a tradeable resource to make robust and reliable decisions, in the context of the uncertain and ambiguous stage of early conceptual design. This paper first presents a survey of the related topics explored in the design research community as they relate to risk based design. Then, a summary of the topics from the NASA-led Risk Colloquium is presented, followed by current efforts within NASA to account for risk in early design. Finally, a list of "risk elements", identified for early-phase conceptual design at NASA, is presented. The purpose is to lay the foundation and develop a roadmap for future work and collaborations for research to eliminate and mitigate these risk elements in early phase design.

The Great East Japan Earthquake: a need to plan for post-disaster surveillance in developed countries

PubMed Central

Matsui, Tamano; Partridge, Jeffrey; Kasai, Takeshi

2011-01-01

After a devastating earthquake and tsunami struck north-eastern Japan in March 2011, the public health system, including the infectious disease surveillance system, was severely compromised. While models for post-disaster surveillance exist, they focus predominantly on developing countries during the early recovery phase. Such models do not necessarily apply to developed countries, which differ considerably in their baseline surveillance systems. Furthermore, there is a need to consider the process by which a surveillance system recovers post-disaster. The event in Japan has highlighted a need to address these concerns surrounding post-disaster surveillance in developed countries. In May 2011, the World Health Organization convened a meeting where post-disaster surveillance was discussed by experts and public health practitioners. In this paper, we describe a post-disaster surveillance approach that was discussed at the meeting, based on what had actually occurred and what may have been, or would be, ideal. Briefly, we describe the evolution of a surveillance system as it returns to the pre-existing system, starting from an event-based approach during the emergency relief phase, a syndromic approach during the early recovery phase, an enhanced sentinel approach during the late recovery phase and a return to baseline during the development phase. Our aim is not to recommend a specific model but to encourage other developed countries to initiate their own discussions on post-disaster surveillance and develop plans according to their needs and capacities. As natural disasters will continue to occur, we hope that developing such plans during the “inter-disaster” period will help mitigate the surveillance challenges that will arise post-disaster. PMID:23908893

EARLY ENTRANCE COPRODUCTION PLANT

DOE Office of Scientific and Technical Information (OSTI.GOV)

David Storm; Govanon Nongbri; Steve Decanio

2004-01-12

The overall objective of this project is the three phase development of an Early Entrance Coproduction Plant (EECP) which uses petroleum coke to produce at least one product from at least two of the following three categories: (1) electric power (or heat), (2) fuels, and (3) chemicals using ChevronTexaco's proprietary gasification technology. The objective of Phase I is to determine the feasibility and define the concept for the EECP located at a specific site; develop a Research, Development, and Testing (RD&T) Plan to mitigate technical risks and barriers; and prepare a Preliminary Project Financing Plan. The objective of Phase IImore » is to implement the work as outlined in the Phase I RD&T Plan to enhance the development and commercial acceptance of coproduction technology. The objective of Phase III is to develop an engineering design package and a financing and testing plan for an EECP located at a specific site. The project's intended result is to provide the necessary technical, economic, and environmental information needed by industry to move the EECP forward to detailed design, construction, and operation. The partners in this project are Texaco Energy Systems LLC or TES (a subsidiary of ChevronTexaco), General Electric (GE), Praxair, and Kellogg Brown & Root (KBR) in addition to the U.S. Department of Energy (DOE). TES is providing gasification technology and Fischer-Tropsch (F-T) technology developed by Rentech, Inc., GE is providing combustion turbine technology, Praxair is providing air separation technology, and KBR is providing engineering. During Phase I, a design basis for the Fischer-Tropsch Synthesis section was developed based on limited experience with the specified feed gas and operating conditions. The objective of this Task in Phase II RD&T work was to confirm the performance of the F-T reactor at the set design conditions. Although much of the research, development, and testing work were done by TES outside of this project, several important issues were addressed in this phase of the project. They included Rejuvenation/Regeneration of the Fischer-Tropsch Catalyst, online Catalyst Withdrawal and Addition from the synthesis reactor, and the Fischer-Tropsch Design Basis Confirmation. In Phase III the results from these RD&T work will be incorporated in developing the engineering design package. This Topical Report documents the Phase II RD&T work that was completed for this task.« less

Lock-in thermal imaging for the early-stage detection of cutaneous melanoma: a feasibility study.

PubMed

Bonmarin, Mathias; Le Gal, Frédérique-Anne

2014-04-01

This paper theoretically evaluates lock-in thermal imaging for the early-stage detection of cutaneous melanoma. Lock-in thermal imaging is based on the periodic thermal excitation of the specimen under test. Resulting surface temperature oscillations are recorded with an infrared camera and allow the detection of variations of the sample's thermophysical properties under the surface. In this paper, the steady-state and transient skin surface temperatures are numerically derived for a different stage of development of the melanoma lesion using a two-dimensional axisymmetric multilayer heat-transfer model. The transient skin surface temperature signals are demodulated according to the digital lock-in principle to compute both a phase and an amplitude image of the lesions. The phase image can be advantageously used to accurately detect cutaneous melanoma at an early stage of development while the maximal phase shift can give precious information about the lesion invasion depth. The ability of lock-in thermal imaging to suppress disturbing subcutaneous thermal signals is demonstrated. The method is compared with the previously proposed pulse-based approaches, and the influence of the modulation frequency is further discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evaluation of early efficacy endpoints for proof-of-concept trials.

PubMed

Chen, Cong; Sun, Linda; Li, Chih-Lin

2013-03-11

A Phase II proof-of-concept (POC) trial usually uses an early efficacy endpoint other than a clinical endpoint as the primary endpoint. Because of the advancement in bioscience and technology, which has yielded a number of new surrogate biomarkers, drug developers often have more candidate endpoints to choose from than they can handle. As a result, selection of endpoint and its effect size as well as choice of type I/II error rates are often at the center of heated debates in design of POC trials. While optimization of the trade-off between benefit and cost is the implicit objective in such a decision-making process, it is seldom explicitly accounted for in practice. In this research note, motivated by real examples from the oncology field, we provide practical measures for evaluation of early efficacy endpoints (E4) for POC trials. We further provide optimal design strategies for POC trials that include optimal Go-No Go decision criteria for initiation of Phase III and optimal resource allocation strategies for conducting multiple POC trials in a portfolio under fixed resources. Although oncology is used for illustration purpose, the same idea developed in this research note also applies to similar situations in other therapeutic areas or in early-stage drug development in that a Go-No Go decision has to rely on limited data from an early efficacy endpoint and cost-effectiveness is the main concern.

Differential involvement of ipsilateral and contralateral spinal cord astrocyte D-serine in carrageenan-induced mirror-image pain: role of σ1 receptors and astrocyte gap junctions.

PubMed

Choi, Hoon-Seong; Roh, Dae-Hyun; Yoon, Seo-Yeon; Choi, Sheu-Ran; Kwon, Soon-Gu; Kang, Suk-Yun; Moon, Ji-Young; Han, Ho-Jae; Beitz, Alvin J; Lee, Jang-Hern

2018-02-01

Although we have recently demonstrated that spinal astrocyte gap junctions mediate the development of mirror-image pain (MIP), it is still unclear which astrocyte-derived factor is responsible for the development of MIP and how its production is controlled. In the present study, we focused on the role of ipsilateral versus contralateral D-serine in the development of MIP and investigated the possible involvement of σ1 receptors and gap junctions in astrocyte D-serine production. Following carrageenan injection, mechanical allodynia was tested at various time points to examine the effect of individual drugs. Immunohistochemistry and Western blot analyses were performed to clarify the expression levels of spinal D-serine, serine racemase, σ1 receptors and connexin 43. The expression of ipsilateral D-serine was up-regulated during the early phase of inflammation, while contralateral D-serine increased during the later phase of inflammation. The pharmacological inhibition of D-serine during the early phase blocked the development of both ipsilateral and contralateral mechanical allodynia. However, the inhibition of D-serine during the later phase of inflammation blocked contralateral, but not ipsilateral mechanical allodynia. Furthermore, the inhibition of σ1 receptors during the earlier phase of inflammation inhibited the increase in ipsilateral D-serine. Conversely, the blockade of astrocyte gap junctions suppressed the up-regulation of contralateral D-serine during the later phase of inflammation. Spinal astrocyte D-serine plays an important role in the development of mirror-image pain. Furthermore, σ1 receptors and astrocyte gap junction signalling mediate ipsilateral and contralateral D-serine production respectively. © 2017 The British Pharmacological Society.

Rewriting the Central European Early Bronze Age Chronology: Evidence from Large-Scale Radiocarbon Dating

PubMed Central

Knipper, Corina; Friedrich, Ronny; Kromer, Bernd; Lindauer, Susanne; Radosavljević, Jelena; Wittenborn, Fabian; Krause, Johannes

2015-01-01

The transition from the Neolithic to the Early Bronze Age in Central Europe has often been considered as a supra-regional uniform process, which led to the growing mastery of the new bronze technology. Since the 1920s, archaeologists have divided the Early Bronze Age into two chronological phases (Bronze A1 and A2), which were also seen as stages of technical progress. On the basis of the early radiocarbon dates from the cemetery of Singen, southern Germany, the beginning of the Early Bronze Age in Central Europe was originally dated around 2300/2200 BC and the transition to more complex casting techniques (i.e., Bronze A2) around 2000 BC. On the basis of 140 newly radiocarbon dated human remains from Final Neolithic, Early and Middle Bronze Age cemeteries south of Augsburg (Bavaria) and a re-dating of ten graves from the cemetery of Singen, we propose a significantly different dating range, which forces us to re-think the traditional relative and absolute chronologies as well as the narrative of technical development. We are now able to date the beginning of the Early Bronze Age to around 2150 BC and its end to around 1700 BC. Moreover, there is no transition between Bronze (Bz) A1 and Bronze (Bz) A2, but a complete overlap between the type objects of the two phases from 1900–1700 BC. We thus present a revised chronology of the assumed diagnostic type objects of the Early Bronze Age and recommend a radiocarbon-based view on the development of the material culture. Finally, we propose that the traditional phases Bz A1 and Bz A2 do not represent a chronological sequence, but regionally different social phenomena connected to the willingness of local actors to appropriate the new bronze technology. PMID:26488413

Role models and professional development in dentistry: an important resource: The views of early career stage dentists at one academic health science centre in England.

PubMed

Mohamed Osama, O; Gallagher, J E

2018-02-01

The importance of role models, and their differing influence in early, mid- and late careers, has been identified in the process of professional development of medical doctors. There is a paucity of evidence within dentistry on role models and their attributes. To explore the views of early career dentists on positive and negative role models across key phases of professional development, together with role models' attributes and perceived influence. This is a phenomenological study collecting qualitative data through semi-structured interviews based on a topic guide. Dentists in junior (core training) hospital posts in one academic health science centre were all invited to participate. Interviews were recorded, transcribed verbatim and analysed using framework analysis. Twelve early career stage dentists, 10 of whom were female, reported having role models, mainly positive, in their undergraduate and early career phases. Participants defined role models' attributes in relation to three distinct domains: clinical attributes, personal qualities and teaching skills. Positive role models were described as "prioritising the patient's best interests", "delivering learner-centred teaching and training" and "exhibiting a positive personality", whilst negative role models demonstrated the converse. Early career dentists reported having largely positive dentist role models during- and post-dental school and report their impact on professional values and aspirations, learning outcomes and career choice. The findings suggest that these early career dentists in junior hospital posts have largely experienced and benefitted from positive role models, notably dentists, perceived as playing an important and creative influence promoting professionalism and shaping the career choices of early career stage dentists. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

CCCT - Investigational Drug Steering Committee

Cancer.gov

The Investigational Drug Steering Committee (IDSC) collaborates with NCI in the design and prioritization of early phase drug development trials conducted by the Experimental Therapeutics Clinical Trials Network (ETCTN).

Low temperatures are required to induce the development of fertile flowers in transgenic male and female early flowering poplar (Populus tremula L.).

PubMed

Hoenicka, Hans; Lehnhardt, Denise; Briones, Valentina; Nilsson, Ove; Fladung, Matthias

2016-05-01

Until now, artificial early flowering poplar systems have mostly led to the development of sterile flowers. In this study, several strategies aimed at inducting fertile flowers in pHSP::AtFT transgenic poplar were evaluated, in particular the influence of temperature and photoperiod. Our results provide evidence that temperature, and not photoperiod, is the key factor required for the development of fertile flowers in early flowering poplar. Fertile flowers were only obtained when a cold treatment phase of several weeks was used after the heat treatment phase. Heat treatments induced AtFT gene activity through activation of the heat-shock promoter (pHSP). Photoperiod did not show a similar influence on flower fertility as pollen grains were obtained under both long- and short-day conditions. Fertility was confirmed in flowers of both male and female plants. For the first time, crosses were successfully performed with transgenic female early flowering poplar. All mature flowers obtained after 8 weeks of inductive treatments were fertile. Gene expression studies also confirmed that cold temperatures influenced expression of poplar genes homologous to 'pollen development genes' from Arabidopsis thaliana (L.) Heynh. Homology and expression patterns suggested a role for PtTDF1, PtBAM1, PtSERK1/2 and PtMS1 on anther and pollen development in poplar flowers. The system developed in this study allows a fast and very reliable induction of fertile poplar flowers in a very short period of time. The non-reproductive phase, usually 7-10 years, can now be shortened to 6-10 months, and fertile flowers can be obtained independently of the season. This system is a reliable tool for breeding purposes (high-speed breeding technology), genomics and biosafety research. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

Southern Impact Testing Alliance (SITA)

NASA Technical Reports Server (NTRS)

Hubbs, Whitney; Roebuck, Brian; Zwiener, Mark; Wells, Brian

2009-01-01

Efforts to form this Alliance began in 2008 to showcase the impact testing capabilities within the southern United States. Impact testing customers can utilize SITA partner capabilities to provide supporting data during all program phases-materials/component/ flight hardware design, development, and qualification. This approach would allow programs to reduce risk by providing low cost testing during early development to flush out possible problems before moving on to larger scale1 higher cost testing. Various SITA partners would participate in impact testing depending on program phase-materials characterization, component/subsystem characterization, full-scale system testing for qualification. SITA partners would collaborate with the customer to develop an integrated test approach during early program phases. Modeling and analysis validation can start with small-scale testing to ensure a level of confidence for the next step large or full-scale conclusive test shots. Impact Testing Facility (ITF) was established and began its research in spacecraft debris shielding in the early 1960's and played a malor role in the International Space Station debris shield development. As a result of return to flight testing after the loss of STS-107 (Columbia) MSFC ITF realized the need to expand their capabilities beyond meteoroid and space debris impact testing. MSFC partnered with the Department of Defense and academic institutions as collaborative efforts to gain and share knowledge that would benefit the Space Agency as well as the DoD. MSFC ITF current capabilities include: Hypervelocity impact testing, ballistic impact testing, and environmental impact testing.

The aerodynamic challenges of the design and development of the space shuttle orbiter

NASA Technical Reports Server (NTRS)

Young, J. C.; Underwood, J. M.; Hillje, E. R.; Whitnah, A. M.; Romere, P. O.; Gamble, J. D.; Roberts, B. B.; Ware, G. M.; Scallion, W. I.; Spencer, B., Jr.

1985-01-01

The major aerodynamic design challenge at the beginning of the United States Space Transportation System (STS) research and development phase was to design a vehicle that would fly as a spacecraft during early entry and as an aircraft during the final phase of entry. The design was further complicated because the envisioned vehicle was statically unstable during a portion of the aircraft mode of operation. The second challenge was the development of preflight aerodynamic predictions with an accuracy consistent with conducting a manned flight on the initial orbital flight. A brief history of the early contractual studies is presented highlighting the technical results and management decisions influencing the aerodynamic challenges. The configuration evolution and the development of preflight aerodynamic predictions will be reviewed. The results from the first four test flights shows excellent agreement with the preflight aerodynamic predictions over the majority of the flight regimes. The only regimes showing significant disagreement is confined primarily to early entry, where prediction of the basic vehicle trim and the influence of the reaction control system jets on the flow field were found to be deficient. Postflight results are analyzed to explain these prediction deficiencies.

Shuttle free-flying teleoperator system experiment definition. Volume 3: program development requirements

NASA Technical Reports Server (NTRS)

1972-01-01

The planning data are presented for subsequent phases of free-flying teleoperator program (FFTO) and includes costs, schedules and supporting research and technology activities required to implement the free-flying teleoperator system and associated flight equipment. The purpose of the data presented is to provide NASA with the information needed to continue development of the FFTO and integrate it into the space shuttle program. The planning data describes three major program phases consisting of activities and events scheduled to effect integrated design, development, fabrication and operation of an FFTO system. Phase A, Concept Generation, represents a study effort directed toward generating and evaluating a number of feasible FFTO experiment system concepts. Phase B, Definition, will include preliminary design and supporting analysis of the FFTO, the shuttle based equipment and ground support equipment. Phase C/D, Design, Development and Operations will include detail design of the operational FFTO, its integration into the space shuttle, hardware fabrication and testing, delivery of flight hardware and support of flight operations. Emphasis is placed on the planning for Phases A and B since these studies will be implemented early in the development cycle. Phase C/D planning is more general and subject to refinement during the definition phase.

Students' Opinions about the Effects of Preclinical Patient Contacts on Their Learning

ERIC Educational Resources Information Center

Diemers, Agnes D.; Dolmans, Diana H. J. M.; Verwijnen, Maarten G. M.; Heineman, Erik; Scherpbier, Albert J. J. A.

2008-01-01

Several reasons have been given why students should have contacts with real patients early in the undergraduate medical curriculum, i.e., in the preclinical phase. However, it is not clear exactly what effects early patient contacts have with regard to knowledge construction and the development of clinical reasoning skills. We sought students'…

Frameworks for Change: Four Recurrent Themes for Quality in Early Childhood Curriculum Initiatives

ERIC Educational Resources Information Center

Burgess, Jennifer; Fleet, Alma

2009-01-01

This paper reports on the first phase of a case study that investigated how early childhood teachers experience organisational change. As one of three levels of quality improvement, State government-funded curriculum initiatives were developed with an aim to promote change. Three curriculum documents, one each focusing on literacy, pedagogy and…

Developing V-Xanes Oxybarometry for Probing Materials Formed in Reducing Environments in the Early Solar Disk

NASA Technical Reports Server (NTRS)

Butterworth, A. L.; Gainsforth, Z.; Jilly-Rehak, C. E.; Righter, K.; Westphal, A. J.

2017-01-01

Vanadium exhibits four oxidation states (V(sup 2+), V(sup 3+), V(sup 4+) and V(sup 5+)) that have been shown to preferentially partition between melt phases dependent on redox conditions, spanning oxygen fugacity across more than 10 log units. We are developing synchrotron-based x-ray absorption spectroscopy of low-fugacity standards for the determination of V oxidation state in highly reducing conditions relevant to the early solar nebula.

Prostate Cancer Clinical Trials Group: The University of Michigan Site

DTIC Science & Technology

2012-04-01

and fusion-negative strata. UM will be the lead site for this trial with the Univ. of Chicago N01 Phase II consortium as the coordinating center. Ten...sensitive prostate cancer: a University of Chicago Phase II Consortium/Department of Defense Prostate Cancer Clinical Trials Consortium study. JE Ward, T...N01 contract with CTEP (University of Chicago – Early Therapeutics Development with Phase II emphasis group). The Program is committed to creating

Development of Infrared Phase Closure Capability in the Infrared-Optical Telescope Array (IOTA)

NASA Technical Reports Server (NTRS)

Traub, Wesley A.

2002-01-01

We completed all major fabrication and testing for the third telescope and phase-closure operation at the Infrared-Optical Telescope Array (IOTA) during this period. In particular we successfully tested the phase-closure operation, using a laboratory light source illuminating the full delay-line optical paths, and using an integrated-optic beam combiner coupled to our Picnic-detector camera. This demonstration is an important and near-final milestone achievement. As of this writing, however, several tasks yet remain, owing to development snags and weather, so the final proof of success, phase-closure observation of a star, is now expected to occur in early 2002, soon after this report has been submitted.

Retrospection of Chernobyl nuclear accident for decision analysis concerning remedial actions in Ukraine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Georgievskiy, Vladimir

2007-07-01

It is considered the efficacy of decisions concerning remedial actions when of-site radiological monitoring in the early and (or) in the intermediate phases was absent or was not informative. There are examples of such situations in the former Soviet Union where many people have been exposed: releases of radioactive materials from 'Krasnoyarsk-26' into Enisey River, releases of radioactive materials from 'Chelabinsk-65' (the Kishtim accident), nuclear tests at the Semipalatinsk Test Site, the Chernobyl nuclear accident etc. If monitoring in the early and (or) in the intermediate phases is absent the decisions concerning remedial actions are usually developed on the basemore » of permanent monitoring. However decisions of this kind may be essentially erroneous. For these cases it is proposed to make retrospection of radiological data of the early and intermediate phases of nuclear accident and to project decisions concerning remedial actions on the base of both retrospective data and permanent monitoring data. In this Report the indicated problem is considered by the example of the Chernobyl accident for Ukraine. Their of-site radiological monitoring in the early and intermediate phases was unsatisfactory. In particular, the pasture-cow-milk monitoring had not been made. All official decisions concerning dose estimations had been made on the base of measurements of {sup 137}Cs in body (40 measurements in 135 days and 55 measurements in 229 days after the Chernobyl accident). For the retrospection of radiological data of the Chernobyl accident dynamic model has been developed. This model has structure similar to the structure of Pathway model and Farmland model. Parameters of the developed model have been identified for agricultural conditions of Russia and Ukraine. By means of this model dynamics of 20 radionuclides in pathways and dynamics of doses have been estimated for the early, intermediate and late phases of the Chernobyl accident. The main results are following: - During the first year after the Chernobyl accident 75-93% of Commitment Effective Dose had been formed; - During the first year after the Chernobyl accident 85-90% of damage from radiation exposure had been formed. During the next 50 years (the late phase of accident) only 10-15% of damage from radiation exposure will have been formed; - Remedial actions (agricultural remedial actions as most effective) in Ukraine are intended for reduction of the damage from consumption of production which is contaminated in the late phase of accident. I.e. agricultural remedial actions have been intended for minimization only 10 % of the total damage from radiation exposure; - Medical countermeasures can minimize radiation exposure damage by an order of magnitude greater than agricultural countermeasures. - Thus, retrospection of nuclear accident has essentially changed type of remedial actions and has given a chance to increase effectiveness of spending by an order of magnitude. This example illustrates that in order to optimize remedial actions it is required to use data of retrospection of nuclear accidents in all cases when monitoring in the early and (or) intermediate phases is unsatisfactory. (author)« less

Phase II Validation of a New Panel of Biomarkers for Early Detection of Ovarian Cancer — EDRN Public Portal

Cancer.gov

While all cancer patients could potentially benefit from earlier detection and prevention, the development of new screening technologies and chemoprevention for epithelial ovarian cancer (EOC) is unique in this regard. EOC is characterized by few early symptoms, presentation at an advanced stage, and poor survival. Presently there is no commercially available test that is diagnostic for either early or advanced stage epithelial ovarian cancer. The most commonly used marker, CA125, identifies a group of cell surface glycoproteins, which have uncertain biological behavior and very limited clinical utility for the detection of early stage disease. In recent years, several approaches have been used in order to develop a test for early detection, including the analysis of serum samples by SELDI-TOF and MALDI-TOF to find proteins or protein fragments of unknown identity that detect the presence/absence of cancer. Unfortunately, at the present time, none of these techniques have been shown to be adequate. Therefore, the development of a test that can detect early stages of the disease could dramatically improve treatment success and long-term survival. We have developed a new blood test based on a different approach: 1) we used known proteins related to cancer biology, 2) we characterized these proteins with several different screening steps using samples obtained from both healthy and cancer patient populations, and 3) validated the results with different techniques. Using split point analysis with four markers, 96 out of 100 EOC patients (96%) were correctly diagnosed with ovarian cancer (including 23 of 24 patients with Stage I/II EOC). In the healthy group, 6 out of 106 individuals were diagnosed incorrectly (5.6%). Working in collaboration with the Early Detection Network (EDRN/NCI/NIH), we performed Phase I discovery study confirming the potential application of this test for early detection of ovarian cancer (Preliminary results). The main objective of this pr

A Status Report on the Parachute Development for NASA's Next Manned Spacecraft

NASA Technical Reports Server (NTRS)

Sinclair, Robert

2008-01-01

NASA has determined that the parachute portion of the Landing System for the Crew Exploration Vehicle (CEV) will be Government Furnished Equipment (GFE). The Earth Landing System has been designated CEV Parachute Assembly System (CPAS). Thus a program team was developed consisting of NASA Johnson Space Center (JSC) and Jacobs Engineering through their Engineering and Science Contract Group (ESCG). Following a rigorous competitive phase, Airborne Systems North America was selected to provide the parachute design, testing and manufacturing role to support this team. The development program has begun with some early flight testing of a Generation 1 parachute system. Future testing will continue to refine the design and complete a qualification phase prior to manned flight of the spacecraft. The program team will also support early spacecraft system testing, including a Pad Abort Flight Test in the Fall of 2008

Neratinib for the treatment of HER2-positive early stage breast cancer.

PubMed

Echavarria, Isabel; López-Tarruella, Sara; Márquez-Rodas, Iván; Jerez, Yolanda; Martin, Miguel

2017-08-01

Despite the advances in the treatment of HER2-positive breast cancer, resistance to actual chemotherapeutic regimens eventually occurs. Neratinib, an orally available pan-inhibitor of the ERBB family, represents an interesting new option for early-stage HER2-positive breast cancer. Areas covered: In this article, the development of neratinib, with a special focus on its potential value in the treatment of early-stage HER2-positive breast cancer, has been reviewed. For this purpose, a literature search was conducted, including preclinical studies, early-phase trials in advanced cancer with neratinib in monotherapy and in combination, and phase II and large phase III trials in the early setting. Management of neratinib-induced toxicity, future perspectives for the drug, and ongoing trials are also discussed in this review. Expert commentary: Neratinib is emerging as a promising oral drug for the treatment of HER2-positive breast cancer. Although FDA and EMA approval is derived from the extended adjuvant treatment, this setting may not be the ideal scenario to obtain the beneficial effects of neratinib. Confirmatory data in the neoadjuvant setting and subgroup analysis from the ExTENET trial might bring some light into the best setting for neratinib therapy. Data from confirmatory trials in the metastatic setting are also required.

Evaluating cardiac risk: exposure response analysis in early clinical drug development.

PubMed

Grenier, Julie; Paglialunga, Sabina; Morimoto, Bruce H; Lester, Robert M

2018-01-01

The assessment of a drug's cardiac liability has undergone considerable metamorphosis by regulators since International Council for Harmonization of Technical Requirement for Pharmaceuticals for Human Use E14 guideline was introduced in 2005. Drug developers now have a choice in how proarrhythmia risk can be evaluated; the options include a dedicated thorough QT (TQT) study or exposure response (ER) modeling of intensive electrocardiogram (ECG) captured in early clinical development. The alternative approach of ER modeling was incorporated into a guidance document in 2015 as a primary analysis tool which could be utilized in early phase dose escalation studies as an option to perform a dedicated TQT trial. This review will describe the current state of ER modeling of intensive ECG data collected during early clinical drug development; the requirements with regard to the use of a positive control; and address the challenges and opportunities of this alternative approach to assessing QT liability.

Development of the osteocranium in Corydoras aeneus (Gill, 1858) Callichthyidae, Siluriformes.

PubMed

Huysentruyt, Frank; Geerinckx, Tom; Brunain, Marleen; Adriaens, Dominique

2011-05-01

Development in the osteocranium of Corydoras aeneus was studied based on 48 cleared and stained specimens and 10 series of serial sections. Development overall follows the general trends observed in siluriform development, with ossifications appearing as a response to functional demands. Early development of the skull occurs in two distinct phases. In a first phase, several new bony elements, all of dermal origin and related to feeding, appear shortly after yolk depletion (4.4 mm SL). Between 5 and 8 mm SL, developmental priorities seem to shift to size increase of the cartilaginous skull and no new bony elements appear. Finally, a second phase of osteogenesis occurs from 8 to 18 mm SL, in which all remaining dermal and perichondral bones appear. Copyright © 2011 Wiley-Liss, Inc.

Analysis of Drug Development Paradigms for Immune Checkpoint Inhibitors.

PubMed

Jardim, Denis L; de Melo Gagliato, Débora; Giles, Francis J; Kurzrock, Razelle

2018-04-15

Immune checkpoint inhibitors have unique toxicities and response kinetics compared with cytotoxic and gene-targeted anticancer agents. We investigated the impact of innovative/accelerated immunotherapy drug development/approval models on the accuracy of safety and efficacy assessments by searching the FDA website. Initial phase I trials for each agent were reviewed and safety and efficacy data compared with that found in later trials leading to regulatory approvals of the same agents. As of June 2017, the FDA approved six checkpoint inhibitors for a variety of cancer types. All checkpoint inhibitors received a priority review status and access to at least two additional FDA special access programs, more often breakthrough therapy designation and accelerated approval. Median clinical development time (investigational new drug application to approval) was 60.77 months [avelumab had the shortest timeline (52.33 months)]. Response rates during early phase I trials (median = 16%) are higher than for phase I trials of other agents (with the exception of gene-targeted agents tested with a biomarker). Doses approved were usually not identical to doses recommended on phase I trials. Approximately 50% of types of immune-related and 43% of types of clinically relevant toxicities from later trials were identified in early-phase trials. Even so, treatment-related mortality remains exceedingly low in later studies (0.33% of patients). In conclusion, efficacy and safety of immune checkpoint inhibitors appear to be reasonably predicted from the dose-finding portion of phase I trials, indicating that the fast-track development of these agents is safe and justified. Clin Cancer Res; 24(8); 1785-94. ©2017 AACR . ©2017 American Association for Cancer Research.

Microstructural Developments Leading to New Advanced High Strength Sheet Steels: A Historical Assessment of Critical Metallographic Observations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matlock, David K; Thomas, Larrin S; Taylor, Mark D

In the past 30+ years significant advancements have been made in the development of higher strength sheet steels with improved combinations of strength and ductility that have enabled important product improvements leading to safer, lighter weight, and more fuel efficient automobiles and in other applications. Properties of the primarily low carbon, low alloy steels are derived through careful control of time-temperature processing histories designed to produce multiphase ferritic based microstructures that include martensite and other constituents including retained austenite. The basis for these developments stems from the early work on dual-phase steels which was the subject of much interest. Inmore » response to industry needs, dual-phase steels have evolved as a unique class of advanced high strength sheet steels (AHSS) in which the thermal and mechanical processing histories have been specifically designed to produce constituent combinations for the purpose of simultaneously controlling strength and deformation behavior, i.e. stress-strain curve shapes. Improvements continue as enhanced dual-phase steels have recently been produced with finer microstructures, higher strengths, and better overall formability. Today, dual phase steels are the primary AHSS products used in vehicle manufacture, and several companies have indicated that the steels will remain as important design materials well into the future. In this presentation, fundamental results from the early work on dual-phase steels will be reviewed and assessed in light of recent steel developments. Specific contributions from industry/university cooperative research leading to product improvements will be highlighted. The historical perspective provided in the evolution of dual-phase steels represents a case-study that provides important framework and lessons to be incorporated in next generation AHSS products.« less

An Expert System-Driven Method for Parametric Trajectory Optimization During Conceptual Design

NASA Technical Reports Server (NTRS)

Dees, Patrick D.; Zwack, Mathew R.; Steffens, Michael; Edwards, Stephen; Diaz, Manuel J.; Holt, James B.

2015-01-01

During the early phases of engineering design, the costs committed are high, costs incurred are low, and the design freedom is high. It is well documented that decisions made in these early design phases drive the entire design's life cycle cost. In a traditional paradigm, key design decisions are made when little is known about the design. As the design matures, design changes become more difficult in both cost and schedule to enact. The current capability-based paradigm, which has emerged because of the constrained economic environment, calls for the infusion of knowledge usually acquired during later design phases into earlier design phases, i.e. bringing knowledge acquired during preliminary and detailed design into pre-conceptual and conceptual design. An area of critical importance to launch vehicle design is the optimization of its ascent trajectory, as the optimal trajectory will be able to take full advantage of the launch vehicle's capability to deliver a maximum amount of payload into orbit. Hence, the optimal ascent trajectory plays an important role in the vehicle's affordability posture yet little of the information required to successfully optimize a trajectory is known early in the design phase. Thus, the current paradigm of optimizing ascent trajectories involves generating point solutions for every change in a vehicle's design parameters. This is often a very tedious, manual, and time-consuming task for the analysts. Moreover, the trajectory design space is highly non-linear and multi-modal due to the interaction of various constraints. When these obstacles are coupled with the Program to Optimize Simulated Trajectories (POST), an industry standard program to optimize ascent trajectories that is difficult to use, expert trajectory analysts are required to effectively optimize a vehicle's ascent trajectory. Over the course of this paper, the authors discuss a methodology developed at NASA Marshall's Advanced Concepts Office to address these issues. The methodology is two-fold: first, capture the heuristics developed by human analysts over their many years of experience; and secondly, leverage the power of modern computing to evaluate multiple trajectories simultaneously and therefore enable the exploration of the trajectory's design space early during the pre- conceptual and conceptual phases of design. This methodology is coupled with design of experiments in order to train surrogate models, which enables trajectory design space visualization and parametric optimal ascent trajectory information to be available when early design decisions are being made.

Understanding cost growth during operations of planetary missions: An explanation of changes

NASA Astrophysics Data System (ADS)

McNeill, J. F.; Chapman, E. L.; Sklar, M. E.

In the development of project cost estimates for interplanetary missions, considerable focus is generally given to the development of cost estimates for the development of ground, flight, and launch systems, i.e., Phases B, C, and D. Depending on the project team, efforts expended to develop cost estimates for operations (Phase E) may be relatively less rigorous than that devoted to estimates for ground and flight systems development. Furthermore, the project team may be challenged to develop a solid estimate of operations cost in the early stages of mission development, e.g., Concept Study Report or Systems Requirement Review (CSR/SRR), Preliminary Design Review (PDR), as mission specific peculiarities that impact cost may not be well understood. In addition, a methodology generally used to develop Phase E cost is engineering build-up, also known as “ grass roots” . Phase E can include cost and schedule risks that are not anticipated at the time of the major milestone reviews prior to launch. If not incorporated into the engineering build-up cost method for Phase E, this may translate into an estimation of the complexity of operations and overall cost estimates that are not mature and at worse, insufficient. As a result, projects may find themselves with thin reserves during cruise and on-orbit operations or project overruns prior to the end of mission. This paper examines a set of interplanetary missions in an effort to better understand the reasons for cost and staffing growth in Phase E. The method used in the study is discussed as well as the major findings summarized as the Phase E Explanation of Change (EoC). Research for the study entailed the review of project materials, including Estimates at Completion (EAC) for Phase E and staffing profiles, major project milestone reviews, e.g., CSR, PDR, Critical Design Review (CDR), the interviewing of select project and mission management, and review of Phase E replan materials. From this work, a detai- ed picture is constructed of why cost grew during the operations phase, even to the level of specific events in the life of the missions. As a next step, the Phase E EoC results were gleaned and synthesized to produce leading indicators, i.e., what may be identifiable signs of cost and staffing growth that may be present as early as PDR or CDR. Both a qualitative and quantitative approach was used to determine leading indicators. These leading indicators will be reviewed and a practical method for their use will be discussed.

Instructional Media Production for Early Childhood Education: A. B. C. Jig-Saw Puzzle, a Model

ERIC Educational Resources Information Center

Yusuf, Mudashiru Olalere; Olanrewaju, Olatayo Solomon; Soetan, Aderonke K.

2015-01-01

In this paper, a. b. c. jig-saw puzzle was produced for early childhood education using local materials. This study was a production based type of research, to serve as a supplemental or total learning resource. Its production followed four phases of development referred to as information, design, production and evaluation. The storyboard cards,…

Cross-Cultural Evaluation of the Autism Detection in Early Childhood (ADEC) in Mexico

ERIC Educational Resources Information Center

Hedley, Darren; Young, Robyn; Angelica, Maria; Gallegos, Juarez; Salazar, Carlos, Marcin

2010-01-01

A Spanish translation of the Autism Detection in Early Childhood (ADEC-SP) was administered to 115 children aged 15-73 months in Mexico. In Phase 1, children with Autistic Disorder (AD), a non-Pervasive Developmental Disorder (PDD) diagnosis or typical development were assessed with the ADEC-SP by a clinician blind to the child's diagnostic…

Unknown loads affect force production capacity in early phases of bench press throws.

PubMed

Hernández Davó, J L; Sabido Solana, R; Sarabia Marínm, J M; Sánchez Martos, Á; Moya Ramón, M

2015-10-01

Explosive strength training aims to improve force generation in early phases of movement due to its importance in sport performance. The present study examined the influence of lack of knowledge about the load lifted in explosive parameters during bench press throws. Thirteen healthy young men (22.8±2.0 years) participated in the study. Participants performed bench press throws with three different loads (30, 50 and 70% of 1 repetition maximum) in two different conditions (known and unknown loads). In unknown condition, loads were changed within sets in each repetition and participants did not know the load, whereas in known condition the load did not change within sets and participants had knowledge about the load lifted. Results of repeated-measures ANOVA revealed that unknown conditions involves higher power in the first 30, 50, 100 and 150 ms with the three loads, higher values of ratio of force development in those first instants, and differences in time to reach maximal rate of force development with 50 and 70% of 1 repetition maximum. This study showed that unknown conditions elicit higher values of explosive parameters in early phases of bench press throws, thereby this kind of methodology could be considered in explosive strength training.

The early phase of /see symbol/ production development in adult Japanese learners of English.

PubMed

Saito, Kazuya; Munro, Murray J

2014-12-01

Although previous research indicates that Japanese speakers' second language (L2) perception and production of English /see symbol/ may improve with increased L2 experience, relatively little is known about the fine phonetic details of their /see symbol/ productions, especially during the early phase of L2 speech learning. This cross-sectional study examined acoustic properties of word-initial /see symbol/ from 60 Japanese learners with a length of residence of between one month and one year in Canada. Their performance was compared to that of 15 native speakers of English and 15 low-proficiency Japanese learners of English. Formant frequencies (F2 and F3) and F1 transition durations were evaluated under three task conditions--word reading, sentence reading, and timed picture description. Learners with as little as two to three months of residence demonstrated target-like F2 frequencies. In addition, increased LOR was predictive of more target-like transition durations. Although the learners showed some improvement in F3 as a function of LOR, they did so mainly at a controlled level of speech production. The findings suggest that during the early phase of L2 segmental development, production accuracy is task-dependent and is influenced by the availability of L1 phonetic cues for redeployment in L2.

Definition of technology development missions for early space stations: Large space structures

NASA Technical Reports Server (NTRS)

Gates, R. M.; Reid, G.

1984-01-01

The objectives studied are the definition of the tested role of an early Space Station for the construction of large space structures. This is accomplished by defining the LSS technology development missions (TDMs) identified in phase 1. Design and operations trade studies are used to identify the best structural concepts and procedures for each TDMs. Details of the TDM designs are then developed along with their operational requirements. Space Station resources required for each mission, both human and physical, are identified. The costs and development schedules for the TDMs provide an indication of the programs needed to develop these missions.

Bid opening report : Federal-aid highway construction contracts : first six months 2001

DOT National Transportation Integrated Search

2000-04-01

This research update provides general human factors design information relevant to the early phases of in-vehicle icon development and design. It reflects a subset of the results to date of a Federal Highway Administration project to develop a set of...

Phase 1 report on the development of predictive model for bridge deck cracking and strength development.

DOT National Transportation Integrated Search

2009-01-01

Early-age cracking, typically caused by drying shrinkage (and often coupled with autogenous and thermal : shrinkage), can have several detrimental effects on long-term behavior and durability. Cracking can also provide : ingress of water that can dri...

Emerging Use of Early Health Technology Assessment in Medical Product Development: A Scoping Review of the Literature.

PubMed

IJzerman, Maarten J; Koffijberg, Hendrik; Fenwick, Elisabeth; Krahn, Murray

2017-07-01

Early health technology assessment is increasingly being used to support health economic evidence development during early stages of clinical research. Such early models can be used to inform research and development about the design and management of new medical technologies to mitigate the risks, perceived by industry and the public sector, associated with market access and reimbursement. Over the past 25 years it has been suggested that health economic evaluation in the early stages may benefit the development and diffusion of medical products. Early health technology assessment has been suggested in the context of iterative economic evaluation alongside phase I and II clinical research to inform clinical trial design, market access, and pricing. In addition, performing early health technology assessment was also proposed at an even earlier stage for managing technology portfolios. This scoping review suggests a generally accepted definition of early health technology assessment to be "all methods used to inform industry and other stakeholders about the potential value of new medical products in development, including methods to quantify and manage uncertainty". The present review also aimed to identify recent published empirical studies employing an early-stage assessment of a medical product. With most included studies carried out to support a market launch, the dominant methodology was early health economic modeling. Further methodological development is required, in particular, by combining systems engineering and health economics to manage uncertainty in medical product portfolios.

Use of Probabilistic Engineering Methods in the Detailed Design and Development Phases of the NASA Ares Launch Vehicle

NASA Technical Reports Server (NTRS)

Fayssal, Safie; Weldon, Danny

2008-01-01

The United States National Aeronautics and Space Administration (NASA) is in the midst of a space exploration program called Constellation to send crew and cargo to the international Space Station, to the moon, and beyond. As part of the Constellation program, a new launch vehicle, Ares I, is being developed by NASA Marshall Space Flight Center. Designing a launch vehicle with high reliability and increased safety requires a significant effort in understanding design variability and design uncertainty at the various levels of the design (system, element, subsystem, component, etc.) and throughout the various design phases (conceptual, preliminary design, etc.). In a previous paper [1] we discussed a probabilistic functional failure analysis approach intended mainly to support system requirements definition, system design, and element design during the early design phases. This paper provides an overview of the application of probabilistic engineering methods to support the detailed subsystem/component design and development as part of the "Design for Reliability and Safety" approach for the new Ares I Launch Vehicle. Specifically, the paper discusses probabilistic engineering design analysis cases that had major impact on the design and manufacturing of the Space Shuttle hardware. The cases represent important lessons learned from the Space Shuttle Program and clearly demonstrate the significance of probabilistic engineering analysis in better understanding design deficiencies and identifying potential design improvement for Ares I. The paper also discusses the probabilistic functional failure analysis approach applied during the early design phases of Ares I and the forward plans for probabilistic design analysis in the detailed design and development phases.

The history of the development of the rectenna

NASA Technical Reports Server (NTRS)

Brown, W. C.

1980-01-01

The history of the development of the rectenna is first reviewed through its early conceptual and developmental phases in which the Air Force and Raytheon Company were primarily involved. The intermediate period of development which involved NASA, Jet Propulsion Laboratory, and Raytheon is then reviewed. Some selective aspects of the current SPS rectenna development are examined.

Mars Rover/Sample Return - Phase A cost estimation

NASA Technical Reports Server (NTRS)

Stancati, Michael L.; Spadoni, Daniel J.

1990-01-01

This paper presents a preliminary cost estimate for the design and development of the Mars Rover/Sample Return (MRSR) mission. The estimate was generated using a modeling tool specifically built to provide useful cost estimates from design parameters of the type and fidelity usually available during early phases of mission design. The model approach and its application to MRSR are described.

Enabling Roles to Reclaim Teacher Agency: Insights from the Advanced Certificate in Teaching (Foundation Phase)

ERIC Educational Resources Information Center

Ebrahim, H. B.; Verbeek, D. C.; Mashiya, J. N.

2011-01-01

In developing the Advanced Certificate in Teaching (ACT) as a professional qualification for continuing teacher education for early schooling at the University of KwaZulu-Natal we asked the following: "What are the enabling roles foundation phase teachers need to play in order to reclaim their space as agents who significantly influence their…

The clinical relevance of luteal phase deficiency: a committee opinion.

PubMed

2012-11-01

Luteal phase deficiency (LPD) has been described in healthy normally menstruating women and in association with other medical conditions. While progesterone is important for the process of implantation and early embryonic development, LPD, as an independent entity causing infertility, has not been proven. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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).

EUFEMED London Conference 2017: Exploratory Medicines Development: Innovation and Risk Management.

PubMed

Van Bortel, Luc; Sourgens, Hildegard; Breithaupt-Grögler, Kerstin; Caplain, Henri; Donazzolo, Yves; Klingmann, Ingrid; Hammond, Michael; Hardman, Timothy C; Stringer, Steffan; de Hoon, Jan

2017-01-01

The first formal conference of the EUropean Federation for Exploratory MEdicines Development (EUFEMED) held in London was the result of a collaborative effort of its founding associations: the Association for Applied Human Pharmacology (AGAH; Germany), the Association for Human Pharmacology in the Pharmaceutical Industry (AHPPI; UK), the Belgian Association of Phase-I Units (BAPU; Belgium), and Club Phase-I (France). The conference focused on innovation and risk management in early clinical drug development. Among other innovations, immunotherapy in oncology and inflammatory diseases were discussed as well as the importance of adaptive trial designs in early clinical drug development. Consideration was given to assessing and mitigating risk in early clinical drug development, and included a preconference workshop. Different measures to minimize risks in healthy volunteers and patients in first-in-human trials were discussed in addition to the importance of non-clinical data, the need for reliable biomarkers, improved communication on adverse events (AEs) and well-trained study sites with ready access to intensive care units and clinical specialists. The need for a European-wide system for prevention of over-volunteering was also discussed. The conference provided opportunity to discuss these developments and concerns and the changing regulatory environment with stakeholders from academia, industry, and regulatory agencies including the European Medicines Agency (EMA). Presentations given by invited speakers are published on http://www.eufemed.eu/london-conference-2017/.

Temporal regulation of expression of immediate early and second phase transcripts by endothelin-1 in cardiomyocytes

PubMed Central

Cullingford, Timothy E; Markou, Thomais; Fuller, Stephen J; Giraldo, Alejandro; Pikkarainen, Sampsa; Zoumpoulidou, Georgia; Alsafi, Ali; Ekere, Collins; Kemp, Timothy J; Dennis, Jayne L; Game, Laurence; Sugden, Peter H; Clerk, Angela

2008-01-01

Background Endothelin-1 stimulates Gq protein-coupled receptors to promote proliferation in dividing cells or hypertrophy in terminally differentiated cardiomyocytes. In cardiomyocytes, endothelin-1 rapidly (within minutes) stimulates protein kinase signaling, including extracellular-signal regulated kinases 1/2 (ERK1/2; though not ERK5), with phenotypic/physiological changes developing from approximately 12 h. Hypertrophy is associated with changes in mRNA/protein expression, presumably consequent to protein kinase signaling, but the connections between early, transient signaling events and developed hypertrophy are unknown. Results Using microarrays, we defined the early transcriptional responses of neonatal rat cardiomyocytes to endothelin-1 over 4 h, differentiating between immediate early gene (IEG) and second phase RNAs with cycloheximide. IEGs exhibited differential temporal and transient regulation, with expression of second phase RNAs within 1 h. Of transcripts upregulated at 30 minutes encoding established proteins, 28 were inhibited >50% by U0126 (which inhibits ERK1/2/5 signaling), with 9 inhibited 25-50%. Expression of only four transcripts was not inhibited. At 1 h, most RNAs (approximately 67%) were equally changed in total and polysomal RNA with approximately 17% of transcripts increased to a greater extent in polysomes. Thus, changes in expression of most protein-coding RNAs should be reflected in protein synthesis. However, approximately 16% of transcripts were essentially excluded from the polysomes, including some protein-coding mRNAs, presumably inefficiently translated. Conclusion The phasic, temporal regulation of early transcriptional responses induced by endothelin-1 in cardiomyocytes indicates that, even in terminally differentiated cells, signals are propagated beyond the primary signaling pathways through transcriptional networks leading to phenotypic changes (that is, hypertrophy). Furthermore, ERK1/2 signaling plays a major role in this response. PMID:18275597

Comparison of diagnosis of early retinal lesions of diabetic retinopathy between a computer system and human experts.

PubMed

Lee, S C; Lee, E T; Kingsley, R M; Wang, Y; Russell, D; Klein, R; Warn, A

2001-04-01

To investigate whether a computer vision system is comparable with humans in detecting early retinal lesions of diabetic retinopathy using color fundus photographs. A computer system has been developed using image processing and pattern recognition techniques to detect early lesions of diabetic retinopathy (hemorrhages and microaneurysms, hard exudates, and cotton-wool spots). Color fundus photographs obtained from American Indians in Oklahoma were used in developing and testing the system. A set of 369 color fundus slides were used to train the computer system using 3 diagnostic categories: lesions present, questionable, or absent (Y/Q/N). A different set of 428 slides were used to test and evaluate the system, and its diagnostic results were compared with those of 2 human experts-the grader at the University of Wisconsin Fundus Photograph Reading Center (Madison) and a general ophthalmologist. The experiments included comparisons using 3 (Y/Q/N) and 2 diagnostic categories (Y/N) (questionable cases excluded in the latter). In the training phase, the agreement rates, sensitivity, and specificity in detecting the 3 lesions between the retinal specialist and the computer system were all above 90%. The kappa statistics were high (0.75-0.97), indicating excellent agreement between the specialist and the computer system. In the testing phase, the results obtained between the computer system and human experts were consistent with those of the training phase, and they were comparable with those between the human experts. The performance of the computer vision system in diagnosing early retinal lesions was comparable with that of human experts. Therefore, this mobile, electronically easily accessible, and noninvasive computer system, could become a mass screening tool and a clinical aid in diagnosing early lesions of diabetic retinopathy.

Early Intervention Services for Early-Phase Psychosis - Centre for integrative psychiatry in Psychiatric Hospital "Sveti Ivan", Croatia.

PubMed

Matić, Katarina; Gereš, Natko; Gerlach, Josefina; Prskalo-Čule, Diana; Zadravec Vrbanc, Tihana; Lovretić, Vanja; Librenjak, Dina; Vuk Pisk, Sandra; Ivezić, Ena; Šimunović Filipčić, Ivona; Jeleč, Vjekoslav; Filipčić, Igor

2018-06-01

There is a growing body of evidence suggesting that early and effective management in the critical early years of schizophrenia can improve long-term outcomes. The objective of this study was to evaluate time to relapse of the patients with early-phase psychosis treated in the Centre for integrative psychiatry (CIP). We performed a retrospective cohort study on the sample of 373 early-phase psychosis patients admitted to Psychiatric Hospital "Sveti Ivan", Zagreb Croatia: from January 1, 2015 to December 31, 2017. The primary outcome was time to relapse. Patients who were admitted to group psychotherapeutic program after the end of acute treatment had 70% lower hazard for relapse (HR=0.30; 95% CI 0.16-0.58). Patients who were included first in the psychotherapeutic program and then treated and controlled in the daily hospital had 74% lower hazard for relapse (HR=0.26; 95% CI 0.10-0.67). In early-phase psychosis, integrative early intervention service has relevant beneficial effects compare to treatment as usual. These results justified the implementation of multimodal early intervention services in treatment of patients with early-phase psychosis.

Crossing eastern cottonwood in the greenhouse

Treesearch

R. E. Farmer; W. L. Nance

1968-01-01

Eastern cottonwood (Populus deltoides Bartr.) is the subject of breeding programs designed to develop planting stock with potential for rapid growth, desirable wood properties, and pest resistance (4). Techniques for making controlled crosses within the species are essential to breeding, and their development constitutes an early phase of genetics...

INDEX AND SHORT DESCRIPTION OF ALL TESTS.

ERIC Educational Resources Information Center

New York Medical Coll., NY.

THE INSTITUTE'S TEST BATTERY IS INTENDED TO ASSESS THE CHILD'S ACHIEVEMENT IN COGNITIVE STYLE, PERCEPTUAL ABILITY, LANGUAGE DEVELOPMENT, AND READING ACHIEVEMENT. THE TWO MAJOR PHASES IN THE INSTITUTE'S RESEARCH PROGRAM ARE EXPLORATION OF EARLY ENVIRONMENTAL FACTORS AND THE DEVELOPMENT OF SCHOOL REMEDIAL, READING, AND ENRICHMENT PROGRAMS. THE INDEX…

Approach to developing reliable space reactor power systems

NASA Technical Reports Server (NTRS)

Mondt, Jack F.; Shinbrot, Charles H.

1991-01-01

During Phase II, the Engineering Development Phase, the SP-100 Project has defined and is pursuing a new approach to developing reliable power systems. The approach to developing such a system during the early technology phase is described along with some preliminary examples to help explain the approach. Developing reliable components to meet space reactor power system requirements is based on a top-down systems approach which includes a point design based on a detailed technical specification of a 100-kW power system. The SP-100 system requirements implicitly recognize the challenge of achieving a high system reliability for a ten-year lifetime, while at the same time using technologies that require very significant development efforts. A low-cost method for assessing reliability, based on an understanding of fundamental failure mechanisms and design margins for specific failure mechanisms, is being developed as part of the SP-100 Program.

Knowledge exchange in the UK CLAHRCs.

PubMed

Racko, Girts

2018-04-09

Purpose The purpose of this paper is to examine how knowledge exchange between academics and clinicians in Collaborations for Leadership in Applied Health Research and Care (CLAHRCs) is influenced by their social position based on their symbolic and social capitals, that is, their personal professional status and connections to high-status professional peers, knowledge brokers, and unfamiliar professional peers. Design/methodology/approach Using an online survey, the author triangulates the cross-sectional measurement of the effects of academic and clinicians' social position in the initial and later phases of CLAHRCs with the longitudinal measurement of these effects over a two-year period. Findings First, academics and clinicians with a higher personal professional status are more likely to develop joint networks and decision making both in the early and later phases of a CLAHRC. Second, academics and clinicians who are more connected to higher status occupational peers are more likely to develop joint networks in the early phase of a knowledge exchange partnership but are less likely to become engaged in joint networks over time. Third, involvement of knowledge brokers in the networks of academics and clinicians is likely to facilitate their inter-professional networking only in the later partnership phase. Practical implications Academics and clinicians' capitals have a distinctive influence on knowledge exchange in the early and later phases of CLAHRCs and on a change in knowledge exchange over a two-year period. Originality/value Prior research on CLAHRCs has examined how knowledge exchange between academics and clinicians can be encouraged by the creation of shared governance mechanisms. The author advances this research by highlighting the role of their social position in facilitating knowledge exchange.

Phase retrieval from local measurements in two dimensions

NASA Astrophysics Data System (ADS)

Iwen, Mark; Preskitt, Brian; Saab, Rayan; Viswanathan, Aditya

2017-08-01

The phase retrieval problem has appeared in a multitude of applications for decades. While ad hoc solutions have existed since the early 1970s, recent developments have provided algorithms that offer promising theoretical guarantees under increasingly realistic assumptions. Motivated by ptychographic imaging, we generalize a recent result on phase retrieval of a one dimensional objective vector x ∈ ℂd to recover a two dimensional sample Q ∈ ℂd x d from phaseless measurements, using a tensor product formulation to extend the previous work.

Development of radiotracers for oncology – the interface with pharmacology

PubMed Central

Sharma, Rohini; Aboagye, Eric

2011-01-01

There is an increasing role for positron emission tomography (PET) in oncology, particularly as a component of early phase clinical trials. As a non-invasive functional imaging modality, PET can be used to assess both pharmacokinetics and pharmacodynamics of novel therapeutics by utilizing radiolabelled compounds. These studies can provide crucial information early in the drug development process that may influence the further development of novel therapeutics. PET imaging probes can also be used as early biomarkers of clinical response and to predict clinical outcome prior to the administration of therapeutic agents. We discuss the role of PET imaging particularly as applied to phase 0 studies and discuss the regulations involved in the development and synthesis of novel radioligands. The review also discusses currently available tracers and their role in the assessment of pharmacokinetics and pharmacodynamics as applied to oncology. LINKED ARTICLES This article is part of a themed section on Imaging. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2011.163.issue-8BJP has previously published an Imaging in Pharmacology themed section, edited by A Davenport and C Daly. To view this section visit http://dx.doi.org/10.1111/bph.2010.159.issue-4 PMID:21175573

Relationships between training load, injury, and fitness in sub-elite collision sport athletes.

PubMed

Gabbett, Tim J; Domrow, Nathan

2007-11-01

The purpose of this study was to develop statistical models that estimate the influence of training load on training injury and physical fitness in collision sport athletes. The incidence of training injuries was studied in 183 rugby league players over two competitive seasons. Participants were assessed for height, body mass, skinfold thickness, vertical jump, 10-m, 20-m and 40-m sprint time, agility, and estimated maximal aerobic power in the off-season, pre-season, mid-season, and end-season. Training load and injury data were summarised into pre-season, early-competition, and late-competition training phases. Individual training load, fitness, and injury data were modelled using a logistic regression model with a binomial distribution and logit link function, while team training load and injury data were modelled using a linear regression model. While physical fitness improved with training, there was no association (P=0.16-0.99) between training load and changes in physical fitness during any of the training phases. However, increases in training load during the early-competition training phase decreased (P= 0.04) agility performance. A relationship (P= 0.01-0.04) was observed between the log of training load and odds of injury during each training phase, resulting in a 1.50 - 2.85 increase in the odds of injury for each arbitrary unit increase in training load. Furthermore, during the pre-season training phase there was a relationship (P= 0.01) between training load and injury incidence within the training load range of 155 and 590 arbitrary units. During the early and late-competition training phases, increases in training load of 175-620 arbitrary units and 145-410 arbitrary units, respectively, resulted in no further increase in injury incidence. These findings demonstrate that increases in training load, particularly during the pre-season training phase, increase the odds of injury in collision sport athletes. However, while increases in training load from 175 to 620 arbitrary units during the early-competition training phase result in no further increase in injury incidence, marked reductions in agility performances can occur. These findings suggest that reductions in training load during the early-competition training phase can reduce the odds of injury without compromising agility performances in collision sport athletes.

Achievements and Perspectives of the Adult Education in Croatia.

ERIC Educational Resources Information Center

Klapan, Anita

Historical development of adult education in Croatia can be identified in seven phases: (1) the beginning of the 20th century and the period between the two World Wars; (2) World War II; (3) period from 1945 to the early 1950s; (4) early 1950s to 1965; (5) period between 1965 and 1980; (6) 1980s; and (7) period after the fall of the Berlin…

Constructing the 'Best' Reliability Data for the Job - Developing Generic Reliability Data from Alternative Sources Early in a Product's Development Phase

NASA Technical Reports Server (NTRS)

Kleinhammer, Roger K.; Graber, Robert R.; DeMott, D. L.

2016-01-01

Reliability practitioners advocate getting reliability involved early in a product development process. However, when assigned to estimate or assess the (potential) reliability of a product or system early in the design and development phase, they are faced with lack of reasonable models or methods for useful reliability estimation. Developing specific data is costly and time consuming. Instead, analysts rely on available data to assess reliability. Finding data relevant to the specific use and environment for any project is difficult, if not impossible. Instead, analysts attempt to develop the "best" or composite analog data to support the assessments. Industries, consortia and vendors across many areas have spent decades collecting, analyzing and tabulating fielded item and component reliability performance in terms of observed failures and operational use. This data resource provides a huge compendium of information for potential use, but can also be compartmented by industry, difficult to find out about, access, or manipulate. One method used incorporates processes for reviewing these existing data sources and identifying the available information based on similar equipment, then using that generic data to derive an analog composite. Dissimilarities in equipment descriptions, environment of intended use, quality and even failure modes impact the "best" data incorporated in an analog composite. Once developed, this composite analog data provides a "better" representation of the reliability of the equipment or component. It can be used to support early risk or reliability trade studies, or analytical models to establish the predicted reliability data points. It also establishes a baseline prior that may updated based on test data or observed operational constraints and failures, i.e., using Bayesian techniques. This tutorial presents a descriptive compilation of historical data sources across numerous industries and disciplines, along with examples of contents and data characteristics. It then presents methods for combining failure information from different sources and mathematical use of this data in early reliability estimation and analyses.

CARBON DIOXIDE SEPARATION BY PHASE ENHANCED GAS-LIQUID ABSORPTION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liang Hu

A new process called phase enhanced gas-liquid absorption has been developed in its early stage. It was found that adding another phase into the absorption system of gas/aqueous phase could enhance the absorption rate. A system with three phases was studied. In the system, gas phase was carbon dioxide. Two liquid phases were used. One was organic phase. Another was aqueous phase. By addition of organic phase into the absorption system of CO{sub 2}-aqueous phase, the absorption rate of CO{sub 2} was increased significantly. CO{sub 2} finally accumulated into aqueous phase. The experimental results proved that (1) Absorption rate ofmore » carbon dioxide was enhanced by adding organic phase into gas aqueous phase system; (2) Organic phase played the role of transportation of gas solute (CO{sub 2}). Carbon dioxide finally accumulated into aqueous phase.« less

Early-Phase 11C-PiB PET in Amyloid Angiopathy-Related Symptomatic Cerebral Hemorrhage: Potential Diagnostic Value?

PubMed Central

Aigbirhio, Franklin I.; Fryer, Tim D.; Menon, David K.; Warburton, Elizabeth A.; Baron, Jean-Claude

2015-01-01

Although late-phase (>35min post-administration) 11C-PiB-PET has good sensitivity in cerebral amyloid angiopathy (CAA), its specificity is poor due to frequently high uptake in healthy aged subjects. By detecting perfusion-like abnormalities, early-phase 11C-PiB-PET might add diagnostic value. Early-frame (1–6min) 11C-PiB-PET was obtained in 11 non-demented patients with probable CAA-related symptomatic lobar intracerebral haemorrhage (70±7yrs), 9 age-matched healthy controls (HCs) and 10 HCs <55yrs. There was a significant decrease in early-phase atrophy-corrected whole-cortex SUV relative to cerebellar vermis (SUVR) in the CAA vs age-matched HC group. None of the age-matched controls fell below the lower 95% confidence limit derived from the young HCs, while 6/11 CAA patients did (sensitivity = 55%, specificity = 100%). Combining both early- and late-phase 11C-PiB data did not change the sensitivity and specificity of late-phase PiB, but combined early- and late-phase positivity entails a very high suspicion of underlying Aβ-related clinical disorder, i.e., CAA or Alzheimer disease (AD). In order to clarify this ambiguity, we then show that the occipital/posterior cingulate ratio is markedly lower in CAA than in AD (N = 7). These pilot data suggest that early-phase 11C-PiB-PET may not only add to late-phase PiB-PET with respect to the unclear situation of late-phase positivity, but also help differentiate CAA from AD. PMID:26439113

Logistics planning for phased programs.

NASA Technical Reports Server (NTRS)

Cook, W. H.

1973-01-01

It is pointed out that the proper and early integration of logistics planning into the phased program planning process will drastically reduce these logistics costs. Phased project planning is a phased approach to the planning, approval, and conduct of major research and development activity. A progressive build-up of knowledge of all aspects of the program is provided. Elements of logistics are discussed together with aspects of integrated logistics support, logistics program planning, and logistics activities for phased programs. Continuing logistics support can only be assured if there is a comprehensive sequential listing of all logistics activities tied to the program schedule and a real-time inventory of assets.

Is there a maternally induced immunological imprinting phase à la Konrad Lorenz?

PubMed

Lemke, H; Lange, H

1999-10-01

In mammals, IgG antibodies are transferred from mothers to the offspring. Since these maternal antibodies result mainly from thymus-dependent immune responses which have undergone immune maturation through somatic hypermutations, they represent the highest quality of the collective maternal immunological experience. Maternal antibodies not only confer passive immunity as long as the newborn's immune system has not fully developed, but also exert an active stimulation as indicated by their regulatory influence on isotype expression, long-term idiotypic alterations, determination of the adult B and T cell repertoire, induction of antigen reactive IgM as well as an affinity enhancement of a proportion of early primary antibodies. The fact that several of these features can only be induced during limited sensitive periods shortly after birth is reminiscent of the behavioural imprinting as defined by Konrad Lorenz. We therefore propose that during early ontogeny there is an immunological imprinting phase with characteristics analogous to behavioural imprinting: (i) the internal imprinting effect is induced by external signals, (ii) in contrast to normal learning, immunological imprinting is also only possible during certain development phases and (iii) it is characterised by an (almost) irreversible result. Hence, if particular immunological experiences are only possible during such sensitive phases, maternal immunoglobulins and consequently the mother's immunological experience is of prime importance for the start of the ontogenetic development of the immune system.

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

PubMed

Buchy, P

2016-10-01

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

Development of a Low Cost 10kW Tubular SOFC Power System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bessette, Norman; Litka, Anthony; Rawson, Jolyon

The DOE program funded from 2003 through early 2013 has brought the Acumentrics SOFC program from an early stage R&D program to an entry level commercial product offering. The development work started as one of the main core teams under the DOE Solid State Energy Conversion Alliance (SECA) program administered by the National Energy Technology Laboratory (NETL) of the DOE. During the first phase of the program, lasting approximately 3-4 years, a 5kW machine was designed, manufactured and tested against the specification developed by NETL. This unit was also shipped to NETL for independent verification testing which validated all ofmore » the results achieved while in the laboratory at Acumentrics. The Acumentrics unit passed all criteria established from operational stability, efficiency, and cost projections. Passing of the SECA Phase I test allowed the program to move into Phase II of the program. During this phase, the overall objective was to further refine the unit meeting a higher level of performance stability as well as further cost reductions. During the first year of this new phase, the NETL SECA program was refocused towards larger size units and operation on coal gasification due to the severe rise in natural gas prices and refocus on the US supply of indigenous coal. At this point, the program was shifted to the U.S. DOE’s Energy Efficiency and Renewable Energy (EERE) division located in Golden, Colorado. With this shift, the focus remained on smaller power units operational on gaseous fuels for a variety of applications including micro combined heat and power (mCHP). To achieve this goal, further enhancements in power, life expectancy and reductions in cost were necessary. The past 5 years have achieved these goals with machines that can now achieve over 40% electrical efficiency and field units that have now operated for close to a year and a half with minimal maintenance. The following report details not only the first phase while under the SECA program and the key achievements but also the results while under EERE’s leadership and the transition to an early commercial product offering.« less

Definition of technology development missions for early Space Station satellite servicing. Volume 2: Technical

NASA Technical Reports Server (NTRS)

Cable, D. A.; Diewald, C. A.; Hills, T. C.; Parmentier, T. J.; Spencer, R. A.; Stone, G. E.

1984-01-01

Volume 2 contains the Technical Report of the approach and results of the Phase 2 study. The phase 2 servicing study was initiated in June 1983, and is being reported in this document. The scope of the contract was to: (1) define in detail five selected technology development missions (TDM); (2) conduct a design requirement analysis to refine definitions of satellite servicing requirements at the space station; and (3) develop a technology plan that would identify and schedule prerequisite precursor technology development, associated. STS flight experiments and space station experiments needed to provide onorbit validation of the evolving technology.

Differential role of afferent and efferent renal nerves in the maintenance of early- and late-phase Dahl S hypertension

PubMed Central

Foss, Jason D.; Fink, Gregory D.

2015-01-01

Clinical data suggest that renal denervation (RDNX) may be an effective treatment for human hypertension; however, it is unclear whether this therapeutic effect is due to ablation of afferent or efferent renal nerves. We have previously shown that RDNX lowers arterial pressure in hypertensive Dahl salt-sensitive (S) rats to a similar degree observed in clinical trials. In addition, we have recently developed a method for selective ablation of afferent renal nerves (renal-CAP). In the present study, we tested the hypothesis that the antihypertensive effect of RDNX in the Dahl S rat is due to ablation of afferent renal nerves by comparing the effect of complete RDNX to renal-CAP during two phases of hypertension in the Dahl S rat. In the early phase, rats underwent treatment after 3 wk of high-NaCl feeding when mean arterial pressure (MAP) was ∼140 mmHg. In the late phase, rats underwent treatment after 9 wk of high NaCl feeding, when MAP was ∼170 mmHg. RDNX reduced MAP ∼10 mmHg compared with sham surgery in both the early and late phase, whereas renal-CAP had no antihypertensive effect. These results suggest that, in the Dahl S rat, the antihypertensive effect of RDNX is not dependent on pretreatment arterial pressure, nor is it due to ablation of afferent renal nerves. PMID:26661098

Hemoglobin phase of oxygenation and deoxygenation in early brain development measured using fNIRS

PubMed Central

Watanabe, Hama; Shitara, Yoshihiko; Aoki, Yoshinori; Inoue, Takanobu; Tsuchida, Shinya; Takahashi, Naoto; Taga, Gentaro

2017-01-01

A crucial issue in neonatal medicine is the impact of preterm birth on the developmental trajectory of the brain. Although a growing number of studies have shown alterations in the structure and function of the brain in preterm-born infants, we propose a method to detect subtle differences in neurovascular and metabolic functions in neonates and infants. Functional near-infrared spectroscopy (fNIRS) was used to obtain time-averaged phase differences between spontaneous low-frequency (less than 0.1 Hz) oscillatory changes in oxygenated hemoglobin (oxy-Hb) and those in deoxygenated hemoglobin (deoxy-Hb). This phase difference was referred to as hemoglobin phase of oxygenation and deoxygenation (hPod) in the cerebral tissue of sleeping neonates and infants. We examined hPod in term, late preterm, and early preterm infants with no evidence of clinical issues and found that all groups of infants showed developmental changes in the values of hPod from an in-phase to an antiphase pattern. Comparison of hPod among the groups revealed that developmental changes in hPod in early preterm infants precede those in late preterm and term infants at term equivalent age but then, progress at a slower pace. This study suggests that hPod measured using fNIRS is sensitive to the developmental stage of the integration of circular, neurovascular, and metabolic functions in the brains of neonates and infants. PMID:28196885

From Pedagogical Museum to Instructional Material Center: Education Libraries at Teacher Training Institutions, 1890s to 1970s

ERIC Educational Resources Information Center

Attebury, Ramirose; Kroth, Michael

2012-01-01

The development of education libraries cannot be understood outside the context of education history. Changes in educational practices and technology spurred three phases of development in the history of education libraries. Early examples, often called curriculum laboratories, developed as spaces to create educational materials where limited…

Precambrian perspectives.

PubMed

Goodwin, A M

1981-07-03

The Precambrian record is interpreted in terms of an evolutionary progression that moves in the direction of increasing continental stability. An early, highly mobile microplate tectonics phase progressed through a more stable, largely intracratonic, ensialic, mobile belt phase to the modern macroplate tectonics phase that involves large, rigid lithospheric plates. Various phases are characterized by distinctive crustal associations. Three controls-bulk earth heat production, crustal fractionation and cratonization, and atmospheric oxygen accumulation-are viewed as the cumulative cause of the trends and events that characterize the crust at different stages of development, from its inception approximately 4.6 billion years ago to the present.

Self-determined motivation in rehabilitating professional rugby union players.

PubMed

Carson, Fraser; Polman, Remco C J

2017-01-01

The aim of the present study was to explore the views of professional rugby union players during the early rehabilitation, late rehabilitation and return to play stages, following anterior cruciate ligament (ACL) injury. A qualitative dominant, mixed methodological approach was utilized with five players who had suffered an ACL injury requiring reconstructive surgery. A longitudinal approach, concurrent with each player's rehabilitation, consisting of twice monthly interviews, a self-report diary and three established questionnaires (MOS-Social Support Survey, Sherbourne & Stewart, 1991; Sport Climate Questionnaire, Deci & Ryan, n.d.; Injury Rehabilitation Questionnaire, Deci & Ryan, n.d.) were completed. Theoretical thematic analysis was conducted on three distinct phases (Early Limited Participation phase, 10 higher order themes; Late Limited Rehabilitation phase, 11 higher order themes; and Return to Play phase, 9 higher order themes) and coded relating to autonomy, competence and relatedness. The findings suggest that increased autonomy and control assist emotional and behavioral responses during rehabilitation and return to play, while development of competence increases self-confidence.

Scientific white paper on concentration-QTc modeling.

PubMed

Garnett, Christine; Bonate, Peter L; Dang, Qianyu; Ferber, Georg; Huang, Dalong; Liu, Jiang; Mehrotra, Devan; Riley, Steve; Sager, Philip; Tornoe, Christoffer; Wang, Yaning

2018-06-01

The International Council for Harmonisation revised the E14 guideline through the questions and answers process to allow concentration-QTc (C-QTc) modeling to be used as the primary analysis for assessing the QTc interval prolongation risk of new drugs. A well-designed and conducted QTc assessment based on C-QTc modeling in early phase 1 studies can be an alternative approach to a thorough QT study for some drugs to reliably exclude clinically relevant QTc effects. This white paper provides recommendations on how to plan and conduct a definitive QTc assessment of a drug using C-QTc modeling in early phase clinical pharmacology and thorough QT studies. Topics included are: important study design features in a phase 1 study; modeling objectives and approach; exploratory plots; the pre-specified linear mixed effects model; general principles for model development and evaluation; and expectations for modeling analysis plans and reports. The recommendations are based on current best modeling practices, scientific literature and personal experiences of the authors. These recommendations are expected to evolve as their implementation during drug development provides additional data and with advances in analytical methodology.

Flight Test of the F/A-18 Active Aeroelastic Wing Airplane

NASA Technical Reports Server (NTRS)

Clarke, Robert; Allen, Michael J.; Dibley, Ryan P.; Gera, Joseph; Hodgkinson, John

2005-01-01

Successful flight-testing of the Active Aeroelastic Wing airplane was completed in March 2005. This program, which started in 1996, was a joint activity sponsored by NASA, Air Force Research Laboratory, and industry contractors. The test program contained two flight test phases conducted in early 2003 and early 2005. During the first phase of flight test, aerodynamic models and load models of the wing control surfaces and wing structure were developed. Design teams built new research control laws for the Active Aeroelastic Wing airplane using these flight-validated models; and throughout the final phase of flight test, these new control laws were demonstrated. The control laws were designed to optimize strategies for moving the wing control surfaces to maximize roll rates in the transonic and supersonic flight regimes. Control surface hinge moments and wing loads were constrained to remain within hydraulic and load limits. This paper describes briefly the flight control system architecture as well as the design approach used by Active Aeroelastic Wing project engineers to develop flight control system gains. Additionally, this paper presents flight test techniques and comparison between flight test results and predictions.

Premenstrual symptoms are associated with psychological and physical symptoms in early pregnancy.

PubMed

Winkel, Susanne; Einsle, Franziska; Wittchen, Hans-Ulrich; Martini, Julia

2013-04-01

The reproductive life of women is characterised by a number of distinct reproductive events and phases (e.g. premenstrual phase, peripartum, perimenopause). The hormonal transitions during these phases are often associated with both psychological and physical symptoms. Associations between these reproductive phases have been shown by numerous studies. However, the relationship between symptoms during the premenstrual phase and during early pregnancy has received little attention thus far, although early pregnancy is a time of dramatic hormonal as well as physical adaptation. Findings are based on a prospective longitudinal study with N = 306 pregnant women (MARI study). Three hundred five women that had menstrual bleeding in the year before pregnancy rated the severity of psychological and physical symptoms during premenstrual phases in the year preceding pregnancy. Besides this, they rated the severity of the same symptoms during early pregnancy (weeks 10 to 12 of gestation). The overall severity of premenstrual symptoms was significantly associated with the overall severity of early pregnancy symptoms (b = 0.4, 95% CI = 0.3-0.5; p < 0.001). The overall severity of early pregnancy symptoms was best predicted by the severity of premenstrual irritability. The best predictor for a particular symptom in early pregnancy mostly was the corresponding premenstrual symptom. The associations between premenstrual and early pregnancy symptoms support the reproductive hormone sensitivity hypothesis that some women are prone to repeatedly experience specific psychological and physical symptoms during different reproductive phases. The findings further imply that the nature of symptoms might be rather consistent between different reproductive phases.

James Webb Space Telescope: Supporting Multiple Ground System Transitions in One Year

NASA Technical Reports Server (NTRS)

Detter, Ryan; Fatig, Curtis; Steck, Jane

2004-01-01

Ideas, requirements, and concepts developed during the very early phases of the mission design often conflict with the reality of a situation once the prime contractors are awarded. This happened for the James Webb Space Telescope (JWST) as well. The high level requirement of a common real-time ground system for both the Integration and Test (I&T), as well as the Operation phase of the mission is meant to reduce the cost and time needed later in the mission development for re-certification of databases, command and control systems, scripts, display pages, etc. In the case of JWST, the early Phase A flight software development needed a real-time ground system and database prior to the spacecraft prime contractor being selected. To compound the situation, the very low level requirements for the real-time ground system were not well defined. These two situations caused the initial real-time ground system to be switched out for a system that was previously used by the Bight software development team. To meet the high-!evel requirement, a third ground system was selected based on the prime spacecraft contractor needs and JWST Project decisions. The JWST ground system team has responded to each of these changes successfully. The lessons learned from each transition have not only made each transition smoother, but have also resolved issues earlier in the mission development than what would normally occur.

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

..., choosing a study population, using a control group and blinding, dose selection, treatment plans...] Draft Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of Cellular... document entitled ``Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of...

Prediction of the Hydrogen Peroxide-Induced Methionine Oxidation Propensity in Monoclonal Antibodies.

PubMed

Agrawal, Neeraj J; Dykstra, Andrew; Yang, Jane; Yue, Hai; Nguyen, Xichdao; Kolvenbach, Carl; Angell, Nicolas

2018-05-01

Methionine oxidation in therapeutic antibodies can impact the product's stability, clinical efficacy, and safety and hence it is desirable to address the methionine oxidation liability during antibody discovery and development phase. Although the current experimental approaches can identify the oxidation-labile methionine residues, their application is limited mostly to the development phase. We demonstrate an in silico method that can be used to predict oxidation-labile residues based solely on the antibody sequence and structure information. Since antibody sequence information is available in the discovery phase, the in silico method can be applied very early on to identify the oxidation-labile methionine residues and subsequently address the oxidation liability. We believe that the in silico method for methionine oxidation liability assessment can aid in antibody discovery and development phase to address the liability in a more rational way. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Synoviocyte-packaged Chlamydia trachomatis induces a chronic aseptic arthritis.

PubMed Central

Inman, R D; Chiu, B

1998-01-01

The basic mechanisms underlying reactive arthritis and specifically the joint injury that follows intra-articular Chlamydia trachomatis infection have not been defined. The present study addresses this question through the development of an experimental model. Stable cell lines were generated from synoviocytes harvested from the knee joints of Lewis rats. The synoviocytes were cocultivated with C. trachomatis to allow invasion by the microbe and were then transferred by intra-articular injection into the knee joints of Lewis rats. The ensuing arthritis could be subdivided into an early phase (

Benzene-induced myelotoxicity: application of flow cytofluorometry for the evaluation of early proliferative change in bone marrow.

PubMed Central

Irons, R D

1981-01-01

A detailed description of flow cytofluorometric DNA cell cycle analysis is presented. A number of studies by the author and other investigators are reviewed in which a method is developed for the analysis of cell cycle phase in bone marrow of experimental animals. Bone marrow cell cycle analysis is a sensitive indicator of changes in bone marrow proliferative activity occurring early in chemically-induced myelotoxicity. Cell cycle analysis, used together with other hematologic methods, has revealed benzene-induced toxicity in proliferating bone marrow cells to be cycle specific, appearing to affect a population in late S phase which then accumulate in G2/M. PMID:7016521

Trajectory of frequency stability in typical development.

PubMed

Frohlich, Joel; Irimia, Andrei; Jeste, Shafali S

2015-03-01

This work explores a feature of brain dynamics, metastability, by which transients are observed in functional brain data. Metastability is a balance between static (stable) and dynamic (unstable) tendencies in electrophysiological brain activity. Furthermore, metastability is a theoretical mechanism underlying the rapid synchronization of cell assemblies that serve as neural substrates for cognitive states, and it has been associated with cognitive flexibility. While much previous research has sought to characterize metastability in the adult human brain, few studies have examined metastability in early development, in part because of the challenges of acquiring adequate, noise free continuous data in young children. To accomplish this endeavor, we studied a new method for characterizing the stability of EEG frequency in early childhood, as inspired by prior approaches for describing cortical phase resets in the scalp EEG of healthy adults. Specifically, we quantified the variance of the rate of change of the signal phase (i.e., frequency) as a proxy for phase resets (signal instability), given that phase resets occur almost simultaneously across large portions of the scalp. We tested our method in a cohort of 39 preschool age children (age =53 ± 13.6 months). We found that our outcome variable of interest, frequency variance, was a promising marker of signal stability, as it increased with the number of phase resets in surrogate (artificial) signals. In our cohort of children, frequency variance decreased cross-sectionally with age (r = -0.47, p = 0.0028). EEG signal stability, as quantified by frequency variance, increases with age in preschool age children. Future studies will relate this biomarker with the development of executive function and cognitive flexibility in children, with the overarching goal of understanding metastability in atypical development.

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

PubMed

Kawakami, Kohsaku

2009-09-01

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

Space Station ECLSS Integration Analysis

NASA Technical Reports Server (NTRS)

1993-01-01

The Space Station Environmental Control and Life Support System (ECLSS) contract with NASA MSFC covered the time frame from 9 May 1985 to 31 Dec. 1992. The contract roughly covered the period of Space Station Freedom (SSF) development from early Phase B through Phase C/D Critical Design Review (CDR). During this time, McDonnell Douglas Aerospace-Huntsville (formerly McDonnell Douglas Space Systems Company) performed an analytical support role to MSFC for the development of analytical math models and engineering trade studies related to the design of the ECLSS for the SSF.

Advanced Life Support Water Recycling Technologies Case Studies: Vapor Phase Catalytic Ammonia Removal and Direct Osmotic Concentration

NASA Technical Reports Server (NTRS)

Flynn, Michael

2004-01-01

Design for microgravity has traditionally not been well integrated early on into the development of advanced life support (ALS) technologies. NASA currently has a many ALS technologies that are currently being developed to high technology readiness levels but have not been formally evaluated for microgravity compatibility. Two examples of such technologies are the Vapor Phase Catalytic Ammonia Removal Technology and the Direct Osmotic Concentration Technology. This presentation will cover the design of theses two systems and will identify potential microgravity issues.

Early Manifestations of Children's Theory of Mind: The Roles of Maternal Mind-Mindedness and Infant Security of Attachment

ERIC Educational Resources Information Center

Laranjo, Jessica; Bernier, Annie; Meins, Elizabeth; Carlson, Stephanie M.

2010-01-01

This study investigated two aspects of mother-child relationships--mothers' mind-mindedness and infant attachment security--in relation to two early aspects of children's theory of mind development (ToM). Sixty-one mother-child dyads (36 girls) participated in testing phases at 12 (T1), 15 (T2), and 26 months of age (T3), allowing for assessment…

Interplanetary Program to Optimize Simulated Trajectories (IPOST). Volume 3: Programmer's manual

NASA Technical Reports Server (NTRS)

Hong, P. E.; Kent, P. D.; Olson, D. W.; Vallado, C. A.

1992-01-01

The Interplanetary Program to Optimize Space Trajectories (IPOST) is intended to support many analysis phases, from early interplanetary feasibility studies through spacecraft development and operations. Here, information is given on the IPOST code.

Development of Middle Stone Age innovation linked to rapid climate change

PubMed Central

Ziegler, Martin; Simon, Margit H.; Hall, Ian R.; Barker, Stephen; Stringer, Chris; Zahn, Rainer

2013-01-01

The development of modernity in early human populations has been linked to pulsed phases of technological and behavioural innovation within the Middle Stone Age of South Africa. However, the trigger for these intermittent pulses of technological innovation is an enigma. Here we show that, contrary to some previous studies, the occurrence of innovation was tightly linked to abrupt climate change. Major innovational pulses occurred at times when South African climate changed rapidly towards more humid conditions, while northern sub-Saharan Africa experienced widespread droughts, as the Northern Hemisphere entered phases of extreme cooling. These millennial-scale teleconnections resulted from the bipolar seesaw behaviour of the Atlantic Ocean related to changes in the ocean circulation. These conditions led to humid pulses in South Africa and potentially to the creation of favourable environmental conditions. This strongly implies that innovational pulses of early modern human behaviour were climatically influenced and linked to the adoption of refugia. PMID:23695699

Development of Middle Stone Age innovation linked to rapid climate change.

PubMed

Ziegler, Martin; Simon, Margit H; Hall, Ian R; Barker, Stephen; Stringer, Chris; Zahn, Rainer

2013-01-01

The development of modernity in early human populations has been linked to pulsed phases of technological and behavioural innovation within the Middle Stone Age of South Africa. However, the trigger for these intermittent pulses of technological innovation is an enigma. Here we show that, contrary to some previous studies, the occurrence of innovation was tightly linked to abrupt climate change. Major innovational pulses occurred at times when South African climate changed rapidly towards more humid conditions, while northern sub-Saharan Africa experienced widespread droughts, as the Northern Hemisphere entered phases of extreme cooling. These millennial-scale teleconnections resulted from the bipolar seesaw behaviour of the Atlantic Ocean related to changes in the ocean circulation. These conditions led to humid pulses in South Africa and potentially to the creation of favourable environmental conditions. This strongly implies that innovational pulses of early modern human behaviour were climatically influenced and linked to the adoption of refugia.

Sleep Deprivation and Caffeine Treatment Potentiate Photic Resetting of the Master Circadian Clock in a Diurnal Rodent.

PubMed

Jha, Pawan Kumar; Bouâouda, Hanan; Gourmelen, Sylviane; Dumont, Stephanie; Fuchs, Fanny; Goumon, Yannick; Bourgin, Patrice; Kalsbeek, Andries; Challet, Etienne

2017-04-19

Circadian rhythms in nocturnal and diurnal mammals are primarily synchronized to local time by the light/dark cycle. However, nonphotic factors, such as behavioral arousal and metabolic cues, can also phase shift the master clock in the suprachiasmatic nuclei (SCNs) and/or reduce the synchronizing effects of light in nocturnal rodents. In diurnal rodents, the role of arousal or insufficient sleep in these functions is still poorly understood. In the present study, diurnal Sudanian grass rats, Arvicanthis ansorgei , were aroused at night by sleep deprivation (gentle handling) or caffeine treatment that both prevented sleep. Phase shifts of locomotor activity were analyzed in grass rats transferred from a light/dark cycle to constant darkness and aroused in early night or late night. Early night, but not late night, sleep deprivation induced a significant phase shift. Caffeine on its own induced no phase shifts. Both sleep deprivation and caffeine treatment potentiated light-induced phase delays and phase advances in response to a 30 min light pulse, respectively. Sleep deprivation in early night, but not late night, potentiated light-induced c-Fos expression in the ventral SCN. Caffeine treatment in midnight triggered c-Fos expression in dorsal SCN. Both sleep deprivation and caffeine treatment potentiated light-induced c-Fos expression in calbindin-containing cells of the ventral SCN in early and late night. These findings indicate that, in contrast to nocturnal rodents, behavioral arousal induced either by sleep deprivation or caffeine during the sleeping period potentiates light resetting of the master circadian clock in diurnal rodents, and activation of calbindin-containing suprachiasmatic cells may be involved in this effect. SIGNIFICANCE STATEMENT Arousing stimuli have the ability to regulate circadian rhythms in mammals. Behavioral arousal in the sleeping period phase shifts the master clock in the suprachiasmatic nuclei and/or slows down the photic entrainment in nocturnal animals. How these stimuli act in diurnal species remains to be established. Our study in a diurnal rodent, the Grass rat, indicates that sleep deprivation in the early rest period induces phase delays of circadian locomotor activity rhythm. Contrary to nocturnal rodents, both sleep deprivation and caffeine-induced arousal potentiate the photic entrainment in a diurnal rodent. Such enhanced light-induced circadian responses could be relevant for developing chronotherapeutic strategies. Copyright © 2017 the authors 0270-6474/17/374343-16$15.00/0.

Multipath noise reduction spread spectrum signals

NASA Technical Reports Server (NTRS)

Meehan, Thomas K. (Inventor)

1994-01-01

The concepts of early-prompt delay tracking, multipath correction of early-prompt delay tracking from correlation shape, and carrier phase multipath correction are addressed. In early-prompt delay tracking, since multipath is always delayed with respect to the direct signals, the system derives phase and pseudorange observables from earlier correlation lags. In multipath correction of early-prompt delay tracking from correlation shape, the system looks for relative variations of amplitude across the code correlation function that do not match the predicted multipath-free code cross-correlation shape. The system then uses deviations from the multipath-free shape to infer the magnitude of multipath, and to generate corrections pseudorange observables. In carrier phase multipath correction, the system looks for variations of phase among plural early and prompt lags. The system uses the measured phase variations, along with the general principle that the multipath errors are larger for later lags, to infer the presence of multipath, and to generate corrections for carrier-phase observables.

Phased Array Probe Optimization for the Inspection of Titanium Billets

NASA Astrophysics Data System (ADS)

Rasselkorde, E.; Cooper, I.; Wallace, P.; Lupien, V.

2010-02-01

The manufacturing process of titanium billets can produce multiple sub-surface defects that are particularly difficult to detect during the early stages of production. Failure to detect these defects can lead to subsequent in-service failure. A new and novel automated quality control system is being developed for the inspection of titanium billets destined for use in aerospace applications. The sensors will be deployed by an automated system to minimise the use of manual inspections, which should improve the quality and reliability of these critical inspections early on in the manufacturing process. This paper presents the first part of the work, which is the design and the simulation of the phased array ultrasonic inspection of the billets. A series of phased array transducers were designed to optimise the ultrasonic inspection of a ten inch diameter billet made from Titanium 6Al-4V. A comparison was performed between different probes including a 2D annular sectorial array.

Clinical trials in drug development: a minimalistic approach.

PubMed

Verweij, Jaap

2012-05-01

Drug development in oncology finds itself at the crossroad of unique opportunities and major challenges. The old paradigms should and can be replaced by a system that better matches the right patients to the right compounds and puts much more emphasis on the early stages of drug development. The clinical phases of drug development will no longer be split into phase I, II, and III studies, but rather into 'functional target pharmacology studies', followed by 'proof of concept studies'. The resulting development flow becomes Apollo-capsule shaped. Although randomized studies will still be needed for drugs using targets in the tumor environment, or for combinations of agents, drug registration might proceed without these if all of the following criteria are met in early development: availability of preclinical convincing evidence that the drug's target is the functional driver behind the disease phenotype, availability of a predictive biomarker that enables appropriate and actual patient selection in early pharmacology studies, a Response Evaluation Criteria In Solid Tumors (RECIST)-based single agent response rate of at least 50%, and/or a progression at first tumor assessment rate of 15% or less, a duration of absence of progression (stable disease) beyond doubt and considered clinically relevant, and no major safety concern. This set is not yet mature, but may be adapted over time. The concerns related to registering agents on the basis of small datasets can be adequately addressed by obligatory postmarketing hypothesis driven studies.

Development and validation of a patient symptom questionnaire to facilitate early diagnosis of thyroid-associated orbitopathy in graves' disease.

PubMed

Mohaseb, Kam; Linder, Mark; Rootman, Jack; Wilkins, G E; Schechter, Martin T; Dolman, Peter J; Singer, Joel

2008-01-01

To construct a patient-based symptom questionnaire to facilitate early referral of thyroid-associated orbitopathy (TAO) in Graves' hyperthyroidism (GH). Phase I of our study involved developing a symptomatology-based questionnaire for the self-reporting of TAO symptoms in patients recently diagnosed with GH. Phase II involved administering the questionnaire along with a standard ophthalmic examination to a screening cohort of patients newly diagnosed with GH. Symptoms highly associated with the clinical diagnosis of TAO were used to construct a tool with the highest possible sensitivity. Phase III involved validation of this tool in a new cohort of patients recently diagnosed with GH. For each patient, the diagnosis of TAO was made by both a standardized orbital ophthalmic exam and the questionnaire. Results from the questionnaire were then compared to the clinical examination. The questionnaire was compared to the standardized examination and found to have a sensitivity of 0.76 and a specificity of 0.82 in the validation phase of the study. This questionnaire may be a useful tool in clinical practice to allow identification of patients with TAO secondary to GH. Future studies using this questionnaire are needed to determine whether earlier identification and management of these patients is associated with reduced morbidity from TAO.

Development and functionality of a handheld computer program to improve fruit and vegetable intake among low-income youth

PubMed Central

Nollen, Nicole L.; Hutcheson, Tresza; Carlson, Susan; Rapoff, Michael; Goggin, Kathy; Mayfield, Carlene; Ellerbeck, Edward

2013-01-01

Mobile technologies hold promise for improving diet and physical activity, but little attention is given to creating programs that adolescents like and will use. This study developed a personal digital assistant (PDA) program to promote increased intake of fruits and vegetables (FV) in predominately low-income, ethnic minority girls. This study used a three-phase community-engaged process, including (i) engagement of a Student Advisory Board (SAB) to determine comfort with PDAs; (ii) early testing of Prototype I and rapid re-design by the SAB and (iii) feasibility testing of Prototype II in a new sample of girls. Phase 1 results showed that girls were comfortable with the PDA. Testing of Prototype I in Phase 2 showed that acceptability was mixed, with girls responding to 47.3% of the prompts. Girls wanted more reminders, accountability in monitoring FV, help in meeting daily goals and free music downloads based on program use. The PDA was reprogrammed and testing of Prototype II in Phase 3 demonstrated marked improvement in use (78.3%), increases in FV intake (1.8 ± 2.6 daily servings) and good overall satisfaction. Findings suggest that mobile technology designed with the early input of youth is a promising way to improve adolescent health behaviors. PMID:22949499

Developing and Implementing a Marketing Strategy for College Recruiting and Admissions.

ERIC Educational Resources Information Center

Johnson, Mark D.; Gilmour, Joseph E.

Analyzed is the development of marketing strategies at two major universities that have been successful in reversing enrollment declines that they experienced in the early 1970's. First, the organizational context of recruiting and admissions is examined, and the major phases of the admissions calendar are reviewed. Then the application of…

Phase Equilibria and Crystallography of Ceramic Oxides

PubMed Central

Wong-Ng, W.; Roth, R. S.; Vanderah, T. A.; McMurdie, H. F.

2001-01-01

Research in phase equilibria and crystallography has been a tradition in the Ceramics Division at National Bureau of Standards/National Institute of Standatrds and Technology (NBS/NIST) since the early thirties. In the early years, effort was concentrated in areas of Portland cement, ceramic glazes and glasses, instrument bearings, and battery materials. In the past 40 years, a large portion of the work was related to electronic materials, including ferroelectrics, piezoelectrics, ionic conductors, dielectrics, microwave dielectrics, and high-temperature superconductors. As a result of the phase equilibria studies, many new compounds have been discovered. Some of these discoveries have had a significant impact on US industry. Structure determinations of these new phases have often been carried out as a joint effort among NBS/NIST colleagues and also with outside collaborators using both single crystal and neutron and x-ray powder diffraction techniques. All phase equilibria diagrams were included in Phase Diagrams for Ceramists, which are collaborative publications between The American Ceramic Society (ACerS) and NBS/NIST. All x-ray powder diffraction patterns have been included in the Powder Diffraction File (PDF). This article gives a brief account of the history of the development of the phase equilibria and crystallographic research on ceramic oxides in the Ceramics Division. Represented systems, particularly electronic materials, are highlighted. PMID:27500068

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

PubMed

2015-12-01

The development of cancer immunotherapies is progressing rapidly with a variety of technological approaches. They consist of "cancer vaccines", which are based on the idea of vaccination, "effector cell therapy", classified as passive immunotherapy, and "inhibition of immunosuppression", which intends to break immunological tolerance to autoantigens or immunosuppressive environments characterizing antitumor immune responses. Recent reports showing clinical evidence of efficacy of immune checkpoint inhibitors and adoptive immunotherapies with tumor-infiltrating lymphocytes and tumor-specific receptor gene-modified T cells indicate the beginning of a new era for cancer immunotherapy. This guidance summarizes ideas that will be helpful to those who plan to develop cancer immunotherapy. The aims of this guidance are to discuss and offer important points in early phase clinical studies of innovative cancer immunotherapy, with future progress in this field, and to contribute to the effective development of cancer immunotherapy aligned with the scope of regulatory science. This guidance covers cancer vaccines, effector cell therapy, and inhibition of immunosuppression, including immune checkpoint inhibitors. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Resting Heart Rate Predicts Depression and Cognition Early after Ischemic Stroke: A Pilot Study.

PubMed

Tessier, Arnaud; Sibon, Igor; Poli, Mathilde; Audiffren, Michel; Allard, Michèle; Pfeuty, Micha

2017-10-01

Early detection of poststroke depression (PSD) and cognitive impairment (PSCI) remains challenging. It is well documented that the function of autonomic nervous system is associated with depression and cognition. However, their relationship has never been investigated in the early poststroke phase. This pilot study aimed at determining whether resting heart rate (HR) parameters measured in early poststroke phase (1) are associated with early-phase measures of depression and cognition and (2) could be used as new tools for early objective prediction of PSD or PSCI, which could be applicable to patients unable to answer usual questionnaires. Fifty-four patients with first-ever ischemic stroke, without cardiac arrhythmia, were assessed for resting HR and heart rate variability (HRV) within the first week after stroke and for depression and cognition during the first week and at 3 months after stroke. Multiple regression analyses controlled for age, gender, and stroke severity revealed that higher HR, lower HRV, and higher sympathovagal balance (low-frequency/high-frequency ratio of HRV) were associated with higher severity of depressive symptoms within the first week after stroke. Furthermore, higher sympathovagal balance in early phase predicted higher severity of depressive symptoms at the 3-month follow-up, whereas higher HR and lower HRV in early phase predicted lower global cognitive functioning at the 3-month follow-up. Resting HR measurements obtained in early poststroke phase could serve as an objective tool, applicable to patients unable to complete questionnaires, to help in the early prediction of PSD and PSCI. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Vocal Development as a Guide to Modeling the Evolution of Language.

PubMed

Oller, D Kimbrough; Griebel, Ulrike; Warlaumont, Anne S

2016-04-01

Modeling of evolution and development of language has principally utilized mature units of spoken language, phonemes and words, as both targets and inputs. This approach cannot address the earliest phases of development because young infants are unable to produce such language features. We argue that units of early vocal development-protophones and their primitive illocutionary/perlocutionary forces-should be targeted in evolutionary modeling because they suggest likely units of hominin vocalization/communication shortly after the split from the chimpanzee/bonobo lineage, and because early development of spontaneous vocal capability is a logically necessary step toward vocal language, a root capability without which other crucial steps toward vocal language capability are impossible. Modeling of language evolution/development must account for dynamic change in early communicative units of form/function across time. We argue for interactive contributions of sender/infants and receiver/caregivers in a feedback loop involving both development and evolution and propose to begin computational modeling at the hominin break from the primate communicative background. Copyright © 2016 Cognitive Science Society, Inc.

Safety Guided Design Based on Stamp/STPA for Manned Vehicle in Concept Design Phase

NASA Astrophysics Data System (ADS)

Ujiie, Ryo; Katahira, Masafumi; Miyamoto, Yuko; Umeda, Hiroki; Leveson, Nancy; Hoshino, Nobuyuki

2013-09-01

In manned vehicles, such as the Soyuz and the Space Shuttle, the crew and computer system cooperate to succeed in returning to the earth. While computers increase the functionality of system, they also increase the complexity of the interaction between the controllers (human and computer) and the target dynamics. In some cases, the complexity can produce a serious accident. To prevent such losses, traditional hazard analysis such as FTA has been applied to system development, however it can be used after creating a detailed system because it focuses on detailed component failures. As a result, it's more difficult to eliminate hazard cause early in the process when it is most feasible.STAMP/STPA is a new hazard analysis that can be applied from the early development phase, with the analysis being refined as more detailed decisions are made. In essence, the analysis and design decisions are intertwined and go hand-in-hand. We have applied STAMP/STPA to a concept design of a new JAXA manned vehicle and tried safety guided design of the vehicle. As a result of this trial, it has been shown that STAMP/STPA can be accepted easily by system engineers and the design has been made more sophisticated from a safety viewpoint. The result also shows that the consequences of human errors on system safety can be analysed in the early development phase and the system designed to prevent them. Finally, the paper will discuss an effective way to harmonize this safety guided design approach with system engineering process based on the result of this experience in this project.

Space Shuttle External Tank Project status

NASA Technical Reports Server (NTRS)

Davis, R. M.

1980-01-01

The External Tank Project is reviewed with emphasis on the DDT&E and production phases and the lightweight tank development. It is noted that the DDT&E phase is progressing well with the structural and ground vibration test article programs complete, the propulsion test article program progressing well, and the component qualification and verification testing 92% complete. New tools and facilities are being brought on line to support the increased build rate for the production phase. The lightweight tank, which will provide additional payload in orbit, is progressing to schedule with first delivery in early 1982.

σK of Clostridium acetobutylicum Is the First Known Sporulation-Specific Sigma Factor with Two Developmentally Separated Roles, One Early and One Late in Sporulation

PubMed Central

Al-Hinai, Mohab A.; Jones, Shawn W.

2014-01-01

Sporulation in the model endospore-forming organism Bacillus subtilis proceeds via the sequential and stage-specific activation of the sporulation-specific sigma factors, σH (early), σF, σE, σG, and σK (late). Here we show that the Clostridium acetobutylicum σK acts both early, prior to Spo0A expression, and late, past σG activation, thus departing from the B. subtilis model. The C. acetobutylicum sigK deletion (ΔsigK) mutant was unable to sporulate, and solventogenesis, the characteristic stationary-phase phenomenon for this organism, was severely diminished. Transmission electron microscopy demonstrated that the ΔsigK mutant does not develop an asymmetric septum and produces no granulose. Complementation of sigK restored sporulation and solventogenesis to wild-type levels. Spo0A and σG proteins were not detectable by Western analysis, while σF protein levels were significantly reduced in the ΔsigK mutant. spo0A, sigF, sigE, sigG, spoIIE, and adhE1 transcript levels were all downregulated in the ΔsigK mutant, while those of the sigH transcript were unaffected during the exponential and transitional phases of culture. These data show that σK is necessary for sporulation prior to spo0A expression. Plasmid-based expression of spo0A in the ΔsigK mutant from a nonnative promoter restored solventogenesis and the production of Spo0A, σF, σE, and σG, but not sporulation, which was blocked past the σG stage of development, thus demonstrating that σK is also necessary in late sporulation. sigK is expressed very early at low levels in exponential phase but is strongly upregulated during the middle to late stationary phase. This is the first sporulation-specific sigma factor shown to have two developmentally separated roles. PMID:24187083

σK of Clostridium acetobutylicum is the first known sporulation-specific sigma factor with two developmentally separated roles, one early and one late in sporulation.

PubMed

Al-Hinai, Mohab A; Jones, Shawn W; Papoutsakis, Eleftherios T

2014-01-01

Sporulation in the model endospore-forming organism Bacillus subtilis proceeds via the sequential and stage-specific activation of the sporulation-specific sigma factors, σ(H) (early), σ(F), σ(E), σ(G), and σ(K) (late). Here we show that the Clostridium acetobutylicum σ(K) acts both early, prior to Spo0A expression, and late, past σ(G) activation, thus departing from the B. subtilis model. The C. acetobutylicum sigK deletion (ΔsigK) mutant was unable to sporulate, and solventogenesis, the characteristic stationary-phase phenomenon for this organism, was severely diminished. Transmission electron microscopy demonstrated that the ΔsigK mutant does not develop an asymmetric septum and produces no granulose. Complementation of sigK restored sporulation and solventogenesis to wild-type levels. Spo0A and σ(G) proteins were not detectable by Western analysis, while σ(F) protein levels were significantly reduced in the ΔsigK mutant. spo0A, sigF, sigE, sigG, spoIIE, and adhE1 transcript levels were all downregulated in the ΔsigK mutant, while those of the sigH transcript were unaffected during the exponential and transitional phases of culture. These data show that σ(K) is necessary for sporulation prior to spo0A expression. Plasmid-based expression of spo0A in the ΔsigK mutant from a nonnative promoter restored solventogenesis and the production of Spo0A, σ(F), σ(E), and σ(G), but not sporulation, which was blocked past the σ(G) stage of development, thus demonstrating that σ(K) is also necessary in late sporulation. sigK is expressed very early at low levels in exponential phase but is strongly upregulated during the middle to late stationary phase. This is the first sporulation-specific sigma factor shown to have two developmentally separated roles.

Intergrated Systems Biology Approach for Ovarian Cancer Biomarker Discovery — EDRN Public Portal

Cancer.gov

The overall objective is to validate serum protein markers for early diagnosis of ovarian cancer with the ultimate goal being to develop a multiparametric panel consisting of 2-4 novel markers with 10 known markers for phase 3 analysis. In phase 1, we will screen for markers able to pass a threshold of 98% specificity and 30% sensitivity in a cohort of 300 women. Markers that pass phase 1 validation will be investigated in a phase 2 PRoBE cohort with a 98% specificity and 70% sensitivity cut-off. Finally, markers that pass phase 2 validation will be evaluated in EDRN CVC laboratory specimens with a cut-off of > 98% specificity and 90% sensitivity.

Charlotte, North Carolina : IVHS early deployment study : attachment 1

DOT National Transportation Integrated Search

1992-01-30

The North Carolina Department of Transportation has been developing an innovative approach to the phased implementation of state-of- the-art IVHS technologies to address traffic congestion problems in the state of North Carolina. One of the geographi...

Phase III Early Restoration Meeting | NOAA Gulf Spill Restoration

Science.gov Websites

Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News Publications Press Releases Story programmatic approach to early restoration planning for Phase III and future early restoration plans. Open

Phase III Early Restoration Meeting - Corpus Christi, TX | NOAA Gulf Spill

Science.gov Websites

Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News programmatic approach to early restoration planning for Phase III and future early restoration plans. Open

Phase III Early Restoration Meeting - Pensacola, FL (rescheduled) | NOAA

Science.gov Websites

Restoration Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News programmatic approach to early restoration planning for Phase III and future early restoration plans. Open

40 CFR 76.8 - Early election for Group 1, Phase II boilers.

Code of Federal Regulations, 2010 CFR

2010-07-01

... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source at...

40 CFR 76.8 - Early election for Group 1, Phase II boilers.

Code of Federal Regulations, 2014 CFR

2014-07-01

... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source at...

40 CFR 76.8 - Early election for Group 1, Phase II boilers.

Code of Federal Regulations, 2011 CFR

2011-07-01

... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source at...

40 CFR 76.8 - Early election for Group 1, Phase II boilers.

Code of Federal Regulations, 2012 CFR

2012-07-01

... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source at...

40 CFR 76.8 - Early election for Group 1, Phase II boilers.

Code of Federal Regulations, 2013 CFR

2013-07-01

... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source at...

Towards early inclusion of children in tuberculosis drugs trials: a consensus statement.

PubMed

Nachman, Sharon; Ahmed, Amina; Amanullah, Farhana; Becerra, Mercedes C; Botgros, Radu; Brigden, Grania; Browning, Renee; Gardiner, Elizabeth; Hafner, Richard; Hesseling, Anneke; How, Cleotilde; Jean-Philippe, Patrick; Lessem, Erica; Makhene, Mamodikoe; Mbelle, Nontombi; Marais, Ben; McIlleron, Helen; McNeeley, David F; Mendel, Carl; Murray, Stephen; Navarro, Eileen; Anyalechi, E Gloria; Porcalla, Ariel R; Powell, Clydette; Powell, Mair; Rigaud, Mona; Rouzier, Vanessa; Samson, Pearl; Schaaf, H Simon; Shah, Seema; Starke, Jeff; Swaminathan, Soumya; Wobudeya, Eric; Worrell, Carol

2015-06-01

Children younger than 18 years account for a substantial proportion of patients with tuberculosis worldwide. Available treatments for paediatric drug-susceptible and drug-resistant tuberculosis, albeit generally effective, are hampered by high pill burden, long duration of treatment, coexistent toxic effects, and an overall scarcity of suitable child-friendly formulations. Several new drugs and regimens with promising activity against both drug-susceptible and drug-resistant strains have entered clinical development and are either in various phases of clinical investigation or have received marketing authorisation for adults; however, none have data on their use in children. This consensus statement, generated from an international panel of opinion leaders on childhood tuberculosis and incorporating reviews of published literature from January, 2004, to May, 2014, addressed four key questions: what drugs or regimens should be prioritised for clinical trials in children? Which populations of children are high priorities for study? When can phase 1 or 2 studies be initiated in children? What are the relevant elements of clinical trial design? The consensus panel found that children can be included in studies at the early phases of drug development and should be an integral part of the clinical development plan, rather than studied after regulatory approval in adults is obtained. Copyright © 2015 Elsevier Ltd. All rights reserved.

Regulatory/Scientific Supports for Micro-, Small-, and Medium-Sized Enterprises (SMEs) With Medicinal Products Provided by the PMDA and EMA.

PubMed

Kondo, Hideyuki; Shibatsuji, Masayoshi; Yasuda, Naoyuki

2018-01-01

Micro-, small-, and medium-sized enterprises (SMEs) have been considered as key players who can bring innovative medicinal products and/or technologies into the field. However, they may need much regulatory/scientific supports to provide their products, technologies, or services to the market in a timely way. Both the Pharmaceuticals and Medical Devices Agency (PMDA) and the European Medicines Agency (EMA), regulatory authorities for medicinal products in Japan and the EU, respectively, have prepared supportive measures for SMEs from the early phase of product/technology development to the postmarketing phase. With respect to supports for SMEs, both agencies have provided similar SME-specific supportive activities, including routine administrative assistance, consultations about product development strategy from an early phase, as well as specific regulatory/scientific issues and fee incentives. In addition, there is a system to register SME status in the EU, which can be a tool for regulators to know how much potential SME-driven activities have and with whom they should communicate to provide necessary supports. Furthermore, as new technologies and novel products from SMEs are not limited to the region where they are developed, close communication about these topics between the PMDA and the EMA will contribute to advancing patients' access to necessary medicinal products.

Astronomy, New Instrumentation, and the News Media

NASA Technical Reports Server (NTRS)

Maran, Stephen P.

2001-01-01

The early work of Bob Tull who invented a photoelectric spectral scanner comprised a crucial phase in the development of astronomical instrumentation. The relationship between the academic astronomy/astrophysics community and journalists has been in flux since the early 1960s. Scientists should recognize that they rely on the press to disseminate scientific information. Public citizens and policy makers are interested in the pursuits of scientific research for which taxes and other public monies are used.

Phase III Early Restoration Meeting - Lake Charles, LA | NOAA Gulf Spill

Science.gov Websites

Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News early restoration planning for Phase III and future early restoration plans. Open House: 5:30pm Public

Soluble Mesothelin Related Peptide (SMRP) and Osteopontin (OPN) as Early Detection Markers for Malignant Mesothelioma (MM) — EDRN Public Portal

Cancer.gov

Phase I: - Identification and assemblage of representative cohorts of individuals with MM, no malignancies but increased risk for MM due to asbestos exposure, and (optionally) lung malignancies other than MM Phase II (A) - Determine the sensitivity and specificity of SMRP and OPN in distinguishing individuals with a clinical diagnosis of malignant mesothelioma from individuals who are asbestos-exposed but without a clinical diagnosis of malignant mesothelioma. Phase II (B) – Determine the comparability of analyte values across contributing centers and determine covariates that influence analyte levels Phase II (C) – Determine the sensitivity and specificity of SMRP and OPN, alone and in combination, in distinguishing individuals with MM from those without. Phase III. Determine the sensitivity and specificity of SMRP and OPN in distinguishing individuals who would subsequently develop malignant mesothelioma from matched individuals who did not subsequently develop malignant mesothelioma. Phase IV. Determine the sensitivity and specificity of SMRP and OPN in other populations of interest.

Neratinib: First Global Approval.

PubMed

Deeks, Emma D

2017-10-01

Neratinib (Nerlynx™) is an oral, irreversible inhibitor of the human epidermal growth factor receptors HER1 (EGFR), HER2 and HER4. The drug originally arose from research by Wyeth (now Pfizer) and is now being developed by Puma Biotechnology primarily for the treatment of HER2-positive (HER+) breast cancer. Neratinib is approved in the USA for the extended adjuvant treatment of patients with HER2+ early-stage breast cancer who have been previously treated with a trastuzumab-based adjuvant regimen, and is in the preregistration phase for this indication in the EU. Neratinib, as monotherapy and/or combination therapy, is also in phase 3 development for metastatic breast cancer and in phase 1/2 development for advanced breast cancer and other solid tumours, including non-small cell lung cancer, colorectal cancer and glioblastoma. This article summarizes the milestones in the development of neratinib leading to this first approval for breast cancer.

Early repositioning through compound set enrichment analysis: a knowledge-recycling strategy.

PubMed

Temesi, Gergely; Bolgár, Bence; Arany, Adám; Szalai, Csaba; Antal, Péter; Mátyus, Péter

2014-04-01

Despite famous serendipitous drug repositioning success stories, systematic projects have not yet delivered the expected results. However, repositioning technologies are gaining ground in different phases of routine drug development, together with new adaptive strategies. We demonstrate the power of the compound information pool, the ever-growing heterogeneous information repertoire of approved drugs and candidates as an invaluable catalyzer in this transition. Systematic, computational utilization of this information pool for candidates in early phases is an open research problem; we propose a novel application of the enrichment analysis statistical framework for fusion of this information pool, specifically for the prediction of indications. Pharmaceutical consequences are formulated for a systematic and continuous knowledge recycling strategy, utilizing this information pool throughout the drug-discovery pipeline.

Fibroblast growth factor signaling is required for early somatic gonad development in zebrafish.

PubMed

Leerberg, Dena M; Sano, Kaori; Draper, Bruce W

2017-09-01

The vertebrate ovary and testis develop from a sexually indifferent gonad. During early development of the organism, primordial germ cells (the gamete lineage) and somatic gonad cells coalesce and begin to undergo growth and morphogenesis to form this bipotential gonad. Although this aspect of development is requisite for a fertile adult, little is known about the genetic regulation of early gonadogenesis in any vertebrate. Here, we provide evidence that fibroblast growth factor (Fgf) signaling is required for the early growth phase of a vertebrate bipotential gonad. Based on mutational analysis in zebrafish, we show that the Fgf ligand 24 (Fgf24) is required for proliferation, differentiation, and morphogenesis of the early somatic gonad, and as a result, most fgf24 mutants are sterile as adults. Additionally, we describe the ultrastructural elements of the early zebrafish gonad and show that distinct somatic cell populations can be identified soon after the gonad forms. Specifically, we show that fgf24 is expressed in an epithelial population of early somatic gonad cells that surrounds an inner population of mesenchymal somatic gonad cells that are in direct contact with the germ cells, and that fgf24 is required for stratification of the somatic tissue. Furthermore, based on gene expression analysis, we find that differentiation of the inner mesenchymal somatic gonad cells into functional cell types in the larval and early juvenile-stage gonad is dependent on Fgf24 signaling. Finally, we argue that the role of Fgf24 in zebrafish is functionally analogous to the role of tetrapod FGF9 in early gonad development.

Develop a Methodology to Evaluate the Effectiveness of QC/QA Specifications (Phase II)

DOT National Transportation Integrated Search

1998-08-01

The Texas Department of Transportation (TxDOT) has been implementing statistically based quality control/quality assurance (QC/QA) specifications for hot mix asphalt concrete pavements since the early 1990s. These specifications have been continuousl...

Lessons Learned for Planning and Estimating Operations Support Requirements

NASA Technical Reports Server (NTRS)

Newhouse, Marilyn

2011-01-01

Operations (phase E) costs are typically small compared to the spacecraft development and test costs. This, combined with the long lead time for realizing operations costs, can lead projects to focus on hardware development schedules and costs, de-emphasizing estimation of operations support requirements during proposal, early design, and replan cost exercises. The Discovery and New Frontiers (D&NF) programs comprise small, cost-capped missions supporting scientific exploration of the solar system. Even moderate yearly underestimates of the operations costs can present significant LCC impacts for deep space missions with long operational durations, and any LCC growth can directly impact the programs ability to fund new missions. The D&NF Program Office at Marshall Space Flight Center recently studied cost overruns for 7 D&NF missions related to phase C/D development of operational capabilities and phase E mission operations. The goal was to identify the underlying causes for the overruns and develop practical mitigations to assist the D&NF projects in identifying potential operations risks and controlling the associated impacts to operations development and execution costs. The study found that the drivers behind these overruns include overly optimistic assumptions regarding the savings resulting from the use of heritage technology, late development of operations requirements, inadequate planning for sustaining engineering and the special requirements of long duration missions (e.g., knowledge retention and hardware/software refresh), and delayed completion of ground system development work. This presentation summarizes the study and the results, providing a set of lessons NASA can use to improve early estimation and validation of operations costs.

Human Dose-Response Data for Francisella tularensis and a Dose- and Time-Dependent Mathematical Model of Early-Phase Fever Associated with Tularemia After Inhalation Exposure.

PubMed

McClellan, Gene; Coleman, Margaret; Crary, David; Thurman, Alec; Thran, Brandolyn

2018-04-25

Military health risk assessors, medical planners, operational planners, and defense system developers require knowledge of human responses to doses of biothreat agents to support force health protection and chemical, biological, radiological, nuclear (CBRN) defense missions. This article reviews extensive data from 118 human volunteers administered aerosols of the bacterial agent Francisella tularensis, strain Schu S4, which causes tularemia. The data set includes incidence of early-phase febrile illness following administration of well-characterized inhaled doses of F. tularensis. Supplemental data on human body temperature profiles over time available from de-identified case reports is also presented. A unified, logically consistent model of early-phase febrile illness is described as a lognormal dose-response function for febrile illness linked with a stochastic time profile of fever. Three parameters are estimated from the human data to describe the time profile: incubation period or onset time for fever; rise time of fever; and near-maximum body temperature. Inhaled dose-dependence and variability are characterized for each of the three parameters. These parameters enable a stochastic model for the response of an exposed population through incorporation of individual-by-individual variability by drawing random samples from the statistical distributions of these three parameters for each individual. This model provides risk assessors and medical decisionmakers reliable representations of the predicted health impacts of early-phase febrile illness for as long as one week after aerosol exposures of human populations to F. tularensis. © 2018 Society for Risk Analysis.

Developmental Spelling and Word Recognition: A Validation of Ehri's Model of Word Recognition Development

ERIC Educational Resources Information Center

Ebert, Ashlee A.

2009-01-01

Ehri's developmental model of word recognition outlines early reading development that spans from the use of logos to advanced knowledge of oral and written language to read words. Henderson's developmental spelling theory presents stages of word knowledge that progress in a similar manner to Ehri's phases. The purpose of this research study was…

Teacher-Child Relationships as Dynamic Systems

ERIC Educational Resources Information Center

O'Connor, Erin

2010-01-01

The purpose of the present study was to examine factors associated with the quality of the teacher-child relationship from first through fifth grade using data from phases I, II and III of the National Institutes of Child Health and Human Development Study of Early Child Care and Youth Development, a prospective study of 1364 children from birth…

Insights into early stage of antibiotic development in small- and medium-sized enterprises: a survey of targets, costs, and durations.

PubMed

Årdal, Christine; Baraldi, Enrico; Theuretzbacher, Ursula; Outterson, Kevin; Plahte, Jens; Ciabuschi, Francesco; Røttingen, John-Arne

2018-01-01

Antibiotic innovation has dwindled to dangerously low levels in the past 30 years. Since resistance continues to evolve, this innovation deficit can have perilous consequences on patients. A number of new incentives have been suggested to stimulate greater antibacterial drug innovation. To design effective solutions, a greater understanding is needed of actual antibiotic discovery and development costs and timelines. Small and medium-sized enterprises (SMEs) undertake most discovery and early phase development for antibiotics and other drugs. This paper attempts to gather a better understanding of SMEs' targets, costs, and durations related to discovery and early phase development of antibacterial therapies. DRIVE-AB, a project focused on developing new economic incentives to stimulate antibacterial innovation, held a European stakeholder meeting in February 2015. All SMEs invited to this meeting ( n  = 44) were subsequently sent a survey to gather more data regarding their areas of activity, completed and expected development costs and timelines, and business models. Twenty-five companies responded to the survey. Respondents were primarily small companies each focusing on developing 1 to 3 new antibiotics, focused on pathogens of public health importance. Most have not yet completed any clinical trials. They have reported ranges of discovery and development out-of-pocket costs that appear to be less expensive than other studies of general pharmaceutical research and development (R&D) costs. The duration ranges reported for completing each phase of R&D are highly variable when compared to previously published general pharmaceutical innovation average durations. However, our sample population is small and may not be fully representative of all relevant antibiotic SMEs. The data collected by this study provide important insights and estimates about R&D in European SMEs focusing on antibiotics, which can be combined with other data to design incentives to stimulate antibacterial innovation. The variation implies that costs and durations are difficult to generalize due to the unique characteristics of each antibiotic project and depend on individual business strategies and circumstances.

Interdyad differences in early mother-infant face-to-face communication: real-time dynamics and developmental pathways.

PubMed

Lavelli, Manuela; Fogel, Alan

2013-12-01

A microgenetic research design with a multiple case study method and a combination of quantitative and qualitative analyses was used to investigate interdyad differences in real-time dynamics and developmental change processes in mother-infant face-to-face communication over the first 3 months of life. Weekly observations of 24 mother-infant dyads with analyses performed dyad by dyad showed that most dyads go through 2 qualitatively different developmental phases of early face-to-face communication: After a phase of mutual attentiveness, mutual engagement begins in Weeks 7-8, with infant smiling and cooing bidirectionally linked with maternal mirroring. This gives rise to sequences of positive feedback that, by the 3rd month, dynamically stabilizes into innovative play routines. However, when there is a lack of bidirectional positive feedback between infant and maternal behaviors, and a lack of permeability of the early communicative patterns to incorporate innovations, the development of the mutual engagement phase is compromised. The findings contribute both to theories of relationship change processes and to clinical work with at-risk mother-infant interactions. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Future Directions for the Early Detection of Colorectal Cancer Recurrence

PubMed Central

Walker, Avery S.; Johnson, Eric K.; Maykel, Justin A.; Stojadinovic, Alex; Nissan, Aviram; Brucher, Bjorn; Champagne, Bradley J.; Steele, Scott R.

2014-01-01

Surgical resection remains a mainstay of treatment and is highly effective for localized colorectal cancer. However, ~30-40% of patients develop recurrence following surgery and 40-50% of recurrences are apparent within the first few years after initial surgical resection. Several variables factor into the ultimate outcome of these patients, including the extent of disease, tumor biology, and patient co-morbidities. Additionally, the time from initial treatment to the development of recurrence is strongly associated with overall survival, particularly in patients who recur within one year of their surgical resection. Current post-resection surveillance strategies involve physical examination, laboratory, endoscopic and imaging studies utilizing various high and low-intensity protocols. Ultimately, the goal is to detect recurrence as early as possible, and ideally in the asymptomatic localized phase, to allow initiation of treatment that may still result in cure. While current strategies have been effective, several efforts are evolving to improve our ability to identify recurrent disease at its earliest phase. Our aim with this article is to briefly review the options available and, more importantly, examine emerging and future options to assist in the early detection of colon and rectal cancer recurrence. PMID:24790655

Polo-like kinase 1 is essential for early embryonic development and tumor suppression.

PubMed

Lu, Lin-Yu; Wood, Jamie L; Minter-Dykhouse, Katherine; Ye, Lin; Saunders, Thomas L; Yu, Xiaochun; Chen, Junjie

2008-11-01

Polo-like kinases (Plks) are serine/threonine kinases that are highly conserved in organisms from yeasts to humans. Previous reports have shown that Plk1 is critical for all stages of mitosis and may play a role in DNA replication during S phase. While much work has focused on Plk1, little is known about the physiological function of Plk1 in vivo. To address this question, we generated Plk1 knockout mice. Plk1 homozygous null mice were embryonic lethal, and early Plk1(-/-) embryos failed to survive after the eight-cell stage. Immunocytochemistry studies revealed that Plk1-null embryos were arrested outside the mitotic phase, suggesting that Plk1 is important for proper cell cycle progression. It has been postulated that Plk1 is a potential oncogene, due to its overexpression in a variety of tumors and tumor cell lines. While the Plk1 heterozygotes were healthy at birth, the incidence of tumors in these animals was threefold greater than that in their wild-type counterparts, demonstrating that the loss of one Plk1 allele accelerates tumor formation. Collectively, our data support that Plk1 is important for early embryonic development and may function as a haploinsufficient tumor suppressor.

How Supervisor Experience Influences Trust, Supervision, and Trainee Learning: A Qualitative Study.

PubMed

Sheu, Leslie; Kogan, Jennifer R; Hauer, Karen E

2017-09-01

Appropriate trust and supervision facilitate trainees' growth toward unsupervised practice. The authors investigated how supervisor experience influences trust, supervision, and subsequently trainee learning. In a two-phase qualitative inductive content analysis, phase one entailed reviewing 44 internal medicine resident and attending supervisor interviews from two institutions (July 2013 to September 2014) for themes on how supervisor experience influences trust and supervision. Three supervisor exemplars (early, developing, experienced) were developed and shared in phase two focus groups at a single institution, wherein 23 trainees validated the exemplars and discussed how each impacted learning (November 2015). Phase one: Four domains of trust and supervision varying with experience emerged: data, approach, perspective, clinical. Early supervisors were detail oriented and determined trust depending on task completion (data), were rule based (approach), drew on their experiences as trainees to guide supervision (perspective), and felt less confident clinically compared with more experienced supervisors (clinical). Experienced supervisors determined trust holistically (data), checked key aspects of patient care selectively and covertly (approach), reflected on individual experiences supervising (perspective), and felt comfortable managing clinical problems and gauging trainee abilities (clinical). Phase two: Trainees felt the exemplars reflected their experiences, described their preferences and learning needs shifting over time, and emphasized the importance of supervisor flexibility to match their learning needs. With experience, supervisors differ in their approach to trust and supervision. Supervisors need to trust themselves before being able to trust others. Trainees perceive these differences and seek supervision approaches that align with their learning needs.

Paleoclimatic analyses of middle Eocene through Oligocene planktic foraminiferal faunas

USGS Publications Warehouse

Keller, G.

1983-01-01

Quantitative faunal analyses and oxygen isotope ranking of individual planktic foraminiferal species from deep sea sequences of three oceans are used to make paleoceanographic and paleoclimatic inferences. Species grouped into surface, intermediate and deep water categories based on ??18O values provide evidence of major changes in water-mass stratification, and individual species abundances indicate low frequency cool-warm oscillations. These data suggest that relatively stable climatic phases with minor cool-warm oscillations of ???0.5 m.y. frequency are separated by rapid cooling events during middle Eocene to early Oligocene time. Five major climatic phases are evident in the water-mass stratification between middle Eocene through Oligocene time. Phase changes occur at P14/P15, P15/P16, P20/P21 and P21/P22 Zone boundaries and are marked by major faunal turnovers, rapid cooling in the isotope record, hiatuses and changes in the eustatic sea level. A general cooling trend between middle Eocene to early late Oligocene is indicated by the successive replacement of warm middle Eocene surface water species by cooler late Eocene intermediate water species and still cooler Oligocene intermediate and deep water species. Increased water-mass stratification in the latest Eocene (P17), indicated by the coexistence of surface, intermediate and deep dwelling species groups, suggest that increased thermal gradients developed between the equator and poles nearly coincident with the development of the psychrosphere. This pattern may be related to significant ice accumulation between late Eocene and early late Oligocene time. ?? 1983.

Systems-Oriented Workplace Learning Experiences for Early Learners: Three Models.

PubMed

O'Brien, Bridget C; Bachhuber, Melissa R; Teherani, Arianne; Iker, Theresa M; Batt, Joanne; O'Sullivan, Patricia S

2017-05-01

Early workplace learning experiences may be effective for learning systems-based practice. This study explores systems-oriented workplace learning experiences (SOWLEs) for early learners to suggest a framework for their development. The authors used a two-phase qualitative case study design. In Phase 1 (spring 2014), they prepared case write-ups based on transcribed interviews from 10 SOWLE leaders at the authors' institution and, through comparative analysis of cases, identified three SOWLE models. In Phase 2 (summer 2014), studying seven 8-week SOWLE pilots, the authors used interview and observational data collected from the seven participating medical students, two pharmacy students, and site leaders to construct case write-ups of each pilot and to verify and elaborate the models. In Model 1, students performed specific patient care activities that addressed a system gap. Some site leaders helped students connect the activities to larger systems problems and potential improvements. In Model 2, students participated in predetermined systems improvement (SI) projects, gaining experience in the improvement process. Site leaders had experience in SI and often had significant roles in the projects. In Model 3, students worked with key stakeholders to develop a project and conduct a small test of change. They experienced most elements of an improvement cycle. Site leaders often had experience with SI and knew how to guide and support students' learning. Each model could offer systems-oriented learning opportunities provided that key elements are in place including site leaders facile in SI concepts and able to guide students in SOWLE activities.

The conceptual framework of evolutionary morphology in the studies of Ernst Haeckel and Fritz Müller.

PubMed

Breidbach, Olaf

2006-03-01

In his Gastraea studies Ernst Haeckel characterized the initial stages of the animal embryo, describing complete and incomplete cleavages in various groups, until the gastrula stage. Thereby, he was able to point out various degrees of developmental diversification in these initial stages of development. As the functional meaning of such cleavages was not clear however, it was difficult to argue about putative functional adaptations. Information about the consequences for tissue formation initiated in this primary phase of development was simply lacking. Haeckel could only provide a vague picture of a highly diversified but systematically inconsistent distribution of various types of early embryogenesis. Thereby he discusses phylogenetically preserved (palingenetic) stages of development and adaptations to certain specific situations of the embryo (cenogenesis). To decide whether such types, in the initial stages of embryogenesis, are ceno- or phaenogenetic is quite difficult. Reference to the highly diversified distribution of certain types within specific groups is an indication that there is no strict adaptive pressure on these early parts of embryonic development. This makes it possible to formulate - as Haeckel did it - the idea, that in these initial phases palingenetic attributes are dominant. Thus, he tried to use these early phases of development for the classification of larger systematic units. The result is a concept of an evolutionary morphology, that was, however, never elaborated in detail by Haeckel. Therefore, it remained without effect for evolutionary biology. On the contrary, following the Darwinian approach towards a comparative analysis of embryogenesis, Fritz Müller presented a series of examples for a comparative developmental biology that allowed one to interpret certain morphological characteristics as the outcome of common evolutionary histories within different species. For various crustacean species, he was able to demonstrate that certain attributes are not to be characterized as functionally relevant adaptations, but are evolutionarily inherited.

The role of audition in early psychic development, with special reference to the use of the pull-toy in the separation-individuation phase.

PubMed

Shopper, M

1978-01-01

The role of audition as an important perceptual modality in early psychic development has been neglected. Some reasons for this neglect are suggested. In the development of psychoanalytic technique, the analyst has changed from a "tactile presence" to a "visual presence," then finally, with the analyst positioning himself behind the couch, to an "auditory presence." Several clinical examples from analytic patients as well as child development in normal and deaf children provide instances of each type of perceptual "presence." It is suggested that, in evaluating analyzability, analysis requires a specific ego ability, namely, tolerance for the analyst as an "auditory presence." It is emphasized that some patients, for reasons of development, constitution, and/or significant stress (separation), cannot work with the analyst as an "auditory presence," but regress to the analyst as a "visual" or "tactile" presence. The importance of audition in early mother/stranger differentiations, and in the peek-a-boo game, is a developmental precursor to the use of audition as a contact modality in the separation and individuation phase. Audition permits active locomotion and separation from tactile and visual contact modalities between toddler and mother, while at the same time maintaining contact via their respective "auditory presence" for each other. The utilization of the pull-toy in mastering the conflicts of the separation-individuation phase is demonstrated. The pull-toy is heir to the teddy bear and ancestor to the tricycle. Greater attentiveness to the auditory perceptual modality may help us understand developmental phenomenon, better evaluate the potential analysand, and clarify clinical problems of audition occurring in dreams and those areas of psychopathology having to do with auditory phenomena. The more refined tripartite conept of "presence" as it relates to the predominant perceptual modality--tactile, visual, auditory--is felt to be a useful conceptualization for both developmental and clinical understanding.

Tumor shrinkage and objective response rates: gold standard for oncology efficacy screening trials, or an outdated end point?

PubMed

Bradbury, Penelope; Seymour, Lesley

2009-01-01

Phase II clinical trials have long been used to screen new cancer therapeutics for antitumor activity ("efficacy") worthy of further evaluation. Traditionally, the primary end point used in these screening trials has been objective response rate (RR), with the desired rate being arbitrarily set by the researchers before initiation of the trial. For cytotoxic agents, especially in common tumor types, response has been a reasonably robust and validated surrogate of benefit. Phase II trials with response as an end point have a modest sample size (15-40 patients) and are completed rapidly allowing early decisions regarding future development of a given agent. More recently, a number of new agents have proven successful in pivotal phase III studies, despite a low or very modest RR demonstrated in early clinical trials. Researchers have postulated that these novel agents, as a class, may not induce significant regression of tumors, and that the use of RR as an end point for phase II studies will result in false negative results, and point out that not all available data is used in making the decision. Others have pointed out that even novel agents have proven unsuccessful in pivotal trials if objective responses are not demonstrated in early clinical trials. We review here the historical and current information regarding objective tumor response.

Early Intervention of Didang Decoction on MLCK Signaling Pathways in Vascular Endothelial Cells of Type 2 Diabetic Rats

PubMed Central

Song, Zhenqiang; Li, Jing; Li, Chunshen

2016-01-01

In the study, type 2 diabetic rat model was established using streptozotocin (STZ) combined with a high-fat diet, and the rats were divided into control and diabetic groups. Diabetic groups were further divided into nonintervening, simvastatin, Didang Decoction (DDD) early-phase intervening, DDD mid-phase intervening, and DDD late-phase intervening groups. The expression level of MLCK was detected using Western Blot analysis, and the levels of cyclic adenosine monophosphate (cAMP), protein kinase C (PKC), and protein kinase A (PKA) were examined using Real Time PCR. Under the electron microscope, the cells in the early-DDD-intervention group and the simvastatin group were significantly more continuous and compact than those in the diabetic group. Compared with the control group, the expression of cAMP-1 and PKA was decreased in all diabetic groups, whereas the expression of MLCK and PKC was increased in early- and mid-phase DDD-intervening groups (P < 0.05); compared with the late-phase DDD-intervening group, the expression of cAMP-1 and PKA was higher, but the level of MLCK and PKC was lower in early-phase DDD-intervening group (P < 0.05). In conclusion, the early use of DDD improves the permeability of vascular endothelial cells by regulating the MLCK signaling pathway. PMID:27703477

Emotion Comprehension: The Impact of Nonverbal Intelligence

ERIC Educational Resources Information Center

Albanese, Ottavia; De Stasio, Simona; Di Chiacchio, Carlo; Fiorilli, Caterina; Pons, Francisco

2010-01-01

A substantial body of research has established that emotion understanding develops throughout early childhood and has identified three hierarchical developmental phases: external, mental, and reflexive. The authors analyzed nonverbal intelligence and its effect on children's improvement of emotion understanding and hypothesized that cognitive…

A Two-Phase Approach to Developing SNAP: an iPhone Application to Support Appointment Scheduling and Management for Women with a BRCA Mutation.

PubMed

Scherr, Courtney Lynam; Feuston, Jessica L; Nixon, Dawn M; Cohen, Stephanie A

2018-04-01

Professional organizations provide surveillance guidelines for BRCA1 and BRCA2 (BRCA) carriers with intact breasts and/or ovaries to facilitate early cancer detection. However, literature indicates adherence to surveillance guidelines is inconsistent at best. Using the Messaging Model for Health Communication Campaigns framework, we undertook a two-phase formative research approach to develop an intervention to promote adherence to surveillance guidelines. Discussion groups identified preferred intervention format and function in phase I. Findings indicated carriers desired a phone application (app) to assist with surveillance management and appointment tracking. Thus, an iPhone app for carriers to track appointments based on published surveillance guidelines was developed. In phase II, we obtained feedback from BRCA carriers via a survey during a prototype demonstration at a regional conference. Participants in phase II wanted reminder capabilities and the ability to add and modify information fields. This feedback informed intervention modifications, resulting in the Scheduling Necessary Advised Procedures (SNAP) iPhone app currently being pilot tested by BRCA carriers throughout the USA.

[Curriculum analysis and comparison between strategies or programs for early child development in Mexico].

PubMed

Vargas-López, Guillermo; Guadarrama-Orozco, Jessica Haydee; Rizzoli-Córdoba, Antonio; Narcizo-Cenobio, Francisco Javier; Medrano-Loera, Gerónimo; Villagrán, Daniel Aceves; O'Shea Cuevas, Gabriel; Muñoz Hernández, Onofre

Most of the strategies or programs that support early child development in Mexico are independent efforts that vary in scale, services offered and means of providing them. For the evaluation of the quality of these programs, an important aspect is the curriculum content. The aim of this study was to analyze and compare the curriculum content of the different strategies or programs focused on the promotion and intervention of early child development, which are offered by the Federal Government in Health and Education sectors in Mexico. We conducted a review of the curriculum content of the strategies and programs. The qualitative phase consisted of a comparative analysis where 75 indicators proposed by the Inter-American Development Bank were identified. The quantitative phase consisted of a descriptive analysis of the indicators. Finally, the analyses were compared to establish the performance of each one. Six strategies or programs were identified. In the analysis of the presence of indicators, the Oportunidades de Aprendizaje (Learning Opportunities, LO) strategy showed a larger number of indicators. In the amplitude analysis, both PEI-CONAFE and LO were the best balanced. Finally, in-depth analysis of the indicators LO and Skills for life were the best balanced while PEI-CONAFE was the best balanced in the social-emotional area, CeNSIA program for language and LO for cognitive development area. LO strategy showed the closest level of contents established by the Inter-American Development Bank. Copyright © 2016 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

[Advances in the pathophysiology and management of infections in the acute phase of stroke].

PubMed

Salat, David; Campos, Mireia; Montaner, Joan

2012-12-15

Infection in the acute phase of stroke has been identified as an independent predictor of poor outcome, both in the short and intermediate term. Various factors raising the risk of developing an infection (exposure to multiple pathogens, disruption of the protective function of the mucous membranes and a state of relative immunosuppression) coexist during the acute phase of stroke. Several risk factors have been identified for their development (especially increasing age and stroke severity). It has been proposed that infection contributes to a worse prognosis through different mechanisms, notably the development of an inflammatory response to brain tissue (with a potential to add secondary damage to that caused by the ischemic insult). Clinical trials evaluating the prophylactic and early administration of antibiotics to reduce the incidence of infection in the acute phase of stroke have yielded inconsistent results. Immunomodulating strategies, which may provide therapeutic alternatives in the future, are currently being evaluated. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Early marijuana initiation: The link between prenatal marijuana exposure, early childhood behavior, and negative adult roles.

PubMed

Goldschmidt, Lidush; Richardson, Gale A; Larkby, Cynthia; Day, Nancy L

We investigated the associations among gestational factors including prenatal marijuana exposure (PME), child behavior at age 3, early age of onset of marijuana use (EAOM, <15years), and adult roles at 22years. Participants were drawn from the Maternal Health Practices and Child Development (MHPCD) Project, a longitudinal study of prenatal substance exposure in offspring who have been studied for over 22years since the prenatal phase. Data from the prenatal, birth, 3-, and 22-year phases (N=608) were used in the present study. Age of onset of offspring substance use was determined based on data from the 14-, 16-, and 22-year phases. The subjects were of lower socioeconomic status, 43% were Caucasian and the remaining were African-American, and 48% were males. Early childhood behavior was significantly (p<0.05) related to EAOM after controlling for PME, birth and childhood environmental risk factors, and Conduct Disorder. EAOM was significantly associated with negative adult roles including increased risk of being arrested (p<0.001), lower educational attainment (p<0.001), having a child without being married (p<0.05), and unemployment at 22years (p<0.001). The correlations between PME and negative adult roles and between early childhood behavior and negative adult roles were also statistically significant. Pathway analysis demonstrated that EAOM significantly mediated the associations between PME and fulfillment of adult roles and between early childhood behavior and adult roles. There are a number of intervention points that could be targeted that would have a long-term impact on lowering the probability of EAOM and less success in adult roles. Copyright © 2016 Elsevier Inc. All rights reserved.

Skin manifestations in sulfur mustard exposed victims with ophthalmologic complications: Association between early and late phase.

PubMed

Hejazi, Somayeh; Soroush, Mohammadreza; Moradi, Ahmad; Khalilazar, Sara; Mousavi, Batool; Firooz, Alireza; Younespour, Shima

2016-01-01

Sulfur mustard (SM) was used during the Iraq-Iran war (1980-1988). Exposed veterans continue to suffer from its ocular, skin, and respiratory complications. We aimed to evaluate associations between early (at the time of acute exposure) and decades later skin manifestations in individuals with severe ophthalmologic complications secondary to sulfur mustard exposure. One hundred forty-nine veterans with severe ocular injuries were evaluated for acute and chronic skin complications. Logistic regression models were used to examine the associations between early and late skin manifestations. Late skin complaints were observed in nearly all survivors who had early skin lesions (131 out of 137; 95.62%). Seven out of 12 patients (58.33%) who did not have early skin lesions ultimately developed late skin complications. There was a significant relationship between the presence of lesions at the time of exposure and developing late skin complaints (two-sided Fisher's exact test, OR = 15.59, p < 0.001). There was an association between having at least one early skin lesion and occurrence of late skin complications. Survivors with blisters at the time of chemical exposure were more likely to complain of itching (95% CI: 3.63-25.97, p < 0.001), burning (OR = 11.16; 95% CI: 2.97-41.89, p < 0.001), pigmentation changes (OR = 10.17; 95% CI: 2.54-40.75, p = 0.001), dryness (OR = 6.71, 95% CI: 1.22-37.01, p = 0.03) or cherry angioma (OR = 2.59; 95% CI:1.21-5.55, p = 0.01) during the late phase. Using multivariate logistic models, early blisters remained significantly associated with latent skin complaints. Of note, the genitalia and great flexure areas were the most involved anatomical sites for both early and late skin lesions in SM exposed survivors. According to this study, the presence of blisters at the time of exposure to SM is the most important predictor of developing dermatologic complications decades later in patients with severe ophthalmologic complications from sulfur mustard exposure.

A Validation of Object-Oriented Design Metrics as Quality Indicators

NASA Technical Reports Server (NTRS)

Basili, Victor R.; Briand, Lionel C.; Melo, Walcelio

1997-01-01

This paper presents the results of a study in which we empirically investigated the suits of object-oriented (00) design metrics introduced in another work. More specifically, our goal is to assess these metrics as predictors of fault-prone classes and, therefore, determine whether they can be used as early quality indicators. This study is complementary to the work described where the same suite of metrics had been used to assess frequencies of maintenance changes to classes. To perform our validation accurately, we collected data on the development of eight medium-sized information management systems based on identical requirements. All eight projects were developed using a sequential life cycle model, a well-known 00 analysis/design method and the C++ programming language. Based on empirical and quantitative analysis, the advantages and drawbacks of these 00 metrics are discussed. Several of Chidamber and Kamerer's 00 metrics appear to be useful to predict class fault-proneness during the early phases of the life-cycle. Also, on our data set, they are better predictors than 'traditional' code metrics, which can only be collected at a later phase of the software development processes.

Temporal Control of Plant Organ Growth by TCP Transcription Factors.

PubMed

Huang, Tengbo; Irish, Vivian F

2015-06-29

The Arabidopsis petal is a simple laminar organ whose development is largely impervious to environmental effects, making it an excellent model for dissecting the regulation of cell-cycle progression and post-mitotic cell expansion that together sculpt organ form. Arabidopsis petals grow via basipetal waves of cell division, followed by a phase of cell expansion. RABBIT EARS (RBE) encodes a C2H2 zinc finger transcriptional repressor and is required for petal development. During the early phase of petal initiation, RBE regulates a microRNA164-dependent pathway that controls cell proliferation at the petal primordium boundaries. The effects of rbe mutations on petal lamina growth suggest that RBE is also required to regulate later developmental events during petal organogenesis. Here, we demonstrate that, early in petal development, RBE represses the transcription of a suite of CIN-TCP genes that in turn act to inhibit the number and duration of cell divisions; the temporal alleviation of that repression results in the transition from cell division to post-mitotic cell expansion and concomitant petal maturation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Early Program Development

NASA Image and Video Library

1970-01-01

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

Diel variation in fig volatiles across syconium development: making sense of scents.

PubMed

Borges, Renee M; Bessière, Jean-Marie; Ranganathan, Yuvaraj

2013-05-01

Plants produce volatile organic compounds (VOCs) in a variety of contexts that include response to abiotic and biotic stresses, attraction of pollinators and parasitoids, and repulsion of herbivores. Some of these VOCs may also exhibit diel variation in emission. In Ficus racemosa, we examined variation in VOCs released by fig syconia throughout syconium development and between day and night. Syconia are globular enclosed inflorescences that serve as developing nurseries for pollinating and parasitic fig wasps. Syconia are attacked by gallers early in their development, serviced by pollinators in mid phase, and are attractive to parasitoids in response to the development of gallers at later stages. VOC bouquets of the different development phases of the syconium were distinctive, as were their day and night VOC profiles. VOCs such as α-muurolene were characteristic of the pollen-receptive diurnal phase, and may serve to attract the diurnally-active pollinating wasps. Diel patterns of release of volatiles could not be correlated with their predicted volatility as determined by Henry's law constants at ambient temperatures. Therefore, factors other than Henry's law constant such as stomatal conductance or VOC synthesis must explain diel variation in VOC emission. A novel use of weighted gene co-expression network analysis (WGCNA) on the volatilome resulted in seven distinct modules of co-emitted VOCs that could be interpreted on the basis of syconium ecology. Some modules were characterized by the response of fig syconia to early galling by parasitic wasps and consisted largely of green leaf volatiles (GLVs). Other modules, that could be characterized by a combination of syconia response to oviposition and tissue feeding by larvae of herbivorous galler pollinators as well as of parasitized wasps, consisted largely of putative herbivore-induced plant volatiles (HIPVs). We demonstrated the usefulness of WGCNA analysis of the volatilome in making sense of the scents produced by the syconia at different stages and diel phases of their development.

Early Detection of Amyloid Plaque in Alzheimer’s Disease Via X-ray Phase CT

DTIC Science & Technology

2015-06-01

medical imaging, and eight (8) papers published in leading international conferences. 15. SUBJECT TERMS Alzheimer disease, Amyloid plaque, X-ray phase...11 4 Introduction A. Overall: As the elderly population increases, dementia caused by Alzheimer’s disease (AD) has become a major...with an emphasis on improving the performance of G1 and G2, and the development of algorithmic solutions to deal with the issue caused by the

Influence of Composition and Process Selection on Densification of Silicon Nitride.

DTIC Science & Technology

1982-05-01

9 Accession For NTIS -GRA&I DTIC TAB F] Unannounced 0 Justificatio, Distribution/ Availability Codes Avail and/or Dist 1 Spec ial NI ...concerned with microstructural development and its influence on resultant properties of Si3 N4. Since the early observation that high alpha phase starting...pressed Si3N4 . Knoch and Gazza (2) subsequently investigated the influence of Si3 N4 starting powders with different alpha/beta phase content on the

Current clinical irrelevance of luteal phase deficiency: a committee opinion.

PubMed

2015-04-01

Luteal phase deficiency (LPD) has been described in healthy normally menstruating women and in association with other medical conditions. Although progesterone is important for the process of implantation and early embryonic development, LPD, as an independent entity causing infertility, has not been proven. This document replaces the document by the same name, last published in 2012 (Fertil Steril 2012;98:1112-7). Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Assessing the duration of drowning episodes during the Early Cretaceous

NASA Astrophysics Data System (ADS)

Godet, A.; Föllmi, K. B.

2013-12-01

Drowning unconformities are stratigraphic key surfaces in the history of carbonate platforms. They mostly consist in the deposition of deep marine facies on top of shallow marine limestones. Although large-scale depositional geometries mimic lowstand systems track architecture, these sedimentary turnovers are developed in relation with major sea level rise, inducing an increase in the rate of creation of accommodation space that outpaces the capacity of carbonate to keep up. This so-called paradox of carbonate platform drowning implies that other parameters than purely eustatic fluctuations are involved in the demise of shallow marine ecosystems. Worldwide and at different time during Earth history, in-depth studies of drowning unconformities revealed that changes in nutrient input, clastic delivery, temperature, or a combination of them may be responsible for a decrease in light penetration in the water column and the progressive suffocation and poisoning of photosynthetic carbonate producers. The examination of such case examples from various stratigraphic intervals and palaeogeographical settings thus helps in identifying and hierarchizing potential triggering mechanisms for drowning unconformities. This is complemented by new data from Early Cretaceous successions from the Helvetic Alps. During this time period, the Helvetic carbonate platform developed along the northern Tethyan margin using both photozoan and heterozoan communities. Phases of healthy production were interrupted by several drowning episodes. The latter are marked in the sedimentary record by condensation and associated phosphogenesis and glauconitisation. From the earliest Valanginian to the early to late Barremian, three drowning unconformities reflect the intermittent installation of a more humid climate and subsequent enhanced trophic conditions, which first induced a switch from photozoan to heterozoan communities and then to long-lasting drowning phases. The latter encompass several sea level rise and fall cycles, and may be linked to strengthened upwelling currents. Moreover during the late Hauterivian - early Barremian time period, the correlation of platform carbonates with basinal sediments, by means of bio-, chemo- and sequence stratigraphy, allows to estimate the duration of a drowning episode. With the return to more oligotrophic conditions during the late Barremian, photozoan, Urgonian-type communities took up again. Their development has been abruptly stopped at the end of the early Aptian by a major emersion phase. The subsequent drowning is documented in various peritethyan areas. This initial crisis is followed by three other drowning phases that ultimately led to the replacement of shallow ecosystems by a deeper marine sedimentation in the Cenomanian. This long-term trend in the evolution of the Helvetic carbonate platform and of other peritethyan ecosystems may have been driven by more global phenomena.

A three-dimensional simulation of transition and early turbulence in a time-developing mixing layer

NASA Technical Reports Server (NTRS)

Cain, A. B.; Reynolds, W. C.; Ferziger, J. H.

1981-01-01

The physics of the transition and early turbulence regimes in the time developing mixing layer was investigated. The sensitivity of the mixing layer to the disturbance field of the initial condition is considered. The growth of the momentum thickness, the mean velocity profile, the turbulence kinetic energy, the Reynolds stresses, the anisotropy tensor, and particle track pictures of computations are all examined in an effort to better understand the physics of these regimes. The amplitude, spectrum shape, and random phases of the initial disturbance field were varied. A scheme of generating discrete orthogonal function expansions on some nonuniform grids was developed. All cases address the early or near field of the mixing layer. The most significant result shows that the secondary instability of the mixing layer is produced by spanwise variations in the straining field of the primary vortex structures.

Development of an internet version of the Lidcombe Program of early stuttering intervention: A trial of Part 1.

PubMed

Van Eerdenbrugh, Sabine; Packman, Ann; Onslow, Mark; O'brian, Sue; Menzies, Ross

2018-04-01

There is evidence that access to treatment for early stuttering is not available for all who need it. An internet version of the Lidcombe Program for early stuttering (Internet-LP) has been developed to deal with this shortfall. The LP is suitable for such development because it is delivered by parents in the child's everyday environment, with training by a speech-language pathologist. A Phase I trial of Internet-LP Part 1, comprising parent training, is reported here. Eight parents of pre-schoolers who stutter were recruited and six completed the trial. Post-trial assessment indicated that the parents scored well for identifying and measuring stuttering and for knowledge about conducting practice sessions, including how to present verbal contingencies during practice sessions. The results prompted minor adjustments to Part 1 and guided the construction of Part 2, which instructs parents during the remainder of the treatment process.

Hypersonic code efficiency and validation studies

NASA Technical Reports Server (NTRS)

Bennett, Bradford C.

1992-01-01

Renewed interest in hypersonic and supersonic flows spurred the development of the Compressible Navier-Stokes (CNS) code. Originally developed for external flows, CNS was modified to enable it to also be applied to internal high speed flows. In the initial phase of this study CNS was applied to both internal flow applications and fellow researchers were taught to run CNS. The second phase of this research was the development of surface grids over various aircraft configurations for the High Speed Research Program (HSRP). The complex nature of these configurations required the development of improved surface grid generation techniques. A significant portion of the grid generation effort was devoted to testing and recommending modifications to early versions of the S3D surface grid generation code.

Determination of the Elasticity of Breast Tissue during the Menstrual Cycle Using Real-Time Shear Wave Elastography.

PubMed

Li, Xiang; Wang, Jian-Nan; Fan, Zhi-Ying; Kang, Shu; Liu, Yan-Jun; Zhang, Yi-Xia; Wang, Xue-Mei

2015-12-01

We examined breast tissue elasticity during the menstrual cycle using real-time shear wave elastography (RT-SWE), a recent technique developed for soft tissue imaging. Written informed consent for RT-SWE was obtained from all eligible patients, who were healthy women aged between 19 and 52 y. Young's moduli of the breast tissue in the early follicular, late phase and luteal phase were compared. There were no significant differences in the mean, maximum and minimum elasticity values (Emean, Emax and Emin) and standard deviation (ESD). RT-SWE of glandular tissue revealed that ESD was increased in the early follicular phase compared with the luteal phase. Means ± SD of Emin, Emax and Emean in glandular tissue were 5.174 ± 2.138, 8.308 ± 3.166 and 6.593 ± 2.510, respectively, and in adipose tissue, 3.589 ± 2.083, 6.733 ± 3.522 and 4.857 ± 2.564, respectively. There were no significant differences in stiffness between glandular and adipose tissues throughout the menstrual cycle, but glandular tissue stiffness was lower in the luteal phase than in the early follicular phase. On the basis of these observations in normal healthy women, we believe we have obtained sufficient information to establish the baseline changes in human breast elasticity during the menstrual cycle. In the future, we intend to compare the elasticity values of healthy breast tissue with those of breast tissue affected by various pathologies. Our results reveal the significant potential of RT-SWE in the rapid and non-invasive clinical diagnosis of breast diseases, such as breast cancers. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Echocardiographic assessment of the incidence of mechanical complications during the early phase of myocardial infarction in the reperfusion era: a French multicentre prospective registry.

PubMed

Gueret, P; Khalife, K; Jobic, Y; Fillipi, E; Isaaz, K; Tassan-Mangina, S; Baixas, C; Motreff, P; Meune, C

2008-01-01

Since the early reports on the incidence of mechanical complications of acute myocardial infarction (AMI) assessed by echocardiography published in the 1980s, the management of patients with AMI has changed considerably, in particular with the progressive development of early revascularisation. The aim of this multicentre study was to assess the incidence of mechanical complications of AMI in the reperfusion era. Nine-hundred and eight consecutive patients were included. Echocardiography was performed on admission and at discharge. Seventy-eight percent of patients were revascularised at the acute phase. The following incidence rates of mechanical complications were observed: mitral regurgitation 28%, secondary to left ventricular (LV) remodelling (43%) or papillary muscle dysfunction (57%); pericardial effusion 6.6%, more frequent after anterior AMI and associated with a lower ejection fraction (EF); LV thrombus 2.4%, mainly after anterior AMI and associated with a lower EF (38+/-10% vs. 48+/-12%; p<0.001); early infarct expansion 4%; septal rupture 0.6%; and acute free wall rupture 0.8%. The following factors were independently associated with the occurrence of mechanical complications by multivariate logistic regression analysis: lack of early revascularisation (OR 3.48, 95%CI 1.36-8.95; p<0.001), LV-EF<50% (OR 1.95, 95%CI 1.42-2.67; p<0.001), Killip class>II (OR 1.91, 95%CI 1.27-2.87; p<0.002) and age > or =70 years (OR 1.42, 95%CI 1.03-1.97; p<0.03). This study demonstrates the favourable prognostic influence of early revascularisation as shown by the low incidence of mechanical complications after AMI, and underlines the persistent relationship between the development of these complications and depressed LV function.

Improving titer while maintaining quality of final formulated drug substance via optimization of CHO cell culture conditions in low-iron chemically defined media.

PubMed

Xu, Jianlin; Rehmann, Matthew S; Xu, Xuankuo; Huang, Chao; Tian, Jun; Qian, Nan-Xin; Li, Zheng Jian

2018-04-01

During biopharmaceutical process development, it is important to improve titer to reduce drug manufacturing costs and to deliver comparable quality attributes of therapeutic proteins, which helps to ensure patient safety and efficacy. We previously reported that relative high-iron concentrations in media increased titer, but caused unacceptable coloration of a fusion protein during early-phase process development. Ultimately, the fusion protein with acceptable color was manufactured using low-iron media, but the titer decreased significantly in the low-iron process. Here, long-term passaging in low-iron media is shown to significantly improve titer while maintaining acceptable coloration during late-phase process development. However, the long-term passaging also caused a change in the protein charge variant profile by significantly increasing basic variants. Thus, we systematically studied the effect of media components, seed culture conditions, and downstream processing on productivity and quality attributes. We found that removing β-glycerol phosphate (BGP) from basal media reduced basic variants without affecting titer. Our goals for late-phase process development, improving titer and matching quality attributes to the early-phase process, were thus achieved by prolonging seed culture age and removing BGP. This process was also successfully scaled up in 500-L bioreactors. In addition, we demonstrated that higher concentrations of reactive oxygen species were present in the high-iron Chinese hamster ovary cell cultures compared to that in the low-iron cultures, suggesting a possible mechanism for the drug substance coloration caused by high-iron media. Finally, hypotheses for the mechanisms of titer improvement by both high-iron and long-term culture are discussed.

Classification of toxicity effects of biotransformed hepatic drugs using whale optimized support vector machines.

PubMed

Tharwat, Alaa; Moemen, Yasmine S; Hassanien, Aboul Ella

2017-04-01

Measuring toxicity is an important step in drug development. Nevertheless, the current experimental methods used to estimate the drug toxicity are expensive and time-consuming, indicating that they are not suitable for large-scale evaluation of drug toxicity in the early stage of drug development. Hence, there is a high demand to develop computational models that can predict the drug toxicity risks. In this study, we used a dataset that consists of 553 drugs that biotransformed in liver. The toxic effects were calculated for the current data, namely, mutagenic, tumorigenic, irritant and reproductive effect. Each drug is represented by 31 chemical descriptors (features). The proposed model consists of three phases. In the first phase, the most discriminative subset of features is selected using rough set-based methods to reduce the classification time while improving the classification performance. In the second phase, different sampling methods such as Random Under-Sampling, Random Over-Sampling and Synthetic Minority Oversampling Technique (SMOTE), BorderLine SMOTE and Safe Level SMOTE are used to solve the problem of imbalanced dataset. In the third phase, the Support Vector Machines (SVM) classifier is used to classify an unknown drug into toxic or non-toxic. SVM parameters such as the penalty parameter and kernel parameter have a great impact on the classification accuracy of the model. In this paper, Whale Optimization Algorithm (WOA) has been proposed to optimize the parameters of SVM, so that the classification error can be reduced. The experimental results proved that the proposed model achieved high sensitivity to all toxic effects. Overall, the high sensitivity of the WOA+SVM model indicates that it could be used for the prediction of drug toxicity in the early stage of drug development. Copyright © 2017 Elsevier Inc. All rights reserved.

Enlisted Personnel Individualized Career System (EPICS) Test and Evaluation

DTIC Science & Technology

1984-01-01

The EPICS program, which was developed using an integrated personnel systems approach ( IPSA ), delays formal school training until after personnel have...received shipboard on-job training complemented by job performance aids (3PAs). Early phases of the program, which involved developing the IPSA EPICS...detailed description of the conception and development of the EPICS IPSA model, the execution of the front-end job design analyses, 3PA and instructional

An information model for use in software management estimation and prediction

NASA Technical Reports Server (NTRS)

Li, Ningda R.; Zelkowitz, Marvin V.

1993-01-01

This paper describes the use of cluster analysis for determining the information model within collected software engineering development data at the NASA/GSFC Software Engineering Laboratory. We describe the Software Management Environment tool that allows managers to predict development attributes during early phases of a software project and the modifications we propose to allow it to develop dynamic models for better predictions of these attributes.

The Framework for Life Cycle Cost Management,

DTIC Science & Technology

1982-01-01

in the early phases of system development before full- scale development and initial production, O&S cost projections are too un- certain to...Ensure that each increment of cost and schedule investment in R&M contributes significantly to the above objectives. DoDD 5000.40, Reliability and...Major systems are characterized by large investments of time and resources in the uncertain periods of development, production, and deployment and in

Structure of interphase chromosomes in the nuclei of Drosophila cells.

PubMed

Banfalvi, Gaspar

2006-10-01

Fluorescent images of interphase chromatin structures and chromosome structures isolated from reversibly permeable Drosophila cells were analyzed. Decondensed chromatin in early S phase (2.0-2.5 C-value) consisted of a veil-like fibrillary network. Fibrillar chromatin formed rodlets later in the early S phase (2.5-2.75 C). Drosophila chromosomes contain several smaller subunits called rodlets. Fibrillar chromatin turned to chromatin ribbon and the early mid-S-phase globular chromosomes (2.75-3.0 C), then to opened fibrous globular forms later in the mid-S-phase (3.0-3.25 C), to late-S-phase supercoiled ribbons (3.25-3.5 C), end-S-phase elongated prechromosomes (3.5-3.75 C), bent and linear chromosomes (3.75-4.0 C). Early-S phase chromatin fibrils in the nuclei of Drosophila cells are thinner than the veil-like structures in mammalian cells. The connectivity of chromosomes shows linear arrangement (3, 1, 2, 4), with larger chromosomes (1 and 2) inside and smaller chromosomes (3, 4) at the two ends in the chromosomal chain.

Early visual processing is enhanced in the midluteal phase of the menstrual cycle.

PubMed

Lusk, Bethany R; Carr, Andrea R; Ranson, Valerie A; Bryant, Richard A; Felmingham, Kim L

2015-12-01

Event-related potential (ERP) studies have revealed an early attentional bias in processing unpleasant emotional images in women. Recent neuroimaging data suggests there are significant differences in cortical emotional processing according to menstrual phase. This study examined the impact of menstrual phase on visual emotional processing in women compared to men. ERPs were recorded from 28 early follicular women, 29 midluteal women, and 27 men while they completed a passive viewing task of neutral and low- and high- arousing pleasant and unpleasant images. There was a significant effect of menstrual phase in early visual processing, as midluteal women displayed significantly greater P1 amplitude at occipital regions to all visual images compared to men. Both midluteal and early follicular women displayed larger N1 amplitudes than men (although this only reached significance for the midluteal group) to the visual images. No sex or menstrual phase differences were apparent in later N2, P3, or LPP. A condition effect demonstrated greater P3 and LPP amplitude to highly-arousing unpleasant images relative to all other stimuli conditions. These results indicate that women have greater early automatic visual processing compared to men, and suggests that this effect is particularly strong in women in the midluteal phase at the earliest stage of visual attention processing. Our findings highlight the importance of considering menstrual phase when examining sex differences in the cortical processing of visual stimuli. Copyright © 2015 Elsevier Ltd. All rights reserved.

76 FR 24032 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-29

... phases: First, for planning; second, for early information technology development; and third, for... collected; and (4) the use of automated collection techniques or other forms of information technology to... the Cooperative Agreements to Support Innovative Exchange Information Technology Systems. Level One...

Chinook salmon emergence phenotypes: describing the relationships between temperature, emergence timing and condition factor in a reaction norm framework

Treesearch

Abby E. Fuhrman; Donald A. Larsen; Ashley Steel; Graham Young; Brian R. Beckman

2017-01-01

Water temperature can have a profound influence on development and distribution of aquatic species. Salmon are particularly vulnerable to temperature changes because their reproductive and early development life phases are spent in freshwater river systems where temperature fluctuates widely both daily and seasonally. Flow regulation downstream of dams can also cause...

Correlation of causal factors that influence construction safety performance: A model.

PubMed

Rodrigues, F; Coutinho, A; Cardoso, C

2015-01-01

The construction sector has presented positive development regarding the decrease in occupational accident rates in recent years. Regardless, the construction sector stands out systematically from other industries due to its high number of fatalities. The aim of this paper is to deeply understand the causality of construction accidents from the early design phase through a model. This study reviewed several research papers presenting various analytical models that correlate the contributing factors to occupational accidents in this sector. This study also analysed different construction projects and conducted a survey of design and site supervision teams. This paper proposes a model developed from the analysis of existing ones, which correlates the causal factors through all the construction phases. It was concluded that effective risk prevention can only be achieved by a global correlation of causal factors including not only production ones but also client requirements, financial climate, design team competence, project and risk management, financial capacity, health and safety policy and early planning. Accordingly, a model is proposed.

Heritage and Advanced Technology Systems Engineering Lessons Learned from NASA Space Missions

NASA Technical Reports Server (NTRS)

Barley, Bryan; Newhouse, Marilyn; Bacskay, Allen

2010-01-01

Use of heritage and new technology is necessary/enabling to implementing small, low cost missions, yet overruns decrease the ability to sustain future mission flight rates The majority of the cost growth drivers seen in the D&NF study were embedded early during formulation phase and later realized during the development and I&T phases Cost drivers can be avoided or significantly decreased by project management and SE emphasis on early identification of risks and realistic analyses SE processes that emphasize an assessment of technology within the mission system to identify technical issues in the design or operational use of the technology. Realistic assessment of new and heritage spacecraft technology assumptions , identification of risks and mitigation strategies. Realistic estimates of effort required to inherit existing or qualify new technology, identification of risks to estimates and develop mitigation strategies. Allocation of project reserves for risk-based mitigation strategies of each individual area of heritage or new technology. Careful tailoring of inheritance processes to ensure due diligence.

Evolution of the Arctic-North Atlantic and the Western Tethys

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ziegler, P.A.

1988-01-01

This volume provides an overview of the late Paleozoic to recent geological evolution of the continents and shelves bordering the North Atlantic Ocean, the Norwegian-Greenland Sea, the Arctic Ocean, and the Mediterranean Sea. The evolution of these seas has been the subject of many studies and compilations, which discuss the evolution of oceanic basins on the basis of their magnetic sea-floor anomalies. The volume presented combines this information with geological data from the adjacent shelf and onshore areas. It retraces the evolution of sedimentary basins developed during the rifting phases that preceded the opening of these oceans and highlights themore » scope of the associated intra-plate phenomena. The author presents a reconstruction of the late Paleozoic and early Mesozoic development of Europe, northernmost Africa and northeastern North America-Greenland and discusses the different orogenic cycles that accompanied the stepwise assembly of Pangea and the early rifting phases heralding its break-up.« less

Optimizing the early phase development of new analgesics by human pain biomarkers.

PubMed

Arendt-Nielsen, Lars; Hoeck, Hans Christian

2011-11-01

Human pain biomarkers are based on standardized acute activation of pain pathways/mechanisms and quantitative assessment of the evoked responses. This approach can be applied to healthy volunteers, to pain patients, and before and after pharmacological interventions to help understanding and profile the mode of action (proof-of-concept) of new and existing analgesic compounds. Standardized stimuli of different modalities can be applied to different tissues (multimodal and multi-tissue) for profiling analgesic compounds with respect to modulation of pain transduction, transmission, specific mechanisms and processing. This approach substantiates which specific compounds may work in particular clinical pain conditions. Human pain biomarkers can be translational and may bridge animal findings in clinical pain conditions, which in turn can provide new possibilities for designing more successful clinical trials. Biomarker based proof-of-concept drug studies in either volunteers or selected patient populations provide inexpensive, fast and reliable mechanism-based information about dose-efficacy relationships. This is important information in the early drug development phase and for designing large expensive clinical trials.

Biomarkers in mood disorders research: developing new and improved therapeutics

PubMed Central

Niciu, Mark J.; Mathews, Daniel C.; Ionescu, Dawn F.; Richards, Erica M.; Furey, Maura L.; Yuan, Peixiong; Nugent, Allison C.; Henter, Ioline D.; Machado-Vieira, Rodrigo; Zarate, Carlos A.

2015-01-01

Background Recently, surrogate neurobiological biomarkers that correlate with target engagement and therapeutic response have been developed and tested in early phase studies of mood disorders. Objective The identification of biomarkers could help develop personalized psychiatric treatments that may impact public health. Methods These biomarkers, which are associated with clinical response post-treatment, can be directly validated using multimodal approaches including genetic tools, proteomics/metabolomics, peripheral measures, neuroimaging, biostatistical predictors, and clinical predictors. Results To date, early phase biomarker studies have sought to identify measures that can serve as “biosignatures”, or biological patterns of clinical response. These studies have also sought to identify clinical predictors and surrogate outcomes associated with pathophysiological domains consistently described in the National Institute of Mental Health’s (NIMH) new Research Domain Criteria (RDoC). Using the N-methyl-D-aspartate (NMDA) antagonist ketamine as an example, we identified changes in several domains (clinical, cognitive, and neurophysiological) that predicted ketamine’s rapid and sustained antidepressant effects in individuals with treatment-resistant major depressive disorder (MDD) or bipolar depression. Discussion These approaches may ultimately provide clues into the neurobiology of psychiatric disorders and may have enormous impact Backon the development of novel therapeutics. PMID:26082563

Longitudinal 1H MR spectroscopy of rat forebrain from infancy to adulthood reveals adolescence as a distinctive phase of neurometabolite development

PubMed Central

Morgan, Jonathan J.; Kleven, Gale A.; Tulbert, Christina D.; Olson, John; Horita, David A.; Ronca, April E.

2013-01-01

The present study represents the first longitudinal, within-subject 1H MRS investigation of the developing rat brain spanning infancy, adolescence, and early adulthood. We obtained neurometabolite profiles from a voxel located in a central location of the forebrain, centered on the striatum, with smaller contributions for cortex, thalamus, and hypothalamus, on postnatal days 7, 35, and 60. Water-scaled metabolite signals were corrected for T1 effects and quantified using the automated processing software LCModel, yielding molal concentrations. Our findings indicate age-related concentration changes in N-acetylaspartate + N-acetylaspartylglutamate, myo-inositol, glutamate + glutamine, taurine, creatine + phosphocreatine, and glycerophosphocholine + phosphocholine. Using a repeated measures design and analysis, we identified significant neurodevelopment change across all three developmental ages and identified adolescence as a distinctive phase in normative neurometabolic brain development. Between postnatal days 35 and 60, changes were observed in concentrations of N-acetylaspartate + N-acetylaspartylglutamate, glutamate + glutamine, and glycerophosphocholine + phosphocholine observed between postnatal days 35 and 60. Our data replicate past studies of early neurometabolite development and, for the first time, link maturational profiles in the same subjects across infancy, adolescence, and adulthood. PMID:23322706

Romano-British wall paintings: Raman spectroscopic analysis of fragments from two urban sites of early military colonisation.

PubMed

Edwards, H G M; Middleton, P S; Hargreaves, M D

2009-08-01

Raman spectroscopic analyses of 1st century AD Romano-British villa wall-painting fragments from two important military and early urban centres at Colchester and Lincoln have demonstrated some interesting contrasts in technique and palette usage. Colchester, the earliest fortified settlement, developed a sophisticated painting and craft industry compared with Lincoln in the assimilation of novel substrate preparation ideas and pigment adoption. The earliest use of the rather rare purple mineral pigment, caput mortuum, hitherto reported in only a few Roman villas elsewhere in mainland Europe, is in evidence in this early phase settlement and the use of gypsum as a special ground preparation agent as an additive to the more common limewash putty to enhance the effect of the use of lazurite as a pigment is worthy of note in this context. Otherwise, the pigments are seen to be those that are quite normally encountered in Roman villas, namely, haematite, goethite, terre verte, and carbon. The results of this study indicate that at Colchester there was a continued development in technique into the colonial phase compared with a stagnation in Lincoln; these scientific results have created a stimulus for further historical research into pigment and techniques development for wall paintings at the fringe of the Roman Empire in the 1st-3rd Centuries AD.

Investigational CD33-targeted therapeutics for acute myeloid leukemia.

PubMed

Walter, Roland B

2018-04-01

There is long-standing interest in drugs targeting the myeloid differentiation antigen CD33 in acute myeloid leukemia (AML). Positive results from randomized trials with the antibody-drug conjugate (ADC) gemtuzumab ozogamicin (GO) validate this approach. Partly stimulated by the success of GO, several CD33-targeted therapeutics are currently in early phase testing. Areas covered: CD33-targeted therapeutics in clinical development include Fc-engineered unconjugated antibodies (BI 836858 [mAb 33.1]), ADCs (SGN-CD33A [vadastuximab talirine], IMGN779), radioimmunoconjugates ( 225 Ac-lintuzumab), bi- and trispecific antibodies (AMG 330, AMG 673, AMV564, 161533 TriKE fusion protein), and chimeric antigen receptor (CAR)-modified immune effector cells. Besides limited data on 225 Ac-lintuzumab showing modest single-agent activity, clinical data are so far primarily available for SGN-CD33A. SGN-CD33A has single-agent activity and has shown encouraging results when combined with an azanucleoside or standard chemotherapeutics. However, concerns about toxicity to the liver and normal hematopoietic cells - the latter leading to early termination of a phase 3 trial - have derailed the development of SGN-CD33A, and its future is uncertain. Expert opinion: Early results from a new generation of CD33-targeted therapeutics are anticipated in the next 2-3 years. Undoubtedly, re-approval of GO in 2017 has changed the landscape and rendered clinical development for these agents more challenging.

Romano-British wall paintings: Raman spectroscopic analysis of fragments from two urban sites of early military colonisation

NASA Astrophysics Data System (ADS)

Edwards, H. G. M.; Middleton, P. S.; Hargreaves, M. D.

2009-08-01

Raman spectroscopic analyses of 1st century AD Romano-British villa wall-painting fragments from two important military and early urban centres at Colchester and Lincoln have demonstrated some interesting contrasts in technique and palette usage. Colchester, the earliest fortified settlement, developed a sophisticated painting and craft industry compared with Lincoln in the assimilation of novel substrate preparation ideas and pigment adoption. The earliest use of the rather rare purple mineral pigment, caput mortuum, hitherto reported in only a few Roman villas elsewhere in mainland Europe, is in evidence in this early phase settlement and the use of gypsum as a special ground preparation agent as an additive to the more common limewash putty to enhance the effect of the use of lazurite as a pigment is worthy of note in this context. Otherwise, the pigments are seen to be those that are quite normally encountered in Roman villas, namely, haematite, goethite, terre verte, and carbon. The results of this study indicate that at Colchester there was a continued development in technique into the colonial phase compared with a stagnation in Lincoln; these scientific results have created a stimulus for further historical research into pigment and techniques development for wall paintings at the fringe of the Roman Empire in the 1st-3rd Centuries AD.

Assessing the comparative effectiveness of newly marketed medications: methodological challenges and implications for drug development.

PubMed

Schneeweiss, S; Gagne, J J; Glynn, R J; Ruhl, M; Rassen, J A

2011-12-01

Comparative-effectiveness research (CER) aims to produce actionable evidence regarding the effectiveness and safety of medical products and interventions as they are used outside of controlled research settings. Although CER evidence regarding medications is particularly needed shortly after market approval, key methodological challenges include (i) potential bias due to channeling of patients to the newly marketed medication because of various patient-, physician-, and system-related factors; (ii) rapid changes in the characteristics of the user population during the early phase of marketing; and (iii) lack of timely data and the often small number of users in the first few months of marketing. We propose a mix of approaches to generate comparative-effectiveness data in the early marketing period, including sequential cohort monitoring with secondary health-care data and propensity score (PS) balancing, as well as extended follow-up of phase III and phase IV trials, indirect comparisons of placebo-controlled trials, and modeling and simulation of virtual trials.

The making of the modern airport executive: Causal connections among key attributes in career development, compromise, and satisfaction in airport management

NASA Astrophysics Data System (ADS)

Byers, David Alan

The purpose of this study was to identify specific career development attributes of contemporary senior-level airport executives and to evaluate the relationship of these attributes to the level of satisfaction airport executives have in their career choice. Attribute sets that were examined included early aviation interests, health factors, psychological factors, demographic factors, formal education, and other aviation-related experiences. A hypothesized causal model that expressed direct and indirect effects among these attributes relative to airport executives' career satisfaction was tested using sample data collected from 708 airport executives from general aviation and commercial service airport throughout the United States. Applying a multiple regression analysis strategy to the model, the overall results revealed that 16% of the variability in airport executives' career satisfaction scores was due to the collective influence of the six research attribute sets, this was significant. The results of the path analysis also indicated that four attribute sets (early aviation interests, health factors, formal education, and other aviation-related experiences) had respective direct significant effects on participants' career satisfaction. Early aviation interests, health factors, and demographic factors had additional indirect effects on career satisfaction; all were mediated by formal education attitude. These results were inconsistent with the hypothesized path model and a revised model was developed to reflect the sample data. The findings suggest that airport executives, as a group, are satisfied with their career choice. Early aviation interests appear to play an important role for influencing the career field selection phase of career development. The study also suggests health factors, formal education, and other aviation-related experiences such as flight training or military experience influence the compromise phase of career development. Each of these four factors had significant effects on career satisfaction. In addition to its applicability to airport executives, the study provides a generalized path model for investigating factors influencing the career development, compromise, and satisfaction process in other vocations.

Development of hypersynchrony in the cortical network during chemoconvulsant-induced epileptic seizures in vivo.

PubMed

Cymerblit-Sabba, Adi; Schiller, Yitzhak

2012-03-01

The prevailing view of epileptic seizures is that they are caused by increased hypersynchronous activity in the cortical network. However, this view is based mostly on electroencephalography (EEG) recordings that do not directly monitor neuronal synchronization of action potential firing. In this study, we used multielectrode single-unit recordings from the hippocampus to investigate firing of individual CA1 neurons and directly monitor synchronization of action potential firing between neurons during the different ictal phases of chemoconvulsant-induced epileptic seizures in vivo. During the early phase of seizures manifesting as low-amplitude rhythmic β-electrocorticography (ECoG) activity, the firing frequency of most neurons markedly increased. To our surprise, the average overall neuronal synchronization as measured by the cross-correlation function was reduced compared with control conditions with ~60% of neuronal pairs showing no significant correlated firing. However, correlated firing was not uniform and a minority of neuronal pairs showed a high degree of correlated firing. Moreover, during the early phase of seizures, correlated firing between 9.8 ± 5.1% of all stably recorded pairs increased compared with control conditions. As seizures progressed and high-frequency ECoG polyspikes developed, the firing frequency of neurons further increased and enhanced correlated firing was observed between virtually all neuronal pairs. These findings indicated that epileptic seizures represented a hyperactive state with widespread increase in action potential firing. Hypersynchrony also characterized seizures. However, it initially developed in a small subset of neurons and gradually spread to involve the entire cortical network only in the later more intense ictal phases.

Army-NASA aircrew/aircraft integration program. Phase 5: A3I Man-Machine Integration Design and Analysis System (MIDAS) software concept document

NASA Technical Reports Server (NTRS)

Banda, Carolyn; Bushnell, David; Chen, Scott; Chiu, Alex; Neukom, Christian; Nishimura, Sayuri; Prevost, Michael; Shankar, Renuka; Staveland, Lowell; Smith, Greg

1992-01-01

This is the Software Concept Document for the Man-machine Integration Design and Analysis System (MIDAS) being developed as part of Phase V of the Army-NASA Aircrew/Aircraft Integration (A3I) Progam. The approach taken in this program since its inception in 1984 is that of incremental development with clearly defined phases. Phase 1 began in 1984 and subsequent phases have progressed at approximately 10-16 month intervals. Each phase of development consists of planning, setting requirements, preliminary design, detailed design, implementation, testing, demonstration and documentation. Phase 5 began with an off-site planning meeting in November, 1990. It is expected that Phase 5 development will be complete and ready for demonstration to invited visitors from industry, government and academia in May, 1992. This document, produced during the preliminary design period of Phase 5, is intended to record the top level design concept for MIDAS as it is currently conceived. This document has two main objectives: (1) to inform interested readers of the goals of the MIDAS Phase 5 development period, and (2) to serve as the initial version of the MIDAS design document which will be continuously updated as the design evolves. Since this document is written fairly early in the design period, many design issues still remain unresolved. Some of the unresolved issues are mentioned later in this document in the sections on specific components. Readers are cautioned that this is not a final design document and that, as the design of MIDAS matures, some of the design ideas recorded in this document will change. The final design will be documented in a detailed design document published after the demonstrations.

Results from conceptual design study of potential early commercial MHD/steam power plants

NASA Technical Reports Server (NTRS)

Hals, F.; Kessler, R.; Swallom, D.; Westra, L.; Zar, J.; Morgan, W.; Bozzuto, C.

1981-01-01

This paper presents conceptual design information for a potential early MHD power plant developed in the second phase of a joint study of such plants. Conceptual designs of plant components and equipment with performance, operational characteristics and costs are reported on. Plant economics and overall performance including full and part load operation are reviewed. Environmental aspects and the methods incorporated in plant design for emission control of sulfur and nitrogen oxides are reviewed. Results from reliability/availability analysis conducted are also included.

Early-life sugar consumption has long-term negative effects on memory function in male rats.

PubMed

Noble, Emily E; Hsu, Ted M; Liang, Joanna; Kanoski, Scott E

2017-09-25

Added dietary sugars contribute substantially to the diet of children and adolescents in the USA, and recent evidence suggests that consuming sugar-sweetened beverages (SSBs) during early life has deleterious effects on hippocampal-dependent memory function. Here, we test whether the effects of early-life sugar consumption on hippocampal function persist into adulthood when access to sugar is restricted to the juvenile/adolescent phase of development. Male rats were given ad libitum access to an 11% weight-by-volume sugar solution (made with high fructose corn syrup-55) throughout the adolescent phase of development (post-natal day (PN) 26-56). The control group received a second bottle of water instead, and both groups received ad libitum standard laboratory chow and water access throughout the study. At PN 56 sugar solutions were removed and at PN 175 rats were subjected to behavioral testing for hippocampal-dependent episodic contextual memory in the novel object in context (NOIC) task, for anxiety-like behavior in the Zero maze, and were given an intraperitoneal glucose tolerance test. Early-life exposure to SSBs conferred long-lasting impairments in hippocampal-dependent memory function later in life- yet had no effect on body weight, anxiety-like behavior, or glucose tolerance. A second experiment demonstrated that NOIC performance was impaired at PN 175 even when SSB access was limited to 2 hours daily from PN 26-56. Our data suggest that even modest SSB consumption throughout early life may have long-term negative consequences on memory function during adulthood.

Navigation and Guidance for Low-Thrust Trajectories, LOTNAV

NASA Astrophysics Data System (ADS)

Cano, J. L.; Bello, M.; Rodriguez-Canabal, J.

A number of interplanetary low-thrust missions have already been flown by many space agencies. Examples of already flown missions based on the use of electric propulsion are Deep Space 1, Hayabusa and SMART-1. Many others are already in the assessment phase or in the development phase itself. In such perspective, it is required by the space agencies the procurement and utilisation of assessment tools for fast prototyping in the areas of mission design and navigation. The Low-Thrust Interplanetary Navigation Tool, which is the subject of this paper, allows the mission analyst performing such type of quick assessment studies for the early phases in the development of low-thrust missions. A number of test cases on low-thrust missions are also presented along with the utilities composing the LOTNAV tool.

Luteal Coasting and Individualization of Human Chorionic Gonadotropin Dose after Gonadotropin-Releasing Hormone Agonist Triggering for Final Oocyte Maturation—A Retrospective Proof-of-Concept Study

PubMed Central

Lawrenz, Barbara; Samir, Suzan; Garrido, Nicolas; Melado, Laura; Engelmann, Nils; Fatemi, Human M.

2018-01-01

Ovarian stimulation in a gonadotropin-releasing hormone (GnRH) antagonist protocol with the use of GnRH agonist for final oocyte maturation is the state-of-the-art treatment in patients with an expected or known high response to avoid or at least reduce significantly the risk for development of ovarian hyperstimulation syndrome (OHSS). Due to a shortened LH surge after administration of GnRH agonist in most patients, the luteal phase will be characterized by luteolysis and luteal phase insufficiency. Maintaining a sufficient luteal phase is crucial for achievement of a pregnancy; however, the optimal approach is still under debate. Administration of human chorionic gonadotropin (hCG) within 72 h rescues the corpora lutea function; however, the so far often used 1,500 IU still bear the risk for development of OHSS. The recently introduced concept of “luteal coasting” individualizes the luteal phase support by monitoring the progesterone concentrations and administering a rescue dosage of hCG when progesterone concentrations drop significantly. This retrospective proof-of-concept study explored the correlation between hCG dosages ranging from 375 up to 1,500 IU and the progesterone levels in the early and mid-luteal phases as well as the likelihood of pregnancy, both early and ongoing. The chance of pregnancy is highest with progesterone level ≥13 ng/ml at 48 h postoocyte retrieval. Among the small sample size of 52 women studied, it appears that appropriate progesterone levels can be achieved with hCG dosages as low as 375 IU. This may well optimize the chance of pregnancy while reducing the risk of OHSS associated with higher doses of hCG supplementation in the luteal phase. PMID:29497400

Hypertension: management perspectives.

PubMed

Borghi, Claudio; Cicero, Arrigo F G

2012-10-01

The increasing worldwide prevalence of hypertension and the related increase in cost due to diagnosis, management and negative outcomes forces public health institutions and clinical researchers to find new strategies to improve blood pressure (BP) control. So what are the possible future perspectives for high BP management? Three main points are briefly discussed in this article: individualized therapy, the known genetic contribution to hypertension development and control, and the improvement of disease management, including perspectives on new antihypertensive drug development. It is likely that the integration of the best available current knowledge with recent diagnostic and therapeutic achievements for the management of hypertension prevention and treatment will lead to the early detection of at-risk conditions, early diagnosis, and individualized and efficacious treatment. The most promising antihypertensive drugs currently in development are innovative renin-angiotensin-aldosterone system modulators. Further drugs have potentially interesting mechanisms of action, but renalase analogs are in the very early phases of development, and available endothelin antagonists have a poor safety profile.

Statistical controversies in clinical research: early-phase adaptive design for combination immunotherapies.

PubMed

Wages, N A; Slingluff, C L; Petroni, G R

2017-04-01

In recent years, investigators have asserted that the 3 + 3 design lacks flexibility, making its use in modern early-phase trial settings, such as combinations and/or biological agents, inefficient. More innovative approaches are required to address contemporary research questions, such as those posed in trials involving immunotherapies. We describe the implementation of an adaptive design for identifying an optimal treatment regimen, defined by low toxicity and high immune response, in an early-phase trial of a melanoma helper peptide vaccine plus novel adjuvant combinations. Operating characteristics demonstrate the ability of the method to effectively recommend optimal regimens in a high percentage of trials with reasonable sample sizes. The proposed design is a practical, early-phase, adaptive method for use with combined immunotherapy regimens. This design can be applied more broadly to early-phase combination studies, as it was used in an ongoing study of two small molecule inhibitors in relapsed/refractory mantle cell lymphoma. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Consistency of a lumbar movement pattern across functional activities in people with low back pain.

PubMed

Marich, Andrej V; Hwang, Ching-Ting; Salsich, Gretchen B; Lang, Catherine E; Van Dillen, Linda R

2017-05-01

Limitation in function is a primary reason people with low back pain seek medical treatment. Specific lumbar movement patterns, repeated throughout the day, have been proposed to contribute to the development and course of low back pain. Varying the demands of a functional activity test may provide some insight into whether people display consistent lumbar movement patterns during functional activities. Our purpose was to examine the consistency of the lumbar movement pattern during variations of a functional activity test in people with low back pain and back-healthy people. 16 back-healthy adults and 32 people with low back pain participated. Low back pain participants were classified based on the level of self-reported functional limitations. Participants performed 5 different conditions of a functional activity test. Lumbar excursion in the early phase of movement was examined. The association between functional limitations and early phase lumbar excursion for each test condition was examined. People with low back pain and high levels of functional limitation demonstrated a consistent pattern of greater early phase lumbar excursion across test conditions (p<0.05). For each test condition, the amount of early phase lumbar excursion was associated with functional limitation (r=0.28-0.62). Our research provides preliminary evidence that people with low back pain adopt consistent movement patterns during the performance of functional activities. Our findings indicate that the lumbar spine consistently moves more readily into its available range in people with low back pain and high levels of functional limitation. How the lumbar spine moves during a functional activity may contribute to functional limitations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Numerical investigation of the early flight phase in ski-jumping.

PubMed

Gardan, N; Schneider, A; Polidori, G; Trenchard, H; Seigneur, J M; Beaumont, F; Fourchet, F; Taiar, R

2017-07-05

The purpose of this study is to develop a numerical methodology based on real data from wind tunnel experiments to investigate the effect of the ski jumper's posture and speed on aerodynamic forces in a wide range of angles of attack. To improve our knowledge of the aerodynamic behavior of the ski jumper and his equipment during the early flight phase of the ski jump, we applied CFD methodology to evaluate the influence of angle of attack (α=14°, 21.5°, 29°, 36.5° and 44°) and speed (u=23, 26 and 29m/s) on aerodynamic forces in the situation of stable attitude of the ski jumper's body and skis. The standard k-ω turbulence model was used to investigate both the influence of the ski jumper's posture and speed on aerodynamic performance during the early flight phase. Numerical results show that the ski jumper's speed has very little impact on the lift and drag coefficients. Conversely, the lift and drag forces acting on the ski jumper's body during the early flight phase of the jump are strongly influenced by the variations of the angle of attack. The present results suggest that the greater the ski jumper's angle of inclination, with respect to the relative flow, the greater the pressure difference between the lower and upper parts of the skier. Further studies will focus on the dependency of the parameters with both the angle of attack α and the body-ski angle β as control variables. It will be possible to test and optimize different ski jumping styles in different ski jumping hills and investigate different environmental conditions such as temperature, altitude or crosswinds. Copyright © 2017 Elsevier Ltd. All rights reserved.

Early neurovascular dysfunction in a transgenic rat model of Alzheimer's disease.

PubMed

Joo, Illsung L; Lai, Aaron Y; Bazzigaluppi, Paolo; Koletar, Margaret M; Dorr, Adrienne; Brown, Mary E; Thomason, Lynsie A M; Sled, John G; McLaurin, JoAnne; Stefanovic, Bojana

2017-04-12

Alzheimer's disease (AD), pathologically characterized by amyloid-β peptide (Aβ) accumulation, neurofibrillary tangle formation, and neurodegeneration, is thought to involve early-onset neurovascular abnormalities. Hitherto studies on AD-associated neurovascular injury have used animal models that exhibit only a subset of AD-like pathologies and demonstrated some Aβ-dependent vascular dysfunction and destabilization of neuronal network. The present work focuses on the early stage of disease progression and uses TgF344-AD rats that recapitulate a broader repertoire of AD-like pathologies to investigate the cerebrovascular and neuronal network functioning using in situ two-photon fluorescence microscopy and laminar array recordings of local field potentials, followed by pathological analyses of vascular wall morphology, tau hyperphosphorylation, and amyloid plaques. Concomitant to widespread amyloid deposition and tau hyperphosphorylation, cerebrovascular reactivity was strongly attenuated in cortical penetrating arterioles and venules of TgF344-AD rats in comparison to those in non-transgenic littermates. Blood flow elevation to hypercapnia was abolished in TgF344-AD rats. Concomitantly, the phase-amplitude coupling of the neuronal network was impaired, evidenced by decreased modulation of theta band phase on gamma band amplitude. These results demonstrate significant neurovascular network dysfunction at an early stage of AD-like pathology. Our study identifies early markers of pathology progression and call for development of combinatorial treatment plans.

Planning and Estimation of Operations Support Requirements

NASA Technical Reports Server (NTRS)

Newhouse, Marilyn E.; Barley, Bryan; Bacskay, Allen; Clardy, Dennon

2010-01-01

Life Cycle Cost (LCC) estimates during the proposal and early design phases, as well as project replans during the development phase, are heavily focused on hardware development schedules and costs. Operations (phase E) costs are typically small compared to the spacecraft development and test costs. This, combined with the long lead time for realizing operations costs, can lead to de-emphasizing estimation of operations support requirements during proposal, early design, and replan cost exercises. The Discovery and New Frontiers (D&NF) programs comprise small, cost-capped missions supporting scientific exploration of the solar system. Any LCC growth can directly impact the programs' ability to fund new missions, and even moderate yearly underestimates of the operations costs can present significant LCC impacts for deep space missions with long operational durations. The National Aeronautics and Space Administration (NASA) D&NF Program Office at Marshall Space Flight Center (MSFC) recently studied cost overruns and schedule delays for 5 missions. The goal was to identify the underlying causes for the overruns and delays, and to develop practical mitigations to assist the D&NF projects in identifying potential risks and controlling the associated impacts to proposed mission costs and schedules. The study found that 4 out of the 5 missions studied had significant overruns at or after launch due to underestimation of the complexity and supporting requirements for operations activities; the fifth mission had not launched at the time of the mission. The drivers behind these overruns include overly optimistic assumptions regarding the savings resulting from the use of heritage technology, late development of operations requirements, inadequate planning for sustaining engineering and the special requirements of long duration missions (e.g., knowledge retention and hardware/software refresh), and delayed completion of ground system development work. This paper updates the D&NF LCC study, looking at the operations (phase E) cost drivers in more detail and extending the study to include 2 additional missions and identifies areas for increased emphasis by project management in order to improve the fidelity of operations estimates.

The hepatocyte phase of Gd-EOB-DTPA-enhanced MRI in the evaluation of hepatic fibrosis and early liver cirrhosis in a rat model: an experimental study.

PubMed

Ma, Chunmei; Liu, Ailian; Wang, Yuanyuan; Geng, Xiaoling; Hao, Li; Song, Qingwei; Sun, Bo; Wang, Heqing; Zhao, Gang

2014-07-17

To evaluate the hepatocyte phase of Gd-EOB-DTPA-enhanced MRI in the early diagnosis of hepatic fibrosis and cirrhosis and assessment of liver function in a rat model. In 2 groups of SD rats, liver fibrosis was induced in experimental animals by repetitive carbon tetrachloride injections, while the control group received saline injections. Five experimental rats and 2 control rats were randomly selected at weeks 4, 8, 12. One week after carbon tetrachloride administration, MRI (FIRM T1WI) scan was performed. Gd-EOB-DTPA (0.08mL) was injected into the rat's tail vein and hepatocyte phase images were obtained after 20min. The pre-enhanced phase and hepatocyte phase signal intensities (SI) were measured, and the relative contrast enhancement index (RCEI) was calculated. ANOVA analysis (LSD) of RCEI values in controls (n=6), hepatic fibrosis (n=7), and histopathologically-determined early cirrhosis group (n=6) was performed. RECI values showed a decreasing trend in the control group, hepatic fibrosis and early cirrhosis groups (1.11±0.43, 0.96±0.22, and 0.57±0.33, respectively). While the difference between the control and early cirrhosis groups was statistically significant (p=0.013), there was no significant difference in the hepatic fibrosis group vs the control (p=0.416) and the hepatic fibrosis group vs the early cirrhosis group (p=0.054). Hepatocyte phase RCEI values obtained with Gd-EOB-DTPA-enhanced MRI scan indicate liver injury in hepatic fibrosis and early cirrhosis. RCEI values are helpful for early diagnosis of liver cirrhosis. Copyright © 2014 Elsevier Inc. All rights reserved.

Facility Composer (Trademark) and PACES (Trademark) Integration: Development of an XML Interface Based on Industry Foundation Classes

DTIC Science & Technology

2007-11-01

Engineer- ing Research Laboratory is currently developing a set of facility ‘architec- tural’ programming tools , called Facility ComposerTM (FC). FC...requirements in the early phases of project development. As the facility program, crite- ria, and requirements are chosen, these tools populate the IFC...developing a set of facility “ar- chitectural” programming tools , called Facility Composer (FC), to support the capture and tracking of facility criteria

NASA/Air Force Cost Model: NAFCOM

NASA Technical Reports Server (NTRS)

Winn, Sharon D.; Hamcher, John W. (Technical Monitor)

2002-01-01

The NASA/Air Force Cost Model (NAFCOM) is a parametric estimating tool for space hardware. It is based on historical NASA and Air Force space projects and is primarily used in the very early phases of a development project. NAFCOM can be used at the subsystem or component levels.

Strategic Environmental Research & Development Program (SERDP): Phase I and Phase II Strategic Investment Plans FY 1992 and Interim Status Report of the Council.

DTIC Science & Technology

1993-10-01

VLF/ELF) communication systems, used for early warning and strategic communications, are dependent on the electron densities in the "C" and "D...information into optical or electronic signals that can be remotely monitored. During FY92, an in-depth and definitive assessment of the feasibility...particularly metal finishing and electronics operations. BENEFITS: The broad program described above will provide the opportunity for EPA, the

Zircon (U-Th)/He evidence for pre-Eocene orogenic exhumation of eastern North Pyrenean massifs, France

NASA Astrophysics Data System (ADS)

Ternois, Sébastien; Vacherat, Arnaud; Pik, Raphaël; Ford, Mary; Tibari, Bouchaïb

2017-04-01

Orogens and their associated foreland basins are considered as part of a single dynamic system evolving from an early, non equilibrated, growth stage to a late, mature, steady-state stage. Most of our understanding in foreland basins, in particular early convergence-stage deposition, comes from the subducting plate, so that the classic paradigm for foreland basins is the pro-wedge. Models that clearly depict the relationship between erosion of the orogenic wedge and sedimentation into its associated foreland basin only focus on the late post-orogenic phase. Relatively little is known and understood about the very long phase of initiation of orogenesis. In the doubly wedged Pyrenean orogen, where we know and understand relatively little about how the early retro-wedge developed, the record of the onset of orogenic denudation from massifs is quite limited, not only in time but also in space. As part of the OROGEN project funded by TOTAL and the BRGM, this study presents first single-grain zircon (U-Th)/He data from two Palaeozoic massifs of the external Northern Pyrenean Zone, the Agly and Salvezines massifs. It aims at constraining the exhumation history of eastern Pyrenean massifs and understanding what is their significance for early orogenic wedge growth. The Pyrenean orogeny was generated from end Santonian (84 Ma) to Oligocene-Miocene due to convergence of the Iberian and European plates. Aquitaine foreland basin history (Ariège region) indicates that convergence took place in two phases, Campanian to Maastrichian and Eocene, separated by a quiet Paleocene phase. Yet, only Eocene cooling events are recorded by low-temperature thermochronometers in the central Pyrenean massifs (Arize and Trois-Seigneurs). Nine bedrock samples were collected along a WNW-ESE traverse (Salvezines and Saint-Arnac granites, Belesta-Caramany gneisses) and analysed for ZHe dating. Zircon (U-Th)/He data for the Agly and Salvezines massifs, together with forward modelling of data for two end-members, Late Cretaceous (Campanian, 75 Ma) and Eocene (50 Ma), show that the easternmost external basement massifs record a first phase of cooling from ˜200°C, between ca. 75 Ma and ca. 60 Ma, which we correlate with the early Pyrenean orogenic phase. Our data provide important new constraints on the timing of early Pyrenean exhumation and temperatures associated with pre-orogenic HT-LP metamorphism but have limited resolution in quantifying the amount of exhumation and shortening at the onset of the convergence in this region. These results are integrated into a tectonic reconstruction of the eastern Pyrenees from an early Cretaceous extensional template to present day

Stressful events and coping related to acute and sub-acute whiplash-associated disorders.

PubMed

Pettersson, Susanne; Bring, Annika; Åsenlöf, Pernilla

2017-03-01

Purpose To describe daily stressors affecting and coping strategies employed by individuals with whiplash-associated disorders (WAD) immediately to one month (acute) and three to four months (sub-acute) after injury events using a daily coping assessment. Levels of pain, anxiety, depressed mood and activity are also compared between phases. Method A descriptive prospective design with a content analysis approach was used. Participants completed daily coping assessments for one week during both acute and sub-acute phases. Main measure was whiplash-associated disorders-daily coping assessment (WAD-DCA). Results Nine participants used words describing recovery in the sub-acute phase; 31 described stressful events during both phases. Most frequently reported stressors were related to "symptoms", "emotions" and "occupations/studies". These were equally reported during both phases. Cognitive coping strategies were employed more often during the sub-acute phase (p = 0.008). The only behavioral strategy that increased in prevalence over time was the "relaxed" strategy (p = 0.001). Anxiety levels declined over time (p = 0.022). Conclusion The reported stressors were largely uniform across both acute and sub-acute phases; however, the use of cognitive coping strategies increased over time. The WAD-DCA captures individual stressors and coping strategies employed during a vulnerable phase of rehabilitation and can thus provide information that is useful to clinical practice. Implications for rehabilitation The WAD-DCA provides valuable information for clinical practice when employed during early phases of whiplash-associated disorder development. Reported stressors during the acute and sub-acute phases are essentially the same, whereas cognitive coping strategies grow in prevalence over time. Tailored treatments in early phases of whip-lash associated disorders may benefit from strategies aimed at matching patient-specific stressors with contextually adapted coping strategies.

Improving the luteal phase after ovarian stimulation: reviewing new options.

PubMed

Yding Andersen, C; Vilbour Andersen, K

2014-05-01

The human chorionic gonadotrophin (HCG) trigger used for final follicular maturation in connection with assisted reproduction treatment combines ovulation induction and early luteal-phase stimulation of the corpora lutea. The use of a gonadotrophin-releasing hormone agonist (GnRHa) for final follicular maturation has, however, for the first time allowed a separation of the ovulatory signal from the early luteal-phase support. This has generated new information that may improve the currently employed luteal-phase support. Thus, combined results from a number of randomized controlled trials using the GnRHa trigger suggest an association between the reproductive outcome after IVF treatment and the mid-luteal-phase serum progesterone concentration. It appears that a minimum mid-luteal progesterone threshold of approximately 80-100 nmol/l exists, which, when surpassed, results in reduced early pregnancy loss and an increased live birth rate. Further, the trade off between the HCG bolus and the subsequent risk of ovarian hyperstimulation syndrome has resulted in a trend to reduce the HCG bolus from 10,000 IU to 6500-5000 IU, which augments the HCG/LH deficiency during the early/mid-luteal phase. The mid-luteal HCG/LH shortage results in an altered progesterone profile, showing the highest concentration during the early luteal phase, contrasting with the mid-luteal peak seen in the natural menstrual cycle. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Brief exposure to methamphetamine (METH) and phencyclidine (PCP) during late development leads to long-term learning deficits in rats.

PubMed

White, Ilsun M; Minamoto, Takehiro; Odell, Joseph R; Mayhorn, Joseph; White, Wesley

2009-04-17

Exposure to methamphetamine (METH) and phencyclidine (PCP) during early development is thought to produce later behavioral deficits. We postulated that exposure to METH and PCP during later development would produce similar behavioral deficits, particularly learning deficits in adulthood. Wistar rats were treated with METH (9 mg/kg), PCP (9 mg/kg), or saline during later development, postnatal days (PD) 50-51, and subsequent behavioral changes were examined including: locomotor activity during the acute drug state (PD 50-51) and the post-drug phase (PD 50-80); social interaction on PD 54-80; and spatial discrimination and reversal in adulthood (after PD 90). METH and PCP differentially affected locomotion during the acute state, but not during the post-drug phase. METH decreased social interaction throughout tests two weeks after drug treatment, whereas PCP decreased social interaction only during the first 8 min of tests. Neither METH nor PCP impaired initial acquisition of spatial discrimination. However, reversal was significantly impaired by PCP, whereas METH produced a mild deficit, compared to controls. Our data provide evidence that exposure to PCP and METH during later development lead to enduring cognitive deficits in adulthood. Selective impairment of reversal may reflect neurological damage in the prefrontal cortex due to early exposure to drugs.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Childers, M.; Barnes, J.

The phased field development of the Lion and Panthere fields, offshore the Ivory Coast, includes a small floating production, storage, and offloading (FPSO) tanker with minimal processing capability as an early oil production system (EPS). For the long-term production scheme, the FPSO will be replaced by a converted jack up mobile offshore production system (MOPS) with full process equipment. The development also includes guyed-caisson well platforms, pipeline export for natural gas to fuel an onshore power plant, and a floating storage and offloading (FSO) tanker for oil export. Pipeline export for oil is a future possibility. This array of innovativemore » strategies and techniques seldom has been brought together in a single project. The paper describes the development plan, early oil, jack up MOPS, and transport and installation.« less

Mesozoic and Cenozoic structural evolution of North Oman: New insights from high-quality 3D seismic from the Lekhwair area

NASA Astrophysics Data System (ADS)

Bazalgette, Loïc; Salem, Hisham

2018-06-01

This paper highlights the role of Triassic-Jurassic extension and late Cretaceous compression in the Mesozoic-Cenozoic (Alpine) structuring of North Oman. The syn/post-Mesozoic regional structural evolution is usually documented as a succession of two stages of deformation. The Alpine 1 phase, late Cretaceous in age, occurred in association with two ophiolite obduction stages (Semail and Masirah ophiolites). It was characterised by strike slip to extensional deformation in the North Oman foreland basin sub-surface. The Alpine 2 phase, Miocene in age, was related to the continental collision responsible for both the Zagros orogen and the uplift of the Oman Mountains. The Alpine 2 deformation was transpressional to compressional. Observation and interpretation of good quality 3D seismic in the Lekhwair High area enabled the distinction of two earlier phases. Early Mesozoic extension occurred concomitantly with the regional Triassic to Jurassic rifting, developing Jurassic-age normal faults. Late Cretaceous compression occurred prior to the main Alpine 1 phase and triggered the inversion of Jurassic-seated normal faults as well as the initiation of compressional folds in the Cretaceous overburden. These early phases have been ignored or overlooked as part of the North Oman history although they are at the origin of structures hosting major local and regional hydrocarbon accumulations.

Canadian and Siberian Boreal Fire Activity during ARCTAS Spring and Summer Phases

NASA Astrophysics Data System (ADS)

Stocks, B. J.; Fromm, M. D.; Soja, A. J.; Servranckx, R.; Lindsey, D.; Hyer, E.

2009-12-01

The summer phase of ARCTAS (Arctic Research of the Composition of the Troposphere from Aircraft and Satellites) was designed specifically around forest fire activity in the Canadian boreal forest, and located in areas of northern Canada where summer forest fires are ubiquitous. Lightning fires are most often allowed to burn naturally in these regions, and a number of large free-burning fires in northern Saskatchewan in late June/early July 2008 provided excellent targets during the summer phase of ARCTAS. Smoke generated by a large number of early spring fires in Kazakhstan and southern Siberia unexpectedly made a significant contribution to arctic haze during the Alaska-based spring phase of ARCTAS, Numerous smoke plumes were sampled during the spring phase of ARCTAS, creating interest in the origin and characteristics of the fires in the source regions of East Asia. This presentation is designed to connect aircraft and satellite smoke chemistry/transport measurements with ground-based measurements of fire activity during the spring and summer phases of ARCTAS. The Canadian Forest Fire Danger Rating System (CFFDRS) is used to determine forest fire danger conditions in regions of fire activity, and these measurements are in turn used to project fire behavior characteristics. Fuel consumption, spread rates, and frontal fire intensity are calculated using the CFFDRS. Energy release rates at ground level are related to convection/smoke column development and smoke injection heights.

Origin and early evolution of photosynthesis

NASA Technical Reports Server (NTRS)

Blankenship, R. E.

1992-01-01

Photosynthesis was well-established on the earth at least 3.5 thousand million years ago, and it is widely believed that these ancient organisms had similar metabolic capabilities to modern cyanobacteria. This requires that development of two photosystems and the oxygen evolution capability occurred very early in the earth's history, and that a presumed phase of evolution involving non-oxygen evolving photosynthetic organisms took place even earlier. The evolutionary relationships of the reaction center complexes found in all the classes of currently existing organisms have been analyzed using sequence analysis and biophysical measurements. The results indicate that all reaction centers fall into two basic groups, those with pheophytin and a pair of quinones as early acceptors, and those with iron sulfur clusters as early acceptors. No simple linear branching evolutionary scheme can account for the distribution patterns of reaction centers in existing photosynthetic organisms, and lateral transfer of genetic information is considered as a likely possibility. Possible scenarios for the development of primitive reaction centers into the heterodimeric protein structures found in existing reaction centers and for the development of organisms with two linked photosystems are presented.

Welcome to the Twilight Zone: a forgotten early phase of human evolutionary studies.

PubMed

Delisle, Richard G

2012-06-01

The field of paleoanthropology arose out of a strange and unacknowledged early phase of development prior to about the 1930s. It is often assumed that a key pillar of the discipline, the unity of humankind--the notion that humans are clearly separated phylogenetically (genealogically) from other non-human primates--was widely accepted from the inception of paleoanthropology around 1860. However, a final consensus on this fundamental question only appeared later on in the 20th century. This paper will focus on two key areas of disagreement, which reveal the unsettled state of this question during this early period: the question of uncertainty with respect to the number, identity and boundary of primate species (including humans) which prevailed in the 18th, 19th and early 20th centuries; and the matter of uncertainty with respect to the nature of the phylogenetic relationships among the various human populations and the other primate species which prevailed between 1864 and 1931. Consideration of these matters reveals that the modern research structure that paleoanthropologists take for granted today is much more recent than believed. Copyright © 2012 Elsevier Ltd. All rights reserved.

Content of endoplasmic reticulum and Golgi complex membranes positively correlates with the proliferative status of brain cells.

PubMed

Silvestre, David C; Maccioni, Hugo J F; Caputto, Beatriz L

2009-03-01

Although the molecular and cellular basis of particular events that lead to the biogenesis of membranes in eukaryotic cells has been described in detail, understanding of the intrinsic complexity of the pleiotropic response by which a cell adjusts the overall activity of its endomembrane system to accomplish these requirements is limited. Here we carried out an immunocytochemical and biochemical examination of the content and quality of the endoplasmic reticulum (ER) and Golgi apparatus membranes in two in vivo situations characterized by a phase of active cell proliferation followed by a phase of declination in proliferation (rat brain tissue at early and late developmental stages) or by permanent active proliferation (gliomas and their most malignant manifestation, glioblastomas multiforme). It was found that, in highly proliferative phases of brain development (early embryo brain cells), the content of ER and Golgi apparatus membranes, measured as total lipid phosphorous content, is higher than in adult brain cells. In addition, the concentration of protein markers of ER and Golgi is also higher in early embryo brain cells and in human glioblastoma multiforme cells than in adult rat brain or in nonpathological human brain cells. Results suggest that the amount of endomembranes and the concentration of constituent functional proteins diminish as cells decline in their proliferative activity.

Investigating Shared Norms in Multicultural Teams: Exploring How Team Member Scripts and Cognitive Adjustment Strategies Impact the Norm Formation Process

ERIC Educational Resources Information Center

McGurrin, Daniel Paul

2015-01-01

The purpose of this study was to understand how shared norms are developed in the early phase of multicultural team (MCT) formation. The development of shared norms is recognized as critical to MCTs' contributions to organizations, and they are a result of the cognitive adjustment of the team members in recognition of their differences (Brandl…

A comparative study of RNA and DNA as internal gene expression controls early in the developmental cycle of Chlamydia pneumoniae.

PubMed

Engström, Patrik; Bailey, Leslie; Onskog, Thomas; Bergström, Sven; Johansson, Jörgen

2010-03-01

Many microbial pathogens invade and proliferate within host cells and the molecular mechanism underlying this behavior is currently being revealed for several bacterial species. Testing clinically relevant antibacterial compounds and elucidating their effects on gene expression requires adequate controls, especially when studying genetically intractable organisms such as Chlamydia spp., for which various gene fusions cannot be constructed. Until now, relative mRNA levels in Chlamydia have been measured using different internal gene expression controls, including 16S rRNA, mRNAs, and DNA. Here, we compared the advantages and disadvantages of various internal expression controls during the early phase of Chlamydia pneumoniae development. The relative abundance of target mRNAs varied using the different internal control RNAs. This was partly due to variation in the transcript stability of the RNA species. Also, seven out of nine of the analyzed RNAs increased fivefold or more between 2 and 14 h postinfection, while the amount of DNA and number of cells remained essentially unaltered. Our results suggest that RNA should not be used as a gene expression control during the early phase of Chlamydia development, and that intrinsic bacterial DNA is preferable for that purpose because it is stable, abundant, and its relative amount is generally correlated with bacterial numbers.

Paroxysmal ocular movements - an early sign in Glut1 deficiency Syndrome.

PubMed

Reis, Sofia; Matias, Joana; Machado, Raquel; Monteiro, José Paulo

2018-05-05

The authors describe a 3-year-old female, diagnosed with GLUT1 deficiency Syndrome, with a previously unreported mutation in exon 7 of the SLC2A1 gene: c.968_972 + 3del P. (Val323Alafs*53), characterized by a classic phenotypic of acquired microcephaly, developmental delay, ataxia, spasticity, and epilepsy. Ketogenic diet was started at the age of 30 months with epilepsy improvement. She presented paroxysmal ocular movements in the first 12 months of life, recently defined as "aberrant gaze saccades", that are present in the early phase of visual system development, being one of the first disease signs, but easily disregarded. Recognizing these particular ocular movements would allow an early diagnosis, followed by ketogenic diet implementation, improving significantly the prognosis and the neurological development of those children.

78 FR 5816 - Guidance for Industry on Clinical Pharmacogenomics: Premarket Evaluation in Early-Phase Clinical...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-28

.... The guidance provides recommendations on when and how genomic principles should be considered and... recommendations on when and how genomic principles should be considered and applied in early-phase clinical... the larger, later adequate, and well-controlled trials (phase 3) that are needed to support marketing...

Words Are Not Enough: Providing the Context for Social Communication and Interaction

ERIC Educational Resources Information Center

Rollins, Pamela Rosenthal

2016-01-01

This article elucidates the unfolding of 3 phases of cognitive development through which typical children move during the first 2 years of life to illuminate the interrelationships among early cognition, communicative intention, and word-learning strategies. The resulting theoretical framework makes clear the developmental prerequisites for social…

"Phronesis" and Moral Education: Treading beyond the Truisms

ERIC Educational Resources Information Center

Kristjánsson, Kristján

2014-01-01

Whereas most latter-day Aristotelian approaches to moral education highlight the early habituation phase of moral development, they rarely have much to say, beyond truisms from the "Nicomachean ethics," about the ultimate Aristotelian goal of cultivating fully fledged "phronesis." The aim of this article is to repair the dearth…

Critical phases in the seed development of common juniper (Juniperus communis).

PubMed

Gruwez, R; Leroux, O; De Frenne, P; Tack, W; Viane, R; Verheyen, K

2013-01-01

Common juniper (Juniperus communis L.) populations in northwest European lowlands are currently declining in size and number. An important cause of this decline is a lack of natural regeneration. Low seed viability seems to be one of the main bottlenecks in this process. Previous research revealed a negative relation between seed viability and both temperature and nitrogen deposition. Additionally, the seeds of common juniper have a variable ripening time, which possibly influences seed viability. However, the underlying mechanisms remain unresolved. In order to elucidate this puzzle, it is important to understand in which phases of seed production the main defects are situated, together with the influence of ripening time. In this study, we compared seed viability of populations with and without successful recruitment. We examined three seed phases: (i) gamete development; (ii) fertilisation and early-embryo development; and (iii) late-embryo development. After the first two phases, we found no difference in the percentage viable seeds between populations with or without recruitment. After late-embryo development, populations without recruitment showed a significantly lower percentage of viable seeds. These results suggest that late-embryo development is a bottleneck in seed development. However, the complex interaction between seed viability and ripening time suggest that the causes should be in the second seed phase, as the accelerated development of male and female gametophytes may disturb the male-female synchrony for successful mating. © 2012 German Botanical Society and The Royal Botanical Society of the Netherlands.

Superfluid 3He—the Early Days

NASA Astrophysics Data System (ADS)

Lee, D. M.; Leggett, A. J.

2011-08-01

A history is given of liquid 3He research from the time when 3He first became available following World War II through 1972 when the discovery of the superfluid phases was made. The Fermi liquid nature was established early on, and the Landau Fermi liquid theory provided a framework for understanding the interactions between the Fermions (quasiparticles). The theory's main triumph was to predict zero sound, which was soon discovered experimentally. Experimental techniques are treated, including adiabatic demagnetization, dilution refrigerator technology, and Pomeranchuk cooling. A description of the superfluid 3He discovery experiments using the latter two of these techniques is given. While existing theories provided a basis for understanding the newly discovered superfluid phases in terms of ℓ>0 Cooper pairs, the unexpected stability of the A phase in the high- P, high- T region of the phase diagram needed for its explanation a creative leap beyond the BCS paradigm. The use of sum rules to interpret some of the unusual magnetic resonance in liquid 3He is discussed. Eventually a complete theory of the spin dynamics of superfluid 3He was developed, which predicted many of the exciting phenomena subsequently discovered.

Both cyclin A and cyclin E have S-phase promoting (SPF) activity in Xenopus egg extracts.

PubMed

Strausfeld, U P; Howell, M; Descombes, P; Chevalier, S; Rempel, R E; Adamczewski, J; Maller, J L; Hunt, T; Blow, J J

1996-06-01

Extracts of activated Xenopus eggs in which protein synthesis has been inhibited support a single round of chromosomal DNA replication. Affinity-depletion of cyclin dependent kinases (Cdks) from these extracts blocks the initiation of DNA replication. We define 'S-phase promoting factor' (SPF) as the Cdk activity required for DNA replication in these Cdk-depleted extracts. Recombinant cyclins A and E, but not cyclin B, showed significant SPF activity. High concentrations of cyclin A promoted entry into mitosis, which inhibited DNA replication. In contrast, high concentrations of cyclin E1 promoted neither nuclear envelope disassembly nor full chromosome condensation. In the early embryo cyclin E1 complexes exclusively with Cdk2 and cyclin A is complexed predominantly with Cdc2; only later in development does cyclin A associate with Cdk2. We show that baculovirus-produced complexes of cyclin A-Cd2, cyclin A-Cdk2 and cyclin E-Cdk2 could each provide SPF activity. These results suggest that although in the early Xenopus embryo cyclin E1-Cdk2 is sufficient to support entry into S-phase, cyclin A-Cdc2 provides a significant additional quantity of SPF as its levels rise during S phase.

Spontaneous splenic rupture during the recovery phase of dengue fever.

PubMed

de Silva, W T T; Gunasekera, M

2015-07-02

Spontaneous splenic rupture is a rare but known complication of dengue fever. Previously reported cases have occurred early during the course of the disease and most cases have led to a fatal outcome. Here we report a case of spontaneous splenic rupture in a patient with dengue fever, which occurred during the recovery phase of the illness. A 28-year-old Sinhalese, Sri Lankan man presented with a history of fever, myalgia and vomiting of 4 days duration. Investigations revealed a diagnosis of dengue fever with no signs of plasma leakage. He was managed in the ward as per local protocol. During the recovery phase the patient developed severe abdominal distention with circulatory failure. Radiology revealed splenic rupture with massive amounts of abdominal free fluid. The patient was resuscitated and Emergency laparotomy with splenectomy was performed. The outcome was excellent with the patient making a complete recovery. Although splenic rupture is a known complication of dengue fever it may be manifested late in the disease process. A high degree of suspicion should be maintained and patients must be monitored even during the recovery phase of dengue fever. Early diagnosis and intervention can prevent mortality.

Development of upper body coordination during sitting in typically developing infants

PubMed Central

KYVELIDOU, ANASTASIA; STUBERG, WAYNE A.; HARBOURNE, REGINA T.; DEFFEYES, JOAN E.; BLANKE, DANIEL; STERGIOU, NICHOLAS

2009-01-01

Pediatric Research Articles Ahead of Print contains articles in unedited manuscript form that have been peer-reviewed and accepted for publication. As a service to our readers, we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting and review of the resulting proof before it is published in its final definitive form. Please note that during the production process errors may be discovered, which could affect the content, and all legal disclaimers that apply to the journal pertain. Our goal was to determine how the actions of the thorax and the pelvis are organized and coordinated to achieve independent sitting posture in typically developing infants. The participants were ten typically developing infants that were evaluated longitudinally from first onset of sitting until sitting independence. Each infant underwent nine testing sessions. The first session included motor evaluation with the Peabody test. The other eight sessions occurred over a period of four months where sitting behavior was evaluated by angular kinematics of the thorax and the pelvis. A physical therapist evaluated sitting behavior in each session and categorized it according to five stages. The phasing relationship of the thorax and the pelvis was calculated and evaluated longitudinally using a one-way ANOVA. With development, the infants progressed from an in-phase (moving in the same direction) to an out-of-phase (moving in an opposite direction) coordinative relationship between the thorax and the pelvis segments. This change was significant for both the sagittal and frontal planes of motion. Clinically, this relationship is important because it provides a method to quantify infant sitting postural development, and can be used to assess efficacy of early interventions for pediatric populations with developmental motor delays. PMID:19190546

CLB5-dependent activation of late replication origins in S. cerevisiae.

PubMed

Donaldson, A D; Raghuraman, M K; Friedman, K L; Cross, F R; Brewer, B J; Fangman, W L

1998-08-01

Replication origins in chromosomes are activated at specific times during the S phase. We show that the B-type cyclins are required for proper execution of this temporal program. clb5 cells activate early origins but not late origins, explaining the previously described long clb5 S phase. Origin firing appears normal in cIb6 mutants. In clb5 clb6 double mutant cells, the late origin firing defect is suppressed, accounting for the normal duration of the phase despite its delayed onset. Therefore, Clb5p promotes the timely activation of early and late origins, but Clb6p can activate only early origins. In clb5 clb6 mutants, the other B-type cyclins (Clb1-4p) promote an S phase during which both early and late replication origins fire.

Amateur Radio on the International Space Station - Phase 2 Hardware System

NASA Technical Reports Server (NTRS)

Bauer, F.; McFadin, L.; Bruninga, B.; Watarikawa, H.

2003-01-01

The International Space Station (ISS) ham radio system has been on-orbit for over 3 years. Since its first use in November 2000, the first seven expedition crews and three Soyuz taxi crews have utilized the amateur radio station in the Functional Cargo Block (also referred to as the FGB or Zarya module) to talk to thousands of students in schools, to their families on Earth, and to amateur radio operators around the world. Early on, the Amateur Radio on the International Space Station (ARISS) international team devised a multi-phased hardware development approach for the ISS ham radio station. Three internal development Phases. Initial Phase 1, Mobile Radio Phase 2 and Permanently Mounted Phase 3 plus an externally mounted system, were proposed and agreed to by the ARISS team. The Phase 1 system hardware development which was started in 1996 has since been delivered to ISS. It is currently operational on 2 meters. The 70 cm system is expected to be installed and operated later this year. Since 2001, the ARISS international team have worked to bring the second generation ham system, called Phase 2, to flight qualification status. At this time, major portions of the Phase 2 hardware system have been delivered to ISS and will soon be installed and checked out. This paper intends to provide an overview of the Phase 1 system for background and then describe the capabilities of the Phase 2 radio system. It will also describe the current plans to finalize the Phase 1 and Phase 2 testing in Russia and outlines the plans to bring the Phase 2 hardware system to full operation.

Towards a Location-based Service for Early Mental Health Interventions in Disaster Response Using Minimalistic Tele-operated Android Robots Technology

NASA Astrophysics Data System (ADS)

Vahidi, H.; Mobasheri, A.; Alimardani, M.; Guan, Q.; Bakillah, M.

2014-04-01

Providing early mental health services during disaster is a great challenge in the disaster response phase. Lack of access to adequate mental-health professionals in the early stages of large-scale disasters dramatically influences the trend of a successful mental health aid. In this paper, a conceptual framework has been suggested for adopting cellphone-type tele-operated android robots in the early stages of disasters for providing the early mental health services for disaster survivors by developing a locationbased and participatory approach. The techniques of enabling GI-services in a Peer-to-Peer (P2P) environment were studied to overcome the limitations of current centralized services. Therefore, the aim of this research study is to add more flexibility and autonomy to GI web services (WMS, WFS, WPS, etc.) and alleviate to some degree the inherent limitations of these centralized systems. A P2P system Architecture is presented for the location-based service using minimalistic tele-operated android robots, and some key techniques of implementing this service using BestPeer were studied for developing this framework.

A Plutocratic Proposal: an ethical way for rich patients to pay for a place on a clinical trial

PubMed Central

Masters, Alexander

2017-01-01

Many potential therapeutic agents are discarded before they are tested in humans. These are not quack medications. They are drugs and other interventions that have been developed by responsible scientists in respectable companies or universities and are often backed up by publications in peer-reviewed journals. These possible treatments might ease suffering and prolong the lives of innumerable patients, yet they have been put aside. In this paper, we outline a novel mechanism—the Plutocratic Proposal—to revive such neglected research and fund early phase clinical trials. The central idea of the Proposal is that any patient who rescues a potential therapeutic agent from neglect by funding early phase clinical trials (either entirely or in large part) should be offered a place on the trial. PMID:28588147

Early Formulation Model-centric Engineering on NASA's Europa Mission Concept Study

NASA Technical Reports Server (NTRS)

Bayer, Todd; Chung, Seung; Cole, Bjorn; Cooke, Brian; Dekens, Frank; Delp, Chris; Gontijo, Ivair; Lewis, Kari; Moshir, Mehrdad; Rasmussen, Robert;

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

PubMed Central

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

2012-01-01

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

A Risk Management Framework to Characterize Black Swan Risks: A Case Study of Lightning Effects on Insensitive High Explosives

NASA Astrophysics Data System (ADS)

Sanders, Gary A.

Effective and efficient risk management processes include the use of high fidelity modeling and simulation during the concept exploration phase as part of the technology and risk assessment activities, with testing and evaluation tasks occurring in later design development phases. However, some safety requirements and design architectures may be dominated by the low probability/high consequence "Black Swan" vulnerabilities that require very early testing to characterize and efficiently mitigate. Failure to address these unique risks has led to catastrophic systems failures including the space shuttle Challenger, Deepwater Horizon, Fukushima nuclear reactor, and Katrina dike failures. Discovering and addressing these risks later in the design and development process can be very costly or even lead to project cancellation. This paper examines the need for risk management process adoption of early hazard phenomenology testing to inform the technical risk assessment, requirements definition and conceptual design. A case study of the lightning design vulnerability of the insensitive high explosives being used in construction, mining, demolition, and defense industries will be presented to examine the impact of this vulnerability testing during the concept exploration phase of the design effort. While these insensitive high explosives are far less sensitive to accidental initiation by fire, impact, friction or even electrical stimuli, their full range of sensitivities have not been characterized and ensuring safe engineering design and operations during events such as lightning storms requires vulnerability testing during the risk assessment phase.

Early Validation of Failure Detection, Isolation, and Recovery Design Using Heterogeneous Modelling and Simulation

NASA Astrophysics Data System (ADS)

van der Plas, Peter; Guerriero, Suzanne; Cristiano, Leorato; Rugina, Ana

2012-08-01

Modelling and simulation can support a number of use cases across the spacecraft development life-cycle. Given the increasing complexity of space missions, the observed general trend is for a more extensive usage of simulation already in the early phases. A major perceived advantage is that modelling and simulation can enable the validation of critical aspects of the spacecraft design before the actual development is started, as such reducing the risk in later phases.Failure Detection, Isolation, and Recovery (FDIR) is one of the areas with a high potential to benefit from early modelling and simulation. With the increasing level of required spacecraft autonomy, FDIR specifications can grow in such a way that the traditional document-based review process soon becomes inadequate.This paper shows that FDIR modelling and simulation in a system context can provide a powerful tool to support the FDIR verification process. It is highlighted that FDIR modelling at this early stage requires heterogeneous modelling tools and languages, in order to provide an adequate functional description of the different components (i.e. FDIR functions, environment, equipment, etc.) to be modelled.For this reason, an FDIR simulation framework is proposed in this paper. This framework is based on a number of tools already available in the Avionics Systems Laboratory at ESTEC, which are the Avionics Test Bench Functional Engineering Simulator (ATB FES), Matlab/Simulink, TASTE, and Real Time Developer Studio (RTDS).The paper then discusses the application of the proposed simulation framework to a real case-study, i.e. the FDIR modelling of a satellite in support of actual ESA mission. Challenges and benefits of the approach are described. Finally, lessons learned and the generality of the proposed approach are discussed.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feye-Treimer, U., E-mail: feye-treimer@helmholtz-berlin.de; Treimer, W.

Purpose: This theoretical work contains a detailed investigation of the potential and sensitivity of phase-based x-ray scattering for cancer detection in biopsies if cancer is in a very early stage of development. Methods: Cancer cells in their early stage of development differ from healthy ones mainly due to their faster growing cell nuclei and the enlargement of their densities. This growth is accompanied by an altered nucleus–plasma relation for the benefit of the cell nuclei, that changes the physical properties especially the index of refraction of the cell and the one of the cell nuclei. Interaction of radiation with mattermore » is known to be highly sensitive to small changes of the index of refraction of matter; therefore a detection of such changes of volume and density of cell nuclei by means of high angular resolved phase-based scattering of x rays might provide a technique to distinguish malignant cells from healthy ones ifthe cell–cell nucleus system is considered as a coherent phase shifting object. Then one can observe from a thin biopsy which represents a monolayer of cells (no multiple scattering) that phase-based x-ray scattering curves from healthy cells differ from those of cancer cells in their early stage of development. Results: Detailed calculations of x-ray scattering patterns from healthy and cancer cell nuclei yield graphs and numbers with which one can distinguish healthy cells from cancer ones, taking into account that both kinds of cells occur in a tissue within a range of size and density. One important result is the role and the influence of the (lateral) coherence width of the radiation on the scattering curves and the sensitivity of phase-based scattering for cancer detection. A major result is that a larger coherence width yields a larger sensitivity for cancer detection. Further import results are calculated limits for critical sizes and densities of cell nuclei in order to attribute the investigated tissue to be healthy or diseased. Conclusions: With this proposed method it should be in principle possible to detect cancer cells in apparently healthy tissues in biopsies and/or in samples of the far border region of abscised or excised tissues. Thus this method could support established methods in diagnostics of cancer-suspicious samples.« less

Early Childhood Settings in 15 Countries: What Are Their Structural Characteristics? The IEA Preprimary Project, Phase 2.

ERIC Educational Resources Information Center

Olmsted, Patricia P., Ed.; Montie, Jeanne, Ed.

This is the second of four monographs reporting the findings of Phase 2 of the International Association for the Evaluation of Educational Achievement (IEA) Preprimary Project, which presents data on the physical characteristics of children's early childhood settings. Early childhood settings were documented in the following 15 countries: (1)…

Current status of topical antiretroviral chemoprophylaxis.

PubMed

Van Damme, Lut; Szpir, Michael

2012-11-01

Recent studies suggest that the vaginal delivery of antiretroviral (ARV) agents - such as tenofovir, dapivirine and UC781 - may be a promising way to reduce the high rates of HIV infection among women in developing countries. This review examines these developments. The Microbicide Trials Network 003 study, a large phase IIb trial, was unable to show that daily dosing with 1% tenofovir vaginal gel was effective for HIV prevention. Nevertheless, preclinical and early-phase clinical trials suggest that ARV drugs - formulated in vaginal gels, rings, films, tablets and diaphragms - could be effective for HIV chemoprophylaxis. Investigations of topical chemoprophylaxis methods have seen mixed results in the past 12-18 months. Product adherence may prove to be one of the field's greatest challenges. Phase II and III trials continue to explore different dosing strategies for topical products that contain one or more ARV agents.

Phase distribution of spliceosomal introns: implications for intron origin

PubMed Central

Nguyen, Hung D; Yoshihama, Maki; Kenmochi, Naoya

2006-01-01

Background The origin of spliceosomal introns is the central subject of the introns-early versus introns-late debate. The distribution of intron phases is non-uniform, with an excess of phase-0 introns. Introns-early explains this by speculating that a fraction of present-day introns were present between minigenes in the progenote and therefore must lie in phase-0. In contrast, introns-late predicts that the nonuniformity of intron phase distribution reflects the nonrandomness of intron insertions. Results In this paper, we tested the two theories using analyses of intron phase distribution. We inferred the evolution of intron phase distribution from a dataset of 684 gene orthologs from seven eukaryotes using a maximum likelihood method. We also tested whether the observed intron phase distributions from 10 eukaryotes can be explained by intron insertions on a genome-wide scale. In contrast to the prediction of introns-early, the inferred evolution of intron phase distribution showed that the proportion of phase-0 introns increased over evolution. Consistent with introns-late, the observed intron phase distributions matched those predicted by an intron insertion model quite well. Conclusion Our results strongly support the introns-late hypothesis of the origin of spliceosomal introns. PMID:16959043

A tale of two timescales: Mixing, mass generation, and phase transitions in the early universe

NASA Astrophysics Data System (ADS)

Dienes, Keith R.; Kost, Jeff; Thomas, Brooks

2016-02-01

Light scalar fields such as axions and string moduli can play an important role in early-universe cosmology. However, many factors can significantly impact their late-time cosmological abundances. For example, in cases where the potentials for these fields are generated dynamically—such as during cosmological mass-generating phase transitions—the duration of the time interval required for these potentials to fully develop can have significant repercussions. Likewise, in scenarios with multiple scalars, mixing amongst the fields can also give rise to an effective timescale that modifies the resulting late-time abundances. Previous studies have focused on the effects of either the first or the second timescale in isolation. In this paper, by contrast, we examine the new features that arise from the interplay between these two timescales when both mixing and time-dependent phase transitions are introduced together. First, we find that the effects of these timescales can conspire to alter not only the total late-time abundance of the system—often by many orders of magnitude—but also its distribution across the different fields. Second, we find that these effects can produce large parametric resonances which render the energy densities of the fields highly sensitive to the degree of mixing as well as the duration of the time interval over which the phase transition unfolds. Finally, we find that these effects can even give rise to a "reoverdamping" phenomenon which causes the total energy density of the system to behave in novel ways that differ from those exhibited by pure dark matter or vacuum energy. All of these features therefore give rise to new possibilities for early-universe phenomenology and cosmological evolution. They also highlight the importance of taking into account the time dependence associated with phase transitions in cosmological settings.

Practitioners' Experiences of Personal Ownership and Autonomy in Their Support for Young Children's Thinking

ERIC Educational Resources Information Center

Robson, Sue; Fumoto, Hiroko

2009-01-01

This article reports the third phase of the Froebel Research Fellowship Project: "The Voice of the Child: ownership and autonomy in early learning". Building on the first and second phases of this study, this phase examined early years practitioners' experiences of supporting young children's thinking in relation to the personal…

Designing a community-based lay health advisor training curriculum to address cancer health disparities.

PubMed

Gwede, Clement K; Ashley, Atalie A; McGinnis, Kara; Montiel-Ishino, F Alejandro; Standifer, Maisha; Baldwin, Julie; Williams, Coni; Sneed, Kevin B; Wathington, Deanna; Dash-Pitts, Lolita; Green, B Lee

2013-05-01

Racial and ethnic minorities have disproportionately higher cancer incidence and mortality than their White counterparts. In response to this inequity in cancer prevention and care, community-based lay health advisors (LHAs) may be suited to deliver effective, culturally relevant, quality cancer education, prevention/screening, and early detection services for underserved populations. APPROACH AND STRATEGIES: Consistent with key tenets of community-based participatory research (CBPR), this project engaged community partners to develop and implement a unique LHA training curriculum to address cancer health disparities among medically underserved communities in a tricounty area. Seven phases of curriculum development went into designing a final seven-module LHA curriculum. In keeping with principles of CBPR and community engagement, academic-community partners and LHAs themselves were involved at all phases to ensure the needs of academic and community partners were mutually addressed in development and implementation of the LHA program. Community-based LHA programs for outreach, education, and promotion of cancer screening and early detection, are ideal for addressing cancer health disparities in access and quality care. When community-based LHAs are appropriately recruited, trained, and located in communities, they provide unique opportunities to link, bridge, and facilitate quality cancer education, services, and research.

Cyclin B in mouse oocytes and embryos: importance for human reproduction and aneuploidy.

PubMed

Polański, Zbigniew; Homer, Hayden; Kubiak, Jacek Z

2012-01-01

Oocyte maturation and early embryo development require precise coordination between cell cycle progression and the developmental programme. Cyclin B plays a major role in this process: its accumulation and degradation is critical for driving the cell cycle through activation and inactivation of the major cell cycle kinase, CDK1. CDK1 activation is required for M-phase entry whereas its inactivation leads to exit from M-phase. The tempo of oocyte meiotic and embryonic mitotic divisions is set by the rate of cyclin B accumulation and the timing of its destruction. By controlling when cyclin B destruction is triggered and by co-ordinating this with the completion of chromosome alignment, the spindle assembly checkpoint (SAC) is a critical quality control system important for averting aneuploidy and for building in the flexibility required to better integrate cell cycle progression with development. In this review we focus on cyclin B metabolism in mouse oocytes and embryos and illustrate how the cell cycle-powered clock (in fact cyclin B-powered clock) controls oocyte maturation and early embryo development, thereby providing important insight into human reproduction and potential causes of Down syndrome.

An ultrastructural analysis of cyst wall development in the metacestode of Hymenolepis diminuta (Cestoda).

PubMed

Richards, K S; Arme, C

1984-12-01

A series of development stages (I-XI) have been devised to describe the development of the cyst wall of the metacestode of Hymenolepis diminuta. The cyst wall possesses tegumentary, muscular, fibrous and inner cyst tissues, the developmental rates and differentiation patterns of which are not identical. The tegumentary tissue differentiates posteriorly. Its microvillus-bearing distal cytoplasm remains simple until scolex retraction, after which rapid increase in depth followed by vacuolation occurs and basal membrane infoldings surround Phase 3 fibrogenesis fibrils. Senescence, which also affects the tegumentary cytons, then ensues. The muscle system development is posteriad and maturation, completed before scolex retraction, is followed by myocyton senescence. Posteriorly differentiated fibroblasts commence Phase 1 fibrogenesis after scolex retraction and the primary fibrous zone is fully established within approximately 6 days. Phase 2 and 3 fibrogenesis develop centrifugally, the fibrils of Phase 2 surrounding the tegumentary cytons and myocytons prior to their senescence, and those of Phase 3 lying more peripherally. The inner cyst tissue, established posteriorly, differentiates anteriorly, centripetally and early, the penultimate stage commencing just before scolex retraction, about 6 days after which the final maturation junctional complexes start development. Neither in vitro excystment nor infectivity of the definitive host can be satisfactorily achieved before the initial development of the primary fibrous zone. This may play a skeletal role during excystment, and is shown to be unaffected by the digestive enzymes which cause loss of cytoplasmic integrity in the outer regions of the cyst.

Wide-field phase imaging for the endoscopic detection of dysplasia and early-stage esophageal cancer

NASA Astrophysics Data System (ADS)

Fitzpatrick, C. R. M.; Gordon, G. S. D.; Sawyer, T. W.; Wilkinson, T. D.; Bohndiek, S. E.

2018-02-01

Esophageal cancer has a 5-year survival rate below 20%, but can be curatively resected if it is detected early. At present, poor contrast for early lesions in white light imaging leads to a high miss rate in standard-of- care endoscopic surveillance. Early lesions in the esophagus, referred to as dysplasia, are characterized by an abundance of abnormal cells with enlarged nuclei. This tissue has a different refractive index profile to healthy tissue, which results in different light scattering properties and provides a source of endogenous contrast that can be exploited for advanced endoscopic imaging. For example, point measurements of such contrast can be made with scattering spectroscopy, while optical coherence tomography generates volumetric data. However, both require specialist interpretation for diagnostic decision making. We propose combining wide-field phase imaging with existing white light endoscopy in order to provide enhanced contrast for dysplasia and early-stage cancer in an image format that is familiar to endoscopists. Wide-field phase imaging in endoscopy can be achieved using coherent illumination combined with phase retrieval algorithms. Here, we present the design and simulation of a benchtop phase imaging system that is compatible with capsule endoscopy. We have undertaken preliminary optical modelling of the phase imaging setup, including aberration correction simulations and an investigation into distinguishing between different tissue phantom scattering coefficients. As our approach is based on phase retrieval rather than interferometry, it is feasible to realize a device with low-cost components for future clinical implementation.

Measurement of wall shear stress in chick embryonic heart using optical coherence tomography

NASA Astrophysics Data System (ADS)

Ma, Zhenhe; Dou, Shidan; Zhao, Yuqian; Wang, Yi; Suo, Yanyan; Wang, Fengwen

2015-03-01

The cardiac development is a complicated process affected by genetic and environmental factors. Wall shear stress (WSS) is one of the components which have been proved to influence the morphogenesis during early stages of cardiac development. To study the mechanism, WSS measurement is a step with significant importance. WSS is caused by blood flow imposed on the inner surface of the heart wall and it can be determined by calculating velocity gradients of blood flow in a direction perpendicular to the wall. However, the WSS of the early stage embryonic heart is difficult to measure since the embryonic heart is tiny and beating fast. Optical coherence tomography (OCT) is a non-invasive imaging modality with high spatial and temporal resolution, which is uniquely suitable for the study of early stage embryonic heart development. In this paper, we introduce a method to measure the WSS of early stage chick embryonic heart based on high speed spectral domain optical coherence tomography (SDOCT). 4D (x,y,z,t) scan was performed on the outflow tract (OFT) of HH18 (~3 days of incubation) chick embryonic heart. After phase synchronization, OFT boundary segmentation, and OFT center line calculation, Doppler angle of the blood flow in the OFT can be achieved (This method has been described in previous publications). Combining with the Doppler OCT results, we calculate absolute blood flow velocity distribution in the OFT. The boundary of the OFT was segmented at each cross-sectional structural image, then geometrical center of the OFT can be calculated. Thus, the gradients of blood flow in radial direction can be calculated. This velocity gradient near the wall is termed wall shear rate and the WSS value is proportional to the wall shear rate. Based on this method, the WSS at different heart beating phase are compare. The result demonstrates that OCT is capable of early stage chicken embryonic heart WSS study.

Comparative Transcriptional Profiling of the Axolotl Limb Identifies a Tripartite Regeneration-Specific Gene Program

PubMed Central

Knapp, Dunja; Schulz, Herbert; Rascon, Cynthia Alexander; Volkmer, Michael; Scholz, Juliane; Nacu, Eugen; Le, Mu; Novozhilov, Sergey; Tazaki, Akira; Protze, Stephanie; Jacob, Tina; Hubner, Norbert; Habermann, Bianca; Tanaka, Elly M.

2013-01-01

Understanding how the limb blastema is established after the initial wound healing response is an important aspect of regeneration research. Here we performed parallel expression profile time courses of healing lateral wounds versus amputated limbs in axolotl. This comparison between wound healing and regeneration allowed us to identify amputation-specific genes. By clustering the expression profiles of these samples, we could detect three distinguishable phases of gene expression – early wound healing followed by a transition-phase leading to establishment of the limb development program, which correspond to the three phases of limb regeneration that had been defined by morphological criteria. By focusing on the transition-phase, we identified 93 strictly amputation-associated genes many of which are implicated in oxidative-stress response, chromatin modification, epithelial development or limb development. We further classified the genes based on whether they were or were not significantly expressed in the developing limb bud. The specific localization of 53 selected candidates within the blastema was investigated by in situ hybridization. In summary, we identified a set of genes that are expressed specifically during regeneration and are therefore, likely candidates for the regulation of blastema formation. PMID:23658691

Embryo developmental events and the egg case of the Aleutian skate Bathyraja aleutica (Gilbert) and the Alaska skate Bathyraja parmifera (Bean).

PubMed

Hoff, G R

2009-02-01

Embryo development events were correlated with egg-case changes for the Aleutian skate Bathyraja aleutica and the Alaska skate Bathyraja parmifera. Yolk absorption underwent two phases: that of steady absorption during early development and that of rapid yolk absorption during the final development stages. Total length (L(T)) for 50% of the pre-hatching embryos egg-case jelly disappearance was 92.04 mm (range 81-102 mm) and 99.36 mm (range 81-100 mm) for B. aleutica and B. parmifera, respectively, allowing the inner chamber to open to seawater flow. The tail filament underwent three phases of growth: rapid elongation during early development (<100 mm embryo L(T)), stasis of tail filament length during the remainder of embryo development and rapid absorption soon after hatching. Complete tail filament development coincided with the disappearance of egg-case jelly. Clasper buds first developed at embryos >70 mm L(T) for both species and the sex ratio was 1:1 well before hatching. Egg cases that were devoid of an ova or developing embryo were c. 5.0 and 6.5% of the egg cases examined for B. aleutica and B. parmifera, respectively. Measurements showed that egg cases containing only egg jelly were smaller in both width and length than those possessing an ova. Embryo stages were punctuated with distinct events that correlated with egg case changes controlling the internal environment of the developing embryo.

Successful crossings with early flowering transgenic poplar: interspecific crossings, but not transgenesis, promoted aberrant phenotypes in offspring.

PubMed

Hoenicka, Hans; Lehnhardt, Denise; Nilsson, Ove; Hanelt, Dieter; Fladung, Matthias

2014-10-01

In forest tree species, the reproductive phase is reached only after many years or even decades of juvenile growth. Different early flowering systems based on the genetic transfer of heat-shock promoter driven flowering-time genes have been proposed for poplar; however, no fertile flowers were reported until now. Here, we studied flower and pollen development in both HSP::AtFT and wild-type male poplar in detail and developed an optimized heat treatment protocol to obtain fertile HSP::AtFT flowers. Anthers from HSP::AtFT poplar flowers containing fertile pollen grains showed arrested development in stage 12 instead of reaching phase 13 as do wild-type flowers. Pollen grains could be isolated under the binocular microscope and were used for intra- and interspecific crossings with wild-type poplar. F1-seedlings segregating the HSP::AtFT gene construct according to Mendelian laws were obtained. A comparison between intra- and interspecific crossings revealed that genetic transformation had no detrimental effects on F1-seedlings. However, interspecific crossings, a broadly accepted breeding method, produced 47% seedlings with an aberrant phenotype. The early flowering system presented in this study opens new possibilities for accelerating breeding of poplar and other forest tree species. Fast breeding and the selection of transgene-free plants, once the breeding process is concluded, can represent an attractive alternative even under very restrictive regulations. © 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

A Framework for Evaluating R&D Impacts and Supply Chain Dynamics Early in a Product Life Cycle. Looking inside the black box of innovation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jordan, Gretchen; Mote, Jonathan; Ruegg, Rosalie

This report provides a framework for evaluation of R&D investments aimed at speeding up the pace of innovation and strengthening domestic manufacturing and supply chains, which make up a portion of the investments of the U.S. Department of Energy's (DOEs) Office of Energy Efficiency and Renewable Energy (EERE). These investments focus on early phases of the product life cycle, characterized as extending from pre-product, late stage R&D, to initial product introduction and through to early market growth. The investments aim to provide support for additional technology, supply-chain, manufacturing, and early market development to enhance or create markets for clean energymore » technologies and strengthen the U.S. industry base.« less

Recruitment Early Warning System. Phase II. Volume 1. Research and Development of the Recruitment EWS (Early Warning System).

DTIC Science & Technology

1985-09-30

DRIVE. RESTON, VA 22091 NATO (703) 476-5500 +’ h, .*Je/_ft, MEND " " E I: v zRm MV WK= I 8 6D.’"-. by L Peter Greenston, Lawrence Goldberg, Sigurd... Lawrence Goldberg, Sigurd Hermansen, and Sherry Andrews September 1985 .’. This report was prepared under the Navy Manpower R&D Program of the Office of...February for seniors, and in the summer for graduates. The seasonal pattern is apparently even more differentiated in the Marine Corps. - 5.~ &,.p

Mapping the Contours of Faith in the Land of Separation: Spiritual Geographies for Children

ERIC Educational Resources Information Center

Kirk, Patty

2004-01-01

According to Jean Piaget, children begin to develop a concept of an object, such as that it has sides that are not visible from the child's perspective or that it is likely to be where one saw it last, in early infancy. By the close of the prelinguistic phase at about 2 years old, the child has developed a mature object concept, one that…

Warfighting Concepts to Future Weapon System Designs (WARCON)

DTIC Science & Technology

2003-09-12

34* Software design documents rise to litigation. "* A Material List "Cost information that may support, or may * Final Engineering Process Maps be...document may include design the system as derived from the engineering design, software development, SRD. MTS Technologies, Inc. 26 FOR OFFICIAL USE...document, early in the development phase. It is software engineers produce the vision of important to establish a standard, formal the design effort. As

Metacognition in Early Phase Psychosis: Toward Understanding Neural Substrates

PubMed Central

Vohs, Jenifer L.; Hummer, Tom A.; Yung, Matthew G.; Francis, Michael M.; Lysaker, Paul H.; Breier, Alan

2015-01-01

Individuals in the early phases of psychotic illness have disturbed metacognitive capacity, which has been linked to a number of poor outcomes. Little is known, however, about the neural systems associated with metacognition in this population. The purpose of this study was to elucidate the neuroanatomical correlates of metacognition. We anticipated that higher levels of metacognition may be dependent upon gray matter density (GMD) of regions within the prefrontal cortex. Examining whole-brain structure in 25 individuals with early phase psychosis, we found positive correlations between increased medial prefrontal cortex and ventral striatum GMD and higher metacognition. These findings represent an important step in understanding the path through which the biological correlates of psychotic illness may culminate into poor metacognition and, ultimately, disrupted functioning. Such a path will serve to validate and promote metacognition as a viable treatment target in early phase psychosis. PMID:26132568

Transient up- and down-regulation of expression of myosin light chain 2 and myostatin mRNA mark the changes from stratified hyperplasia to muscle fiber hypertrophy in larvae of gilthead sea bream (Sparus aurata L.).

PubMed

Georgiou, Stella; Alami-Durante, Hélène; Power, Deborah M; Sarropoulou, Elena; Mamuris, Zissis; Moutou, Katerina A

2016-02-01

Hyperplasia and hypertrophy are the two mechanisms by which muscle develops and grows. We study these two mechanisms, during the early development of white muscle in Sparus aurata, by means of histology and the expression of structural and regulatory genes. A clear stage of stratified hyperplasia was identified early in the development of gilthead sea bream but ceased by 35 dph when hypertrophy took over. Mosaic recruitment of new white fibers began as soon as 60 dph. The genes mlc2a and mlc2b were expressed at various levels during the main phases of hyperplasia and hypertrophy. The genes myog and mlc2a were significantly up-regulated during the intensive stratified formation of new fibers and their expression was significantly correlated. Expression of mstn1 and igf1 increased at 35 dph, appeared to regulate the hyperplasia-to-hypertrophy transition, and may have stimulated the expression of mlc2a, mlc2b and col1a1 at the onset of mosaic hyperplasia. The up-regulation of mstn1 at transitional phases in muscle development indicates a dual regulatory role of myostatin in fish larval muscle growth.

Effects of temperature and salinity on larval survival and development in the invasive shrimp Palaemon macrodactylus (Caridea: Palaemonidae) along the reproductive season

NASA Astrophysics Data System (ADS)

Guadalupe Vázquez, M.; Bas, Claudia C.; Kittlein, Marcelo; Spivak, Eduardo D.

2015-05-01

The invasive shrimp Palaemon macrodactylus is associated mainly with brackish waters. Previous studies raised the question if tolerance to low salinities differs between larvae and adults. To answer this question, the combined effects of two temperatures (20 and 25 °C) and four salinities (5, 12, 23 and 34 psu) on survival and development of larvae that hatched at the beginning, in the midpoint and near the end of a reproductive season (denoted early, middle season and late larvae respectively) were examined. The three types of larvae were able to survive and reach juvenile phase at salinities between 12 and 34 psu and at both temperatures. At 5 psu all larvae died, but 45% molted at least once. Temperature and salinity to a lesser extent, had effects on the duration of development and on the number of larval stages in all larval types. Development was longer at the lower temperature, especially in middle season and late larvae. Most early larvae reached the juvenile phase through 5 larval stages; the number of larval stages of middle season and late larvae was higher at 20 °C and in late larvae also low salinity produced extra stages. Low salinity (12 psu) and, in early and middle season larvae, low temperature produced lighter and smaller individuals. Response of larvae to environmental factors seems to be related in part to the previous conditions (maternal effects and/or embryo development conditions). The narrower salinity tolerance of larvae compared to adults and the ability of zoea I to survive at least some days at 5 psu may be related with an export larval strategy.

Anesthesia-Induced Hypothermia Attenuates Early-Phase Blood-Brain Barrier Disruption but Not Infarct Volume following Cerebral Ischemia.

PubMed

Liu, Yu-Cheng; Lee, Yu-Da; Wang, Hwai-Lee; Liao, Kate Hsiurong; Chen, Kuen-Bao; Poon, Kin-Shing; Pan, Yu-Ling; Lai, Ted Weita

2017-01-01

Blood-brain barrier (BBB) disruption is thought to facilitate the development of cerebral infarction after a stroke. In a typical stroke model (such as the one used in this study), the early phase of BBB disruption reaches a peak 6 h post-ischemia and largely recovers after 8-24 h, whereas the late phase of BBB disruption begins 48-58 h post-ischemia. Because cerebral infarct develops within 24 h after the onset of ischemia, and several therapeutic agents have been shown to reduce the infarct volume when administered at 6 h post-ischemia, we hypothesized that attenuating BBB disruption at its peak (6 h post-ischemia) can also decrease the infarct volume measured at 24 h. We used a mouse stroke model obtained by combining 120 min of distal middle cerebral arterial occlusion (dMCAo) with ipsilateral common carotid arterial occlusion (CCAo). This model produced the most reliable BBB disruption and cerebral infarction compared to other models characterized by a shorter duration of ischemia or obtained with dMCAO or CCAo alone. The BBB permeability was measured by quantifying Evans blue dye (EBD) extravasation, as this tracer has been shown to be more sensitive for the detection of early-phase BBB disruption compared to other intravascular tracers that are more appropriate for detecting late-phase BBB disruption. We showed that a 1 h-long treatment with isoflurane-anesthesia induced marked hypothermia and attenuated the peak of BBB disruption when administered 6 h after the onset of dMCAo/CCAo-induced ischemia. We also demonstrated that the inhibitory effect of isoflurane was hypothermia-dependent because the same treatment had no effect on ischemic BBB disruption when the mouse body temperature was maintained at 37°C. Importantly, inhibiting the peak of BBB disruption by hypothermia had no effect on the volume of brain infarct 24 h post-ischemia. In conclusion, inhibiting the peak of BBB disruption is not an effective neuroprotective strategy, especially in comparison to the inhibitors of the neuronal death signaling cascade; these, in fact, can attenuate the infarct volume measured at 24 h post-ischemia when administered at 6 h in our same stroke model.

Cdc7 is required throughout the yeast S phase to activate replication origins.

PubMed

Donaldson, A D; Fangman, W L; Brewer, B J

1998-02-15

The long-standing conclusion that the Cdc7 kinase of Saccharomyces cerevisiae is required only to trigger S phase has been challenged by recent data that suggests it acts directly on individual replication origins. We tested the possibility that early- and late-activated origins have different requirements for Cdc7 activity. Cells carrying a cdc7(ts) allele were first arrested in G1 at the cdc7 block by incubation at 37 degrees C, and then were allowed to enter S phase by brief incubation at 23 degrees C. During the S phase, after return to 37 degrees C, early-firing replication origins were activated, but late origins failed to fire. Similarly, a plasmid with a late-activated origin was defective in replication. As a consequence of the origin activation defect, duplication of chromosomal sequences that are normally replicated from late origins was greatly delayed. Early-replicating regions of the genome duplicated at approximately their normal time. The requirements of early and late origins for Cdc7 appear to be temporally rather than quantitatively different, as reducing overall levels of Cdc7 by growth at semi-permissive temperature reduced activation at early and late origins approximately equally. Our results show that Cdc7 activates early and late origins separately, with late origins requiring the activity later in S phase to permit replication initiation.

Characterization of Early Age Curing and Shrinkage of Metakaolin-Based Inorganic Binders with Different Rheological Behavior by Fiber Bragg Grating Sensors.

PubMed

Palumbo, Giovanna; Iadicicco, Agostino; Messina, Francesco; Ferone, Claudio; Campopiano, Stefania; Cioffi, Raffaele; Colangelo, Francesco

2017-12-22

This paper reports results related to early age temperature and shrinkage measurements by means fiber Bragg gratings (FBGs), which were embedded in geopolymer matrices. The sensors were properly packaged in order to discriminate between different shrinkage behavior and temperature development. Geopolymer systems based on metakaolin were investigated, which dealt with different commercial aluminosilicate precursors and siliceous filler contents. The proposed measuring system will allow us to control, in a very accurate way, the early age phases of the binding systems made by metakaolin geopolymer. A series of experiments were conducted on different compositions; moreover, rheological issues related to the proposed experimental method were also assessed.

Available Tools to Facilitate Early Patient Access to Medicines in the EU and the USA: Analysis of Conditional Approvals and the Implications for Personalized Medicine.

PubMed

Leyens, Lada; Richer, Étienne; Melien, Øyvind; Ballensiefen, Wolfgang; Brand, Angela

2015-01-01

Scientific knowledge and our understanding of the human body and diseases have limited any possible treatment tailoring to each patient. The technological advances enabling the integration of various data sets (e.g. '-omics', microbiome, epigenetics and environmental exposure) have facilitated a greater understanding of the human body, the molecular basis of disease and all the factors influencing disease onset, progression and response to treatment, thereby ushering in the era of personalized medicine. We evaluate the regulatory approaches available to facilitate early patient access to efficacious and safe compounds in the EU and the USA in order to make more informed recommendations in the future as to the gaps in regulations for early patient access. An in-depth analysis of conditional approvals (EU) and accelerated approvals (USA) is performed based on the publicly available information (European public assessment reports and a summary review of products approved under both programmes). The types of product, indications, time to approval and type of evidence submitted were analysed. Between 2007 and early 2015, 17 products were conditionally approved in the EU and 25 in the USA, most of them in the area of oncology and based on evidence from phase II clinical trial data. Early approval of promising products based on data from early phases of development is already possible in the EU and the USA. Some of the improvements could entail implementing a rolling assessment of evidence in Europe and extending the scope of early dialogues. © 2015 S. Karger AG, Basel.

Early neurovascular dysfunction in a transgenic rat model of Alzheimer’s disease

PubMed Central

Joo, Illsung L.; Lai, Aaron Y.; Bazzigaluppi, Paolo; Koletar, Margaret M.; Dorr, Adrienne; Brown, Mary E.; Thomason, Lynsie A. M.; Sled, John G.; McLaurin, JoAnne; Stefanovic, Bojana

2017-01-01

Alzheimer’s disease (AD), pathologically characterized by amyloid-β peptide (Aβ) accumulation, neurofibrillary tangle formation, and neurodegeneration, is thought to involve early-onset neurovascular abnormalities. Hitherto studies on AD-associated neurovascular injury have used animal models that exhibit only a subset of AD-like pathologies and demonstrated some Aβ-dependent vascular dysfunction and destabilization of neuronal network. The present work focuses on the early stage of disease progression and uses TgF344-AD rats that recapitulate a broader repertoire of AD-like pathologies to investigate the cerebrovascular and neuronal network functioning using in situ two-photon fluorescence microscopy and laminar array recordings of local field potentials, followed by pathological analyses of vascular wall morphology, tau hyperphosphorylation, and amyloid plaques. Concomitant to widespread amyloid deposition and tau hyperphosphorylation, cerebrovascular reactivity was strongly attenuated in cortical penetrating arterioles and venules of TgF344-AD rats in comparison to those in non-transgenic littermates. Blood flow elevation to hypercapnia was abolished in TgF344-AD rats. Concomitantly, the phase-amplitude coupling of the neuronal network was impaired, evidenced by decreased modulation of theta band phase on gamma band amplitude. These results demonstrate significant neurovascular network dysfunction at an early stage of AD-like pathology. Our study identifies early markers of pathology progression and call for development of combinatorial treatment plans. PMID:28401931

Analysis of Dibenzothiophene Desulfurization in a Recombinant Pseudomonas putida Strain▿

PubMed Central

Calzada, Javier; Zamarro, María T.; Alcón, Almudena; Santos, Victoria E.; Díaz, Eduardo; García, José L.; Garcia-Ochoa, Felix

2009-01-01

Biodesulfurization was monitored in a recombinant Pseudomonas putida CECT5279 strain. DszB desulfinase activity reached a sharp maximum at the early exponential phase, but it rapidly decreased at later growth phases. A model two-step resting-cell process combining sequentially P. putida cells from the late and early exponential growth phases was designed to significantly increase biodesulfurization. PMID:19047400

Supporting universal prevention programs: a two-phased coaching model.

PubMed

Becker, Kimberly D; Darney, Dana; Domitrovich, Celene; Keperling, Jennifer Pitchford; Ialongo, Nicholas S

2013-06-01

Schools are adopting evidence-based programs designed to enhance students' emotional and behavioral competencies at increasing rates (Hemmeter et al. in Early Child Res Q 26:96-109, 2011). At the same time, teachers express the need for increased support surrounding implementation of these evidence-based programs (Carter and Van Norman in Early Child Educ 38:279-288, 2010). Ongoing professional development in the form of coaching may enhance teacher skills and implementation (Noell et al. in School Psychol Rev 34:87-106, 2005; Stormont et al. 2012). There exists a need for a coaching model that can be applied to a variety of teacher skill levels and one that guides coach decision-making about how best to support teachers. This article provides a detailed account of a two-phased coaching model with empirical support developed and tested with coaches and teachers in urban schools (Becker et al. 2013). In the initial universal coaching phase, all teachers receive the same coaching elements regardless of their skill level. Then, in the tailored coaching phase, coaching varies according to the strengths and needs of each teacher. Specifically, more intensive coaching strategies are used only with teachers who need additional coaching supports, whereas other teachers receive just enough support to consolidate and maintain their strong implementation. Examples of how coaches used the two-phased coaching model when working with teachers who were implementing two universal prevention programs (i.e., the PATHS curriculum and PAX Good Behavior Game [PAX GBG]) provide illustrations of the application of this model. The potential reach of this coaching model extends to other school-based programs as well as other settings in which coaches partner with interventionists to implement evidence-based programs.

An investigation of low ergonomics risk awareness, among staffs at early product development phase in Malaysia automotive industries

NASA Astrophysics Data System (ADS)

Aziz, Fazilah Abdul; Razali, Noraini; Najmiyah Jaafar, Nur

2016-02-01

Currently there are many automotive companies still unable to effectively prevent consequences of poor ergonomics in their manufacturing processes. This study purpose is to determine the surrounding factors that influence low ergonomics risk awareness among staffs at early product development phase in Malaysia automotive industry. In this study there are four variables, low ergonomic risk awareness, inappropriate method and tools, tight development schedule and lack of management support. The survey data were gathered from 245 respondents of local automotive companies in Malaysia. The data was analysed through multiple regression and moderated regression using the IBM SPSS software. Study results revealed that low ergonomic risk awareness has influenced by inappropriate method and tool, and tight development schedule. There were positive linear relationships between low ergonomic risk awareness and inappropriate method and tools, and tight development schedule. The more inappropriate method and tools applied; the lower their ergonomic risk awareness. The more tight development schedule is the lower ergonomic risk awareness. The relationship between low ergonomic risk awareness and inappropriate method and tools depends on staff's age, and education level. Furthermore the relationship between low ergonomic risk awareness and tight development schedule depends on staff's working experience and number of project involvement. The main contribution of this paper was identified the number of factors of low ergonomics risk awareness and offers better understanding on ergonomics among researchers and automotive manufacturer's employees during product development process.

Parents and Infants: An Interactive Network. I. Introduction.

ERIC Educational Resources Information Center

Yarrow, Leon J.

This symposium introduction outlines the first phase of an investigation of the mother-father-infant triad as an interactive system, influencing both parent attitudes and behaviors and child development. The focus of the research was on the early determinants of parental behavior. Subjects were 67 middle class, white parents and their first-born…

Exemplary Programs for the Handicapped. Volume I. Final Report.

ERIC Educational Resources Information Center

Freedman, Ruth; And Others

Presented is the final report of a study which assessed the effectiveness of 50 Bureau of Education for the Handicapped programs and selected 17 of the programs as providing exemplary services for handicapped people in the areas of career education, early childhood education, and manpower development. Considered separately are the three phases of…

Trauma and Early Adolescent Development: Case Examples from a Trauma-Informed Public Health Middle School Program

ERIC Educational Resources Information Center

Frydman, Jason Scott; Mayor, Christine

2017-01-01

Middle-school-age children are faced with a variety of developmental tasks, including the beginning phases of individuation from the family, building peer groups, social and emotional transitions, and cognitive shifts associated with the maturation process. This article summarizes how traumatic events impair and complicate these developmental…

Private Schools in France: Evolution of a System.

ERIC Educational Resources Information Center

Teese, Richard

1986-01-01

Reviews the major phases of development of the relationship between French private education and the state from the early 1950s when private schools (mostly Catholic) began receiving state subsidies. Concludes that the framework of subsidies has enabled Catholic schools to elaborate new social roles as well as to strengthen their traditional place…

The Law Enforcement Officer Stress Survey (LEOSS): Evaluation of Psychometric Properties

ERIC Educational Resources Information Center

Van Hasselt, Vincent B.; Sheehan, Donald C.; Malcolm, Abigail S.; Sellers, Alfred H.; Baker, Monty T.; Couwels, Judy

2008-01-01

This study establishes the reliability and validity of the Law Enforcement Officer Stress Survey (LEOSS), a short early-warning stress-screening measure for law enforcement officers. The initial phase of LEOSS development employed the behavioral-analytic model to construct a 25-item instrument specifically geared toward evaluation of stress in…

Black Vocational Technical and Industrial Arts Education: Development and History.

ERIC Educational Resources Information Center

Hall, Clyde W.

Since coverage of the history of industrial training of blacks in the United States is lacking, the author has compiled a single volume tracing this history from the plantation era. All phases are described--early schools prior to 1865, private and public industrial institutions of higher education, private institutions of higher education…

Chronology and pyroclastic stratigraphy of the May 18, 1980, eruption of Mount St. Helens, Washington

NASA Technical Reports Server (NTRS)

Criswell, C. William

1987-01-01

The eruption of Mount St. Helens on May 18, 1980 can be subdivided into six phases: the paroxysmal phase I, the early Plinian phase II, the early ash flow phase III, the climactic phase IV, the late ash flow phase V, and phase VI, the activity of which consisted of a low-energy ash plume. These phases are correlated with stratigraphic subunits of ash-fall tephra and pyroclastic flow deposits. Sustained vertical discharge of phase II produced evolved dacite with high S/Cl ratios. Ash flow activity of phase III is attributed to decreases in gas content, indicated by reduced S/Cl ratios and increased clast density of the less evolved gray pumice. Climactic events are attributed to vent clearing and exhaustion of the evolved dacite.

Early intervention for psychosis

PubMed Central

Marshall, Max; Rathbone, John

2014-01-01

Background Proponents of early intervention have argued that outcomes might be improved if more therapeutic efforts were focused on the early stages of schizophrenia or on people with prodromal symptoms. Early intervention in schizophrenia has two elements that are distinct from standard care: early detection, and phase-specific treatment (phase-specific treatment is a psychological, social or physical treatment developed, or modified, specifically for use with people at an early stage of the illness). Early detection and phase-specific treatment may both be offered as supplements to standard care, or may be provided through a specialised early intervention team. Early intervention is now well established as a therapeutic approach in America, Europe and Australasia. Objectives To evaluate the effects of: (a) early detection; (b) phase-specific treatments; and (c) specialised early intervention teams in the treatment of people with prodromal symptoms or first-episode psychosis. Search methods We searched the Cochrane Schizophrenia Group Trials Register (March 2009), inspected reference lists of all identified trials and reviews and contacted experts in the field. Selection criteria We included all randomised controlled trials (RCTs) designed to prevent progression to psychosis in people showing prodromal symptoms, or to improve outcome for people with first-episode psychosis. Eligible interventions, alone and in combination, included: early detection, phase-specific treatments, and care from specialised early intervention teams. We accepted cluster-randomised trials but excluded non-randomised trials. Data collection and analysis We reliably selected studies, quality rated them and extracted data. For dichotomous data, we estimated relative risks (RR), with the 95% confidence intervals (CI). Where possible, we calculated the number needed to treat/harm statistic (NNT/H) and used intention-to-treat analysis (ITT). Main results Studies were diverse, mostly small, undertaken by pioneering researchers and with many methodological limitations (18 RCTs, total n=1808). Mostly, meta-analyses were inappropriate. For the six studies addressing prevention of psychosis for people with prodromal symptoms, olanzapine seemed of little benefit (n=60, 1 RCT, RR conversion to psychosis 0.58 CI 0.3 to 1.2), and cognitive behavioural therapy (CBT) equally so (n=60, 1 RCT, RR conversion to psychosis 0.50 CI 0.2 to 1.7). A risperidone plus CBT plus specialised team did have benefit over specialist team alone at six months (n=59, 1 RCT, RR conversion to psychosis 0.27 CI 0.1 to 0.9, NNT 4 CI 2 to 20), but this was not seen by 12 months (n=59, 1 RCT, RR 0.54 CI 0.2 to 1.3). Omega 3 fatty acids (EPA) had advantage over placebo (n=76, 1 RCT, RR transition to psychosis 0.13 CI 0.02 to 1.0, NNT 6 CI 5 to 96). We know of no replications of this finding. The remaining trials aimed to improve outcome in first-episode psychosis. Phase-specific CBT for suicidality seemed to have little effect, but the single study was small (n=56, 1 RCT, RR suicide 0.81 CI 0.05 to 12.26). Family therapy plus a specialised team in the Netherlands did not clearly affect relapse (n=76, RR 1.05 CI 0.4 to 3.0), but without the specialised team in China it may (n=83, 1 RCT, RR admitted to hospital 0.28 CI 0.1 to 0.6, NNT 3 CI 2 to 6). The largest and highest quality study compared specialised team with standard care. Leaving the study early was reduced (n=547, 1 RCT, RR 0.59 CI 0.4 to 0.8, NNT 9 CI 6 to 18) and compliance with treatment improved (n=507, RR stopped treatment 0.20 CI 0.1 to 0.4, NNT 9 CI 8 to 12). The mean number of days spent in hospital at one year were not significantly different (n=507, WMD, −1.39 CI −2.8 to 0.1), neither were data for ‘Not hospitalised’ by five years (n=547, RR 1.05 CI 0.90 to 1.2). There were no significant differences in numbers ‘not living independently’ by one year (n=507, RR 0.55 CI 0.3 to 1.2). At five years significantly fewer participants in the treatment group were ‘not living independently’ (n=547, RR 0.42 CI 0.21 to 0.8, NNT 19 CI 14 to 62). When phase-specific treatment (CBT) was compared with befriending no significant differences emerged in the number of participants being hospitalised over the 12 months (n=62, 1 RCT, RR 1.08 CI 0.59 to 1.99). Phase-specific treatment E-EPA oils suggested no benefit (n=80, 1 RCT, RR no response 0.90 CI 0.6 to 1.4) as did phase-specific treatment brief intervention (n=106, 1 RCT, RR admission 0.86 CI 0.4 to 1.7). Phase-specific ACE found no benefit but participants given vocational intervention were more likely to be employed (n=41, 1 RCT, RR 0.39 CI 0.21 to 0.7, NNT 2 CI 2 to 4). Phase-specific cannabis and psychosis therapy did not show benefit (n=47, RR cannabis use 1.30 CI 0.8 to 2.2) and crisis assessment did not reduce hospitalisation (n=98, RR 0.85 CI 0.6 to 1.3). Weight was unaffected by early behavioural intervention. Authors’ conclusions There is emerging, but as yet inconclusive evidence, to suggest that people in the prodrome of psychosis can be helped by some interventions. There is some support for specialised early intervention services, but further trials would be desirable, and there is a question of whether gains are maintained. There is some support for phase-specific treatment focused on employment and family therapy, but again, this needs replicating with larger and longer trials. PMID:21678345

Automatic Debugging Support for UML Designs

NASA Technical Reports Server (NTRS)

Schumann, Johann; Swanson, Keith (Technical Monitor)

2001-01-01

Design of large software systems requires rigorous application of software engineering methods covering all phases of the software process. Debugging during the early design phases is extremely important, because late bug-fixes are expensive. In this paper, we describe an approach which facilitates debugging of UML requirements and designs. The Unified Modeling Language (UML) is a set of notations for object-orient design of a software system. We have developed an algorithm which translates requirement specifications in the form of annotated sequence diagrams into structured statecharts. This algorithm detects conflicts between sequence diagrams and inconsistencies in the domain knowledge. After synthesizing statecharts from sequence diagrams, these statecharts usually are subject to manual modification and refinement. By using the "backward" direction of our synthesis algorithm. we are able to map modifications made to the statechart back into the requirements (sequence diagrams) and check for conflicts there. Fed back to the user conflicts detected by our algorithm are the basis for deductive-based debugging of requirements and domain theory in very early development stages. Our approach allows to generate explanations oil why there is a conflict and which parts of the specifications are affected.

Giant cell arteritis and polymyalgia rheumatica: current challenges and opportunities.

PubMed

Dejaco, Christian; Brouwer, Elisabeth; Mason, Justin C; Buttgereit, Frank; Matteson, Eric L; Dasgupta, Bhaskar

2017-10-01

The fields of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) have advanced rapidly, resulting in a new understanding of these diseases. Fast-track strategies and improved awareness programmes that prevent irreversible sight loss through early diagnosis and treatment are a notable advance. Ultrasonography and other imaging techniques have been introduced into routine clinical practice and there have been promising reports on the efficacy of biologic agents, particularly IL-6 antagonists such as tocilizumab, in treating these conditions. Along with these developments, which should improve outcomes in patients with GCA and PMR, new questions and unmet needs have emerged; future research should address which pathogenetic mechanisms contribute to the different phases and clinical phenotypes of GCA, what role imaging has in the early diagnosis and monitoring of GCA and PMR, and in which patients and phases of these diseases novel biologic drugs should be used. This article discusses the implications of recent developments in our understanding of GCA and PMR, as well as the unmet needs concerning epidemiology, pathogenesis, imaging and treatment of these diseases.

Mechanisms of the early phases of plant gravitropism

NASA Technical Reports Server (NTRS)

Kiss, J. Z.

2000-01-01

Gravitropism is directed growth of a plant or plant organ in response to gravity and can be divided into the following temporal sequence: perception, transduction, and response. This article is a review of the research on the early events of gravitropism (i.e., phenomena associated with the perception and transduction phases). The two major hypotheses for graviperception are the protoplast-pressure and starch-statolith models. While most researchers support the concept of statoliths, there are suggestions that plants have multiple mechanisms of perception. Evidence supports the hypothesis that the actin cytoskeleton is involved in graviperception/transduction, but the details of these mechanisms remain elusive. A number of recent developments, such as increased use of the molecular genetic approach, magnetophoresis, and laser ablation, have facilitated research in graviperception and have allowed for refinement of the current models. In addition, the entire continuum of acceleration forces from hypo- to hyper-gravity have been useful in studying perception mechanisms. Future interdisciplinary molecular approaches and the availability of sophisticated laboratories on the International Space Station should help to develop new insights into mechanisms of gravitropism in plants.

MLViS: A Web Tool for Machine Learning-Based Virtual Screening in Early-Phase of Drug Discovery and Development

PubMed Central

Korkmaz, Selcuk; Zararsiz, Gokmen; Goksuluk, Dincer

2015-01-01

Virtual screening is an important step in early-phase of drug discovery process. Since there are thousands of compounds, this step should be both fast and effective in order to distinguish drug-like and nondrug-like molecules. Statistical machine learning methods are widely used in drug discovery studies for classification purpose. Here, we aim to develop a new tool, which can classify molecules as drug-like and nondrug-like based on various machine learning methods, including discriminant, tree-based, kernel-based, ensemble and other algorithms. To construct this tool, first, performances of twenty-three different machine learning algorithms are compared by ten different measures, then, ten best performing algorithms have been selected based on principal component and hierarchical cluster analysis results. Besides classification, this application has also ability to create heat map and dendrogram for visual inspection of the molecules through hierarchical cluster analysis. Moreover, users can connect the PubChem database to download molecular information and to create two-dimensional structures of compounds. This application is freely available through www.biosoft.hacettepe.edu.tr/MLViS/. PMID:25928885

Two-Phase Flow Research on the ISS for Thermal Control Applications

NASA Technical Reports Server (NTRS)

Motil, Brian J.

2013-01-01

With the era of full utilization of the ISS now upon us, this presentation will discuss some of the highest-priority areas for two-phase flow systems with thermal control applications. These priorities are guided by recommendations of a 2011 NRC Decadal Survey report, Recapturing a Future for Space Exploration, Life and Physical Sciences for a New Era as well as an internal NASA exercise in response to the NRC report conducted in early 2012. Many of these proposals are already in various stages of development, while others are still conceptual.

Proposal of one-shot-type spectroscopic-tomography for non-invasive medical-measurement

NASA Astrophysics Data System (ADS)

Sato, Shun; Fujiwara, Masaru; Abeygunawardhana, Pradeep K. W.; Suzuki, Satoru; Nishiyama, Akira; Ishimaru, Ichiro

2013-06-01

The one-shot-type spectroscopic-tomography is proposed to develop the medical-patient-condition monitoring systems. The optical-setup is configured with the relative-inclined phase-shifter for improving the time resolution and the phase-shift array for improving visibility. We obtained the line-spectroscopic imaging and could recognize the Hg bright-line-spectrum that is a component of the light-source. The realization of the optical stethoscope for early diagnosis of cancer can be expected by obtaining the 2-dimensional spectroscopic distribution with rotating interferometer.

DTN Implementation and Utilization Options on the International Space Station

NASA Technical Reports Server (NTRS)

Nichols, Kelvin; Holbrook, Mark; Pitts, Lee; Gifford, Kevin; Jenkins, Andrew; Kuzminsky, Sebastian

2010-01-01

This slide presentation reviews the implementation and future uses of Delay/Disruption Tolerant Networking (DTN) for space communication, using the International Space Station as the primary example. The presentation includes: (1) A brief introduction of the current communications architecture of the ISS (2) How current payload operations are handled in the non-DTN environment (3) Making the case to implement DTN into the current payload science operations model (4) Phase I DTN Operations: early implementation with BioServe's CGBA Payload (5) Phase II DTN Operations: Developing the HOSC DTN Gateway

Juvenile Dermatomyositis: Key Roles of Muscle Magnetic Resonance Imaging and Early Aggressive Treatment.

PubMed

Corral-Magaña, O; Bauzá-Alonso, A F; Escudero-Góngora, M M; Lacruz, L; Martín-Santiago, A

2017-09-12

Juvenile dermatomyositis is a rare systemic connective tissue disease with onset during childhood. It presents clinically with proximal muscle weakness and characteristic skin involvement. Diagnosis is based on the Bohan and Peter criteria, though many authors are now substituting biopsy with muscle magnetic resonance imaging (MRI) for both diagnosis and follow-up. Without intensive early treatment, complications such as calcinosis cutis and lipodystrophy can develop in the chronic phases of the disease. Early recognition is therefore key to management. We present a series of 5 patients who were diagnosed with Juvenile dermatomyositis on muscle MRI without undergoing muscle biopsy and who received early treatment. We draw attention to the usefulness of muscle MRI for the diagnosis of muscle involvement and to the importance of early initiation of intensive treatment to prevent complications. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Phase Transitions in the Early Universe: The Cosmology of Non-Minimal Scalar Sectors

NASA Astrophysics Data System (ADS)

Kost, Jeffrey D.

Light scalar fields such as axions and string moduli can play an important role in early-universe cosmology. However, many factors can significantly impact their late-time cosmological abundances. For example, in cases where the potentials for these fields are generated dynamically--such as during cosmological mass-generating phase transitions--the duration of the time interval required for these potentials to fully develop can have significant repercussions. Likewise, in scenarios with multiple scalars, mixing amongst the fields can also give rise to an effective timescale that modifies the resulting late-time abundances. Previous studies have focused on the effects of either the first or the second timescale in isolation. In this thesis, by contrast, we examine the new features that arise from the interplay between these two timescales when both mixing and time-dependent phase transitions are introduced together. First, we find that the effects of these timescales can conspire to alter not only the total late-time abundance of the system--often by many orders of magnitude--but also its distribution across the different fields. Second, we find that these effects can produce large parametric resonances which render the energy densities of the fields highly sensitive to the degree of mixing as well as the duration of the time interval over which the phase transition unfolds. Finally, we find that these effects can even give rise to a "re-overdamping" phenomenon which causes the total energy density of the system to behave in novel ways that differ from those exhibited by pure dark matter or vacuum energy. All of these features therefore give rise to new possibilities for early-universe phenomenology and cosmological evolution. They also highlight the importance of taking into account the time dependence associated with phase transitions in cosmological settings. In the second part of this thesis, we proceed to study the early-universe cosmology of a Kaluza-Klein (KK) tower of scalar fields in the presence of a mass-generating phase transition, focusing on the time-development of the total tower energy density (or relic abundance) as well as its distribution across the different KK modes. We find that both of these features are extremely sensitive to the details of the phase transition and can behave in a variety of ways significant for late-time cosmology. In particular, we find that the interplay between the temporal properties of the phase transition and the mixing it generates are responsible for both enhancements and suppressions in the late-time abundances, sometimes by many orders of magnitude. We map out the complete model parameter space and determine where traditional analytical approximations are valid and where they fail. In the latter cases we also provide new analytical approximations which successfully model our results. Finally, we apply this machinery to the example of an axion-like field in the bulk, mapping these phenomena over an enlarged axion parameter space that extends beyond those accessible to standard treatments. An important by-product of our analysis is the development of an alternate "UV-based" effective truncation of KK theories which has a number of interesting theoretical properties that distinguish it from the more traditional "IR-based" truncation typically used in the literature.

Timing of the endometrial biopsy may be critical for the accurate diagnosis of luteal phase deficiency.

PubMed

Castelbaum, A J; Wheeler, J; Coutifaris, C B; Mastroianni, L; Lessey, B A

1994-03-01

To determine the optimal time to perform the endometrial biopsy for the detection of "out-of-phase" endometrium. Two endometrial biopsies were performed during a single menstrual cycle in each subject. The patient's chronological day was determined by counting forward from the midcycle LH surge, as assessed by urinary LH detection. The "early" biopsy was done on day LH + 7.4 +/- 0.8, and the "late" biopsy on day LH + 11.6 +/- 0.7. Each biopsy was independently read by two pathologists and was considered out of phase if the histologic date was > or = 3 days delayed compared with the chronological date. Infertility practice of an academic teaching hospital. Thirty-three ovulatory women seeking evaluation for infertility. Number of patients with out-of-phase endometrium detected by the early versus the late biopsy. There was a significantly greater detection rate for out-of-phase endometrium using the early biopsy (12.1% to 18.2% incidence depending on the observer) compared with the later biopsy (6.1% to 9.1% incidence). A majority of the early out-of-phase biopsies corrected by the time of the later biopsy. Our findings indicate that an endometrial biopsy performed in the midluteal phase may detect a greater number of women with delayed endometrial maturation during the temporal window of embryo implantation. The observation that most of the women with out-of-phase midluteal biopsies had normal late luteal endometrium may represent a cryptic form of luteal phase deficiency.

Phase III Early Restoration Meeting - Galveston, TX | NOAA Gulf Spill

Science.gov Websites

Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News planning for Phase III and future early restoration plans. Open House: 6:00pm Public Meeting: 6:30pm

Phase III Early Restoration Meeting - Port Arthur, TX | NOAA Gulf Spill

Science.gov Websites

Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News planning for Phase III and future early restoration plans. Open House: 6:00pm Public Meeting: 6:30pm

Phase III Early Restoration Meeting - Panama City, FL | NOAA Gulf Spill

Science.gov Websites

Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News planning for Phase III and future early restoration plans. Open House: 6:00pm Public Meeting: 6:30pm

A simple two-stage design for quantitative responses with application to a study in diabetic neuropathic pain.

PubMed

Whitehead, John; Valdés-Márquez, Elsa; Lissmats, Agneta

2009-01-01

Two-stage designs offer substantial advantages for early phase II studies. The interim analysis following the first stage allows the study to be stopped for futility, or more positively, it might lead to early progression to the trials needed for late phase II and phase III. If the study is to continue to its second stage, then there is an opportunity for a revision of the total sample size. Two-stage designs have been implemented widely in oncology studies in which there is a single treatment arm and patient responses are binary. In this paper the case of two-arm comparative studies in which responses are quantitative is considered. This setting is common in therapeutic areas other than oncology. It will be assumed that observations are normally distributed, but that there is some doubt concerning their standard deviation, motivating the need for sample size review. The work reported has been motivated by a study in diabetic neuropathic pain, and the development of the design for that trial is described in detail. Copyright 2008 John Wiley & Sons, Ltd.

Divergence of developmental trajectories is triggered interactively by early social and ecological experience in a cooperative breeder

PubMed Central

Bohn, Lena; Oberhummer, Evelyne

2017-01-01

Cooperative breeders feature the highest level of social complexity among vertebrates. Environmental constraints foster the evolution of this form of social organization, selecting for both well-developed social and ecological competences. Cooperative breeders pursue one of two alternative social trajectories: delaying reproduction to care for the offspring of dominant breeders or dispersing early to breed independently. It is yet unclear which ecological and social triggers determine the choice between these alternatives and whether diverging developmental trajectories exist in cooperative vertebrates predisposing them to dispersal or philopatry. Here we experimentally reared juveniles of cooperatively breeding cichlid fish by varying the social environment and simulated predation threat in a two-by-two factorial long-term experiment. First, we show that individuals develop specialized behavioral competences, originating already in the early postnatal phase. Second, these specializations predisposed individuals to pursue different developmental trajectories and either to disperse early or to extend philopatry in adulthood. Thus, our results contrast with the proposition that social specializations in early ontogeny should be restricted to eusocial species. Importantly, social and ecological triggers were both required for the generation of divergent life histories. Our results thus confirm recent predictions from theoretical models that organisms should combine relevant information from different environmental cues to develop integrated phenotypes. PMID:29078289

The Use of Underground Research Laboratories to Support Repository Development Programs. A Roadmap for the Underground Research Facilities Network.

DOE Office of Scientific and Technical Information (OSTI.GOV)

MacKinnon, Robert J.

2015-10-26

Under the auspices of the International Atomic Energy Agency (IAEA), nationally developed underground research laboratories (URLs) and associated research institutions are being offered for use by other nations. These facilities form an Underground Research Facilities (URF) Network for training in and demonstration of waste disposal technologies and the sharing of knowledge and experience related to geologic repository development, research, and engineering. In order to achieve its objectives, the URF Network regularly sponsors workshops and training events related to the knowledge base that is transferable between existing URL programs and to nations with an interest in developing a new URL. Thismore » report describes the role of URLs in the context of a general timeline for repository development. This description includes identification of key phases and activities that contribute to repository development as a repository program evolves from an early research and development phase to later phases such as construction, operations, and closure. This information is cast in the form of a matrix with the entries in this matrix forming the basis of the URF Network roadmap that will be used to identify and plan future workshops and training events.« less

X-ray phase-contrast imaging of the breast—advances towards clinical implementation

PubMed Central

Herzen, J; Willner, M; Grandl, S; Scherer, K; Bamberg, F; Reiser, M F; Pfeiffer, F; Hellerhoff, K

2014-01-01

Breast cancer constitutes about one-quarter of all cancers and is the leading cause of cancer death in women. To reduce breast cancer mortality, mammographic screening programmes have been implemented in many Western countries. However, these programmes remain controversial because of the associated radiation exposure and the need for improvement in terms of diagnostic accuracy. Phase-contrast imaging is a new X-ray-based technology that has been shown to provide enhanced soft-tissue contrast and improved visualization of cancerous structures. Furthermore, there is some indication that these improvements of image quality can be maintained at reduced radiation doses. Thus, X-ray phase-contrast mammography may significantly contribute to advancements in early breast cancer diagnosis. Feasibility studies of X-ray phase-contrast breast CT have provided images that allow resolution of the fine structure of tissue that can otherwise only be obtained by histology. This implies that X-ray phase-contrast imaging may also lead to the development of entirely new (micro-) radiological applications. This review provides a brief overview of the physical characteristics of this new technology and describes recent developments towards clinical implementation of X-ray phase-contrast imaging of the breast. PMID:24452106

Rapid RNA Exchange in Aqueous Two-Phase System and Coacervate Droplets

NASA Astrophysics Data System (ADS)

Jia, Tony Z.; Hentrich, Christian; Szostak, Jack W.

2014-02-01

Compartmentalization in a prebiotic setting is an important aspect of early cell formation and is crucial for the development of an artificial protocell system that effectively couples genotype and phenotype. Aqueous two-phase systems (ATPSs) and complex coacervates are phase separation phenomena that lead to the selective partitioning of biomolecules and have recently been proposed as membrane-free protocell models. We show in this study through fluorescence recovery after photobleaching (FRAP) microscopy that despite the ability of such systems to effectively concentrate RNA, there is a high rate of RNA exchange between phases in dextran/polyethylene glycol ATPS and ATP/poly-L-lysine coacervate droplets. In contrast to fatty acid vesicles, these systems would not allow effective segregation and consequent evolution of RNA, thus rendering these systems ineffective as model protocells.

MOD-5A wind turbine generator program design report: Volume 1: Executive Summary

NASA Technical Reports Server (NTRS)

1984-01-01

The design, development and analysis of the 7.3 MW MOD-5A wind turbine generator covering work performed between July 1980 and June 1984 is discussed. The report is divided into four volumes: Volume 1 summarizes the entire MOD-5A program, Volume 2 discusses the conceptual and preliminary design phases, Volume 3 describes the final design of the MOD-5A, and Volume 4 contains the drawings and specifications developed for the final design. Volume 1, the Executive Summary, summarizes all phases of the MOD-5A program. The performance and cost of energy generated by the MOD-5A are presented. Each subsystem - the rotor, drivetrain, nacelle, tower and foundation, power generation, and control and instrumentation subsystems - is described briefly. The early phases of the MOD-5A program, during which the design was analyzed and optimized, and new technologies and materials were developed, are discussed. Manufacturing, quality assurance, and safety plans are presented. The volume concludes with an index of volumes 2 and 3.

Don't Mess with the NEST

NASA Astrophysics Data System (ADS)

Larson, Michael

2012-03-01

This presentation will describe the history of the Nuclear Emergency Support Team (NEST) and its evolution over the years. NEST was formed due to a number of nuclear extortion threats received in the early 1970s. From the beginning NEST developed an extensive exercise program to test and expand capabilities. The Nuclear Assessment Program (NAP) was developed, in part, to determine if NEST deployments were required. A major revamp of the NEST program occurred in 1994. Many other organizations work in conjunction with NEST in particular the FBI and DOD. Considerable research and development has been performed in the areas of Access, Search, Diagnostics, Device Assessment, and Disablement. Extensive searches of material appearing in the unclassified literature have been and are being performed to see what is being said about nuclear materials and devices. A comprehensive study of Improvised Nuclear Devices (IND) is ongoing to determine what a terrorist can and cannot do. NEST now consists of four phases with the latest additions of Phase III, Disposition and Phase IV, Nuclear Forensics. LLNL-ABS-521775

Guidance, Navigation and Control (GN&C): Best Practices for Human-Rated Spacecraft Systems

NASA Technical Reports Server (NTRS)

Lebsock, Ken; West, John

2008-01-01

In 2007 the NESC completed an in-depth assessment to identify, define and document engineering considerations for the Design Development Test and Evaluation (DDT&E) of human-rated spacecraft systems. This study had been requested by the Astronaut Office at JSC to help them to better understand what is required to ensure safe, robust, and reliable human-rated spacecraft systems. The 22 GN&C engineering Best Practices described in this paper are a condensed version of what appears in the NESC Technical Report. These Best Practices cover a broad range from fundamental system architectural considerations to more specific aspects (e.g., stability margin recommendations) of GN&C system design and development. 15 of the Best Practices address the early phases of a GN&C System development project and the remaining 7 deal with the later phases. Some of these Best Practices will cross-over between both phases. We recognize that this set of GN&C Best Practices will not be universally applicable to all projects and mission applications.

[Satellite symposium: Asthma in the World. Asthma among children in Latin America].

PubMed

Mallol, J

2004-01-01

The prevalence of respiratory symptoms related to asthma in children from Latin America has been largely ignored. This region participated in phases I and III of the International Study of Asthma and Allergies in Childhood (ISAAC) with 17 participating centers in phase I and 78 centers in phase III. Data were obtained on asthma, rhinitis and eczema from countries and centers with markedly different climactic, cultural and environmental conditions and socioeconomic development. The results for phase I are presented herein because data from phase III are currently being revised at the ISAAC international data control center and will be officially available in the second half of 2004. Phase I provided important information on the prevalence of asthma in the participating countries and demonstrated wide variation among centers in the same country and among countries. The participating Latin American countries are all developing countries and share more or less the same problems related to low socioeconomic status. Therefore, the results and figures should be analyzed within that context. The range for accumulative and current asthma symptoms in children from the Latin American countries that participated in phase I (89,000) were as follows: the prevalence of asthma ranged from 5.5% to 28% in children aged 13-14 years and from 4.1% to 26.9% in children aged 6-7 years. The prevalence of wheezing in the previous 12 months ranged from 6.6% to 27% in children aged 13-14 years and from 8.6% to 32.1% in children aged 6-7 years. The high figures for asthma in a region with a high level of gastrointestinal parasites infestation, a high burden of acute respiratory and gastrointestinal infections occurring early in life, severe environmental and hygiene problems, suggest that these factors, considered as protective in other (developed) regions of the world, do not have the same effect in this region. Furthermore, those aggressive environmental conditions acting together from very early in life might condition different asthmatic phenotypes with more severe clinical presentation in infancy (first 2 years of life), lower atopy and enhanced airways reactivity. The present study indicates that the prevalence of asthma and related symptoms in Latin America is as high and variable as described previously for industrialized or developed regions of the world and that the environmental risk factors, mainly related with poverty, could be responsible for the different clinical and functional presentations of asthma in children from developing regions.

Immediate Effects of a Single Session of Motor Skill Training on the Lumbar Movement Pattern During a Functional Activity in People With Low Back Pain: A Repeated-Measures Study.

PubMed

Marich, Andrej V; Lanier, Vanessa M; Salsich, Gretchen B; Lang, Catherine E; Van Dillen, Linda R

2018-04-06

People with low back pain (LBP) may display an altered lumbar movement pattern of early lumbar motion compared to people with healthy backs. Modifying this movement pattern during a clinical test decreases pain. It is unknown whether similar effects would be seen during a functional activity. The objective of this study is was to examine the lumbar movement patterns before and after motor skill training, effects on pain, and characteristics that influenced the ability to modify movement patterns. The design consisted of a repeated-measures study examining early-phase lumbar excursion in people with LBP during a functional activity test. Twenty-six people with chronic LBP received motor skill training, and 16 people with healthy backs were recruited as a reference standard. Twenty minutes of motor skill training to decrease early-phase lumbar excursion during the performance of a functional activity were used as a treatment intervention. Early-phase lumbar excursion was measured before and after training. Participants verbally reported increased pain, decreased pain, or no change in pain during performance of the functional activity test movement in relation to their baseline pain. The characteristics of people with LBP that influenced the ability to decrease early-phase lumbar excursion were examined. People with LBP displayed greater early-phase lumbar excursion before training than people with healthy backs (LBP: mean = 11.2°, 95% CI = 9.3°-13.1°; healthy backs: mean = 7.1°, 95% CI = 5.8°-8.4°). Following training, the LBP group showed a decrease in the amount of early-phase lumbar excursion (mean change = 4.1°, 95% CI = 2.4°-5.8°); 91% of people with LBP reported that their pain decreased from baseline following training. The longer the duration of LBP (β = - 0.22) and the more early-phase lumbar excursion before training (β = - 0.82), the greater the change in early-phase lumbar excursion following training. The long-term implications of modifying the movement pattern and whether the decrease in pain attained was clinically significant are unknown. People with LBP were able to modify their lumbar movement pattern and decrease their pain with the movement pattern within a single session of motor skill training.

Tectonic evolution of the Gaoua region, Burkina Faso: Implications for mineralization

NASA Astrophysics Data System (ADS)

Baratoux, L.; Metelka, V.; Naba, S.; Ouiya, P.; Siebenaller, L.; Jessell, M. W.; Naré, A.; Salvi, S.; Béziat, D.; Franceschi, G.

2015-12-01

The interpretation of high-resolution airborne geophysical data integrated with field structural and lithological observations were employed in the creation of a litho-structural framework for the Gaoua region, Burkina Faso. The granite-greenstone domain of Paleoproterozoic age was affected by multiple deformation and mineralization events. The early tectonic phase is characterized by the emplacement of voluminous tholeiitic and calc-alkaline lavas, probably in a volcanic arc setting. The copper mineralization in Gongondy, Dienemera and Mt Biri is concentrated in a diorite/andesite breccia, and is interpreted as porphyry-copper style formed at an early stage of the evolution of the area. Evidence for the first deformation event D1Ga corresponding to N-S shortening was only found in the E-W trending mafic unit bordering the Gaoua batholith to the south. A second deformation phase D2Ga occurred under greenschist facies conditions and lead to a development of more or less penetrative metamorphic foliation and its subsequent folding under overall E-W compression. At later stages, the D2Ga switched to a transcurrent regime characterized by intense N-S to NW-trending steeply dipping shear zones. The first significant gold mineralization event is related to this transcurrent tectonic phase. During subsequent D3Ga, intense network of brittle to brittle-ductile NW and NE faults developed. Economic gold concentrations are attributed to the D3Ga event and are associated with the remobilization of early disseminated low grade gold concentrations. Significant deposits in the area are Nassara, Gomblora, Batié West and Kampti. The last deformation event D4Ga resulted in E-W trending thrust faults and crenulation cleavage planes, under overall N-S compression. No mineralization events related to this stage have been seen.

Modelling PK/QT relationships from Phase I dose-escalation trials for drug combinations and developing quantitative risk assessments of clinically relevant QT prolongations.

PubMed

Sinclair, Karen; Kinable, Els; Grosch, Kai; Wang, Jixian

2016-05-01

In current industry practice, it is difficult to assess QT effects at potential therapeutic doses based on Phase I dose-escalation trials in oncology due to data scarcity, particularly in combinations trials. In this paper, we propose to use dose-concentration and concentration-QT models jointly to model the exposures and effects of multiple drugs in combination. The fitted models then can be used to make early predictions for QT prolongation to aid choosing recommended dose combinations for further investigation. The models consider potential correlation between concentrations of test drugs and potential drug-drug interactions at PK and QT levels. In addition, this approach allows for the assessment of the probability of QT prolongation exceeding given thresholds of clinical significance. The performance of this approach was examined via simulation under practical scenarios for dose-escalation trials for a combination of two drugs. The simulation results show that invaluable information of QT effects at therapeutic dose combinations can be gained by the proposed approaches. Early detection of dose combinations with substantial QT prolongation is evaluated effectively through the CIs of the predicted peak QT prolongation at each dose combination. Furthermore, the probability of QT prolongation exceeding a certain threshold is also computed to support early detection of safety signals while accounting for uncertainty associated with data from Phase I studies. While the prediction of QT effects is sensitive to the dose escalation process, the sensitivity and limited sample size should be considered when providing support to the decision-making process for further developing certain dose combinations. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Quantification of three-dimensional cell-mediated collagen remodeling using graph theory.

PubMed

Bilgin, Cemal Cagatay; Lund, Amanda W; Can, Ali; Plopper, George E; Yener, Bülent

2010-09-30

Cell cooperation is a critical event during tissue development. We present the first precise metrics to quantify the interaction between mesenchymal stem cells (MSCs) and extra cellular matrix (ECM). In particular, we describe cooperative collagen alignment process with respect to the spatio-temporal organization and function of mesenchymal stem cells in three dimensions. We defined two precise metrics: Collagen Alignment Index and Cell Dissatisfaction Level, for quantitatively tracking type I collagen and fibrillogenesis remodeling by mesenchymal stem cells over time. Computation of these metrics was based on graph theory and vector calculus. The cells and their three dimensional type I collagen microenvironment were modeled by three dimensional cell-graphs and collagen fiber organization was calculated from gradient vectors. With the enhancement of mesenchymal stem cell differentiation, acceleration through different phases was quantitatively demonstrated. The phases were clustered in a statistically significant manner based on collagen organization, with late phases of remodeling by untreated cells clustering strongly with early phases of remodeling by differentiating cells. The experiments were repeated three times to conclude that the metrics could successfully identify critical phases of collagen remodeling that were dependent upon cooperativity within the cell population. Definition of early metrics that are able to predict long-term functionality by linking engineered tissue structure to function is an important step toward optimizing biomaterials for the purposes of regenerative medicine.

Feasibility study for early removal of HEU from CPP-651-Phase II

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, C.V.; Henry, R.; Milligan, C.

1997-09-01

A two-phase feasibility study was initiated in late 1996 to identify a way to expedite the removal of SNM from the CPP-651 vault. The first phase of this study provided preliminary information that appeared promising, but needed additional detailed planning and evaluate to validate the concepts and conclusions. The focus of Phase 2 was to provide the validation via resource-loaded schedules and more detailed cost estimates. Section 1 describes the purpose and objectives of the Phase 2 tasks and the programmatic drivers that influence related CPP-651 high-enriched uranium (HEU) management issues. Section 2 identifies the evaluation criteria and methodology andmore » the transfer issues and barriers preventing shipment. Section 3 provides site-specific background information for the CPP-651 facility and the Idaho National Engineering and Environmental Laboratory (INEEL) and describes the development of the basic material removal schedule, the proposed base case plan for removal of SNM, and the proposed HEU material management/shipping issues and strategies. Section 4 identifies the proposed options for accelerated removal of SNM and how they were evaluated via detailed scheduling, resource histograms, and cost analysis. Section 5 summarizes principal tasks for implementing this plan and other related HEU CPP-651 management issues that require continued planning efforts to assure successful implementation of this proposed early removal strategy.« less

Genome-wide analysis of replication timing by next-generation sequencing with E/L Repli-seq.

PubMed

Marchal, Claire; Sasaki, Takayo; Vera, Daniel; Wilson, Korey; Sima, Jiao; Rivera-Mulia, Juan Carlos; Trevilla-García, Claudia; Nogues, Coralin; Nafie, Ebtesam; Gilbert, David M

2018-05-01

This protocol is an extension to: Nat. Protoc. 6, 870-895 (2014); doi:10.1038/nprot.2011.328; published online 02 June 2011Cycling cells duplicate their DNA content during S phase, following a defined program called replication timing (RT). Early- and late-replicating regions differ in terms of mutation rates, transcriptional activity, chromatin marks and subnuclear position. Moreover, RT is regulated during development and is altered in diseases. Here, we describe E/L Repli-seq, an extension of our Repli-chip protocol. E/L Repli-seq is a rapid, robust and relatively inexpensive protocol for analyzing RT by next-generation sequencing (NGS), allowing genome-wide assessment of how cellular processes are linked to RT. Briefly, cells are pulse-labeled with BrdU, and early and late S-phase fractions are sorted by flow cytometry. Labeled nascent DNA is immunoprecipitated from both fractions and sequenced. Data processing leads to a single bedGraph file containing the ratio of nascent DNA from early versus late S-phase fractions. The results are comparable to those of Repli-chip, with the additional benefits of genome-wide sequence information and an increased dynamic range. We also provide computational pipelines for downstream analyses, for parsing phased genomes using single-nucleotide polymorphisms (SNPs) to analyze RT allelic asynchrony, and for direct comparison to Repli-chip data. This protocol can be performed in up to 3 d before sequencing, and requires basic cellular and molecular biology skills, as well as a basic understanding of Unix and R.

Origin of chemically distinct discs in the Auriga cosmological simulations

NASA Astrophysics Data System (ADS)

Grand, Robert J. J.; Bustamante, Sebastián; Gómez, Facundo A.; Kawata, Daisuke; Marinacci, Federico; Pakmor, Rüdiger; Rix, Hans-Walter; Simpson, Christine M.; Sparre, Martin; Springel, Volker

2018-03-01

The stellar disc of the Milky Way shows complex spatial and abundance structure that is central to understanding the key physical mechanisms responsible for shaping our Galaxy. In this study, we use six very high resolution cosmological zoom-in simulations of Milky Way-sized haloes to study the prevalence and formation of chemically distinct disc components. We find that our simulations develop a clearly bimodal distribution in the [α/Fe]-[Fe/H] plane. We find two main pathways to creating this dichotomy, which operate in different regions of the galaxies: (a) an early (z > 1) and intense high-[α/Fe] star formation phase in the inner region (R ≲ 5 kpc) induced by gas-rich mergers, followed by more quiescent low-[α/Fe] star formation; and (b) an early phase of high-[α/Fe] star formation in the outer disc followed by a shrinking of the gas disc owing to a temporarily lowered gas accretion rate, after which disc growth resumes. In process (b), a double-peaked star formation history around the time and radius of disc shrinking accentuates the dichotomy. If the early star formation phase is prolonged (rather than short and intense), chemical evolution proceeds as per process (a) in the inner region, but the dichotomy is less clear. In the outer region, the dichotomy is only evident if the first intense phase of star formation covers a large enough radial range before disc shrinking occurs; otherwise, the outer disc consists of only low-[α/Fe] sequence stars. We discuss the implication that both processes occurred in the Milky Way.

Biomonitoring of human fetal exposure to environmental chemicals in early pregnancy.

PubMed

Cooke, Gerard M

2014-01-01

The first trimester of human fetal life, a period of extremely rapid development of physiological systems, represents the most rapid growth phase in human life. Interference in the establishment of organ systems may result in abnormal development that may be manifest immediately or programmed for later abnormal function. Exposure to environmental chemicals may be affecting development at these early stages, and yet there is limited knowledge of the quantities and identities of the chemicals to which the fetus is exposed during early pregnancy. Clearly, opportunities for assessing fetal chemical exposure directly are extremely limited. Hence, this review describes indirect means of assessing fetal exposure in early pregnancy to chemicals that are considered disrupters of development. Consideration is given to such matrices as maternal hair, fingernails, urine, saliva, sweat, breast milk, amniotic fluid and blood, and fetal matrices such as cord blood, cord tissue, meconium, placenta, and fetal liver. More than 150 articles that presented data from chemical analysis of human maternal and fetal tissues and fluids were reviewed. Priority was given to articles where chemical analysis was conducted in more than one matrix. Where correlations between maternal and fetal matrices were determined, these articles were included and are highlighted, as these may provide the basis for future investigations of early fetal exposure. The determination of fetal chemical exposure, at the time of rapid human growth and development, will greatly assist regulatory agencies in risk assessments and establishment of advisories for risk management concerning environmental chemicals.

The clinical utility index as a practical multiattribute approach to drug development decisions.

PubMed

Poland, B; Hodge, F L; Khan, A; Clemen, R T; Wagner, J A; Dykstra, K; Krishna, R

2009-07-01

We identify some innovative approaches to predicting overall patient benefit from investigational drugs to support development decisions. We then illustrate calculation of a probabilistic clinical utility index (CUI), an implementation of multiattribute utility that focuses on clinical attributes. We recommend use of the CUI for the support of early drug development decisions because of its practicality, reasonable accuracy, and transparency to decision makers, at stages in which financial factors that may dominate later-phase decisions are less critical.

Software development for airborne radar

NASA Astrophysics Data System (ADS)

Sundstrom, Ingvar G.

Some aspects for development of software in a modern multimode airborne nose radar are described. First, an overview of where software is used in the radar units is presented. The development phases-system design, functional design, detailed design, function verification, and system verification-are then used as the starting point for the discussion. Methods, tools, and the most important documents are described. The importance of video flight recording in the early stages and use of a digital signal generators for performance verification is emphasized. Some future trends are discussed.

Protocol for the systematic review of the reporting of transoral robotic surgery.

PubMed

Main, Barry G; Blencowe, Natalie S; Howes, Noah; Cousins, Sian; Avery, Kerry N L; Gormley, Alexander; Radford, Phil; Elliott, Daisy; Byrne, Benjamin; Wilson, Nicholas; Hinchliffe, Robert; Blazeby, Jane M

2018-01-23

Transoral robotic surgery (TORS) has been adopted in some parts of the world as an innovative approach to the resection of oropharyngeal tumours. The development, details and outcomes of early-to-later phase evaluation of this technique and the quality of evidence to support its adoption into practice have hitherto not been summarised. The aim of this review is to identify and summarise the early and later phase studies of, and evidence for, TORS and to understand how early phase studies report intervention development, governance procedures and selection and reporting of outcomes to optimise methods for using the Idea, Development, Exploration, Assessment, Long-term follow-up (IDEAL) framework for surgical innovation that informs evidence-based practice. The protocol has been written in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols checklist. Electronic searches in OVID SP versions of Medline and EMBASE, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews from the start of indexing to 30 April 2017 will identify studies reporting TORS. At least two independent researchers will identify studies for inclusion. Two researchers will extract data from each paper. Studies will be categorised into IDEAL stages of study design from 'pre-IDEAL' to randomised controlled trials (stage 3). Data will be collected about the (1) novel intervention and criteria for modification, (2) governance arrangements and patient information provision, (3) outcome domains selected and reported and (4) quality of study design, conduct and reporting. Descriptive statistics and a narrative synthesis will be presented. The results of this systematic review will be presented at relevant conferences. The methods will be used to inform future reviews exploring other novel surgical innovations. The findings will be published in a peer-reviewed journal. This study does not require ethical approval. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Long working hours and sleep disturbances: the Whitehall II prospective cohort study.

PubMed

Virtanen, Marianna; Ferrie, Jane E; Gimeno, David; Vahtera, Jussi; Elovainio, Marko; Singh-Manoux, Archana; Marmot, Michael G; Kivimäki, Mika

2009-06-01

To examine whether exposure to long working hours predicts various forms of sleep disturbance; short sleep, difficulty falling asleep, frequent waking, early waking and waking without feeling refreshed. Prospective study with 2 measurements of working hours (phase 3, 1991-1994 and phase 5, 1997-1999) and 2 measurements of subjective sleep disturbances (phase 5 and phase 7, 2002-2004). The Whitehall II study of British civil servants. Full time workers free of sleep disturbances at phase 5 and employed at phases 5 and 7 (n = 937-1594) or at phases 3, 5, and 7 (n = 886-1510). Working more than 55 hours a week, compared with working 35-40 hours a week, was related to incident sleep disturbances; demographics-adjusted odds ratio (95% CI) 1.98 (1.05, 3.76) for shortened sleeping hours, 3.68 (1.58, 8.58) for difficulty falling asleep; and 1.98 (1.04, 3.77) for waking without feeling refreshed. Repeat exposure to long working hours was associated with odds ratio 3.24 (1.45, 7.27) for shortened sleep, 6.66 (2.64, 16.83) for difficulty falling asleep, and 2.23 (1.16, 4.31) for early morning awakenings. Some associations were attenuated after adjustment for other risk factors. To a great extent, similar results were obtained using working hours as a continuous variable. Imputation of missing values supported the findings on shortened sleep and difficulty in falling asleep. Working long hours appears to be a risk factor for the development of shortened sleeping hours and difficulty falling asleep.

A study of characteristics of intercity transportation systems. Phase 1: Definition of transportation comparison methodology

NASA Technical Reports Server (NTRS)

English, J. M.; Smith, J. L.; Lifson, M. W.

1978-01-01

Decision making in early transportation planning must be responsive to complex value systems representing various policies and objectives. The assessment of alternative transportation concepts during the early initial phases of the system life cycle, when supportive research and technology development activities are defined, requires estimates of transportation, environmental, and socio-economic impacts throughout the system life cycle, which is a period of some 40 or 50 years. A unified methodological framework for comparing intercity passenger and freight transportation systems is described and is extended to include the comparison of long term transportation trends arising from implementation of the various R & D programs. The attributes of existing and future transportation systems are reviewed in order to establish measures for comparison, define value functions, and attribute weightings needed for comparing alternative policy actions for furthering transportation goals. Comparison criteria definitions and an illustrative example are included.

Study on the hydration and microstructure of Portland cement containing diethanol-isopropanolamine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, Suhua, E-mail: yc982@163.com; Li, Weifeng; Zhang, Shenbiao

2015-01-15

Diethanol-isopropanolamine (DEIPA) is a tertiary alkanolamine used in the formulation of cement grinding-aid additives and concrete early-strength agents. In this research, isothermal calorimetry was used to study the hydration kinetics of Portland cement with DEIPA. A combination of X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), differential scanning calorimetry (DSC)–thermogravimetric (TG) analysis and micro-Raman spectroscopy was used to investigate the phase development in the process of hydration. Mercury intrusion porosimetry was used to study the pore size distribution and porosity. The results indicate that DEIPA promotes the formation of ettringite (AFt) and enhances the second hydration rate of the aluminatemore » and ferrite phases, the transformation of AFt into monosulfoaluminate (AFm) and the formation of microcrystalline portlandite (CH) at early stages. At later stages, DEIPA accelerates the hydration of alite and reduces the pore size and porosity.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ro, Stephen; Matzner, Christopher D., E-mail: ro@astro.utoronto.ca

Wave-driven outflows and non-disruptive explosions have been implicated in pre-supernova outbursts, supernova impostors, luminous blue variable eruptions, and some narrow-line and superluminous supernovae. To model these events, we investigate the dynamics of stars set in motion by strong acoustic pulses and wave trains, focusing on nonlinear wave propagation, shock formation, and an early phase of the development of a weak shock. We identify the shock formation radius, showing that a heuristic estimate based on crossing characteristics matches an exact expansion around the wave front and verifying both with numerical experiments. Our general analytical condition for shock formation applies to one-dimensionalmore » motions within any static environment, including both eruptions and implosions. We also consider the early phase of shock energy dissipation. We find that waves of super-Eddington acoustic luminosity always create shocks, rather than damping by radiative diffusion. Therefore, shock formation is integral to super-Eddington outbursts.« less

Pharmacodynamics, pharmacokinetics and clinical efficacy of neratinib in HER2-positive breast cancer and breast cancer with HER2 mutations.

PubMed

Kourie, Hampig Raphael; Chaix, Marie; Gombos, Andrea; Aftimos, Phillippe; Awada, Ahmad

2016-08-01

Despite the availability of several potent HER2-directed targeted agents, primary and acquired resistance continues to influence patient outcomes in HER2-positive breast cancer. Neratinib is an irreversible pan-HER tyrosine kinase inhibitor in late-phase clinical development. This review article focuses on neratinib in the treatment of HER2-positive breast cancer - early and metastatic stage - and HER2-mutant breast cancer, with particular emphasis on the pharmacokinetics and pharmacodynamics of the drug. The phase III ExteNET trial shows that neratinib improves 2-year invasive disease-free survival after trastuzumab-based adjuvant therapy in early-stage HER2-positive breast cancer, and in particular HER2+/HR+ tumors. Survival data are awaited. The investigational role of neratinib in high-risk patients or conversely in de-escalation dual regimens with other anti-HER2 therapies and without chemotherapy are of interest. Phase II trials show that neratinib has efficacy, either as monotherapy or in combination with other chemotherapeutic or endocrine agents, in patients with HER2-positive metastatic breast cancer and in tumors harboring HER2 mutations. The role of neratinib in therapeutic algorithms of HER2-positive patients, as well as delaying CNS events, awaits the results of ongoing trials such as NALA. Diarrhea, the main toxicity of neratinib, can be effectively managed with early loperamide prophylaxis.

The emergence of modern type rain forests and mangroves and their traces in the palaeobotanical record during the Late Cretaceous and early Tertiary

NASA Astrophysics Data System (ADS)

Mohr, Barbara; Coiffard, Clément

2014-05-01

The origin of modern rain forests is still very poorly known. This ecosystem could have potentially fully evolved only after the development of relatively high numbers of flowering plant families adapted to rain forest conditions. During the early phase of angiosperm evolution in the early Cretaceous the palaeo-equatorial region was located in a seasonally dry climatic belt, so that during this phase, flowering plants often show adaptations to drought, rather than to continuously wet climate conditions. Therefore it is not surprising that except for the Nymphaeales, the most basal members of extant angiosperm families have members that do not necessarily occur in the continuously wet tropics today. However, during the late Early Cretaceous several clades emerged that later would give rise to families that are typically found today mostly in (shady) moist places in warmer regions. This is especially seen among the monocotyledons, a group of the mesangiosperms, that developed in many cases large leaves often with very specific venation patterns that make these leaves very unique and well recognizable. Especially members of three groups are here of interest: the arum family (Araceae), the palms (Arecaceae) and the Ginger and allies (Zingiberales). The earliest fossil of Araceae are restricted to low latitudes during the lower Cretaceous. Arecaceae and Zingiberales do not appear in the fossil record before the early late Cretaceous and occur at mid latitudes. During the Late Cretaceous, Araceae are represented at mid latitudes by non-tropical early diverging members and at low latitudes by derived rainforest members. Palms became widespread during the Late Cretataceous and also Nypa, a typical element of tropical to subtropical mangrove environments evolved during this time period. During the Paleocene Arecaceae appear to be restricted to lower latitudes as well as Zingiberales. All three groups are again widespread during the Eocene, reaching higher latitudes and probably diversifying at mid latitudes. Later on, they slowly became restricted to lower latitudes as seen today. This fluctuation appears to be linked to climate change and are still reflected by the regional diversity of these groups, which reflect rather well rain forest evolution. When tracing the fossil record of rain forest plants we clearly see a pattern that suggests the onset of this type of environment during the late Late Cretaceous and spread during the early Tertiary with phases of retreat during the Oligocene and from the mid-Miocene onwards.

Thrombopoietic agents.

PubMed

Stasi, Roberto; Bosworth, Jenny; Rhodes, Elizabeth; Shannon, Muriel S; Willis, Fenella; Gordon-Smith, Edward C

2010-01-01

Thrombopoietin (TPO) is the key cytokine involved in thrombopoiesis, and is the endogenous ligand for the thrombopoietin receptor that is expressed on the surface of platelets, megakaryocytes, and megakaryocytic precursors. First-generation thrombopoietic agents were recombinant forms of human TPO, and their development was discontinued after prolonged thrombocytopenia due to neutralizing auto-antibodies cross-reacting with endogenous TPO was observed. Second-generation thrombopoiesis-stimulating molecules are now available, which have unique pharmacological properties and no sequence homology to endogenous TPO. Two of these new agents, romiplostim and eltrombopag, have already completed phase III trials in primary immune thrombocytopenia and have been granted marketing authorization for use in this disease. Phase II and III trials with these novel drugs are ongoing in other conditions characterized by thrombocytopenia, such as chemotherapy, chronic liver disease, and the myelodysplastic syndromes. Most of the other second-generation thrombopoietic growth factors are in early phase clinical development. Copyright 2010 Elsevier Ltd. All rights reserved.

Evaluation of new antiemetic agents and definition of antineoplastic agent emetogenicity--an update.

PubMed

Grunberg, Steven M; Osoba, David; Hesketh, Paul J; Gralla, Richard J; Borjeson, Sussanne; Rapoport, Bernardo L; du Bois, Andreas; Tonato, Maurizio

2005-02-01

Development of effective antiemetic therapy depends upon an understanding of both the antiemetic agents and the emetogenic challenges these agents are designed to address. New potential antiemetic agents should be studied in an orderly manner, proceeding from phase I to phase II open-label trials and then to randomized double-blind phase III trials comparing new agents and regimens to best standard therapy. Use of placebos in place of antiemetic therapy against highly or moderately emetogenic chemotherapy is unacceptable. Nausea and vomiting should be evaluated separately and for both the acute and delayed periods. Defining the emetogenicity of new antineoplastic agents is a challenge, since such data are often not reliably recorded during early drug development. A four-level classification system is proposed for emetogenicity of intravenous antineoplastic agents. A separate four-level classification system for emetogenicity of oral antineoplastic agents, which are often given over an extended period of time, is also proposed.

Silicide formation process of Er films with Ta and TaN capping layers.

PubMed

Choi, Juyun; Choi, Seongheum; Kim, Jungwoo; Na, Sekwon; Lee, Hoo-Jeong; Lee, Seok-Hee; Kim, Hyoungsub

2013-12-11

The phase development and defect formation during the silicidation reaction of sputter-deposited Er films on Si with ∼20-nm-thick Ta and TaN capping layers were examined. TaN capping effectively prevented the oxygen incorporation from the annealing atmosphere, which resulted in complete conversion to the ErSi2-x phase. However, significant oxygen penetration through the Ta capping layer inhibited the ErSi2-x formation, and incurred the growth of several Er-Si-O phases, even consuming the ErSi2-x layer formed earlier. Both samples produced a number of small recessed defects at an early silicidation stage. However, large rectangular or square-shaped surface defects, which were either pitlike or pyramidal depending on the capping layer identity, were developed as the annealing temperature increased. The origin of different defect generation mechanisms was suggested based on the capping layer-dependent silicidation kinetics.

Increased plasmacytoid dendritic cells in Guillain-Barré syndrome.

PubMed

Wang, Yu-Zhong; Feng, Xun-Gang; Wang, Qian; Xing, Chun-Ye; Shi, Qi-Guang; Kong, Qing-Xia; Cheng, Pan-Pan; Zhang, Yong; Hao, Yan-Lei; Yuki, Nobuhiro

2015-06-15

Guillain-Barré syndrome (GBS) is a post-infectious autoimmune disease. Dendritic cells (DCs) can recognize the pathogen and modulate the host immune response. Exploring the role of DCs in GBS will help our understanding of the disease development. In this study, we aimed to analyze plasmacytoid and conventional DCs in peripheral blood of patients with GBS at different stages of the disease: acute phase as well as early and late recovery phases. There was a significant increase of plasmacytoid DCs in the acute phase (p=0.03 vs healthy donors). There was a positive correlation between percentage of plasmacytoid DCs and the clinical severity of patients with GBS (r=0.61, p<0.001). Quantitative polymerase chain reaction and flow cytometry confirmed the aberrant plasmacytoid DCs in GBS. Thus, plasmacytoid DCs may participate in the development of GBS. Copyright © 2015 Elsevier B.V. All rights reserved.

Impact of prematurity and nutrition on the developing gut microbiome and preterm infant growth.

PubMed

Grier, Alex; Qiu, Xing; Bandyopadhyay, Sanjukta; Holden-Wiltse, Jeanne; Kessler, Haeja A; Gill, Ann L; Hamilton, Brooke; Huyck, Heidie; Misra, Sara; Mariani, Thomas J; Ryan, Rita M; Scholer, Lori; Scheible, Kristin M; Lee, Yi-Horng; Caserta, Mary T; Pryhuber, Gloria S; Gill, Steven R

2017-12-11

Identification of factors that influence the neonatal gut microbiome is urgently needed to guide clinical practices that support growth of healthy preterm infants. Here, we examined the influence of nutrition and common practices on the gut microbiota and growth in a cohort of preterm infants. With weekly gut microbiota samples spanning postmenstrual age (PMA) 24 to 46 weeks, we developed two models to test associations between the microbiota, nutrition and growth: a categorical model with three successive microbiota phases (P1, P2, and P3) and a model with two periods (early and late PMA) defined by microbiota composition and PMA, respectively. The more significant associations with phase led us to use a phase-based framework for the majority of our analyses. Phase transitions were characterized by rapid shifts in the microbiota, with transition out of P1 occurring nearly simultaneously with the change from meconium to normal stool. The rate of phase progression was positively associated with gestational age at birth, and delayed transition to a P3 microbiota was associated with growth failure. We found distinct bacterial metabolic functions in P1-3 and significant associations between nutrition, microbiota phase, and infant growth. The phase-dependent impact of nutrition on infant growth along with phase-specific metabolic functions suggests a pioneering potential for improving growth outcomes by tailoring nutrient intake to microbiota phase.

From research to practice: how OPUS treatment was accepted and implemented throughout Denmark.

PubMed

Nordentoft, Merete; Melau, Marianne; Iversen, Tina; Petersen, Lone; Jeppesen, Pia; Thorup, Anne; Bertelsen, Mette; Hjorthøj, Carsten Rygaard; Hastrup, Lene Halling; Jørgensen, Per

2015-04-01

The early phases of psychosis have been hypothesized to constitute a critical period, a window of opportunity. At the same time, the early phases of psychosis are associated with increased risk of unwanted outcome, such as suicidal behaviour and social isolation. This was the background for the emergence of early intervention services, and in Denmark, the OPUS trial was initiated as part of that process. Modified assertive community treatment, together with family involvement and social skills training, constituted the core elements in the original programme. A total of 547 patients with first-episode psychosis were included in the trial. To summarize briefly the results of the OPUS trial: the OPUS treatment was superior to standard treatment in reducing psychotic and negative symptoms and substance abuse, in increasing user satisfaction and adherence to treatment, and in reducing use of bed days and days in supported housing. Moreover, relatives included in the OPUS treatment were less strained and had a higher level of knowledge about schizophrenia and higher user satisfaction. The OPUS treatment was implemented throughout Denmark. Training courses were developed and manuals and books were published. Regional health authorities had access to national grants for implementing early intervention services; as a result, OPUS teams were disseminated throughout the country. The content of the treatment is now further developed, and new elements are being tried out - such as individual placement and support, lifestyle changes, cognitive remediation, specialized treatment for substance abuse and different kinds of user involvement. © 2013 Wiley Publishing Asia Pty Ltd.

Logistical challenges and design considerations for studies using acute anterior cruciate ligament injury as a potential model for early posttraumatic osteoarthritis.

PubMed

Lattermann, Christian; Jacobs, Cale A; Bunnell, Mary Proffitt; Jochimsen, Kate N; Abt, John P; Reinke, Emily K; Gammon, Lee G; Huebner, Janet L; Kraus, Virginia B; Spindler, Kurt P

2017-03-01

Anterior cruciate ligament (ACL) injuries are common and lead to posttraumatic osteoarthritis (PTOA) in a high percentage of patients. Research has been ineffective in identifying successful treatment options for people suffering from symptomatic PTOA resulting in a shift of focus toward the young, ACL injured patients at risk of developing PTOA. Randomized clinical trials examining the very early phase after ACL injury are ideal to study this population; however, these trials face significant challenges regarding recruitment as well as reproducibility of patient-reported outcomes (PROs) and inflammatory and/or chondrodegenerative biomarkers associated with early PTOA. The aim of this work was to develop an approach to allow for early recruitment into an RCT for early treatment following ACL injury and to analyze the variability of commonly used measures and biomarkers at various time points after injury. This paper reports the study design and data related to the first month of treatment for the placebo group of an ongoing 2-year clinical trial to evaluate the effect of an early intra-articular intervention after ACL injury. The results of this study suggest that acute ACL injury results in early changes of both inflammatory and chondrodegenerative biomarkers. These results also provide vital information for researchers to consider when developing future protocols, both related to the logistics of early patient enrollment as well as the appropriate timing of biomarker and patient-reported outcome collection. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:641-650, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Development, modelling, and pilot testing of a complex intervention to support end-of-life care provided by Danish general practitioners.

PubMed

Winthereik, Anna Kirstine; Neergaard, Mette Asbjoern; Jensen, Anders Bonde; Vedsted, Peter

2018-06-20

Most patients in end-of-life with life-threatening diseases prefer to be cared for and die at home. Nevertheless, the majority die in hospitals. GPs have a pivotal role in providing end-of-life care at patients' home, and their involvement in the palliative trajectory enhances the patient's possibility to stay at home. The aim of this study was to develop and pilot-test an intervention consisting of continuing medical education (CME) and electronic decision support (EDS) to support end-of-life care in general practice. We developed an intervention in line with the first phases of the guidelines for complex interventions drawn up by the Medical Research Council. Phase 1 involved the development of the intervention including identification of key barriers to provision of end-of-life care for GPs and of facilitators of change. Furthermore the actual modelling of two components: CME meeting and EDS. Phase 2 focused on pilot-testing and intervention assessment by process evaluation. In phase 1 lack of identification of patients at the end of life and limited palliative knowledge among GPs were identified as barriers. The CME meeting and the EDS were developed. The CME meeting was a four-hour educational meeting performed by GPs and specialists in palliative care. The EDS consisted of two parts: a pop-up window for each patient with palliative needs and a list of all patients with palliative needs in the practice. The pilot testing in phase 2 showed that the CME meeting was performed as intended and 120 (14%) of the GPs in the region attended. The EDS was integrated in existing electronic records but was shut down early for external reasons; 50 (5%) GPs signed up. The pilot-testing demonstrated a need to strengthen the implementation as attending rate was low in the current set-up. We developed a complex intervention to support GPs in providing end-of-life care. The pilot-test showed general acceptance of the CME meetings. The EDS was shut down early and needs further evaluation before examining the whole intervention in a larger study, where evaluation could be based on patient-related outcomes and impact on end-of-life care. Clinicaltrials.gov ( NCT02050256 ) January 30, 2014.

Developmental intervals during the larval and juvenile stages of the Antarctic myctophid fish Electrona antarctica in relation to changes in feeding and swimming functions

NASA Astrophysics Data System (ADS)

Moteki, Masato; Tsujimura, Eri; Hulley, Percy-Alexander

2017-06-01

The Antarctic myctophid fish species Electrona antarctica is believed to play a key role in the Southern Ocean food web, but there have been few studies on its early life history. This study examined the developmental changes in the external morphology and osteology of E. antarctica from the early larva to juvenile stages through the transformation phase and inferred changes in its behaviour and feeding mode. Once the larvae reached 12-13 mm body length (BL), they adopted a primordial suction feeding mode along with the acquisition of early swimming capabilities. Thereafter, both swimming and feeding functions were enhanced through fin development and ossification and acquisition of elements of the jaw and suspensorium. These processes indicate that larvae transition from the planktonic to nektonic phase upon reaching 12-13 mm BL when they enhance their both swimming and feeding abilities with growth. Transformation occurred when larvae reached 19-21 mm BL with changes such as discontinuous increases in eye diameter and upper jaw length and the appearance of photophores and dense body pigmentation. Osteological development of swimming- and feeding-related structures were mostly complete after transformation. Rapid changes in external morphology and osteology during the transformation stage are most likely related to ontogenetic vertical migration into deep waters.

Myosin Heads Are Displaced from Actin Filaments in the In Situ Beating Rat Heart in Early Diabetes

PubMed Central

Jenkins, Mathew J.; Pearson, James T.; Schwenke, Daryl O.; Edgley, Amanda J.; Sonobe, Takashi; Fujii, Yutaka; Ishibashi-Ueda, Hatsue; Kelly, Darren J.; Yagi, Naoto; Shirai, Mikiyasu

2013-01-01

Diabetes is independently associated with a specific cardiomyopathy, characterized by impaired cardiac muscle relaxation and force development. Using synchrotron radiation small-angle x-ray scattering, this study investigated in the in situ heart and in real-time whether changes in cross-bridge disposition and myosin interfilament spacing underlie the early development of diabetic cardiomyopathy. Experiments were conducted using anesthetized Sprague-Dawley rats 3 weeks after treatment with either vehicle (control) or streptozotocin (diabetic). Diffraction patterns were recorded during baseline and dobutamine infusions simultaneous with ventricular pressure-volumetry. From these diffraction patterns myosin mass transfer to actin filaments was assessed as the change in intensity ratio (I1,0/I1,1). In diabetic hearts cross-bridge disposition was most notably abnormal in the diastolic phase (p < 0.05) and to a lesser extent the systolic phase (p < 0.05). In diabetic rats only, there was a transmural gradient of contractile depression. Elevated diabetic end-diastolic intensity ratios were correlated with the suppression of diastolic function (p < 0.05). Furthermore, the expected increase in myosin head transfer by dobutamine was significantly blunted in diabetic animals (p < 0.05). Interfilament spacing did not differ between groups. We reveal that impaired cross-bridge disposition and radial transfer may thus underlie the early decline in ventricular function observed in diabetic cardiomyopathy. PMID:23473489

Knee flexion with quadriceps cocontraction: A new therapeutic exercise for the early stage of ACL rehabilitation.

PubMed

Biscarini, Andrea; Contemori, Samuele; Busti, Daniele; Botti, Fabio M; Pettorossi, Vito E

2016-12-08

Quadriceps strengthening exercises designed for the early phase of anterior cruciate ligament (ACL) rehabilitation should limit the anterior tibial translation developed by quadriceps contraction near full knee extension, in order to avoid excessive strain on the healing tissue. We hypothesize that knee-flexion exercises with simultaneous voluntary contraction of quadriceps (voluntary quadriceps cocontraction) can yield considerable levels of quadriceps activation while preventing the tibia from translating forward relative to the femur. Electromyographic activity in quadriceps and hamstring muscles was measured in 20 healthy males during isometric knee-flexion exercises executed near full knee extension with maximal voluntary effort of quadriceps cocontraction and external resistance (R) ranging from 0% to 60% of the 1-repetition maximum (1RM). Biomechanical modeling was applied to derive the shear (anterior/posterior) tibiofemoral force developed in each exercise condition. Isometric knee-flexion exercises with small external resistance (R=10% 1RM) and maximal voluntary effort of quadriceps cocontraction yielded a net posterior (ACL-unloading) tibial pull (P=0.005) and levels of activation of 32%, 50%, and 45% of maximum voluntary isometric contraction, for the rectus femoris, vastus medialis, and vastus lateralis, respectively. This exercise might potentially rank as one of the most appropriate quadriceps strengthening interventions in the early phase of ACL rehabilitation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Wake Vortex Detection: Phased Microphone vs. Linear Infrasonic Array

NASA Technical Reports Server (NTRS)

Shams, Qamar A.; Zuckerwar, Allan J.; Sullivan, Nicholas T.; Knight, Howard K.

2014-01-01

Sensor technologies can make a significant impact on the detection of aircraft-generated vortices in an air space of interest, typically in the approach or departure corridor. Current state-of-the art sensor technologies do not provide three-dimensional measurements needed for an operational system or even for wake vortex modeling to advance the understanding of vortex behavior. Most wake vortex sensor systems used today have been developed only for research applications and lack the reliability needed for continuous operation. The main challenges for the development of an operational sensor system are reliability, all-weather operation, and spatial coverage. Such a sensor has been sought for a period of last forty years. Acoustic sensors were first proposed and tested by National Oceanic and Atmospheric Administration (NOAA) early in 1970s for tracking wake vortices but these acoustic sensors suffered from high levels of ambient noise. Over a period of the last fifteen years, there has been renewed interest in studying noise generated by aircraft wake vortices, both numerically and experimentally. The German Aerospace Center (DLR) was the first to propose the application of a phased microphone array for the investigation of the noise sources of wake vortices. The concept was first demonstrated at Berlins Airport Schoenefeld in 2000. A second test was conducted in Tarbes, France, in 2002, where phased microphone arrays were applied to study the wake vortex noise of an Airbus 340. Similarly, microphone phased arrays and other opto-acoustic microphones were evaluated in a field test at the Denver International Airport in 2003. For the Tarbes and Denver tests, the wake trajectories of phased microphone arrays and lidar were compared as these were installed side by side. Due to a built-in pressure equalization vent these microphones were not suitable for capturing acoustic noise below 20 Hz. Our group at NASA Langley Research Center developed and installed an infrasonic array at the Newport News-Williamsburg International Airport early in the year 2013. A pattern of pressure burst, high-coherence intervals, and diminishing-coherence intervals was observed for all takeoff and landing events without exception. The results of a phased microphone vs. linear infrasonic array comparison will be presented.

Non-invasive detection of the early phase of kidney injury by photoacoustic/computed tomography imaging.

PubMed

Pan, Wanma; Peng, Wen; Ning, Fengling; Zhang, Yu; Zhang, Yunfei; Wang, Yinhang; Xie, Weiyi; Zhang, Jing; Xin, Hong; Li, Cong; Zhang, Xuemei

2018-06-29

The early diagnosis of kidney diseases, which can remarkably impair the quality of life and are costly, has encountered great difficulties. Therefore, the development of methods for early diagnosis has great clinical significance. In this study, we used an emerging technique of photoacoustic (PA) imaging, which has relatively high spatial resolution and good imaging depth. Two kinds of PA gold nanoparticle (GNP)-based bioprobes were developed based on their superior photo detectability, size controllability and biocompatibility. The kidney injury mouse model was developed by unilateral ureteral obstruction for 96 h and the release of obstruction model). Giving 3.5 and 5.5 nm bioprobes by tail vein injection, we found that the 5.5 nm probe could be detected in the bladder in the model group, but not in the control group. These results were confirmed by computed tomography imaging. Furthermore, the model group did not show changes in the blood biochemical indices (BUN and Scr) and histologic examination. The 5.5 nm GNPs were found to be the critical point for early diagnosis of kidney injury. This new method was faster and more sensitive and accurate for the detection of renal injury, compared with conventional methods, and can be used for the development of a PA GNP-based bioprobe for diagnosing renal injury.

Non-invasive detection of the early phase of kidney injury by photoacoustic/computed tomography imaging

NASA Astrophysics Data System (ADS)

Pan, Wanma; Peng, Wen; Ning, Fengling; Zhang, Yu; Zhang, Yunfei; Wang, Yinhang; Xie, Weiyi; Zhang, Jing; Xin, Hong; Li, Cong; Zhang, Xuemei

2018-06-01

The early diagnosis of kidney diseases, which can remarkably impair the quality of life and are costly, has encountered great difficulties. Therefore, the development of methods for early diagnosis has great clinical significance. In this study, we used an emerging technique of photoacoustic (PA) imaging, which has relatively high spatial resolution and good imaging depth. Two kinds of PA gold nanoparticle (GNP)-based bioprobes were developed based on their superior photo detectability, size controllability and biocompatibility. The kidney injury mouse model was developed by unilateral ureteral obstruction for 96 h and the release of obstruction model). Giving 3.5 and 5.5 nm bioprobes by tail vein injection, we found that the 5.5 nm probe could be detected in the bladder in the model group, but not in the control group. These results were confirmed by computed tomography imaging. Furthermore, the model group did not show changes in the blood biochemical indices (BUN and Scr) and histologic examination. The 5.5 nm GNPs were found to be the critical point for early diagnosis of kidney injury. This new method was faster and more sensitive and accurate for the detection of renal injury, compared with conventional methods, and can be used for the development of a PA GNP-based bioprobe for diagnosing renal injury.

Anisotropic Magnetohydrodynamic Turbulence Driven by Parametric Decay Instability: The Onset of Phase Mixing and Alfvén Wave Turbulence

NASA Astrophysics Data System (ADS)

Shoda, Munehito; Yokoyama, Takaaki

2018-06-01

We conduct a 3D magnetohydrodynamic (MHD) simulation of the parametric decay instability of Alfvén waves and resultant compressible MHD turbulence, which is likely to develop in the solar wind acceleration region. Because of the presence of the mean magnetic field, the nonlinear stage is characterized by filament-like structuring and anisotropic cascading. By calculating the timescales of phase mixing and the evolution of Alfvén wave turbulence, we have found that the early nonlinear stage is dominated by phase mixing, while the later phase is dominated by imbalanced Alfvén wave turbulence. Our results indicate that the regions in the solar atmosphere with large density fluctuation, such as the coronal bottom and wind acceleration region, are heated by phase-mixed Alfvén waves, while the other regions are heated by Alfvén wave turbulence.

Fluctuation-driven electroweak phase transition. [in early universe

NASA Technical Reports Server (NTRS)

Gleiser, Marcelo; Kolb, Edward W.

1992-01-01

We examine the dynamics of the electroweak phase transition in the early Universe. For Higgs masses in the range 46 less than or = M sub H less than or = 150 GeV and top quark masses less than 200 GeV, regions of symmetric and asymmetric vacuum coexist to below the critical temperature, with thermal equilibrium between the two phases maintained by fluctuations of both phases. We propose that the transition to the asymmetric vacuum is completed by percolation of these subcritical fluctuations. Our results are relevant to scenarios of baryogenesis that invoke a weakly first-order phase transition at the electroweak scale.

Taking the brakes off the learning curve.

PubMed

Gheysen, Freja; Lasne, Gabriel; Pélégrini-Issac, Mélanie; Albouy, Genevieve; Meunier, Sabine; Benali, Habib; Doyon, Julien; Popa, Traian

2017-03-01

Motor learning is characterized by patterns of cerebello-striato-cortical activations shifting in time, yet the early dynamic and function of these activations remains unclear. Five groups of subjects underwent either continuous or intermittent theta-burst stimulation of one cerebellar hemisphere, or no stimulation just before learning a new motor sequence during fMRI scanning. We identified three phases during initial learning: one rapid, one slow, and one quasi-asymptotic performance phase. These phases were not changed by left cerebellar stimulation. Right cerebellar inhibition, however, accelerated learning and enhanced brain activation in critical motor learning-related areas during the first phase, continuing with reduced brain activation but high-performance in late phase. Right cerebellar excitation did not affect the early learning process, but slowed learning significantly in late phase, along with increased brain activation. We conclude that the right cerebellum is a key factor coordinating other neuronal loops in the early acquisition of an explicit motor sequential skill. Hum Brain Mapp 38:1676-1691, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A late wake time phase delays the human dim light melatonin rhythm.

PubMed

Burgess, Helen J; Eastman, Charmane I

2006-03-13

Short sleep/dark durations, due to late bedtimes or early wake times or both, are common in modern society. We have previously shown that a series of days with a late bedtime phase delays the human dim light melatonin rhythm, as compared to a series of days with an early bedtime, despite a fixed wake time. Here we compared the effect of an early versus late wake time with a fixed bedtime on the human dim light melatonin rhythm. Fourteen healthy subjects experienced 2 weeks of short 6h nights with an early wake time fixed at their habitual weekday wake time and 2 weeks of long 9 h nights with a wake time that occurred 3h later than the early wake time, in counterbalanced order. We found that after 2 weeks with the late wake time, the dim light melatonin onset delayed by 2.4 h and the dim light melatonin offset delayed by 2.6 h (both p < 0.001), as compared to after 2 weeks with the early wake time. These results highlight the substantial influence that wake time, likely via the associated morning light exposure, has on the timing of the human circadian clock. Furthermore, the results suggest that when people truncate their sleep by waking early their circadian clocks phase advance and when people wake late their circadian clocks phase delay.

Challenges Facing Early Phase Trials Sponsored by the National Cancer Institute: An Analysis of Corrective Action Plans to Improve Accrual

PubMed Central

Massett, Holly A.; Mishkin, Grace; Rubinstein, Larry; Ivy, S. Percy; Denicoff, Andrea; Godwin, Elizabeth; DiPiazza, Kate; Bolognese, Jennifer; Zwiebel, James A.; Abrams, Jeffrey S.

2016-01-01

Accruing patients in a timely manner represents a significant challenge to early phase cancer clinical trials. The NCI Cancer Therapy Evaluation Program analyzed 19 months of corrective action plans (CAPs) received for slow-accruing Phase 1 and 2 trials to identify slow accrual reasons, evaluate whether proposed corrective actions matched these reasons, and assess the CAP impact on trial accrual, duration, and likelihood of meeting primary scientific objectives. Of the 135 CAPs analyzed, 69 were for Phase 1 trials and 66 for Phase 2 trials. Primary reasons cited for slow accrual were safety/toxicity (Phase 1: 48%), design/protocol concerns (Phase 1: 42%, Phase 2: 33%), and eligibility criteria (Phase 1: 41%, Phase 2: 35%). The most commonly proposed corrective actions were adding institutions (Phase 1: 43%, Phase 2: 85%) and amending the trial to change eligibility or design (Phase 1: 55%, Phase 2: 44%). Only 40% of CAPs provided proposed corrective actions that matched the reasons given for slow accrual. Seventy percent of trials were closed to accrual at time of analysis (Phase 1=48; Phase 2=46). Of these, 67% of Phase 1 and 70% of Phase 2 trials met their primary objectives, but they were active three times longer than projected. Among closed trials, 24% had an accrual rate increase associated with a greater likelihood of meeting their primary scientific objectives. Ultimately, trials receiving CAPs saw improved accrual rates. Future trials may benefit from implementing CAPs early in trial lifecycles, but it may be more beneficial to invest in earlier accrual planning. PMID:27401246

Early diagenesis and recrystallization of bone

NASA Astrophysics Data System (ADS)

Keenan, Sarah W.; Engel, Annette Summers

2017-01-01

One of the most challenging problems in paleobiology is determining how bone transforms from a living tissue into a fossil. The geologic record is replete with vertebrate fossils preserved from a range of depositional environments, including wetland systems. However, thermodynamic models suggest that bone (modeled as hydroxylapatite) is generally unstable in a range of varying geochemical conditions and should readily dissolve if it does not alter to a more thermodynamically stable phase, such as a fluorine-enriched apatite. Here, we assess diagenesis of alligator bone from fleshed, articulated skeletons buried in wetland soils and from de-fleshed bones in experimental mesocosms with and without microbial colonization. When microbial colonization of bone was inhibited, bioapatite recrystallization to a more stable apatite phase occurred after one month of burial. Ca-Fe-phosphate phases in bone developed after several months to years due to ion substitutions from the protonation of the hydroxyl ion. These rapid changes demonstrate a continuum of structural and bonding transformations to bone that have not been observed previously. When bones were directly in contact with sediment and microbial cells, rapid bioerosion and compositional alteration occurred after one week, but slowed after one month because biofilms reduced exposed surfaces and subsequent bioapatite lattice substitutions. Microbial contributions are likely essential in forming stable apatite phases during early diagenesis and for enabling bone preservation and fossilization.

HIV/AIDS Clinical Trials

MedlinePlus

... Participants Studies with Female Participants What's this? Age Group: What's this? Child (birth-17) Adult (18-65) Senior (66+) Phase: What's this? Early Phase 1 Phase 1 Phase 2 Phase 3 Phase 4 Funded By: What's this? NIH Other U.S. Federal ...

Menstrual phase-related differences in the pulsatility index on the central retinal artery suggest an oestrogen vasodilatation effect that antagonizes with progesterone.

PubMed

Viana, Luiz Carlos; Faria, Marcos; Pettersen, Heverton; Sampaio, Marcos; Geber, Selmo

2011-03-01

The actual effect of steroid hormones on cerebral microcirculation is still controversial. Therefore, the aim of our study was to investigate vascular flow variations in the central retinal artery that may exist during the ovulatory menstrual cycle. A total of 34 healthy women were included in this observational, longitudinal, and prospective study. All participants were submitted to dopplerfluxometric evaluation of the eyes in order to study the pulsatility index (PI) of the central retinal arteries, during four phases of the menstrual cycle: early follicular, mid follicular, periovulatory, and mid luteal phases. Subjects' ages ranged from 14 to 47 years old (mean: 29.7 ± 10.1) and PI did not differ among age groups. The PI of the central retinal artery was different among the four phases of the menstrual cycle. PI showed a significant decrease from early follicular phase (1.72) to mid follicular phase (1.57) (p = 0.037), and was similar during periovulatory phase (1.56) and significantly increased in mid luteal phase (1.70). After that it returned to the values observed in the early follicular phase. Our results suggest the existence of an oestrogen vasodilatation effect on the central retinal artery that is menstrual phase-related and antagonized by progesterone.

A more rational approach to new-product development.

PubMed

Bonabeau, Eric; Bodick, Neil; Armstrong, Robert W

2008-03-01

Companies often treat new-product development as a monolithic process, but it can be more rationally divided into two parts: an early stage that focuses on evaluating prospects and eliminating bad bets, and a late stage that maximizes the remaining candidates' market potential. Recognizing the value of this approach, Eli Lilly designed and piloted Chorus, an autonomous unit dedicated solely to the early stage. This article demonstrates how segmenting development in this way can speed it up and make it more cost-effective. Two classes of decision-making errors can impede NPD, the authors say. First, managers often ignore evidence challenging their assumptions that projects will succeed. As a result, many projects go forward despite multiple red flags; some even reach the market, only to fail dramatically after their introduction. Second, companies sometimes terminate projects prematurely because people fail to conduct the right experiments to reveal products' potential. Most companies promote both kinds of errors by focusing disproportionately on late-stage development; they lack the early, truth-seeking functions that would head such errors off. In segmented NPD, however, the early-stage organization maintains loyalty to the experiment rather than the product, whereas the late-stage organization pursues commercial success. Chorus has significantly improved NPD efficiency and productivity at Lilly. Although the unit absorbs just one-tenth of Lilly's investment in early-stage development, it delivers a substantially greater fraction of the molecules slated for late Phase II trials--at almost twice the speed and less than a third of the cost of the standard process, sometimes shaving as much as two years off the usual development time.

Peer Exclusion During the Pubertal Transition: The Role of Social Competence.

PubMed

Carter, Rona; Halawah, Amira; Trinh, Sarah L

2018-01-01

For some youth, early puberty is accompanied by peer exclusion. Yet early developers may experience less peer exclusion if they have social competence, which would bolster their ability to develop and maintain positive relationships with their peers. Accordingly, the present study tests whether pubertal timing and tempo predicts decrements in children's social competence and whether decrements in social competence account for associations between puberty (timing and tempo) and peer exclusion over time. Longitudinal data were drawn from 1364 families (48% female; 76% White; M = 9.32 years, SD = .48, at Wave 3) who participated in Waves 3-5 (i.e., grades 4-6) of Phase III of the NICHD-SECCYD. The results from latent growth curve models indicated that earlier pubertal timing and more rapid pubertal tempo among girls were associated with high initial levels of peer exclusion. Moreover, mediation analyses revealed that early developers' susceptibility to peer exclusion was associated with their initial level of social competence. In boys, pubertal timing and tempo were not directly associated with peer exclusion; instead, indirect effects of pubertal timing on peer exclusion (intercept, slope) occurred through initial levels of social competence. On average, early developers' who had low levels of social competence also had high initial levels of peer exclusion but experienced decrements in peer exclusion over time. The association between the intercepts for puberty and peer exclusion and the slopes for social competence and peer exclusion were stronger for boys than girls. Overall, our findings suggest that early developers' susceptibility to and experiences of peer exclusion are associated with their development of social competence.

Life cycle analysis within pharmaceutical process optimization and intensification: case study of active pharmaceutical ingredient production.

PubMed

Ott, Denise; Kralisch, Dana; Denčić, Ivana; Hessel, Volker; Laribi, Yosra; Perrichon, Philippe D; Berguerand, Charline; Kiwi-Minsker, Lioubov; Loeb, Patrick

2014-12-01

As the demand for new drugs is rising, the pharmaceutical industry faces the quest of shortening development time, and thus, reducing the time to market. Environmental aspects typically still play a minor role within the early phase of process development. Nevertheless, it is highly promising to rethink, redesign, and optimize process strategies as early as possible in active pharmaceutical ingredient (API) process development, rather than later at the stage of already established processes. The study presented herein deals with a holistic life-cycle-based process optimization and intensification of a pharmaceutical production process targeting a low-volume, high-value API. Striving for process intensification by transfer from batch to continuous processing, as well as an alternative catalytic system, different process options are evaluated with regard to their environmental impact to identify bottlenecks and improvement potentials for further process development activities. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Can metamorphosis survival during larval development in spiny lobster Sagmariasus verreauxi be improved through quantitative genetic inheritance?

PubMed

Nguyen, Nguyen H; Fitzgibbon, Quinn P; Quinn, Jane; Smith, Greg; Battaglene, Stephen; Knibb, Wayne

2018-05-04

One of the major impediments to spiny lobster aquaculture is the high cost of hatchery production due to the long and complex larval cycle and poor survival during the many moult stages, especially at metamorphosis. We examined if the key trait of larval survival can be improved through selection by determining if genetic variance exists for this trait. Specifically, we report, for the first time, genetic parameters (heritability and correlations) for early survival rates recorded at five larval phases; early-phyllosoma stages (instars 1-6; S1), mid-phyllosoma stages (instars; 7-12; S2), late-phyllosoma stages (instars 13-17; S3), metamorphosis (S4) and puerulus stage (S5) in hatchery-reared spiny lobster Sagmariasus verreauxi. The data were collected from a total of 235,060 larvae produced from 18 sires and 30 dams over nine years (2006 to 2014). Parentage of the offspring and full-sib families was verified using ten microsatellite markers. Analysis of variance components showed that the estimates of heritability for all the five phases of larval survival obtained from linear mixed model were generally similar to those obtained from threshold logistic generalised models (0.03-0.47 vs. 0.01-0.50). The heritability estimates for survival traits recorded in the early larval phases (S1 and S2) were higher than those estimated in later phases (S3, S4 and S5). The existence of the additive genetic component in larval survival traits indicate that they could be improved through selection. Both phenotypic and genetic correlations among the five survival measures studied were moderate to high and positive. The genetic associations between successive rearing periods were stronger than those that are further apart. Our estimates of heritability and genetic correlations reported here in a spiny lobster species indicate that improvement in the early survival especially during metamorphosis can be achieved through genetic selection in this highly economic value species.

Early 20th Century Arctic Warming Intensified by Pacific and Atlantic Multidecadal Variability

NASA Astrophysics Data System (ADS)

Tokinaga, H.; Xie, S. P.; Mukougawa, H.

2017-12-01

We investigate the influence of Pacific and Atlantic multidecadal variability on the Arctic temperature, with a particular focus on the early 20th century Arctic warming. Arctic surface air temperature increased rapidly over the early 20th century, at rates comparable to those of recent decades despite much weaker greenhouse gas forcing than at present. We find that the concurrent phase shift of Pacific and Atlantic multidecadal variability is the major driver for the early 20th century Arctic warming. Atmospheric model simulations reproduce the early Arctic warming when the interdecadal variability of sea surface temperature (SST) is properly prescribed. The early Arctic warming is associated with the cold-to-warm phase shifts of Atlantic and Pacific multidecadal variability modes, a SST pattern reminiscent of the positive phase of the Pacific decadal and Atlantic multidecadal oscillations. The extratropical North Atlantic and North Pacific SST warming strengthens surface westerly winds over northern Eurasia, intensifying the warming there. The equatorial Pacific warming deepens the Aleutian low, advecting warm air to the North American Arctic. Coupled ocean-atmosphere simulations support the constructive intensification of Arctic warming by a concurrent, cold-to-warm phase shift of the Pacific and Atlantic multidecadal variability. Our results aid attributing the historical Arctic warming and thereby constrain the amplified warming projected for this important region.

The quantum defect: Early history and recent developments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rau, A.R.; Inokuti, M.

1997-03-01

The notion of the quantum defect is important in atomic and molecular spectroscopy and also in unifying spectroscopy with collision theory. In the latter context, the quantum defect may be viewed as an ancestor of the phase shift. However, the origin of the term {open_quotes}quantum defect{close_quotes} does not seem to be explained in standard textbooks. It occurred in a 1921 paper by Schr{umlt o}dinger, preceding quantum mechanics, yet giving the correct meaning as an index of the short-range interactions with the core of an atom. We present the early history of the quantum-defect idea, and sketch its recent developments. {copyright}more » {ital 1997 American Association of Physics Teachers.}« less

The Swiss Cystic Fibrosis Infant Lung Development (SCILD) cohort.

PubMed

Korten, Insa; Kieninger, Elisabeth; Yammine, Sophie; Regamey, Nicolas; Nyilas, Sylvia; Ramsey, Kathryn; Casaulta, Carmen; Latzin, Philipp; For The Scild Study Group

2018-04-26

The Swiss Cystic Fibrosis Infant Lung Development (SCILD) cohort is a prospective birth cohort study investigating the initiating events of cystic fibrosis lung disease during infancy, and their influence on the trajectory of disease progression throughout early childhood. Infants with cystic fibrosis are recruited throughout Switzerland after diagnosis by new-born screening. It is the first European population-based prospective cohort study of infants with cystic fibrosis taking advantage of a nationwide new-born screening programme. The study was established in 2011 and recruitment is ongoing. The cohort study is currently divided into three study phases (phase 1: diagnosis to age 1 year; phase 2: age 1 to 3 years; and phase 3: age 3 to 6 years). Study participants have weekly telephone interviews, weekly anterior nasal swab collection and two study visits in the first year of life. They also complete follow-up study visits at 3 and 6 years of age. Data for this study are derived from questionnaires, lung function measurements, telephone interviews, nasal swab material and magnetic resonance imaging. To date, 70 infants have been recruited into the study and 56 have completed phase 1, including a baseline study visit at 6 weeks of age, weekly surveillance and a study visit at one year of age. More than 2500 data points on respiratory health and almost 2000 nasal samples have been collected. Phases 2 and 3 will commence in 2018. The dataset of the SCILD cohort combines lung function data, the collection of environmental and sociodemographic factors, documentation of respiratory symptoms, and microbiological analyses. The design not only allows tracking of the cystic fibrosis lung disease independent of clinical status, but also surveillance of early disease prior to severe clinical symptoms. This cohort profile provides details on the study design and summarizes the first published results of the SCILD cohort.

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.

Supra- and Sub-Baseline Phosphocreatine Recovery in Developing Brain after Transient Hypoxia-Ischaemia: Relation to Baseline Energetics, Insult Severity and Outcome

ERIC Educational Resources Information Center

Iwata, Osuke; Iwata, Sachiko; Bainbridge, Alan; De Vita, Enrico; Matsuishi, Toyojiro; Cady, Ernest B.; Robertson, Nicola J.

2008-01-01

Following hypoxia-ischaemia (HI), an early biomarker of insult severity is desirable to target neuroprotective therapies to patients most likely to benefit; currently there are no biomarkers within the "latent phase" period before the establishment of secondary energy failure. Brief transient phosphocreatine (PCr) recovery overshoot (measured…

Phase Transitions: In the Brain, Socio-­Dramatic Play and Meaningful Early Learning

ERIC Educational Resources Information Center

Fromberg, Doris Pronin

2017-01-01

There are similar, non-linear complex dynamical systems that underlie the epigenetic development of young children. This paper discusses the confluence of research on brain functions; a body or research that informs the characteristics of young children's play and imagination; and the ways in which young children acquire fresh perceptions and…

Developing a Precareer Network: An Exercise in Identifying, Using, and Making Investments in Social Capital

ERIC Educational Resources Information Center

Reardon, Karen A.; Walsh, Anne M.

2017-01-01

Research on the use of experiential exercises to encourage exploration of professional networks shows that such exercises are effective and provide value for students seeking to enter or navigate careers. Often students in the early phase of their undergraduate experience are unaware of the process involved in building a professional network or…

Careers and people

NASA Astrophysics Data System (ADS)

2016-12-01

The 2016 Paolo Farinella Prize has been awarded to Greek physicist Kleomenis Tsiganis at the Aristotle University of Thessaloniki, for his work on the applications of celestial mechanics to the dynamics of planetary systems, including the development of the “Nice model”, which describes the migrations of Jupiter, Saturn, Uranus and Neptune during the early phases of the solar system's evolution.

Validation, Edits, and Application Processing Phase II and Error-Prone Model Report.

ERIC Educational Resources Information Center

Gray, Susan; And Others

The impact of quality assurance procedures on the correct award of Basic Educational Opportunity Grants (BEOGs) for 1979-1980 was assessed, and a model for detecting error-prone applications early in processing was developed. The Bureau of Student Financial Aid introduced new comments into the edit system in 1979 and expanded the pre-established…

An Analysis of Excellent Early Educational Practices: Preliminary Report.

ERIC Educational Resources Information Center

White, Burton L.

This document reports the first phase of a longitudinal research project designed to produce information on how to raise children so their basic abilities may develop optimally during the first six years of life. Although this Preschool Project has been in operation five years, the study is not yet completed because statements about the effects of…

Inspecting School Social Quality: Assessing and Improving School Effectiveness in the Social Domain

ERIC Educational Resources Information Center

Dijkstra, Anne Bert; Daas, Remmert; De la Motte, Per Ingvar; Ehren, Melanie

2017-01-01

Purpose: School inspection of school social quality is, in contrast to inspection in the cognitive domain, still in its early phase of development. While schools are shown to affect social outcomes, the interplay of mechanisms makes it difficult to isolate the effect of the school. This paper aims to evaluate different approaches to inspecting…

Trophic or full nutritional support?

PubMed

Arabi, Yaseen M; Al-Dorzi, Hasan M

2018-06-04

Full nutritional support during the acute phase of critical illness has traditionally been recommended to reduce catabolism and prevent malnutrition. Approaches to achieve full nutrition include early initiation of nutritional support, targeting full nutritional requirement as soon as possible and initiation of supplemental parenteral nutrition when enteral nutrition does not reach the target. Existing evidence supports early enteral nutrition over delayed enteral nutrition or early parenteral nutrition. Recent randomized controlled trials have demonstrated that permissive underfeeding or trophic feeding is associated with similar outcomes compared with full feeding in the acute phase of critical illness. In patients with refeeding syndrome, patients with high nutritional risk and patients with shock, early enteral nutrition targeting full nutritional targets may be associated with worse outcomes compared with less aggressive enteral nutrition strategy. A two-phase approach for nutritional support may more appropriately account for the physiologic changes during critical illness than one-phase approach. Further evidence is awaited for the optimal protein amount during critical illness and for feeding patients at high nutritional risk or with acute gastrointestinal injury.

Anaphase-promoting complex/cyclosome-CDH1-mediated proteolysis of the forkhead box M1 transcription factor is critical for regulated entry into S phase.

PubMed

Park, Hyun Jung; Costa, Robert H; Lau, Lester F; Tyner, Angela L; Raychaudhuri, Pradip

2008-09-01

The forkhead box M1 (FoxM1) transcription factor is overexpressed in many cancers, and in mouse models it is required for tumor progression. FoxM1 activates expression of the cell cycle genes required for both S and M phase progression. Here we demonstrate that FoxM1 is degraded in late mitosis and early G(1) phase by the anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase. FoxM1 interacts with the APC/C complex and its adaptor, Cdh1. Expression of Cdh1 stimulated degradation of the FoxM1 protein, and depletion of Cdh1 resulted in stabilization of the FoxM1 protein in late mitosis and in early G(1) phase of the cell cycle. Cdh1 has been implicated in regulating S phase entry. We show that codepletion of FoxM1 inhibits early S phase entry observed in Cdh1-depleted cells. The N-terminal region of FoxM1 contains both destruction box (D box) and KEN box sequences that are required for targeting by Cdh1. Mutation of either the D box sequence or the KEN box sequence stabilized FoxM1 and blocked Cdh1-induced proteolysis. Cells expressing a nondegradable form of FoxM1 entered S phase rapidly following release from M phase arrest. Together, our observations show that FoxM1 is one of the targets of Cdh1 in late M or early G(1) phase and that its proteolysis is important for regulated entry into S phase.

Characterization of Early Age Curing and Shrinkage of Metakaolin-Based Inorganic Binders with Different Rheological Behavior by Fiber Bragg Grating Sensors

PubMed Central

Palumbo, Giovanna; Iadicicco, Agostino; Messina, Francesco; Campopiano, Stefania; Cioffi, Raffaele; Colangelo, Francesco

2017-01-01

This paper reports results related to early age temperature and shrinkage measurements by means fiber Bragg gratings (FBGs), which were embedded in geopolymer matrices. The sensors were properly packaged in order to discriminate between different shrinkage behavior and temperature development. Geopolymer systems based on metakaolin were investigated, which dealt with different commercial aluminosilicate precursors and siliceous filler contents. The proposed measuring system will allow us to control, in a very accurate way, the early age phases of the binding systems made by metakaolin geopolymer. A series of experiments were conducted on different compositions; moreover, rheological issues related to the proposed experimental method were also assessed. PMID:29271912

Astigmatism in the Early Treatment for Retinopathy of Prematurity Study: findings to 3 years of age

PubMed Central

Davitt, Bradley V.; Dobson, Velma; Quinn, Graham E.; Hardy, Robert J.; Tung, Betty; Good, William V.

2009-01-01

Purpose To examine the prevalence of astigmatism (≥ 1.00 diopter (D)) and high astigmatism (≥ 2.00 D) at 6 and 9 months post-term and 2 and 3 years postnatal, in preterm children with birth weight < 1251g who developed high-risk prethreshold retinopathy of prematurity (ROP) and participated in the Early Treatment for ROP (ETROP) Study. Design Randomized controlled clinical trial Participants 401 infants who developed prethreshold ROP in one or both eyes and were randomized after they were determined to have a high risk (≥ 15%) of poor structural outcome without treatment, using the RM-ROP2 risk management program. Refractive error was measured by cycloplegic retinoscopy. Eyes with additional retinal, glaucoma, or cataract surgery were excluded. Intervention Eyes were randomized to receive laser photocoagulation at high-risk prethreshold ROP (early treated (ET)) or to be conventionally managed (CM), receiving treatment only if threshold ROP developed. Main Outcome Measures Astigmatism and high astigmatism at each visit. Astigmatism was classified as “with-the rule” (75° – 105° (WTR)), “against-the-rule” (0° – 15° and 165° – 180° (ATR), or “oblique” (16° – 74° and 106° – 164° (OBL)). Results The prevalence of astigmatism in ET and CM eyes was similar at each test age. For both groups, there was an increase in prevalence of astigmatism from approximately 32% at 6 months to approximately 42% by 3 years, mostly occurring between 6 and 9 months. Among eyes that could be refracted, astigmatism was not influenced by zone of acute-phase ROP, presence of plus disease, or retinal residua of ROP. Eyes with astigmatism and high astigmatism most often had WTR astigmatism. Conclusions By age 3 years, nearly 43% of eyes treated at high-risk prethreshold ROP developed astigmatism ≥ 1.00 D and nearly 20% had astigmatism ≥ 2.00 D. Presence of astigmatism was not influenced by timing of treatment of acute-phase ROP, characteristics of acute-phase or cicatricial ROP. These findings reinforce the need for follow-up eye examinations in infants with high risk prethreshold ROP. PMID:19091409

Dynamic changes of nutrient composition throughout the entire life cycle of black soldier fly

PubMed Central

Liu, Xiu; Chen, Xuan; Wang, Hui; Yang, Qinqin; ur Rehman, Kashif; Li, Wu; Cai, Minmin; Li, Qing; Mazza, Lorenzo; Zhang, Jibin; Yu, Ziniu

2017-01-01

Black soldier fly (BSF) larvae, Hermetia illucens L., develops on organic wastes, reducing ecological pollution and converting waste biomass into protein and fat rich insect biomass. BSF can replace increasingly expensive protein sources used in poultry, aquaculture and livestock compound diet formulation, such as fish meal and soybean meal, which holds the potential to alleviate future food and feed insecurity. The fate of nutritional spectra in BSF during its life cycle phases is still poorly understood. This study assessed metabolic changes in nutrition composition of BSF from egg to adult. A rapid increase of crude fat content was observed since the development of 4–14 days of larvae with its maximum level reaching 28.4% in dry mass, whereas the crude protein displayed a continuous decreasing trend in the same development phases with minimum level of 38% at larval phase (12 days) and peak level of 46.2% at early pupa stage. A sharp drop in crude fat was noticed from early prepupae to late pupae (24.2%, 8.2% respectively). However crude protein shows its maximum value being 57.6% at postmortem adult stage with 21.6% fat level. In addition, fatty acids, amino acids, minerals and vitamins composition in different development stages of BSF were presented and compared. Findings from this study could provide podium to food and feed industry for framing a strategy for specific molecular nutritional component intake into the diets of humans, aquaculture and animals. It is also indicated that BSF is a possible insect which can be applied to combating the food scarcity of countries where micronutrient deficiency is prevalent. Moreover it contributes to advance exploring for developmental and metabolic biology of this edible insect. PMID:28796830

Risk management in international manned space program operations.

PubMed

Seastrom, J W; Peercy, R L; Johnson, G W; Sotnikov, B J; Brukhanov, N

2004-02-01

New, innovative joint safety policies and requirements were developed in support of the Shuttle/Mir program, which is the first phase of the International Space Station program. This work has resulted in a joint multinational analysis culminating in joint certification for mission readiness. For these planning and development efforts, each nation's risk programs and individual safety practices had to be integrated into a comprehensive and compatible system that reflects the joint nature of the endeavor. This paper highlights the major incremental steps involved in planning and program integration during development of the Shuttle/Mir program. It traces the transition from early development to operational status and highlights the valuable lessons learned that apply to the International Space Station program (Phase 2). Also examined are external and extraneous factors that affected mission operations and the corresponding solutions to ensure safe and effective Shuttle/Mir missions. c2003 Published by Elsevier Ltd.

Process change evaluation framework for allogeneic cell therapies: impact on drug development and commercialization.

PubMed

Hassan, Sally; Huang, Hsini; Warren, Kim; Mahdavi, Behzad; Smith, David; Jong, Simcha; Farid, Suzanne S

2016-04-01

Some allogeneic cell therapies requiring a high dose of cells for large indication groups demand a change in cell expansion technology, from planar units to microcarriers in single-use bioreactors for the market phase. The aim was to model the optimal timing for making this change. A development lifecycle cash flow framework was created to examine the implications of process changes to microcarrier cultures at different stages of a cell therapy's lifecycle. The analysis performed under assumptions used in the framework predicted that making this switch earlier in development is optimal from a total expected out-of-pocket cost perspective. From a risk-adjusted net present value view, switching at Phase I is economically competitive but a post-approval switch can offer the highest risk-adjusted net present value as the cost of switching is offset by initial market penetration with planar technologies. The framework can facilitate early decision-making during process development.

Unveiling changes in the landscape of patient populations in cancer early drug development

PubMed Central

Hierro, Cinta; Azaro, Analía; Argilés, Guillem; Elez, Elena; Gómez, Patricia; Carles, Joan; Rodon, Jordi

2017-01-01

The introduction of new Molecularly Targeted Agents (MTA) has changed the landscape in Early Drug Development (EDD) over the last two decades, leading to an improvement in clinical trial design. Previous Phase 1 (Ph1) studies with cytotoxics focused on safety objectives, only recruiting heavily pre-treated cancer patients, have been left behind. In this review, we will illustrate the slow although unstoppable change that has increasingly been observed in those populations candidate to participate in EDD trials with the advent of MTA. As more evidence regarding oncogene addiction becomes available, molecular-biomarker driven selection has been implemented among Molecularly-Selected Population (MSP) studies. New Window-Of-Opportunity (WOO) and Phase 0 (Ph0) studies have been developed in order to assess whether a MTA produces the hypothetical proposed biological effect. The rising need of getting early pharmacokinetics and pharmacodynamics data has led to the conduction of Healthy Volunteer (HV) studies, in part favoured for the particular and different toxicity profile of these MTA. However, several challenges will need to be addressed in order to boost the implementation of these new clinical trial designs in the forthcoming years. Among the problems to overcome, we would highlight a better coordination effort between centers for ensuring adequate patient accrual among small patient populations and a deepening into the ethics implied in enrolling patients in studies with no therapeutic intent. However, these tribulations will be certainly compensated by the possibility of opening a new horizon of treatment for diseases with dismal prognosis. PMID:27835915

Comparison of Occlusive and Open Application in a Psoriasis Plaque Test Design, Exemplarily Using Investigations of Mapracorat 0.1% Ointment versus Vehicle and Reference Drugs.

PubMed

Wigger-Alberti, Walter; Williams, Ragna; von Mackensen, Yi-Ling; Hoffman-Wecker, Maciej; Grossmann, Ulrike; Staedtler, Gerald; Nkulikiyinka, Richard; Shakery, Kaweh

2017-01-01

Psoriasis plaque tests (PPTs) are important tools in the early phases of antipsoriatic drug development. Two distinct PPT design variants (open vs. occluded drug application) are commonly used, but no previous work has aimed to directly compare and contrast their performance. We compared the antipsoriatic efficacy of mapracorat 0.1% ointment and reference drugs reported in 2 separate studies, representing open and occluded PPT designs. The drug effect size was measured by sonography (mean change in echo-poor band thickness), chromametry, and standardized clinical assessment. Antipsoriatic effects were detectable for the study drugs in both occluded and open PPTs. Differences between the potency of antipsoriatic drugs and vehicle were observable. The total antipsoriatic effect size appeared to be higher in the occluded PPT than the open PPT, despite the shorter treatment duration (2 vs. 4 weeks). Effect dynamics over time revealed greater differences between some study drugs in the open PPT compared to the occluded PPT. Taking the higher technical challenges for the open PPT into account, we recommend the occluded PPT as a standard screening setting in early drug development. In special cases, considering certain drug aspects or study objectives that would require procedural adaptations, an open PPT could be the better-suited design. Finally, both PPT models show clear advantages: classification as phase I studies, small number of psoriatic subjects, relatively short study duration, excellent discrimination between compounds and concentrations, parallel measurement of treatment response, and go/no go decisions very early in clinical development. © 2017 S. Karger AG, Basel.

Localization of DNA methyltransferase-1 during oocyte differentiation, in vitro maturation and early embryonic development in cow

PubMed Central

Lodde, V.; Modina, S.C.; Franciosi, F.; Zuccari, E.; Tessaro, I.; Luciano, A.M.

2009-01-01

DNA methyltransferase-1 (Dnmt1) is involved in the maintenance of DNA methylation patterns and is crucial for normal mammalian development. The aim of the present study was to assess the localization of Dnmt1 in cow, during the latest phases of oocyte differentiation and during the early stages of segmentation. Dnmt1 expression and localization were assessed in oocytes according to the chromatin configuration, which in turn provides an important epigenetic mechanism for the control of global gene expression and represents a morphological marker of oocyte differentiation. We found that the initial chromatin condensation was accompanied by a slight increase in the level of global DNA methylation, as assessed by 5-methyl-cytosine immunostaining followed by laser scanning confocal microscopy analysis (LSCM). RT-PCR confirmed the presence of Dnmt1 transcripts throughout this phase of oocyte differentiation. Analogously, Dnmt1 immunodetection and LSCM indicated that the protein was always present and localized in the cytoplasm, regardless the chromatin configuration and the level of global DNA methylation. Moreover, our data indicate that while Dnmt1 is retained in the cytoplasm in metaphase II stage oocytes and zygotes, it enters the nuclei of 8–16 cell stage embryos. As suggested in mouse, the functional meaning of the presence of Dnmt1 in the bovine embryo nuclei could be the maintainement of the methylation pattern of imprinted genes. In conclusion, the present work provides useful elements for the study of Dnmt1 function during the late stage of oocyte differentiation, maturation and early embryonic development in mammals. PMID:22073356

Development of Carbon Dioxide Removal Systems for Advanced Exploration Systems 2016-2017

NASA Technical Reports Server (NTRS)

Knox, James C.; Peters, Warren; Cmarik, Gregory E.; Watson, David; Coker, Robert; Miller, Lee

2017-01-01

A long-term goal for NASA is to enable crewed missions to Mars: first to the vicinity of Mars, and then to the Mars surface. These missions present new challenges for all aspects of spacecraft design in comparison with the International Space Station, as resupply is unavailable in the transit phase, and early return is not possible. Additionally, mass, power, and volume must be minimized for all phases to reduce propulsion needs. In this paper we describe current and planned developments in the area of carbon dioxide removal to support future crewed Mars missions. Activities are also described that apply to both the resolution of anomalies observed in the ISS CDRA and the design of life support systems for future missions.

Metaproteomics Reveals Functional Shifts in Microbial and Human Proteins During Infant Gut Colonization Case

DOE PAGES

Young, Jacque C.; Pan, Chongle; Adams, Rachel M.; ...

2015-01-01

The microbial colonization of the human gastrointestinal tract plays an important role in establishing health and homeostasis. However, the time-dependent functional signatures of microbial and human proteins during early colonization of the gut have yet to be determined. Thus, we employed shotgun proteomics to simultaneously monitor microbial and human proteins in fecal samples from a preterm infant during the first month of life. Microbial community complexity and functions increased over time, with compositional changes that were consistent with previous metagenomic and rRNA gene data indicating three distinct colonization phases. Overall microbial community functions were established relatively early in development andmore » remained stable. Human proteins detected included those responsible for epithelial barrier function and antimicrobial activity. Some neutrophil-derived proteins increased in abundance early in the study period, suggesting activation of the innate immune system. Moreover, abundances of cytoskeletal and mucin proteins increased later in the time course, suggestive of subsequent adjustment to the increased microbial load. Our study provides the first snapshot of coordinated human and microbial protein expression in the infant gut during early development.« less

Luteal phase deficiency: abnormal gonadotropin and progesterone secretion patterns.

PubMed

Soules, M R; Clifton, D K; Cohen, N L; Bremner, W J; Steiner, R A

1989-10-01

Luteal phase deficiency (LPD) is a reproductive disorder associated with infertility and spontaneous abortion. This study was undertaken to determine whether LPD might be related to an abnormal pattern of gonadotropin secretion. We tested this hypothesis by evaluating the pattern of pulsatile LH secretion in both the follicular and luteal phases of the menstrual cycle in normal women (n = 21) and women with LPD (n = 20), which was diagnosed on the basis of two out of phase endometrial biopsies. In addition, we sought to determine whether changes in progesterone (P) pulse patterns could account for the decrease in average serum P levels in women with LPD. To this end, we examined the pulse patterns of P and compared these patterns between normal women and those with LPD. Frequent blood sampling was performed in both groups to determine their respective hormone secretion patterns. In the follicular phase, blood samples were obtained every 10 min for 12 h; in the luteal phase the samples were obtained every 10 min for 12 h; in the luteal LH, FSH, and P were assayed in each sample. Pulse detection was performed by an adaptive threshold method of pulse analysis. The LH pulse frequency was significantly higher in the women with LPD than in the normal women in the early follicular phase [P less than 0.05; LPD, 12.8 +/- 1.4 (+/- SE); normal, 8.2 +/- 0.7 pulses/12 h]. LH pulse frequency was similar in the early and late follicular phases in the women with LPD, whereas it was higher in the late follicular phase in normal women. Mean serum FSH levels were not different between groups in both the early and late follicular phases. In the luteal phase the P pulse amplitude and mean serum P level were significantly lower in the LPD group than in the normal women (P less than 0.01). We conclude that 1) a too rapid LH pulse pattern in the early follicular phase may lead to inadequate LH support of the corpus luteum and become manifest as LPD; 2) the mechanism for inadequate P secretion in LPD is decreased P pulse amplitude; 3) the finding of similar serum FSH levels in the two groups in both the early and late follicular phases did not support compromised folliculogenesis as an etiological factor for LPD.

Mechanisms underlying hemodynamic and neuroendocrine stress reactivity at different phases of the menstrual cycle

PubMed Central

Gordon, Jennifer L.; Girdler, Susan S.

2014-01-01

This study examined the association of menstrual cycle phase with stress reactivity as well as the hormonal and neuroendocrine mechanisms contributing to cycle effects. Fifty-seven women underwent a modified Trier Social Stress Test (TSST) during the early follicular, late follicular and luteal phases of the menstrual cycle. Greater increases in cardiac index (CI) and greater decreases in vascular resistance index (VRI) during speech were observed in the luteal phase relative to other phases, while greater increases in epinephrine (EPI) was observed during the late follicular and luteal phases compared to the early follicular phase. Luteal phase estradiol predicted luteal EPI reactivity but not CI or VRI reactivity while luteal phase EPI reactivity predicted luteal phase CI and VRI reactivity. Thus, cycle-related changes in EPI reactivity may be a stronger determinant of cycle effects on hemodynamic reactivity than sex hormones per se. PMID:24397365

Pressure-Induced Dissolution and Reentrant Formation of Condensed, Liquid-Liquid Phase-Separated Elastomeric α-Elastin.

PubMed

Cinar, Hasan; Cinar, Süleyman; Chan, Hue Sun; Winter, Roland

2018-05-08

We investigated the combined effects of temperature and pressure on liquid-liquid phase separation (LLPS) phenomena of α-elastin up to the multi-kbar regime. FT-IR spectroscopy, CD, UV/Vis absorption, phase-contrast light and fluorescence microscopy techniques were employed to reveal structural changes and mesoscopic phase states of the system. A novel pressure-induced reentrant LLPS was observed in the intermediate temperature range. A molecular-level picture, in particular on the role of hydrophobic interactions, hydration, and void volume in controlling LLPS phenomena is presented. The potential role of the LLPS phenomena in the development of early cellular compartmentalization is discussed, which might have started in the deep sea, where pressures up to the kbar level are encountered. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Designing a Community-Based Lay Health Advisor Training Curriculum to Address Cancer Health Disparities

PubMed Central

Gwede, Clement K.; Ashley, Atalie A.; McGinnis, Kara; Montiel-Ishino, F. Alejandro; Standifer, Maisha; Baldwin, Julie; Williams, Coni; Sneed, Kevin B.; Wathington, Deanna; Dash-Pitts, Lolita; Green, B. Lee

2012-01-01

Introduction Racial and ethnic minorities have disproportionately higher cancer incidence and mortality than their White counterparts. In response to this inequity in cancer prevention and care, community-based lay health advisors (LHAs) may be suited to deliver effective, culturally relevant, quality cancer education, prevention/screening, and early detection services for underserved populations. Approach and Strategies Consistent with key tenets of community-based participatory research (CBPR), this project engaged community partners to develop and implement a unique LHA training curriculum to address cancer health disparities among medically underserved communities in a tricounty area. Seven phases of curriculum development went into designing a final seven-module LHA curriculum. In keeping with principles of CBPR and community engagement, academic–community partners and LHAs themselves were involved at all phases to ensure the needs of academic and community partners were mutually addressed in development and implementation of the LHA program. Discussion and Conclusions Community-based LHA programs for outreach, education, and promotion of cancer screening and early detection, are ideal for addressing cancer health disparities in access and quality care. When community-based LHAs are appropriately recruited, trained, and located in communities, they provide unique opportunities to link, bridge, and facilitate quality cancer education, services, and research. PMID:22982709

Small scale affinity purification and high sensitivity reversed phase nanoLC-MS N-glycan characterization of mAbs and fusion proteins.

PubMed

Higel, Fabian; Seidl, Andreas; Demelbauer, Uwe; Sörgel, Fritz; Frieß, Wolfgang

2014-01-01

N-glycosylation is a complex post-translational modification with potential effects on the efficacy and safety of therapeutic proteins and known influence on the effector function of biopharmaceutical monoclonal antibodies (mAbs). Comprehensive characterization of N-glycosylation is therefore important in biopharmaceutical development. In early development, e.g. during pool or clone selection, however, only minute protein amounts of multiple samples are available for analytics. High sensitivity and high throughput methods are thus needed. An approach based on 96-well plate sample preparation and nanoLC-MS of 2- anthranilic acid or 2-aminobenzoic acid (AA) labeled N-glycans for the characterization of biopharmaceuticals in early development is reported here. With this approach, 192 samples can be processed simultaneously from complex matrices (e.g., cell culture supernatant) to purified 2-AA glycans, which are then analyzed by reversed phase nanoLC-MS. Attomolar sensitivity has been achieved by use of nanoelectrospray ionization, resulting in detailed glycan maps of mAbs and fusion proteins that are exemplarily shown in this work. Reproducibility, robustness and linearity of the approach are demonstrated, making use in a routine manner during pool or clone selection possible. Other potential fields of application, such as glycan biomarker discovery from serum samples, are also presented.

Small scale affinity purification and high sensitivity reversed phase nanoLC-MS N-glycan characterization of mAbs and fusion proteins

PubMed Central

Higel, Fabian; Seidl, Andreas; Demelbauer, Uwe; Sörgel, Fritz; Frieß, Wolfgang

2014-01-01

N-glycosylation is a complex post-translational modification with potential effects on the efficacy and safety of therapeutic proteins and known influence on the effector function of biopharmaceutical monoclonal antibodies (mAbs). Comprehensive characterization of N-glycosylation is therefore important in biopharmaceutical development. In early development, e.g. during pool or clone selection, however, only minute protein amounts of multiple samples are available for analytics. High sensitivity and high throughput methods are thus needed. An approach based on 96-well plate sample preparation and nanoLC-MS of 2- anthranilic acid or 2-aminobenzoic acid (AA) labeled N-glycans for the characterization of biopharmaceuticals in early development is reported here. With this approach, 192 samples can be processed simultaneously from complex matrices (e.g., cell culture supernatant) to purified 2-AA glycans, which are then analyzed by reversed phase nanoLC-MS. Attomolar sensitivity has been achieved by use of nanoelectrospray ionization, resulting in detailed glycan maps of mAbs and fusion proteins that are exemplarily shown in this work. Reproducibility, robustness and linearity of the approach are demonstrated, making use in a routine manner during pool or clone selection possible. Other potential fields of application, such as glycan biomarker discovery from serum samples, are also presented. PMID:24848368

Changes in insulin-like growth factor-binding protein-3 messenger ribonucleic acid in endothelial cells of the human corpus luteum: a possible role in luteal development and rescue.

PubMed

Fraser, H M; Lunn, S F; Kim, H; Duncan, W C; Rodger, F E; Illingworth, P J; Erickson, G F

2000-04-01

In the human menstrual cycle, extensive angiogenesis accompanies luteinization; and the process is physiologically important for corpus luteum (CL) function. During luteolysis, the vasculature collapses, and the endothelial cells die. In a conceptual cycle, the CL persists both functionally and structurally beyond the luteoplacental shift. Although luteal rescue is not associated with increased angiogenesis, endothelial survival is extended. Despite the central role of the luteal vasculature in fertility, the mechanisms regulating its development and demise are poorly understood. There is increasing evidence that insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) may be important effectors of luteal function. Here, we have found that IGFBP-3 messenger RNA is expressed in the endothelium of the human CL and that the levels of message change during luteal development and rescue by human CG. The signal was strong during the early luteal phase, but it showed significant reduction during the mid- and late luteal phases. Interestingly, administration of human CG caused a marked increase in the levels of IGFBP-3 messenger RNA in luteal endothelial cells that was comparable to that observed during the early luteal phase. We conclude that endothelial cell IGFBP-3 expression is a physiological property of the CL of menstruation and pregnancy. These observations raise the intriguing possibility that the regulated expression of endothelial IGFBP-3 may play a role in controlling angiogenesis and cell responses in the human CL by autocrine/paracrine mechanisms.

Therapist adherence is associated with outcome in cognitive-behavioral therapy for bulimia nervosa.

PubMed

Folke, Sofie; Daniel, Sarah I F; Gondan, Matthias; Lunn, Susanne; Tækker, Louise; Poulsen, Stig

2017-06-01

Studies of therapist adherence in relation to treatment outcome have produced mixed results. The aim of the present study was to investigate change in therapist adherence to cognitive-behavioral therapy (CBT) for bulimia nervosa over time, and to investigate the relationship between adherence and client outcome in early, middle, and late phases of treatment. Thirty-six clients received the focused form of "enhanced" CBT (CBT-E) for bulimia nervosa. Trained observers rated audiotapes of 92 full-length therapy sessions from early (Session 3), middle (Session 11), and late phases (Session 20) of treatment using the Cognitive-Behavioral Therapy Treatment Protocol Adherence Scale. Change in adherence across the 3 treatment phases was examined using multilevel analysis. The relationship between early, middle, and late adherence levels and end-of-treatment binging frequency was examined using multilevel Poisson regression analysis. Adherence decreased significantly over the course of treatment. Higher levels of therapist adherence in early and middle phases of treatment were associated with reduced binging frequency, whereas higher levels of adherence measured late in treatment was not. Results indicate that therapists' adherence to the CBT-E treatment protocol decreases over time and that high levels of protocol adherence in early and middle phases of treatment are more important for positive client outcomes than high levels of adherence in the end of treatment. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Retinopathy of Prematurity: Therapeutic Strategies Based on Pathophysiology.

PubMed

Cayabyab, Rowena; Ramanathan, Rangasamy

2016-01-01

Retinopathy of prematurity (ROP) continues to be a major preventable cause of blindness and visual handicaps globally. With improved perinatal care, improved survival of moderately preterm infants, and limited resources for oxygen delivery and monitoring, more mature preterm infants are developing severe ROP in developing countries. The pathophysiology of ROP is characterized by two phases. Phase I ROP is due to vaso-obliteration beginning immediately after birth secondary to a marked decrease in vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1). Phase II begins around 33 weeks' postmenstrual age (PMA). During this phase, VEGF levels increase, especially if there is retinal hypoxia with increasing retinal metabolism and demand for oxygen leading to abnormal vasoproliferation. Since the original description of ROP in 1942 by Terry et al. [Am J Ophthalmol 1942;25:203-204], four epidemics of ROP have been observed. Prevention or early treatment of ROP involves careful titration of oxygen saturation by pulse oximeter (SpO2). Optimal SpO2 target remains elusive. Most of the large trials have focused on either a low SpO2 (85-89%) or a high SpO2 (91-95%) from the first day of birth to 36 weeks' PMA. Although the incidence of severe ROP and bronchopulmonary dysplasia decreased significantly, predischarge mortality was higher in these studies. Use of graded SpO2 during the 2 different phases of ROP (early, low SpO2 during phase I vs. late, high SpO2 during phase II) may be the best approach to prevent this disabling condition. Further trials should focus on this strategy. Other biological agents that are currently being studied include IGF-1 with IGF-binding protein-3 (rhIGF-1 + rhIGFBP-3) and propranolol. For advanced stages of ROP, laser ablation of avascular retina, early treatment of ROP (ETROP) protocol, intravitreal injection of anti-VEGF antibodies (e.g. bevacizumab) and vitrectomy are used to protect central vision and prevent retinal detachment. Long-term complications such as refractory errors, recurrence of ROP and risk of retinal detachment require continued follow-up with an ophthalmologist through adolescence and beyond. Optimal nutrition including adequate intake of omega-3 polyunsaturated fatty acids and decreasing infection/inflammation to promote normal vascularization are important strategies. Screening guidelines for ROP based on local incidence of ROP in different regions of the world are very important. Oxygen therapy is clearly a modifiable risk factor to decrease ROP that needs further study. Understanding the two phases of ROP will help to identify appropriate therapeutic strategies and improve visual outcomes in many preterm infants globally. © 2016 S. Karger AG, Basel.

Signaling molecules involved in the transition of growth to development of Dictyostelium discoideum.

PubMed

Mir, Hina A; Rajawat, Jyotika; Pradhan, Shalmali; Begum, Rasheedunnisa

2007-03-01

The social amoeba Dictyostelium discoideum, a powerful paradigm provides clear insights into the regulation of growth and development. In addition to possessing complex individual cellular functions like a unicellular eukaryote, D. discoideum cells face the challenge of multicellular development. D. discoideum undergoes a relatively simple differentiation process mainly by cAMP mediated pathway. Despite this relative simplicity, the regulatory signaling pathways are as complex as those seen in metazoan development. However, the introduction of restriction-enzyme-mediated integration (REMI) technique to produce developmental gene knockouts has provided novel insights into the discovery of signaling molecules and their role in D. discoideum development. Cell cycle phase is an important aspect for differentiation of D. discoideum, as cells must reach a specific stage to enter into developmental phase and specific cell cycle regulators are involved in arresting growth phase genes and inducing the developmental genes. In this review, we present an overview of the signaling molecules involved in the regulation of growth to differentiation transition (GDT), molecular mechanism of early developmental events leading to generation of cAMP signal and components of cAMP relay system that operate in this paradigm.

Prediction of Phase Behavior of Spray-Dried Amorphous Solid Dispersions: Assessment of Thermodynamic Models, Standard Screening Methods and a Novel Atomization Screening Device with Regard to Prediction Accuracy

PubMed Central

Chavez, Pierre-François; Meeus, Joke; Robin, Florent; Schubert, Martin Alexander; Somville, Pascal

2018-01-01

The evaluation of drug–polymer miscibility in the early phase of drug development is essential to ensure successful amorphous solid dispersion (ASD) manufacturing. This work investigates the comparison of thermodynamic models, conventional experimental screening methods (solvent casting, quench cooling), and a novel atomization screening device based on their ability to predict drug–polymer miscibility, solid state properties (Tg value and width), and adequate polymer selection during the development of spray-dried amorphous solid dispersions (SDASDs). Binary ASDs of four drugs and seven polymers were produced at 20:80, 40:60, 60:40, and 80:20 (w/w). Samples were systematically analyzed using modulated differential scanning calorimetry (mDSC) and X-ray powder diffraction (XRPD). Principal component analysis (PCA) was used to qualitatively assess the predictability of screening methods with regards to SDASD development. Poor correlation was found between theoretical models and experimentally-obtained results. Additionally, the limited ability of usual screening methods to predict the miscibility of SDASDs did not guarantee the appropriate selection of lead excipient for the manufacturing of robust SDASDs. Contrary to standard approaches, our novel screening device allowed the selection of optimal polymer and drug loading and established insight into the final properties and performance of SDASDs at an early stage, therefore enabling the optimization of the scaled-up late-stage development. PMID:29518936

Challenges Facing Early Phase Trials Sponsored by the National Cancer Institute: An Analysis of Corrective Action Plans to Improve Accrual.

PubMed

Massett, Holly A; Mishkin, Grace; Rubinstein, Larry; Ivy, S Percy; Denicoff, Andrea; Godwin, Elizabeth; DiPiazza, Kate; Bolognese, Jennifer; Zwiebel, James A; Abrams, Jeffrey S

2016-11-15

Accruing patients in a timely manner represents a significant challenge to early phase cancer clinical trials. The NCI Cancer Therapy Evaluation Program analyzed 19 months of corrective action plans (CAP) received for slow-accruing phase I and II trials to identify slow accrual reasons, evaluate whether proposed corrective actions matched these reasons, and assess the CAP impact on trial accrual, duration, and likelihood of meeting primary scientific objectives. Of the 135 CAPs analyzed, 69 were for phase I trials and 66 for phase II trials. Primary reasons cited for slow accrual were safety/toxicity (phase I: 48%), design/protocol concerns (phase I: 42%, phase II: 33%), and eligibility criteria (phase I: 41%, phase II: 35%). The most commonly proposed corrective actions were adding institutions (phase I: 43%, phase II: 85%) and amending the trial to change eligibility or design (phase I: 55%, phase II: 44%). Only 40% of CAPs provided proposed corrective actions that matched the reasons given for slow accrual. Seventy percent of trials were closed to accrual at time of analysis (phase I = 48; phase II = 46). Of these, 67% of phase I and 70% of phase II trials met their primary objectives, but they were active three times longer than projected. Among closed trials, 24% had an accrual rate increase associated with a greater likelihood of meeting their primary scientific objectives. Ultimately, trials receiving CAPs saw improved accrual rates. Future trials may benefit from implementing CAPs early in trial life cycles, but it may be more beneficial to invest in earlier accrual planning. Clin Cancer Res; 22(22); 5408-16. ©2016 AACRSee related commentary by Mileham and Kim, p. 5397. ©2016 American Association for Cancer Research.

[CERN-MEDICIS (Medical Isotopes Collected from ISOLDE): a new facility].

PubMed

Viertl, David; Buchegger, Franz; Prior, John O; Forni, Michel; Morel, Philippe; Ratib, Osman; Bühler Léo H; Stora, Thierry

2015-06-17

CERN-MEDICIS is a facility dedicated to research and development in life science and medical applications. The research platform was inaugurated in October 2014 and will produce an increasing range of innovative isotopes using the proton beam of ISOLDE for fundamental studies in cancer research, for new imaging and therapy protocols in cell and animal models and for preclinical trials, possibly extended to specific early phase clinical studies (phase 0) up to phase I trials. CERN, the University Hospital of Geneva (HUG), the University Hospital of Lausanne (CHUV), the Swiss Institute for Experimental Cancer (ISREC) at Swiss Federal Institutes of Technology (EPFL) that currently support the project will benefit of the initial production that will then be extended to other centers.

Users perspectives on interactive distance technology enabling home-based motor training for stroke patients.

PubMed

Ehn, Maria; Hansson, Pär; Sjölinder, Marie; Boman, Inga-Lill; Folke, Mia; Sommerfeld, Disa; Borg, Jörgen; Palmcrantz, Susanne

2015-01-01

The aim of this work has been to develop a technical support enabling home-based motor training after stroke. The basis for the work plan has been to develop an interactive technical solution supporting three different groups of stroke patients: (1) patients with stroke discharged from hospital with support from neuro team; (2) patients with stroke whose support from neuro team will be phased out and (3) patients living with impaired motor functions long-term. The technology has been developed in close collaboration with end-users using a method earlier evaluated and described [12]. This paper describes the main functions of the developed technology. Further, results from early user-tests with end-users, performed to identify needs for improvements to be carried out during further technical development. The developed technology will be tested further in a pilot study of the safety and, usefulness of the technology when applied as a support for motor training in three different phases of the post-stroke rehabilitation process.

Relative role of pre-monsoon conditions and intraseasonal oscillations in determining early-vs-late indian monsoon intensity in a GCM

NASA Astrophysics Data System (ADS)

Ghosh, Rohit; Chakraborty, Arindam; Nanjundiah, Ravi S.

2018-01-01

The aim of this paper is to identify relative roles of different land-atmospheric conditions, apart from sea surface temperature (SST), in determining early vs. late summer monsoon intensity over India in a high resolution general circulation model (GCM). We find that in its early phase (June-July; JJ), pre-monsoon land-atmospheric processes play major role to modulate the precipitation over Indian region. These effects of pre-monsoon conditions decrease substantially during its later phase (August-September; AS) for which the interannual variation is mainly governed by the low frequency northward propagating intraseasonal oscillations. This intraseasonal variability which is related to mean vertical wind shear has a significant role during the early phase of monsoon as well. Further, using multiple linear regression, we show that interannual variation of early and late monsoon rainfall over India is best explained when all these land-atmospheric parameters are taken together. Our study delineates the relative role of different processes affecting early versus later summer monsoon rainfall over India that can be used for determining its subseasonal predictability.

Toward a clinically useful method of predicting early breast-feeding attrition.

PubMed

Lewallen, Lynne Porter; Dick, Margaret J; Wall, Yolanda; Zickefoose, Kimberly Taylor; Hannah, Susan Hensley; Flowers, Janet; Powell, Wanda

2006-08-01

The overall purpose of this study was to revise and test an instrument to identify, during the early postpartum period, women at risk for early breast-feeding attrition. This study was completed in two phases: the first phase tested a revision of the Breast-Feeding Attrition Prediction Tool (BAPT); the second, a new instrument, the Breast-Feeding Attitude Scale (BrAS), which was adapted from the BAPT. The two phases of this study involved 415 pregnant and postpartum women. Women answered questions either by phone (pregnant women) or in their hospital rooms after delivery (postpartum women). Data were analyzed using t tests and reliability analysis. The BAPT did not predict early breast-feeding attrition; however, the BrAS did differentiate between the attitudes of breast-feeding women and those of formula-feeding women and had adequate reliability. Women at risk for early breast-feeding attrition should be identified early so nursing interventions can be directed toward preventing early unintended weaning. Although the BrAS did not reliably identify women at risk in this sample, it did highlight important differences between breast-feeding and formula-feeding women that can be used in designing preconceptional or prenatal educational assessments and interventions.

UWB Tracking Software Development

NASA Technical Reports Server (NTRS)

Gross, Julia; Arndt, Dickey; Ngo, Phong; Phan, Chau; Dusl, John; Ni, Jianjun; Rafford, Melinda

2006-01-01

An Ultra-Wideband (UWB) two-cluster Angle of Arrival (AOA) tracking prototype system is currently being developed and tested at NASA Johnson Space Center for space exploration applications. This talk discusses the software development efforts for this UWB two-cluster AOA tracking system. The role the software plays in this system is to take waveform data from two UWB radio receivers as an input, feed this input into an AOA tracking algorithm, and generate the target position as an output. The architecture of the software (Input/Output Interface and Algorithm Core) will be introduced in this talk. The development of this software has three phases. In Phase I, the software is mostly Matlab driven and calls C++ socket functions to provide the communication links to the radios. This is beneficial in the early stage when it is necessary to frequently test changes in the algorithm. Phase II of the development is to have the software mostly C++ driven and call a Matlab function for the AOA tracking algorithm. This is beneficial in order to send the tracking results to other systems and also to improve the tracking update rate of the system. The third phase is part of future work and is to have the software completely C++ driven with a graphics user interface. This software design enables the fine resolution tracking of the UWB two-cluster AOA tracking system.

Molecular regulation of sex change induced by methyltestosterone -feeding and methyltestosterone -feeding withdrawal in the protogynous orange-spotted grouper.

PubMed

Wang, Qing; Liu, Yun; Peng, Cheng; Wang, Xiang; Xiao, Ling; Wang, Dengdong; Chen, Jiaxing; Zhang, Haifa; Zhao, Huihong; Li, Shuisheng; Zhang, Yong; Lin, Haoran

2017-08-01

The sex identity of fish can be easily manipulated by exogenous hormones. Treatment with 17-methyltestosterone (MT) has been widely used to induce a male fate, but the molecular and cellular processes underlying sex changes induced by MT treatments and the withdrawal of MT are not well studied. In this study, we systematically investigated gonadal histology, gene expression profiles, sex steroid hormone levels, and cellular changes during sex changes induced by MT-feeding and MT-feeding withdrawal in the protogynous orange-spotted grouper, Epinephelus coioides. Based on gonadal histology, we demonstrated that MT-feeding-induced sex reversal can be divided into early and late phases: in the early phase, male and female germ cells coexist, and MT-feeding withdrawal leads to a female fate; in the late phase, only male germ cells are observed, and MT-feeding withdrawal does not reverse the process, leading to a male fate. In both the early and late phases, cytochrome P450 family19 subfamily A member 1 (cyp19a1a) gene expression increased in response to MT-feeding withdrawal. Finally, by tracing doublesex- and Mab-3-related transcription factor 1 (dmrt1)-expressing cells, we found that gonia-like cells in the germinal epithelium might be the major germ cell sources for developing testes during sex reversal. Collectively, our findings provide insights into the molecular and cellular mechanisms underlying sex changes induced by exogenous hormones. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

SN 2013fs and SN 2013fr: exploring the circumstellar-material diversity in Type II supernovae

NASA Astrophysics Data System (ADS)

Bullivant, Christopher; Smith, Nathan; Williams, G. Grant; Mauerhan, Jon C.; Andrews, Jennifer E.; Fong, Wen-Fai; Bilinski, Christopher; Kilpatrick, Charles D.; Milne, Peter A.; Fox, Ori D.; Cenko, S. Bradley; Filippenko, Alexei V.; Zheng, WeiKang; Kelly, Patrick L.; Clubb, Kelsey I.

2018-05-01

We present photometry and spectroscopy of SN 2013fs and SN 2013fr in the first ˜100 d post-explosion. Both objects showed transient, relatively narrow H α emission lines characteristic of SNe IIn, but later resembled normal SNe II-P or SNe II-L, indicative of fleeting interaction with circumstellar material (CSM). SN 2013fs was discovered within 8 h of explosion; one of the earliest SNe discovered thus far. Its light curve exhibits a plateau, with spectra revealing strong CSM interaction at early times. It is a less luminous version of the transitional SN IIn PTF11iqb, further demonstrating a continuum of CSM interaction intensity between SNe II-P and SNe IIn. It requires dense CSM within 6.5 × 1014 cm of the progenitor, from a phase of advanced pre-SN mass loss beginning shortly before explosion. Spectropolarimetry of SN 2013fs shows little continuum polarization (˜0.5 per cent, consistent with zero), but noticeable line polarization during the plateau phase. SN 2013fr morphed from an SN IIn at early times to an SN II-L. After the first epoch, its narrow lines probably arose from host-galaxy emission, but the bright, narrow H α emission at early times may be intrinsic to the SN. As for SN 2013fs, this would point to a short-lived phase of strong CSM interaction if proven to be intrinsic, suggesting a continuum between SNe IIn and SNe II-L. It is a low-velocity SN II-L like SN 2009kr, but more luminous. SN 2013fr also developed an infrared excess at later times, due to warm CSM dust that requires a more sustained phase of strong pre-SN mass loss.

Risk Evaluation in the Pre-Phase A Conceptual Design of Spacecraft

NASA Technical Reports Server (NTRS)

Fabisinski, Leo L., III; Maples, Charlotte Dauphne

2010-01-01

Typically, the most important decisions in the design of a spacecraft are made in the earliest stages of its conceptual design the Pre-Phase A stages. It is in these stages that the greatest number of design alternatives is considered, and the greatest number of alternatives is rejected. The focus of Pre-Phase A conceptual development is on the evaluation and comparison of whole concepts and the larger-scale systems comprising those concepts. This comparison typically uses general Figures of Merit (FOMs) to quantify the comparative benefits of designs and alternative design features. Along with mass, performance, and cost, risk should be one of the major FOMs in evaluating design decisions during the conceptual design phases. However, risk is often given inadequate consideration in conceptual design practice. The reasons frequently given for this lack of attention to risk include: inadequate mission definition, lack of rigorous design requirements in early concept phases, lack of fidelity in risk assessment methods, and under-evaluation of risk as a viable FOM for design evaluation. In this paper, the role of risk evaluation in early conceptual design is discussed. The various requirements of a viable risk evaluation tool at the Pre-Phase A level are considered in light of the needs of a typical spacecraft design study. A technique for risk identification and evaluation is presented. The application of the risk identification and evaluation approach to the conceptual design process is discussed. Finally, a computational tool for risk profiling is presented and applied to assess the risk for an existing Pre-Phase A proposal. The resulting profile is compared to the risks identified for the proposal by other means.

Anaphase-Promoting Complex/Cyclosome-Cdh1-Mediated Proteolysis of the Forkhead Box M1 Transcription Factor Is Critical for Regulated Entry into S Phase▿

PubMed Central

Park, Hyun Jung; Costa, Robert H.; Lau, Lester F.; Tyner, Angela L.; Raychaudhuri, Pradip

2008-01-01

The forkhead box M1 (FoxM1) transcription factor is overexpressed in many cancers, and in mouse models it is required for tumor progression. FoxM1 activates expression of the cell cycle genes required for both S and M phase progression. Here we demonstrate that FoxM1 is degraded in late mitosis and early G1 phase by the anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase. FoxM1 interacts with the APC/C complex and its adaptor, Cdh1. Expression of Cdh1 stimulated degradation of the FoxM1 protein, and depletion of Cdh1 resulted in stabilization of the FoxM1 protein in late mitosis and in early G1 phase of the cell cycle. Cdh1 has been implicated in regulating S phase entry. We show that codepletion of FoxM1 inhibits early S phase entry observed in Cdh1-depleted cells. The N-terminal region of FoxM1 contains both destruction box (D box) and KEN box sequences that are required for targeting by Cdh1. Mutation of either the D box sequence or the KEN box sequence stabilized FoxM1 and blocked Cdh1-induced proteolysis. Cells expressing a nondegradable form of FoxM1 entered S phase rapidly following release from M phase arrest. Together, our observations show that FoxM1 is one of the targets of Cdh1 in late M or early G1 phase and that its proteolysis is important for regulated entry into S phase. PMID:18573889

Control of follicle-stimulating hormone by estradiol and the inhibins: critical role of estradiol at the hypothalamus during the luteal-follicular transition.

PubMed

Welt, Corrine K; Pagan, Yanira L; Smith, Patricia C; Rado, Kimberly B; Hall, Janet E

2003-04-01

To test the hypothesis that estradiol, inhibin A, and inhibin B contribute differentially to FSH negative feedback in specific phases of the menstrual cycle, daily blood samples were obtained across a control cycle and after selective estrogen blockade with tamoxifen. To examine the site of estradiol-negative feedback in control and tamoxifen treatment cycles, early follicular phase GnRH (free alpha-subunit) pulse frequency was assessed in normal women, and FSH levels were examined in GnRH-deficient women in whom hypothalamic output was fixed with GnRH administration. FSH was higher in the early follicular phase in the presence of estrogen receptor blockade (15.7 +/- 3.1 vs. 13.2 +/- 1.9 IU/liter; P < 0.05) but was not increased in the late follicular phase. In the luteal phase, FSH was elevated (10.1 +/- 0.7 vs. 7.3 +/- 0.6 IU/liter; P < 0.01). In normal women, free alpha-subunit pulse frequency increased (7.3 +/- 0.4 vs. 4.8 +/- 0.4 pulses per 8 h; P < 0.003), but in GnRH-deficient women, there was no FSH increase (11.1 +/- 1.6 vs. 12.5 +/- 3.6 IU/liter) in the early follicular phase in the presence of estrogen blockade. In conclusion, estradiol exerts a greater role over inhibin in FSH-negative feedback regulation during the luteal phase and the luteal-follicular transition. In contrast, inhibin A and/or B plays a more critical role as the follicular phase progresses. In addition, these studies support a primary if not exclusive hypothalamic site of estrogen-negative feedback in the early follicular phase.

Development of a tool to assess adherence to a model of the division of responsibility in feeding young children: using response mapping to capacitate validation measures.

PubMed

Lohse, Barbara; Satter, Ellyn; Arnold, Kristen

2014-04-01

Accurate early assessment and targeted intervention with problematic parent/child feeding dynamics is critical for the prevention and treatment of child obesity. The division of responsibility in feeding (sDOR), articulated by the Satter Feeding Dynamics Model (fdSatter), has been demonstrated clinically as an effective approach to reduce child feeding problems, including those leading to obesity. Lack of a tested instrument to examine adherence to fdSatter stimulated initial construction of the Satter Feeding Dynamics Inventory (fdSI). The aim of this project was to refine the item pool to establish translational validity, making the fdSI suitable for advanced psychometric analysis. Cognitive interviews (n = 80) with caregivers of varied socioeconomic strata informed revisions that demonstrated face and content validity. fdSI responses were mapped to interviews using an iterative, multi-phase thematic approach to provide an instrument ready for construct validation. fdSI development required five interview phases over 32 months: Foundational; Refinement; Transitional; Assurance; and Launching. Each phase was associated with item reduction and revision. Thirteen items were removed from the 38-item Foundational phase and seven were revised in the Refinement phase. Revisions, deletions, and additions prompted by Transitional and Assurance phase interviews resulted in the 15-item Launching phase fdSI. Only one Foundational phase item was carried through all development phases, emphasizing the need to test for item comprehension and interpretation before psychometric analyses. Psychometric studies of item pools without encrypted meanings will facilitate progress toward a tool that accurately detects adherence to sDOR. Ability to measure sDOR will facilitate focus on feeding behaviors associated with reduced risk of childhood obesity.

Development of an occupational advice intervention for patients undergoing lower limb arthroplasty (the OPAL study).

PubMed

Baker, Paul; Coole, Carol; Drummond, Avril; McDaid, Catriona; Khan, Sayeed; Thomson, Louise; Hewitt, Catherine; McNamara, Iain; McDonald, David; Fitch, Judith; Rangan, Amar

2018-06-28

There are an increasing number of patients of working age undergoing hip and knee replacements. Currently there is variation in the advice and support given about sickness absence, recovery to usual activities and return to work after these procedures. Earlier, sustainable, return to work improves the health of patients and benefits their employers and society. An intervention that encourages and supports early recovery to usual activities, including work, has the potential to reduce the health and socioeconomic burden of hip and knee replacements. A two-phase research programme delivered over 27 months will be used to develop and subsequently test the feasibility of an occupational advice intervention to facilitate return to work and usual activities in patients undergoing lower limb arthroplasty. The 2 phases will incorporate a six-stage intervention mapping process: Phase 1: Intervention mapping stages 1-3: 1 Needs assessment (including rapid evidence synthesis, prospective cohort analysis and structured stakeholder interviews) 2 Identification of intended outcomes and performance objectives 3 Selection of theory-based methods and practical strategies Phase 2: Intervention mapping stages 4-6: 4 Development of components and materials for the occupational advice intervention using a modified Delphi process 5 Adoption and implementation of the intervention 6 Evaluation and feasibility testing The study will be undertaken in four National Health Service (NHS) hospitals in the United Kingdom and two Higher Education Institutions. OPAL (Occupational advice for Patients undergoing Arthroplasty of the Lower limb) aims to develop an occupational advice intervention to support early recovery to usual activities including work, which is tailored to the requirements of patients undergoing hip and knee replacements. The developed intervention will then be assessed with a specific focus on evaluating its feasibility as a potential trial intervention to improve speed of recovery to usual activities including work. The study was registered retrospectively with the International Standard Randomised Controlled Trials Number (ISRCTN): 27426982 (Date 20/12/2016) and the International prospective register of systematic reviews (PROSPERO): CRD42016045235 (Date 04/08/2016).

Interviewing strategically to elicit admissions from guilty suspects.

PubMed

Tekin, Serra; Granhag, Pär Anders; Strömwall, Leif; Giolla, Erik Mac; Vrij, Aldert; Hartwig, Maria

2015-06-01

In this article we introduce a novel interviewing tactic to elicit admissions from guilty suspects. By influencing the suspects' perception of the amount of evidence the interviewer holds against them, we aimed to shift the suspects' counterinterrogation strategies from less to more forthcoming. The proposed tactic (SUE-Confrontation) is a development of the Strategic Use of Evidence (SUE) framework and aims to affect the suspects' perception by confronting them with statement-evidence inconsistencies. Participants (N = 90) were asked to perform several mock criminal tasks before being interviewed using 1 of 3 interview techniques: (a) SUE-Confrontation, (b) Early Disclosure of Evidence, or (c) No Disclosure of Evidence. As predicted, the SUE-Confrontation interview generated more statement-evidence inconsistencies from suspects than the Early Disclosure interview. Importantly, suspects in the SUE-Confrontation condition (vs. Early and No disclosure conditions) admitted more self-incriminating information and also perceived the interviewer to have had more information about the critical phase of the crime (the phase where the interviewer lacked evidence). The findings show the adaptability of the SUE-technique and how it may be used as a tool for eliciting admissions. (c) 2015 APA, all rights reserved).

The bradykinin B2 receptor in the early immune response against Listeria infection.

PubMed

Kaman, Wendy E; Wolterink, Arthur F W M; Bader, Michael; Boele, Linda C L; van der Kleij, Desiree

2009-02-01

The endogenous danger signal bradykinin was recently found implicated in the development of immunity against parasites via dendritic cells. We here report an essential role of the B(2) (B(2)R) bradykinin receptor in the early immune response against Listeria infection. Mice deficient in B(2)R (B(2)R(-/-) mice) were shown to suffer from increased hepatic bacterial burden and concomitant dramatic weight loss during infection with Listeria monocytogenes. Levels of cytokines known to play a pivotal role in the early phase immune response against L. monocytogenes, IL-12p70 and IFN-gamma, were reduced in B(2)R(-/-) mice. To extend these findings to the human system, we show that bradykinin potentiates the production of IL-12p70 in human monocyte-derived dendritic cells. Thus, we show that bradykinin and the B(2)R play a role in early innate immune functions during bacterial infection.

Development of the Fish Medaka in Microgravity

NASA Technical Reports Server (NTRS)

Wolgemuth, Debra J.

1995-01-01

The goal of these experiments was to determine the effect of microgravity on the early development of the fish medaka. There were two objectives for this flight series. The primary objective was to assess the effects of microgravity on different stages of development and to ascertain whether the relevant developmental questions can be addressed at the gross morphological level or if the issues involve more subtle questions about regulation at the molecular and cellular levels. The secondary objective was the assessment of the utility of flight hardware with the capabilities to perform embryological studies. We have been able to take advantage of the flight testing phase of the STL-B hardware to also study the effects of microgravity on the early development of the fish, Medaka. Our initial studies involved monitoring the early Medaka development and raising flight embryos for breeding. Images of the developing embryos were collected either via video which was either taken by the astronauts or broadcast to Earth. Sample video images were digitized and stored on a hard drive resident within the on-board STL-B unit. Embryos were fixed at specific intervals, returned to Earth and are being analyzed for the timing and location of molecular events associated with controlling the morphological pattern for the onset of adult structures.

Conceptual framework of the eco-physiological phases of insect diapause development justified by transcriptomic profiling

PubMed Central

Štětina, Tomáš; Poupardin, Rodolphe; Korbelová, Jaroslava; Bruce, Alexander William

2017-01-01

Insects often overcome unfavorable seasons in a hormonally regulated state of diapause during which their activity ceases, development is arrested, metabolic rate is suppressed, and tolerance of environmental stress is bolstered. Diapausing insects pass through a stereotypic succession of eco-physiological phases termed “diapause development.” The phasing is varied in the literature, and the whole concept is sometimes criticized as being too artificial. Here we present the results of transcriptional profiling using custom microarrays representing 1,042 genes in the drosophilid fly, Chymomyza costata. Fully grown, third-instar larvae programmed for diapause by a photoperiodic (short-day) signal were assayed as they traversed the diapause developmental program. When analyzing the gradual dynamics in the transcriptomic profile, we could readily distinguish distinct diapause developmental phases associated with induction/initiation, maintenance, cold acclimation, and termination by cold or by photoperiodic signal. Accordingly, each phase is characterized by a specific pattern of gene expression, supporting the physiological relevance of the concept of diapause phasing. Further, we have dissected in greater detail the changes in transcript levels of elements of several signaling pathways considered critical for diapause regulation. The phase of diapause termination is associated with enhanced transcript levels in several positive elements stimulating direct development (the 20-hydroxyecdysone pathway: Ecr, Shd, Broad; the Wnt pathway: basket, c-jun) that are countered by up-regulation in some negative elements (the insulin-signaling pathway: Ilp8, PI3k, Akt; the target of rapamycin pathway: Tsc2 and 4EBP; the Wnt pathway: shaggy). We speculate such up-regulations may represent the early steps linked to termination of diapause programming. PMID:28720705

Development and marketing of a prosthetic urinary control valve system

NASA Technical Reports Server (NTRS)

Tenney, J. B., Jr.; Rabinowitz, R.; Rogers, D. W.; Harrison, H. N.

1983-01-01

An implantable prosthetic for the control of urinary incontinence was developed and marketed. Three phases are presented: bench development studies, animal trials, and human clinical trials. This work was performed under the direction of a Research Team at Rochester General Hospital (RGH). Bench trials were completed on prototype hardware and provided early verification of the device's ability to withstand repeated cyclic testing. Configurational variants were evaluated and a preferred design concept was established. Silicone rubber (medical grade) was selected as the preferred material for the prosthesis.

[Semiquantitative measurement of progesterone receptors in luteal-phase-defect endometrial cells during secretory phase].

PubMed

Ma, Q; Han, Z; Huang, W

1998-03-01

To investigate the changes of endometrial progesterone receptor (PR) of luteal-phase-defect (LPD) patients during the secretory phase, thirteen patients with complaints of infertility or habitual abortion were studied. During the early-mid secretory phase, endometrial tissue was obtained by dilatation and curettage (D & C) for histological and receptor study: meanwhile serum E2, P, FSH, LH and PRL were measured. Based on histologic diagnosis, the patients were divided into two groups: the LPD group (n = 7) and the normal control group(n = 6). PR content was determined by immunohisto-chemical (IHC) assay. The results showed that during the early-mid luteal phase a significantly low PR content on endometrial glandular nucleus was observed in LPD group, compared with normal control(6.75 +/- 2.57 vs 9.50 +/- 1.64 P < 0.05), but no difference in serum progesterone was noted between the two groups. These findings suggest that during early-mid secretory phase, PR content on endometrial glandular nucleus decreases in LPD cases, which results in deficient response of endometrium to proper stimulus of progesterone. This change may cause endometrial secretory deficiency and blockade of embreyo implantation. That is why infertility or habitual abortion happened.

"Intermetamorphic" developmental stages in 150 million-year-old achelatan lobsters--The case of the species tenera Oppel, 1862.

PubMed

Haug, Joachim T; Haug, Carolin

2016-03-01

We re-investigated the fossil species tenera Oppel, 1862, an achelatan lobster (traditionally named Palinurina tenera) found in 150 million years old limestones of southern Germany. All known specimens attributed to this species show a mixture of characters, which in modern forms occur either in larvae or post-larval juveniles. Hence these specimens provide insight into a phase in ontogeny that is no longer present in the developmental sequence of any modern achelatan lobster, as the latter ones skip this phase and replace it by a drastic metamorphosis. Comparable cases have been described earlier, yet did only comprise single stages or two successive ones at most. In the here described case four developmental stages are preserved. The reconstructed ontogeny of tenera therefore represents the currently best known sequence of an early achelatan lobster that covers this specific intermediate phase. The largest known stage most likely still represents an immature of a yet undiscovered adult. These findings support the interpretation that early achelatan lobsters developed in a more gradual ontogenetic sequence than modern forms. It furthermore demonstrates that it was even more gradual than anticipated previously. Copyright © 2015 Elsevier Ltd. All rights reserved.

Late Jurassic-Early Cretaceous episodic development of the Bangong Meso-Tethyan subduction: Evidence from elemental and Sr-Nd isotopic geochemistry of arc magmatic rocks, Gaize region, central Tibet, China

NASA Astrophysics Data System (ADS)

Zhang, Yu-Xiu; Li, Zhi-Wu; Yang, Wen-Guang; Zhu, Li-Dong; Jin, Xin; Zhou, Xiao-Yao; Tao, Gang; Zhang, Kai-Jun

2017-03-01

The Bangong Meso-Tethys plays a critical role in the development of the Tethyan realm and the initial elevation of the Tibetan Plateau. However, its precise subduction polarity, and history still remain unclear. In this study, we synthesize a report for the Late Jurassic-Early Cretaceous two-phase magmatic rocks in the Gaize region at the southern margin of the Qiangtang block located in central Tibet. These rocks formed during the Late Jurassic-earliest Cretaceous (161-142 Ma) and Early Cretaceous (128-106 Ma), peaking at 146 Ma and 118 Ma, respectively. The presence of inherited zircons indicates that an Archean component exists in sediments in the shallow Qiangtang crust, and has a complex tectonomagmatic history. Geochemical and Sr-Nd isotopic data show that the two-phase magmatic rocks exhibit characteristics of arc magmatism, which are rich in large-ion incompatible elements (LIIEs), but are strongly depleted in high field strength elements (HFSEs). The Late Jurassic-earliest Cretaceous magmatic rocks mixed and mingled among mantle-derived mafic magmas, subduction-related sediments, or crustally-derived felsic melts and fluids, formed by a northward and steep subduction of the Bangong Meso-Tethys ocean crust. The magmatic gap at 142-128 Ma marks a flat subduction of the Meso-Tethys. The Early Cretaceous magmatism experienced a magma MASH (melting, assimilation, storage, and homogenization) process among mantle-derived mafic magmas, or crustally-derived felsic melts and fluids, as a result of the Meso-Tethys oceanic slab roll-back, which triggered simultaneous back-arc rifting along the southern Qiangtang block margin.

Long-lasting effects of dexamethasone on immune cells and wound healing in the zebrafish.

PubMed

Sharif, Faiza; Steenbergen, Peter J; Metz, Juriaan R; Champagne, Danielle L

2015-01-01

This study assessed the lasting impact of dexamethasone (DEX) exposure during early development on tissue repair capacity at later life stages (5, 14, and 24 days post fertilization [dpf]) in zebrafish larvae. Using the caudal fin amputation model, we show that prior exposure to DEX significantly delays but does not prevent wound healing at all life stages studied. DEX-induced impairments on wound healing were fully restored to normal levels with longer post amputation recovery time. Further analyses revealed that DEX mainly exerted its detrimental effects in the early phase (0-5 hours) of wound-healing process. Specifically, we observed the following events: (1) massive amount of cell death both by necrosis and apoptosis; (2) significant reduction in the number as well as misplacement of macrophages at the wound site; (3) aberrant migration and misplacement of neutrophils and macrophages at the wound site. These events were accompanied by significant (likely compensatory) changes in the expression of genes involved in tissue patterning, including up-regulation of FKBP5 6 hours post DEX exposure and that of Wnt3a and RARγ at 24 hours post amputation. Taken together, this study provides evidence that DEX exposure during early sensitive periods of development appears to cause permanent alterations in the cellular/molecular immune processes that are involved in the early phase of wound healing in zebrafish. These findings are consistent with previous studies showing that antenatal course of DEX is associated with immediate and lasting alterations of the immune system in rodent models and humans. Therefore, the current findings support the use of the larval zebrafish model to study the impact of stress and stress hormone exposure in immature organisms on health risks in later life. © 2015 by the Wound Healing Society.

Development of a highly sensitive bioluminescent enzyme immunoassay for hepatitis B virus surface antigen capable of detecting divergent mutants.

PubMed

Minekawa, Takayuki; Takehara, Shizuka; Takahashi, Masaharu; Okamoto, Hiroaki

2013-08-01

Hepatitis B virus (HBV) infections are sometimes overlooked when using commercial kits to measure hepatitis B virus surface antigen (HBsAg) due to their low sensitivities and reactivities to mutant strains of various genotypes. We developed an ultrasensitive bioluminescent enzyme immunoassay (BLEIA) for HBsAg using firefly luciferase, which is adaptable to a variety of HBsAg mutants, by combining four monoclonal antibodies with a polyclonal antibody against HBsAg. The measurement of seroconversion panels showed trace amounts of HBsAg during the early infection phase by the BLEIA because of its high sensitivity of 5 mIU/ml. The BLEIA detected HBsAg as early as did PCR in five of seven series and from 2.1 to 9.4 days earlier than commercial immunoassay methods. During the late infection phase, the BLEIA successfully detected HBsAg even 40 days after the disappearance of HBV DNA and the emergence of antibodies against HBsAg. The HBsAg BLEIA successfully detected all 13 recombinant HBsAg and 45 types of HBsAg mutants with various mutations within amino acids 90 to 164 in the S gene product. Some specimens had higher values determined by the BLEIA than those by a commercial chemiluminescent immunoassay; this suggests that such discrepancies were caused by the dissociation of preS1/preS2 peptides from the particle surface. With its highly sensitive detection of low-titer HBsAg, including various mutants, the HBsAg BLEIA is considered to be useful for the early diagnosis and prevention of HBV infection because of the shorter window of infection prior to detection, which facilitates early prediction of recurrence in HBV-infected individuals.

The stereotypical molecular cascade in neovascular age-related macular degeneration: the role of dynamic reciprocity.

PubMed

Kent, D

2015-11-01

This review summarises our current understanding of the molecular basis of subretinal neovascularisation (SRNV) in age-related macular degeneration (AMD). The term neovascular AMD (NVAMD) is derived from the dominant early clinical features of haemorrhage, fluid, and lipid in the subretinal space (SRS) and the historical role of fluorescein angiography in detecting the presence of NV tissue. However, at the cellular level, SRNV resembles an aberrant but stereotypical tissue repair response that incorporates both an early inflammatory phase and a late fibrotic phase in addition to the neovascular (NV) component that dominates the early clinical presentation. This review will seek not only to highlight the important molecules involved in each of these components but to demonstrate that the development of SRNV has its origins in the earliest events in non-NV AMD pathogenesis. Current evidence suggests that this early-stage pathogenesis is characterised by complement-mediated immune dysregulation, leading to a state of chronic inflammation in the retinal pigment epithelium/Bruch's membrane/choriocapillaris complex. These initial events can be seamlessly and inextricably linked to late-stage development of SRNV in AMD by the process of dynamic reciprocity (DyR), the ongoing bidirectional communication between cells, and their surrounding matrix. Moreover, this correlation between disease onset and eventual outcome is reflected in the temporal and spatial correlation between chronic inflammation, NV, and fibrosis within the reparative microenvironment of the SRS. In summary, the downstream consequences of the earliest dysfunctional molecular events in AMD can result in the late-stage entity we recognize clinically as SRNV and is characterized by a spectrum of predictable, related, and stereotypical processes referred to as DyR.

Nonstandard Work Schedules and Developmentally Generative Parenting Practices: An Application of Propensity Score Techniques

ERIC Educational Resources Information Center

Grzywacz, Joseph G.; Daniel, Stephanie S.; Tucker, Jenna; Walls, Jill; Leerkes, Esther

2011-01-01

Data from the National Institute for Child Health and Human Development Study of Early Child Care (Phase I) and propensity score techniques were used to determine whether working full time in a nonstandard schedule job during the child's first year predicted parenting practices over 3 years. Results indicated that women who worked full time in a…

Self-Concept and Depression among Children Who Experienced the Death of a Family Member

ERIC Educational Resources Information Center

Nguyen, Hong T.; Scott, Amy N.

2013-01-01

The present study investigates the moderating effects of physical and academic self-concept on depression among children who experienced the death of a family member. Data from Phase III of the National Institute of Child Health and Human Development Study of Early Child Care was used in the present study. Having a higher physical self-concept…

The Design and Implementation of a Physical Education Program to Promote Children's Creativity in the Early Years

ERIC Educational Resources Information Center

Zachopoulou, Evridiki; Trevlas, Efthimios; Konstadinidou, Elisavet

2006-01-01

The purpose of this study was to design and implement a physical education program to promote creativity in preschool children. The study was based on the following phases: (a) to design and formulate 20 physical education lessons in order to provide children with opportunities to develop their creative thinking through the use of movement…

Directing the Teaching and Learning Research Programme: Or "Trying to Fly a Glider Made of Jelly"

ERIC Educational Resources Information Center

Pollard, Andrew

2010-01-01

TLRP's generic phase (1999-2009) is believed to have been the largest ever UK investment in educational research. This paper describes the critique from which TLRP emerged, its strategic positioning and the roles of successive directors and their teams in its development. The paper offers an early stock take of TLRP's achievements from the…

New and emerging technologies for the treatment of inherited retinal diseases: a horizon scanning review.

PubMed

Smith, J; Ward, D; Michaelides, M; Moore, A T; Simpson, S

2015-09-01

The horizon scanning review aimed to identify new and emerging technologies in development that have the potential to slow or stop disease progression and/or reverse sight loss in people with inherited retinal diseases (IRDs). Potential treatments were identified using recognized horizon scanning methods. These included a combination of online searches using predetermined search terms, suggestions from clinical experts and patient and carer focus groups, and contact with commercial developers. Twenty-nine relevant technologies were identified. These included 9 gene therapeutic approaches, 10 medical devices, 5 pharmacological agents, and 5 regenerative and cell therapies. A further 11 technologies were identified in very early phases of development (typically phase I or pre-clinical) and were included in the final report to give a complete picture of developments 'on the horizon'. Clinical experts and patient and carer focus groups provided helpful information and insights, such as the availability of specialised services for patients, the potential impacts of individual technologies on people with IRDs and their families, and helped to identify additional relevant technologies. This engagement ensured that important areas of innovation were not missed. Most of the health technologies identified are still at an early stage of development and it is difficult to estimate when treatments might be available. Further, well designed trials that generate data on efficacy, applicability, acceptability, and costs of the technologies, as well as the long-term impacts for various conditions are required before these can be considered for adoption into routine clinical practice.

Impact of IgG Fc-Oligosaccharides on Recombinant Monoclonal Antibody Structure, Stability, Safety, and Efficacy.

PubMed

Liu, Hongcheng; Nowak, Christine; Andrien, Bruce; Shao, Mei; Ponniah, Gomathinayagam; Neill, Alyssa

2017-09-01

Glycosylation of the conserved asparagine residue in the CH2 domain is the most common posttranslational modification of recombinant monoclonal antibodies. Ideally, a consistent oligosaccharide profile should be maintained from early clinical material to commercial material for the development of recombinant monoclonal therapeutics, though variation in the profile is a typical result of process changes. The risk of oligosaccharide variation posed to further development is required to be thoroughly evaluated based on its impact on antibody structure, stability, efficacy and safety. The variation should be controlled within a range so that there is no detrimental impact on safety and efficacy and thus allowing the use of early phase safety and efficacy data to support project advancement to later phase. This review article focuses on the current scientific understanding of the commonly observed oligosaccharides found in recombinant monoclonal antibodies and their impact on structure, stability and biological functions, which are the basis to evaluate safety and efficacy. It also provides a brief discussion on critical quality attribute (CQA) assessment with regard to oligosaccharides based on the mechanism of action (MOA). © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1173-1181, 2017. © 2017 American Institute of Chemical Engineers.

Liver Full Reference Set Application: David Lubman - Univ of Michigan (2011) — EDRN Public Portal

Cancer.gov

In this work we will perform the next step in the biomarker development and validation. This step will be the Phase 2 validation of glycoproteins that have passed Phase 1 blinded validation using ELISA kits based on target glycoproteins selected based on our previous work. This will be done in a large Phase 2 sample set obtained in a multicenter study funded by the EDRN. The assays will be performed in our research lab located in the Center for Cancer Proteomics in the University of Michigan Medical Center. This study will include patients in whom serum was stored for future validation and includes samples from early HCC (n = 158), advanced cases (n=214) and cirrhotic controls (n = 417). These samples will be supplied by the EDRN (per Dr. Jo Ann Rinaudo) and will be analyzed in a blinded fashion by Dr. Feng from the Fred Hutchinson Cancer Center. This phase 2 study was designed to have above 90% power at one-sided 5% type-I error for comparing the joint sensitivity and specificity for differentiating early stage HCC from cirrhotic patients between AFP and a new marker. Sample sizes of 200 for early stage HCC and 400 for cirrhotics were required to achieve the stated power (14). We will select our candidates for this larger phase validation set based on the results of previous work. These will include HGF and CD14 and the results of these assays will be used to evaluate the performance of each of these markers and combinations of HGF and CD14 and AFP and HGF. It is expected that each assay will be repeated three times for each marker and will also be performed for AFP as the standard for comparison. 250 uL of each sample is requested for analysis.

Quantitative phase imaging of platelets in patients with chronic renal failure treated with hemodialysis

NASA Astrophysics Data System (ADS)

Vasilenko, Irina; Vlasova, Elizaveta; Metelin, Vladislav; Kardasheva, Ziver

2018-02-01

The development of robust non-invasive laboratory screening methods for early diagnosis on the out-patient basis seems quite relevant for practical medicine. It is known, that platelet is an original biosensor, a detector of early changes in hemostasis condition. The aim of this study was to assess a potential of the quantitative phase imaging (QPI) technique for real time evaluation the influence of low-molecular weight and unfractionated heparin on platelets in patients with the end-stage of chronic renal failure, who were treated with program hemodialysis (PHD). The main group consisted of 21 patients who were administered a low-molecular weight heparin for hypocoagulation during the procedure of hemodialysis. The control group (15 patients) received unfractionated heparin. Morphodensitometric state of living platelets we evaluated by QPI using computer phase-interference microscope MIM (Moscow, Russia). We analyzed the optical-geometrical parameters and the morphological features of living platelets which reflected the degree of their activation at the beginning of PHD (before administration of heparin), in 15 minutes after it and at the end of the procedure. The results allow us to conclude that the use of low-molecular weight heparin provides better ratio of efficacy/safety and causes a reduction of the platelet activation during the hemodialysis procedure. Practical implementation of QPI for clinical monitoring of platelets makes it possible to obtain important information on hemostasis cell. It opens new opportunities to assess the efficacy of treatment, as well as for early diagnosis of complications for disease.

Lipase member H is a novel secreted protein selectively upregulated in human lung adenocarcinomas and bronchioloalveolar carcinomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seki, Yasuhiro; Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology; Yoshida, Yukihiro

2014-01-24

Highlights: • Most of the adenocarcinomas and bronchioloalveolar carcinomas were LIPH-positive. • LIPH is necessary for the proliferation of lung cancer cells in vitro. • A high level of LIPH in serum is correlated with better survival in early phase lung-cancer patients after surgery. - Abstract: Lung cancer is one of the most frequent causes of cancer-related death worldwide. However, molecular markers for lung cancer have not been well established. To identify novel genes related to lung cancer development, we surveyed publicly available DNA microarray data on lung cancer tissues. We identified lipase member H (LIPH, also known as mPA-PLA1)more » as one of the significantly upregulated genes in lung adenocarcinoma. LIPH was expressed in several adenocarcinoma cell lines when they were analyzed by quantitative real-time polymerase chain reaction (qPCR), western blotting, and sandwich enzyme-linked immunosorbent assay (ELISA). Immunohistochemical analysis detected LIPH expression in most of the adenocarcinomas and bronchioloalveolar carcinomas tissue sections obtained from lung cancer patients. LIPH expression was also observed less frequently in the squamous lung cancer tissue samples. Furthermore, LIPH protein was upregulated in the serum of early- and late-phase lung cancer patients when they were analyzed by ELISA. Interestingly, high serum level of LIPH was correlated with better survival in early phase lung cancer patients after surgery. Thus, LIPH may be a novel molecular biomarker for lung cancer, especially for adenocarcinoma and bronchioloalveolar carcinoma.« less

Volunteering for early phase gene transfer research in Parkinson disease.

PubMed

Kim, S Y H; Holloway, R G; Frank, S; Beck, C A; Zimmerman, C; Wilson, R; Kieburtz, K

2006-04-11

For early phase trials of novel interventions-such as gene transfer for Parkinson disease (PD)--whose focus is primarily on safety and tolerability, it is important that participants have a realistic understanding of the goals of such research. Recently, some have expressed concern that patients with PD may have unrealistic expectations. The authors examined why patients with PD might volunteer for invasive early phase research by interviewing 92 patients with PD and comparing those who would (n = 46) and those who would not (n = 46) participate in a hypothetical phase I gene-transfer study. The two groups' demographic, clinical, functional, and quality of life measures, as well as their understanding of the research protocol, were similar. The groups did not differ on their perception of potential for personal benefit nor on the level of likelihood of benefit they saw as a precondition for volunteering. However, those willing to participate tended to perceive lower probability of risk, were tolerant of greater probability of risk, and were more optimistic about the phase I study's potential benefits to society. They also appeared more decisive and action-oriented than the unwilling group. It is likely that the decision whether to participate in early phase PD gene transfer studies will depend mostly on patients' attitudes regarding risk, optimism about science, and an action orientation, rather than on their clinical, functional, or demographic characteristics.

Capturing security requirements for software systems.

PubMed

El-Hadary, Hassan; El-Kassas, Sherif

2014-07-01

Security is often an afterthought during software development. Realizing security early, especially in the requirement phase, is important so that security problems can be tackled early enough before going further in the process and avoid rework. A more effective approach for security requirement engineering is needed to provide a more systematic way for eliciting adequate security requirements. This paper proposes a methodology for security requirement elicitation based on problem frames. The methodology aims at early integration of security with software development. The main goal of the methodology is to assist developers elicit adequate security requirements in a more systematic way during the requirement engineering process. A security catalog, based on the problem frames, is constructed in order to help identifying security requirements with the aid of previous security knowledge. Abuse frames are used to model threats while security problem frames are used to model security requirements. We have made use of evaluation criteria to evaluate the resulting security requirements concentrating on conflicts identification among requirements. We have shown that more complete security requirements can be elicited by such methodology in addition to the assistance offered to developers to elicit security requirements in a more systematic way.

Capturing security requirements for software systems

PubMed Central

El-Hadary, Hassan; El-Kassas, Sherif

2014-01-01

Security is often an afterthought during software development. Realizing security early, especially in the requirement phase, is important so that security problems can be tackled early enough before going further in the process and avoid rework. A more effective approach for security requirement engineering is needed to provide a more systematic way for eliciting adequate security requirements. This paper proposes a methodology for security requirement elicitation based on problem frames. The methodology aims at early integration of security with software development. The main goal of the methodology is to assist developers elicit adequate security requirements in a more systematic way during the requirement engineering process. A security catalog, based on the problem frames, is constructed in order to help identifying security requirements with the aid of previous security knowledge. Abuse frames are used to model threats while security problem frames are used to model security requirements. We have made use of evaluation criteria to evaluate the resulting security requirements concentrating on conflicts identification among requirements. We have shown that more complete security requirements can be elicited by such methodology in addition to the assistance offered to developers to elicit security requirements in a more systematic way. PMID:25685514

Early Numeracy Assessment: The Development of the Preschool Numeracy Scales

PubMed Central

Purpura, David J.; Lonigan, Christopher J.

2015-01-01

Research Findings The focus of this study was to construct and validate twelve 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 precursors to later mathematics skill by the Common Core State Standards (CCSS; 2010). Participants were 393 preschool children ages 3 to 5 years old. Measure development and validation occurred through three analytic phases designed to ensure that the measures were brief, reliable, and valid. These measures included: one-to-one counting, cardinality, counting subsets, subitizing, number comparison, set comparison, number order, numeral identification, set-to-numerals, story problems, number combinations, and verbal counting. Practice or Policy Teachers have extensive demands on their time, yet, they are tasked with ensuring that all students’ academic needs are met. To identify individual instructional needs and measure progress, they need to be able to efficiently assess children’s numeracy skills. The measures developed in this study are not only reliable and valid, but also easy to use and can be utilized for measuring the effects of targeted instruction on individual numeracy skills. PMID:25709375

Early detection of sporadic pancreatic cancer: strategic map for innovation--a white paper.

PubMed

Kenner, Barbara J; Chari, Suresh T; Cleeter, Deborah F; Go, Vay Liang W

2015-07-01

Innovation leading to significant advances in research and subsequent translation to clinical practice is urgently necessary in early detection of sporadic pancreatic cancer. Addressing this need, the Early Detection of Sporadic Pancreatic Cancer Summit Conference was conducted by Kenner Family Research Fund in conjunction with the 2014 American Pancreatic Association and Japan Pancreas Society Meeting. International interdisciplinary scientific representatives engaged in strategic facilitated conversations based on distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. Ideas generated from the summit have led to the development of a Strategic Map for Innovation built upon 3 components: formation of an international collaborative effort, design of an actionable strategic plan, and implementation of operational standards, research priorities, and first-phase initiatives. Through invested and committed efforts of leading researchers and institutions, philanthropic partners, government agencies, and supportive business entities, this endeavor will change the future of the field and consequently the survival rate of those diagnosed with pancreatic cancer.

Early Detection of Sporadic Pancreatic Cancer

PubMed Central

Kenner, Barbara J.; Chari, Suresh T.; Cleeter, Deborah F.; Go, Vay Liang W.

2015-01-01

Abstract Innovation leading to significant advances in research and subsequent translation to clinical practice is urgently necessary in early detection of sporadic pancreatic cancer. Addressing this need, the Early Detection of Sporadic Pancreatic Cancer Summit Conference was conducted by Kenner Family Research Fund in conjunction with the 2014 American Pancreatic Association and Japan Pancreas Society Meeting. International interdisciplinary scientific representatives engaged in strategic facilitated conversations based on distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. Ideas generated from the summit have led to the development of a Strategic Map for Innovation built upon 3 components: formation of an international collaborative effort, design of an actionable strategic plan, and implementation of operational standards, research priorities, and first-phase initiatives. Through invested and committed efforts of leading researchers and institutions, philanthropic partners, government agencies, and supportive business entities, this endeavor will change the future of the field and consequently the survival rate of those diagnosed with pancreatic cancer. PMID:25938853

Spatiotemporal dynamics of OCT4 protein localization during preimplantation development in mice.

PubMed

Fukuda, Atsushi; Mitani, Atsushi; Miyashita, Toshiyuki; Kobayashi, Hisato; Umezawa, Akihiro; Akutsu, Hidenori

2016-11-01

Spatiotemporal expression of transcription factors is crucial for genomic reprogramming. Pou5f1 (Oct4) is an essential transcription factor for reprogramming. A recent study reported that OCT4A, which is crucial for establishment and maintenance of pluripotent cells, is expressed in oocytes, but maternal OCT4A is dispensable for totipotency induction. Whereas another study reported that OCT4B, which is not related to pluripotency, is predominantly expressed instead of OCT4A during early preimplantation phases in mice. To determine the expression states of OCT4 in murine preimplantation embryos, we conducted in-depth expression and functional analyses. We found that pluripotency-related OCT4 mainly localizes to the cytoplasm in early preimplantation phases, with no major nuclear localization until the 8-16-cell stage despite high expression in both oocytes and early embryos. RNA-sequencing analysis using oocytes and early preimplantation embryos could not identify the splice variants creating alternative forms of OCT4 protein. Forced expression of OCT4 in zygotes by the injection of polyadenylated mRNA clearly showed nuclear localization of OCT4 protein around 3-5-fold greater than physiological levels and impaired developmental competency in a dose-dependent manner. Embryos with modest overexpression of OCT4 could develop to the 16-cell stage; however, more than 50% of the embryos were arrested at this stage, similar to the results for OCT4 depletion. In contrast, extensive overexpression of OCT4 resulted in complete arrest at the 2-cell stage accompanied by downregulation of zygotically activated genes and repetitive elements related to the totipotent state. These results demonstrated that OCT4 protein localization was spatiotemporally altered during preimplantation development, and strict control of Oct4 protein levels was essential for proper totipotential reprogramming. © 2016 Society for Reproduction and Fertility.

Context and explicit threat cue modulation of the startle reflex: Preliminary evidence of distinctions between adolescents with principal fear disorders versus distress disorders

PubMed Central

Waters, Allison M.; Nazarian, Maria; Mineka, Susan; Zinbarg, Richard E.; Griffith, James W.; Naliboff, Bruce; Ornitz, Edward M.; Craske, Michelle G.

2014-01-01

Anxiety and depression are prevalent, impairing disorders. High comorbidity has raised questions about how to define and classify them. Structural models emphasise distinctions between “fear” and “distress” disorders while other initiatives propose they be defined by neurobiological indicators that cut across disorders. This study examined startle reflex (SR) modulation in adolescents with principal fear disorders (specific phobia; social phobia) (n = 20), distress disorders (unipolar depressive disorders, dysthymia, generalized anxiety disorder; post-traumatic stress disorder) (n = 9), and controls (n = 29) during (a) baseline conditions, (b) threat context conditions (presence of contraction pads over the biceps muscle), and (c) an explicit threat cue paradigm involving phases that signalled safety from aversive stimuli (early and late stages of safe phases; early stages of danger phases) and phases that signalled immediate danger of an aversive stimulus (late stages of danger phases). Adolescents with principal fear disorders showed larger SRs than other groups throughout safe phases and early stages of danger phases. SRs did not differ between groups during late danger phases. Adolescents with principal distress disorders showed attenuated SRs during baseline and context conditions compared to other groups. Preliminary findings support initiatives to redefine emotional disorders based on neurobiological functioning. PMID:24679992

A novel fully-humanised 3D skin equivalent to model early melanoma invasion

PubMed Central

Hill, David S; Robinson, Neil D P; Caley, Matthew P; Chen, Mei; O’Toole, Edel A; Armstrong, Jane L; Przyborski, Stefan; Lovat, Penny E

2015-01-01

Metastatic melanoma remains incurable, emphasising the acute need for improved research models to investigate the underlying biological mechanisms mediating tumour invasion and metastasis, and to develop more effective targeted therapies to improve clinical outcome. Available animal models of melanoma do not accurately reflect human disease and current in vitro human skin equivalent models incorporating melanoma cells are not fully representative of the human skin microenvironment. We have developed a robust and reproducible, fully-humanised 3D skin equivalent comprising a stratified, terminally differentiated epidermis and a dermal compartment consisting of fibroblast-generated extracellular matrix. Melanoma cells incorporated into the epidermis were able to invade through the basement membrane and into the dermis, mirroring early tumour invasion in vivo. Comparison of our novel 3D melanoma skin equivalent with melanoma in situ and metastatic melanoma indicates this model accurately recreates features of disease pathology, making it a physiologically representative model of early radial and vertical growth phase melanoma invasion. PMID:26330548

Integrated payload and mission planning, phase 3. Volume 4: Optimum utilization of Spacelab racks and pallets

NASA Technical Reports Server (NTRS)

Logston, R. G.; Budris, G. D.

1977-01-01

The methodology to optimize the utilization of Spacelab racks and pallets and to apply this methodology to the early STS Spacelab missions was developed. A review was made of Spacelab Program requirements and flow plans, generic flow plans for racks and pallets were examined, and the principal optimization criteria and methodology were established. Interactions between schedule, inventory, and key optimization factors; schedule and cost sensitivity to optional approaches; and the development of tradeoff methodology were addressed. This methodology was then applied to early spacelab missions (1980-1982). Rack and pallet requirements and duty cycles were defined, a utilization assessment was made, and several trade studies performed involving varying degrees of Level IV integration, inventory level, and shared versus dedicated Spacelab racks and pallets.

Systematic framework to evaluate the status of physical activity research for persons with multiple sclerosis.

PubMed

Dixon-Ibarra, Alicia; Vanderbom, Kerri; Dugala, Anisia; Driver, Simon

2014-04-01

Exploring the current state of health behavior research for individuals with multiple sclerosis is essential to understanding the next steps required to reducing preventable disability. A way to link research to translational health promotion programs is by utilizing the Behavioral Epidemiological Framework, which describes a sequence of phases used to categorize health-related behavioral research. This critical audit of the literature examines the current state of physical activity research for persons with multiple sclerosis by utilizing the proposed Behavioral Epidemiological Framework. After searching MEDLINE, PUBMED, PsycINFO, Google Scholar and several major areas within EBSCOHOST (2000 to present), retrieved articles were categorized according to the framework phases and coding rules. Of 139 articles, 49% were in phase 1 (establishing links between behavior and health), 18% phase 2 (developing methods for measuring behavior), 24% phase 3 (identifying factors influencing behavior and implications for theory), and 9% phase 4 and 5 (evaluating interventions to change behavior and translating research into practice). Emphasis on phase 1 research indicates the field is in its early stages of development. Providing those with multiple sclerosis with necessary tools through health promotion programs is needed to reduce secondary conditions and co-morbidities. Reassessment of the field of physical activity and multiple sclerosis in the future could provide insight into whether the field is evolving over time or remaining stagnant. Published by Elsevier Inc.

High throughput screening of active pharmaceutical ingredients by UPLC.

PubMed

Al-Sayah, Mohammad A; Rizos, Panagiota; Antonucci, Vincent; Wu, Naijun

2008-07-01

Ultra performance LC (UPLC) was evaluated as an efficient screening approach to facilitate method development for drug candidates. Three stationary phases were screened: C-18, phenyl, and Shield RP 18 with column dimensions of 150 mm x 2.1 mm, 1.7 microm, which should theoretically generate 35,000 plates or 175% of the typical column plate count of a conventional 250 mm x 4.6 mm, 5 microm particle column. Thirteen different active pharmaceutical ingredients (APIs) were screened using this column set with a standardized mobile-phase gradient. The UPLC method selectivity results were compared to those obtained for these compounds via methods developed through laborious trial and error screening experiments using numerous conventional HPLC mobile and stationary phases. Peak capacity was compared for columns packed with 5 microm particles and columns packed with 1.7 microm particles. The impurities screened by UPLC were confirmed by LC/MS. The results demonstrate that simple, high efficiency UPLC gradients are a feasible and productive alternative to more conventional multiparametric chromatographic screening approaches for many compounds in the early stages of drug development.

Cassini Attitude Control Flight Software: from Development to In-Flight Operation

NASA Technical Reports Server (NTRS)

Brown, Jay

2008-01-01

The Cassini Attitude and Articulation Control Subsystem (AACS) Flight Software (FSW) has achieved its intended design goals by successfully guiding and controlling the Cassini-Huygens planetary mission to Saturn and its moons. This paper describes an overview of AACS FSW details from early design, development, implementation, and test to its fruition of operating and maintaining spacecraft control over an eleven year prime mission. Starting from phases of FSW development, topics expand to FSW development methodology, achievements utilizing in-flight autonomy, and summarize lessons learned during flight operations which can be useful to FSW in current and future spacecraft missions.