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Sample records for trial crest lead-in

  1. Which patients with ES-SCLC are most likely to benefit from more aggressive radiotherapy: A secondary analysis of the Phase III CREST trial.

    Science.gov (United States)

    Slotman, Ben J; Faivre-Finn, Corinne; van Tinteren, Harm; Keijser, Astrid; Praag, John; Knegjens, Joost; Hatton, Matthew; van Dam, Iris; van der Leest, Annija; Reymen, Bart; Stigt, Jos; Haslett, Kate; Tripathi, Devashish; Smit, Egbert F; Senan, Suresh

    2017-06-01

    In ES-SCLC patients with residual intrathoracic disease after first-line chemotherapy, the addition of thoracic radiotherapy reduces the risk of intrathoracic recurrence, and improves 2-year survival. To identify patient subgroups for future trials investigating higher dose (extra)thoracic radiotherapy, we investigated the prognostic importance of number and sites of metastases in patients included in the CREST trial. Additional data on sites and numbers of metastases were collected from individual records of 260 patients from the top 9 recruiting centers in the randomized CREST trial (53% of 495 study patients), which compared thoracic radiotherapy (TRT) to no TRT in ES-SCLC patients after any response to chemotherapy. All patients received prophylactic cranial irradiation. The clinical characteristics and outcomes of the 260 patients analyzed here did not differ significantly from that of the other 235 patients included in the CREST trial, except that fewer patients had a WHO=0 performance status (24% vs 45%), and a higher proportion had WHO=2 (15% vs 5%; pradiotherapy in ES-SCLC should focus on patients with fewer than 3 distant metastases. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  2. Restenosis after carotid artery stenting and endarterectomy: a secondary analysis of CREST, a randomised controlled trial.

    Science.gov (United States)

    Lal, Brajesh K; Beach, Kirk W; Roubin, Gary S; Lutsep, Helmi L; Moore, Wesley S; Malas, Mahmoud B; Chiu, David; Gonzales, Nicole R; Burke, J Lee; Rinaldi, Michael; Elmore, James R; Weaver, Fred A; Narins, Craig R; Foster, Malcolm; Hodgson, Kim J; Shepard, Alexander D; Meschia, James F; Bergelin, Robert O; Voeks, Jenifer H; Howard, George; Brott, Thomas G

    2012-09-01

    In the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), the composite primary endpoint of stroke, myocardial infarction, or death during the periprocedural period or ipsilateral stroke thereafter did not differ between carotid artery stenting and carotid endarterectomy for symptomatic or asymptomatic carotid stenosis. A secondary aim of this randomised trial was to compare the composite endpoint of restenosis or occlusion. Patients with stenosis of the carotid artery who were asymptomatic or had had a transient ischaemic attack, amaurosis fugax, or a minor stroke were eligible for CREST and were enrolled at 117 clinical centres in the USA and Canada between Dec 21, 2000, and July 18, 2008. In this secondary analysis, the main endpoint was a composite of restenosis or occlusion at 2 years. Restenosis and occlusion were assessed by duplex ultrasonography at 1, 6, 12, 24, and 48 months and were defined as a reduction in diameter of the target artery of at least 70%, diagnosed by a peak systolic velocity of at least 3·0 m/s. Studies were done in CREST-certified laboratories and interpreted at the Ultrasound Core Laboratory (University of Washington). The frequency of restenosis was calculated by Kaplan-Meier survival estimates and was compared during a 2-year follow-up period. We used proportional hazards models to assess the association between baseline characteristics and risk of restenosis. Analyses were per protocol. CREST is registered with ClinicalTrials.gov, number NCT00004732. 2191 patients received their assigned treatment within 30 days of randomisation and had eligible ultrasonography (1086 who had carotid artery stenting, 1105 who had carotid endarterectomy). In 2 years, 58 patients who underwent carotid artery stenting (Kaplan-Meier rate 6·0%) and 62 who had carotid endarterectomy (6·3%) had restenosis or occlusion (hazard ratio [HR] 0·90, 95% CI 0·63-1·29; p=0·58). Female sex (1·79, 1·25-2·56), diabetes (2·31, 1·61-3·31

  3. Costs and cost-effectiveness of carotid stenting versus endarterectomy for patients at standard surgical risk: results from the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST).

    Science.gov (United States)

    Vilain, Katherine R; Magnuson, Elizabeth A; Li, Haiyan; Clark, Wayne M; Begg, Richard J; Sam, Albert D; Sternbergh, W Charles; Weaver, Fred A; Gray, William A; Voeks, Jenifer H; Brott, Thomas G; Cohen, David J

    2012-09-01

    The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) demonstrated similar rates of the primary composite end point between carotid artery stenting (CAS) and carotid endarterectomy (CEA), although the risk of stroke was higher with CAS, and the risk of myocardial infarction was higher with CEA. Given the large number of patients who are candidates for these procedures, an understanding of their relative cost and cost-effectiveness may have important implications for health care policy and treatment guidelines. We performed a formal economic evaluation alongside the CREST trial. Costs were estimated from all trial participants over the first year of follow-up using a combination of resource use data and hospital billing data. Patient-level health use scores were obtained using data from the SF-36. We then used a Markov disease-simulation model calibrated to the CREST results to project 10-year costs and quality-adjusted life expectancy for the 2 treatment groups. Although initial procedural costs were $1025/patient higher with CAS, postprocedure costs and physician costs were lower such that total costs for the index hospitalization were similar for the CAS and CEA groups ($15 055 versus $14 816; mean difference, $239/patient; 95% CI for difference, -$297 to $775). Neither follow-up costs after discharge nor total 1-year costs differed significantly. For the CREST population, model-based projections over a 10-year time horizon demonstrated that CAS would result in a mean incremental cost of $524/patient and a reduction in quality-adjusted life expectancy of 0.008 years compared with CEA. Probabilistic sensitivity analysis demonstrated that CEA was economically attractive at an incremental cost-effectiveness threshold of $50 000/quality-adjusted life-year gained in 54% of samples, whereas CAS was economically attractive in 46%. Despite slightly lower in-trial costs and lower rates of stroke with CEA compared with CAS, projected 10-year outcomes

  4. Lack of beta1 integrins in enteric neural crest cells leads to a Hirschsprung-like phenotype

    DEFF Research Database (Denmark)

    Breau, Marie A; Pietri, Thomas; Eder, Olivier

    2006-01-01

    The enteric nervous system arises mainly from vagal and sacral neural crest cells that colonise the gut between 9.5 and 14 days of development in mice. Using the Cre-LoxP system, we removed beta1 integrins in the neural crest cells when they emerge from the neural tube. beta1-null enteric neural...

  5. Neural crest cells: from developmental biology to clinical interventions.

    Science.gov (United States)

    Noisa, Parinya; Raivio, Taneli

    2014-09-01

    Neural crest cells are multipotent cells, which are specified in embryonic ectoderm in the border of neural plate and epiderm during early development by interconnection of extrinsic stimuli and intrinsic factors. Neural crest cells are capable of differentiating into various somatic cell types, including melanocytes, craniofacial cartilage and bone, smooth muscle, and peripheral nervous cells, which supports their promise for cell therapy. In this work, we provide a comprehensive review of wide aspects of neural crest cells from their developmental biology to applicability in medical research. We provide a simplified model of neural crest cell development and highlight the key external stimuli and intrinsic regulators that determine the neural crest cell fate. Defects of neural crest cell development leading to several human disorders are also mentioned, with the emphasis of using human induced pluripotent stem cells to model neurocristopathic syndromes. © 2014 Wiley Periodicals, Inc.

  6. CREST Revealed

    DEFF Research Database (Denmark)

    Rapp, Hermann; Parisi, Cristiana; Bridgeman, Alfia

    This report covers the period from 1993 when the CREST project was initiated, to its launch in 1996, and considers the environment that prompted its instigation. The report looks at the massive cooperation of Government, industry and a range of different service providers that all came together......, under the central control of the CREST project team. It proposes five reasons why the CREST project was successful and examines why the CREST system continues to be at the heart of UK settlement, 20 years on....

  7. Sagittal crest formation in great apes and gibbons.

    Science.gov (United States)

    Balolia, Katharine L; Soligo, Christophe; Wood, Bernard

    2017-06-01

    The frequency of sagittal crest expression and patterns of sagittal crest growth and development have been documented in hominoids, including some extinct hominin taxa, and the more frequent expression of the sagittal crest in males has been traditionally linked with the need for larger-bodied individuals to have enough attachment area for the temporalis muscle. In the present study, we investigate sagittal cresting in a dentally mature sample of four hominoid taxa (Pan troglodytes schweinfurthii, Gorilla gorilla gorilla, Pongo pygmaeus pygmaeus and Hylobates lar). We investigate whether sagittal crest size increases with age beyond dental maturity in males and females of G. g. gorilla and Po. pyg. pygmaeus, and whether these taxa show sex differences in the timing of sagittal crest development. We evaluate the hypothesis that the larger sagittal crest of males may not be solely due to the requirement for a larger surface area than the un-crested cranial vault can provide for the attachment of the temporalis muscle, and present data on sex differences in temporalis muscle attachment area and sagittal crest size relative to cranial size. Gorilla g. gorilla and Po. pyg. pygmaeus males show significant relationships between tooth wear rank and sagittal crest size, and they show sagittal crest size differences between age groups that are not found in females. The sagittal crest emerges in early adulthood in the majority of G. g. gorilla males, whereas the percentage of G. g. gorilla females possessing a sagittal crest increases more gradually. Pongo pyg. pygmaeus males experience a three-fold increase in the number of specimens exhibiting a sagittal crest in mid-adulthood, consistent with a secondary growth spurt. Gorilla g. gorilla and Po. pyg. pygmaeus show significant sex differences in the size of the temporalis muscle attachment area, relative to cranial size, with males of both taxa showing positive allometry not shown in females. Gorilla g

  8. Recycling signals in the neural crest

    OpenAIRE

    Taneyhill, Lisa A.; Bronner-Fraser, Marianne E.

    2006-01-01

    Vertebrate neural crest cells are multipotent and differentiate into structures that include cartilage and the bones of the face, as well as much of the peripheral nervous system. Understanding how different model vertebrates utilize signaling pathways reiteratively during various stages of neural crest formation and differentiation lends insight into human disorders associated with the neural crest.

  9. Recycling signals in the neural crest.

    Science.gov (United States)

    Taneyhill, Lisa A; Bronner-Fraser, Marianne

    2005-01-01

    Vertebrate neural crest cells are multipotent and differentiate into structures that include cartilage and the bones of the face, as well as much of the peripheral nervous system. Understanding how different model vertebrates utilize signaling pathways reiteratively during various stages of neural crest formation and differentiation lends insight into human disorders associated with the neural crest.

  10. The Effect of Iliac Crest Autograft on the Outcome of Fusion in the Setting of Degenerative Spondylolisthesis

    Science.gov (United States)

    Radcliff, Kristen; Hwang, Raymond; Hilibrand, Alan; Smith, Harvey E.; Gruskay, Jordan; Lurie, Jon D.; Zhao, Wenyan; Albert, Todd; Weinstein, James

    2012-01-01

    Background: There is considerable controversy about the long-term morbidity associated with the use of posterior autologous iliac crest bone graft for lumbar spine fusion procedures compared with the use of bone-graft substitutes. The hypothesis of this study was that there is no long-term difference in outcome for patients who had posterior lumbar fusion with or without iliac crest autograft. Methods: The study population includes patients enrolled in the degenerative spondylolisthesis cohort of the Spine Patient Outcomes Research Trial who underwent lumbar spinal fusion. Patients were divided according to whether they had or had not received posterior autologous iliac crest bone graft. Results: There were 108 patients who had fusion with iliac crest autograft and 246 who had fusion without iliac crest autograft. There were no baseline differences between groups in demographic characteristics, comorbidities, or baseline clinical scores. At baseline, the group that received iliac crest bone graft had an increased percentage of patients who had multilevel fusions (32% versus 21%; p = 0.033) and L5-S1 surgery (37% versus 26%; p = 0.031) compared with the group without iliac crest autograft. Operative time was higher in the iliac crest bone-graft group (233.4 versus 200.9 minutes; p case-by-case basis for lumbar spinal fusion. Level of Evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence. PMID:22878599

  11. Apoptosis in neural crest cells by functional loss of APC tumor suppressor gene

    Science.gov (United States)

    Hasegawa, Sumitaka; Sato, Tomoyuki; Akazawa, Hiroshi; Okada, Hitoshi; Maeno, Akiteru; Ito, Masaki; Sugitani, Yoshinobu; Shibata, Hiroyuki; Miyazaki, Jun-ichi; Katsuki, Motoya; Yamauchi, Yasutaka; Yamamura, Ken-ichi; Katamine, Shigeru; Noda, Tetsuo

    2002-01-01

    Apc is a gene associated with familial adenomatous polyposis coli (FAP) and its inactivation is a critical step in colorectal tumor formation. The protein product, adenomatous polyposis coli (APC), acts to down-regulate intracellular levels of β-catenin, a key signal transducer in the Wnt signaling. Conditional targeting of Apc in the neural crest of mice caused massive apoptosis of cephalic and cardiac neural crest cells at about 11.5 days post coitum, resulting in craniofacial and cardiac anomalies at birth. Notably, the apoptotic cells localized in the regions where β-catenin had accumulated. In contrast to its role in colorectal epithelial cells, inactivation of APC leads to dysregulation of β-catenin/Wnt signaling with resultant apoptosis in certain tissues including neural crest cells. PMID:11756652

  12. Whistler wave trapping in a density crest

    International Nuclear Information System (INIS)

    Sugai, H.; Niki, H.; Inutake, M.; Takeda, S.

    1979-11-01

    The linear trapping process of whistler waves in a field-aligned density crest is investigated theoretically and experimentally below ω = ωsub(c)/2 (half gyrofrequency). The conditions of the crest trapping are derived in terms of the frequency ω/ωsub(c), the incident wave-normal angle theta sub(i), and the density ratio n sub(i)/n sub(o), where n sub(i) and n sub(o) denote the density at the incident point and that at the ridge, respectively. The oscillation length of the trapped ray path is calculated for a parabolic density profile. The experiment on antenna-excited whistler wave has been performed in a large magnetized plasma with the density crest. The phase and amplitude profile of the whistler wave is measured along and across the crest. The measurement has verified characteristic behaviors of the crest trapping. (author)

  13. Sagittal crest formation in great apes and gibbons

    OpenAIRE

    Balolia, K. L.; Soligo, C.; Wood, B.

    2017-01-01

    The frequency of sagittal crest expression and patterns of sagittal crest growth and development have been documented in hominoids, including some extinct hominin taxa, and the more frequent expression of the sagittal crest in males has been traditionally linked with the need for larger-bodied individuals to have enough attachment area for the temporalis muscle. In the present study, we investigate sagittal cresting in a dentally mature sample of four hominoid taxa (Pan troglodytes schweinfur...

  14. Hepatocyte growth factor/scatter factor-MET signaling in neural crest-derived melanocyte development.

    Science.gov (United States)

    Kos, L; Aronzon, A; Takayama, H; Maina, F; Ponzetto, C; Merlino, G; Pavan, W

    1999-02-01

    The mechanisms governing development of neural crest-derived melanocytes, and how alterations in these pathways lead to hypopigmentation disorders, are not completely understood. Hepatocyte growth factor/scatter factor (HGF/SF) signaling through the tyrosine-kinase receptor, MET, is capable of promoting the proliferation, increasing the motility, and maintaining high tyrosinase activity and melanin synthesis of melanocytes in vitro. In addition, transgenic mice that ubiquitously overexpress HGF/SF demonstrate hyperpigmentation in the skin and leptomenigenes and develop melanomas. To investigate whether HGF/ SF-MET signaling is involved in the development of neural crest-derived melanocytes, transgenic embryos, ubiquitously overexpressing HGF/SF, were analyzed. In HGF/SF transgenic embryos, the distribution of melanoblasts along the characteristic migratory pathway was not affected. However, additional ectopically localized melanoblasts were also observed in the dorsal root ganglia and neural tube, as early as 11.5 days post coitus (p.c.). We utilized an in vitro neural crest culture assay to further explore the role of HGF/SF-MET signaling in neural crest development. HGF/SF added to neural crest cultures increased melanoblast number, permitted differentiation into pigmented melanocytes, promoted melanoblast survival, and could replace mast-cell growth factor/Steel factor (MGF) in explant cultures. To examine whether HGF/SF-MET signaling is required for the proper development of melanocytes, embryos with a targeted Met null mutation (Met-/-) were analysed. In Met-/- embryos, melanoblast number and location were not overtly affected up to 14 days p.c. These results demonstrate that HGF/SF-MET signaling influences, but is not required for, the initial development of neural crest-derived melanocytes in vivo and in vitro.

  15. AKT signaling displays multifaceted functions in neural crest development.

    Science.gov (United States)

    Sittewelle, Méghane; Monsoro-Burq, Anne H

    2018-05-31

    AKT signaling is an essential intracellular pathway controlling cell homeostasis, cell proliferation and survival, as well as cell migration and differentiation in adults. Alterations impacting the AKT pathway are involved in many pathological conditions in human disease. Similarly, during development, multiple transmembrane molecules, such as FGF receptors, PDGF receptors or integrins, activate AKT to control embryonic cell proliferation, migration, differentiation, and also cell fate decisions. While many studies in mouse embryos have clearly implicated AKT signaling in the differentiation of several neural crest derivatives, information on AKT functions during the earliest steps of neural crest development had remained relatively scarce until recently. However, recent studies on known and novel regulators of AKT signaling demonstrate that this pathway plays critical roles throughout the development of neural crest progenitors. Non-mammalian models such as fish and frog embryos have been instrumental to our understanding of AKT functions in neural crest development, both in neural crest progenitors and in the neighboring tissues. This review combines current knowledge acquired from all these different vertebrate animal models to describe the various roles of AKT signaling related to neural crest development in vivo. We first describe the importance of AKT signaling in patterning the tissues involved in neural crest induction, namely the dorsal mesoderm and the ectoderm. We then focus on AKT signaling functions in neural crest migration and differentiation. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Neural crest contributions to the lamprey head

    Science.gov (United States)

    McCauley, David W.; Bronner-Fraser, Marianne

    2003-01-01

    The neural crest is a vertebrate-specific cell population that contributes to the facial skeleton and other derivatives. We have performed focal DiI injection into the cranial neural tube of the developing lamprey in order to follow the migratory pathways of discrete groups of cells from origin to destination and to compare neural crest migratory pathways in a basal vertebrate to those of gnathostomes. The results show that the general pathways of cranial neural crest migration are conserved throughout the vertebrates, with cells migrating in streams analogous to the mandibular and hyoid streams. Caudal branchial neural crest cells migrate ventrally as a sheet of cells from the hindbrain and super-pharyngeal region of the neural tube and form a cylinder surrounding a core of mesoderm in each pharyngeal arch, similar to that seen in zebrafish and axolotl. In addition to these similarities, we also uncovered important differences. Migration into the presumptive caudal branchial arches of the lamprey involves both rostral and caudal movements of neural crest cells that have not been described in gnathostomes, suggesting that barriers that constrain rostrocaudal movement of cranial neural crest cells may have arisen after the agnathan/gnathostome split. Accordingly, neural crest cells from a single axial level contributed to multiple arches and there was extensive mixing between populations. There was no apparent filling of neural crest derivatives in a ventral-to-dorsal order, as has been observed in higher vertebrates, nor did we find evidence of a neural crest contribution to cranial sensory ganglia. These results suggest that migratory constraints and additional neural crest derivatives arose later in gnathostome evolution.

  17. Numerical Simulation of 3-D Wave Crests

    Institute of Scientific and Technical Information of China (English)

    YU Dingyong; ZHANG Hanyuan

    2003-01-01

    A clear definition of 3-D wave crest and a description of the procedures to detect the boundary of wave crest are presented in the paper. By using random wave theory and directional wave spectrum, a MATLAB-platformed program is designed to simulate random wave crests for various directional spectral conditions in deep water. Statistics of wave crests with different directional spreading parameters and different directional functions are obtained and discussed.

  18. Regulation of Msx genes by a Bmp gradient is essential for neural crest specification.

    Science.gov (United States)

    Tribulo, Celeste; Aybar, Manuel J; Nguyen, Vu H; Mullins, Mary C; Mayor, Roberto

    2003-12-01

    There is evidence in Xenopus and zebrafish embryos that the neural crest/neural folds are specified at the border of the neural plate by a precise threshold concentration of a Bmp gradient. In order to understand the molecular mechanism by which a gradient of Bmp is able to specify the neural crest, we analyzed how the expression of Bmp targets, the Msx genes, is regulated and the role that Msx genes has in neural crest specification. As Msx genes are directly downstream of Bmp, we analyzed Msx gene expression after experimental modification in the level of Bmp activity by grafting a bead soaked with noggin into Xenopus embryos, by expressing in the ectoderm a dominant-negative Bmp4 or Bmp receptor in Xenopus and zebrafish embryos, and also through Bmp pathway component mutants in the zebrafish. All the results show that a reduction in the level of Bmp activity leads to an increase in the expression of Msx genes in the neural plate border. Interestingly, by reaching different levels of Bmp activity in animal cap ectoderm, we show that a specific concentration of Bmp induces msx1 expression to a level similar to that required to induce neural crest. Our results indicate that an intermediate level of Bmp activity specifies the expression of Msx genes in the neural fold region. In addition, we have analyzed the role that msx1 plays on neural crest specification. As msx1 has a role in dorsoventral pattering, we have carried out conditional gain- and loss-of-function experiments using different msx1 constructs fused to a glucocorticoid receptor element to avoid an early effect of this factor. We show that msx1 expression is able to induce all other early neural crest markers tested (snail, slug, foxd3) at the time of neural crest specification. Furthermore, the expression of a dominant negative of Msx genes leads to the inhibition of all the neural crest markers analyzed. It has been previously shown that snail is one of the earliest genes acting in the neural crest

  19. Utility of Phox2b immunohistochemical stain in neural crest tumours and non-neural crest tumours in paediatric patients.

    Science.gov (United States)

    Warren, Mikako; Matsuno, Ryosuke; Tran, Henry; Shimada, Hiroyuki

    2018-03-01

    This study evaluated the utility of Phox2b in paediatric tumours. Previously, tyrosine hydroxylase (TH) was the most widely utilised sympathoadrenal marker specific for neural crest tumours with neuronal/neuroendocrine differentiation. However, its sensitivity is insufficient. Recently Phox2b has emerged as another specific marker for this entity. Phox2b immunohistochemistry (IHC) was performed on 159 paediatric tumours, including (group 1) 65 neural crest tumours with neuronal differentiation [peripheral neuroblastic tumours (pNT)]: 15 neuroblastoma undifferentiated (NB-UD), 10 NB poorly differentiated (NB-PD), 10 NB differentiating (NB-D), 10 ganglioneuroblastoma intermixed (GNBi), 10 GNB nodular (GNBn) and 10 ganglioneuroma (GN); (group 2) 23 neural crest tumours with neuroendocrine differentiation [pheochromocytoma/paraganglioma (PCC/PG)]; (group 3) 27 other neural crest tumours including one composite rhabdomyosarcoma/neuroblastoma; and (group 4) 44 non-neural crest tumours. TH IHC was performed on groups 1, 2 and 3. Phox2b was expressed diffusely in pNT (n = 65 of 65), strongly in NB-UD and NB-PD and with less intensity in NB-D, GNB and GN. Diffuse TH was seen in all NB-PD, NB-D, GNB and GN, but nine of 15 NB-UD and a nodule in GNBn did not express TH (n = 55 of 65). PCC/PG expressed diffuse Phox2b (n = 23 of 23) and diffuse TH, except for one tumour (n = 22 of 23). In composite rhabdomyosarcoma, TH was expressed only in neuroblastic cells and Phox2b was diffusely positive in neuroblastic cells and focally in rhabdomyosarcoma. All other tumours were negative for Phox2b (n = none of 44). Phox2b was a specific and sensitive marker for pNT and PCC/PG, especially useful for identifying NB-UD often lacking TH. Our study also presented a composite rhabdomyosarcoma/neuroblastoma of neural crest origin. © 2017 John Wiley & Sons Ltd.

  20. Cryoglobulinemic vasculitis in a patient with CREST syndrome.

    Science.gov (United States)

    Hurst, Rebecca L; Berianu, Florentina; Ginsburg, William W; Klein, Christopher J; Englestad, Janean K; Kennelly, Kathleen D

    2014-10-01

    Cryoglobulinemic vasculitis is a rare entity. Although it has been reported in diffuse systemic sclerosis, it has not been reported in calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly and telangiectasia (CREST) syndrome. We report a patient with cryoglobulinemic vasculitis with CREST syndrome who did not have typical clinical features of vasculitis. This 58-year-old woman presented with mild generalized weakness and a diagnosis of CREST syndrome, which included Raynaud's syndrome, dysphagia and telangiectasias. She was positive for serum cryoglobulins, which led to a sural nerve biopsy. The biopsy results were consistent with cryoglobulinemic vasculitis. Cryoglobulinemic vasculitis has not been previously reported in CREST syndrome to our knowledge. Additionally, the patient also had limited clinical symptoms. Our patient displays the importance of checking for cryoglobulins and obtaining a nerve biopsy when the serum is positive. Both of these diagnostic tests were integral for directing appropriate treatment for this patient. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Neural Crest-Derived Mesenchymal Cells Require Wnt Signaling for Their Development and Drive Invagination of the Telencephalic Midline

    Science.gov (United States)

    Choe, Youngshik; Zarbalis, Konstantinos S.; Pleasure, Samuel J.

    2014-01-01

    Embryonic neural crest cells contribute to the development of the craniofacial mesenchyme, forebrain meninges and perivascular cells. In this study, we investigated the function of ß-catenin signaling in neural crest cells abutting the dorsal forebrain during development. In the absence of ß-catenin signaling, neural crest cells failed to expand in the interhemispheric region and produced ectopic smooth muscle cells instead of generating dermal and calvarial mesenchyme. In contrast, constitutive expression of stabilized ß-catenin in neural crest cells increased the number of mesenchymal lineage precursors suggesting that ß-catenin signaling is necessary for the expansion of neural crest-derived mesenchymal cells. Interestingly, the loss of neural crest-derived mesenchymal stem cells (MSCs) leads to failure of telencephalic midline invagination and causes ventricular system defects. This study shows that ß-catenin signaling is required for the switch of neural crest cells to MSCs and mediates the expansion of MSCs to drive the formation of mesenchymal structures of the head. Furthermore, loss of these structures causes striking defects in forebrain morphogenesis. PMID:24516524

  2. Neural crest-derived mesenchymal cells require Wnt signaling for their development and drive invagination of the telencephalic midline.

    Directory of Open Access Journals (Sweden)

    Youngshik Choe

    Full Text Available Embryonic neural crest cells contribute to the development of the craniofacial mesenchyme, forebrain meninges and perivascular cells. In this study, we investigated the function of ß-catenin signaling in neural crest cells abutting the dorsal forebrain during development. In the absence of ß-catenin signaling, neural crest cells failed to expand in the interhemispheric region and produced ectopic smooth muscle cells instead of generating dermal and calvarial mesenchyme. In contrast, constitutive expression of stabilized ß-catenin in neural crest cells increased the number of mesenchymal lineage precursors suggesting that ß-catenin signaling is necessary for the expansion of neural crest-derived mesenchymal cells. Interestingly, the loss of neural crest-derived mesenchymal stem cells (MSCs leads to failure of telencephalic midline invagination and causes ventricular system defects. This study shows that ß-catenin signaling is required for the switch of neural crest cells to MSCs and mediates the expansion of MSCs to drive the formation of mesenchymal structures of the head. Furthermore, loss of these structures causes striking defects in forebrain morphogenesis.

  3. Diprosopia revisited in light of the recognized role of neural crest cells in facial development.

    Science.gov (United States)

    Carles, D; Weichhold, W; Alberti, E M; Léger, F; Pigeau, F; Horovitz, J

    1995-01-01

    The aim of this study is to compare the theory of embryogenesis of the face with human diprosopia. This peculiar form of conjoined twinning is of great interest because 1) only the facial structures are duplicated and 2) almost all cases have a rather monomorphic pattern. The hypothesis is that an initial duplication of the notochord leads to two neural plates and subsequently duplicated neural crests. In those conditions, derivatives of the neural crests will be partially or totally duplicated; therefore, in diprosopia, the duplicated facial structures would be considered to be neural crest derivatives. If these structures are identical to those that are experimentally demonstrated to be neural crest derivatives in animals, these findings are an argument to apply this theory of facial embryogenesis in man. Serial horizontal sections of the face of two diprosopic fetuses (11 and 21 weeks gestation) were studied macro- and microscopically to determine the external and internal structures that are duplicated. Complete postmortem examination was performed in search for additional malformations. The face of both fetuses showed a very similar morphologic pattern with duplication of ocular, nasal, and buccal structures. The nasal fossae and the anterior part of the tongue were also duplicated, albeit the posterior part and the pharyngolaryngeal structures were unique. Additional facial clefts were present in both fetuses. Extrafacial anomalies were represented by a craniorachischisis, two fused vertebral columns and, in the older fetus, by a complex cardiac malformation morphologically identical to malformations induced by removal or grafting of additional cardiac neural crest cells in animals. These pathological findings could identify the facial structures that are neural crest derivatives in man. They are similar to those experimentally demonstrated to be neural crest derivatives in animals. In this respect, diprosopia could be considered as the end of a spectrum

  4. Review: the role of neural crest cells in the endocrine system.

    Science.gov (United States)

    Adams, Meghan Sara; Bronner-Fraser, Marianne

    2009-01-01

    The neural crest is a pluripotent population of cells that arises at the junction of the neural tube and the dorsal ectoderm. These highly migratory cells form diverse derivatives including neurons and glia of the sensory, sympathetic, and enteric nervous systems, melanocytes, and the bones, cartilage, and connective tissues of the face. The neural crest has long been associated with the endocrine system, although not always correctly. According to current understanding, neural crest cells give rise to the chromaffin cells of the adrenal medulla, chief cells of the extra-adrenal paraganglia, and thyroid C cells. The endocrine tumors that correspond to these cell types are pheochromocytomas, extra-adrenal paragangliomas, and medullary thyroid carcinomas. Although controversies concerning embryological origin appear to have mostly been resolved, questions persist concerning the pathobiology of each tumor type and its basis in neural crest embryology. Here we present a brief history of the work on neural crest development, both in general and in application to the endocrine system. In particular, we present findings related to the plasticity and pluripotency of neural crest cells as well as a discussion of several different neural crest tumors in the endocrine system.

  5. SCENARIO OF AN ACCIDENT OF SOIL DAMS IN CASE OF WATER SPILL OVER A DAM CREST BY USING FAULT TREE ANALYSIS

    Directory of Open Access Journals (Sweden)

    Kuznetsov Dmitriy Viktorovich

    2016-04-01

    Full Text Available The scenario of a hydrodynamic accident of water flow over a crest of a soil dam is considered by the method of fault tree analysis, for which the basic reasons and controlled diagnostic indicators of an accident have been defined. Logical operators “AND”/”OR” were used for creation of a sequence of logically connected events, leading to an undesired event in the scenario of accident. The scenario of the accident was plotted in case of three basic reasons - an excessive settling of a dam crest, an excess flood, an inoperable spillway, taking into account the sequence of the events’ development and with observance of the necessary conditions leading to an accident. “Technical” reasons were observed in the present scenario, force majeure events were not considered. The provided scenario of the accident consists of two branches of events’ development: the left one that depends on an upstream level, and the right one that depends on settling of a dam crest. In each of the considered events an accident “the water spill over a crest of a soil dam” is possible only in case of execution of two different conditions at the same time, i.e. in case of an appropriate upstream level and the appropriate mark of a crest of a soil dam. The conditions of the accident are defined by diagnostic indices - the upstream level and settling of a dam crest, which at the same time are safety criteria of the hydraulic structure for soil dams. They allow defining the technical condition of the construction. Four possible technical conditions are suggested for the definition of technical statuses - normative, operable, limited operable, abnormal. Criteria of safety are the boundaries of the state: for loading and impact - it is the upstream level, for geometrical compliance of the construction - it is a dam crest mark.

  6. Applications of Mesenchymal Stem Cells and Neural Crest Cells in Craniofacial Skeletal Research

    Directory of Open Access Journals (Sweden)

    Satoru Morikawa

    2016-01-01

    Full Text Available Craniofacial skeletal tissues are composed of tooth and bone, together with nerves and blood vessels. This composite material is mainly derived from neural crest cells (NCCs. The neural crest is transient embryonic tissue present during neural tube formation whose cells have high potential for migration and differentiation. Thus, NCCs are promising candidates for craniofacial tissue regeneration; however, the clinical application of NCCs is hindered by their limited accessibility. In contrast, mesenchymal stem cells (MSCs are easily accessible in adults, have similar potential for self-renewal, and can differentiate into skeletal tissues, including bones and cartilage. Therefore, MSCs may represent good sources of stem cells for clinical use. MSCs are classically identified under adherent culture conditions, leading to contamination with other cell lineages. Previous studies have identified mouse- and human-specific MSC subsets using cell surface markers. Additionally, some studies have shown that a subset of MSCs is closely related to neural crest derivatives and endothelial cells. These MSCs may be promising candidates for regeneration of craniofacial tissues from the perspective of developmental fate. Here, we review the fundamental biology of MSCs in craniofacial research.

  7. Requirement for Foxd3 in the maintenance of neural crest progenitors.

    Science.gov (United States)

    Teng, Lu; Mundell, Nathan A; Frist, Audrey Y; Wang, Qiaohong; Labosky, Patricia A

    2008-05-01

    Understanding the molecular mechanisms of stem cell maintenance is crucial for the ultimate goal of manipulating stem cells for the treatment of disease. Foxd3 is required early in mouse embryogenesis; Foxd3(-/-) embryos fail around the time of implantation, cells of the inner cell mass cannot be maintained in vitro, and blastocyst-derived stem cell lines cannot be established. Here, we report that Foxd3 is required for maintenance of the multipotent mammalian neural crest. Using tissue-specific deletion of Foxd3 in the neural crest, we show that Foxd3(flox/-); Wnt1-Cre mice die perinatally with a catastrophic loss of neural crest-derived structures. Cranial neural crest tissues are either missing or severely reduced in size, the peripheral nervous system consists of reduced dorsal root ganglia and cranial nerves, and the entire gastrointestinal tract is devoid of neural crest derivatives. These results demonstrate a global role for this transcriptional repressor in all aspects of neural crest maintenance along the anterior-posterior axis, and establish an unprecedented molecular link between multiple divergent progenitor lineages of the mammalian embryo.

  8. Development of teeth in chick embryos after mouse neural crest transplantations.

    Science.gov (United States)

    Mitsiadis, Thimios A; Chéraud, Yvonnick; Sharpe, Paul; Fontaine-Pérus, Josiane

    2003-05-27

    Teeth were lost in birds 70-80 million years ago. Current thinking holds that it is the avian cranial neural crest-derived mesenchyme that has lost odontogenic capacity, whereas the oral epithelium retains the signaling properties required to induce odontogenesis. To investigate the odontogenic capacity of ectomesenchyme, we have used neural tube transplantations from mice to chick embryos to replace the chick neural crest cell populations with mouse neural crest cells. The mouse/chick chimeras obtained show evidence of tooth formation showing that avian oral epithelium is able to induce a nonavian developmental program in mouse neural crest-derived mesenchymal cells.

  9. Real-Time Audio Processing on the T-CREST Multicore Platform

    DEFF Research Database (Denmark)

    Ausin, Daniel Sanz; Pezzarossa, Luca; Schoeberl, Martin

    2017-01-01

    of the audio signal. This paper presents a real-time multicore audio processing system based on the T-CREST platform. T-CREST is a time-predictable multicore processor for real-time embedded systems. Multiple audio effect tasks have been implemented, which can be connected together in different configurations...... forming sequential and parallel effect chains, and using a network-onchip for intercommunication between processors. The evaluation of the system shows that real-time processing of multiple effect configurations is possible, and that the estimation and control of latency ensures real-time behavior.......Multicore platforms are nowadays widely used for audio processing applications, due to the improvement of computational power that they provide. However, some of these systems are not optimized for temporally constrained environments, which often leads to an undesired increase in the latency...

  10. DNA methyltransferase 3b is dispensable for mouse neural crest development.

    Directory of Open Access Journals (Sweden)

    Bridget T Jacques-Fricke

    Full Text Available The neural crest is a population of multipotent cells that migrates extensively throughout vertebrate embryos to form diverse structures. Mice mutant for the de novo DNA methyltransferase DNMT3b exhibit defects in two neural crest derivatives, the craniofacial skeleton and cardiac ventricular septum, suggesting that DNMT3b activity is necessary for neural crest development. Nevertheless, the requirement for DNMT3b specifically in neural crest cells, as opposed to interacting cell types, has not been determined. Using a conditional DNMT3b allele crossed to the neural crest cre drivers Wnt1-cre and Sox10-cre, neural crest DNMT3b mutants were generated. In both neural crest-specific and fully DNMT3b-mutant embryos, cranial neural crest cells exhibited only subtle migration defects, with increased numbers of dispersed cells trailing organized streams in the head. In spite of this, the resulting cranial ganglia, craniofacial skeleton, and heart developed normally when neural crest cells lacked DNMT3b. This indicates that DNTM3b is not necessary in cranial neural crest cells for their development. We conclude that defects in neural crest derivatives in DNMT3b mutant mice reflect a requirement for DNMT3b in lineages such as the branchial arch mesendoderm or the cardiac mesoderm that interact with neural crest cells during formation of these structures.

  11. Pax7 lineage contributions to the mammalian neural crest.

    Directory of Open Access Journals (Sweden)

    Barbara Murdoch

    Full Text Available Neural crest cells are vertebrate-specific multipotent cells that contribute to a variety of tissues including the peripheral nervous system, melanocytes, and craniofacial bones and cartilage. Abnormal development of the neural crest is associated with several human maladies including cleft/lip palate, aggressive cancers such as melanoma and neuroblastoma, and rare syndromes, like Waardenburg syndrome, a complex disorder involving hearing loss and pigment defects. We previously identified the transcription factor Pax7 as an early marker, and required component for neural crest development in chick embryos. In mammals, Pax7 is also thought to play a role in neural crest development, yet the precise contribution of Pax7 progenitors to the neural crest lineage has not been determined.Here we use Cre/loxP technology in double transgenic mice to fate map the Pax7 lineage in neural crest derivates. We find that Pax7 descendants contribute to multiple tissues including the cranial, cardiac and trunk neural crest, which in the cranial cartilage form a distinct regional pattern. The Pax7 lineage, like the Pax3 lineage, is additionally detected in some non-neural crest tissues, including a subset of the epithelial cells in specific organs.These results demonstrate a previously unappreciated widespread distribution of Pax7 descendants within and beyond the neural crest. They shed light regarding the regionally distinct phenotypes observed in Pax3 and Pax7 mutants, and provide a unique perspective into the potential roles of Pax7 during disease and development.

  12. Overflow Characteristic of Cylindrical Shape Crest Weirs Over Horizontal Bed

    OpenAIRE

    Emad4 AbdulGabbar

    2013-01-01

    The most common types of weirs are the broad-crested weir, the sharp-crested weir, the circular crested weir and the ogee crested weir. Advantages of the cylindrical weir shape include the stable overflow pattern, the ease to pass floating debris, the simplicity of design compared to ogee crest design and the associated lower costs. In present study, it was investigated the overflow characteristics of circular weirs in laboratory for various cylinder radii of three sizes (11.4, 9.0, 6.3 cm), ...

  13. WAC Bennett Dam - the characterization of a crest sinkhole

    Energy Technology Data Exchange (ETDEWEB)

    Stewart, R.A.; Gaffran, P.C. [British Columbia Hydro, Burnaby, BC (Canada); Watts, B.D. [Klohn-Crippen Consultants Ltd., Richmond, BC (Canada); Sobkowicz, J.C. [Thurber Engineering Ltd., Vancouver, BC (Canada); Kupper, A.G. [AGRA Earth and Environmental, Edmonton, AB (Canada)

    1998-11-01

    In June, 1996, a small hole was discovered in the asphaltic concrete road on the crest of the 183 m high WAC Bennett Dam on the Peace River in northeastern British Columbia. Examination of the hole resulted in a sinkhole on the dam crest. The sinkhole was 2.5 m in diameter and 7 m deep. Speculation was that the cavity was likely associated in some way with a buried survey benchmark tube. An investigation was immediately planned and executed to characterize the sinkhole, to determine the extent of damage and the safety status of this very large dam. British Columbia`s Dam Safety Regulator made the decision to lower the reservoir level. During the reservoir drawdown, various surface geophysical techniques were used to investigate the condition of the dam beyond the sinkholes. Intrusive investigations of the sinkhole were also planned. This involved trial drilling and downhole geophysical surveys in intact portions of the core at locations far from the sinkhole. The objectives and criteria developed for the investigation program are summarized. Scope of key activities at the sinkhole and important lessons learned during the investigation are also described. 9 refs., 15 figs.

  14. Germ layers, the neural crest and emergent organization in development and evolution.

    Science.gov (United States)

    Hall, Brian K

    2018-04-10

    Discovered in chick embryos by Wilhelm His in 1868 and named the neural crest by Arthur Milnes Marshall in 1879, the neural crest cells that arise from the neural folds have since been shown to differentiate into almost two dozen vertebrate cell types and to have played major roles in the evolution of such vertebrate features as bone, jaws, teeth, visceral (pharyngeal) arches, and sense organs. I discuss the discovery that ectodermal neural crest gave rise to mesenchyme and the controversy generated by that finding; the germ layer theory maintained that only mesoderm could give rise to mesenchyme. A second topic of discussion is germ layers (including the neural crest) as emergent levels of organization in animal development and evolution that facilitated major developmental and evolutionary change. The third topic is gene networks, gene co-option, and the evolution of gene-signaling pathways as key to developmental and evolutionary transitions associated with the origin and evolution of the neural crest and neural crest cells. © 2018 Wiley Periodicals, Inc.

  15. CREST--classification resources for environmental sequence tags.

    Directory of Open Access Journals (Sweden)

    Anders Lanzén

    Full Text Available Sequencing of taxonomic or phylogenetic markers is becoming a fast and efficient method for studying environmental microbial communities. This has resulted in a steadily growing collection of marker sequences, most notably of the small-subunit (SSU ribosomal RNA gene, and an increased understanding of microbial phylogeny, diversity and community composition patterns. However, to utilize these large datasets together with new sequencing technologies, a reliable and flexible system for taxonomic classification is critical. We developed CREST (Classification Resources for Environmental Sequence Tags, a set of resources and tools for generating and utilizing custom taxonomies and reference datasets for classification of environmental sequences. CREST uses an alignment-based classification method with the lowest common ancestor algorithm. It also uses explicit rank similarity criteria to reduce false positives and identify novel taxa. We implemented this method in a web server, a command line tool and the graphical user interfaced program MEGAN. Further, we provide the SSU rRNA reference database and taxonomy SilvaMod, derived from the publicly available SILVA SSURef, for classification of sequences from bacteria, archaea and eukaryotes. Using cross-validation and environmental datasets, we compared the performance of CREST and SilvaMod to the RDP Classifier. We also utilized Greengenes as a reference database, both with CREST and the RDP Classifier. These analyses indicate that CREST performs better than alignment-free methods with higher recall rate (sensitivity as well as precision, and with the ability to accurately identify most sequences from novel taxa. Classification using SilvaMod performed better than with Greengenes, particularly when applied to environmental sequences. CREST is freely available under a GNU General Public License (v3 from http://apps.cbu.uib.no/crest and http://lcaclassifier.googlecode.com.

  16. OP-1 compared with iliac crest autograft in instrumented posterolateral fusion a randomized, multicenter non-inferiority trial

    NARCIS (Netherlands)

    Delawi, Diyar; Jacobs, Wilco; Van Susante, Job L C; Rillardon, Ludovic; Prestamburgo, Domenico; Specchia, Nicola; Gay, Emmanuel; Verschoor, Nico; Garcia-Fernandez, Carlos; Guerado, Enrique; Van Ufford, Henriette Quarles; Kruyt, Moyo C.; Dhert, Wouter J A; Cumhur Oner, F.

    2016-01-01

    Background: Spinal fusion with the use of autograft is a commonly performed procedure. However, harvesting of bone from the iliac crest is associated with complications. Bone morphogenetic proteins (BMPs) are extensively used as alternatives, often without sufficient evidence of safety and efficacy.

  17. Degradation processes and the methods of securing wall crests

    Directory of Open Access Journals (Sweden)

    Maciej Trochonowicz

    2017-12-01

    Full Text Available The protection of historical ruins requires solution of doctrinal and technical problems. Technical problems concern above all preservation of walls, which are exposed to the influence of atmospheric factors. The problem that needs to be solved in any historic ruin is securing of wall crests. Form of protection of the wall crests depends on many factors, mainly technical features of the wall and architectural and conservatory vision. The following article presents three aspects important for protection of wall crests. Firstly, analysis of features of the wall as a structure, secondly the characteristics of destructive agents, thirdly forms of protection of wall crests. In the summary of the following article, advantages and disadvantages of each method of preservation of the wall crests were presented.

  18. Development of teeth in chick embryos after mouse neural crest transplantations

    OpenAIRE

    Mitsiadis, Thimios A.; Chéraud, Yvonnick; Sharpe, Paul; Fontaine-Pérus, Josiane

    2003-01-01

    Teeth were lost in birds 70–80 million years ago. Current thinking holds that it is the avian cranial neural crest-derived mesenchyme that has lost odontogenic capacity, whereas the oral epithelium retains the signaling properties required to induce odontogenesis. To investigate the odontogenic capacity of ectomesenchyme, we have used neural tube transplantations from mice to chick embryos to replace the chick neural crest cell populations with mouse neural crest cells. The mouse/chick ...

  19. The neural crest migrating into the 21st century

    Science.gov (United States)

    Bronner, Marianne E.; Simões-Costa, Marcos

    2016-01-01

    From the initial discovery of the neural crest over 150 years ago to the seminal studies of Le Douarin and colleagues in the latter part of the 20th century, understanding of the neural crest has moved from the descriptive to the experimental. Now, in the 21st century, neural crest research has migrated into the genomic age. Here we reflect upon the major advances in neural crest biology and the open questions that will continue to make research on this incredible vertebrate cell type an important subject in developmental biology for the century to come. PMID:26970616

  20. Crest syndrome

    International Nuclear Information System (INIS)

    Koch, B.; Roedl, W.

    1988-01-01

    If a patient has peri- and intra-articular calcinosis, as well as acro-osteolysis and esophageal hypomotility, and rheumatic symptoms, Crest syndrome should be considered as a manifestation of progressive systemic sclerosis. In connection with relevant symptoms on the skin and visceral involvement, radiological studies offer the possibility of classifying progressive systemic sclerosis more accurately. (orig.) [de

  1. Insights into neural crest development from studies of avian embryos

    OpenAIRE

    Gandhi, Shashank; Bronner, Marianne E.

    2018-01-01

    The neural crest is a multipotent and highly migratory cell type that contributes to many of the defining features of vertebrates, including the skeleton of the head and most of the peripheral nervous system. 150 years after the discovery of the neural crest, avian embryos remain one of the most important model organisms for studying neural crest development. In this review, we describe aspects of neural crest induction, migration and axial level differences, highlighting what is known about ...

  2. Flow structure in front of the broad-crested weir

    Directory of Open Access Journals (Sweden)

    Zachoval Zbyněk

    2015-01-01

    Full Text Available The paper deals with research focused on description of flow structure in front of broad-crested weir. Based on experimental measurement, the flow structure in front of the weir (the recirculation zone of flow and tornado vortices and flow structure on the weir crest has been described. The determined flow character has been simulated using numerical model and based on comparing results the suitable model of turbulence has been recommended.

  3. A Comparative Study of Growth Patterns in Crested Langurs and Vervet Monkeys

    Directory of Open Access Journals (Sweden)

    Debra R. Bolter

    2011-01-01

    Full Text Available The physical growth patterns of crested langurs and vervet monkeys are investigated for several unilinear dimensions. Long bone lengths, trunk height, foot length, epiphyseal fusion of the long bones and the pelvis, and cranial capacity are compared through six dental growth stages in male Trachypithecus cristatus (crested langurs and Cercopithecus aethiops (vervet monkeys. Results show that the body elements of crested langurs mature differently than those of vervets. In some dimensions, langurs and vervets grow comparably, in others vervets attain adult values in advance of crested langurs, and in one feature the langurs are accelerated. Several factors may explain this difference, including phylogeny, diet, ecology, and locomotion. This study proposes that locomotor requirements affect differences in somatic growth between the species.

  4. Lessons learned from the EU project T-CREST

    DEFF Research Database (Denmark)

    Schoeberl, Martin

    2016-01-01

    A three year EU project, such a T-CREST, with partners from all over Europe and with backgrounds from different domains is a challenging endeavor. Successful execution of such a project depends on more factors than simply performing excellent research. Within the three-year project T-CREST eight...... partners from academia and industry developed and evaluated a time-predictable multi-core processor with an accompanying compiler and a worst-case execution time analysis tool. The tight cooperation of the partners and the shared vision of the need of new computer architectures for future real-time systems...... enabled the successful completion of the T-CREST project. The T-CREST platform is now available, with most components in open source, to be used for future real-time systems and as a platform for further research....

  5. Neural crest stem cell population in craniomaxillofacial development and tissue repair

    Directory of Open Access Journals (Sweden)

    M La Noce

    2014-10-01

    Full Text Available Neural crest cells, delaminating from the neural tube during migration, undergo an epithelial-mesenchymal transition and differentiate into several cell types strongly reinforcing the mesoderm of the craniofacial body area – giving rise to bone, cartilage and other tissues and cells of this human body area. Recent studies on craniomaxillofacial neural crest-derived cells have provided evidence for the tremendous plasticity of these cells. Actually, neural crest cells can respond and adapt to the environment in which they migrate and the cranial mesoderm plays an important role toward patterning the identity of the migrating neural crest cells. In our experience, neural crest-derived stem cells, such as dental pulp stem cells, can actively proliferate, repair bone and give rise to other tissues and cytotypes, including blood vessels, smooth muscle, adipocytes and melanocytes, highlighting that their use in tissue engineering is successful. In this review, we provide an overview of the main pathways involved in neural crest formation, delamination, migration and differentiation; and, in particular, we concentrate our attention on the translatability of the latest scientific progress. Here we try to suggest new ideas and strategies that are needed to fully develop the clinical use of these cells. This effort should involve both researchers/clinicians and improvements in good manufacturing practice procedures. It is important to address studies towards clinical application or take into consideration that studies must have an effective therapeutic prospect for humans. New approaches and ideas must be concentrated also toward stem cell recruitment and activation within the human body, overcoming the classical grafting.

  6. Xenopus reduced folate carrier regulates neural crest development epigenetically.

    Directory of Open Access Journals (Sweden)

    Jiejing Li

    Full Text Available Folic acid deficiency during pregnancy causes birth neurocristopathic malformations resulting from aberrant development of neural crest cells. The Reduced folate carrier (RFC is a membrane-bound receptor for facilitating transfer of reduced folate into the cells. RFC knockout mice are embryonic lethal and develop multiple malformations, including neurocristopathies. Here we show that XRFC is specifically expressed in neural crest tissues in Xenopus embryos and knockdown of XRFC by specific morpholino results in severe neurocristopathies. Inhibition of RFC blocked the expression of a series of neural crest marker genes while overexpression of RFC or injection of 5-methyltetrahydrofolate expanded the neural crest territories. In animal cap assays, knockdown of RFC dramatically reduced the mono- and trimethyl-Histone3-K4 levels and co-injection of the lysine methyltransferase hMLL1 largely rescued the XRFC morpholino phenotype. Our data revealed that the RFC mediated folate metabolic pathway likely potentiates neural crest gene expression through epigenetic modifications.

  7. Ontogeny in the tube-crested dinosaur Parasaurolophus (Hadrosauridae and heterochrony in hadrosaurids

    Directory of Open Access Journals (Sweden)

    Andrew A. Farke

    2013-10-01

    Full Text Available The tube-crested hadrosaurid dinosaur Parasaurolophus is remarkable for its unusual cranial ornamentation, but little is known about its growth and development, particularly relative to well-documented ontogenetic series for lambeosaurin hadrosaurids (such as Corythosaurus, Lambeosaurus, and Hypacrosaurus. The skull and skeleton of a juvenile Parasaurolophus from the late Campanian-aged (∼75.5 Ma Kaiparowits Formation of southern Utah, USA, represents the smallest and most complete specimen yet described for this taxon. The individual was approximately 2.5 m in body length (∼25% maximum adult body length at death, with a skull measuring 246 mm long and a femur 329 mm long. A histological section of the tibia shows well-vascularized, woven and parallel-fibered primary cortical bone typical of juvenile ornithopods. The histological section revealed no lines of arrested growth or annuli, suggesting the animal may have still been in its first year at the time of death. Impressions of the upper rhamphotheca are preserved in association with the skull, showing that the soft tissue component for the beak extended for some distance beyond the limits of the oral margin of the premaxilla. In marked contrast with the lengthy tube-like crest in adult Parasaurolophus, the crest of the juvenile specimen is low and hemicircular in profile, with an open premaxilla-nasal fontanelle. Unlike juvenile lambeosaurins, the nasal passages occupy nearly the entirety of the crest in juvenile Parasaurolophus. Furthermore, Parasaurolophus initiated development of the crest at less than 25% maximum skull size, contrasting with 50% of maximum skull size in hadrosaurs such as Corythosaurus. This early development may correspond with the larger and more derived form of the crest in Parasaurolophus, as well as the close relationship between the crest and the respiratory system. In general, ornithischian dinosaurs formed bony cranial ornamentation at a relatively younger age

  8. Hydraulic evaluation of the Crest Wing wave energy converter

    Energy Technology Data Exchange (ETDEWEB)

    Kofoed, J.P.; Antonishen, M.

    2008-09-15

    The Crest Wing Wave Energy Converter is currently being developed by Henning Pilgaard, of WaveEnergyFyn, Denmark. It is meant to act like a carpet on the water, conforming to the shape of each wave and using that movement to generate power. The thought of making a WEC that acts like a carpet on top of the waves is not new; ongoing or past projects such as the Pelamis and Cockerel Raft were designed with this thought in mind. The real difference with the Crest Wing is that it has skirt drafts, that extend down into the water and create suction; this increases the effective mass of the WEC while minimizing the material use. Special attention was given to the design of the first and last floaters as they are meant to act as a smooth transition between wave and machine. Their purpose is to make sure that no air gets under the two middle floaters so that suction is not broken and the device continues to function well. In summary the Crest Wing functions and is able to produce power with a good overall efficiency. The configuration with relative reference PTO (Power Take Off) is superior. It has not been proven that the idea of mounting skirts on the floaters is leading to a better performance. Thus, the study leads to the conclusion that the idea of making a simple hinged raft type device is good, and it is likely that the construction cost for a device of this type can be kept down. However, the study also leaves the chance that some limited draft of skirts in combination with inlet/outlet devices, could prove beneficial. In case of further testing on this device, an effort should be made to design and construct a more easily and accurately controlled PTO model in the test setup. This could greatly improve the quality of the output of such tests. (ln)

  9. The CREST reactive-burn model for explosives

    Directory of Open Access Journals (Sweden)

    Maheswaran M-A.

    2011-01-01

    Full Text Available CREST is an innovative reactive-burn model that has been developed at AWE for simulating shock initiation and detonation propagation behaviour in explosives. The model has a different basis from other reactive-burn models in that its reaction rate is independent of local flow variables behind the shock wave e.g. pressure and temperature. The foundation for CREST, based on a detailed analysis of data from particle-velocity gauge experiments, is that the reaction rate depends only on the local shock strength and the time since the shock passed. Since a measure of shock strength is the entropy of the non-reacted explosive, which remains constant behind a shock, CREST uses an entropy-dependent reaction rate. This paper will provide an overview of the CREST model and its predictive capability. In particular, it will be shown that the model can predict a wide range of experimental phenomena for both shock initiation (e.g. the effects of porosity and initial temperature on sustained-shock and thin-flyer initiation and detonation propagation (e.g. the diameter effect curve and detonation failure cones using a single set of coefficients.

  10. Anosmin-1 is essential for neural crest and cranial placodes formation in Xenopus.

    Science.gov (United States)

    Bae, Chang-Joon; Hong, Chang-Soo; Saint-Jeannet, Jean-Pierre

    2018-01-15

    During embryogenesis vertebrates develop a complex craniofacial skeleton associated with sensory organs. These structures are primarily derived from two embryonic cell populations the neural crest and cranial placodes, respectively. Neural crest cells and cranial placodes are specified through the integrated action of several families of signaling molecules, and the subsequent activation of a complex network of transcription factors. Here we describe the expression and function of Anosmin-1 (Anos1), an extracellular matrix protein, during neural crest and cranial placodes development in Xenopus laevis. Anos1 was identified as a target of Pax3 and Zic1, two transcription factors necessary and sufficient to generate neural crest and cranial placodes. Anos1 is expressed in cranial neural crest progenitors at early neurula stage and in cranial placode derivatives later in development. We show that Anos1 function is required for neural crest and sensory organs development in Xenopus, consistent with the defects observed in Kallmann syndrome patients carrying a mutation in ANOS1. These findings indicate that anos1 has a conserved function in the development of craniofacial structures, and indicate that anos1-depleted Xenopus embryos represent a useful model to analyze the pathogenesis of Kallmann syndrome. Copyright © 2017. Published by Elsevier Inc.

  11. Design Guidelines for Low Crested Structures

    DEFF Research Database (Denmark)

    Burcharth, H. F.; Lamberti, Alberto

    2004-01-01

    1998-2002. The Guidelines comprise engineering aspects related to morphological impact and structure stability, biological aspects related to ecological impact, and socio-economical aspects related to the implementation of LCS-schemes. The guidelines are limited to submerged and regularly overtopped......The paper presents an overview of the design guidelines for low crested structures (LCS's) to be applied in coastal protection schemes. The design guidelines are formulated as a part of the research project: Environmental Design of Low Crested Coastal Defence Structures (DELOS) within the EC 5FP...

  12. Robo signaling regulates the production of cranial neural crest cells.

    Science.gov (United States)

    Li, Yan; Zhang, Xiao-Tan; Wang, Xiao-Yu; Wang, Guang; Chuai, Manli; Münsterberg, Andrea; Yang, Xuesong

    2017-12-01

    Slit/Robo signaling plays an important role in the guidance of developing neurons in developing embryos. However, it remains obscure whether and how Slit/Robo signaling is involved in the production of cranial neural crest cells. In this study, we examined Robo1 deficient mice to reveal developmental defects of mouse cranial frontal and parietal bones, which are derivatives of cranial neural crest cells. Therefore, we determined the production of HNK1 + cranial neural crest cells in early chick embryo development after knock-down (KD) of Robo1 expression. Detection of markers for pre-migratory and migratory neural crest cells, PAX7 and AP-2α, showed that production of both was affected by Robo1 KD. In addition, we found that the transcription factor slug is responsible for the aberrant delamination/EMT of cranial neural crest cells induced by Robo1 KD, which also led to elevated expression of E- and N-Cadherin. N-Cadherin expression was enhanced when blocking FGF signaling with dominant-negative FGFR1 in half of the neural tube. Taken together, we show that Slit/Robo signaling influences the delamination/EMT of cranial neural crest cells, which is required for cranial bone development. Copyright © 2017. Published by Elsevier Inc.

  13. Overflow Characteristic of Cylindrical Shape Crest Weirs Over Horizontal Bed

    Directory of Open Access Journals (Sweden)

    Emad4 AbdulGabbar

    2013-05-01

    Full Text Available The most common types of weirs are the broad-crested weir, the sharp-crested weir, the circular crested weir and the ogee crested weir. Advantages of the cylindrical weir shape include the stable overflow pattern, the ease to pass floating debris, the simplicity of design compared to ogee crest design and the associated lower costs. In present study, it was investigated the overflow characteristics of circular weirs in laboratory for various cylinder radii of three sizes (11.4, 9.0, 6.3 cm, and the models fixed on the channel bed vertically to the direction of flow. The result shows that the increase in the ratio of head to weir radius ratio (Hw/R value causes an increase in discharge coefficient (Cd value for the same height of weir. It was observed that the cylinder size (i.e. radius of cylindrical weir (R has an effect on the (Cd. The flow magnification factor (qw/qs increases with an increase in (Hw/R value and values of (qw/qs were always higher than one for all values of (Hw/R, this means that weirs of cylindrical shape performed better than those of sharp crest for any value of weir radius tested in this study.

  14. Creative Copper Crests

    Science.gov (United States)

    Knab, Thomas

    2011-01-01

    In this article, the author discusses how to create an art activity that would link the computer-created business cards of fourth-grade students with an upcoming school-wide medieval event. Creating family crests from copper foil would be a great connection, since they, like business cards, are an individual's way to identify themselves to others.…

  15. Numerical simulation of lowest-order short-crested wave instabilities

    DEFF Research Database (Denmark)

    Fuhrman, David R.; Madsen, Per A.; Bingham, Harry

    2006-01-01

    instabilities. These correctly lead to well-known (nearly symmetric) recurrence cycles below a previously established breaking threshold steepness, and to an asymmetric evolution (characterized by a permanent transfer of energy to the lower side-band) above this threshold, with dissipation from a smoothing...... that the unstable evolution of these initially three-dimensional waves leads to an asymmetric evolution, even for weakly nonlinear cases presumably well below breaking. This is characterized by an energy transfer to the lower side-band, which is also accompanied by a similar transfer to more distant upper side......-bands. At larger steepness, the evolution leads to a permanent downshift of both the mean and peak frequencies, driven in part by dissipation, effectively breaking the quasi-recurrence cycle. A single case involving a class Ib short-crested wave instability at relatively large steepness is also considered, which...

  16. Stability of Cubipod Armoured Roundheads in Short Crested Waves

    DEFF Research Database (Denmark)

    Burcharth, Hans F.; Andersen, Thomas Lykke; Medina, Josep R.

    2011-01-01

    The paper presents a comparison of the stability of concrete cube armour and Cubipod armour in a breakwater roundhead with slope 1:1.5, exposed to both 2-D (long-crested) and 3-D (short-crested) waves. The model tests were performed at the Hydraulics and Coastal Engineering Laboratory at Aalborg...... University, Denmark. The model tests showed that Cubipod armour is more stable than cube armour when exposed to longer waves (steepness approx. 0.025) and has equal stability to cubes in shorter waves. The Cubipod armour layer contained due to its high porosity approximately 6-17% less concrete than the cube...

  17. Neural crest does not contribute to the neck and shoulder in the axolotl (Ambystoma mexicanum).

    Science.gov (United States)

    Epperlein, Hans-Henning; Khattak, Shahryar; Knapp, Dunja; Tanaka, Elly M; Malashichev, Yegor B

    2012-01-01

    A major step during the evolution of tetrapods was their transition from water to land. This process involved the reduction or complete loss of the dermal bones that made up connections to the skull and a concomitant enlargement of the endochondral shoulder girdle. In the mouse the latter is derived from three separate embryonic sources: lateral plate mesoderm, somites, and neural crest. The neural crest was suggested to sustain the muscle attachments. How this complex composition of the endochondral shoulder girdle arose during evolution and whether it is shared by all tetrapods is unknown. Salamanders that lack dermal bone within their shoulder girdle were of special interest for a possible contribution of the neural crest to the endochondral elements and muscle attachment sites, and we therefore studied them in this context. We grafted neural crest from GFP+ fluorescent transgenic axolotl (Ambystoma mexicanum) donor embryos into white (d/d) axolotl hosts and followed the presence of neural crest cells within the cartilage of the shoulder girdle and the connective tissue of muscle attachment sites of the neck-shoulder region. Strikingly, neural crest cells did not contribute to any part of the endochondral shoulder girdle or to the connective tissue at muscle attachment sites in axolotl. Our results in axolotl suggest that neural crest does not serve a general function in vertebrate shoulder muscle attachment sites as predicted by the "muscle scaffold theory," and that it is not necessary to maintain connectivity of the endochondral shoulder girdle to the skull. Our data support the possibility that the contribution of the neural crest to the endochondral shoulder girdle, which is observed in the mouse, arose de novo in mammals as a developmental basis for their skeletal synapomorphies. This further supports the hypothesis of an increased neural crest diversification during vertebrate evolution.

  18. Neural crest does not contribute to the neck and shoulder in the axolotl (Ambystoma mexicanum.

    Directory of Open Access Journals (Sweden)

    Hans-Henning Epperlein

    Full Text Available BACKGROUND: A major step during the evolution of tetrapods was their transition from water to land. This process involved the reduction or complete loss of the dermal bones that made up connections to the skull and a concomitant enlargement of the endochondral shoulder girdle. In the mouse the latter is derived from three separate embryonic sources: lateral plate mesoderm, somites, and neural crest. The neural crest was suggested to sustain the muscle attachments. How this complex composition of the endochondral shoulder girdle arose during evolution and whether it is shared by all tetrapods is unknown. Salamanders that lack dermal bone within their shoulder girdle were of special interest for a possible contribution of the neural crest to the endochondral elements and muscle attachment sites, and we therefore studied them in this context. RESULTS: We grafted neural crest from GFP+ fluorescent transgenic axolotl (Ambystoma mexicanum donor embryos into white (d/d axolotl hosts and followed the presence of neural crest cells within the cartilage of the shoulder girdle and the connective tissue of muscle attachment sites of the neck-shoulder region. Strikingly, neural crest cells did not contribute to any part of the endochondral shoulder girdle or to the connective tissue at muscle attachment sites in axolotl. CONCLUSIONS: Our results in axolotl suggest that neural crest does not serve a general function in vertebrate shoulder muscle attachment sites as predicted by the "muscle scaffold theory," and that it is not necessary to maintain connectivity of the endochondral shoulder girdle to the skull. Our data support the possibility that the contribution of the neural crest to the endochondral shoulder girdle, which is observed in the mouse, arose de novo in mammals as a developmental basis for their skeletal synapomorphies. This further supports the hypothesis of an increased neural crest diversification during vertebrate evolution.

  19. Short-crested waves in deep water: a numerical investigation of recent laboratory experiments

    DEFF Research Database (Denmark)

    Fuhrman, David R.; Madsen, Per A.

    2006-01-01

    A numerical study of quasi-steady, doubly-periodic monochromatic short-crested wave patterns in deep water is conducted using a high-order Boussinesq-type model. Simulations using linear wavemaker conditions in the nonlinear model are initially used to approximate conditions from recent laboratory...... experiments. The computed patterns share many features with those observed in wavetanks, including bending (both frontwards and backwards) of the wave crests, dipping at the crest centerlines, and a pronounced long modulation in the direction of propagation. A new and simple explanation for these features...

  20. Adipose stromal cells contain phenotypically distinct adipogenic progenitors derived from neural crest.

    Directory of Open Access Journals (Sweden)

    Yoshihiro Sowa

    Full Text Available Recent studies have shown that adipose-derived stromal/stem cells (ASCs contain phenotypically and functionally heterogeneous subpopulations of cells, but their developmental origin and their relative differentiation potential remain elusive. In the present study, we aimed at investigating how and to what extent the neural crest contributes to ASCs using Cre-loxP-mediated fate mapping. ASCs harvested from subcutaneous fat depots of either adult P0-Cre/or Wnt1-Cre/Floxed-reporter mice contained a few neural crest-derived ASCs (NCDASCs. This subpopulation of cells was successfully expanded in vitro under standard culture conditions and their growth rate was comparable to non-neural crest derivatives. Although NCDASCs were positive for several mesenchymal stem cell markers as non-neural crest derivatives, they exhibited a unique bipolar or multipolar morphology with higher expression of markers for both neural crest progenitors (p75NTR, Nestin, and Sox2 and preadipocytes (CD24, CD34, S100, Pref-1, GATA2, and C/EBP-delta. NCDASCs were able to differentiate into adipocytes with high efficiency but their osteogenic and chondrogenic potential was markedly attenuated, indicating their commitment to adipogenesis. In vivo, a very small proportion of adipocytes were originated from the neural crest. In addition, p75NTR-positive neural crest-derived cells were identified along the vessels within the subcutaneous adipose tissue, but they were negative for mural and endothelial markers. These results demonstrate that ASCs contain neural crest-derived adipocyte-restricted progenitors whose phenotype is distinct from that of non-neural crest derivatives.

  1. Establishing neural crest identity: a gene regulatory recipe

    Science.gov (United States)

    Simões-Costa, Marcos; Bronner, Marianne E.

    2015-01-01

    The neural crest is a stem/progenitor cell population that contributes to a wide variety of derivatives, including sensory and autonomic ganglia, cartilage and bone of the face and pigment cells of the skin. Unique to vertebrate embryos, it has served as an excellent model system for the study of cell behavior and identity owing to its multipotency, motility and ability to form a broad array of cell types. Neural crest development is thought to be controlled by a suite of transcriptional and epigenetic inputs arranged hierarchically in a gene regulatory network. Here, we examine neural crest development from a gene regulatory perspective and discuss how the underlying genetic circuitry results in the features that define this unique cell population. PMID:25564621

  2. The 'Unicorn' dinosaur that wasn't: a new reconstruction of the crest of Tsintaosaurus and the early evolution of the lambeosaurine crest and rostrum.

    Directory of Open Access Journals (Sweden)

    Albert Prieto-Márquez

    Full Text Available The lambeosaurine Tsintaosaurus spinorhinus has traditionally been reconstructed with an elevated, hollow, spike-like crest composed entirely of the nasal bones, although this has been disputed. Here, we provide a new reconstruction of the skull of this species based on reexamination and reinterpretation of the morphology and articular relationships of the type and Paratype skulls and a fragmentary crest. We confirm the presence of a supracranial crest composed of the elevated nasal bones, but also including the premaxillae. We hypothesize that the crest is a tall, lobate, hollow structure that projects dorsally and slightly caudally a distance greater than the height of the skull along the quadrate. In our reconstruction, the nasal passage passes through the crest, but enters the skull rostral to the tubular process of the nasals, not through it. Tsintaosaurus spinorhinus is rediagnosed on the basis of a suite of cranial autapomorphies including a circumnarial fossa subdivided into three accessory fossae, prefrontal with ascending rostral process and lateral flange, nasals fused sagittally to form elongate tubular process that rises dorsally from skull roof, each nasal being expanded rostrocaudally into a rhomboid distal process, and medial processes of premaxillae at the summit of the cranial crest inserted between rhomboid processes of nasals. Tsintaosaurus spinorhinus lacks characters that are present in more derived lambeosaurines (parasaurolophins and lambeosaurins, such as rotation of the caudal margin of the crest to an acute angle with the skull roof, lateral processes of the nasals that enclose part of the intracranial cavity and participate in the formation of the walls of the common median chamber, and a smooth narial fossa lacking ridges and accessory fossae. We hypothesize that ancestrally the rostrum of lambeosaurines may have been more similar to that in Saurolophinae, and became subsequently reduced in complexity during

  3. The 'Unicorn' dinosaur that wasn't: a new reconstruction of the crest of Tsintaosaurus and the early evolution of the lambeosaurine crest and rostrum.

    Science.gov (United States)

    Prieto-Márquez, Albert; Wagner, Jonathan R

    2013-01-01

    The lambeosaurine Tsintaosaurus spinorhinus has traditionally been reconstructed with an elevated, hollow, spike-like crest composed entirely of the nasal bones, although this has been disputed. Here, we provide a new reconstruction of the skull of this species based on reexamination and reinterpretation of the morphology and articular relationships of the type and Paratype skulls and a fragmentary crest. We confirm the presence of a supracranial crest composed of the elevated nasal bones, but also including the premaxillae. We hypothesize that the crest is a tall, lobate, hollow structure that projects dorsally and slightly caudally a distance greater than the height of the skull along the quadrate. In our reconstruction, the nasal passage passes through the crest, but enters the skull rostral to the tubular process of the nasals, not through it. Tsintaosaurus spinorhinus is rediagnosed on the basis of a suite of cranial autapomorphies including a circumnarial fossa subdivided into three accessory fossae, prefrontal with ascending rostral process and lateral flange, nasals fused sagittally to form elongate tubular process that rises dorsally from skull roof, each nasal being expanded rostrocaudally into a rhomboid distal process, and medial processes of premaxillae at the summit of the cranial crest inserted between rhomboid processes of nasals. Tsintaosaurus spinorhinus lacks characters that are present in more derived lambeosaurines (parasaurolophins and lambeosaurins), such as rotation of the caudal margin of the crest to an acute angle with the skull roof, lateral processes of the nasals that enclose part of the intracranial cavity and participate in the formation of the walls of the common median chamber, and a smooth narial fossa lacking ridges and accessory fossae. We hypothesize that ancestrally the rostrum of lambeosaurines may have been more similar to that in Saurolophinae, and became subsequently reduced in complexity during evolution of the group.

  4. Convergent Evolution of Head Crests in Two Domesticated Columbids Is Associated with Different Missense Mutations in EphB2

    Science.gov (United States)

    Vickrey, Anna I.; Domyan, Eric T.; Horvath, Martin P.; Shapiro, Michael D.

    2015-01-01

    Head crests are important display structures in wild bird species and are also common in domesticated lineages. Many breeds of domestic rock pigeon (Columba livia) have crests of reversed occipital feathers, and this recessive trait is associated with a nonsynonymous coding mutation in the intracellular kinase domain of EphB2 (Ephrin receptor B2). The domestic ringneck dove (Streptopelia risoria) also has a recessive crested morph with reversed occipital feathers, and interspecific crosses between crested doves and pigeons produce crested offspring, suggesting a similar genetic basis for this trait in both species. We therefore investigated EphB2 as a candidate for the head crest phenotype of ringneck doves and identified a nonsynonymous coding mutation in the intracellular kinase domain that is significantly associated with the crested morph. This mutation is over 100 amino acid positions away from the crest mutation found in rock pigeons, yet both mutations are predicted to negatively affect the function of ATP-binding pocket. Furthermore, bacterial toxicity assays suggest that “crest” mutations in both species severely impact kinase activity. We conclude that head crests are associated with different mutations in the same functional domain of the same gene in two different columbid species, thereby representing striking evolutionary convergence in morphology and molecules. PMID:26104009

  5. Hydraulic model tests of an innovative dike crest design

    NARCIS (Netherlands)

    Verhagen, H.J.; Kortenhaus, A.; Bollinger, K.; Dassayanake, D.

    2007-01-01

    Report on laboratory tests on a crest drainage dike; investigation if a channel in the crest of the dike is able to decrease the amount of overtopping over the dike. Chapter 2 provides details about findings from previous studies and the relevance of those findings to this research project.

  6. Modelling collective cell migration of neural crest.

    Science.gov (United States)

    Szabó, András; Mayor, Roberto

    2016-10-01

    Collective cell migration has emerged in the recent decade as an important phenomenon in cell and developmental biology and can be defined as the coordinated and cooperative movement of groups of cells. Most studies concentrate on tightly connected epithelial tissues, even though collective migration does not require a constant physical contact. Movement of mesenchymal cells is more independent, making their emergent collective behaviour less intuitive and therefore lending importance to computational modelling. Here we focus on such modelling efforts that aim to understand the collective migration of neural crest cells, a mesenchymal embryonic population that migrates large distances as a group during early vertebrate development. By comparing different models of neural crest migration, we emphasize the similarity and complementary nature of these approaches and suggest a future direction for the field. The principles derived from neural crest modelling could aid understanding the collective migration of other mesenchymal cell types. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Adenocarcinoma of the third portion of the duodenum in a man with CREST syndrome

    Directory of Open Access Journals (Sweden)

    Fragulidis Georgios

    2008-10-01

    Full Text Available Abstract Background CREST (Calcinosis, Raynaud's phenomenon, Esophageal dysmotility, Sclerodactyly and Telangiectasias syndrome has been rarely associated with other malignancies (lung, esophagus.This is the first report of a primary adenocarcinoma of the third portion of the duodenum in a patient with CREST syndrome. Case presentation A 54-year-old male patient with CREST syndrome presented with colicky postprandial pain of the upper abdomen, diminished food uptake and a 6-Kg-body weight loss during the previous 2 months. An ulcerative lesion in the third portion of the duodenum was revealed during duodenoscopy, with a diagnosis of adenocarcinoma on biopsy specimen histology. The patient underwent a partial pancreatoduodenectomy. No adjuvant therapy was instituted and follow-up is negative for local recurrence or metastases 21 months postoperatively. Conclusion CREST syndrome has been associated with colon cancer, gastric polyps, familial adenomatous polyposis (FAP syndrome and Crohn's disease; however, this is the first report of a primary adenocarcinoma of the duodenum in a patient with CREST syndrome. However, any etiologic relationship remains to be further investigated.

  8. The ‘Unicorn’ Dinosaur That Wasn’t: A New Reconstruction of the Crest of Tsintaosaurus and the Early Evolution of the Lambeosaurine Crest and Rostrum

    Science.gov (United States)

    Prieto-Márquez, Albert; Wagner, Jonathan R.

    2013-01-01

    The lambeosaurine Tsintaosaurus spinorhinus has traditionally been reconstructed with an elevated, hollow, spike-like crest composed entirely of the nasal bones, although this has been disputed. Here, we provide a new reconstruction of the skull of this species based on reexamination and reinterpretation of the morphology and articular relationships of the type and Paratype skulls and a fragmentary crest. We confirm the presence of a supracranial crest composed of the elevated nasal bones, but also including the premaxillae. We hypothesize that the crest is a tall, lobate, hollow structure that projects dorsally and slightly caudally a distance greater than the height of the skull along the quadrate. In our reconstruction, the nasal passage passes through the crest, but enters the skull rostral to the tubular process of the nasals, not through it. Tsintaosaurus spinorhinus is rediagnosed on the basis of a suite of cranial autapomorphies including a circumnarial fossa subdivided into three accessory fossae, prefrontal with ascending rostral process and lateral flange, nasals fused sagittally to form elongate tubular process that rises dorsally from skull roof, each nasal being expanded rostrocaudally into a rhomboid distal process, and medial processes of premaxillae at the summit of the cranial crest inserted between rhomboid processes of nasals. Tsintaosaurus spinorhinus lacks characters that are present in more derived lambeosaurines (parasaurolophins and lambeosaurins), such as rotation of the caudal margin of the crest to an acute angle with the skull roof, lateral processes of the nasals that enclose part of the intracranial cavity and participate in the formation of the walls of the common median chamber, and a smooth narial fossa lacking ridges and accessory fossae. We hypothesize that ancestrally the rostrum of lambeosaurines may have been more similar to that in Saurolophinae, and became subsequently reduced in complexity during evolution of the group

  9. A new fossil dolphin Dilophodelphis fordycei provides insight into the evolution of supraorbital crests in Platanistoidea (Mammalia, Cetacea)

    Science.gov (United States)

    Boersma, Alexandra T.; McCurry, Matthew R.; Pyenson, Nicholas D.

    2017-05-01

    Many odontocete groups have developed enlarged facial crests, although these crests differ in topography, composition and function. The most elaborate crests occur in the South Asian river dolphin (Platanista gangetica), in which they rise dorsally as delicate, pneumatized wings anterior of the facial bones. Their position wrapping around the melon suggests their involvement in sound propagation for echolocation. To better understand the origin of crests in this lineage, we examined facial crests among fossil and living Platanistoidea, including a new taxon, Dilophodelphis fordycei, nov. gen. and sp., described herein, from the Early Miocene Astoria Formation of Oregon, USA. We measured the physical extent and thickness of platanistoid crests, categorized their relative position and used computed tomography scans to examine their internal morphology and relative bone density. Integrating these traits in a phylogenetic context, we determined that the onset of crest elaboration or enlargement and the evolution of crest pneumatization among the platanistoids were separate events, with crest enlargement beginning in the Oligocene. However, we find no evidence for pneumatization until possibly the Early Miocene, although certainly by the Middle Miocene. Such an evolutionary context, including data from the fossil record, should inform modelling efforts that seek to understand the diversity of sound generation morphology in Odontoceti.

  10. File list: InP.PSC.05.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.PSC.05.AllAg.hESC_derived_neural_crests hg19 Input control Pluripotent stem cell hESC derived neural... crests SRX1091573,SRX059369,SRX059361 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.PSC.05.AllAg.hESC_derived_neural_crests.bed ...

  11. File list: InP.PSC.50.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.PSC.50.AllAg.hESC_derived_neural_crests hg19 Input control Pluripotent stem cell hESC derived neural... crests SRX1091573,SRX059369,SRX059361 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.PSC.50.AllAg.hESC_derived_neural_crests.bed ...

  12. Flow characteristics at trapezoidal broad-crested side weir

    Directory of Open Access Journals (Sweden)

    Říha Jaromír

    2015-06-01

    Full Text Available Broad-crested side weirs have been the subject of numerous hydraulic studies; however, the flow field at the weir crest and in front of the weir in the approach channel still has not been fully described. Also, the discharge coefficient of broad-crested side weirs, whether slightly inclined towards the stream or lateral, still has yet to be clearly determined. Experimental research was carried out to describe the flow characteristics at low Froude numbers in the approach flow channel for various combinations of in- and overflow discharges. Three side weir types with different oblique angles were studied. Their flow characteristics and discharge coefficients were analyzed and assessed based on the results obtained from extensive measurements performed on a hydraulic model. The empirical relation between the angle of side weir obliqueness, Froude numbers in the up- and downstream channels, and the coefficient of obliqueness was derived.

  13. Role of cranial neural crest cells in visceral arch muscle positioning and morphogenesis in the Mexican axolotl, Ambystoma mexicanum.

    Science.gov (United States)

    Ericsson, Rolf; Cerny, Robert; Falck, Pierre; Olsson, Lennart

    2004-10-01

    The role of cranial neural crest cells in the formation of visceral arch musculature was investigated in the Mexican axolotl, Ambystoma mexicanum. DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine, perchlorate) labeling and green fluorescent protein (GFP) mRNA injections combined with unilateral transplantations of neural folds showed that neural crest cells contribute to the connective tissues but not the myofibers of developing visceral arch muscles in the mandibular, hyoid, and branchial arches. Extirpations of individual cranial neural crest streams demonstrated that neural crest cells are necessary for correct morphogenesis of visceral arch muscles. These do, however, initially develop in their proper positions also in the absence of cranial neural crest. Visceral arch muscles forming in the absence of neural crest cells start to differentiate at their origins but fail to extend toward their insertions and may have a frayed appearance. Our data indicate that visceral arch muscle positioning is controlled by factors that do not have a neural crest origin. We suggest that the cranial neural crest-derived connective tissues provide directional guidance important for the proper extension of the cranial muscles and the subsequent attachment to the insertion on the correct cartilage. In a comparative context, our data from the Mexican axolotl support the view that the cranial neural crest plays a fundamental role in the development of not only the skeleton of the vertebrate head but also in the morphogenesis of the cranial muscles and that this might be a primitive feature of cranial development in vertebrates. 2004 Wiley-Liss, Inc.

  14. Diversification of crested wheatgrass stands in Utah

    Science.gov (United States)

    April Hulet

    2009-01-01

    Agropyron cristatum [L.] Gaertner (crested wheatgrass) continues to be seeded on burned wildlands. Effective control methods need to be developed to convert these seedings to more diverse native plant communities. This research was designed to determine effective ways to control A. cristatum and establish native species while...

  15. Can FDG-PET/CT replace blind bone marrow biopsy of the posterior iliac crest in Ewing sarcoma?

    International Nuclear Information System (INIS)

    Kasalak, Oemer; Glaudemans, Andor W.J.M.; Overbosch, Jelle; Kwee, Thomas C.; Jutte, Paul C.

    2018-01-01

    To determine and compare the value of 18 F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT) to blind bone marrow biopsy (BMB) of the posterior iliac crest in detecting metastatic bone marrow involvement in newly diagnosed Ewing sarcoma. This retrospective study included 20 patients with newly diagnosed Ewing sarcoma who underwent pretreatment FDG-PET/CT and a total of 38 blind BMBs (two unilateral and 18 bilateral) of the posterior iliac crest. FDG-PET/CT scans were evaluated for bone marrow involvement, both in the posterior iliac crest and other sites, and compared to blind BMB results. FDG-PET/CT was positive for bone marrow involvement in 7/38 posterior iliac crests, whereas BMB was positive in 5/38 posterior iliac crests. FDG-PET/CT and BMB results in the posterior iliac crest agreed in 36/38 cases (94.7%, 95% confidence interval [CI]: 82.7-98.5%). On a patient level, FDG-PET/CT was positive for bone marrow involvement in 4/20 patients, whereas BMB of the posterior iliac crest was positive in 3/20 patients. On a patient level, FDG-PET/CT and BMB results agreed in 19/20 patients (95.0%, 95% CI: 76.4-99.1%). The only discrepancies between FDG-PET/CT and BMB were observed in two BMBs of one patient. Both BMBs in this patient were negative, whereas FDG-PET/CT indicated bilateral posterior iliac crest involvement and also extensive bone marrow involvement elsewhere. FDG-PET/CT appears to be a valuable method for metastatic bone marrow assessment in newly diagnosed Ewing sarcoma. The routine use of blind BMB of the posterior iliac crest should be reconsidered when FDG-PET/CT is available. (orig.)

  16. Can FDG-PET/CT replace blind bone marrow biopsy of the posterior iliac crest in Ewing sarcoma?

    Energy Technology Data Exchange (ETDEWEB)

    Kasalak, Oemer; Glaudemans, Andor W.J.M.; Overbosch, Jelle; Kwee, Thomas C. [University of Groningen, Department of Radiology, Nuclear Medicine and Molecular Imaging, University Medical Center Groningen (Netherlands); Jutte, Paul C. [University of Groningen, Department of Orthopedics, University Medical Center Groningen (Netherlands)

    2018-03-15

    To determine and compare the value of {sup 18}F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT) to blind bone marrow biopsy (BMB) of the posterior iliac crest in detecting metastatic bone marrow involvement in newly diagnosed Ewing sarcoma. This retrospective study included 20 patients with newly diagnosed Ewing sarcoma who underwent pretreatment FDG-PET/CT and a total of 38 blind BMBs (two unilateral and 18 bilateral) of the posterior iliac crest. FDG-PET/CT scans were evaluated for bone marrow involvement, both in the posterior iliac crest and other sites, and compared to blind BMB results. FDG-PET/CT was positive for bone marrow involvement in 7/38 posterior iliac crests, whereas BMB was positive in 5/38 posterior iliac crests. FDG-PET/CT and BMB results in the posterior iliac crest agreed in 36/38 cases (94.7%, 95% confidence interval [CI]: 82.7-98.5%). On a patient level, FDG-PET/CT was positive for bone marrow involvement in 4/20 patients, whereas BMB of the posterior iliac crest was positive in 3/20 patients. On a patient level, FDG-PET/CT and BMB results agreed in 19/20 patients (95.0%, 95% CI: 76.4-99.1%). The only discrepancies between FDG-PET/CT and BMB were observed in two BMBs of one patient. Both BMBs in this patient were negative, whereas FDG-PET/CT indicated bilateral posterior iliac crest involvement and also extensive bone marrow involvement elsewhere. FDG-PET/CT appears to be a valuable method for metastatic bone marrow assessment in newly diagnosed Ewing sarcoma. The routine use of blind BMB of the posterior iliac crest should be reconsidered when FDG-PET/CT is available. (orig.)

  17. A comparative evaluation of the in vitro penetration performance of the improved Crest complete toothbrush versus the Current Crest complete toothbrush, the Colgate Precision toothbrush and the Oral-B P40 toothbrush.

    Science.gov (United States)

    Volpenhein, D W; Handel, S E; Hughes, T J; Wild, J

    1996-01-01

    Removal of plaque and debris from interproximal surfaces during toothbrushing has generally been difficult to achieve, in large part because traditional flat-bristled toothbrushes do not offer good interproximal penetration. As a result, a number of varying bristle designs have been developed, with the rippled-design brush shown to be particularly effective at removing interproximal plaque. Recently, an existing brush, the original Crest Complete, was modified to offer a more deeply rippled version. This study evaluated the interproximal penetration of four bristle designs: rippled pattern (original Crest Complete), deeper rippled pattern (improved Crest Complete), multi-level (Colgate Precision), and flat-tufted (Oral-B P40). The study used a previously reported in vitro model for determining interproximal penetration of manual toothbrushes (J Clin Dent 5:27-33, 1994). In order to effectively mimic the in-use characteristics of toothbrushing, this model is based on analysis of videotaped consumer brushing habits, tooth morphology, and in vivo plaque tenacity characteristics and uses the three most predominantly used brushing techniques (circular, up-and-down, and back-and-forth, with the brush held at both 45 and 90 degrees to the tooth surface). In addition, the model's brush stroke length, brush force, and brush speed are likewise based on analysis of consumer brushing patterns. The results of the study indicate that the new Crest Complete with deeper rippled bristles provided significantly superior (p Colgate Precision and Oral-B brushes overall and for three of the four brush strokes tested. In addition, the new Crest Complete was found to provide significantly superior interproximal penetration to the original Crest Complete overall and in circular and up-and-down strokes, and the original Crest Complete provided superior overall interproximal penetration to the Colgate and Oral-B brushes.

  18. Animal models for studying neural crest development: is the mouse different?

    Science.gov (United States)

    Barriga, Elias H; Trainor, Paul A; Bronner, Marianne; Mayor, Roberto

    2015-05-01

    The neural crest is a uniquely vertebrate cell type and has been well studied in a number of model systems. Zebrafish, Xenopus and chick embryos largely show consistent requirements for specific genes in early steps of neural crest development. By contrast, knockouts of homologous genes in the mouse often do not exhibit comparable early neural crest phenotypes. In this Spotlight article, we discuss these species-specific differences, suggest possible explanations for the divergent phenotypes in mouse and urge the community to consider these issues and the need for further research in complementary systems. © 2015. Published by The Company of Biologists Ltd.

  19. Amphioxus and lamprey AP-2 genes: implications for neural crest evolution and migration patterns

    Science.gov (United States)

    Meulemans, Daniel; Bronner-Fraser, Marianne

    2002-01-01

    The neural crest is a uniquely vertebrate cell type present in the most basal vertebrates, but not in cephalochordates. We have studied differences in regulation of the neural crest marker AP-2 across two evolutionary transitions: invertebrate to vertebrate, and agnathan to gnathostome. Isolation and comparison of amphioxus, lamprey and axolotl AP-2 reveals its extensive expansion in the vertebrate dorsal neural tube and pharyngeal arches, implying co-option of AP-2 genes by neural crest cells early in vertebrate evolution. Expression in non-neural ectoderm is a conserved feature in amphioxus and vertebrates, suggesting an ancient role for AP-2 genes in this tissue. There is also common expression in subsets of ventrolateral neurons in the anterior neural tube, consistent with a primitive role in brain development. Comparison of AP-2 expression in axolotl and lamprey suggests an elaboration of cranial neural crest patterning in gnathostomes. However, migration of AP-2-expressing neural crest cells medial to the pharyngeal arch mesoderm appears to be a primitive feature retained in all vertebrates. Because AP-2 has essential roles in cranial neural crest differentiation and proliferation, the co-option of AP-2 by neural crest cells in the vertebrate lineage was a potentially crucial event in vertebrate evolution.

  20. Effects of epidermal growth factor on neural crest cells in tissue culture

    International Nuclear Information System (INIS)

    Erickson, C.A.; Turley, E.A.

    1987-01-01

    Epidermal growth factor (EGF) stimulates the release of hyaluronic acid (HA) and chondroitin sulfate proteoglycan (CSPG) from quail trunk neural crest cultures in a dose-dependent fashion. It also promotes the expression of cell-associated heparan sulfate proteoglycan (HSPG) as detected by immunofluorescence and immunoprecipitation of the 3 H-labeled proteoglycan. Furthermore, EGF stimulates [ 3 H]thymidine incorporation into total cell DNA. These results raise the possibility that EGF or an analogous growth factor is involved in regulation of neural crest cell morphogenesis

  1. Degradation processes and the methods of securing wall crests

    OpenAIRE

    Maciej Trochonowicz; Bogusław Szmygin

    2017-01-01

    The protection of historical ruins requires solution of doctrinal and technical problems. Technical problems concern above all preservation of walls, which are exposed to the influence of atmospheric factors. The problem that needs to be solved in any historic ruin is securing of wall crests. Form of protection of the wall crests depends on many factors, mainly technical features of the wall and architectural and conservatory vision. The following article presents three aspects important for ...

  2. Aebp2 as an epigenetic regulator for neural crest cells.

    Directory of Open Access Journals (Sweden)

    Hana Kim

    Full Text Available Aebp2 is a potential targeting protein for the mammalian Polycomb Repression Complex 2 (PRC2. We generated a mutant mouse line disrupting the transcription of Aebp2 to investigate its in vivo roles. Aebp2-mutant homozygotes were embryonic lethal while heterozygotes survived to adulthood with fertility. In developing mouse embryos, Aebp2 is expressed mainly within cells of neural crest origin. In addition, many heterozygotes display a set of phenotypes, enlarged colon and hypopigmentation, similar to those observed in human patients with Hirschsprung's disease and Waardenburg syndrome. These phenotypes are usually caused by the absence of the neural crest-derived ganglia in hindguts and melanocytes. ChIP analyses demonstrated that the majority of the genes involved in the migration and development process of neural crest cells are downstream target genes of AEBP2 and PRC2. Furthermore, expression analyses confirmed that some of these genes are indeed affected in the Aebp2 heterozygotes. Taken together, these results suggest that Aebp2 may regulate the migration and development of the neural crest cells through the PRC2-mediated epigenetic mechanism.

  3. ADAM10 is essential for cranial neural crest-derived maxillofacial bone development

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Yu, E-mail: tanyu2048@163.com; Fu, Runqing, E-mail: furunqing@sjtu.edu.cn; Liu, Jiaqiang, E-mail: liujqmj@163.com; Wu, Yong, E-mail: wyonger@gmail.com; Wang, Bo, E-mail: wb228@126.com; Jiang, Ning, E-mail: 179639060@qq.com; Nie, Ping, E-mail: nieping1011@sina.com; Cao, Haifeng, E-mail: 0412chf@163.com; Yang, Zhi, E-mail: wcums1981@163.com; Fang, Bing, E-mail: fangbing@sjtu.edu.cn

    2016-07-08

    Growth disorders of the craniofacial bones may lead to craniofacial deformities. The majority of maxillofacial bones are derived from cranial neural crest cells via intramembranous bone formation. Any interruption of the craniofacial skeleton development process might lead to craniofacial malformation. A disintegrin and metalloprotease (ADAM)10 plays an essential role in organ development and tissue integrity in different organs. However, little is known about its function in craniofacial bone formation. Therefore, we investigated the role of ADAM10 in the developing craniofacial skeleton, particularly during typical mandibular bone development. First, we showed that ADAM10 was expressed in a specific area of the craniofacial bone and that the expression pattern dynamically changed during normal mouse craniofacial development. Then, we crossed wnt1-cre transgenic mice with adam10-flox mice to generate ADAM10 conditional knockout mice. The stereomicroscopic, radiographic, and von Kossa staining results showed that conditional knockout of ADAM10 in cranial neural crest cells led to embryonic death, craniofacial dysmorphia and bone defects. Furthermore, we demonstrated that impaired mineralization could be triggered by decreased osteoblast differentiation, increased cell death. Overall, these findings show that ADAM10 plays an essential role in craniofacial bone development. -- Highlights: •We firstly reported that ADAM10 was essentially involved in maxillofacial bone development. •ADAM10 cKO mice present craniofacial dysmorphia and bone defects. •Impaired osteoblast differentiation,proliferation and apoptosis underlie the bone deformity.

  4. ADAM10 is essential for cranial neural crest-derived maxillofacial bone development

    International Nuclear Information System (INIS)

    Tan, Yu; Fu, Runqing; Liu, Jiaqiang; Wu, Yong; Wang, Bo; Jiang, Ning; Nie, Ping; Cao, Haifeng; Yang, Zhi; Fang, Bing

    2016-01-01

    Growth disorders of the craniofacial bones may lead to craniofacial deformities. The majority of maxillofacial bones are derived from cranial neural crest cells via intramembranous bone formation. Any interruption of the craniofacial skeleton development process might lead to craniofacial malformation. A disintegrin and metalloprotease (ADAM)10 plays an essential role in organ development and tissue integrity in different organs. However, little is known about its function in craniofacial bone formation. Therefore, we investigated the role of ADAM10 in the developing craniofacial skeleton, particularly during typical mandibular bone development. First, we showed that ADAM10 was expressed in a specific area of the craniofacial bone and that the expression pattern dynamically changed during normal mouse craniofacial development. Then, we crossed wnt1-cre transgenic mice with adam10-flox mice to generate ADAM10 conditional knockout mice. The stereomicroscopic, radiographic, and von Kossa staining results showed that conditional knockout of ADAM10 in cranial neural crest cells led to embryonic death, craniofacial dysmorphia and bone defects. Furthermore, we demonstrated that impaired mineralization could be triggered by decreased osteoblast differentiation, increased cell death. Overall, these findings show that ADAM10 plays an essential role in craniofacial bone development. -- Highlights: •We firstly reported that ADAM10 was essentially involved in maxillofacial bone development. •ADAM10 cKO mice present craniofacial dysmorphia and bone defects. •Impaired osteoblast differentiation,proliferation and apoptosis underlie the bone deformity.

  5. A study on ionospheric scintillation near the EIA crest in relation to equatorial electrodynamics

    Science.gov (United States)

    Chatterjee, S.; Chakraborty, S. K.; Veenadhari, B.; Banola, S.

    2014-02-01

    Equatorial electrojet (EEJ) data, which are considered as a proxy index of equatorial electric field, are analyzed in conjunction with equatorial ionosonde, total electron content (TEC) and scintillation data near the equatorial ionization anomaly (EIA) crest for the equinoctial months of high solar activity years (2011-2012) to identify any precursor index of postsunset evolution of equatorial electron density irregularities and subsequent occurrence of scintillation near the northern EIA crest. Only geomagnetically quiet and normal electrojet days are considered. The diurnal profiles of EEJ on the scintillation days exhibit a secondary enhancement in the afternoon to presunset hours following diurnal peaks. A series of electrodynamical processes conducive for generation of irregularities emerge following secondary enhancement of EEJ. Latitudinal profile of TEC exhibits resurgence in EIA structure around the postsunset period. Diurnal TEC profile near the EIA crest resembles postsunset secondary enhancement on the days with afternoon enhancement in EEJ. Occurrence of equatorial spread F and postsunset scintillation near the EIA crest seems to follow the secondary enhancement events in EEJ. Both the magnitude and duration of enhanced EEJ are found to be important for postsunset intensification of EIA structure and subsequent occurrence of equatorial irregularities. A critical value combining the two may be considered an important precursor for postsunset occurrence of scintillation near the EIA crest. The results are validated using archived data for the years 1989-1990 and explained in terms of modulation effects of enhanced equatorial fountain.

  6. Jaccoud's arthropathy and pulmonary fibrosis in CREST syndrome

    International Nuclear Information System (INIS)

    Spinel B, Nestor; Montenegro, Pablo; Rondon Federico; Restrepo, Jose F; Iglesias G, Antonio

    2010-01-01

    We report a case of a 48 years old patient with diagnosis of incomplete CREST syndrome (variant limited systemic sclerosis) in who we documented the presence of Jaccoud's arthropathy of the hands and pulmonary involvement by pulmonary fibrosis type usual interstitial pneumonia, with positivity for rheumatoid factor and anti-cyclic citrullinated peptide antibody.

  7. Retinoic acid temporally orchestrates colonization of the gut by vagal neural crest cells.

    Science.gov (United States)

    Uribe, Rosa A; Hong, Stephanie S; Bronner, Marianne E

    2018-01-01

    The enteric nervous system arises from neural crest cells that migrate as chains into and along the primitive gut, subsequently differentiating into enteric neurons and glia. Little is known about the mechanisms governing neural crest migration en route to and along the gut in vivo. Here, we report that Retinoic Acid (RA) temporally controls zebrafish enteric neural crest cell chain migration. In vivo imaging reveals that RA loss severely compromises the integrity and migration of the chain of neural crest cells during the window of time window when they are moving along the foregut. After loss of RA, enteric progenitors accumulate in the foregut and differentiate into enteric neurons, but subsequently undergo apoptosis resulting in a striking neuronal deficit. Moreover, ectopic expression of the transcription factor meis3 and/or the receptor ret, partially rescues enteric neuron colonization after RA attenuation. Collectively, our findings suggest that retinoic acid plays a critical temporal role in promoting enteric neural crest chain migration and neuronal survival upstream of Meis3 and RET in vivo. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Adrenergic innervation of the developing chick heart: neural crest ablations to produce sympathetically aneural hearts

    International Nuclear Information System (INIS)

    Kirby, M.; Stewart, D.

    1984-01-01

    Ablation of various regions of premigratory trunk neural crest which gives rise to the sympathetic trunks was used to remove sympathetic cardiac innervation. Neuronal uptake of [ 3 H]-norepinephrine was used as an index of neuronal development in the chick atrium. Following ablation of neural crest over somites 10-15 or 15-20, uptake was significantly decreased in the atrium at 16 and 17 days of development. Ablation of neural crest over somites 5-10 and 20-25 caused no decrease in [ 3 H]-norepinephrine uptake. Removal of neural crest over somites 5-25 or 10-20 caused approximately equal depletions of [ 3 H]-norepinephrine uptake in the atrium. Cardiac norepinephrine concentration was significantly depressed following ablation of neural crest over somites 5-25 but not over somites 10-20. Light-microscopic and histofluorescent preparations confirmed the absence of sympathetic trunks in the region of the normal origin of the sympathetic cardiac nerves following neural crest ablation over somites 10-20. The neural tube and dorsal root ganglia were damaged in the area of the neural-crest ablation; however, all of these structures were normal cranial and caudal to the lesioned area. Development of most of the embryos as well as the morphology of all of the hearts was normal following the lesion. These results indicate that it is possible to produce sympathetically aneural hearts by neural-crest ablation; however, sympathetic cardiac nerves account for an insignificant amount of cardiac norepinephrine

  9. Influence and timing of arrival of murine neural crest on pancreatic beta cell development and maturation.

    Science.gov (United States)

    Plank, Jennifer L; Mundell, Nathan A; Frist, Audrey Y; LeGrone, Alison W; Kim, Thomas; Musser, Melissa A; Walter, Teagan J; Labosky, Patricia A

    2011-01-15

    Interactions between cells from the ectoderm and mesoderm influence development of the endodermally-derived pancreas. While much is known about how mesoderm regulates pancreatic development, relatively little is understood about how and when the ectodermally-derived neural crest regulates pancreatic development and specifically, beta cell maturation. A previous study demonstrated that signals from the neural crest regulate beta cell proliferation and ultimately, beta cell mass. Here, we expand on that work to describe timing of neural crest arrival at the developing pancreatic bud and extend our knowledge of the non-cell autonomous role for neural crest derivatives in the process of beta cell maturation. We demonstrated that murine neural crest entered the pancreatic mesenchyme between the 26 and 27 somite stages (approximately 10.0 dpc) and became intermingled with pancreatic progenitors as the epithelium branched into the surrounding mesenchyme. Using a neural crest-specific deletion of the Forkhead transcription factor Foxd3, we ablated neural crest cells that migrate to the pancreatic primordium. Consistent with previous data, in the absence of Foxd3, and therefore the absence of neural crest cells, proliferation of insulin-expressing cells and insulin-positive area are increased. Analysis of endocrine cell gene expression in the absence of neural crest demonstrated that, although the number of insulin-expressing cells was increased, beta cell maturation was significantly impaired. Decreased MafA and Pdx1 expression illustrated the defect in beta cell maturation; we discovered that without neural crest, there was a reduction in the percentage of insulin-positive cells that co-expressed Glut2 and Pdx1 compared to controls. In addition, transmission electron microscopy analyses revealed decreased numbers of characteristic insulin granules and the presence of abnormal granules in insulin-expressing cells from mutant embryos. Together, these data demonstrate that

  10. Constitutively active Notch1 converts cranial neural crest-derived frontonasal mesenchyme to perivascular cells in vivo

    Directory of Open Access Journals (Sweden)

    Sophie R. Miller

    2017-03-01

    Full Text Available Perivascular/mural cells originate from either the mesoderm or the cranial neural crest. Regardless of their origin, Notch signalling is necessary for their formation. Furthermore, in both chicken and mouse, constitutive Notch1 activation (via expression of the Notch1 intracellular domain is sufficient in vivo to convert trunk mesoderm-derived somite cells to perivascular cells, at the expense of skeletal muscle. In experiments originally designed to investigate the effect of premature Notch1 activation on the development of neural crest-derived olfactory ensheathing glial cells (OECs, we used in ovo electroporation to insert a tetracycline-inducible NotchΔE construct (encoding a constitutively active mutant of mouse Notch1 into the genome of chicken cranial neural crest cell precursors, and activated NotchΔE expression by doxycycline injection at embryonic day 4. NotchΔE-targeted cells formed perivascular cells within the frontonasal mesenchyme, and expressed a perivascular marker on the olfactory nerve. Hence, constitutively activating Notch1 is sufficient in vivo to drive not only somite cells, but also neural crest-derived frontonasal mesenchyme and perhaps developing OECs, to a perivascular cell fate. These results also highlight the plasticity of neural crest-derived mesenchyme and glia.

  11. Genotyping-by-sequencing data of 272 crested wheatgrass (Agropyron cristatum genotypes

    Directory of Open Access Journals (Sweden)

    Pingchuan Li

    2017-12-01

    Full Text Available Crested wheatgrass [Agropyron cristatum L. (Gaertn.] is an important cool-season forage grass widely used for early spring grazing. However, the genomic resources for this non-model plant are still lacking. Our goal was to generate the first set of next generation sequencing data using the genotyping-by-sequencing technique. A total of 272 crested wheatgrass plants representing seven breeding lines, five cultivars and five geographically diverse accessions were sequenced with an Illumina MiSeq instrument. These sequence datasets were processed using different bioinformatics tools to generate contigs for diploid and tetraploid plants and SNPs for diploid plants. Together, these genomic resources form a fundamental basis for genomic studies of crested wheatgrass and other wheatgrass species. The raw reads were deposited into Sequence Read Archive (SRA database under NCBI accession SRP115373 (https://www.ncbi.nlm.nih.gov/sra?term=SRP115373 and the supplementary datasets are accessible in Figshare (10.6084/m9.figshare.5345092. Keywords: Crested wheatgrass, Genotyping-by-sequencing, Diploid, Tetraploid, Raw sequence data

  12. Novel structural components of the ventral disc and lateral crest in Giardia intestinalis.

    Directory of Open Access Journals (Sweden)

    Kari D Hagen

    2011-12-01

    Full Text Available Giardia intestinalis is a ubiquitous parasitic protist that is the causative agent of giardiasis, one of the most common protozoan diarrheal diseases in the world. Giardia trophozoites attach to the intestinal epithelium using a specialized and elaborate microtubule structure, the ventral disc. Surrounding the ventral disc is a less characterized putatively contractile structure, the lateral crest, which forms a continuous perimeter seal with the substrate. A better understanding of ventral disc and lateral crest structure, conformational dynamics, and biogenesis is critical for understanding the mechanism of giardial attachment to the host. To determine the components comprising the ventral disc and lateral crest, we used shotgun proteomics to identify proteins in a preparation of isolated ventral discs. Candidate disc-associated proteins, or DAPs, were GFP-tagged using a ligation-independent high-throughput cloning method. Based on disc localization, we identified eighteen novel DAPs, which more than doubles the number of known disc-associated proteins. Ten of the novel DAPs are associated with the lateral crest or outer edge of the disc, and are the first confirmed components of this structure. Using Fluorescence Recovery After Photobleaching (FRAP with representative novel DAP::GFP strains we found that the newly identified DAPs tested did not recover after photobleaching and are therefore structural components of the ventral disc or lateral crest. Functional analyses of the novel DAPs will be central toward understanding the mechanism of ventral disc-mediated attachment and the mechanism of disc biogenesis during cell division. Since attachment of Giardia to the intestine via the ventral disc is essential for pathogenesis, it is possible that some proteins comprising the disc could be potential drug targets if their loss or disruption interfered with disc biogenesis or function, preventing attachment.

  13. Results of operative treatment of avulsion fractures of the iliac crest apophysis in adolescents.

    Science.gov (United States)

    Li, Xigong; Xu, Sanzhong; Lin, Xiangjin; Wang, Quan; Pan, Jun

    2014-04-01

    Avulsion fracture of the iliac crest apophysis is a rare condition that commonly occurs in adolescent athletes. Conservative treatment for this injury can produce excellent functional outcomes. However, the rehabilitation process requires a rather long immobilisation period. This study aimed to evaluate the use of cannulated screws for fixation of avulsion fractures of iliac crest apophysis. Ten patients with avulsion fractures of iliac crest apophysis were treated by open reduction and internal fixation using cannulated screws. The mean age of patients was 14.6 years (range, 13-15 years). The mean intraoperative blood loss was 14.9 ml (range, 10-25 ml). The mean operative time was 40.3 min (range, 33-52 min). The mean follow-up period was 11.2 months (range, 6-20 months). At the 4-week follow-up, all patients returned to previously normal activity without pain and had no evidence of lower extremity muscle weakness. At the final follow-up, all patients resumed their athletic activity without any complications. Open reduction and internal fixation for the treatment of avulsion fracture of iliac crest apophysis can be recommended for patients requiring rapid rehabilitation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Myocardial function and perfusion in the CREST syndrome variant of progressive systemic sclerosis. Exercise radionuclide evaluation and comparison with diffuse scleroderma

    International Nuclear Information System (INIS)

    Follansbee, W.P.; Curtiss, E.I.; Medsger, T.A. Jr.; Owens, G.R.; Steen, V.D.; Rodnan, G.P.

    1984-01-01

    Myocardial function and perfusion were evaluated in 22 patients with progressive systemic sclerosis with the CREST syndrome using exercise and radionuclide techniques, pulmonary function testing, and chest roentgenography. The results were compared with a similar study of 26 patients with progressive systemic sclerosis with diffuse scleroderma. The prevalence of thallium perfusion abnormalities was similar in the groups with CREST syndrome and diffuse scleroderma, (64 percent versus 77 percent), but the defects were significantly smaller in the CREST syndrome (p less than 0.01). Reperfusion thallium defects in the absence of extramural coronary artery disease were seen in 38 percent of patients with diffuse scleroderma. This finding was not seen in any of the patients with the CREST syndrome. In diffuse scleroderma, abnormalities of both right and left ventricular function were related to larger thallium perfusion defects. In the CREST syndrome, abnormalities of left ventricular function were minor, were seen only during exercise, and were unrelated to thallium perfusion defects. Abnormal resting right ventricular function was seen in 36 percent of the patients with the CREST syndrome and was associated with an isolated decrease in diffusing capacity of carbon monoxide. It is concluded that the cardiac manifestations of the CREST syndrome are distinct from those found in diffuse scleroderma. Unlike diffuse scleroderma, abnormalities of left ventricular function in the CREST syndrome are minor and are unrelated to abnormalities of coronary perfusion. Right ventricular dysfunction in the CREST syndrome appears to be primarily related to pulmonary vascular disease

  15. Incisional Colopexy for Treatment of Chronic, Recurrent Colocloacal Prolapse in a Sulphur-Crested Cockatoo (Cacatua galerita)

    NARCIS (Netherlands)

    van Zeeland, Yvonne; Schoemaker, Nico; van Sluijs, Freek

    2014-01-01

    Objective To report a surgical technique for treatment of chronic, recurrent cloacal prolapse in a sulphur-crested cockatoo (Cacatua galerita). Study Design Clinical report Animals Sulphur-crested cockatoo (n = 1) Methods The bird was admitted with a 2-year history of periodic lethargy, decreased

  16. Regeneration of neural crest derivatives in the Xenopus tadpole tail

    Directory of Open Access Journals (Sweden)

    Slack Jonathan MW

    2007-05-01

    Full Text Available Abstract Background After amputation of the Xenopus tadpole tail, a functionally competent new tail is regenerated. It contains spinal cord, notochord and muscle, each of which has previously been shown to derive from the corresponding tissue in the stump. The regeneration of the neural crest derivatives has not previously been examined and is described in this paper. Results Labelling of the spinal cord by electroporation, or by orthotopic grafting of transgenic tissue expressing GFP, shows that no cells emigrate from the spinal cord in the course of regeneration. There is very limited regeneration of the spinal ganglia, but new neurons as well as fibre tracts do appear in the regenerated spinal cord and the regenerated tail also contains abundant peripheral innervation. The regenerated tail contains a normal density of melanophores. Cell labelling experiments show that melanophores do not arise from the spinal cord during regeneration, nor from the mesenchymal tissues of the skin, but they do arise by activation and proliferation of pre-existing melanophore precursors. If tails are prepared lacking melanophores, then the regenerates also lack them. Conclusion On regeneration there is no induction of a new neural crest similar to that seen in embryonic development. However there is some regeneration of neural crest derivatives. Abundant melanophores are regenerated from unpigmented precursors, and, although spinal ganglia are not regenerated, sufficient sensory systems are produced to enable essential functions to continue.

  17. TeV electron measurement with CREST experiment

    Science.gov (United States)

    Park, Nahee; Anderson, T.; Bower, C.; Coutu, S.; Gennaro, J.; Geske, M.; Muller, D.; Musser, J.; Nutter, S.

    CREST, the Cosmic Ray Electron Synchrotron Telescope is a balloon-borne experiment de-signed to measure the spectrum of multi-TeV electrons by the detection of the x-ray synchrotron photons generated in the magnetic field of the Earth. Electrons in the TeV range are expected to reflect the properties of local sources because fluxes from remote locations are suppressed by radiative losses during propagation. Since CREST needs to intersect only a portion of the kilometers-long trail of photons generated by the high-energy electron, the method yields a larger effective area than the physical size of the detector, boosting detection areas. The in-strument is composed of an array of 1024 BaF2 crystals and a set of scintillating veto counters. A long duration balloon flight in Antarctica is currently planned for the 2010-11 season.

  18. MR imaging findings of medial tibial crest friction

    International Nuclear Information System (INIS)

    Klontzas, Michail E.; Akoumianakis, Ioannis D.; Vagios, Ilias; Karantanas, Apostolos H.

    2013-01-01

    Objective: Medial tibial condyle bone marrow edema (BME), associated with soft tissue edema (STe) surrounding the medial collateral ligament, was incidentally observed in MRI examinations of young and athletic individuals. The aim of the present study was to 1. Prospectively investigate the association between these findings and coexistence of localized pain, and 2. Explore the possible contribution of the tibial morphology to its pathogenesis. Methods: The medial tibial condyle crest was evaluated in 632 knee MRI examinations. The angle and depth were measured by two separate evaluators. The presence of STe and BME was recorded. A third evaluator blindly assessed the presence of pain at this site. Results: BME associated with STe was found in 24 patients (with no history of previous trauma, osteoarthritis, tumor or pes anserine bursitis). The mean crest angle was 151.3° (95%CI 147.4–155.3°) compared to 159.4° (95%CI 158.8–160°) in controls (Mann–Whitney test, P < 0.0001). MRI findings were highly predictive of localized pain (sensitivity 92% specificity 99%, Fisher's exact test, P < 0.0001). Conclusion: Friction at the medial tibial condyle crest is a painful syndrome. MRI is a highly specific and sensitive imaging modality for its diagnosis

  19. MR imaging findings of medial tibial crest friction

    Energy Technology Data Exchange (ETDEWEB)

    Klontzas, Michail E., E-mail: miklontzas@gmail.com; Akoumianakis, Ioannis D., E-mail: ioannis.akoumianakis@gmail.com; Vagios, Ilias, E-mail: iliasvagios@gmail.com; Karantanas, Apostolos H., E-mail: akarantanas@gmail.com

    2013-11-01

    Objective: Medial tibial condyle bone marrow edema (BME), associated with soft tissue edema (STe) surrounding the medial collateral ligament, was incidentally observed in MRI examinations of young and athletic individuals. The aim of the present study was to 1. Prospectively investigate the association between these findings and coexistence of localized pain, and 2. Explore the possible contribution of the tibial morphology to its pathogenesis. Methods: The medial tibial condyle crest was evaluated in 632 knee MRI examinations. The angle and depth were measured by two separate evaluators. The presence of STe and BME was recorded. A third evaluator blindly assessed the presence of pain at this site. Results: BME associated with STe was found in 24 patients (with no history of previous trauma, osteoarthritis, tumor or pes anserine bursitis). The mean crest angle was 151.3° (95%CI 147.4–155.3°) compared to 159.4° (95%CI 158.8–160°) in controls (Mann–Whitney test, P < 0.0001). MRI findings were highly predictive of localized pain (sensitivity 92% specificity 99%, Fisher's exact test, P < 0.0001). Conclusion: Friction at the medial tibial condyle crest is a painful syndrome. MRI is a highly specific and sensitive imaging modality for its diagnosis.

  20. A negative modulatory role for rho and rho-associated kinase signaling in delamination of neural crest cells

    Directory of Open Access Journals (Sweden)

    Kalcheim Chaya

    2008-10-01

    Full Text Available Abstract Background Neural crest progenitors arise as epithelial cells and then undergo a process of epithelial to mesenchymal transition that precedes the generation of cellular motility and subsequent migration. We aim at understanding the underlying molecular network. Along this line, possible roles of Rho GTPases that act as molecular switches to control a variety of signal transduction pathways remain virtually unexplored, as are putative interactions between Rho proteins and additional known components of this cascade. Results We investigated the role of Rho/Rock signaling in neural crest delamination. Active RhoA and RhoB are expressed in the membrane of epithelial progenitors and are downregulated upon delamination. In vivo loss-of-function of RhoA or RhoB or of overall Rho signaling by C3 transferase enhanced and/or triggered premature crest delamination yet had no effect on cell specification. Consistently, treatment of explanted neural primordia with membrane-permeable C3 or with the Rock inhibitor Y27632 both accelerated and enhanced crest emigration without affecting cell proliferation. These treatments altered neural crest morphology by reducing stress fibers, focal adhesions and downregulating membrane-bound N-cadherin. Reciprocally, activation of endogenous Rho by lysophosphatidic acid inhibited emigration while enhancing the above. Since delamination is triggered by BMP and requires G1/S transition, we examined their relationship with Rho. Blocking Rho/Rock function rescued crest emigration upon treatment with noggin or with the G1/S inhibitor mimosine. In the latter condition, cells emigrated while arrested at G1. Conversely, BMP4 was unable to rescue cell emigration when endogenous Rho activity was enhanced by lysophosphatidic acid. Conclusion Rho-GTPases, through Rock, act downstream of BMP and of G1/S transition to negatively regulate crest delamination by modifying cytoskeleton assembly and intercellular adhesion.

  1. File list: Pol.PSC.20.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.PSC.20.AllAg.hESC_derived_neural_crests hg19 RNA polymerase Pluripotent stem cell hESC derived neural... crests http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.PSC.20.AllAg.hESC_derived_neural_crests.bed ...

  2. File list: Pol.PSC.05.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.PSC.05.AllAg.hESC_derived_neural_crests hg19 RNA polymerase Pluripotent stem cell hESC derived neural... crests http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.PSC.05.AllAg.hESC_derived_neural_crests.bed ...

  3. File list: Pol.PSC.10.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.PSC.10.AllAg.hESC_derived_neural_crests hg19 RNA polymerase Pluripotent stem cell hESC derived neural... crests http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.PSC.10.AllAg.hESC_derived_neural_crests.bed ...

  4. The detection of great crested newts year round via environmental DNA analysis.

    Science.gov (United States)

    Rees, Helen C; Baker, Claire A; Gardner, David S; Maddison, Ben C; Gough, Kevin C

    2017-07-26

    Analysis of environmental DNA (eDNA) is a method that has been used for the detection of various species within water bodies. The great crested newt (Triturus cristatus) has a short eDNA survey season (mid-April to June). Here we investigate whether this season could be extended into other months using the current methodology as stipulated by Natural England. Here we present data to show that in monthly water samples taken from two ponds (March 2014-February 2015) we were able to detect great crested newt DNA in all months in at least one of the ponds. Similar levels of great crested newt eDNA (i.e. highly positive identification) were detected through the months of March-August, suggesting it may be possible to extend the current survey window. In order to determine how applicable these observations are for ponds throughout the rest of the UK, further work in multiple other ponds over multiple seasons is suggested. Nevertheless, the current work clearly demonstrates, in two ponds, the efficacy and reproducibility of eDNA detection for determining the presence of great crested newts.

  5. Imidacloprid Exposure Suppresses Neural Crest Cells Generation during Early Chick Embryo Development.

    Science.gov (United States)

    Wang, Chao-Jie; Wang, Guang; Wang, Xiao-Yu; Liu, Meng; Chuai, Manli; Lee, Kenneth Ka Ho; He, Xiao-Song; Lu, Da-Xiang; Yang, Xuesong

    2016-06-15

    Imidacloprid is a neonicotinoid pesticide that is widely used in the control pests found on crops and fleas on pets. However, it is still unclear whether imidacloprid exposure could affect early embryo development-despite some studies having been conducted on the gametes. In this study, we demonstrated that imidacloprid exposure could lead to abnormal craniofacial osteogenesis in the developing chick embryo. Cranial neural crest cells (NCCs) are the progenitor cells of the chick cranial skull. We found that the imidacloprid exposure retards the development of gastrulating chick embryos. HNK-1, PAX7, and Ap-2α immunohistological stainings indicated that cranial NCCs generation was inhibited after imidacloprid exposure. Double immunofluorescent staining (Ap-2α and PHIS3 or PAX7 and c-Caspase3) revealed that imidacloprid exposure inhibited both NCC proliferation and apoptosis. In addition, it inhibited NCCs production by repressing Msx1 and BMP4 expression in the developing neural tube and by altering expression of EMT-related adhesion molecules (Cad6B, E-Cadherin, and N-cadherin) in the developing neural crests. We also determined that imidacloprid exposure suppressed cranial NCCs migration and their ability to differentiate. In sum, we have provided experimental evidence that imidacloprid exposure during embryogenesis disrupts NCCs development, which in turn causes defective cranial bone development.

  6. File list: Unc.PSC.20.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.PSC.20.AllAg.hESC_derived_neural_crests hg19 Unclassified Pluripotent stem cell hESC derived neural... crests SRX059366 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.PSC.20.AllAg.hESC_derived_neural_crests.bed ...

  7. File list: Unc.PSC.05.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.PSC.05.AllAg.hESC_derived_neural_crests hg19 Unclassified Pluripotent stem cell hESC derived neural... crests SRX059366 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.PSC.05.AllAg.hESC_derived_neural_crests.bed ...

  8. In vivo impact of Dlx3 conditional inactivation in Neural Crest-Derived Craniofacial Bones

    Science.gov (United States)

    Duverger, Olivier; Isaac, Juliane; Zah, Angela; Hwang, Joonsung; Berdal, Ariane; Lian, Jane B.; Morasso, Maria I.

    2012-01-01

    Mutations in DLX3 in humans lead to defects in craniofacial and appendicular bones, yet the in vivo activity related to Dlx3 function during normal skeletal development have not been fully elucidated. Here we used a conditional knockout approach to analyze the effects of neural crest deletion of Dlx3 on craniofacial bones development. At birth, mutant mice exhibit a normal overall positioning of the skull bones, but a change in the shape of the calvaria was observed. Molecular analysis of the genes affected in the frontal bones and mandibles from these mice identified several bone markers known to affect bone development, with a strong prediction for increased bone formation and mineralization in vivo. Interestingly, while a subset of these genes were similarly affected in frontal bones and mandibles (Sost, Mepe, Bglap, Alp, Ibsp, Agt), several genes, including Lect1 and Calca, were specifically affected in frontal bones. Consistent with these molecular alterations, cells isolated from the frontal bone of mutant mice exhibited increased differentiation and mineralization capacities ex vivo, supporting cell autonomous defects in neural crest cells. However, adult mutant animals exhibited decreased bone mineral density in both mandibles and calvaria, as well as a significant increase in bone porosity. Together, these observations suggest that mature osteoblasts in the adult respond to signals that regulate adult bone mass and remodeling. This study provides new downstream targets for Dlx3 in craniofacial bone, and gives additional evidence of the complex regulation of bone formation and homeostasis in the adult skeleton. PMID:22886599

  9. Synthesis on accumulation of putative neurotransmitters by cultured neural crest cells

    International Nuclear Information System (INIS)

    Maxwell, G.D.; Sietz, P.D.; Rafford, C.E.

    1982-01-01

    The events mediating the differentiation of embryonic neural crest cells into several types of neurons are incompletely understood. In order to probe one aspect of this differentiation, we have examined the capacity of cultured quail trunk neural crest cells to synthesize, from radioactive precursors, and store several putative neurotransmitter compounds. These neural crest cultures develop the capacity to synthesize and accumulate acetylcholine and the catecholamines norepinephrine and dopamine. In contrast, detectable but relatively little synthesis and accumulation of 5-hydroxytryptamine gamma-aminobutyric acid, or octopamine from the appropriate radiolabeled precursors were observed. The capacity for synthesis and accumulation of radiolabeled acetylcholine and catecholamines is very low or absent at 2 days in vitro. Between 3 and 7 days in vitro, there is a marked rise in both catecholamine and acetylcholine accumulation in the cultures. These findings suggest that, under the particular conditions used in these experiments, the development of neurotransmitter biosynthesis in trunk neural crest cells ijs restricted and resembles, at least partially, the pattern observed in vivo. The development of this capacity to synthesize and store radiolabeled acetylcholine and catecholamines from the appropriate radioactive precursors coincides closely with the development of the activities of the synthetic enzymes choline acetyltransferase and dopamine beta-hydroxylase reported by others

  10. Characterization of Pax3 and Sox10 transgenic Xenopus laevis embryos as tools to study neural crest development.

    Science.gov (United States)

    Alkobtawi, Mansour; Ray, Heather; Barriga, Elias H; Moreno, Mauricio; Kerney, Ryan; Monsoro-Burq, Anne-Helene; Saint-Jeannet, Jean-Pierre; Mayor, Roberto

    2018-03-06

    The neural crest is a multipotent population of cells that originates a variety of cell types. Many animal models are used to study neural crest induction, migration and differentiation, with amphibians and birds being the most widely used systems. A major technological advance to study neural crest development in mouse, chick and zebrafish has been the generation of transgenic animals in which neural crest specific enhancers/promoters drive the expression of either fluorescent proteins for use as lineage tracers, or modified genes for use in functional studies. Unfortunately, no such transgenic animals currently exist for the amphibians Xenopus laevis and tropicalis, key model systems for studying neural crest development. Here we describe the generation and characterization of two transgenic Xenopus laevis lines, Pax3-GFP and Sox10-GFP, in which GFP is expressed in the pre-migratory and migratory neural crest, respectively. We show that Pax3-GFP could be a powerful tool to study neural crest induction, whereas Sox10-GFP could be used in the study of neural crest migration in living embryos. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Structural Stability Of Detached Low Crested Breakwaters

    DEFF Research Database (Denmark)

    Burcharth, Hans F.; Kramer, Morten; Lamberti, Alberto

    2006-01-01

    The aim of the paper is to describe hydraulic stability of rock-armoured low-crested structures on the basis of new experimental tests and prototype observations. Rock armour stability results from earlier model tests under non-depth-limited long-crested head-on waves are reviewed. Results from new...... determining armour stone size in shallow water conditions is given together with a rule of thumb for the required stone size in depth-limited design waves. Rock toe stability is discussed on the basis of prototype experience, hard bottom 2-D tests in depth-limited waves and an existing hydraulic stability...... formula. Toe damage predicted by the formula is in agreement with experimental results. In field sites, damage at the toe induced by scour or by sinking is observed and the volume of the berm is often insufficient to avoid regressive erosion of the armour layer. Stone sinking and settlement in selected...

  12. CREST Calcinosis Affecting the Lumbar and Cervical Spine and the Use of Minimally-Invasive Surgery

    OpenAIRE

    Faraj, Kassem; Perez-Cruet, Kristin; Perez-Cruet, Mick

    2017-01-01

    Calcinosis in CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) syndrome can affect the spinal and paraspinal areas. We present the first case to our knowledge where a CREST syndrome patient required surgery for spinal calcinosis in both the cervical and lumbar areas.?A 66-year-old female with a history of CREST syndrome presented with right-sided lower extremity radicular pain. A computed tomography (CT) scan showed bilateral lumbar masses (5...

  13. SOX10-Nano-Lantern Reporter Human iPS Cells; A Versatile Tool for Neural Crest Research.

    Directory of Open Access Journals (Sweden)

    Tomoko Horikiri

    Full Text Available The neural crest is a source to produce multipotent neural crest stem cells that have a potential to differentiate into diverse cell types. The transcription factor SOX10 is expressed through early neural crest progenitors and stem cells in vertebrates. Here we report the generation of SOX10-Nano-lantern (NL reporter human induced pluripotent stem cells (hiPS by using CRISPR/Cas9 systems, that are beneficial to investigate the generation and maintenance of neural crest progenitor cells. SOX10-NL positive cells are produced transiently from hiPS cells by treatment with TGFβ inhibitor SB431542 and GSK3 inhibitor CHIR99021. We found that all SOX10-NL-positive cells expressed an early neural crest marker NGFR, however SOX10-NL-positive cells purified from differentiated hiPS cells progressively attenuate their NL-expression under proliferation. We therefore attempted to maintain SOX10-NL-positive cells with additional signaling on the plane and sphere culture conditions. These SOX10-NL cells provide us to investigate mass culture with neural crest cells for stem cell research.

  14. Augmented Indian hedgehog signaling in cranial neural crest cells leads to craniofacial abnormalities and dysplastic temporomandibular joint in mice.

    Science.gov (United States)

    Yang, Ling; Gu, Shuping; Ye, Wenduo; Song, Yingnan; Chen, YiPing

    2016-04-01

    Extensive studies have pinpointed the crucial role of Indian hedgehog (Ihh) signaling in the development of the appendicular skeleton and the essential function of Ihh in the formation of the temporomandibular joint (TMJ). In this study, we have investigated the effect of augmented Ihh signaling in TMJ development. We took a transgenic gain-of-function approach by overexpressing Ihh in the cranial neural crest (CNC) cells using a conditional Ihh transgenic allele and the Wnt1-Cre allele. We found that Wnt1-Cre-mediated tissue-specific overexpression of Ihh in the CNC lineage caused severe craniofacial abnormalities, including cleft lip/palate, encephalocele, anophthalmos, micrognathia, and defective TMJ development. In the mutant TMJ, the glenoid fossa was completely absent, whereas the condyle and the articular disc appeared relatively normal with slightly delayed chondrocyte differentiation. Our findings thus demonstrate that augmented Ihh signaling is detrimental to craniofacial development, and that finely tuned Ihh signaling is critical for TMJ formation. Our results also provide additional evidence that the development of the condyle and articular disc is independent of the glenoid fossa.

  15. File list: NoD.PSC.10.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.PSC.10.AllAg.hESC_derived_neural_crests hg19 No description Pluripotent stem cell hESC derived neural... crests http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/NoD.PSC.10.AllAg.hESC_derived_neural_crests.bed ...

  16. File list: NoD.PSC.20.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.PSC.20.AllAg.hESC_derived_neural_crests hg19 No description Pluripotent stem cell hESC derived neural... crests http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/NoD.PSC.20.AllAg.hESC_derived_neural_crests.bed ...

  17. Modeling Cerebrovascular Pathophysiology in Amyloid-β Metabolism using Neural-Crest-Derived Smooth Muscle Cells

    Directory of Open Access Journals (Sweden)

    Christine Cheung

    2014-10-01

    Full Text Available Summary: There is growing recognition of cerebrovascular contributions to neurodegenerative diseases. In the walls of cerebral arteries, amyloid-beta (Aβ accumulation is evident in a majority of aged people and patients with cerebral amyloid angiopathy. Here, we leverage human pluripotent stem cells to generate vascular smooth muscle cells (SMCs from neural crest progenitors, recapitulating brain-vasculature-specific attributes of Aβ metabolism. We confirm that the lipoprotein receptor, LRP1, functions in our neural-crest-derived SMCs to mediate Aβ uptake and intracellular lysosomal degradation. Hypoxia significantly compromises the contribution of SMCs to Aβ clearance by suppressing LRP1 expression. This enabled us to develop an assay of Aβ uptake by using the neural crest-derived SMCs with hypoxia as a stress paradigm. We then tested several vascular protective compounds in a high-throughput format, demonstrating the value of stem-cell-based phenotypic screening for novel therapeutics and drug repurposing, aimed at alleviating amyloid burden. : The contribution of blood vessel pathologies to neurodegenerative disorders is relatively neglected, partly due to inadequate human tissues for research. By using human stem cells, Cheung et al. establish a method of generating vascular smooth muscle cells (SMCs from neural crest progenitors, the primary precursors that give rise to brain blood vessels. These stem-cell-derived SMCs display defective amyloid processing under chronic hypoxia, a phenomenon well documented in the cerebral vasculatures of aged people and patients with Alzheimer’s disease.

  18. Quill injury - cause od death of captive indian crested porcupine(Hystrix indica, Kerr, 1792

    Directory of Open Access Journals (Sweden)

    Tanja Švara

    2015-03-01

    Full Text Available Indian crested porcupine (Hystrix indica is a member of the family of Old World porcupines (Hystricidae. Its body is covered with multiple layers of quills, which serve for warning and attack if animal is threatened. However, the literature data on injuries caused by Indian crested porcupine are absent. We describe pathomorphological lesions in an Indian crested porcupine from the Ljubljana Zoo, which died after a fight with a younger male that caused a perforative quill injury of the thoracic wall, followed by septicaemia. Macroscopic, microscopic and bacteriological findings were detailed

  19. Long-throated flumes and broad-crested weirs

    NARCIS (Netherlands)

    Bos, M.G.

    1985-01-01

    Vital for water management are structures that can measure the flow in a wide variety of channels. Chapter 1 introduces the long-throated flume and the broad-crested weir; it explains why this family of structures can meet the boundary conditions and hydraulic demands of most measuring

  20. Nuchal crest avulsion fracture in 2 horses : a cause of headshaking : clinical communication

    Directory of Open Access Journals (Sweden)

    A. Voigt

    2009-05-01

    Full Text Available The medical records of 2 Thoroughbred horses that developed headshaking after blunt trauma to the occipital region are reviewed. The history, signalment, clinical signs, diagnostic methods, diagnosis and treatment were recorded in each case. Both horses displayed headshaking, while one horse repeatedly lifted its upper lip and pawed excessively at the ground. In both horses, diagnostic imaging of the occipital region revealed avulsion fragments of the nuchal crest and a nuchal desmitis in association with hyperfibrinogenaemia. The presence of an avulsion fragment of the nuchal crest with associated nuchal desmitis should be considered in horses presenting with headshaking and may respond favourably to conservative therapy.

  1. A Native Arbuscular Mycorrhizal Fungus, Acaulospora scrobiculata Stimulated Growth of Mongolian Crested Wheatgrass ( Agropyron cristatum (L. Gaertn.

    Directory of Open Access Journals (Sweden)

    Burenjargal Otgonsuren

    2010-12-01

    Full Text Available Agr opyron cristatum (L. Gaertn. (crested wheatgrass is an endemic plant species, which dominates most area of the Mongolian steppe and forest steppe. In the present study, spores of arbuscular mycorrhizal fungi in the rhizosphere soil of crested wheatgrass were isolated with wet- sieving/decanting methods, and the major species was identifi ed as Acaulospora scrobiculata Trappe. For arbuscular-mycorrhizal resynthesis, the spores of A. scrobiculata were propagated with corn pot-culture technique and inoculated onto the roots of crested wheatgrass seedlings. The inoculated crested wheatgrass seedlings exhibited vigor in growth, and examination of the root structure revealed the occurrence of arbuscules and vesicles in the cortical cells. These results demonstrated that A. scrobiculata could effectively form arbuscular mycorrhizas with crested wheatgrass and promote its growth, which can be used to restore Mongolian grassland.

  2. Evolution of neural crest and placodes: amphioxus as a model for the ancestral vertebrate?

    Science.gov (United States)

    Holland, L. Z.; Holland, N. D.

    2001-01-01

    Recent studies of protochordates (ascidian tunicates and amphioxus) have given insights into possible ancestors of 2 of the characteristic features of the vertebrate head: neural crest and placodes. The neural crest probably evolved from cells on either side of the neural plate-epidermis boundary in a protochordate ancestral to the vertebrates. In amphioxus, homologues of several vertebrate neural crest marker genes (BMP2/4, Pax3/7, Msx, Dll and Snail) are expressed at the edges of the neural plate and/or adjacent nonneural ectoderm. Some of these markers are also similarly expressed in tunicates. In protochordates, however, these cells, unlike vertebrate neural crest, neither migrate as individuals through embryonic tissues nor differentiate into a wide spectrum of cell types. Therefore, while the protochordate ancestor of the vertebrates probably had the beginnings of a genetic programme for neural crest formation, this programme was augmented in the earliest vertebrates to attain definitive neural crest. Clear homologues of vertebrate placodes are lacking in protochordates. However, both amphioxus and tunicates have ectodermal sensory cells. In tunicates these are all primary neurons, sending axons to the central nervous system, while in amphioxus, the ectodermal sensory cells include both primary neurons and secondary neurons lacking axons. Comparisons of developmental gene expression suggest that the anterior ectoderm in amphioxus may be homologous to the vertebrate olfactory placode, the only vertebrate placode with primary, not secondary, neurons. Similarly, biochemical, morphological and gene expression data suggest that amphioxus and tunicates also have homologues of the adenohypophysis, one of the few vertebrate structures derived from nonneurogenic placodes. In contrast, the origin of the other vertebrate placodes is very uncertain.

  3. The Neural Border: Induction, Specification and Maturation of the territory that generates Neural Crest cells.

    Science.gov (United States)

    Pla, Patrick; Monsoro-Burq, Anne H

    2018-05-28

    The neural crest is induced at the edge between the neural plate and the nonneural ectoderm, in an area called the neural (plate) border, during gastrulation and neurulation. In recent years, many studies have explored how this domain is patterned, and how the neural crest is induced within this territory, that also participates to the prospective dorsal neural tube, the dorsalmost nonneural ectoderm, as well as placode derivatives in the anterior area. This review highlights the tissue interactions, the cell-cell signaling and the molecular mechanisms involved in this dynamic spatiotemporal patterning, resulting in the induction of the premigratory neural crest. Collectively, these studies allow building a complex neural border and early neural crest gene regulatory network, mostly composed by transcriptional regulations but also, more recently, including novel signaling interactions. Copyright © 2018. Published by Elsevier Inc.

  4. The CREST Simulation Development Process: Training the Next Generation.

    Science.gov (United States)

    Sweet, Robert M

    2017-04-01

    The challenges of training and assessing endourologic skill have driven the development of new training systems. The Center for Research in Education and Simulation Technologies (CREST) has developed a team and a methodology to facilitate this development process. Backwards design principles were applied. A panel of experts first defined desired clinical and educational outcomes. Outcomes were subsequently linked to learning objectives. Gross task deconstruction was performed, and the primary domain was classified as primarily involving decision-making, psychomotor skill, or communication. A more detailed cognitive task analysis was performed to elicit and prioritize relevant anatomy/tissues, metrics, and errors. Reference anatomy was created using a digital anatomist and clinician working off of a clinical data set. Three dimensional printing can facilitate this process. When possible, synthetic or virtual tissue behavior and textures were recreated using data derived from human tissue. Embedded sensors/markers and/or computer-based systems were used to facilitate the collection of objective metrics. A learning Verification and validation occurred throughout the engineering development process. Nine endourology-relevant training systems were created by CREST with this approach. Systems include basic laparoscopic skills (BLUS), vesicourethral anastomosis, pyeloplasty, cystoscopic procedures, stent placement, rigid and flexible ureteroscopy, GreenLight PVP (GL Sim), Percutaneous access with C-arm (CAT), Nephrolithotomy (NLM), and a vascular injury model. Mixed modalities have been used, including "smart" physical models, virtual reality, augmented reality, and video. Substantial validity evidence for training and assessment has been collected on systems. An open source manikin-based modular platform is under development by CREST with the Department of Defense that will unify these and other commercial task trainers through the common physiology engine, learning

  5. Genomic diversity and evolution of the head crest in the rock pigeon.

    Science.gov (United States)

    Shapiro, Michael D; Kronenberg, Zev; Li, Cai; Domyan, Eric T; Pan, Hailin; Campbell, Michael; Tan, Hao; Huff, Chad D; Hu, Haofu; Vickrey, Anna I; Nielsen, Sandra C A; Stringham, Sydney A; Hu, Hao; Willerslev, Eske; Gilbert, M Thomas P; Yandell, Mark; Zhang, Guojie; Wang, Jun

    2013-03-01

    The geographic origins of breeds and the genetic basis of variation within the widely distributed and phenotypically diverse domestic rock pigeon (Columba livia) remain largely unknown. We generated a rock pigeon reference genome and additional genome sequences representing domestic and feral populations. We found evidence for the origins of major breed groups in the Middle East and contributions from a racing breed to North American feral populations. We identified the gene EphB2 as a strong candidate for the derived head crest phenotype shared by numerous breeds, an important trait in mate selection in many avian species. We also found evidence that this trait evolved just once and spread throughout the species, and that the crest originates early in development by the localized molecular reversal of feather bud polarity.

  6. [Comparison of the Latissimus dorsi insertions on the iliac crest in chimpanzee (Pan troglodytes) and in man].

    Science.gov (United States)

    Vacher, C; Ben Hadj Yahia, S; Braun, M; Journeau, P

    2014-03-01

    Comparing to other primates, one of the most important specificities of the human anatomy are consequences of bipedalism. Although bone consequences are well known (lumbar lordosis, horizontal position of the foramen magnum, lengthening of the lower limbs, reduction of the pelvis, specialization of the foot), consequences of our locomotion on the Latissimus dorsi are still unclear. One dissection of a chimpanzee Latissimus dorsi (Pan troglodytes) has been performed and compared to 30 human Latissimus dorsi dissections (10 fresh cadavers and 20 formoled cadavers). In each dissection, the existence of direct muscular insertions on the iliac crest has been investigated and the constitution of the thoracolumbar fascia has been described. In chimpanzee dissection, a muscular direct insertion of the Latissimus dorsi was present on the iliac crest of 9 cm long. The TLF was made of the superficial and the deep fascias of the Latissimus dorsi and the superficial fascia of the erector spinae muscles which was deeper. In man, there was no direct muscular insertion of the Latissimus dorsi in 90 % of cases, the TLF was constituted the same way. This study suggests that the Latissimus dorsi has been separated from the iliac crest in man during the evolution because of the permanent bipedalism and that it stayed inserted on the iliac crest in chimpanzee because of the brachiation. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  7. First report and breeding record of the Chinese Crested Tern Thalasseus bernsteini on the Korean Peninsula

    Directory of Open Access Journals (Sweden)

    Se-Kyu Song

    2017-06-01

    Full Text Available The Chinese Crested Tern Thalasseus bernsteini is a critically endangered species (as designated by the IUCN (International Union for Conservation of Nature and Natural Resources. This report expands the known breeding grounds of these birds eastward. An individual of the Chinese Crested Tern was first observed at an uninhabited island of Jeollanam-do in Korea on April 28, 2016. On May 9, 2016 five Chinese Crested Terns (consisting of 2 breeding pairs and a single bird were observed. Nests from the breeding pairs were found, at a distance of 0.6 m from each other; each pair was observed incubating one egg in the nest. To our knowledge, this is the easternmost record of breeding grounds for the Chinese Crested Tern.

  8. Age-related changes in vertebral and iliac crest 3D bone microstructure-differences and similarities

    DEFF Research Database (Denmark)

    Thomsen, Jesper Skovhus; Jensen, Michael Vinkel; Niklassen, Andreas Steenholt

    2015-01-01

    Summary Age-related changes of vertebra and iliac crest 3D microstructure were investigated, and we showed that they were in general similar. The 95th percentile of vertebral trabecular thickness distribution increased with age for women. Surprisingly, vertebral and iliac crest bone microstructure...... was only weakly correlated (r = 0.38 to 0.75), despite the overall similar age-related changes.Introduction The purposes of the study were to determine the age-related changes in iliac and vertebral bone microstructure for women and men over a large age range and to investigate the relationship between...... the bone microstructure at these skeletal sites.Methods Matched sets of transiliac crest bone biopsies and lumbar vertebral body (L2) specimens from 41 women (19–96 years) and 39 men (23–95 years) were micro-computed tomography (μCT) scanned, and the 3D microstructure was quantified.Results For both women...

  9. Twist1 Controls a Cell-Specification Switch Governing Cell Fate Decisions within the Cardiac Neural Crest

    Science.gov (United States)

    Vincentz, Joshua W.; Firulli, Beth A.; Lin, Andrea; Spicer, Douglas B.; Howard, Marthe J.; Firulli, Anthony B.

    2013-01-01

    Neural crest cells are multipotent progenitor cells that can generate both ectodermal cell types, such as neurons, and mesodermal cell types, such as smooth muscle. The mechanisms controlling this cell fate choice are not known. The basic Helix-loop-Helix (bHLH) transcription factor Twist1 is expressed throughout the migratory and post-migratory cardiac neural crest. Twist1 ablation or mutation of the Twist-box causes differentiation of ectopic neuronal cells, which molecularly resemble sympathetic ganglia, in the cardiac outflow tract. Twist1 interacts with the pro-neural factor Sox10 via its Twist-box domain and binds to the Phox2b promoter to repress transcriptional activity. Mesodermal cardiac neural crest trans-differentiation into ectodermal sympathetic ganglia-like neurons is dependent upon Phox2b function. Ectopic Twist1 expression in neural crest precursors disrupts sympathetic neurogenesis. These data demonstrate that Twist1 functions in post-migratory neural crest cells to repress pro-neural factors and thereby regulate cell fate determination between ectodermal and mesodermal lineages. PMID:23555309

  10. Disproportionately severe calcinosis cutis in an 88-year-old patient with CREST syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Buchowski, J.M.; Ahn, N.U.; Ahn, U.M. [Dept. of Orthopaedic Surgery, Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States); McCarthy, E.F. [Dept. of Orthopaedic Surgery, Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States); Dept. of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Mehta, M.B. [Clinical Associates, Good Samaritan Hospital, Baltimore, MD (United States)

    2001-08-01

    An 88-year-old woman with CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias) presented with hyperglycemia, intravascular depletion, and atrial fibrillation. The patient was found to have unusually severe calcinosis cutis in both legs extending from the knees to the ankles bilaterally, as well as Raynaud's phenomenon, sclerodactyly, and telangiectasias. The patient was normocalcemic and normophosphatemic. Although subcutaneous calcification is often seen with CREST syndrome, this case is unusual in that the area of involvement was much larger than previously described. Furthermore, the amount of calcinosis was disproportionately severe and was the major cause of symptoms and disability compared with the other components of the syndrome. (orig.)

  11. Changes in cholinergic parameters associated with failure of conotruncal septation in embryonic chick hearts after neural crest ablation

    International Nuclear Information System (INIS)

    Kirby, M.L.; Aronstam, R.S.; Buccafusco, J.J.

    1985-01-01

    Cells from the neural crest over occipital somites migrate to the heart, where they give rise to parasympathetic postganglionic neurons as well as ectomesenchymal elements which contribute to conotruncal septation. With a microcautery needle, the neural crest over occipital somites was ablated bilaterally in chicken embryos at an early stage of development. Histological examination on incubation day 15 revealed conotruncal malformations, involving malformation or absence of the conotruncal septum in all embryos. Two peaks of embryo mortality were observed. One peak (incubation days 6-8) occurred at the same time as conotruncal septal closure; the second peak (incubation days 11-13) was concurrent with the onset of functional parasympathetic innervation. A disruption of parasympathetic innervation was indicated by: (1) a decrease in acetylcholinesterase staining, (2) a decrease (27%) in the number of ganglion cells in the conotruncus, (3) decreases in the acetylcholine content of atrium (31%) and ventricle (39%), and (4) a decrease (21%) in muscarinic acetylcholine receptor density on incubation day 15. Radiolabeled ligand-binding studies revealed no change in the affinity of cardiac muscarinic receptors for [ 3 H]methylscopolamine (K/sub D/ . 0.17-0.21 nM). Agonist-binding affinity and sensitivity to guanine nucleotides were similarly unaffected. The reasons for the limited extent of the parasympathetic lesion are unclear, but may involve recruitment of precursor cells from other regions of the neural crest, partial regeneration of the neural crest following surgical removal, or an alteration in the contribution of incoming sympathetic or preganglionic parasympathetic elements. No such plasticity was associated with neural crest contributions to the structural development of the conotruncus. Malformations were observed in all lesioned embryos

  12. Comparison of the breeding biology of sympatric red-tailed Hawks, White-tailed Hawks, and Crested Caracaras in south Texas

    Science.gov (United States)

    Actkinson, M.A.; Kuvlesky, W.P.; Boal, C.W.; Brennan, L.A.; Hernandez, F.

    2009-01-01

    We compared the breeding biology of sympatric nesting Red-tailed Hawks (Buteo jamaicensis), White-tailed Hawks (Buteo albicaudatus), and Crested Caracaras (Caracara cheriway) in south Texas during 2003 and 2004. We monitored 46 breeding attempts by Red-tailed Hawks, 56 by White-tailed Hawks, and 27 by Crested Caracaras. Observed nesting success was similar for Red-tailed Hawks (62%) and Crested Caracaras (61%), but lower for White-tailed Hawks (51%). Daily survival rates (0.99) were the same for all three species. Red-tailed Hawks and White-tailed Hawks both fledged 1.13 young per nesting pair and Crested Caracaras fledged 1.39 young per nesting pair. All three species nested earlier in 2004 than in 2003; in addition, the overall nesting density of these three species almost doubled from 2003 (1.45 pairs/km2) to 2004 (2.71 pairs/km2). Estimated productivity of all three species was within the ranges reported from other studies. Given extensive and progressive habitat alteration in some areas of south Texas, and the limited distributions of White-tailed Hawks and Crested Caracaras, the presence of large ranches managed for free-range cattle production and hunting leases likely provides important habitat and may be key areas for conservation of these two species. ?? 2009 The Raptor Research Foundation, Inc.

  13. The neural crest, a multifaceted structure of the vertebrates.

    Science.gov (United States)

    Dupin, Elisabeth; Le Douarin, Nicole M

    2014-09-01

    In this review, several features of the cells originating from the lateral borders of the primitive neural anlagen, the neural crest (NC) are considered. Among them, their multipotentiality, which together with their migratory properties, leads them to colonize the developing body and to participate in the development of many tissues and organs. The in vitro analysis of the developmental capacities of single NC cells (NCC) showed that they present several analogies with the hematopoietic cells whose differentiation involves the activity of stem cells endowed with different arrays of developmental potentialities. The permanence of such NC stem cells in the adult organism raises the problem of their role at that stage of life. The NC has appeared during evolution in the vertebrate phylum and is absent in their Protocordates ancestors. The major role of the NCC in the development of the vertebrate head points to a critical role for this structure in the remarkable diversification and radiation of this group of animals. © 2014 Wiley Periodicals, Inc.

  14. Phylogenetic patterns and correlation of key structures for jumping: bone crests and cross-sectional areas of muscles in Leptodactylus (Anura, Leptodactylidae).

    Science.gov (United States)

    Ponssa, María Laura; Fratani, Jéssica; Abdala, Virginia

    2018-05-01

    Anurans are characterized by their saltatory mode of locomotion, which is associated with a specific morphology. The coordinated action of the muscles and bones of the pelvic girdle is key to the transmission of the force of the hindlimbs to the axial skeleton during jumping. Two features are critical for optimal locomotory performance: the cross-sectional area of muscle and the bone crest attachment sites. The first character is a proxy of the force exerted by the muscle, whereas the crests are muscle attachments sites related to muscle force. The provisory relationship between these features has previously been identified and bone crest size can be used to infer the magnitude and, therefore, muscle force in fossils records. In this work, we explore the correlation between the cross-sectional area of essential muscles to the jumping mechanism (longissimus dorsi, extensor iliotibialis B, tenuissimus, puboischiofemoralis internus B, coccygeo-sacralis and coccygeo-iliacus) and the bone crests where these muscles are inserted (dorsal tubercle, dorsal crest and urostylar crest) in species of the genus Leptodactylus. This genus, along with other leptodactylids, exhibits a diversity of locomotor modes, including jumping, hopping, swimming and burrowing. We therefore analyzed the morphometric variation in the two features, cross-sectional area and bone crest area, expecting a correlation with different locomotor types. Our results showed: (i) a correlation between the urostylar crest and the cross-sectional area of the related muscles; (ii) that the bone crest surface area of urostyle and ilium and the cross-sectional area of the corresponding muscles can be utilized to infer locomotor faculties in leptodactylid frogs; and (iii) that the evolution of both characters demonstrates a general tendency from lower values in leptodactylid ancestors to higher values in the Leptodactylus genus. The results attest to the importance of the comparison of current ecological and

  15. Histone deacetylase 1 and 2 are essential for murine neural crest proliferation, pharyngeal arch development, and craniofacial morphogenesis.

    Science.gov (United States)

    Milstone, Zachary J; Lawson, Grace; Trivedi, Chinmay M

    2017-12-01

    Craniofacial anomalies involve defective pharyngeal arch development and neural crest function. Copy number variation at 1p35, containing histone deacetylase 1 (Hdac1), or 6q21-22, containing Hdac2, are implicated in patients with craniofacial defects, suggesting an important role in guiding neural crest development. However, the roles of Hdac1 and Hdac2 within neural crest cells remain unknown. The neural crest and its derivatives express both Hdac1 and Hdac2 during early murine development. Ablation of Hdac1 and Hdac2 within murine neural crest progenitor cells cause severe hemorrhage, atrophic pharyngeal arches, defective head morphogenesis, and complete embryonic lethality. Embryos lacking Hdac1 and Hdac2 in the neural crest exhibit decreased proliferation and increased apoptosis in both the neural tube and the first pharyngeal arch. Mechanistically, loss of Hdac1 and Hdac2 upregulates cyclin-dependent kinase inhibitors Cdkn1a, Cdkn1b, Cdkn1c, Cdkn2b, Cdkn2c, and Tp53 within the first pharyngeal arch. Our results show that Hdac1 and Hdac2 function redundantly within the neural crest to regulate proliferation and the development of the pharyngeal arches by means of repression of cyclin-dependent kinase inhibitors. Developmental Dynamics 246:1015-1026, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  16. Krox20 defines a subpopulation of cardiac neural crest cells contributing to arterial valves and bicuspid aortic valve.

    Science.gov (United States)

    Odelin, Gaëlle; Faure, Emilie; Coulpier, Fanny; Di Bonito, Maria; Bajolle, Fanny; Studer, Michèle; Avierinos, Jean-François; Charnay, Patrick; Topilko, Piotr; Zaffran, Stéphane

    2018-01-03

    Although cardiac neural crest cells are required at early stages of arterial valve development, their contribution during valvular leaflet maturation remains poorly understood. Here, we show in mouse that neural crest cells from pre-otic and post-otic regions make distinct contributions to the arterial valve leaflets. Genetic fate-mapping analysis of Krox20-expressing neural crest cells shows a large contribution to the borders and the interleaflet triangles of the arterial valves. Loss of Krox20 function results in hyperplastic aortic valve and partially penetrant bicuspid aortic valve formation. Similar defects are observed in neural crest Krox20 -deficient embryos. Genetic lineage tracing in Krox20 -/- mutant mice shows that endothelial-derived cells are normal, whereas neural crest-derived cells are abnormally increased in number and misplaced in the valve leaflets. In contrast, genetic ablation of Krox20 -expressing cells is not sufficient to cause an aortic valve defect, suggesting that adjacent cells can compensate this depletion. Our findings demonstrate a crucial role for Krox20 in arterial valve development and reveal that an excess of neural crest cells may be associated with bicuspid aortic valve. © 2018. Published by The Company of Biologists Ltd.

  17. Polyurethane resins derived from castor oil (Ricinus communis) for tibial crest deviation in dogs

    International Nuclear Information System (INIS)

    Maria, P.P.; Padilha Filho, J.G.; Canola, J.C.; Castro, M.B.

    2004-01-01

    Medial patellar luxation is one of the most common orthopedic problems in small breeds of dogs and tibial crest deviation is a frequent accompaining anatomical abnormality. For that reason, the purpose of this study was to evaluate the behavior of castor oil derived polyurethane implants when apllied to experimental defects created on the medial side of the proximal tibia of normal puppies. Twelve dogs were randomly divided in 3 groups of 4 animals and were submitted to the same treatment. Histopathological study was performed respectively at 30 (GI), 60 (GII) and 90 (GIII) days post-surgery. Evaluations methods included clinical assessment, radiology, gross and macroscopic study, tomography and statistical analysis. Clinically, there were no signs of implant rejection. Radiology revealed intense periosteal reaction and new bone formation. On gross examination, there was thickening and lateral deviation of the tibial crest and new bone neoformation. On microscopic examination, there was fibrous tissue around the polyurethane, periosteal proliferation on the medial side of the tibia and no bone proliferation towards the implant. Cat scans reveled lateral deviation of the tibial crest in eleven animals, which was statistically significant (p [pt

  18. Expression of cardiac neural crest and heart genes isolated by modified differential display.

    Science.gov (United States)

    Martinsen, Brad J; Groebner, Nathan J; Frasier, Allison J; Lohr, Jamie L

    2003-08-01

    The invasion of the cardiac neural crest (CNC) into the outflow tract (OFT) and subsequent outflow tract septation are critical events during vertebrate heart development. We have performed four modified differential display screens in the chick embryo to identify genes that may be involved in CNC, OFT, secondary heart field, and heart development. The screens included differential display of RNA isolated from three different axial segments containing premigratory cranial neural crest cells; of RNA from distal outflow tract, proximal outflow tract, and atrioventricular tissue of embryonic chick hearts; and of RNA isolated from left and right cranial tissues, including the early heart fields. These screens have resulted in the identification of the five cDNA clones presented here, which are expressed in the cardiac neural crest, outflow tract and developing heart in patterns that are unique in heart development.

  19. Testing of an oral dosing technique for double-crested cormorants, Phalacocorax auritus, laughing gulls, Leucophaeus atricilla, homing pigeons, Columba livia, and western sandpipers, Calidris mauri, with artificially weather MC252 oil.

    Science.gov (United States)

    Dean, K M; Cacela, D; Carney, M W; Cunningham, F L; Ellis, C; Gerson, A R; Guglielmo, C G; Hanson-Dorr, K C; Harr, K E; Healy, K A; Horak, K E; Isanhart, J P; Kennedy, L V; Link, J E; Lipton, I; McFadden, A K; Moye, J K; Perez, C R; Pritsos, C A; Pritsos, K L; Muthumalage, T; Shriner, S A; Bursian, S J

    2017-12-01

    Scoping studies were designed to determine if double-crested cormorants (Phalacocorax auritus), laughing gulls (Leucophaues atricilla), homing pigeons (Columba livia) and western sandpipers (Calidris mauri) that were gavaged with a mixture of artificially weathered MC252 oil and food for either a single day or 4-5 consecutive days showed signs of oil toxicity. Where volume allowed, samples were collected for hematology, plasma protein electrophoresis, clinical chemistry and electrolytes, oxidative stress and organ weigh changes. Double-crested cormorants, laughing gulls and western sandpipers all excreted oil within 30min of dose, while pigeons regurgitated within less than one hour of dosing. There were species differences in the effectiveness of the dosing technique, with double-crested cormorants having the greatest number of responsive endpoints at the completion of the trial. Statistically significant changes in packed cell volume, white cell counts, alkaline phosphatase, alanine aminotransferase, creatine phosphokinase, gamma glutamyl transferase, uric acid, chloride, sodium, potassium, calcium, total glutathione, glutathione disulfide, reduced glutathione, spleen and liver weights were measured in double-crested cormorants. Homing pigeons had statistically significant changes in creatine phosphokinase, total glutathione, glutathione disulfide, reduced glutathione and Trolox equivalents. Laughing gulls exhibited statistically significant decreases in spleen and kidney weight, and no changes were observed in any measurement endpoints tested in western sandpipers. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. The F-box protein Cdc4/Fbxw7 is a novel regulator of neural crest development in Xenopus laevis

    Directory of Open Access Journals (Sweden)

    Hartley Rebecca S

    2010-01-01

    Full Text Available Abstract Background The neural crest is a unique population of cells that arise in the vertebrate ectoderm at the neural plate border after which they migrate extensively throughout the embryo, giving rise to a wide range of derivatives. A number of proteins involved in neural crest development have dynamic expression patterns, and it is becoming clear that ubiquitin-mediated protein degradation is partly responsible for this. Results Here we demonstrate a novel role for the F-box protein Cdc4/Fbxw7 in neural crest development. Two isoforms of Xenopus laevis Cdc4 were identified, and designated xCdc4α and xCdc4β. These are highly conserved with vertebrate Cdc4 orthologs, and the Xenopus proteins are functionally equivalent in terms of their ability to degrade Cyclin E, an established vertebrate Cdc4 target. Blocking xCdc4 function specifically inhibited neural crest development at an early stage, prior to expression of c-Myc, Snail2 and Snail. Conclusions We demonstrate that Cdc4, an ubiquitin E3 ligase subunit previously identified as targeting primarily cell cycle regulators for proteolysis, has additional roles in control of formation of the neural crest. Hence, we identify Cdc4 as a protein with separable but complementary functions in control of cell proliferation and differentiation.

  1. Crest Level Optimization of the Multi Level Overtopping based Wave Energy Converter Seawave Slot-Cone Generator

    DEFF Research Database (Denmark)

    Kofoed, Jens Peter; Osaland, E.

    2005-01-01

    The paper describes the optimization of the crest levels and geometrical layout of the SSG structure, focusing on maximizing the obtained potential energy in the overtopping water. During wave tank testing at AAU average overtopping rates into the individual reservoirs have been measured. The ini......The paper describes the optimization of the crest levels and geometrical layout of the SSG structure, focusing on maximizing the obtained potential energy in the overtopping water. During wave tank testing at AAU average overtopping rates into the individual reservoirs have been measured....... The initial tests led to an expression describing the derivative of the overtopping rate with respect to the vertical distance. Based on this, numerical optimizations of the crest levels, for a number of combinations of wave conditions, have been performed. The hereby found optimal crest levels have been...

  2. SCENARIO OF AN ACCIDENT OF SOIL DAMS IN CASE OF WATER SPILL OVER A DAM CREST BY USING FAULT TREE ANALYSIS

    OpenAIRE

    Kuznetsov Dmitriy Viktorovich

    2016-01-01

    The scenario of a hydrodynamic accident of water flow over a crest of a soil dam is considered by the method of fault tree analysis, for which the basic reasons and controlled diagnostic indicators of an accident have been defined. Logical operators “AND”/”OR” were used for creation of a sequence of logically connected events, leading to an undesired event in the scenario of accident. The scenario of the accident was plotted in case of three basic reasons - an excessive settling of a dam cres...

  3. Alpha male replacements and delayed dispersal in crested macaques (Macaca nigra).

    Science.gov (United States)

    Marty, Pascal R; Hodges, Keith; Agil, Muhammad; Engelhardt, Antje

    2017-07-01

    In species with a high male reproductive skew, competition between males for the top dominant position is high and escalated fights are common between competitors. As a consequence, challenges incur potentially high costs. Selection should favor males who time an alpha male challenge to maximize chances of a successful outcome minimizing costs. Despite the importance of alpha male replacements for individual males, we know little about the timing of challenges and the condition of the challenger. We investigated the timing and process of alpha male replacements in a species living in multi-male groups with high male reproductive skew, the crested macaque. We studied four wild groups over 6 years in the Tangkoko Reserve, North Sulawesi, Indonesia, during which 16 alpha male replacements occurred. Although unusual for cercopithecines, male crested macaques delayed their natal dispersal until they attained maximum body mass and therefore fighting ability whereupon they emigrated and challenged the alpha male in another group. Accordingly, all observed alpha male replacements were from outside males. Ours is the first report of such a pattern in a primate species living in multi-male groups. Although the majority of alpha male replacements occurred through direct male-male challenges, many also took place opportunistically (i.e., after the alpha male had already been injured or had left the group). Furthermore, alpha male tenures were very short (averaging ca. 12 months). We hypothesize that this unusual pattern of alpha male replacements in crested macaques is related to the species-specific combination of high male reproductive skew with a large number of males per group. Am. J. Primatol. 79:e22448, 2017. © 2015 The Authors. American Journal of Primatology Published by Wiley Periodicals, Inc. © 2015 The Authors. American Journal of Primatology Published by Wiley Periodicals, Inc.

  4. Isolation and characterization of eight novel microsatellite loci in the double-crested cormorant (Phalacrocorax auritus)

    Science.gov (United States)

    Mercer, Dacey; Haig, Susan; Mullins, Thomas

    2010-01-01

    We describe the isolation and characterization of eight microsatellite loci from the double-crested cormorant (Phalacrocorax auritus). Genetic variability was assessed using 60 individuals from three populations. All loci were variable with the number of alleles ranging from two to 17 per locus, and observed heterozygosity varying from 0.05 to 0.89. No loci showed signs of linkage disequilibrium and all loci conformed to Hardy–Weinberg equilibrium frequencies. Further, all loci amplified and were polymorphic in two related Phalacrocorax species. These loci should prove useful for population genetic studies of the double-crested cormorant and other pelecaniform species.

  5. Hydraulic Evaluation of the Crest Wing Wave Energy Converter

    DEFF Research Database (Denmark)

    Kofoed, Jens Peter; Antonishen, Michael Patrick

    This report presents the results of an experimental study of the wave energy converting abilities of the Crest Wing wave energy converter (WEC). The Crest Wing is a WEC that uses its movement in matching the shape of an oncoming wave to generate power. Model tests have been performed using a scale...... model (length scale 1:30), provided by WaveEnergyFyn, in regular and irregular wave states that can be found in Assessment of Wave Energy Devices. Best Practice as used in Denmark (Frigaard et al., 2008). The tests were carried out at Dept. of Civil Engineering, Aalborg (Frigaard et al., 2008......). The tests were carried out at Dept. of Civil Engineering, Aalborg University (AAU) in the 3D deep water wave tank. The displacement and force applied to a power take off system, provided by WaveEnergyFyn, were measured and used to calculate total power take off....

  6. Reconstruction of iliac crest with rib to prevent donor site complications: A prospective study of 26 cases

    Directory of Open Access Journals (Sweden)

    Dave B

    2007-01-01

    Full Text Available Background: The tricortical bone graft from the iliac crest are used to reconstruct the post corpectomy spinal defects. The donor iliac area defect is large and may give rise to pain at donor site, instability of pelvis, fracture of ilium, donor site muscle herniation or abdominal content herniation. Rib removed during thoracotomy was used by us to reconstruct the iliac crest defect. Materials and Methods: Twenty-six patients who underwent thoracotomy for dorsal spine corpectomy or curettage for various spinal pathologies from June 2002 to May 2004 were included in the study. After adequate decompression the spine was reconstructed by tricortical bone graft from iliac crest and reconstruction of the iliac crest was done with the rib removed for exposure during thoracotomy. Results: The mean follow up was 15 months. All patients had good graft incorporation which was evaluated on the basis of local tenderness and radiographs. One patient had graft displacement. Conclusion: The reconstruction of iliac crest by rib is a simple and effective procedure to prevent donor site complications.

  7. Age-related changes in vertebral and iliac crest 3D bone microstructure--differences and similarities.

    Science.gov (United States)

    Thomsen, J S; Jensen, M V; Niklassen, A S; Ebbesen, E N; Brüel, A

    2015-01-01

    Age-related changes of vertebra and iliac crest 3D microstructure were investigated, and we showed that they were in general similar. The 95th percentile of vertebral trabecular thickness distribution increased with age for women. Surprisingly, vertebral and iliac crest bone microstructure was only weakly correlated (r = 0.38 to 0.75), despite the overall similar age-related changes. The purposes of the study were to determine the age-related changes in iliac and vertebral bone microstructure for women and men over a large age range and to investigate the relationship between the bone microstructure at these skeletal sites. Matched sets of transiliac crest bone biopsies and lumbar vertebral body (L2) specimens from 41 women (19-96 years) and 39 men (23-95 years) were micro-computed tomography (μCT) scanned, and the 3D microstructure was quantified. For both women and men, bone volume per total volume (BV/TV), connectivity density (CD), and trabecular number (Tb.N) decreased significantly, while structure model index (SMI) and trabecular separation (Tb.Sp) increased significantly with age at either skeletal site. Vertebral trabecular thickness (Tb.Th) was independent of age for both women and men, while iliac Tb.Th decreased significantly with age for men, but not for women. In general, the vertebral and iliac age-related changes were similar. The 95th percentile of the Tb.Th distribution increased significantly with age for women but was independent of age for men at the vertebral body, while it was independent of age for either sex at the iliac crest. The Tb.Th probability density functions at the two skeletal sites became significantly more similar with age for women, but not for men. The microstructural parameters at the iliac crest and the vertebral bodies were only moderately correlated from r = 0.38 for SMI in women to r = 0.75 for Tb.Sp in men. Age-related changes in vertebral and iliac bone microstructure were in general similar. The iliac

  8. The hypoxia factor Hif-1α controls neural crest chemotaxis and epithelial to mesenchymal transition

    Science.gov (United States)

    Barriga, Elias H.; Maxwell, Patrick H.

    2013-01-01

    One of the most important mechanisms that promotes metastasis is the stabilization of Hif-1 (hypoxia-inducible transcription factor 1). We decided to test whether Hif-1α also was required for early embryonic development. We focused our attention on the development of the neural crest, a highly migratory embryonic cell population whose behavior has been likened to cancer metastasis. Inhibition of Hif-1α by antisense morpholinos in Xenopus laevis or zebrafish embryos led to complete inhibition of neural crest migration. We show that Hif-1α controls the expression of Twist, which in turn represses E-cadherin during epithelial to mesenchymal transition (EMT) of neural crest cells. Thus, Hif-1α allows cells to initiate migration by promoting the release of cell–cell adhesions. Additionally, Hif-1α controls chemotaxis toward the chemokine SDF-1 by regulating expression of its receptor Cxcr4. Our results point to Hif-1α as a novel and key regulator that integrates EMT and chemotaxis during migration of neural crest cells. PMID:23712262

  9. Donor site complications in bone grafting: comparison of iliac crest, calvarial, and mandibular ramus bone.

    Science.gov (United States)

    Scheerlinck, Laura M E; Muradin, Marvick S M; van der Bilt, Andries; Meijer, Gert J; Koole, Ronald; Van Cann, Ellen M

    2013-01-01

    To compare the donor site complication rate and length of hospital stay following the harvest of bone from the iliac crest, calvarium, or mandibular ramus. Ninety-nine consecutively treated patients were included in this retrospective observational single-center study. Iliac crest bone was harvested in 55 patients, calvarial bone in 26 patients, and mandibular ramus bone in 18 patients. Harvesting of mandibular ramus bone was associated with the lowest percentages of major complications (5.6%), minor complications (22.2%), and total complications (27.8%). Harvesting of iliac crest bone was related to the highest percentages of minor complications (56.4%) and total complications (63.6%), whereas harvesting of calvarial bone induced the highest percentage of major complications (19.2%). The length of the hospital stay was significantly influenced by the choice of donor site (P = .003) and age (P = .009); young patients with the mandibular ramus as the donor site had the shortest hospital stay. Harvesting of mandibular ramus bone was associated with the lowest percentage of complications and the shortest hospital stay. When the amount of bone to be obtained is deemed sufficient, mandibular ramus bone should be the first choice for the reconstruction of maxillofacial defects.

  10. Repair of articular cartilage defects in the knee with autologous iliac crest cartilage in a rabbit model.

    Science.gov (United States)

    Jing, Lizhong; Zhang, Jiying; Leng, Huijie; Guo, Qinwei; Hu, Yuelin

    2015-04-01

    To demonstrate that iliac crest cartilage may be used to repair articular cartilage defects in the knees of rabbits. Full-thickness cartilage defects were created in the medial femoral condyle on both knees of 36 New Zealand white rabbits. The 72 defects were randomly assigned to be repaired with ipsilateral iliac crest cartilage (Group I), osteochondral tissues removed at defect creation (Group II), or no treatment (negative control, Group III). Animals were killed at 6, 12, and 24 weeks post-operatively. The repaired tissues were harvested for magnetic resonance imaging (MRI), histological studies (haematoxylin and eosin and immunohistochemical staining), and mechanical testing. At 6 weeks, the iliac crest cartilage graft was not yet well integrated with the surrounding articular cartilage, but at 12 weeks, the graft deep zone had partial ossification. By 24 weeks, the hyaline cartilage-like tissue was completely integrated with the surrounding articular cartilage. Osteochondral autografts showed more rapid healing than Group I at 6 weeks and complete healing at 12 weeks. Untreated defects were concave or partly filled with fibrous tissue throughout the study. MRI showed that Group I had slower integration with surrounding normal cartilage compared with Group II. The mechanical properties of Group I were significantly lower than those of Group II at 12 weeks, but this difference was not significant at 24 weeks. Iliac crest cartilage autografts were able to repair knee cartilage defects with hyaline cartilage and showed comparable results with osteochondral autografts in the rabbit model.

  11. A Multicentric, Open-Label, Randomized, Comparative Clinical Trial of Two Different Doses of Expanded hBM-MSCs Plus Biomaterial versus Iliac Crest Autograft, for Bone Healing in Nonunions after Long Bone Fractures: Study Protocol

    Directory of Open Access Journals (Sweden)

    Enrique Gómez-Barrena

    2018-01-01

    Full Text Available ORTHOUNION is a multicentre, open, comparative, three-arm, randomized clinical trial (EudraCT number 2015-000431-32 to compare the efficacy, at one and two years, of autologous human bone marrow-derived expanded mesenchymal stromal cell (hBM-MSC treatments versus iliac crest autograft (ICA to enhance bone healing in patients with diaphyseal and/or metaphysodiaphyseal fracture (femur, tibia, and humerus status of atrophic or oligotrophic nonunion (more than 9 months after the acute fracture, including recalcitrant cases after failed treatments. The primary objective is to determine if the treatment with hBM-MSCs combined with biomaterial is superior to ICA in obtaining bone healing. If confirmed, a secondary objective is set to determine if the dose of 100 × 106 hBM-MSCs is noninferior to that of 200 × 106 hBM-MSCs. The participants (n=108 will be randomly assigned to either the experimental low dose (n=36, the experimental high dose (n=36, or the comparator arm (n=36 using a central randomization service. The trial will be conducted in 20 clinical centres in Spain, France, Germany, and Italy under the same clinical protocol. The confirmation of superiority for the proposed ATMP in nonunions may foster the future of bone regenerative medicine in this indication. On the contrary, absence of superiority may underline its limitations in clinical use.

  12. A Multicentric, Open-Label, Randomized, Comparative Clinical Trial of Two Different Doses of Expanded hBM-MSCs Plus Biomaterial versus Iliac Crest Autograft, for Bone Healing in Nonunions after Long Bone Fractures: Study Protocol.

    Science.gov (United States)

    Gómez-Barrena, Enrique; Padilla-Eguiluz, Norma G; Avendaño-Solá, Cristina; Payares-Herrera, Concepción; Velasco-Iglesias, Ana; Torres, Ferran; Rosset, Philippe; Gebhard, Florian; Baldini, Nicola; Rubio-Suarez, Juan C; García-Rey, Eduardo; Cordero-Ampuero, José; Vaquero-Martin, Javier; Chana, Francisco; Marco, Fernando; García-Coiradas, Javier; Caba-Dessoux, Pedro; de la Cuadra, Pablo; Hernigou, Philippe; Flouzat-Lachaniette, Charles-Henri; Gouin, François; Mainard, Didier; Laffosse, Jean Michel; Kalbitz, Miriam; Marzi, Ingo; Südkamp, Norbert; Stöckle, Ulrich; Ciapetti, Gabriela; Donati, Davide Maria; Zagra, Luigi; Pazzaglia, Ugo; Zarattini, Guido; Capanna, Rodolfo; Catani, Fabio

    2018-01-01

    ORTHOUNION is a multicentre, open, comparative, three-arm, randomized clinical trial (EudraCT number 2015-000431-32) to compare the efficacy, at one and two years, of autologous human bone marrow-derived expanded mesenchymal stromal cell (hBM-MSC) treatments versus iliac crest autograft (ICA) to enhance bone healing in patients with diaphyseal and/or metaphysodiaphyseal fracture (femur, tibia, and humerus) status of atrophic or oligotrophic nonunion (more than 9 months after the acute fracture, including recalcitrant cases after failed treatments). The primary objective is to determine if the treatment with hBM-MSCs combined with biomaterial is superior to ICA in obtaining bone healing. If confirmed, a secondary objective is set to determine if the dose of 100 × 10 6 hBM-MSCs is noninferior to that of 200 × 10 6 hBM-MSCs. The participants ( n = 108) will be randomly assigned to either the experimental low dose ( n = 36), the experimental high dose ( n = 36), or the comparator arm ( n = 36) using a central randomization service. The trial will be conducted in 20 clinical centres in Spain, France, Germany, and Italy under the same clinical protocol. The confirmation of superiority for the proposed ATMP in nonunions may foster the future of bone regenerative medicine in this indication. On the contrary, absence of superiority may underline its limitations in clinical use.

  13. Variation in sagebrush communities historically seeded with crested wheatgrass in the eastern great basin

    Science.gov (United States)

    Although crested wheatgrass (CWG; Agropyron cristatum [L.] Gaertn.) has been one of the most commonly seeded exotic species in the western United States, long-term successional trajectories of seeded sites are poorly characterized, especially for big sagebrush (Artemisia tridentana Nutt.) ecosystems...

  14. The CREST-E study of creatine for Huntington disease: A randomized controlled trial.

    Science.gov (United States)

    Hersch, Steven M; Schifitto, Giovanni; Oakes, David; Bredlau, Amy-Lee; Meyers, Catherine M; Nahin, Richard; Rosas, Herminia Diana

    2017-08-08

    To investigate whether creatine administration could slow progressive functional decline in adults with early symptoms of Huntington disease. We conducted a multicenter, randomized, double-blind, placebo-controlled study of up to 40 g daily of creatine monohydrate in participants with stage I and II HD treated for up to 48 months. The primary outcome measure was the rate of change in total functional capacity (TFC) between baseline and end of follow-up. Secondary outcome measures included changes in additional clinical scores, tolerability, and quality of life. Safety was assessed by adverse events and laboratory studies. At 46 sites in North America, Australia, and New Zealand, 553 participants were randomized to creatine (275) or placebo (278). The trial was designed to enroll 650 patients, but was halted for futility after the first interim analysis. The estimated rates of decline in the primary outcome measure (TFC) were 0.82 points per year for participants on creatine, 0.70 points per year for participants on placebo, favoring placebo (nominal 95% confidence limits -0.11 to 0.35). Adverse events, mainly gastrointestinal, were significantly more common in participants on creatine. Serious adverse events, including deaths, were more frequent in the placebo group. Subgroup analysis suggested that men and women may respond differently to creatine treatment. Our data do not support the use of creatine treatment for delaying functional decline in early manifest HD. NCT00712426. This study provides Class II evidence that for patients with early symptomatic HD, creatine monohydrate is not beneficial for slowing functional decline. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

  15. Complications encountered in patients bearers with crest syndrome in rheumatological service of the Hospital San Juan de Dios until September 2009

    International Nuclear Information System (INIS)

    Mendez Rodriguez, Alexis

    2010-01-01

    Systematic sclerosis is a disease that has caused much morbidity and dependence in patients. Despite not being the disease most prevalent in rheumatological practice, it has been perhaps one that has generated more interest in the complex pathophysiology; but, also a great sense of frustration with the great therapeutic limitations especially when is diagnosed in advanced stages. The research was conducted in order to motivate early clinical search of the major complications found in patients CREST syndrome, in rheumatological service of the Hospital San Juan de Dios until September 2009 the total of cases with a diagnosis of CREST were reviewed in outpatient records, the study population have been of 41 patients. The different clinical manifestations of the patient were taken into account, among other aspects: immunological studies, established treatments and diagnosis methods as conventional radiology, endoscopic studies, echocardiogram, capillaroscopy. This job has determined among other things, that the majority of patients with CREST come from Desamparados and the Southern Zone, representing 31.7 and 29.2%, respectively, 98% are women and 76% of patients engaged in domestic chores and no mortality case was found in relation to CREST [es

  16. File list: ALL.PSC.05.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  17. File list: ALL.PSC.50.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.PSC.50.AllAg.hESC_derived_neural_crests hg19 All antigens Pluripotent stem cell hESC derived neural...X1091539,SRX059364 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.PSC.50.AllAg.hESC_derived_neural_crests.bed ...

  18. Assessing the efficiency of aluminium phosphide and arsenic trioxide in controlling the Indian crested porcupine (hystrix indica) in an irrigated forest plantation or Punjab, Pakistan

    International Nuclear Information System (INIS)

    Khan, A.A.

    2010-01-01

    The Indian crested porcupine, Hystrix indica, is widely distributed in the irrigated forests of Punjab, Pakistan and causes serious damage to trees, nursery stocking, field crops and vegetables. Field trials were conducted to determine the efficacy of aluminium phosphide (Phostoxin, 3g tablets) and arsenic trioxide bait (at 2.5g per apple) against the porcupine in a forest plantation. For fumigation with phostoxin, tablets were used at the rate of four, five, six and seven tablets per den. Observations showed that four tablets were ineffective, five and six tablets provided partial control, while seven tablets provided complete control of porcupines. Baiting with arsenic trioxide also resulted in 89 % reduction of the porcupine population occupying the treated dens. (author)

  19. Taxane-induced morphea in a patient with CREST syndrome

    Directory of Open Access Journals (Sweden)

    Susan Michele Bouchard

    2010-07-01

    Full Text Available The taxanes, docetaxel and paclitaxel, are microtubule stabilizing chemotherapeutic agents that have demonstrated antineoplastic effects in a variety of solid tumors. They have been linked to the development of localized cutaneous sclerosis in some patients. We present a case of docetaxel-induced cutaneous sclerosis of the lower extremities in a patient with pre-existing CREST syndrome. We propose that patients with a history of limited or diffuse systemic sclerosis should be given taxane chemotherapy with caution, as these patients may have an immunological predisposition for the development of drug-induced morphea.

  20. Gastrointestinal and external parasites of the white-crested elaenia Elaenia albiceps chilensis (Aves, Tyrannidae in Chile

    Directory of Open Access Journals (Sweden)

    Danny Fuentes

    Full Text Available The objective of this study is to evaluate the ectoparasites and helminths of the white-crested elaenia, Elaenia albiceps chilensis. Feather mites Anisophyllodes elaeniae, Trouessartia elaeniae, and Analges sp. were detected in 51% of birds (n=106, whereas 24% were infected with lice (Tyranniphilopterus delicatulus, Menacanthus cfr. distinctus, and Ricinus cfr. invadens. Helminths Viguiera sp. and Capillaria sp. were found in five of the birds that were necropsied (n=20. With the exception of A. elaeniae, T. elaeniae, and T. delicatulus, all parasites represented new records found for the white-crested elaenia, and therefore for the Chilean repertoire of biodiversity.

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  3. File list: His.PSC.50.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.PSC.50.AllAg.hESC_derived_neural_crests hg19 Histone Pluripotent stem cell hESC derived neural...30,SRX059362,SRX1091539,SRX059364 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.PSC.50.AllAg.hESC_derived_neural_crests.bed ...

  4. Migration flyway of the Mediterranean breeding Lesser Crested Tern ...

    African Journals Online (AJOL)

    The Lesser Crested Tern Thalasseus bengalensis emigratus breeding population in the Mediterranean is found exclusively in Libya, on the two coastal islands of Gara and Elba and one wetland on the mainland coast at Benghazi. In order to improve knowledge of the species migration to wintering quarters in West Africa, ...

  5. Augmented BMPRIA-mediated BMP signaling in cranial neural crest lineage leads to cleft palate formation and delayed tooth differentiation.

    Directory of Open Access Journals (Sweden)

    Lu Li

    Full Text Available The importance of BMP receptor Ia (BMPRIa mediated signaling in the development of craniofacial organs, including the tooth and palate, has been well illuminated in several mouse models of loss of function, and by its mutations associated with juvenile polyposis syndrome and facial defects in humans. In this study, we took a gain-of-function approach to further address the role of BMPR-IA-mediated signaling in the mesenchymal compartment during tooth and palate development. We generated transgenic mice expressing a constitutively active form of BmprIa (caBmprIa in cranial neural crest (CNC cells that contributes to the dental and palatal mesenchyme. Mice bearing enhanced BMPRIa-mediated signaling in CNC cells exhibit complete cleft palate and delayed odontogenic differentiation. We showed that the cleft palate defect in the transgenic animals is attributed to an altered cell proliferation rate in the anterior palatal mesenchyme and to the delayed palatal elevation in the posterior portion associated with ectopic cartilage formation. Despite enhanced activity of BMP signaling in the dental mesenchyme, tooth development and patterning in transgenic mice appeared normal except delayed odontogenic differentiation. These data support the hypothesis that a finely tuned level of BMPRIa-mediated signaling is essential for normal palate and tooth development.

  6. Oral Crest Lengthening for Increasing Removable Denture Retention by Means of CO2 Laser

    Directory of Open Access Journals (Sweden)

    Samir Nammour

    2014-01-01

    Full Text Available The loss of teeth and their replacement by artificial denture is associated with many problems. The denture needs a certain amount of ridge height to give it retention and a long-term function. Crest lengthening procedures are performed to provide a better anatomic environment and to create proper supporting structures for more stability and retention of the denture. The purpose of our study is to describe and evaluate the effectiveness of CO2 laser-assisted surgery in patients treated for crest lengthening (vestibular deepening. There have been various surgical techniques described in order to restore alveolar ridge height by pushing muscles attaching of the jaws. Most of these techniques cause postoperative complications such as edemas, hemorrhage, pain, infection, slow healing, and rebound to initial position. Our clinical study describes the treatment planning and clinical steps for the crest lengthening with the use of CO2 laser beam (6–15 Watts in noncontact, energy density range: 84.92–212.31 J/cm2, focus, and continuous mode with a focal point diameter of 0.3 mm. At the end of each surgery, dentures were temporarily relined with a soft material. Patients were asked to mandatorily wear their relined denture for a minimum of 4–6 weeks and to remove it for hygienic purposes. At the end of each surgery, the deepest length of the vestibule was measured by the operator. No sutures were made and bloodless wounds healed in second intention without grafts. Results pointed out the efficiency of the procedure using CO2 laser. At 8 weeks of post-op, the mean of crest lengthening was stable without rebound. Only a loss of 15% was noticed. To conclude, the use of CO2 laser is an effective option for crest lengthening.

  7. Pa2G4 is a novel Six1 co-factor that is required for neural crest and otic development☆

    Science.gov (United States)

    Neilson, Karen M.; Abbruzzesse, Genevieve; Kenyon, Kristy; Bartolo, Vanessa; Krohn, Patrick; Alfandari, Dominique; Moody, Sally A.

    2016-01-01

    Mutations in SIX1 and in its co-factor, EYA1, underlie Branchiootorenal Spectrum disorder (BOS), which is characterized by variable branchial arch, otic and kidney malformations. However, mutations in these two genes are identified in only half of patients. We screened for other potential co-factors, and herein characterize one of them, Pa2G4 (aka Ebp1/Plfap). In human embryonic kidney cells, Pa2G4 binds to Six1 and interferes with the Six1-Eya1 complex. In Xenopus embryos, knock-down of Pa2G4 leads to down-regulation of neural border zone, neural crest and cranial placode genes, and concomitant expansion of neural plate genes. Gain-of-function leads to a broader neural border zone, expanded neural crest and altered cranial placode domains. In loss-of-function assays, the later developing otocyst is reduced in size, which impacts gene expression. In contrast, the size of the otocyst in gain-of-function assays is not changed but the expression domains of several otocyst genes are reduced. Together these findings establish an interaction between Pa2G4 and Six1, and demonstrate that it has an important role in the development of tissues affected in BOS. Thereby, we suggest that pa2g4 is a potential candidate gene for BOS. PMID:27940157

  8. RECONSTRUCTION OF ATROPHIC MAXILLA BY ANTERIOR ILIAC CREST BONE GRAFTING VIA NEUROAXIAL BLOCKADE TECHNIQUE: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Erol CANSIZ

    2017-01-01

    Full Text Available Anterior iliac crest bone grafting is a well-established modality in the treatment of alveolar bone deficiencies. However, this procedure may also have considerable postoperative morbidity which is mostly related to general anesthesia. Postoperative pain-related complications can be managed by neuroaxial blockade techniques which provide adequate surgical analgesia and reduce postoperative pain. This clinical report describes the reconstruction of a severely atrophic maxilla with anterior iliac crest bone grafting using combined spinal epidural anesthesia. Neuroaxial blockade techniques may be a useful alternative to eliminate general anesthesia related challenges of anterior iliac crest bone grafting procedures.

  9. File list: Oth.PSC.05.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  10. File list: Oth.PSC.10.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  11. File list: Oth.PSC.50.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.PSC.50.AllAg.hESC_derived_neural_crests hg19 TFs and others Pluripotent stem cell hESC derived neural...X1091550,SRX059360,SRX1091547,SRX059367,SRX059368 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.PSC.50.AllAg.hESC_derived_neural_crests.bed ...

  12. I131-meta-iodobenzylguanidine in the diagnosis and treatment of neural crest tumours

    International Nuclear Information System (INIS)

    Hoefnagel, C.A.; Hartog Jager, F.C.A. den; Taal, B.G.; Engelsman, E.; Kraker, J. de; Voute, P.A.

    1988-01-01

    Iodine-131-meta-iodobenzylguanidine (I-131-MIBG) was used for scintigraphic detection and therapy of neural crest tumours. The methodology of both techniques is described. Based upon experience with I-131-MIBG-scintigraphy in 170 patients with neural crest tumours, of whom 46 received multiple therapeutic doses of I-131-MIBG, and upon the cumulative reports in the literature, the role of I-131-MIBG in diagnosis and treatment of each of these diseases is indicated. I-131-MIBG-scintigraphy is one of the most sensitive and specific techniques for the diagnosis, staging and follow-up of phaeochromocytoma and neuroblastoma and I-131-MIBG-therapy may induce remission in a number of these patients. In carcinoid and medullary thyroid carcinoma the diagnostic sensitivity is less; however, once the diagnosis has been made, it is useful to establish that the tumour concentrates I-131-MIBG, to see if the patients at some point in time may be amenable to I-131-MIBG-therapy

  13. Endorsement of the CONSORT guidelines, trial registration, and the quality of reporting randomised controlled trials in leading nursing journals: A cross-sectional analysis.

    Science.gov (United States)

    Jull, Andrew; Aye, Phyu Sin

    2015-06-01

    To establish the reporting quality of trials published in leading nursing journals and investigate associations between CONSORT Statement or trial registration endorsment and reporting of design elements. The top 15 nursing journals were searched using Medline for randomised controlled trials published in 2012. Journals were categorised as CONSORT and trial registration promoting based on requirements of submitting authors or the journal's webpage as at January 2014. Data on sequence generation, allocation concealment, follow up, blinding, baseline equivalence and sample size calculation were extracted by one author and independently verified by the second author against source data. Seven journals were CONSORT promoting and three of these journals were also trial registration promoting. 114 citations were identified and 83 were randomised controlled trials. Eighteen trials (21.7%) were registered and those published in trial registration promoting journals were more likely to be registered (RR 2.64 95%CI 1.14-6.09). We assessed 68.7% of trials to be low risk of bias for sequence generation, 20.5% for allocation concealment, 38.6% for blinding, 55.4% for completeness of follow up and 79.5% for baseline equivalence. Trials published in CONSORT promoting journals were more likely to be at low risk of bias for blinding (RR 2.33, 95%CI 1.01-5.34) and completeness of follow up (RR 1.77, 95%CI 1.02-3.10), but journal endorsement of the CONSORT Statement or trial registration otherwise had no significant effect. Trials published in CONSORT and trial registration promoting journals were more likely to have high quality sample size calculations (RR 2.91, 95%CI 1.18-7.19 and RR 1.69, 95%CI 1.08-2.64, respectively). Simple endorsement of the CONSORT Statement and trials registration is insufficient action to encourage improvement of the quality of trial reporting across the most important of trial design elements. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Disruption of Smad4 in neural crest cells leads to mid-gestation death with pharyngeal arch, craniofacial and cardiac defects

    Science.gov (United States)

    Nie, Xuguang; Deng, Chu-xia; Wang, Qin; Jiao, Kai

    2008-01-01

    TGFβ/BMP signaling pathways are essential for normal development of neural crest cells (NCCs). Smad4 encodes the only common Smad protein in mammals, which is a critical nuclear mediator of TGFβ/BMP signaling. In this work, we sought to investigate the roles of Smad4 for development of NCCs. To overcome the early embryonic lethality of Smad4 null mice, we specifically disrupted Smad4 in NCCs using a Cre/loxP system. The mutant mice died at mid-gestation with defects in facial primordia, pharyngeal arches, outflow tract and cardiac ventricles. Further examination revealed that mutant embryos displayed severe molecular defects starting from E9.5. Expression of multiple genes, including Msx1, 2, Ap-2α, Pax3, and Sox9, which play critical roles for NCC development, was downregulated by NCC disruption of Smad4. Moreover, increased cell death was observed in pharyngeal arches from E10.5. However, the cell proliferation rate in these areas was not substantially altered. Taken together, these findings provide compelling genetic evidence that Smad4-mediated activities of TGFβ/BMP signals are essential for appropriate NCC development. PMID:18334251

  15. Pelvic instability after bone graft harvesting from posterior iliac crest: report of nine patients

    Energy Technology Data Exchange (ETDEWEB)

    Chan, K.; Pathria, M.; Jacobson, J. [Dept. of Radiology, Univ. of California, San Diego, CA (United States); Resnick, D. [Dept. of Radiology, Veterans Affairs Medical Center, San Diego, CA (United States)

    2001-05-01

    Objective. To report the imaging findings in nine patients who developed pelvic instability after bone graft harvest from the posterior aspect of the iliac crest.Design and patients. A retrospective study was performed of the imaging studies of nine patients who developed pelvic pain after autologous bone graft was harvested from the posterior aspect of the ilium for spinal arthrodesis. Plain films, bone scans, and CT and MR examinations of the pelvis were reviewed. Pertinent aspects of the clinical history of these patients were noted, including age, gender and clinical symptoms.Results. The age of the patients ranged from 52 to 77 years (average 69 years) and all were women. The bone graft had been derived from the posterior aspect of the iliac crest about the sacroiliac joint. All patients subsequently developed subluxation of the pubic symphysis. Eight patients had additional insufficiency fractures of the iliac crest adjacent to the bone graft donor site, and five patients also revealed subluxation of the sacroiliac joint. Two had insufficiency fractures of the sacrum and one had an additional fracture of the pubic ramus.Conclusions. Pelvic instability is a potential complication of bone graft harvesting from the posterior aspect of the iliac crest. The pelvic instability is manifested by insufficiency fractures of the ilium and subluxation of the sacroiliac joints and pubic symphysis. (orig.)

  16. Pelvic instability after bone graft harvesting from posterior iliac crest: report of nine patients

    International Nuclear Information System (INIS)

    Chan, K.; Pathria, M.; Jacobson, J.; Resnick, D.

    2001-01-01

    Objective. To report the imaging findings in nine patients who developed pelvic instability after bone graft harvest from the posterior aspect of the iliac crest.Design and patients. A retrospective study was performed of the imaging studies of nine patients who developed pelvic pain after autologous bone graft was harvested from the posterior aspect of the ilium for spinal arthrodesis. Plain films, bone scans, and CT and MR examinations of the pelvis were reviewed. Pertinent aspects of the clinical history of these patients were noted, including age, gender and clinical symptoms.Results. The age of the patients ranged from 52 to 77 years (average 69 years) and all were women. The bone graft had been derived from the posterior aspect of the iliac crest about the sacroiliac joint. All patients subsequently developed subluxation of the pubic symphysis. Eight patients had additional insufficiency fractures of the iliac crest adjacent to the bone graft donor site, and five patients also revealed subluxation of the sacroiliac joint. Two had insufficiency fractures of the sacrum and one had an additional fracture of the pubic ramus.Conclusions. Pelvic instability is a potential complication of bone graft harvesting from the posterior aspect of the iliac crest. The pelvic instability is manifested by insufficiency fractures of the ilium and subluxation of the sacroiliac joints and pubic symphysis. (orig.)

  17. CREST-SAFE: Snow LST validation, wetness profiler creation, and depth/SWE product development

    Science.gov (United States)

    Perez Diaz, C. L.; Lakhankar, T.; Romanov, P.; Khanbilvardi, R.; Munoz Barreto, J.; Yu, Y.

    2017-12-01

    CREST-SAFE: Snow LST validation, wetness profiler creation, and depth/SWE product development The Field Snow Research Station (also referred to as Snow Analysis and Field Experiment, SAFE) is operated by the NOAA Center for Earth System Sciences and Remote Sensing Technologies (CREST) in the City University of New York (CUNY). The field station is located within the premises of the Caribou Municipal Airport (46°52'59'' N, 68°01'07'' W) and in close proximity to the National Weather Service (NWS) Regional Forecast Office. The station was established in 2010 to support studies in snow physics and snow remote sensing. The Visible Infrared Imager Radiometer Suite (VIIRS) Land Surface Temperature (LST) Environmental Data Record (EDR) and Moderate Resolution Imaging Spectroradiometer (MODIS) LST product (provided by the Terra and Aqua Earth Observing System satellites) were validated using in situ LST (T-skin) and near-surface air temperature (T-air) observations recorded at CREST-SAFE for the winters of 2013 and 2014. Results indicate that T-air correlates better than T-skin with VIIRS LST data and that the accuracy of nighttime LST retrievals is considerably better than that of daytime. Several trends in the MODIS LST data were observed, including the underestimation of daytime values and night-time values. Results indicate that, although all the data sets showed high correlation with ground measurements, day values yielded slightly higher accuracy ( 1°C). Additionally, we created a liquid water content (LWC)-profiling instrument using time-domain reflectometry (TDR) at CREST-SAFE and tested it during the snow melt period (February-April) immediately after installation in 2014. Results displayed high agreement when compared to LWC estimates obtained using empirical formulas developed in previous studies, and minor improvement over wet snow LWC estimates. Lastly, to improve on global snow cover mapping, a snow product capable of estimating snow depth and snow water

  18. Differences in neural crest sensitivity to ethanol account for the infrequency of anterior segment defects in the eye compared with craniofacial anomalies in a zebrafish model of fetal alcohol syndrome.

    Science.gov (United States)

    Eason, Jessica; Williams, Antionette L; Chawla, Bahaar; Apsey, Christian; Bohnsack, Brenda L

    2017-09-01

    Ethanol (ETOH) exposure during pregnancy is associated with craniofacial and neurologic abnormalities, but infrequently disrupts the anterior segment of the eye. In these studies, we used zebrafish to investigate differences in the teratogenic effect of ETOH on craniofacial, periocular, and ocular neural crest. Zebrafish eye and neural crest development was analyzed by means of live imaging, TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay, immunostaining, detection of reactive oxygen species, and in situ hybridization. Our studies demonstrated that foxd3-positive neural crest cells in the periocular mesenchyme and developing eye were less sensitive to ETOH than sox10-positive craniofacial neural crest cells that form the pharyngeal arches and jaw. ETOH increased apoptosis in the retina, but did not affect survival of periocular and ocular neural crest cells. ETOH also did not increase reactive oxygen species within the eye. In contrast, ETOH increased ventral neural crest apoptosis and reactive oxygen species production in the facial mesenchyme. In the eye and craniofacial region, sod2 showed high levels of expression in the anterior segment and in the setting of Sod2 knockdown, low levels of ETOH decreased migration of foxd3-positive neural crest cells into the developing eye. However, ETOH had minimal effect on the periocular and ocular expression of transcription factors (pitx2 and foxc1) that regulate anterior segment development. Neural crest cells contributing to the anterior segment of the eye exhibit increased ability to withstand ETOH-induced oxidative stress and apoptosis. These studies explain the rarity of anterior segment dysgenesis despite the frequent craniofacial abnormalities in fetal alcohol syndrome. Birth Defects Research 109:1212-1227, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  19. Prenuptial perfume: Alloanointing in the social rituals of the crested auklet ( Aethia cristatella) and the transfer of arthropod deterrents

    Science.gov (United States)

    Douglas, Hector D.

    2008-01-01

    Alloanointing, the transfer of chemicals between conspecifics, is known among mammals, but hitherto, the behavior has not been documented for birds. The crested auklet ( Aethia cristatella), a colonial seabird of Alaskan and Siberian waters, alloanoints during courtship with fragrant aldehydes that are released from specialized wick-like feathers located in the interscapular region. Crested auklets solicit anointment at the colony, and prospective mates rub bill, breast, head, and neck over wick feathers of their partners. This distributes aldehydes over the head, neck, and face where the birds cannot self-preen. The resulting chemical concentrations are sufficient to deter ectoparasites. Auklets that emit more odorant can transfer more defensive chemicals to mates and are thus more sexually attractive. Behavioral studies showed that crested auklets are attracted to their scent. Wild birds searched for dispensers that emitted their scent and rubbed their bills on the dispensers and engaged in vigorous anointment behaviors. In captive experiments, naïve crested auklets responded more strongly to synthetic auklet scent than controls, and the greatest behavioral response occurred during early courtship. This study extends scientific knowledge regarding functions of alloanointing. Alloanointing had previously been attributed to scent marking and individual recognition in vertebrates. Alloanointing is described here in the context of an adaptive social cue — the transfer of arthropod deterrents between prospective mates.

  20. Bone thickness of the infrazygomatic crest area in skeletal Class III growing patients: A computed tomographic study

    International Nuclear Information System (INIS)

    Lee, Hyub Soo; Choi, Hang Moon; Choi, Dong Soon; Jang, Insan; Cha, Bong Kuen

    2013-01-01

    This study was performed to investigate the bone thickness of the infrazygomatic crest area by computed tomography (CT) for placement of a miniplate as skeletal anchorage for maxillary protraction in skeletal Class III children. CT images of skeletal Class III children (7 boys, 9 girls, mean age: 11.4 years) were taken parallel to the Frankfurt horizontal plane. The bone thickness of the infrazygomatic crest area was measured at 35 locations on the right and left sides, perpendicular to the bone surface. The bone was thickest (5.0 mm) in the upper zygomatic bone and thinnest (1.1 mm) in the anterior wall of the maxillary sinus. Generally, there was a tendency for the bone to be thicker at the superior and lateral area of the zygomatic process of the maxilla. There was no clinically significant difference in bone thickness between the right and left sides; however, it was thicker in male than in female subjects. In the infrazygomatic crest area, the superior and lateral area of the zygomatic process of the maxilla had the most appropriate thickness for placement of a miniplate in growing skeletal Class III children with a retruded maxilla.

  1. Bone thickness of the infrazygomatic crest area in skeletal Class III growing patients: A computed tomographic study

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hyub Soo; Choi, Hang Moon; Choi, Dong Soon; Jang, Insan; Cha, Bong Kuen [College of Dentistry and Research Institute of Oral Science, Gangneung-Wonju National University, Gangneung (Korea, Republic of)

    2013-12-15

    This study was performed to investigate the bone thickness of the infrazygomatic crest area by computed tomography (CT) for placement of a miniplate as skeletal anchorage for maxillary protraction in skeletal Class III children. CT images of skeletal Class III children (7 boys, 9 girls, mean age: 11.4 years) were taken parallel to the Frankfurt horizontal plane. The bone thickness of the infrazygomatic crest area was measured at 35 locations on the right and left sides, perpendicular to the bone surface. The bone was thickest (5.0 mm) in the upper zygomatic bone and thinnest (1.1 mm) in the anterior wall of the maxillary sinus. Generally, there was a tendency for the bone to be thicker at the superior and lateral area of the zygomatic process of the maxilla. There was no clinically significant difference in bone thickness between the right and left sides; however, it was thicker in male than in female subjects. In the infrazygomatic crest area, the superior and lateral area of the zygomatic process of the maxilla had the most appropriate thickness for placement of a miniplate in growing skeletal Class III children with a retruded maxilla.

  2. Safety and efficacy of an 8-week regimen of grazoprevir plus ruzasvir plus uprifosbuvir compared with grazoprevir plus elbasvir plus uprifosbuvir in participants without cirrhosis infected with hepatitis C virus genotypes 1, 2, or 3 (C-CREST-1 and C-CREST-2, part A)

    DEFF Research Database (Denmark)

    Gane, Edward J; Pianko, Stephen; Roberts, Stuart K

    2017-01-01

    BACKGROUND: New hepatitis C virus (HCV) therapies with pan-genotypic efficacy are needed. The goals of part A of C-CREST-1 and C-CREST-2 were to compare the efficacies of two doses (300 mg or 450 mg once daily) of uprifosbuvir (MK-3682; NS5B inhibitor) in an 8-week regimen combined with grazoprev...

  3. Embryonic cell-cell adhesion: a key player in collective neural crest migration.

    Science.gov (United States)

    Barriga, Elias H; Mayor, Roberto

    2015-01-01

    Cell migration is essential for morphogenesis, adult tissue remodeling, wound healing, and cancer cell migration. Cells can migrate as individuals or groups. When cells migrate in groups, cell-cell interactions are crucial in order to promote the coordinated behavior, essential for collective migration. Interestingly, recent evidence has shown that cell-cell interactions are also important for establishing and maintaining the directionality of these migratory events. We focus on neural crest cells, as they possess extraordinary migratory capabilities that allow them to migrate and colonize tissues all over the embryo. Neural crest cells undergo an epithelial-to-mesenchymal transition at the same time than perform directional collective migration. Cell-cell adhesion has been shown to be an important source of planar cell polarity and cell coordination during collective movement. We also review molecular mechanisms underlying cadherin turnover, showing how the modulation and dynamics of cell-cell adhesions are crucial in order to maintain tissue integrity and collective migration in vivo. We conclude that cell-cell adhesion during embryo development cannot be considered as simple passive resistance to force, but rather participates in signaling events that determine important cell behaviors required for cell migration. © 2015 Elsevier Inc. All rights reserved.

  4. Is mitochondrial DNA divergence of near easter crested newts, Triturus karelinii group, reflected by differentiation of skull shape

    NARCIS (Netherlands)

    Ivanovic, A.; Uzum, N.; Wielstra, B.M.; Olgun, K.; Litvinchuk, S.N.; Kalezic, M.L.; Arntzen, J.W.

    2013-01-01

    The Eurasian Triturus karelinii group of crested newts comprises three distinct, geographically coherent mitochondrial DNA lineages, designated as the eastern, central and western lineage. These three lineages are genetically as diverged as other, morphologically well-differentiated crested newt

  5. Laboratory Experiments on Low-crested Breakwaters

    DEFF Research Database (Denmark)

    Kramer, Morten; Zanuttigh, B.; van der Meer, J.W.

    2005-01-01

    New unique laboratory experiments on low-crested structures (LCSs) have been performed within the DELOS project. The experiments were carried out in three European laboratories aiming at extending and completing existing available information with respect to a wide range of engineering design...... in a wave channel at small scale, and scale effects regarding wave transmission and reflection were studied in a wave channel at a large scale facility. The paper describes the experiments and associated databank with respect to objectives, test program, set-ups and measurements. Results, guidelines...... and recommendations elaborated from the tests are included in the other companion papers of the Coastal Engineering Special Issue on DELOS....

  6. The usefulness of panoramic radiography using a lead ruler for dental implant planning

    International Nuclear Information System (INIS)

    Lee, Sang Hee; Lee, Seong Geun; Kim, Sung Min; Oh, Kyong Seung; Huh, Jin Do; Joh, Young Duk

    2000-01-01

    If damage to the neurovascular bundle of the mandibular canal during dental implant surgery of the mandible is to be prevented, accurate measurement of the distance between the alveolar crest and the mandibular canal, as seen on panoramic radiographs, is important. The purpose of this study was to compare the accuracy of panoramic radiography using a lead ruler with that of computed tomography for the measurement of the distance between the alveolar crest and superior border of the mandibular canal and to evaluate the usefulness of panoramic radiography using a lead ruler. For control study, panoramic radiography of the dry mandible was undertaken using a lead ruler, and computed tomography was added. The distances between the alveolar crest and the superior border of the mandibular canal and between the alveolar crest and the lowest border of the body of the mandible were measured at the level of the 2nd premolar to the 3rd molar. These measurements were compared with actual measurements of the dry mandible in the same areas. The cases of 87 patients (49 men, 38 women; age range, 20-84 (mean, 42) years) who had undergone panoramic radiography using a lead ruler were reviewed. They were categorized according to sex, the presence of teeth, and whether under or over 50 years of age. All measurements were compared and analyzed using the Student t-test. Measured values obtained from a panoramic radiograph using a lead ruler (magnification:100.32% ± 5.92) and from a computed tomograph (magnification:100.22 ± 5.55) deviated less from actual measurements on the dry mandible (p greater than 0.05). The distance from the 2nd premolar to the 3rd molar was greater in male adults (19.62 mm ± 3.95) than in female (17.54 mm ± 4.04) (p less than 0.05), except the 3rd molar. In addition, the distance was greater in dentulous patients (18.81 mm ± 3.33) than in edentulous (16.23 mm ± 1.75) (p less than 0.05), except the 3rd molar. There was, however, no significant difference

  7. Phenothiourea sensitizes zebrafish cranial neural crest and extraocular muscle development to changes in retinoic acid and IGF signaling.

    Directory of Open Access Journals (Sweden)

    Brenda L Bohnsack

    Full Text Available 1-Phenyl 2-thiourea (PTU is a tyrosinase inhibitor commonly used to block pigmentation and aid visualization of zebrafish development. At the standard concentration of 0.003% (200 µM, PTU inhibits melanogenesis and reportedly has minimal other effects on zebrafish embryogenesis. We found that 0.003% PTU altered retinoic acid and insulin-like growth factor (IGF regulation of neural crest and mesodermal components of craniofacial development. Reduction of retinoic acid synthesis by the pan-aldehyde dehydrogenase inhibitor diethylbenzaldehyde, only when combined with 0.003% PTU, resulted in extraocular muscle disorganization. PTU also decreased retinoic acid-induced teratogenic effects on pharyngeal arch and jaw cartilage despite morphologically normal appearing PTU-treated controls. Furthermore, 0.003% PTU in combination with inhibition of IGF signaling through either morpholino knockdown or pharmacologic inhibition of tyrosine kinase receptor phosphorylation, disrupted jaw development and extraocular muscle organization. PTU in and of itself inhibited neural crest development at higher concentrations (0.03% and had the greatest inhibitory effect when added prior to 22 hours post fertilization (hpf. Addition of 0.003% PTU between 4 and 20 hpf decreased thyroxine (T4 in thyroid follicles in the nasopharynx of 96 hpf embryos. Treatment with exogenous triiodothyronine (T3 and T4 improved, but did not completely rescue, PTU-induced neural crest defects. Thus, PTU should be used with caution when studying zebrafish embryogenesis as it alters the threshold of different signaling pathways important during craniofacial development. The effects of PTU on neural crest development are partially caused by thyroid hormone signaling.

  8. Iliac Crest Donor Site for Children With Cleft Lip and Palate Undergoing Alveolar Bone Grafting: A Long-term Assessment.

    Science.gov (United States)

    Wheeler, Jonathan; Sanders, Megan; Loo, Stanley; Moaveni, Zac; Bartlett, Glenn; Keall, Heather; Pinkerton, Mark

    2016-05-01

    The authors aimed to accurately assess the donor site morbidity from iliac crest bone grafts for secondary bone grafting in patients with cleft lip and palate alveolar defects. Fifty patients between 3 months and 10 years following alveolar bone grafting for cleft lip and palate were entered into the study. Two-thirds of patients had no significant concerns about the donor site. The remaining third had some concerns about the appearance of their hips and less than 10% of patients expressing strong agreement with statements about concerns with shape, appearance, and self-consciousness about the iliac crest donor site. Examination findings showed the average length of scar being 5.4 cm and a third of patients having some minor palpable boney irregularities of the iliac crest. The authors found that the alveolar crest donor site is well tolerated by patients long term but has a measurable morbidity long term.

  9. Neural Crest Cells Isolated from the Bone Marrow of Transgenic Mice Express JCV T-Antigen.

    Directory of Open Access Journals (Sweden)

    Jennifer Gordon

    Full Text Available JC virus (JCV, a common human polyomavirus, is the etiological agent of the demyelinating disease, progressive multifocal leukoencephalopathy (PML. In addition to its role in PML, studies have demonstrated the transforming ability of the JCV early protein, T-antigen, and its association with some human cancers. JCV infection occurs in childhood and latent virus is thought to be maintained within the bone marrow, which harbors cells of hematopoietic and non-hematopoietic lineages. Here we show that non-hematopoietic mesenchymal stem cells (MSCs isolated from the bone marrow of JCV T-antigen transgenic mice give rise to JCV T-antigen positive cells when cultured under neural conditions. JCV T-antigen positive cells exhibited neural crest characteristics and demonstrated p75, SOX-10 and nestin positivity. When cultured in conditions typical for mesenchymal cells, a population of T-antigen negative cells, which did not express neural crest markers arose from the MSCs. JCV T-antigen positive cells could be cultured long-term while maintaining their neural crest characteristics. When these cells were induced to differentiate into neural crest derivatives, JCV T-antigen was downregulated in cells differentiating into bone and maintained in glial cells expressing GFAP and S100. We conclude that JCV T-antigen can be stably expressed within a fraction of bone marrow cells differentiating along the neural crest/glial lineage when cultured in vitro. These findings identify a cell population within the bone marrow permissible for JCV early gene expression suggesting the possibility that these cells could support persistent viral infection and thus provide clues toward understanding the role of the bone marrow in JCV latency and reactivation. Further, our data provides an excellent experimental model system for studying the cell-type specificity of JCV T-antigen expression, the role of bone marrow-derived stem cells in the pathogenesis of JCV-related diseases

  10. Sexual signalling in female crested macaques and the evolution of primate fertility signals.

    Science.gov (United States)

    Higham, James P; Heistermann, Michael; Saggau, Carina; Agil, Muhammad; Perwitasari-Farajallah, Dyah; Engelhardt, Antje

    2012-06-18

    Female signals of fertility have evolved in diverse taxa. Among the most interesting study systems are those of multimale multifemale group-living primates, where females signal fertility to males through multiple signals, and in which there is substantial inter-specific variation in the composition and reliability of such signals. Among the macaques, some species display reliable behavioural and/or anogenital signals while others do not. One cause of this variation may be differences in male competitive regimes: some species show marked sexual dimorphism and reproductive skew, with males fighting for dominance, while others show low dimorphism and skew, with males queuing for dominance. As such, there is variation in the extent to which rank is a reliable proxy for male competitiveness, which may affect the extent to which it is in females' interest to signal ovulation reliably. However, data on ovulatory signals are absent from species at one end of the macaque continuum, where selection has led to high sexual dimorphism and male reproductive skew. Here we present data from 31 cycles of 19 wild female crested macaques, a highly sexually dimorphic species with strong mating skew. We collected measures of ovarian hormone data from faeces, sexual swelling size from digital images, and male and female behaviour. We show that both sexual swelling size and female proceptivity are graded-signals, but relatively reliable indicators of ovulation, with swelling size largest and female proceptive behaviours most frequent around ovulation. Sexual swelling size was also larger in conceptive cycles. Male mating behaviour was well timed to female ovulation, suggesting that males had accurate information about this. Though probabilistic, crested macaque ovulatory signals are relatively reliable. We argue that in species where males fight over dominance, male dominance rank is surrogate for competitiveness. Under these circumstances it is in the interest of females to increase

  11. Sexual signalling in female crested macaques and the evolution of primate fertility signals

    Directory of Open Access Journals (Sweden)

    Higham James P

    2012-06-01

    Full Text Available Abstract Background Female signals of fertility have evolved in diverse taxa. Among the most interesting study systems are those of multimale multifemale group-living primates, where females signal fertility to males through multiple signals, and in which there is substantial inter-specific variation in the composition and reliability of such signals. Among the macaques, some species display reliable behavioural and/or anogenital signals while others do not. One cause of this variation may be differences in male competitive regimes: some species show marked sexual dimorphism and reproductive skew, with males fighting for dominance, while others show low dimorphism and skew, with males queuing for dominance. As such, there is variation in the extent to which rank is a reliable proxy for male competitiveness, which may affect the extent to which it is in females’ interest to signal ovulation reliably. However, data on ovulatory signals are absent from species at one end of the macaque continuum, where selection has led to high sexual dimorphism and male reproductive skew. Here we present data from 31 cycles of 19 wild female crested macaques, a highly sexually dimorphic species with strong mating skew. We collected measures of ovarian hormone data from faeces, sexual swelling size from digital images, and male and female behaviour. Results We show that both sexual swelling size and female proceptivity are graded-signals, but relatively reliable indicators of ovulation, with swelling size largest and female proceptive behaviours most frequent around ovulation. Sexual swelling size was also larger in conceptive cycles. Male mating behaviour was well timed to female ovulation, suggesting that males had accurate information about this. Conclusion Though probabilistic, crested macaque ovulatory signals are relatively reliable. We argue that in species where males fight over dominance, male dominance rank is surrogate for competitiveness. Under these

  12. Retrospective radiographic study of marginal bone changes of 88 implants placed with split crest technique in the maxillary latero-posterior area

    Directory of Open Access Journals (Sweden)

    S. Longoni

    2016-04-01

    Full Text Available Aim This article presents a retrospective study on the behavior of implants placed with split crest technique in lateroposterior maxillary class IV atrophy. Materials and Methods Subjects who underwent implant placement following split crest technique in the maxillary latero-posterior area were enrolled in the present retrospective study. After a mean period of 6.2 years of function implant survival and success rates were assessed. Moreover, radiographic examination was made on digital periapical radiographs and by means of a specific software. Bone level changes were measured as the difference between the peri-implants crestal bone level and the implants shoulder during the last patient’s visit recall examination. Results A total of 30 patients satisfied the inclusion criteria and were included in the study; the subjects were treated with 88 implants (64 transmucosal and 24 submerged. The observation period for all patients treated with split crest technique varied between 4 and 8 years (mean 6.2 years. The implants survival rate was 96.6% and the prostheses survival rate was 100%. Bone resorption ranged between 2.3 mm and 2.7 mm. Conclusion Implants inserted in conjunction with split crest technique seems to be a promising therapy with similar results as conventional implant surgery.

  13. Evaluation of MODIS Land Surface Temperature with In Situ Snow Surface Temperature from CREST-SAFE

    Science.gov (United States)

    Perez Diaz, C. L.; Lakhankar, T.; Romanov, P.; Munoz, J.; Khanbilvardi, R.; Yu, Y.

    2016-12-01

    This paper presents the procedure and results of a temperature-based validation approach for the Moderate Resolution Imaging Spectroradiometer (MODIS) Land Surface Temperature (LST) product provided by the National Aeronautics and Space Administration (NASA) Terra and Aqua Earth Observing System satellites using in situ LST observations recorded at the Cooperative Remote Sensing Science and Technology Center - Snow Analysis and Field Experiment (CREST-SAFE) during the years of 2013 (January-April) and 2014 (February-April). A total of 314 day and night clear-sky thermal images, acquired by the Terra and Aqua satellites, were processed and compared to ground-truth data from CREST-SAFE with a frequency of one measurement every 3 min. Additionally, this investigation incorporated supplementary analyses using meteorological CREST-SAFE in situ variables (i.e. wind speed, cloud cover, incoming solar radiation) to study their effects on in situ snow surface temperature (T-skin) and T-air. Furthermore, a single pixel (1km2) and several spatially averaged pixels were used for satellite LST validation by increasing the MODIS window size to 5x5, 9x9, and 25x25 windows for comparison. Several trends in the MODIS LST data were observed, including the underestimation of daytime values and nighttime values. Results indicate that, although all the data sets (Terra and Aqua, diurnal and nocturnal) showed high correlation with ground measurements, day values yielded slightly higher accuracy ( 1°C), both suggesting that MODIS LST retrievals are reliable for similar land cover classes and atmospheric conditions. Results from the CREST-SAFE in situ variables' analyses indicate that T-air is commonly higher than T-skin, and that a lack of cloud cover results in: lower T-skin and higher T-air minus T-skin difference (T-diff). Additionally, the study revealed that T-diff is inversely proportional to cloud cover, wind speed, and incoming solar radiation. Increasing the MODIS window size

  14. Biological responses of Crested and Least auklets to volcanic destruction of nesting habitat in the Aleutian Islands, Alaska

    Science.gov (United States)

    Drew, Gary S.; Piatt, John F.; Williams, Jeffrey C.

    2018-01-01

    Crested Auklets (Aethia cristatella) and Least Auklets (A. pusilla) are crevice-nesting birds that breed in large mixed colonies at relatively few sites in the Aleutian Island archipelago, Bering Sea, Gulf of Alaska, and Sea of Okhotsk. Many of these colonies are located on active volcanic islands. The eruption of Kasatochi volcano, in the central Aleutians, on August 7, 2008, completely buried all crevice-nesting seabird habitat on the island. This provided an opportunity to examine the response of a large, mixed auklet colony to a major geological disturbance. Time-lapse imagery of nesting habitat indicated that both species returned to the largest pre-eruption colony site for several years, but subsequently abandoned it within 5 yr after the eruption. In 2010, a rockfall site in a cove north of the old colony site began to accumulate talus, and groups of auklets were observed using the site in 2011. Use of the new colony appeared to coincide with the abandonment of the old colony site by both species, though surface counts suggested that Least Auklets shifted to the new colony sooner than Crested Auklets. At-sea surveys of seabirds before and after the eruption indicated that both Crested and Least auklets shifted their at-sea distributions from the waters around Kasatochi Island to nearby Koniuji Island. In combination, at-sea counts and colony time-lapse imagery indicated that Crested and Least auklets using Kasatochi responded to the volcanic disturbance and complete loss of nesting habitat at the main colony on Kasatochi with dispersal either to newly created habitat on Kasatochi or to an alternate colony on a nearby island.

  15. Fluorescence-Activated Cell Sorting of EGFP-Labeled Neural Crest Cells From Murine Embryonic Craniofacial Tissue

    Directory of Open Access Journals (Sweden)

    Saurabh Singh

    2005-01-01

    Full Text Available During the early stages of embryogenesis, pluripotent neural crest cells (NCC are known to migrate from the neural folds to populate multiple target sites in the embryo where they differentiate into various derivatives, including cartilage, bone, connective tissue, melanocytes, glia, and neurons of the peripheral nervous system. The ability to obtain pure NCC populations is essential to enable molecular analyses of neural crest induction, migration, and/or differentiation. Crossing Wnt1-Cre and Z/EG transgenic mouse lines resulted in offspring in which the Wnt1-Cre transgene activated permanent EGFP expression only in NCC. The present report demonstrates a flow cytometric method to sort and isolate populations of EGFP-labeled NCC. The identity of the sorted neural crest cells was confirmed by assaying expression of known marker genes by TaqMan Quantitative Real-Time Polymerase Chain Reaction (QRT-PCR. The molecular strategy described in this report provides a means to extract intact RNA from a pure population of NCC thus enabling analysis of gene expression in a defined population of embryonic precursor cells critical to development.

  16. Randomized prospective study comparing tri-cortical iliac crest autograft to allograft in the lateral column lengthening component for operative correction of adult acquired flatfoot deformity.

    Science.gov (United States)

    Dolan, Christopher M; Henning, Jeffrey A; Anderson, John G; Bohay, Donald R; Kornmesser, Marc J; Endres, Terrence J

    2007-01-01

    Operative treatment of stage II posterior tibial tendon insufficiency (PTTI) is controversial. Many soft-tissue and bony procedures and various combinations of the two have been reported for treatment of stage II PTTI. Orthopaedists recognize the lateral column lengthening component of the procedure as a successful reconstructive technique. The use of cortical allograft for lateral column lengthening in the correction of pes planus in the pediatric patient population has been routine. In the adult population, however, tricortical iliac crest autograft has been the bone graft of choice. Harvest of this autograft can precipitate significant morbidity and cost. Therefore, we undertook this randomized controlled trial to compare graft incorporation and healing of allograft and autograft in the lateral column lengthening component of adult flatfoot reconstruction. Lateral column lengthening was done as a component of operative correction for stage II PTTI in adult patients (older than 18 years) by two surgeons using similar procedures. The patients were randomized to either the allograft or autograft procedures. The primary endpoint was graft incorporation and healing as assessed by radiographs. The study included 33 randomized feet in 31 patients. We followed 18 feet in the allograft group and 15 in the autograft group to the point of union. There were 21 women and 10 men. There were no delayed unions, nonunions, or hardware failures. All patients in both groups achieved bony union by the 12-week followup evaluation. Two superficial foot infections were successfully treated with oral antibiotics. Two patients in the autograft group continued to have hip donor site pain at 3 months. This study suggests that union rates of allograft and autograft (iliac crest bone graft) are equal. The use of allograft in the lateral column lengthening component of operative correction of adult stage II PTTI appears to be a viable alternative to the use of iliac crest autograft and

  17. Dicer activity in neural crest cells is essential for craniofacial organogenesis and pharyngeal arch artery morphogenesis

    Science.gov (United States)

    Nie, Xuguang; Wang, Qin; Jiao, Kai

    2014-01-01

    MicroRNAs (miRNAs) play important roles in regulating gene expression during numerous biological/pathological processes. Dicer encodes an RNase III endonuclease that is essential for generating most, if not all, functional miRNAs. In this work, we applied a conditional gene inactivation approach to examine the function of Dicer during neural crest cell (NCC) development. Mice with NCC-specific inactivation of Dicer died perinatally. Cranial and cardiac NCC migration into target tissues was not affected by Dicer disruption, but their subsequent development was disturbed. NCC derivatives and their associated mesoderm-derived cells displayed massive apoptosis, leading to severe abnormalities during craniofacial morphogenesis and organogenesis. In addition, the 4th pharyngeal arch artery (PAA) remodeling was affected, resulting in interrupted aortic arch artery type B (IAA-B) in mutant animals. Taken together, our results show that Dicer activity in NCCs is essential for craniofacial development and pharyngeal arch artery morphogenesis. PMID:21256960

  18. Nesting habitat requirements and nestling diet in the Mediterranean populations of Crested Tits Lophophanes cristatus

    NARCIS (Netherlands)

    Atienzar, F.; Barba, E.; Holleman, L.J.M.; Belda, E.J.

    2009-01-01

    Most bird species show specific habitat requirements for breeding and feeding. We studied the pattern of habitat occupation, nestling diet and breeding performance of Crested Tits Lophophanes cristatus in a “typical” (coniferous) and an “atypical” (Holm Oak Quercus ilex) forest in eastern Spain

  19. A numerical study of lowest-order short-crested water wave instabilities

    DEFF Research Database (Denmark)

    Fuhrman, David R.; Madsen, Per A.

    2005-01-01

    This work presents the first numerical simulations of the long-term evolution of doubly-periodic short-crested wave instabilities, which are the simplest cases involving the three-dimensional instability of genuinely three-dimensional progressive water waves. The simulated evolutions reveal quali...

  20. Comparison of fracture site callus with iliac crest bone marrow as the source of plastic-adherent cells

    Directory of Open Access Journals (Sweden)

    Achmad Zaki

    2013-05-01

    Full Text Available Background: Red marrow has been described as the main source of mesenchymal stem cells although its aspiration and isolation from bone marrow was reported to have significant donor site morbidity. Since secondary bone healing occurs through formation of callus as the result of proliferation and differentiation of mesenchymal stem cells, callus may become alternative source for mesenchymal stem cells. In this study, we compared the number of plastic-adherent cells from fracture site callus and bone marrow of iliac crest after two and four weeks of culture.Methods: Sixteen New Zealand rabbits were fracturized at the femoral shaft. Then, these rabbits were taken care. After two weeks of fracturization, 3 mL iliac crest bone marrow aspiration and callus extraction of eight rabbits were cultured (group I. The other eight rabbits were treated equally after four weeks of fracturization (group II. Simultaneously, the cultures were observed after one and two weeks. Four weeks later, they were harvested. Cells were counted using Neubauer hemocytometer. The average number of cells between the sources and groups were statistically analyzed using the unpaired t-test. Results: In group I, there were 2.6 ± 0.1 x 104 cells in the culture of iliac crest bone marrow aspirate and 2.5 ± 0.1 x 104 cells in culture of callus extract from fracture site (p = 0.34. In group II, there were 2.7 ± 0.1 x 104 cells and 2.1 ± 0.1 x 104 cells, respectively (p < 0.001.Conclusion: Fracture site callus at the second week post-fracturization may be potential as source of plastic-adherent cells compared with iliac crest bone marrow. (Med J Indones. 2013;22:70-5Keywords: Bone marrow, fracture site callus, iliac crest, long bone, mesenchymal stem cell, plastic-adherent cells

  1. Dissecting CNBP, a zinc-finger protein required for neural crest development, in its structural and functional domains.

    Science.gov (United States)

    Armas, Pablo; Agüero, Tristán H; Borgognone, Mariana; Aybar, Manuel J; Calcaterra, Nora B

    2008-10-17

    Cellular nucleic-acid-binding protein (CNBP) plays an essential role in forebrain and craniofacial development by controlling cell proliferation and survival to mediate neural crest expansion. CNBP binds to single-stranded nucleic acids and displays nucleic acid chaperone activity in vitro. The CNBP family shows a conserved modular organization of seven Zn knuckles and an arginine-glycine-glycine (RGG) box between the first and second Zn knuckles. The participation of these structural motifs in CNBP biochemical activities has still not been addressed. Here, we describe the generation of CNBP mutants that dissect the protein into regions with structurally and functionally distinct properties. Mutagenesis approaches were followed to generate: (i) an amino acid replacement that disrupted the fifth Zn knuckle; (ii) N-terminal deletions that removed the first Zn knuckle and the RGG box, or the RGG box alone; and (iii) a C-terminal deletion that eliminated the three last Zn knuckles. Mutant proteins were overexpressed in Escherichia coli, purified, and used to analyze their biochemical features in vitro, or overexpressed in Xenopus laevis embryos to study their function in vivo during neural crest cell development. We found that the Zn knuckles are required, but not individually essential, for CNBP biochemical activities, whereas the RGG box is essential for RNA-protein binding and nucleic acid chaperone activity. Removal of the RGG box allowed CNBP to preserve a weak single-stranded-DNA-binding capability. A mutant mimicking the natural N-terminal proteolytic CNBP form behaved as the RGG-deleted mutant. By gain-of-function and loss-of-function experiments in Xenopus embryos, we confirmed the participation of CNBP in neural crest development, and we demonstrated that the CNBP mutants lacking the N-terminal region or the RGG box alone may act as dominant negatives in vivo. Based on these data, we speculate about the existence of a specific proteolytic mechanism for the

  2. The lamprey: a jawless vertebrate model system for examining origin of the neural crest and other vertebrate traits.

    Science.gov (United States)

    Green, Stephen A; Bronner, Marianne E

    2014-01-01

    Lampreys are a group of jawless fishes that serve as an important point of comparison for studies of vertebrate evolution. Lampreys and hagfishes are agnathan fishes, the cyclostomes, which sit at a crucial phylogenetic position as the only living sister group of the jawed vertebrates. Comparisons between cyclostomes and jawed vertebrates can help identify shared derived (i.e. synapomorphic) traits that might have been inherited from ancestral early vertebrates, if unlikely to have arisen convergently by chance. One example of a uniquely vertebrate trait is the neural crest, an embryonic tissue that produces many cell types crucial to vertebrate features, such as the craniofacial skeleton, pigmentation of the skin, and much of the peripheral nervous system (Gans and Northcutt, 1983). Invertebrate chordates arguably lack unambiguous neural crest homologs, yet have cells with some similarities, making comparisons with lampreys and jawed vertebrates essential for inferring characteristics of development in early vertebrates, and how they may have evolved from nonvertebrate chordates. Here we review recent research on cyclostome neural crest development, including research on lamprey gene regulatory networks and differentiated neural crest fates. Copyright © 2014 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

  3. Recent population size, trends, and limiting factors for the double-crested Cormorant in Western North America

    Science.gov (United States)

    Adkins, Jessica Y.; Roby, Daniel D.; Lyons, Donald E.; Courtot, Karen N.; Collis, Ken; Carter, Harry R.; Shuford, W. David; Capitolo, Phillip J.

    2014-01-01

    The status of the double-crested cormorant (Phalacrocorax auritus) in western North America was last evaluated during 1987–2003. In the interim, concern has grown over the potential impact of predation by double-crested cormorants on juvenile salmonids (Oncorhynchusspp.), particularly in the Columbia Basin and along the Pacific coast where some salmonids are listed for protection under the United States Endangered Species Act. Recent re-evaluations of double-crested cormorant management at the local, flyway, and federal level warrant further examination of the current population size and trends in western North America. We collected colony size data for the western population (British Columbia, Washington, Oregon, Idaho, California, Nevada, Utah, Arizona, and the portions of Montana, Wyoming, Colorado and New Mexico west of the Continental Divide) by conducting aircraft-, boat-, or ground-based surveys and by cooperating with government agencies, universities, and non-profit organizations. In 2009, we estimated approximately 31,200 breeding pairs in the western population. We estimated that cormorant numbers in the Pacific Region (British Columbia, Washington, Oregon, and California) increased 72% from 1987–1992 to circa 2009. Based on the best available data for this period, the average annual growth rate (λ) of the number of breeding birds in the Pacific Region was 1.03, versus 1.07 for the population east of the Continental Divide during recent decades. Most of the increase in the Pacific Region can be attributed to an increase in the size of the nesting colony on East Sand Island in the Columbia River estuary, which accounts for about 39% of all breeding pairs in the western population and is the largest known breeding colony for the species (12,087 breeding pairs estimated in 2009). In contrast, numbers of breeding pairs estimated in coastal British Columbia and Washington have declined by approximately 66% during this same period. Disturbance at breeding

  4. Cut loose and run: The complex role of ADAM proteases during neural crest cell development.

    Science.gov (United States)

    Alfandari, Dominique; Taneyhill, Lisa A

    2018-02-24

    ADAM metalloproteases have been shown to play critical roles during development. In this review, we will describe functional evidence that implicates ADAM proteins during the genesis, migration and differentiation of neural crest cells. We will restrict our analysis to the transmembrane ADAMs as other reviews have addressed the role of extracellular metalloproteases (Christian et al. [2013] Critical Reviews in Biochemistry and Molecular Biology 48:544-560). This review will describe advances that have been obtained mainly through the use of two vertebrate model systems, the frog, and avian embryos. The role of the principal substrates of ADAMs, the cadherins, has been extensively described in other reviews, most recently in (Cousin [1997] Mechanisms of Development 148:79-88; Taneyhill and Schiffmacher [2017] Genesis, 55). The function of ADAMs in the migration of other cell types, including the immune system, wound healing and cancer has been described previously in (Dreymueller et al. [2017] Mediators of Inflammation 2017: 9621724). Our goal is to illustrate both the importance of ADAMs in controlling neural crest behavior and how neural crest cells have helped us understand the molecular interactions, substrates, and functions of ADAM proteins in vivo. © 2018 Wiley Periodicals, Inc.

  5. Spatial correlation of the ionsphere total electron content at the equatorial anomaly crest

    International Nuclear Information System (INIS)

    Huang, Y.

    1984-01-01

    The spatial correlation of the ionospheric total electron content (TEC) at the equatorial anomaly crest was studied by recording Faraday rotation angle of the ETS-II geostationary satellite at Lunping and Kaohsiung whose subionospheric points are located at 23.0 0 N, 121.0 0 N, and 20.9 0 N, 121.1 0 E, respectively, and are about 280 km apart. The results show that the spatial correlation of TEC at the equatorial crest region is smaller than that at other places. The day-to-day variabilities of TEC differences between two subionospheric points are quite large. The day-to-day variabilities of the fountain effect seem to play an important role

  6. Financial Management of a Large Multi-site Randomized Clinical Trial

    Science.gov (United States)

    Sheffet, Alice J.; Flaxman, Linda; Tom, MeeLee; Hughes, Susan E.; Longbottom, Mary E.; Howard, Virginia J.; Marler, John R.; Brott, Thomas G.

    2014-01-01

    Background The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) received five years’ funding ($21,112,866) from the National Institutes of Health to compare carotid stenting to surgery for stroke prevention in 2,500 randomized participants at 40 sites. Aims Herein we evaluate the change in the CREST budget from a fixed to variable-cost model and recommend strategies for the financial management of large-scale clinical trials. Methods Projections of the original grant’s fixed-cost model were compared to the actual costs of the revised variable-cost model. The original grant’s fixed-cost budget included salaries, fringe benefits, and other direct and indirect costs. For the variable-cost model, the costs were actual payments to the clinical sites and core centers based upon actual trial enrollment. We compared annual direct and indirect costs and per-patient cost for both the fixed and variable models. Differences between clinical site and core center expenditures were also calculated. Results Using a variable-cost budget for clinical sites, funding was extended by no-cost extension from five to eight years. Randomizing sites tripled from 34 to 109. Of the 2,500 targeted sample size, 138 (5.5%) were randomized during the first five years and 1,387 (55.5%) during the no-cost extension. The actual per-patient costs of the variable model were 9% ($13,845) of the projected per-patient costs ($152,992) of the fixed model. Conclusions Performance-based budgets conserve funding, promote compliance, and allow for additional sites at modest additional cost. Costs of large-scale clinical trials can thus be reduced through effective management without compromising scientific integrity. PMID:24661748

  7. Biomechanical competence of six different bone screws for reconstructive surgery in three different transplants: Fibular, iliac crest, scapular and artificial bone.

    Science.gov (United States)

    Pietsch, Arnold P; Raith, Stefan; Ode, Jan-Eric; Teichmann, Jan; Lethaus, Bernd; Möhlhenrich, Stephan C; Hölzle, Frank; Duda, Georg N; Steiner, Timm

    2016-06-01

    The goal of this study was to determine a combination of screw and transplantation type that offers optimal primary stability for reconstructive surgery. Fibular, iliac crest, and scapular transplants were tested along with artificial bone substrate. Six different kinds of bone screws (Medartis(©)) were compared, each type utilized with one of six specimens from human transplants (n = 6). Controlled screw-in-tests were performed and the required torque was protocolled. Subsequently, pull-out-tests were executed to determine the retention forces. The artificial bone substitute material showed significantly higher retention forces than real bone samples. The self-drilling screws achieved the significantly highest retention values in the synthetic bone substitute material. Cancellous screws achieved the highest retention in the fibular transplants, while self-drilling and cancellous screws demonstrated better retention than cortical screws in the iliac crest. In the scapular graft, no significant differences were found between the screw types. In comparison to the human transplant types, the cortical screws showed the significantly highest values in the fibula and the lowest values in the iliac crest. The best retention was found in the combination of cancellous screws with fibular graft (514.8 N + -252.3 N). For the flat bones (i.e., scapular and illiac crest) we recommend the cancellous screws. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  8. A role for chemokine signaling in neural crest cell migration and craniofacial development

    Science.gov (United States)

    Killian, Eugenia C. Olesnicky; Birkholz, Denise A.; Artinger, Kristin Bruk

    2009-01-01

    Neural crest cells (NCCs) are a unique population of multipotent cells that migrate along defined pathways throughout the embryo and give rise to many diverse cell types including pigment cells, craniofacial cartilage and the peripheral nervous system (PNS). Aberrant migration of NCCs results in a wide variety of congenital birth defects including craniofacial abnormalities. The chemokine Sdf1 and its receptors, Cxcr4 and Cxcr7, have been identified as key components in the regulation of cell migration in a variety of tissues. Here we describe a novel role for the zebrafish chemokine receptor Cxcr4a in the development and migration of cranial NCCs (CNCCs). We find that loss of Cxcr4a, but not Cxcr7b results in aberrant CNCC migration, defects in the neurocranium, as well as cranial ganglia dismorphogenesis. Moreover, overexpression of either Sdf1b or Cxcr4a causes aberrant CNCC migration and results in ectopic craniofacial cartilages. We propose a model in which Sdf1b signaling from the pharyngeal arch endoderm and optic stalk to Cxcr4a expressing CNCCs is important for both the proper condensation of the CNCCs into pharyngeal arches and the subsequent patterning and morphogenesis of the neural crest derived tissues. PMID:19576198

  9. Estimation of Overtopping Rates on Slopes in Wave Power Devices and Other Low Crested Structures

    DEFF Research Database (Denmark)

    Kofoed, Jens Peter; Burcharth, Hans Falk

    2002-01-01

    Motivated by questions raised by developers of wave energy devices based on wave overtopping concepts, model tests have been performed to study overtopping of structures with limited draught, low crest freeboards and slope geometries designed to increase overtopping and thereby also the captured...

  10. Financial management of a large multisite randomized clinical trial.

    Science.gov (United States)

    Sheffet, Alice J; Flaxman, Linda; Tom, MeeLee; Hughes, Susan E; Longbottom, Mary E; Howard, Virginia J; Marler, John R; Brott, Thomas G

    2014-08-01

    The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) received five years' funding ($21 112 866) from the National Institutes of Health to compare carotid stenting to surgery for stroke prevention in 2500 randomized participants at 40 sites. Herein we evaluate the change in the CREST budget from a fixed to variable-cost model and recommend strategies for the financial management of large-scale clinical trials. Projections of the original grant's fixed-cost model were compared to the actual costs of the revised variable-cost model. The original grant's fixed-cost budget included salaries, fringe benefits, and other direct and indirect costs. For the variable-cost model, the costs were actual payments to the clinical sites and core centers based upon actual trial enrollment. We compared annual direct and indirect costs and per-patient cost for both the fixed and variable models. Differences between clinical site and core center expenditures were also calculated. Using a variable-cost budget for clinical sites, funding was extended by no-cost extension from five to eight years. Randomizing sites tripled from 34 to 109. Of the 2500 targeted sample size, 138 (5·5%) were randomized during the first five years and 1387 (55·5%) during the no-cost extension. The actual per-patient costs of the variable model were 9% ($13 845) of the projected per-patient costs ($152 992) of the fixed model. Performance-based budgets conserve funding, promote compliance, and allow for additional sites at modest additional cost. Costs of large-scale clinical trials can thus be reduced through effective management without compromising scientific integrity. © 2014 The Authors. International Journal of Stroke © 2014 World Stroke Organization.

  11. Blood pressure changes associated with sibutramine and weight management - an analysis from the 6-week lead-in period of the sibutramine cardiovascular outcomes trial (SCOUT)

    DEFF Research Database (Denmark)

    Sharma, A M; Caterson, I D; Coutinho, W

    2009-01-01

    OBJECTIVE: To explore vital sign changes among patient subgroups during the 6-week lead-in period of the sibutramine cardiovascular outcomes (SCOUT) trial. METHODS: SCOUT is an ongoing, double-blind, randomized, placebo-controlled outcome trial in overweight/obese patients at high risk of a cardi......OBJECTIVE: To explore vital sign changes among patient subgroups during the 6-week lead-in period of the sibutramine cardiovascular outcomes (SCOUT) trial. METHODS: SCOUT is an ongoing, double-blind, randomized, placebo-controlled outcome trial in overweight/obese patients at high risk...... of a cardiovascular event. During the 6-week lead-in period, 10,742 patients received sibutramine and weight management. Vital sign changes were assessed post hoc by initial blood pressure (mmHg) categorized as normal (or=140/>or=90); weight change...... categories (weight gain/no weight change, >0 to 2.5% weight loss, >2.5 to 5% weight loss and >5% weight loss) and current antihypertensive medication class use (none, one, or two or more). To assess the impact of sibutramine on blood pressure and pulse rate, only patients (N = 10,025) who reported no change...

  12. The effects of prepulse-blink reflex trial repetition and prepulse change on blink reflex modification at short and long lead intervals.

    Science.gov (United States)

    Lipp, O V; Siddle, D A

    1998-01-01

    Prepulse inhibition and facilitation of the blink reflex are said to reflect different responses elicited by the lead stimulus, transient detection and orienting response respectively. Two experiments investigated the effects of trial repetition and lead stimulus change on blink modification. It was hypothesized that these manipulations will affect orienting and thus blink facilitation to a greater extent than they will affect transient detection and thus blink inhibition. In Experiment 1 (N = 64), subjects were trained with a sequence of 12 lead stimulus and 12 blink stimulus alone presentations, and 24 lead stimulus-blink stimulus pairings. Lead interval was 120 ms for 12 of the trials and 2000 ms for the other 12. For half the subjects this sequence was followed by a change in pitch of the lead stimulus. In Experiment 2 (N = 64), subjects were trained with a sequence of 36 blink alone stimuli and 36 lead stimulus-blink stimulus pairings. The lead interval was 120 ms for half the subjects and 2000 ms for the other half. The pitch of the lead stimulus on prestimulus trials 31-33 was changed for half the subjects in each group. In both experiments, the amount of blink inhibition decreased during training whereas the amount of blink facilitation remained unchanged. Lead stimulus change had no effect on blink modification in either experiment although it resulted in enhanced skin conductance responses and greater heart rate deceleration in Experiment 2. The present results are not consistent with the notion that blink facilitation is linked to orienting whereas blink inhibition reflects a transient detection mechanism.

  13. Diet of double-crested cormorants wintering in Texas

    Science.gov (United States)

    Campo, J.J.; Thompson, B.C.; Barron, J.C.; Telfair II, R. C.; Durocher, P.; Gutreuter, S.

    1993-01-01

    The diets of 420 Double-crested Cormorants (Phalacrocorax auritus) were studied during November 1986-March 1987 on eight public reservoirs in Texas. Prey included 29 fish species and the mean live weight of fish per bird was 122 g. Fishes a??415 mm long were ingested, but those a??125 mm accounted for 90% of cormorant food contents by number. Shad (Dorosoma spp.) and sunfishes (Lepomis spp.) accounted for 90% of the total food items by number. Consumption of fishes (percent by weight) was different for male vs. female and adult vs. juvenile cormorants. Total consumption of fish by weight was consistent throughout the period; however, fewer but much larger fish were consumed after 15 February. Cormorants ate fishes that were most abundant in reservoirs. Sport fishes made up a substantial portion of cormorant food by weight, but not by number on some reservoirs. Cormorants ate very few large sport fish, however.

  14. Computerized determination of 3-D connectivity density in human iliac crest bone biopsies

    DEFF Research Database (Denmark)

    Thomsen, J.S.; Mosekilde, Li.; Barlach, J.

    1996-01-01

    Combining the physical disector principle with an algorithm for automatic non-linear alignment of disector pairs we have developed a software system for direct measurement of 3D connectivity densities in iliac crest bone biopsies. The method was applied to biopsies from 14 non-selected autopsy...... cases: 7 men (age range 20-84 yr) and 7 women (age range 20-86 yr). The study reveals decreases in both trabecular bone mass and connectivity density with age in women....

  15. Reproductive behavior of the Red-crested Finch Coryphospingus cucullatus (Aves: Thraupidae in southeastern Brazil

    Directory of Open Access Journals (Sweden)

    Paulo V.Q. Zima

    Full Text Available ABSTRACT Several behavioral aspects of the Red-crested Finch Coryphospingus cucullatus (Statius Müller, 1776 are poorly studied. Here we provide reproductive information on 16 active nests. This information may be valuable to elucidate the phylogenetic relationships of this bird, and to design plans to manage it. Nesting activities occurred from October to February. Clutches consisted of two to three eggs (2.06 ± 0.25, which were laid on consecutive days. Incubation usually started the morning the females laid their last egg and lasted 11.27 ± 0.47 days. Hatching was synchronous, or happened at a one-day interval. The nestling stage lasted 12 ± 0.89 days. Only females incubated the eggs and they fed the young more often than the males did. Overall nesting success, from incubation to fledging, was 28.2%. Nest architecture and egg color proved to be diagnostic characteristics of Coryphospingus , supporting its maintenance as a distinct genus within the recently proposed sub-family Tachyphoninae. Red-crested Finches showed a preference for certain nesting sites, i.e., forest borders or a Cerrado in late regeneration stage. This information can be useful to programs aiming to release illegally trapped individuals.

  16. Iliac crest autograft versus alternative constructs for anterior cervical spine surgery: Pros, cons, and costs

    Science.gov (United States)

    Epstein, Nancy E.

    2012-01-01

    Background: Grafting choices available for performing anterior cervical diskectomy/fusion (ACDF) procedures have become a major concern for spinal surgeons, and their institutions. The “gold standard”, iliac crest autograft, may still be the best and least expensive grafting option; it deserves to be reassessed along with the pros, cons, and costs for alternative grafts/spacers. Methods: Although single or multilevel ACDF have utilized iliac crest autograft for decades, the implant industry now offers multiple alternative grafting and spacer devices; (allografts, cages, polyether-etherketone (PEEK) amongst others). While most studies have focused on fusion rates and clinical outcomes following ACDF, few have analyzed the “value-added” of these various constructs (e.g. safety/efficacy, risks/complications, costs). Results: The majority of studies document 95%-100% fusion rates when iliac crest autograft is utilized to perform single level ACDF (X-ray or CT confirmed at 6-12 postoperative months). Although many allograft studies similarly quote 90%-100% fusion rates (X-ray alone confirmed at 6-12 postoperative months), a recent “post hoc analysis of data from a prospective multicenter trial” (Riew KD et. al., CSRS Abstract Dec. 2011; unpublished) revealed a much higher delayed fusion rate using allografts at one year 55.7%, 2 years 87%, and four years 92%. Conclusion: Iliac crest autograft utilized for single or multilevel ACDF is associated with the highest fusion, lowest complication rates, and significantly lower costs compared with allograft, cages, PEEK, or other grafts. As spinal surgeons and institutions become more cost conscious, we will have to account for the “value added” of these increasingly expensive graft constructs. PMID:22905321

  17. Concentration profiling of minerals in iliac crest bone tissue of opium addicted humans using inductively coupled plasma and discriminant analysis techniques.

    Science.gov (United States)

    Mani-Varnosfaderani, Ahmad; Jamshidi, Mahbobeh; Yeganeh, Ali; Mahmoudi, Mani

    2016-02-20

    Opium addiction is one of the main health problems in developing countries and induces serious defects on the human body. In this work, the concentrations of 32 minerals including alkaline, heavy and toxic metals have been determined in the iliac crest bone tissue of 22 opium addicted individuals using inductively coupled plasma-optical emission spectroscopy (ICP-OES). The bone tissues of 30 humans with no physiological and metabolomic diseases were used as the control group. For subsequent analyses, the linear and quadratic discriminant analysis techniques have been used for classification of the data into "addicted" and "non-addicted" groups. Moreover, the counter-propagation artificial neural network (CPANN) has been used for clustering of the data. The results revealed that the CPANN is a robust model and thoroughly classifies the data. The area under the curve for the receiver operating characteristic curve for this model was more than 0.91. Investigation of the results revealed that the opium consumption causes a deficiency in the level of Calcium, Phosphate, Potassium and Sodium in iliac crest bone tissue. Moreover, this type of addiction induces an increment in the level of toxic and heavy metals such as Co, Cr, Mo and Ni in iliac crest tissue. The correlation analysis revealed that there were no significant dependencies between the age of the samples and the mineral content of their iliac crest, in this study. The results of this work suggest that the opium addicted individuals need thorough and restricted dietary and medical care programs after recovery phases, in order to have healthy bones. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Meis2 is essential for cranial and cardiac neural crest development

    Czech Academy of Sciences Publication Activity Database

    Machoň, Ondřej; Mašek, Jan; Machoňová, Olga; Krauss, S.; Kozmik, Zbyněk

    2015-01-01

    Roč. 15, Nov 6 (2015) ISSN 1471-213X R&D Projects: GA ČR GAP305/12/2042; GA MŠk(CZ) LK11214 Institutional support: RVO:68378050 Keywords : Meis2 * Persistent truncus arteriosus * Neural crest * Craniofacial skeleton * Cranial nerves Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.096, year: 2015

  19. CREST biorepository for translational studies on malignant mesothelioma, lung cancer and other respiratory tract diseases: Informatics infrastructure and standardized annotation.

    Science.gov (United States)

    Ugolini, Donatella; Neri, Monica; Bennati, Luca; Canessa, Pier Aldo; Casanova, Georgia; Lando, Cecilia; Leoncini, Giacomo; Marroni, Paola; Parodi, Barbara; Simonassi, Claudio; Bonassi, Stefano

    2012-03-01

    Advances in molecular epidemiology and translational research have led to the need for biospecimen collection. The Cancer of the Respiratory Tract (CREST) biorepository is concerned with pleural malignant mesothelioma (MM) and lung cancer (LC). The biorepository staff has collected demographic and epidemiological data directly from consenting subjects using a structured questionnaire, in agreement with The Public Population Project in Genomics (P(3)G). Clinical and follow-up data were collected. Sample data were also recorded. The architecture is based on a database designed with Microsoft Access. Data standardization was carried out to conform with established conventions or procedures. As from January 31, 2011, the overall number of recruited subjects was 1,857 (454 LC, 245 MM, 130 other cancers and 1,028 controls). Due to its infrastructure, CREST was able to join international projects, sharing samples and/or data with other research groups in the field. The data management system allows CREST to be involved, through a minimum data set, in the national project for the construction of the Italian network of Oncologic BioBanks (RIBBO), and in the infrastructure of a pan-European biobank network (BBMRI). The CREST biorepository is a valuable tool for translational studies on respiratory tract diseases, because of its simple and efficient infrastructure.

  20. Can FDG-PET/CT replace blind bone marrow biopsy of the posterior iliac crest in Ewing sarcoma?

    NARCIS (Netherlands)

    Kasalak, Omer; Glaudemans, Andor W. J. M.; Overbosch, Jelle; Jutte, Paul C.; Kwee, Thomas C.

    OBJECTIVE: To determine and compare the value of (18)F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) to blind bone marrow biopsy (BMB) of the posterior iliac crest in detecting metastatic bone marrow involvement in newly diagnosed Ewing sarcoma. MATERIALS AND

  1. Properties of Neural Crest-Like Cells Differentiated from Human Embryonic Stem Cells

    Czech Academy of Sciences Publication Activity Database

    Křivánek, J.; Švandová, Eva; Králik, J.; Hajda, S.; Fedr, Radek; Vinařský, V.; Jaroš, J.; Souček, Karel

    2014-01-01

    Roč. 60, č. 2014 (2014), s. 30-38 ISSN 0015-5500 R&D Projects: GA ČR(CZ) GAP304/11/1418 Institutional support: RVO:68081707 Keywords : stem cell differentiation * neural crest * odontogenesis Subject RIV: BO - Biophysics; ED - Physiology (UZFG-Y) Impact factor: 1.000, year: 2014

  2. A Colonial Conundrum: Boy with Sulphur-Crested Cockatoo

    Directory of Open Access Journals (Sweden)

    Elisabeth Findlay

    2008-12-01

    Full Text Available This paper presents a detailed analysis of the perplexing painting Boy with Sulphur-Crested Cockatoo. Unfortunately, there is little information on the provenance of the portrait, including the identity of the artist, sitter and patron. It will be argued that it is the work of Augustus Earle and that it is a portrait of Daniel Cooper II and was commissioned by his uncle, also named Daniel Cooper. The aim of this article is to start to unravel the ambiguities of the image, and I suggest that the painting is a strong statement on the rights of freed convicts in Australian colonial society

  3. New Results from the NOAA CREST Lidar Network (CLN Observations in the US Eastcoast

    Directory of Open Access Journals (Sweden)

    Moshary Fred

    2016-01-01

    Full Text Available This paper presents coordinated ground-based observations by the NOAA-CREST Lidar Network (CLN for profiling of aerosols, cloud, water vapor, and wind along the US east coast including Caribbean region at Puerto Rico. The instrumentation, methodology and observation capability are reviewed. The applications to continental and intercontinental-scale transport of smoke and dust plumes, and their large scale regional impact are discussed.

  4. 50 CFR 21.48 - Depredation order for double-crested cormorants to protect public resources.

    Science.gov (United States)

    2010-10-01

    ..., BARTER, EXPORTATION, AND IMPORTATION OF WILDLIFE AND PLANTS (CONTINUED) MIGRATORY BIRD PERMITS Control of..., wildlife, plants, and their habitats) caused by double-crested cormorants. (b) In what areas can this..., Minnesota, Mississippi, Missouri, New York, North Carolina, Ohio, Oklahoma, South Carolina, Tennessee, Texas...

  5. Multielement analysis of iliac crest bone by neutron activation

    International Nuclear Information System (INIS)

    Aras, N.K.; Yilmaz, G.; Korkusuz, F.; Olmez, I.; Sepici, B.; Eksioglu, F.; Bode, P.

    2000-01-01

    Bone samples from iliac crest were obtained from apparently healthy female (n = 4) and male (n = 8) subjects with ages between 15-50. Cortical and trabecular parts were separated and soft tissues like fat, muscle and blood were removed. Calcium, Mg, Na, Cl, Fe, Zn, Br, Sr, and Cs were determined by instrumental neutron activation analysis and other techniques, and their relations were discussed. Fairly good agreement was obtained with literature data. These values may serve as reference values for subjects from a Turkish population. (author)

  6. Discharge coefficient of a rectangular sharp-edged broad-crested weir

    OpenAIRE

    Zachoval Zbyněk; Knéblová Michaela; Roušar Ladislav; Rumann Ján; Šulc Jan

    2014-01-01

    his paper is concerned with the determination of the relationship for the calculation of the discharge coefficient at free overflow over a rectangular sharp-edged broad-crested weir without lateral contraction. The determination was made on the basis of new measurement in a range of the relative thickness of the weir from 0.12 to 0.30 and newly in a large range of relative height of the weir extremely from 0.24 to 6.8 which greatly expands the application possibilities of low weirs. In additi...

  7. Crest Factor Reduction in MC-CDMA Employing Carrier Interferometry Codes

    Directory of Open Access Journals (Sweden)

    Natarajan Balasubramaniam

    2004-01-01

    Full Text Available This paper addresses signal compactness issues in MC-CDMA employing carrier interferometry codes using the measure of crest factor (CF. Carrier interferometry codes, applied to N -carrier MC-CDMA systems, enable 2N users to simultaneously share the system bandwidth with minimal degradation in performance (relative to the N -orthogonal-user case. First, for a fully loaded ( K=N and K=2N users MC-CDMA system with practical values of N , it is shown that the CF in downlink transmission demonstrates desirable properties of low mean and low variance. The downlink CF degrades when the number of users in the system decreases. Next, the high CF observed in the uplink is characterized and the poor CF in a partially loaded downlink as well as uplink is effectively combated using Schroeder's analytical CF reduction techniques.

  8. Medical image of the week: CREST plus ILD

    Directory of Open Access Journals (Sweden)

    Oliva I

    2013-06-01

    Full Text Available A 60 year old female with a history of fibromyalgia presented with dyspnea and skin changes, predominantly on the hands. Physical exam and imaging showed classic findings of limited cutaneous systemic sclerosis (scleroderma CREST syndrome. Calcinosis cutis (Figure 1A, Raynaud’s (not shown but endorsed by the patient, Esophageal dysmotility (Figure 1B, dilated esophagus, Sclerodactyly (Figure 1C, and Teleganectasias (Figure 1D were all present. Ground glass opacities were seen predominantly in the bilateral lower lung zones, associated with increased reticular markings (Figure 2A, and traction bronchiectasis (Figure 2B. Pulmonary involvement is noted in the majority of scleroderma patients. Interstitial lung disease (ILD is common and often portends a poor prognosis.

  9. Clinical effectiveness of 99mTc-diphosphonate scintigraphy of revascularized iliac crest flaps

    International Nuclear Information System (INIS)

    Smeele, L.E.; Hoekstra, O.S.; Winters, H.A.H.; Leemans, C.R.

    1996-01-01

    Clinical assessment of the perfusion of the musculocutaneous portion of composite iliac crest free flaps was compared to 99m Tc-diphosphonate (HDP) uptake in 14 patients who underwent primary oromandibular reconstruction after ablative cancer surgery. Bone scanning was performed on average at the 9-10th postoperative day (range 4-48) 3 h after intravenous injection of 550 MBq 99m Tc-HDP. Eleven patients showed complete concordance between 99m Tc-HDP uptake and soft-tissue status. Two patients showed uptake and viable muscle in spite of necrotic skin. One patient had a viable musculocutaneous flap but a photopenic defect in the bone graft; 6 months later, a small corresponding part of the bone was sequestrated. In this study, bone scanning and clinical assessment of muscle perfusion were 100% accurate in predicting viability of bone graft. Skin viability was a less reliable parameter. It is concluded that bone scanning is not indicated as routine investigation for revascularized iliac crest flaps and that clinical assessment of muscle perfusion is a reliable monitor of the early function of such flaps. (au) 8 refs

  10. Structural peculiarities of the sedimentary cover of the MAR crest depressions (5°-8°N) in the Equatorial Atlantics

    Science.gov (United States)

    Skolotnev, S. G.; Tsukanov, N. V.; Turko, N. N.; Peyve, A. A.

    2003-04-01

    The analysis of the bottom relief structure investigated with multibeam SIMRAD 12S and sedimentary cover of depressions investigeted with PARASAUND in the MAR crest zone near Sierra-Leone Fault (22 Cruise of the RV "Akademik Nikolay Strachov", and 10 Cruise of the RV "Akademik Ioffe") point on the complicated character of the tectonic activity distribution in this region. The left-lateral displacements of the rift velley and the absence of transform faults are typical for this region. Two extremely deep rift depressions (up to 5000 m) are located in the rift valley: one on 5°54'N latitude (Markov depression) and the other on 5°46'N latitude. About 40 m sediments cover their bottom. On contary, in the depression located parallel to the rift valley directly to the west from the two mentioned rift depressions the sedimentary cover is absent and bottom has very dissected, apparently volcanic, relief. In the MAR crest zone in 20 miles to the south-west from the Markov and 5°46'N depressions one can see a system of depressions oriented both parallel and oblique to the rift valley. There are filled by the sediments of different thickness. The sedimentary cover of these depressions often is tired and deformed by diapir and horst uplifts. Dredging data show, that basalts, which represent, according to their petro-geo-chemical characteristics the enriched MORB basalts and alkaline basalts compose these uplifts. Irregular distribution and character of composition of the sediments in the depressions of crest zone of the MAR segment under consideration along with high volcanic activity outside the axial spreding zone show that tectonic and volcanic activity in this area are distributed all over the crest zone. The complicated character of this activity is obviosly caused by two reasons. From one hand it may be a deep mantle plum, as inferred from basalt composition and from the other hand it may be the lithosphere blocks displacements along the left-lateral strike slips.

  11. Dental anomalies in different cleft groups related to neural crest developmental fields contributes to the understanding of cleft aetiology

    DEFF Research Database (Denmark)

    Riis, Louise Claudius; Kjær, Inger; Mølsted, Kirsten

    2014-01-01

    OBJECTIVE: To analyze dental deviations in three cleft groups and relate findings to embryological neural crest fields (frontonasal, maxillary, and palatal). The overall purpose was to evaluate how fields are involved in different cleft types. DESIGN: Retrospective audit of clinical photographs...

  12. Unraveling the rapid radiation of crested newts, Triturus cristatus superspecies, using complete mitogenomic sequences

    NARCIS (Netherlands)

    Wielstra, B.M.; Arntzen, J.W.

    2011-01-01

    Background - The rapid radiation of crested newts (Triturus cristatus superspecies) comprises four morphotypes: 1) the T. karelinii group, 2) T. carnifex - T. macedonicus, 3) T. cristatus and 4) T. dobrogicus. These vary in body build and the number of rib-bearing pre-sacral vertebrae (NRBV). The

  13. In vivo transplantation of enteric neural crest cells into mouse gut; Engraftment, functional integration and long-term safety

    NARCIS (Netherlands)

    J.E. Cooper (Julie E.); C. Mccann; D. Natarajan (Dipa); S. Choudhury; W. Boesmans (Werend); J.-M. Delalande (Jean-Marie); P.V. Berghe (Pieter Vanden); A.J. Burns (Alan); N. Thapar (Nikhil)

    2016-01-01

    textabstractObjectives: Enteric neuropathies are severe gastrointestinal disorders with unsatisfactory outcomes. We aimed to investigate the potential of enteric neural stem cell therapy approaches for such disorders by transplanting mouse enteric neural crest cells (ENCCs) into ganglionic and

  14. Progress towards a measurement of the UHE cosmic ray electron flux using the CREST Instrument

    Science.gov (United States)

    Musser, Jim; Wakely, Scott; Coutu, Stephane; Geske, Matthew; Nutter, Scott; Tarle, Gregory; Park, Nahee; Schubnell, Michael; Gennaro, Joseph; Muller, Dietrich

    2012-07-01

    Electrons of energy beyond about 3 TeV have never been detected in the flux of cosmic rays at Earth despite strong evidence of their presence in a number of supernova remnants (e.g., SN 1006). The detection of high energy electrons at Earth would be extremely significant, yielding information about the spatial distribution of nearby cosmic ray sources. With the Cosmic Ray Electron Synchrotron Telescope (CREST), our collaboration has adopted a novel approach to the detection of electrons of energies between 2 and 50 TeV which results in a substantial increase in the acceptance and sensitivity of the apparatus relative to its physics size. The first LDB flight of the CREST detector took place in January 2012, with a float duration of approximately 10 days. In this paper we describe the flight performance of the instrument, and progress in the analysis of the data obtained in this flight.

  15. Weight and blood pressure response to weight management and sibutramine in diabetic and non-diabetic high-risk patients: an analysis from the 6-week lead-in period of the sibutramine cardiovascular outcomes (SCOUT) trial

    DEFF Research Database (Denmark)

    Van Gaal, L F; Caterson, I D; Coutinho, W

    2010-01-01

    To assess treatment responses to sibutramine and weight management in diabetic patients during the lead-in period of the Sibutramine Cardiovascular OUTcomes (SCOUT) trial.......To assess treatment responses to sibutramine and weight management in diabetic patients during the lead-in period of the Sibutramine Cardiovascular OUTcomes (SCOUT) trial....

  16. Nymphal Linguatulosis in Indian Crested Porcupines (Histrix Indica in Southwest of Iran

    Directory of Open Access Journals (Sweden)

    Mohammad Rajabloo

    2015-10-01

    Full Text Available Linguatula serrata is one of the important zoonotic parasites. Carnivores serve as definitive host. The larvae existed in mesenteric lymph nodes (MLNs, liver, lungs, etc of intermediate herbivores. The definitive host becomes infected by ingesting viscera containing the infective nymphal stage. Humans may be infected with Linguatula either by ingestion of nymphs resulting in a condition called nasopharyngeal linguatulosis or Halzoun syndrome or by ingestionof infective eggs which develop in internal organs resulting in visceral linguatulosis. Indian crested porcupine (Hystrix indica is a common rodent in Middle East. Based on some tradition, consumption of Histrix meat andviscera is common in some parts of Iran. The present study reports the occurrence of Linguatula serrata nymph in H. indica as a new intermediate host from southwest of Iran.

  17. Spatial ecology of the critically endangered Fijian crested iguana, Brachylophus vitiensis, in an extremely dense population: implications for conservation.

    Science.gov (United States)

    Morrison, Suzanne F; Biciloa, Pita; Harlow, Peter S; Keogh, J Scott

    2013-01-01

    The Critically Endangered Fijian crested iguana, Brachylophus vitiensis, occurs at extreme density at only one location, with estimates of >10,000 iguanas living on the 70 hectare island of Yadua Taba in Fiji. We conducted a mark and recapture study over two wet seasons, investigating the spatial ecology and intraspecific interactions of the strictly arboreal Fijian crested iguana. This species exhibits moderate male-biased sexual size dimorphism, which has been linked in other lizard species to territoriality, aggression and larger male home ranges. We found that male Fijian crested iguanas exhibit high injury levels, indicative of frequent aggressive interactions. We did not find support for larger home range size in adult males relative to adult females, however male and female residents were larger than roaming individuals. Males with established home ranges also had larger femoral pores relative to body size than roaming males. Home range areas were small in comparison to those of other iguana species, and we speculate that the extreme population density impacts considerably on the spatial ecology of this population. There was extensive home range overlap within and between sexes. Intersexual overlap was greater than intrasexual overlap for both sexes, and continuing male-female pairings were observed among residents. Our results suggest that the extreme population density necessitates extensive home range overlap even though the underlying predictors of territoriality, such as male biased sexual size dimorphism and high aggression levels, remain. Our findings should be factored in to conservation management efforts for this species, particularly in captive breeding and translocation programs.

  18. Spatial ecology of the critically endangered Fijian crested iguana, Brachylophus vitiensis, in an extremely dense population: implications for conservation.

    Directory of Open Access Journals (Sweden)

    Suzanne F Morrison

    Full Text Available The Critically Endangered Fijian crested iguana, Brachylophus vitiensis, occurs at extreme density at only one location, with estimates of >10,000 iguanas living on the 70 hectare island of Yadua Taba in Fiji. We conducted a mark and recapture study over two wet seasons, investigating the spatial ecology and intraspecific interactions of the strictly arboreal Fijian crested iguana. This species exhibits moderate male-biased sexual size dimorphism, which has been linked in other lizard species to territoriality, aggression and larger male home ranges. We found that male Fijian crested iguanas exhibit high injury levels, indicative of frequent aggressive interactions. We did not find support for larger home range size in adult males relative to adult females, however male and female residents were larger than roaming individuals. Males with established home ranges also had larger femoral pores relative to body size than roaming males. Home range areas were small in comparison to those of other iguana species, and we speculate that the extreme population density impacts considerably on the spatial ecology of this population. There was extensive home range overlap within and between sexes. Intersexual overlap was greater than intrasexual overlap for both sexes, and continuing male-female pairings were observed among residents. Our results suggest that the extreme population density necessitates extensive home range overlap even though the underlying predictors of territoriality, such as male biased sexual size dimorphism and high aggression levels, remain. Our findings should be factored in to conservation management efforts for this species, particularly in captive breeding and translocation programs.

  19. Spatial Ecology of the Critically Endangered Fijian Crested Iguana, Brachylophus vitiensis, in an Extremely Dense Population: Implications for Conservation

    Science.gov (United States)

    Morrison, Suzanne F.; Biciloa, Pita; Harlow, Peter S.; Keogh, J. Scott

    2013-01-01

    The Critically Endangered Fijian crested iguana, Brachylophus vitiensis, occurs at extreme density at only one location, with estimates of >10,000 iguanas living on the 70 hectare island of Yadua Taba in Fiji. We conducted a mark and recapture study over two wet seasons, investigating the spatial ecology and intraspecific interactions of the strictly arboreal Fijian crested iguana. This species exhibits moderate male-biased sexual size dimorphism, which has been linked in other lizard species to territoriality, aggression and larger male home ranges. We found that male Fijian crested iguanas exhibit high injury levels, indicative of frequent aggressive interactions. We did not find support for larger home range size in adult males relative to adult females, however male and female residents were larger than roaming individuals. Males with established home ranges also had larger femoral pores relative to body size than roaming males. Home range areas were small in comparison to those of other iguana species, and we speculate that the extreme population density impacts considerably on the spatial ecology of this population. There was extensive home range overlap within and between sexes. Intersexual overlap was greater than intrasexual overlap for both sexes, and continuing male-female pairings were observed among residents. Our results suggest that the extreme population density necessitates extensive home range overlap even though the underlying predictors of territoriality, such as male biased sexual size dimorphism and high aggression levels, remain. Our findings should be factored in to conservation management efforts for this species, particularly in captive breeding and translocation programs. PMID:24019902

  20. Neuropilin-1 interacts with the second branchial arch microenvironment to mediate chick neural crest cell dynamics

    Science.gov (United States)

    McLennan, Rebecca; Kulesa, Paul M.

    2011-01-01

    Cranial neural crest cells (NCCs) require neuropilin signaling to reach and invade the branchial arches. Here, we use an in vivo chick model to investigate whether the neuropilin-1 knockdown phenotype is specific to the second branchial arch (ba2), changes in NCC behaviors and phenotypic consequences, and whether neuropilins work together to facilitate entry into and invasion of ba2. We find that cranial NCCs with reduced neuropilin-1 expression displayed shorter protrusions and decreased cell body and nuclear length-to-width ratios characteristic of a loss in polarity and motility, after specific interaction with ba2. Directed NCC migration was rescued by transplantation of transfected cells into rhombomere 4 of younger hosts. Lastly, reduction of neuropilin-2 expression by shRNA either solely or with reduction of neuropilin-1 expression did not lead to a stronger head phenotype. Thus, NCCs, independent of rhombomere origin, require neuropilin-1, but not neuropilin-2 to maintain polarity and directed migration into ba2. PMID:20503363

  1. Temporary hindlimb paresis following dystocia due to foetal macrosomia in a Celebes crested macaque (Macaca nigra).

    Science.gov (United States)

    Debenham, John James; Bettembourg, Vanessa; Østevik, Liv; Modig, Michaela; Jâderlund, Karin Hultin; Lervik, Andreas

    2017-04-01

    A multiparous Celebes crested macaque presented with dystocia due to foetal macrosomia, causing foetal mortality and hindlimb paresis. After emergency caesarean section, recovery of motor function took 1 month before hindlimbs were weight bearing and 2 months before re-integration with the troop. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Age-related changes in molar topography and shearing crest length in a wild population of mountain Gorillas from Volcanoes National Park, Rwanda.

    Science.gov (United States)

    Glowacka, Halszka; McFarlin, Shannon C; Catlett, Kierstin K; Mudakikwa, Antoine; Bromage, Timothy G; Cranfield, Michael R; Stoinski, Tara S; Schwartz, Gary T

    2016-05-01

    Great ape teeth must remain functional over long lifespans. The molars of the most folivorous apes, the mountain gorillas, must maintain shearing function for 40+ years while the animals consume large quantities of mechanically challenging foods. While other folivorous primates experience dental senescence, which compromises their occlusal surfaces and affects their reproductive success as they age, it is unknown whether dental senescence also occurs in mountain gorillas. In this article, we quantified and evaluated how mountain gorilla molars change throughout their long lifespans. We collected high-resolution replicas of M(1)s (n = 15), M(2)s (n = 13), and M(3)s (n = 11) from a cross-sectional sample of wild mountain gorilla skeletons from the Virunga Volcanoes, ranging in age from 4 to 43 years. We employed dental topographic analyses to track how aspects of occlusal slope, angularity, relief index, and orientation patch count rotated change with age. In addition, we measured the relative length of shearing crests in two- and three-dimensions. Occlusal topography was found to decrease, while 2D relative shearing crest length increased, and 3D relative crest lengths were maintained with age. Our findings indicate that shearing function is maintained throughout the long lifetimes of mountain gorillas. Unlike the dental senescence experienced by other folivorous primates, mountain gorillas do not appear to possess senesced molars despite their long lifetimes, mechanically challenging diets, and decreases in occlusal topography with age. © 2016 Wiley Periodicals, Inc.

  3. Differentiation defect in neural crest-derived smooth muscle cells in patients with aortopathy associated with bicuspid aortic valves

    Directory of Open Access Journals (Sweden)

    Jiao Jiao

    2016-08-01

    Full Text Available Individuals with bicuspid aortic valves (BAV are at a higher risk of developing thoracic aortic aneurysms (TAA than patients with trileaflet aortic valves (TAV. The aneurysms associated with BAV most commonly involve the ascending aorta and spare the descending aorta. Smooth muscle cells (SMCs in the ascending and descending aorta arise from neural crest (NC and paraxial mesoderm (PM, respectively. We hypothesized defective differentiation of the neural crest stem cells (NCSCs-derived SMCs but not paraxial mesoderm cells (PMCs-derived SMCs contributes to the aortopathy associated with BAV. When induced pluripotent stem cells (iPSCs from BAV/TAA patients were differentiated into NCSC-derived SMCs, these cells demonstrated significantly decreased expression of marker of SMC differentiation (MYH11 and impaired contraction compared to normal control. In contrast, the PMC-derived SMCs were similar to control cells in these aspects. The NCSC-SMCs from the BAV/TAA also showed decreased TGF-β signaling based on phosphorylation of SMAD2, and increased mTOR signaling. Inhibition of mTOR pathway using rapamycin rescued the aberrant differentiation. Our data demonstrates that decreased differentiation and contraction of patient's NCSC-derived SMCs may contribute to that aortopathy associated with BAV.

  4. Interpreting clinical trial results by deductive reasoning: In search of improved trial design.

    Science.gov (United States)

    Kurbel, Sven; Mihaljević, Slobodan

    2017-10-01

    Clinical trial results are often interpreted by inductive reasoning, in a trial design-limited manner, directed toward modifications of the current clinical practice. Deductive reasoning is an alternative in which results of relevant trials are combined in indisputable premises that lead to a conclusion easily testable in future trials. © 2017 WILEY Periodicals, Inc.

  5. Investigating the Longer-Term Impact of the CREST Inquiry-Based Learning Programme on Student Self-regulated Processes and Related Motivations: Views of Students and Teachers

    Science.gov (United States)

    Moote, Julie

    2017-07-01

    This study investigates the impact of participation in the CREativity in Science and Technology (CREST) programme on student self-regulated processes and related motivations. The CREST scheme, a student-run science project managed by the British Science Association, is currently being implemented in schools across the UK to increase student engagement and motivation in science. Through implementing a rigorous quasi-experimental research design using two intervention conditions and one control group with immediate as well as 3-month delayed post-test data, the results documented both the immediate and longer-term positive impact of CREST participation on students' self-reported levels of self-regulation. The present study also investigates changes in teachers' perceptions of students' self-regulated learning through CREST programme participation. Group differences regarding changes in student self-reported self-regulation were not matched when looking at the teacher-reported self-regulated learning results at both immediate post-test and delayed post-test. These discrepancies are discussed in relation to analyses conducted on the other motivational constructs measured.

  6. Distress prevention by grooming others in crested black macaques.

    Science.gov (United States)

    Aureli, Filippo; Yates, Kerrie

    2010-02-23

    Allogrooming is probably one of the most common and most studied social behaviours in a variety of animals. Whereas the short-term benefits for the groomee have often been investigated, little is known about the effects for the groomer. Our study focused on the short-term effects of grooming another group member in seven adult female crested black macaques (Macaca nigra). We found reductions in self-directed behaviour, an indicator of anxiety, and aggressive tendencies soon after grooming, when compared to matched-control periods. These findings can be interpreted as evidence of distress prevention, possibly mediated by an increase in tolerance. Indeed, a former groomee was more likely to be the nearest neighbour of the former groomer in the 10 min after grooming ended. Thus, the role of grooming in short-term distress alleviation can be applicable to the groomer as well as the groomee. These short-term effects, together with the longer-term effects of large and/or strong grooming networks confirm that grooming, as well as receiving grooming, has great importance for social dynamics.

  7. Stage-specific control of neural crest stem cell proliferation by the small rho GTPases Cdc42 and Rac1

    DEFF Research Database (Denmark)

    Fuchs, Sebastian; Herzog, Dominik; Sumara, Grzegorz

    2009-01-01

    -renewal and proliferation of later stage, but not early migratory NCSCs. This stage-specific requirement for small Rho GTPases is due to changes in NCSCs that, during development, acquire responsiveness to mitogenic EGF acting upstream of both Cdc42 and Rac1. Thus, our data reveal distinct mechanisms for growth control......The neural crest (NC) generates a variety of neural and non-neural tissues during vertebrate development. Both migratory NC cells and their target structures contain cells with stem cell features. Here we show that these populations of neural crest-derived stem cells (NCSCs) are differentially...

  8. Stem cell property of postmigratory cranial neural crest cells and their utility in alveolar bone regeneration and tooth development.

    Science.gov (United States)

    Chung, Il-Hyuk; Yamaza, Takayoshi; Zhao, Hu; Choung, Pill-Hoon; Shi, Songtao; Chai, Yang

    2009-04-01

    The vertebrate neural crest is a multipotent cell population that gives rise to a variety of different cell types. We have discovered that postmigratory cranial neural crest cells (CNCCs) maintain mesenchymal stem cell characteristics and show potential utility for the regeneration of craniofacial structures. We are able to induce the osteogenic differentiation of postmigratory CNCCs, and this differentiation is regulated by bone morphogenetic protein (BMP) and transforming growth factor-beta signaling pathways. After transplantation into a host animal, postmigratory CNCCs form bone matrix. CNCC-formed bones are distinct from bones regenerated by bone marrow mesenchymal stem cells. In addition, CNCCs support tooth germ survival via BMP signaling in our CNCC-tooth germ cotransplantation system. Thus, we conclude that postmigratory CNCCs preserve stem cell features, contribute to craniofacial bone formation, and play a fundamental role in supporting tooth organ development. These findings reveal a novel function for postmigratory CNCCs in organ development, and demonstrate the utility of these CNCCs in regenerating craniofacial structures.

  9. Is dibotermin alfa a cost-effective substitute for autologous iliac crest bone graft in single level lumbar interbody spine fusion?

    Science.gov (United States)

    Svedbom, Axel; Paech, Daniel; Leonard, Catherine; Donnell, David; Song, Fujian; Boszcyk, Bronek; Rothenfluh, Dominique A; Lloyd, Andrew; Borgman, Benny

    2015-11-01

    To evaluate the cost-effectiveness of dibotermin alfa compared with autologous iliac crest bone graft (ICBG) for patients undergoing single level lumbar interbody spinal fusion in a UK hospital setting. An individual patient data (IPD) meta-analysis of six randomized controlled clinical trials and two single arm trials compared dibotermin alfa on an absorbable collagen implantation matrix (ACIM) (n = 456) and ICBG (n = 244) on resource use, re-operation rates, and SF-6D (Short form 6-dimension) health utility (total N = 700). Failure-related second surgery, operating time, post-operative hospital stay, and quality-adjusted life years (QALYs) derived from the IPD meta-analysis were included as inputs in an economic evaluation undertaken to assess the cost-effectiveness of dibotermin alfa/ACIM versus ICBG for patients undergoing single level lumbar interbody spinal fusion. A four year time horizon and the United Kingdom (UK) National Health Service (NHS) and Personal Social Services (PSS) perspective was adopted in the base case, with sensitivity analyses performed to gauge parameter uncertainty. In the base case analysis, patients treated using dibotermin alfa/ACIM (12 mg pack) accrued 0.055 incremental QALYs at an incremental cost of £ 737, compared with patients treated with ICBG. This resulted in an incremental cost-effectiveness ratio (ICER) of £ 13,523, indicating that at a willingness-to-pay threshold of £ 20,000, dibotermin alfa/ACIM is a cost-effective intervention relative to ICBG from the NHS and PSS perspective. In a UK hospital setting, dibotermin alfa/ACIM is a cost-effective substitute for ICBG for patients who require lumbar interbody arthrodesis.

  10. Dietary intake of Deepwater Horizon oil-injected live food fish by double-crested cormorants resulted in oxidative stress.

    Science.gov (United States)

    Pritsos, Karen L; Perez, Cristina R; Muthumalage, Thivanka; Dean, Karen M; Cacela, Dave; Hanson-Dorr, Katie; Cunningham, Fred; Bursian, Steven J; Link, Jane E; Shriner, Susan; Horak, Katherine; Pritsos, Chris A

    2017-12-01

    The Deepwater Horizon oil spill released 134 million gallons of crude oil into the Gulf of Mexico making it the largest oil spill in US history and exposing fish, birds, and marine mammals throughout the Gulf of Mexico to its toxicity. Fish eating waterbirds such as the double-crested cormorant (Phalacrocorax auritus) were exposed to the oil both by direct contact with the oil and orally through preening and the ingestion of contaminated fish. This study investigated the effects of orally ingestedMC252 oil-contaminated live fish food by double-crested cormorants on oxidative stress. Total, reduced, and oxidized glutathione levels, superoxide dismutase and glutathione peroxidase activities, total antioxidant capacity and lipid peroxidation were assessed in the liver tissues of control and treated cormorants. The results suggest that ingestion of the oil-contaminated fish resulted in significant increase in oxidative stress in the liver tissues of these birds. The oil-induced increase in oxidative stress could have detrimental impacts on the bird's life-history. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Influence of chronic alcoholism and oestrogen deficiency on the variation of stoichiometry of hydroxyapatite within alveolar bone crest of rats.

    Science.gov (United States)

    Marchini, Adriana M P S; Deco, Camila P; Lodi, Karina B; Marchini, Leonardo; Santo, Ana M E; Rocha, Rosilene F

    2012-10-01

    Previous findings suggest that chronic alcoholism and oestrogenic deficiency may affect bones in general (including alveolar bone) and increase individuals' susceptibility to the development of periodontal disease. The aim of this study was to assess possible alterations in the chemical composition of alveolar bone in rats subjected to chronic alcoholism, oestrogen deficiency or both. Fifty-four rats were initially divided into two groups: ovariectomized (Ovx), and Sham operated (Sham). A month after surgery, the groups were sub-divided and received the following dietary intervention for eight weeks: 20% alcohol, isocaloric diet and ad libitum diet. Samples of the mandible, in the alveolar bone crest region, were analyzed to verify possible changes in the stoichiometric composition of bone hydroxyapatite, by measuring the relationship between the concentration of calcium and phosphorus (Ca/P ratios), using micro X-ray fluorescence spectrometry. The ad libitum groups presented the highest average values of Ca/P ratios, while the groups with dietary restrictions presented the smallest average values. The Ovx ad libitum group presented the highest values of Ca/P ratios (2.03 ± 0.04). However, these values were not considered statistically different (p>0.05) from the Sham ad libitum group (2.01 ± 0.01). The Ovx alcohol group presented lower values for Ca/P ratios (1.92 ± 0.06), being the only group statistically different (palcohol consumption at 20% significantly changed the stoichiometry composition of hydroxyapatite in the alveolar bone crest, leading to a reduction in Ca/P ratios. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Discharge Coefficient of Rectangular Short-Crested Weir with Varying Slope Coefficients

    Directory of Open Access Journals (Sweden)

    Yuejun Chen

    2018-02-01

    Full Text Available Rectangular short-crested weirs are widely used for simple structure and high discharge capacity. As one of the most important and influential factors of discharge capacity, side slope can improve the hydraulic characteristics of weirs at special conditions. In order to systemically study the effects of upstream and downstream slope coefficients S1 and S2 on overflow discharge coefficient in a rectangular short-crested weir the Volume of Fluid (VOF method and the Renormalization Group (RNG κ-ε turbulence model are used. In this study, the slope coefficient ranges from V to 3H:1V and each model corresponds to five total energy heads of H0 ranging from 8.0 to 24.0 cm. Comparisons of discharge coefficients and free surface profiles between simulated and laboratory results display a good agreement. The simulated results show that the difference of discharge coefficients will decrease with upstream slopes and increase with downstream slopes as H0 increases. For a given H0, the discharge coefficient has a convex parabolic relation with S1 and a piecewise linearity relation with S2. The maximum discharge coefficient is always obtained at S2 = 0.8. There exists a difference between upstream and downstream slope coefficients in the influence range of free surface curvatures. Furthermore, a proposed discharge coefficient equation by nonlinear regression is a function of upstream and downstream slope coefficients.

  13. Breeding Double-crested Cormorants and Wading Birds on Isla Alcatraz, Sonora, México

    Science.gov (United States)

    Jennifer N. Duberstein; Virginia Jimenez-Serrania; Tad A. Pfister; Kirsten E. Lindquist; Lorayne Meltzer

    2005-01-01

    Isla Alcatraz is a small volcanic island in the Eastern Midriff Island region of the Gulf of California, approximately 1.4 km from the fishing community of Bahía de Kino, Sonora, México. The island falls under the protection of the Gulf Island Reserve system for wildlife and migratory birds. Isla Alcatraz is home to one of the largest Double-crested Cormorant (

  14. Theoretical Investigation of Peak-Delay Force Reduction for Caissons Exposed to Non-breaking Short-Crested Waves

    DEFF Research Database (Denmark)

    Burcharth, H. F.; Liu, Z.

    In nature coastal structures are exposed to oblique short-crested waves. The effect of wave incident angle on total wave force on a long caisson are twofold. The one is the force reduction due to the reduction of instantaneous point pressure on the caisson, named point-pressure force reduction....... The other is the force reduction due to the fact that the peak pressures do not occur simultaneously along the caisson, named peak-delay force reduction. These two reduction effects can also be expected with short-crested waves, as the short-crestedness of waves means the spreading of wave energy over...... a range of incident angles. The peak-delay force reduction, i.e. no simultaneous peak along caisson, is of particular interest because the equipment improvement in construction enables the building of considerably long caissons. In Japan length of caissons exceeds often 100m. This paper will concentrate...

  15. Arteriovenous fistula of the superior gluteal artery as a complication of posterior iliac crest bone graft harvesting: 3D-CT angiography and arterial embolization

    OpenAIRE

    Kong, Chae-Gwan; Park, Jong-Beom; Won, Yoo-Dong; Riew, K. Daniel

    2009-01-01

    Superior gluteal artery injuries are rare, but potentially serious complications that occur during posterior iliac crest bone graft harvesting. The authors reported an arteriovenous fistula of the superior gluteal artery, which occurred as a complication during posterior iliac crest bone graft harvesting and was diagnosed with 3D-CT angiography, then treated with arterial embolization.

  16. The Melanocyte Fate in Neural Crest is Triggered by Myb Proteins through Activation of c-kit

    Czech Academy of Sciences Publication Activity Database

    Karafiát, Vít; Dvořáková, Marta; Pajer, Petr; Čermák, Vladimír; Dvořák, Michal

    2007-01-01

    Roč. 64, č. 21 (2007), s. 2975-2984 ISSN 1420-682X R&D Projects: GA MŠk(CZ) LC06061; GA ČR GA204/06/1728 Institutional research plan: CEZ:AV0Z50520514 Keywords : c-myb proto-oncogene * v-mybAMV oncogene * neural crest * cell fate determination * melanocytes * c-kit signal Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.239, year: 2007

  17. 77 FR 47628 - Eagle Mountain Pumped Storage Hydroelectric Project; Eagle Crest Energy; Notice of Meeting...

    Science.gov (United States)

    2012-08-09

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [P-13123-002-CA] Eagle Mountain Pumped Storage Hydroelectric Project; Eagle Crest Energy; Notice of Meeting Postponement On July 17, 2012, the...), on the Eagle Mountain Pumped Storage Hydroelectric Project. However, the meeting has been postponed...

  18. 76 FR 22393 - Eagle Mountain Pumped Storage Hydroelectric Project, Eagle Crest Energy; Notice of Cancellation...

    Science.gov (United States)

    2011-04-21

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [P-13123-002-CA] Eagle Mountain Pumped Storage Hydroelectric Project, Eagle Crest Energy; Notice of Cancellation of Teleconference On March 15... Mountain Pumped Storage Hydroelectric Project. This meeting has been cancelled. We will reschedule this...

  19. Enteric neural crest cells regulate vertebrate stomach patterning and differentiation.

    Science.gov (United States)

    Faure, Sandrine; McKey, Jennifer; Sagnol, Sébastien; de Santa Barbara, Pascal

    2015-01-15

    In vertebrates, the digestive tract develops from a uniform structure where reciprocal epithelial-mesenchymal interactions pattern this complex organ into regions with specific morphologies and functions. Concomitant with these early patterning events, the primitive GI tract is colonized by the vagal enteric neural crest cells (vENCCs), a population of cells that will give rise to the enteric nervous system (ENS), the intrinsic innervation of the GI tract. The influence of vENCCs on early patterning and differentiation of the GI tract has never been evaluated. In this study, we report that a crucial number of vENCCs is required for proper chick stomach development, patterning and differentiation. We show that reducing the number of vENCCs by performing vENCC ablations induces sustained activation of the BMP and Notch pathways in the stomach mesenchyme and impairs smooth muscle development. A reduction in vENCCs also leads to the transdifferentiation of the stomach into a stomach-intestinal mixed phenotype. In addition, sustained Notch signaling activity in the stomach mesenchyme phenocopies the defects observed in vENCC-ablated stomachs, indicating that inhibition of the Notch signaling pathway is essential for stomach patterning and differentiation. Finally, we report that a crucial number of vENCCs is also required for maintenance of stomach identity and differentiation through inhibition of the Notch signaling pathway. Altogether, our data reveal that, through the regulation of mesenchyme identity, vENCCs act as a new mediator in the mesenchymal-epithelial interactions that control stomach development. © 2015. Published by The Company of Biologists Ltd.

  20. Loss of FTO antagonises Wnt signaling and leads to developmental defects associated with ciliopathies.

    Directory of Open Access Journals (Sweden)

    Daniel P S Osborn

    Full Text Available Common intronic variants in the Human fat mass and obesity-associated gene (FTO are found to be associated with an increased risk of obesity. Overexpression of FTO correlates with increased food intake and obesity, whilst loss-of-function results in lethality and severe developmental defects. Despite intense scientific discussions around the role of FTO in energy metabolism, the function of FTO during development remains undefined. Here, we show that loss of Fto leads to developmental defects such as growth retardation, craniofacial dysmorphism and aberrant neural crest cells migration in Zebrafish. We find that the important developmental pathway, Wnt, is compromised in the absence of FTO, both in vivo (zebrafish and in vitro (Fto(-/- MEFs and HEK293T. Canonical Wnt signalling is down regulated by abrogated β-Catenin translocation to the nucleus whilst non-canonical Wnt/Ca(2+ pathway is activated via its key signal mediators CaMKII and PKCδ. Moreover, we demonstrate that loss of Fto results in short, absent or disorganised cilia leading to situs inversus, renal cystogenesis, neural crest cell defects and microcephaly in Zebrafish. Congruently, Fto knockout mice display aberrant tissue specific cilia. These data identify FTO as a protein-regulator of the balanced activation between canonical and non-canonical branches of the Wnt pathway. Furthermore, we present the first evidence that FTO plays a role in development and cilia formation/function.

  1. Reporting quality of randomized controlled trial abstracts: survey of leading general dental journals.

    Science.gov (United States)

    Hua, Fang; Deng, Lijia; Kau, Chung How; Jiang, Han; He, Hong; Walsh, Tanya

    2015-09-01

    The authors conducted a study to assess the reporting quality of randomized controlled trial (RCT) abstracts published in leading general dental journals, investigate any improvement after the release of the Consolidated Standards of Reporting Trials (CONSORT) for Abstracts guidelines, and identify factors associated with better reporting quality. The authors searched PubMed for RCTs published in 10 leading general dental journals during the periods from 2005 to 2007 (pre-CONSORT period) and 2010 to 2012 (post-CONSORT period). The authors evaluated and scored the reporting quality of included abstracts by using the original 16-item CONSORT for Abstracts checklist. The authors used risk ratios and the t test to compare the adequate reporting rate of each item and the overall quality in the 2 periods. The authors used univariate and multivariate regressions to identify predictors of better reporting quality. The authors included and evaluated 276 RCT abstracts. Investigators reported significantly more checklist items during the post-CONSORT period (mean [standard deviation {SD}], 4.53 [1.69]) than during the pre-CONSORT period (mean [SD], 3.87 [1.10]; mean difference, -0.66 [95% confidence interval, -0.99 to -0.33]; P 80%). In contrast, the authors saw sufficient reporting of randomization, recruitment, outcome in the results section, and funding in none of the pre-CONSORT abstracts and less than 2% of the post-CONSORT abstracts. On the basis of the multivariate analysis, a higher impact factor (P general dental journals has improved significantly, but there is still room for improvement. Joint efforts by authors, reviewers, journal editors, and other stakeholders to improve the reporting of dental RCT abstracts are needed. Copyright © 2015 American Dental Association. Published by Elsevier Inc. All rights reserved.

  2. Transcrition factor c-Myb is involved in the regulation of the epithelial-mesenchymal transition in the avian neural crest

    Czech Academy of Sciences Publication Activity Database

    Karafiát, Vít; Dvořáková, Marta; Krejčí, E.; Králová, Jarmila; Pajer, Petr; Šnajdr, P.; Mandíková, Sonja; Bartůněk, Petr; Grim, M.; Dvořák, Michal

    2005-01-01

    Roč. 62, č. 21 (2005), s. 2516-2525 ISSN 1420-682X R&D Projects: GA ČR GA304/03/0463; GA AV ČR IAA5052309 Institutional research plan: CEZ:AV0Z50520514 Keywords : c-myb gene * epithelial-mesenchymal transition * neural crest Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.582, year: 2005

  3. Pulsed vs. CW low level light therapy on osteoarticular signs and symptoms in limited scleroderma (CREST syndrome)

    Science.gov (United States)

    Barolet, Daniel

    2012-03-01

    Limited cutaneous systemic sclerosis (lcSSc) was formerly known as CREST syndrome in reference to the associated clinical features: Calcinosis, Raynaud's phenomenon, Esophageal dysfunction, Sclerodactyly, and Telangiectasias. The transforming growth factor beta (TGF-β) has been identified has a major player in the pathogenic process, while low level light therapy (LLLT) has been shown to modulate this cytokine superfamily. This case study was conducted to assess the efficacy of 940nm using microsecond domain pulsing and continuous wave mode (CW) on osteoarticular signs and symptoms associated with lcSSc. The patient was treated two to three times a week for 13 weeks, using a sequential pulsing mode on one elbow, and a CW mode on the other. Efficacy assessments included inflammation, symptoms, pain, and health scales, patient satisfaction, clinical global impression, and adverse effects monitoring. Significant functional and morphologic improvements were observed after LLLT, with best results seen with the pulsing mode. No significant adverse effects were noted. Two mechanisms of action may be at play. The 940nm wavelength provides inside-out heating possibly vasodilating capillaries which in turn increases catabolic processes leading to a reduction of in situ calcinosis. LLLT may also improve symptoms by triggering a cascade of cellular reactions, including the modulation of inflammatory mediators.

  4. Sonic Hedgehog promotes the survival of neural crest cells by limiting apoptosis induced by the dependence receptor CDON during branchial arch development.

    Science.gov (United States)

    Delloye-Bourgeois, Céline; Rama, Nicolas; Brito, José; Le Douarin, Nicole; Mehlen, Patrick

    2014-09-26

    Cell-adhesion molecule-related/Downregulated by Oncogenes (CDO or CDON) was identified as a receptor for the classic morphogen Sonic Hedgehog (SHH). It has been shown that, in cell culture, CDO also behaves as a SHH dependence receptor: CDO actively triggers apoptosis in absence of SHH via a proteolytic cleavage in CDO intracellular domain. We present evidence that CDO is also pro-apoptotic in the developing neural tube where SHH is known to act as a survival factor. SHH, produced by the ventral foregut endoderm, was shown to promote survival of facial neural crest cells (NCCs) that colonize the first branchial arch (BA1). We show here that the survival activity of SHH on neural crest cells is due to SHH-mediated inhibition of CDO pro-apoptotic activity. Silencing of CDO rescued NCCs from apoptosis observed upon SHH inhibition in the ventral foregut endoderm. Thus, the pair SHH/dependence receptor CDO may play an important role in neural crest cell survival during the formation of the first branchial arch. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Search for the Missing lncs: Gene Regulatory Networks in Neural Crest Development and Long Non-coding RNA Biomarkers of Hirschsprung's Disease

    Science.gov (United States)

    Hirschsprung’s disease (HSCR), a birth defect characterized by variable aganglionosis of the gut, affects about 1 in 5000 births, and is a consequence of abnormal development of neural crest cells, from which enteric ganglia derive. In the companion article in this issue (Shen et...

  6. The Wnt Co-Receptor Lrp5 Is Required for Cranial Neural Crest Cell Migration in Zebrafish.

    Directory of Open Access Journals (Sweden)

    Bernd Willems

    Full Text Available During vertebrate neurulation, cranial neural crest cells (CNCCs undergo epithelial to mesenchymal transition (EMT, delaminate from the neural plate border, and migrate as separate streams into different cranial regions. There, they differentiate into distinct parts of the craniofacial skeleton. Canonical Wnt signaling has been shown to be essential for this process at different levels but the involved receptors remained unclear. Here we show that the frizzled co-receptor low-density-lipoprotein (LDL receptor-related protein 5 (Lrp5 plays a crucial role in CNCC migration and morphogenesis of the cranial skeleton. Early during induction and migration of CNCCs, lrp5 is expressed ubiquitously but later gets restricted to CNCC derivatives in the ventral head region besides different regions in the CNS. A knock-down of lrp5 does not interfere with induction of CNCCs but leads to reduced proliferation of premigratory CNCCs. In addition, cell migration is disrupted as CNCCs are found in clusters at ectopic positions in the dorsomedial neuroepithelium after lrp5 knock-down and transient CRISPR/Cas9 gene editing. These migratory defects consequently result in malformations of the craniofacial skeleton. To date, Lrp5 has mainly been associated with bone homeostasis in mammals. Here we show that in zebrafish, lrp5 also controls cell migration during early morphogenetic processes and contributes to shaping the craniofacial skeleton.

  7. Immunohistochemical and morphological features of a small bowel leiomyoma in a black crested macaque (Macaca nigra

    Directory of Open Access Journals (Sweden)

    Aristizabal-Arbelaez Mónica

    2012-06-01

    Full Text Available Abstract Background Spontaneous gastrointestinal neoplasms in non-human primates are commonly seen in aged individuals. Due to genetic similarities between human and non-human primates, scientists have shown increasing interest in terms of comparative oncology studies. Case presentation The present study is related to a case of an intestinal leiomyoma in a black crested macaque (Macaca nigra, kept on captivity by Matecaña Zoo, Pereira City, Colombia. The animal had abdominal distension, anorexia, vomiting, diarrhea and behavioral changes. Clinical examination showed an increased volume in the upper right abdominal quadrant caused by a neoplastic mass. The patient died during the surgical procedure. Necropsy revealed several small nodules in the peritoneum with adhesion to different portions of the small and large intestines, liver, stomach and diaphragm. Tissue samples were collected, routinely processed and stained by H&E. Microscopic examination revealed a mesenchymal tumor limited to tunica muscularis, resembling normal smooth muscle cells. Neoplastic cells were positive for alpha-smooth muscle actin and vimentin, and negative for cytokeratin AE1/AE3 by immunohistochemistry. Those morphological and immunohistochemical findings allowed to diagnose the intestinal leiomyoma referred above. Conclusion Neoplastic diseases in primates have multifaceted causes. Their manifestations are understudied, leading to a greater difficulty in detection and measurement of the real impact provides by this disease.

  8. T-CREST: Time-predictable multi-core architecture for embedded systems

    DEFF Research Database (Denmark)

    Schoeberl, Martin; Abbaspourseyedi, Sahar; Jordan, Alexander

    2015-01-01

    -core architectures that are optimized for the WCET instead of the average-case execution time. The resulting time-predictable resources (processors, interconnect, memory arbiter, and memory controller) and tools (compiler, WCET analysis) are designed to ease WCET analysis and to optimize WCET performance. Compared...... domain shows that the WCET can be reduced for computation-intensive tasks when distributing the tasks on several cores and using the network-on-chip for communication. With three cores the WCET is improved by a factor of 1.8 and with 15 cores by a factor of 5.7.The T-CREST project is the result...

  9. A predictive model to inform adaptive management of double-crested cormorants and fisheries in Michigan

    Science.gov (United States)

    Tsehaye, Iyob; Jones, Michael L.; Irwin, Brian J.; Fielder, David G.; Breck, James E.; Luukkonen, David R.

    2015-01-01

    The proliferation of double-crested cormorants (DCCOs; Phalacrocorax auritus) in North America has raised concerns over their potential negative impacts on game, cultured and forage fishes, island and terrestrial resources, and other colonial water birds, leading to increased public demands to reduce their abundance. By combining fish surplus production and bird functional feeding response models, we developed a deterministic predictive model representing bird–fish interactions to inform an adaptive management process for the control of DCCOs in multiple colonies in Michigan. Comparisons of model predictions with observations of changes in DCCO numbers under management measures implemented from 2004 to 2012 suggested that our relatively simple model was able to accurately reconstruct past DCCO population dynamics. These comparisons helped discriminate among alternative parameterizations of demographic processes that were poorly known, especially site fidelity. Using sensitivity analysis, we also identified remaining critical uncertainties (mainly in the spatial distributions of fish vs. DCCO feeding areas) that can be used to prioritize future research and monitoring needs. Model forecasts suggested that continuation of existing control efforts would be sufficient to achieve long-term DCCO control targets in Michigan and that DCCO control may be necessary to achieve management goals for some DCCO-impacted fisheries in the state. Finally, our model can be extended by accounting for parametric or ecological uncertainty and including more complex assumptions on DCCO–fish interactions as part of the adaptive management process.

  10. Static Histomorphometry of the iliac crest after 360 days of antiorthostatic bed rest with and without countermeasures

    Science.gov (United States)

    Thomsen, J. S.; Morukov, B. V.; Vico, L.; Saparin, P. I.; Gowin, W.

    The loss of bone during immobilization is well-known and investigated, whereas the structural changes human cancellous bone undergoes during disuse is less well examined. The aim of the study was to examine the influence of hypokinesia on the static histomorphometric measures of the iliac crest using a 360-day-long bed rest experiment, simulating exposure to microgravity. Eight healthy males underwent 360 days of 5° head-down tilt bed rest. Three subjects were treated with the bisphosphonate Xidifon (900 mg/day) combined with a treadmill and ergonometer exercise regimen (1--2 hours/day) for the entire study period. Five subjects underwent 120 days of bed rest without countermeasures followed by 240 days of bed rest with the treadmill and ergonometer exercise regimen. Transiliac bone biopsies were obtained either at day 0 and 360 or at day 0, 120, and 360 at alternating sides of the ileum. The biopsies were embedded in methylmethacrylate, cut in 7-μm-thick sections, stained with Goldner trichrome, and static histomorphometry was performed. 120 days of bed rest without countermeasures resulted in decreased trabecular bone volume (-6.3%, p = 0.046) and trabecular number (-10.2%, p = 0.080) and increased trabecular separation (14.7%, p = 0.020), whereas 240 days of subsequent bed rest with exercise treatment prevented further significant deterioration of the histomorphometric measures. 360 days of bed rest with bisphosphonate and exercise treatment did not induce any significant changes in any of the histomorphometric measures. The study showed that 120 days of antiorthostatic bed rest without countermeasures induced significant deterioration of iliac crest trabecular bone histomorphometric properties. There are indications that the immobilization induced changes involve a loss of trabeculae rather than a general thinning of the trabeculae. On average, the countermeasures consisting of either bisphosphonate and exercise or exercise alone were able to either prevent

  11. Expression of the capacity to release [3H]norepinephrine by neural crest cultures

    International Nuclear Information System (INIS)

    Maxwell, G.D.; Sietz, P.D.

    1983-01-01

    Cultures of trunk neural crest cells from quail embryos were tested for their ability to release [ 3 H]norepinephrine [( 3 H]NE) in response to depolarization. After 7 days in vitro, exposure of the cultures to either the alkaloid veratridine or 40 mM K+ results in the evoked release of [ 3 H]NE. The release evoked by veratridine is blocked in the presence of tetrodotoxin. The release evoked by increased K+ is blocked by the calcium antagonist cobalt. Release in response to the nicotinic cholinergic agonist 1,1-dimethyl-4-phenylpiperazine was also observed. The amount of evoked release is highly correlated with the number of histochemically demonstrable catecholamine-containing cells in a given culture. Autoradiography reveals that the radioactivity taken up by these cultures is located in a subpopulation of cells whose morphology resembles that of the histochemically detectable catecholamine-containing cell population. Whereas capacity for the release of [ 3 H] NE is readily detectable after 7 days in vitro, it is detectable only with difficulty after 4 days in vitro. There is a greater than 6-fold increase in uptake capacity over the period of 4 to 7 days in vitro. These results demonstrate that neural crest cultures grown without their normal synaptic inputs or targets can exhibit the capacity for stimulus secretion coupling characteristic of synaptic neurotransmitter release

  12. Epithelial–Mesenchymal Transitions during Neural Crest and Somite Development

    Directory of Open Access Journals (Sweden)

    Chaya Kalcheim

    2015-12-01

    Full Text Available Epithelial-to-mesenchymal transition (EMT is a central process during embryonic development that affects selected progenitor cells of all three germ layers. In addition to driving the onset of cellular migrations and subsequent tissue morphogenesis, the dynamic conversions of epithelium into mesenchyme and vice-versa are intimately associated with the segregation of homogeneous precursors into distinct fates. The neural crest and somites, progenitors of the peripheral nervous system and of skeletal tissues, respectively, beautifully illustrate the significance of EMT to the above processes. Ongoing studies progressively elucidate the gene networks underlying EMT in each system, highlighting the similarities and differences between them. Knowledge of the mechanistic logic of this normal ontogenetic process should provide important insights to the understanding of pathological conditions such as cancer metastasis, which shares some common molecular themes.

  13. 76 FR 15971 - Eagle Mountain Pumped Storage Hydroelectric Project; Eagle Crest Energy; Notice of Teleconference

    Science.gov (United States)

    2011-03-22

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [P-13123-002-CA] Eagle Mountain Pumped Storage Hydroelectric Project; Eagle Crest Energy; Notice of Teleconference a. Date and Time of Meeting: Friday, April 15, 2011 at 9 a.m. (Pacific Time). b. Place: By copy of this notice we are inviting all...

  14. 76 FR 22699 - Eagle Mountain Pumped Storage Hydroelectric Project, Eagle Crest Energy; Notice of Teleconference

    Science.gov (United States)

    2011-04-22

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [P-13123-002--CA] Eagle Mountain Pumped Storage Hydroelectric Project, Eagle Crest Energy; Notice of Teleconference a. Date and Time of Meeting: Friday, May 6, 2011 at 1 p.m. (Pacific Time). b. Place: By copy of this notice we are inviting all...

  15. Inca: a novel p21-activated kinase-associated protein required for cranial neural crest development.

    Science.gov (United States)

    Luo, Ting; Xu, Yanhua; Hoffman, Trevor L; Zhang, Tailin; Schilling, Thomas; Sargent, Thomas D

    2007-04-01

    Inca (induced in neural crest by AP2) is a novel protein discovered in a microarray screen for genes that are upregulated in Xenopus embryos by the transcriptional activator protein Tfap2a. It has no significant similarity to any known protein, but is conserved among vertebrates. In Xenopus, zebrafish and mouse embryos, Inca is expressed predominantly in the premigratory and migrating neural crest (NC). Knockdown experiments in frog and fish using antisense morpholinos reveal essential functions for Inca in a subset of NC cells that form craniofacial cartilage. Cells lacking Inca migrate successfully but fail to condense into skeletal primordia. Overexpression of Inca disrupts cortical actin and prevents formation of actin "purse strings", which are required for wound healing in Xenopus embryos. We show that Inca physically interacts with p21-activated kinase 5 (PAK5), a known regulator of the actin cytoskeleton that is co-expressed with Inca in embryonic ectoderm, including in the NC. These results suggest that Inca and PAK5 cooperate in restructuring cytoskeletal organization and in the regulation of cell adhesion in the early embryo and in NC cells during craniofacial development.

  16. Can footwall unloading explain late Cenozoic uplift of the Sierra Nevada crest?

    Science.gov (United States)

    Thompson, G.A.; Parsons, T.

    2009-01-01

    Globally, normal-fault displacement bends and warps rift flanks upwards, as adjoining basins drop downwards. Perhaps the most evident manifestations are the flanks of the East African Rift, which cuts across the otherwise minimally deformed continent. Flank uplift was explained by Vening Meinesz (1950, Institut Royal Colonial Belge, Bulletin des Seances, v. 21, p. 539-552), who recognized that isostasy should cause uplift of a normal-faulted footwall and subsidence of its hanging wall. Uplift occurs because slip on a dipping normal fault creates a broader root of less-dense material beneath the footwall, and a narrowed one beneath the hanging wall. In this paper, we investigate the potential influence of this process on the latest stages of Sierra Nevada uplift. Through theoretical calculations and 3D finite element modelling, we find that cumulative slip of about 4km on range-front faults would have produced about 1.3km peak isostatic uplift at the ridge crest. Numerical models suggest that the zone of uplift is narrow, with the width controlled by bending resistance of the seismogenic crust. We conclude that footwall unloading cannot account for the entire elevation of the Sierran crest above sea level, but if range-front faulting initiated in an already elevated plateau like the adjacent Basin and Range Province, then a hybrid model of pre-existing regional uplift and localized footwall unloading can account for the older and newer uplift phases suggested by the geologic record.

  17. Neuronal regeneration in injured rat spinal cord after human dental pulp derived neural crest stem cell transplantation.

    Science.gov (United States)

    Kabatas, S; Demir, C S; Civelek, E; Yilmaz, I; Kircelli, A; Yilmaz, C; Akyuva, Y; Karaoz, E

    2018-01-01

    This study aimed to analyze the effect of human Dental Pulp-Neural Crest Stem Cells (hDP-NCSCs) delivery on lesion site after spinal cord injury (SCI), and to observe the functional recovery after transplantation. Neural Crest Stem Cells (NCSCs) were isolated from human Dental Pulp (hDP). The experimental rat population was divided into four groups (n = 6/24). Their behavioral motility was scored regularly. After 4-weeks, rats were sacrificed, and their spinal cords were examined for Green Fluorescent Protein (GFP) labeled hDP-NCSCs by immunofluorescence (IF) staining. In early post-injury (p.i) period, the ultrastructure of spinal cord tissue was preserved in Group 4. The majority of cells forming the ependymal region around the central canal were found to be hDP-NCSCs. While the grey-and-white-matter around the ependymal region was composed of e.g. GFP cells, with astrocytic-like appearance. The scores showed significant motor recovery in hind limb functions in Group 4. However, no obvious change was observed in other groups. Cells e.g., mesenchymal (Vimentin+) which express GFP+ cells in the gray-and-white-matter around the ependymal region could indicate the potential to self-renewal and plasticity. Thus, transplantation of hDP-NCSCs might be an effective strategy to improve functional recovery following spinal cord trauma (Fig. 10, Ref. 32).

  18. The evolution of the adult body form of the crested newt (Triturus cristatus superspecies, Caudata, Salamandridae)

    NARCIS (Netherlands)

    Vukov, T.D.; Sotiropoulos, K.; Wielstra, B.M.; Dzukic, G.; Kalezic, M.

    2011-01-01

    We characterized the adult body form of the crested newt (Triturus cristatus superspecies) and explored its evolution. From seven morphometric traits, we determined that body size, interlimb distance and head width define the body form. None of the morphometric traits showed a phylogenetic signal.

  19. Genomic signatures of near-extinction and rebirth of the crested ibis and other endangered bird species

    DEFF Research Database (Denmark)

    Li, Shengbin; Li, Bo; Cheng, Cheng

    2014-01-01

    sequences of multiple crested ibis individuals, its thriving co-habitant, the little egret, Egretta garzetta, and the recently sequenced genomes of 41 other avian species that are under various degrees of survival threats, including the bald eagle, we carry out comparative analyses for genomic signatures...

  20. 78 FR 25263 - Eagle Mountain Pumped Storage Hydroelectric Project; Eagle Crest Energy; Notice of Meeting With...

    Science.gov (United States)

    2013-04-30

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [P-13123-002--CA] Eagle Mountain Pumped Storage Hydroelectric Project; Eagle Crest Energy; Notice of Meeting With the Bureau of Land Management a... Hydroelectric Project. e. All local, state, and federal agencies, tribes, and interested parties, are hereby...

  1. 77 FR 43280 - Eagle Mountain Pumped Storage Hydroelectric Project, Eagle Crest Energy; Notice of Meeting With...

    Science.gov (United States)

    2012-07-24

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [P-13123-002-CA] Eagle Mountain Pumped Storage Hydroelectric Project, Eagle Crest Energy; Notice of Meeting With the Bureau of Land Management a... Mountain Pumped Storage Hydroelectric Project. e. All local, state, and federal agencies, tribes, and...

  2. Can microsatellite markers resolve phylogenetic relationships between closely related crested newt species (Triturus cristatus superspecies)?

    Czech Academy of Sciences Publication Activity Database

    Mikulíček, P.; Crnobrnja-Isailović, J.; Piálek, Jaroslav

    2007-01-01

    Roč. 28, č. 4 (2007), s. 467-474 ISSN 0173-5373 R&D Projects: GA ČR GA206/01/0695; GA MŠk LC06073 Institutional research plan: CEZ:AV0Z60930519 Keywords : crested newt * microsatelitte markers Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.929, year: 2007

  3. Grafton and local bone have comparable outcomes to iliac crest bone in instrumented single-level lumbar fusions.

    Science.gov (United States)

    Kang, James; An, Howard; Hilibrand, Alan; Yoon, S Tim; Kavanagh, Eoin; Boden, Scott

    2012-05-20

    Prospective multicenter randomized clinical trail. The goal of our 2-year prospective study was to perform a randomized clinical trial comparing the outcomes of Grafton demineralized bone matrix (DBM) Matrix with local bone with that of iliac crest bone graft (ICBG) in a single-level instrumented posterior lumbar fusion. There has been extensive research and development in identifying a suitable substitute to replace autologous ICBG that is associated with known morbidities. DBMs are a class of commercially available grafting agents that are prepared from allograft bone. Many such products have been commercially available for clinical use; however, their efficacy for spine fusion has been mostly based on anecdotal evidence rather than randomized controlled clinical trials. Forty-six patients were randomly assigned (2:1) to receive Grafton DBM Matrix with local bone (30 patients) or autologous ICBG (16 patients). The mean age was 64 (females [F] = 21, males [M] = 9) in the DBM group and 65 (F = 9, M = 5) in the ICBG group. An independent radiologist evaluated plain radiographs and computed tomographic scans at 6-month, 1-year, and 2-year time points. Clinical outcomes were measured using Oswestry Disability Index (ODI) and Medical Outcomes Study 36-Item Short Form Health Survey. Forty-one patients (DBM = 28 and ICBG = 13) completed the 2-year follow-up. Final fusion rates were 86% (Grafton Matrix) versus 92% (ICBG) (P = 1.0 not significant). The Grafton group showed slightly better improvement in ODI score than the ICBG group at the final 2-year follow-up (Grafton [16.2] and ICBG [22.7]); however, the difference was not statistically significant (P = 0.2346 at 24 mo). Grafton showed consistently higher physical function scores at 24 months; however, differences were not statistically significant (P = 0.0823). Similar improvements in the physical component summary scores were seen in both the Grafton and ICBG groups. There was a statistically significant greater mean

  4. Climate Forcing of Ripple Migration and Crest Alignment in the Last 400 kyr in Meridiani Planum, Mars

    Science.gov (United States)

    Fenton, Lori K.; Carson, Helen C.; Michaels, Timothy I.

    2018-04-01

    The plains ripples of Meridiani Planum are the first paleo-aeolian bedforms on Mars to have had their last migration episode constrained in time (to 50-200 ka). Here we test how variations in orbital configuration, air pressure, and atmospheric dust loading over the past 400 kyr affect bedform mobility and crest alignment. Using the National Aeronautics and Space Administration Ames Mars Global Climate Model, we ran a series of sensitivity tests under a number of different conditions, seeking changes in wind patterns relative to those modeled for present-day conditions. Results indicate that enhanced sand drift potential in Meridiani Planum correlates with (1) high axial obliquity, (2) a longitude of perihelion (Lp) near southern summer solstice, and (3) a greater air pressure. The last pulse of westward plains ripple migration likely occurred during the most recent obliquity (relative) maximum, from 111 to 86 ka. At Lp coinciding with southern summer solstice, the Mars Global Climate Model produced a westward resultant drift direction, consistent with the observed north-south plains ripple crest alignment. However, smaller superposed ripples, aligned NNE-SSW, are consistent with a strengthened northern summer Hadley return flow, occurring when Lp coincided with northern summer solstice. The superposed NNE-SSW ripples likely formed as the axial obliquity decreased during the last relative maximum and Lp swung toward northern summer, from 86 to 72 ka. The timeline of bedform activity supports the proposed sequence of CO2 sequestration in the south polar residual cap over the past 400 kyr.

  5. Local time, seasonal, and solar cycle dependency of longitudinal variations of TEC along the crest of EIA over India

    Science.gov (United States)

    Sunda, Surendra; Vyas, B. M.

    2013-10-01

    global wave number 4 structure in the Indian longitudinal region spanning from ~70 to 95°E forming the upward slope of the peak in the total electron content (TEC) are reported along the crest of equatorial ionization anomaly (EIA). The continuous and simultaneous measurements from five GPS stations of GPS Aided Geo Augmented Navigation (GAGAN) network are used in this study. The long-term database (2004-2012) is utilized for examining the local time, seasonal, and solar cycle dependency on the longitudinal variations of TEC. Our results confirm the existence of longitudinal variations of TEC in accordance with wave number 4 longitudinal structure including its strength. The results suggest that these variations, in general, start to develop at ~09 LT, achieve maximum strength at 12-15 LT, and decay thereafter, the decay rate depending on the season. They are more pronounced in equinoctial season followed by summer and winter. The longitudinal variations persist beyond midnight in equinox seasons, whereas in winter, they are conspicuously absent. Interestingly, they also exhibit significant solar cycle dependence in the solstices, whereas in the equinoxes, they are independent of solar activity. The comparison of crest-to-trough ratio (CTR) in the eastern (92°E) and western (72°E) extreme longitudes reveals higher CTR on the eastern side than over the western extreme, suggesting the role of nonmigrating tides in modulating the ExB vertical drift and the consequential EIA crest formation.

  6. 78 FR 26358 - Eagle Mountain Pumped Storage Hydroelectric Project, Eagle Crest Energy; Notice of Meeting With...

    Science.gov (United States)

    2013-05-06

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [P-13123-002-CA] Eagle Mountain Pumped Storage Hydroelectric Project, Eagle Crest Energy; Notice of Meeting With the Bureau of Land Management a... Policy and Management Act and the Federal Power Act), on the Eagle Mountain Pumped Storage Hydroelectric...

  7. Numerical Analysis of Slopes Stability and Shallow Foundations Behavior at Crest under Real Seismic Loading - Reinforcement Effect

    International Nuclear Information System (INIS)

    Mekdash, H.; Hage Chehade, F.; Sadek, M.; Abdel Massih, D.; El Hachem, E.; Youssef, E.

    2011-01-01

    The aim of this paper is to analyze the slopes stability under seismic loading using a global numerical dynamic approach. This approach allows important parameters that are generally ignored by traditional engineering methods such as the soil deformability, the dynamic amplification, non linear soil behavior, the spatial and temporal variability of the seismic loading and the reinforcement element. The present study is conducted by using measures recorded during real earthquakes (Turkey, 1999) and (Lebanon, 2008). Elastoplastic soil behavior analysis leads to monitor the evolution of the slope state after an earthquake and to clarify the most probable failure circles. A parametric study according to the reinforcement length, position, inclination and the number of elements has been studied in order to define the optimal reinforcement scheme for slopes under seismic loading. This study contains also the stability analysis of an existing foundation near the slope's crest. It will focus on the reinforcement in order to give recommendation for the most appropriate scheme that minimize the settlement of the foundation due to earthquake effect. (author)

  8. The status of whitebark pine along the Pacific Crest National Scenic Trail on the Umpqua National Forest.

    Science.gov (United States)

    Ellen Michaels Goheen; Donald J. Goheen; Katy Marshall; Robert S. Danchok; John A. Petrick; Diane E. White

    2002-01-01

    Because of concern over widespread population declines, the distribution, stand conditions, and health of whitebark pine (Pinus albicaulis Englem.) were evaluated along the Pacific Crest National Scenic Trail on the Umpqua National Forest. Whitebark pine occurred on 76 percent of the survey transects. In general, whitebark pine was found in stands...

  9. Lead editorial: Trials – using the opportunities of electronic publishing to improve the reporting of randomised trials

    Directory of Open Access Journals (Sweden)

    Grimshaw Jeremy M

    2006-03-01

    Full Text Available Abstract This editorial introduces the new online, open access, peer-reviewed journal Trials. The journal considers manuscripts on any aspect of the design, performance, and findings of randomised controlled trials in any discipline related to health care, and also encourages the publication of protocols. Trialists will be able to provide the necessary detail for a true and complete scientific record. They will be able to communicate not only all outcome measures, as well as varying analyses and interpretations, but also in-depth descriptions of what they did and honest reflections about what they learnt. Trials also encourages articles covering generic issues related to trials, for example focussing on the design, conduct, analysis, interpretation, or reporting.

  10. Assessment of GPS Multifrequency Signal Characteristics During Periods of Ionospheric Scintillations from an Anomaly Crest Location

    Science.gov (United States)

    Goswami, S.; Paul, K. S.; Paul, A.

    2017-09-01

    Multifrequency GPS transmissions have provided the opportunity for testing the applicability of the principle of frequency diversity for scintillation mitigation. Published results addressing this issue with quantified estimates are not available in literature, at least from the anomaly crest location of the Indian longitude sector. Multifrequency scattering within the same L band is often the attributed cause behind simultaneous decorrelated signal fluctuations. The present paper aims to provide proportion of time during scintillation patches that decorrelations are found across GPS L1, L2, and L5 frequencies associated with high S4, corresponding high values of scattering coefficients, and large receiver position deviations thereby seriously compromising the performance of satellite-based navigation system. Results from the anomaly crest station at Calcutta indicate maximum 40% of scintillation time during February-April 2014 and 33% during August-October 2014 that the signals are decorrelated. It is important to note that it is only during these time intervals that the principle of frequency diversity could be applied for scintillation mitigation.

  11. Development and characterization of polymorphic microsatellitemarkers for the crested caracara, Caracara cheriway

    Science.gov (United States)

    Vaughn, Erin E.; Dwyer, James F.; Morrison, Joan L.; Culver, Melanie

    2015-01-01

    We isolated novel microsatellites from the crested caracara (Caracara cheriway) with a shotgun pyrosequencing approach. We tested 80 loci for polymorphism among 20 individuals from the threatened Florida population. Fourteen loci were polymorphic. The mean number of alleles was 2.21 (range 2–3) and the mean observed heterozygosity was 0.41 (range 0.15–0.65). None of the 14 polymorphic loci exhibited significant linkage disequilibrium nor did they deviate significantly from Hardy–Weinberg expectations. We also report 16 monomorphic loci.

  12. Differential changes in serum uric acid concentrations in sibutramine promoted weight loss in diabetes: results from four weeks of the lead-in period of the SCOUT trial

    Directory of Open Access Journals (Sweden)

    Caterson Ian D

    2009-10-01

    Full Text Available Abstract Background and aims Elevated levels of serum uric acid are associated with an increased risk of cardiovascular morbidity and mortality. The response of uric acid to weight loss therapy (lifestyle plus sibutramine in an overweight and obese cardiovascular high risk population was studied. Methods and results Data from a four week single-blind lead-in period of the Sibutramine Cardiovascular OUTcomes (SCOUT study were analyzed. 2584 patients (24% had diabetes mellitus (DM only, 1748 (16% had cardiovascular disease (CVD only and 6397 (60% had both DM + CVD. Uric acid concentrations (mean ± standard deviation at screening were significantly higher among patients with CVD compared to patients without CVD (p Conclusion A four week daily intake of sibutramine and life style changes was associated with significant reductions in mean uric acid levels. Changes in renal glucose load in diabetes seem to counteract a potential uricosuric effect of sibutramine. Trial Registration The trial is registered at ClinicalTrial.gov number: NCT00234832.

  13. CREST: Center for Renewable Energy Science and Technology

    Energy Technology Data Exchange (ETDEWEB)

    Billo, Richard E. [Univ. of Texas, Arlington, TX (United States); Rajeshwar, Krishnan [Univ. of Texas, Arlington, TX (United States)

    2012-03-20

    The DOE project addressed an approach to the hydrogen economy by researching hydrogen generation from low cost domestic fossil fuel sources. Specifically, the CREST research team developed new processes for extracting hydrogen from southwestern lignite for the production of clean synthetic fuels such as synthetic crude oil that is free of sulfur, carbon dioxide and other pollutants that can be shipped to nearby Texas refineries and power plants for development of transportation fuels and power generation. Research was also undertaken to convert any potential by-products of this process such as CO2 to useful chemicals and gases which may be recycled and used as feedstock to the synthetic fuel process. Finally, to ensure the proposed process is functional beyond bench scale, a detailed design of a pilot plant was completed. The overall project was divided into five tasks including a management task as outlined below.

  14. Organochlorine contaminants and reproductive success of double-crested cormorants from Green Bay, Wisconsin, USA

    Science.gov (United States)

    Custer, T.W.; Custer, Christine M.; Hines, R.K.; Gutreuter, S.; Stromborg, K.L.; Allen, P. David; Melancon, M.J.

    1999-01-01

    In 1994 and 1995, nesting success of double-crested cormorants (Phalacrocorax auritus) was measured at Cat Island, in southern Green Bay, Lake Michigan, Wisconsin, USA. Sample eggs at pipping and unhatched eggs were collected and analyzed for organochlorines (including total polychlorinated biphenyls [PCBs] and DDE), hepatic microsomal ethoxyresorufin-O-dealkylase (EROD) activity in embryos, and eggshell thickness. Of 1,570 eggs laid, 32% did not hatch and 0.4% had deformed embryos. Of 632 chicks monitored from hatching to 12 d of age, 9% were missing or found dead; no deformities were observed. The PCB concentrations in sample eggs from clutches with deformed embryos (mean = 10.2 μg/g wet weight) and dead embryos (11.4 μg/g) were not significantly higher than concentrations in sample eggs from nests where all eggs hatched (12.1 μg/g). A logistic regression of hatching success versus DDE, dieldrin, and PCB concentrations in sibling eggs identified DDE and not dieldrin or PCBs as a significant risk factor. A logistic regression of hatching success versus DDE and eggshell thickness implicated DDE and not eggshell thickness as a significant risk factor. Even though the insecticide DDT was banned in the early 1970s, we suggest that DDE concentrations in double-crested cormorant eggs in Green Bay are still having an effect on reproduction in this species.

  15. Pulsed versus continuous wave low-level light therapy on osteoarticular signs and symptoms in limited scleroderma (CREST syndrome): a case report

    Science.gov (United States)

    Barolet, Daniel

    2014-11-01

    Limited cutaneous systemic sclerosis (lcSSc) was formerly known as CREST syndrome in reference to the associated clinical features: calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasias. The transforming growth factor beta has been identified as a major player in the pathogenic process, where low-level light therapy (LLLT) has been shown to modulate this cytokine superfamily. This case study was conducted to assess the efficacy of 940 nm using millisecond pulsing and continuous wave (CW) modes on osteoarticular signs and symptoms associated with lcSSc. The patient was treated two to three times a week for 13 weeks using a sequential pulsing mode on one elbow and a CW mode on the other. Efficacy assessments included inflammation, symptoms, pain, health scales, patient satisfaction, clinical global impression, and adverse effects monitoring. Considerable functional and morphologic improvements were observed after LLLT, with the best results seen with the pulsing mode. No adverse effects were noted. Pulsed LLLT represents a treatment alternative for osteoarticular signs and symptoms in limited scleroderma (CREST syndrome).

  16. Do cheatgrass, snake river wheatgrass, and crested wheatgrass sense different availabilities of N and P in soils conditioned by a cheatgrass invasion?

    Science.gov (United States)

    Long-term invasion by cheatgrass often increases availability of soil N and P thereby fostering increased competitive ability. We designed an experiment to test if cheatgrass (exotic annual), Snake River wheatgrass (native perennial), and crested wheatgrass (exotic perennial) all benefit from this e...

  17. Lead dust in Broken Hill homes: effect of remediation on indoor lead levels.

    Science.gov (United States)

    Boreland, F; Lyle, D M

    2006-02-01

    This study was undertaken to determine whether home remediation effectively reduced indoor lead levels in Broken Hill, a long-established silver-lead-zinc mining town in outback Australia. A before-after study of the effect of home remediation on indoor lead levels was embedded into a randomized controlled trial of the effectiveness of remediation for reducing elevated blood lead levels in young children. Moist towelettes were used to measure lead loading (microg/m2) on internal windowsills and internal and entry floors of 98 homes; samples were collected before, immediately after, and 2, 4, 6, 8, and 10 months after remediation. Data were log(10) transformed for the analysis. Remediation reduced average indoor lead levels by approximately 50%, and lead levels remained low for the duration of the follow-up period (10 months). The greatest gains were made in homes with the highest initial lead levels; homes with low preremediation lead levels showed little or no benefit. Before remediation, homes located in areas with high soil lead levels or with "poor" dust proofing had higher lead levels than those in areas with lower soil lead levels or with "medium" or "good" dust proofing; these relative differences remained after remediation. There was no evidence that lead loading was reduced by an increased opportunity to become aware of lead issues. We conclude that remediation is an effective strategy for reducing the lead exposure of children living in homes with high indoor lead levels.

  18. Interaction of adult human neural crest-derived stem cells with a nanoporous titanium surface is sufficient to induce their osteogenic differentiation

    Directory of Open Access Journals (Sweden)

    Matthias Schürmann

    2014-07-01

    Full Text Available Osteogenic differentiation of various adult stem cell populations such as neural crest-derived stem cells is of great interest in the context of bone regeneration. Ideally, exogenous differentiation should mimic an endogenous differentiation process, which is partly mediated by topological cues. To elucidate the osteoinductive potential of porous substrates with different pore diameters (30 nm, 100 nm, human neural crest-derived stem cells isolated from the inferior nasal turbinate were cultivated on the surface of nanoporous titanium covered membranes without additional chemical or biological osteoinductive cues. As controls, flat titanium without any topological features and osteogenic medium was used. Cultivation of human neural crest-derived stem cells on 30 nm pores resulted in osteogenic differentiation as demonstrated by alkaline phosphatase activity after seven days as well as by calcium deposition after 3 weeks of cultivation. In contrast, cultivation on flat titanium and on membranes equipped with 100 nm pores was not sufficient to induce osteogenic differentiation. Moreover, we demonstrate an increase of osteogenic transcripts including Osterix, Osteocalcin and up-regulation of Integrin β1 and α2 in the 30 nm pore approach only. Thus, transplantation of stem cells pre-cultivated on nanostructured implants might improve the clinical outcome by support of the graft adherence and acceleration of the regeneration process.

  19. Volcanic eruption of the mid-ocean ridge along the East Pacific Rise crest at 9°45-52'N: direct submersible observations of seafloor phenomena associated with an eruption event in April, 1991

    Science.gov (United States)

    Haymon, R.M.; Fornari, D.J.; Von Damm, Karen L.; Lilley, M.D.; Perfit, M.R.; Edmond, J.M.; Shanks, Wayne C.; Lutz, R.A.; Grebmeier, J.M.; Carbotte, S.; Wright, D.; McLaughlin, E.; Smith, M.; Beedle, N.; Olson, E.

    1993-01-01

    In April, 1991, we witnessed from the submersible Alvin a suite of previously undocumented seafloor phenomena accompanying an in-progress eruption of the mid-ocean ridge on the East Pacific Rise crest at 9°45′N–52′N. The volume of the eruption could not be precisely determined, although comparison of pre- and post-eruption SeaBeam bathymetry indicate that any changes in ridge crest morphology resulting from the eruption were < 10 m high.

  20. Accuracy of using computer-aided rapid prototyping templates for mandible reconstruction with an iliac crest graft

    Science.gov (United States)

    2014-01-01

    Background This study aimed to evaluate the accuracy of surgical outcomes in free iliac crest mandibular reconstructions that were carried out with virtual surgical plans and rapid prototyping templates. Methods This study evaluated eight patients who underwent mandibular osteotomy and reconstruction with free iliac crest grafts using virtual surgical planning and designed guiding templates. Operations were performed using the prefabricated guiding templates. Postoperative three-dimensional computer models were overlaid and compared with the preoperatively designed models in the same coordinate system. Results Compared to the virtual osteotomy, the mean error of distance of the actual mandibular osteotomy was 2.06 ± 0.86 mm. When compared to the virtual harvested grafts, the mean error volume of the actual harvested grafts was 1412.22 ± 439.24 mm3 (9.12% ± 2.84%). The mean error between the volume of the actual harvested grafts and the shaped grafts was 2094.35 ± 929.12 mm3 (12.40% ± 5.50%). Conclusions The use of computer-aided rapid prototyping templates for virtual surgical planning appears to positively influence the accuracy of mandibular reconstruction. PMID:24957053

  1. PDGF controls contact inhibition of locomotion by regulating N-cadherin during neural crest migration.

    Science.gov (United States)

    Bahm, Isabel; Barriga, Elias H; Frolov, Antonina; Theveneau, Eric; Frankel, Paul; Mayor, Roberto

    2017-07-01

    A fundamental property of neural crest (NC) migration is contact inhibition of locomotion (CIL), a process by which cells change their direction of migration upon cell contact. CIL has been proven to be essential for NC migration in amphibians and zebrafish by controlling cell polarity in a cell contact-dependent manner. Cell contact during CIL requires the participation of the cell adhesion molecule N-cadherin, which starts to be expressed by NC cells as a consequence of the switch between E- and N-cadherins during epithelial-to-mesenchymal transition (EMT). However, the mechanism that controls the upregulation of N-cadherin remains unknown. Here, we show that platelet-derived growth factor receptor alpha (PDGFRα) and its ligand platelet-derived growth factor A (PDGF-A) are co-expressed in migrating cranial NC. Inhibition of PDGF-A/PDGFRα blocks NC migration by inhibiting N-cadherin and, consequently, impairing CIL. Moreover, we identify phosphatidylinositol-3-kinase (PI3K)/AKT as a downstream effector of the PDGFRα cellular response during CIL. Our results lead us to propose PDGF-A/PDGFRα signalling as a tissue-autonomous regulator of CIL by controlling N-cadherin upregulation during EMT. Finally, we show that once NC cells have undergone EMT, the same PDGF-A/PDGFRα works as an NC chemoattractant, guiding their directional migration. © 2017. Published by The Company of Biologists Ltd.

  2. ADAM13 Induces Cranial Neural Crest by Cleaving Class B Ephrins and Regulating Wnt Signaling

    OpenAIRE

    Wei, Shuo; Xu, Guofeng; Bridges, Lance C.; Williams, Phoebe; White, Judith M.; DeSimone, Douglas W.

    2010-01-01

    The cranial neural crest (CNC) are multipotent embryonic cells that contribute to craniofacial structures and other cells and tissues of the vertebrate head. During embryogenesis, CNC is induced at the neural plate boundary through the interplay of several major signaling pathways. Here we report that the metalloproteinase activity of ADAM13 is required for early induction of CNC in Xenopus. In both cultured cells and X. tropicalis embryos, membrane-bound Ephrins (Efns) B1 and B2 were identif...

  3. Effect of low dose 131I-MIBG therapy in metastatic neural crest tumors: Evaluation by RECIST and quality of life questionnaire

    International Nuclear Information System (INIS)

    Basu, S.; Joseph, J.K.

    2004-01-01

    Full text: The primary aim of 131I-MIBG therapy in advanced metastatic or recurrent neural crest tumors is palliation i.e. disease control and improvement of health related quality of life. No clear guidelines regarding the dosage and schedule of 131I-MIBG therapy in neural crest tumors exist at present. In general, a fixed dose of 100-300 mCi has been suggested for each therapy. We share our experience of 131I-MIBG therapy in various subgroups of neural crest tumors and discuss the response assessed by the RECIST and the quality of life questionnaire. A total number of 14 patients were treated with indigenously produced 131I-MIBG, which was administered as continuous intravenous infusion over a period of 2-4 hours. Patient isolation according to guidelines set by the national regulatory authority and thyroid blockade with Lugol's iodide were strictly adhered to. Antihypertensive measures were undertaken in case of pheochromocytoma and paraganglioma to prevent effects of catecholamine release during or following 131I-MIBG infusion. The primaries included neuroblastoma (n=7), pheochromocytoma (n=5) and paraganglioma (n=2). The cases of neuroblastoma included patients with progressive disease where the conventional chemotherapy had failed, while those of pheochromocytoma and paraganglioma were cases with recurrent / metastatic disease following surgery. In cases of multiple therapies, the minimum interval between two consecutive therapies was 12 weeks. Regular renal and haematological profiles were monitored in all the cases. Response to therapy was assessed by RECIST. The findings of 131I-MIBG scintigraphy were incorporated with CT scan in assessing the target lesions. Biochemical response was evaluated by 24 hours urinary VMA estimation. The quality of life status was evaluated by the conventional questionnaire. A total of 27 therapies were administered in 14 patients. In five treated cases of pheochromocytoma, three received multiple therapies. Follow up results

  4. Postotic and preotic cranial neural crest cells differently contribute to thyroid development.

    Science.gov (United States)

    Maeda, Kazuhiro; Asai, Rieko; Maruyama, Kazuaki; Kurihara, Yukiko; Nakanishi, Toshio; Kurihara, Hiroki; Miyagawa-Tomita, Sachiko

    2016-01-01

    Thyroid development and formation vary among species, but in most species the thyroid morphogenesis consists of five stages: specification, budding, descent, bilobation and folliculogenesis. The detailed mechanisms of these stages have not been fully clarified. During early development, the cranial neural crest (CNC) contributes to the thyroid gland. The removal of the postotic CNC (corresponding to rhombomeres 6, 7 and 8, also known as the cardiac neural crest) results in abnormalities of the cardiovascular system, thymus, parathyroid glands, and thyroid gland. To investigate the influence of the CNC on thyroid bilobation process, we divided the CNC into two regions, the postotic CNC and the preotic CNC (from the mesencephalon to rhombomere 5) regions and examined. We found that preotic CNC-ablated embryos had a unilateral thyroid lobe, and confirmed the presence of a single lobe or the absence of lobes in postotic CNC-ablated chick embryos. The thyroid anlage in each region-ablated embryos was of a normal size at the descent stage, but at a later stage, the thyroid in preotic CNC-ablated embryos was of a normal size, conflicting with a previous report in which the thyroid was reduced in size in the postotic CNC-ablated embryos. The postotic CNC cells differentiated into connective tissues of the thyroid in quail-to-chick chimeras. In contrast, the preotic CNC cells did not differentiate into connective tissues of the thyroid. We found that preotic CNC cells encompassed the thyroid anlage from the specification stage to the descent stage. Finally, we found that endothelin-1 and endothelin type A receptor-knockout mice and bosentan (endothelin receptor antagonist)-treated chick embryos showed bilobation anomalies that included single-lobe formation. Therefore, not only the postotic CNC, but also the preotic CNC plays an important role in thyroid morphogenesis. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. The Crest of the Peacock Non-European Roots of Mathematics (Third Edition)

    CERN Document Server

    Joseph, George Gheverghese

    2011-01-01

    From the Ishango Bone of central Africa and the Inca quipu of South America to the dawn of modern mathematics, The Crest of the Peacock makes it clear that human beings everywhere have been capable of advanced and innovative mathematical thinking. George Gheverghese Joseph takes us on a breathtaking multicultural tour of the roots and shoots of non-European mathematics. He shows us the deep influence that the Egyptians and Babylonians had on the Greeks, the Arabs' major creative contributions, and the astounding range of successes of the great civilizations of India and China. The third editio

  6. Low-latitude scintillation occurrences around the equatorial anomaly crest over Indonesia

    Directory of Open Access Journals (Sweden)

    P. Abadi

    2014-01-01

    Full Text Available We investigated low-latitude ionospheric scintillation in Indonesia using two GPS receivers installed at Bandung (107.6° E, 6.9° S; magnetic latitude 17.5° S and Pontianak (109.3° E, 0.02° S; magnetic latitude 8.9° S. This study aimed to characterise climatological and directional ionospheric scintillation occurrences, which are useful not only for the physics of ionospheric irregularities but also for practical use in GNSS (global navigation satellite system-based navigation. We used the deployed instrument's amplitude scintillation (S4 index data from 2009, 2010, and 2011; the yearly SSN (sunspot-smoothed numbers were 3.1, 16.5, and 55.9, respectively. In summary, (1 scintillation occurrences in the post-sunset period (18:00–01:00 LT during equinox months (plasma bubble season at the two sites can be ascribed to the plasma bubble; (2 using directional analyses of the two sites, we found that the distribution of scintillation occurrences is generally concentrated between the two sites, indicating the average location of the EIA (equatorial ionisation anomaly crest; (3 scintillation occurrence enhancements for the two sites in field-aligned directions are herein reported for the first time by ground-based observation in a low-latitude region; (4 distribution of scintillation occurrences at Pontianak are concentrated in the southern sky, especially in the southwest direction, which is very likely associated with the plasma bubble tilted westward with increasing latitude; and (5 scintillation occurrence in the post-midnight period in the non-plasma-bubble season is the most intriguing variable occurring between the two sites (i.e. post-midnight scintillations are observed more at Bandung than Pontianak. Most of the post-midnight scintillations observed at Bandung are concentrated in the northern sky, with low elevation angles. This might be due to the amplitude of irregularities in certain directions, which may be effectively enhanced by

  7. A comparative evaluation of the in vitro penetration performance of the improved Crest Complete toothbrush versus the Colgate Total toothbrush and the Oral-B Advantage toothbrush.

    Science.gov (United States)

    Volpenhein, D W; Hartman, W L

    1996-01-01

    Removal of plaque and debris from interproximal surfaces during toothbrushing has generally been difficult to achieve, in large part because traditional flat-bristled toothbrushes do not offer good interproximal penetration. As a result, a number of varying bristle designs have been developed, with the rippled-design brush shown to be particularly effective at removing interproximal plaque. Recently, an existing rippled brush, the original Crest Complete, was modified to offer longer rippled outer tufts to clean along the gumline more effectively. Therefore, this study evaluated the overall and gumline interproximal penetration of three bristle designs: rippled, raised pattern (Improved Crest Complete); and two multi-level patterns (Colgate Total and Oral-B Advantage). The study used a previously reported in vitro model for determining interproximal penetration of manual toothbrushes (J Clin Dent 5:27-33, 1994). In order to effectively mimic the in-use characteristics of toothbrushing, this model is based on analysis of videotaped consumer brushing habits, tooth morphology, and in vivo plaque tenacity characteristics, and uses the three most predominantly used brushing techniques (circular, up-and-down, and back-and-forth with the brush held at both 45 degrees and 90 degrees to the tooth surface). In addition, the model's brush stroke length, brush force, and brush speed are likewise based on an analysis of consumer brushing patterns. The results of this study indicate that the Improved Crest Complete with longer rippled outer bristles provided significantly superior (p Colgate Total and Oral-B Advantage brushes.

  8. Marek’s disease in the holland white crested chickens

    Directory of Open Access Journals (Sweden)

    Spalević Ljiljana

    2016-01-01

    Full Text Available Marek’s disease is a viral lymphoproliferative disease of poultry characterized by the creation of lymphoma in muscle, skin, eye or internal organs. Virus maturing into infective forms in follicular epithelium from where enters in the external environment where long time remains infectious. Poultry are infected by dust and remains the holder of the virus throughout their lives. The virus is transmitted vertically. The disease can occur in three forms: nervous, visceral and skin. Affected poultry may have any shape or combination of these. The aim of this study was to determine the cause of the disorder the health status in the flock of holland white crested chickens. Flock had 25 chickens whose ages ranged from 4-16 weeks. Observation, we noticed that the chickens are cachectic, showing signs of sporadic diarrhea and died 3 hens and 2 roosters. Pathoanatomical examination is ascertained changes in certain internal organs. The liver was enlarged with lymphoid proliferate on the surface and in the parenchyma, spleen increased several times and marbled, glandular stomach (proventriculus dilated with petechial hemorrhages on mucose. Changed organs was examination histopathological. In the liver were observed multifocal lymphoid infiltration with subsequent atrophy of the parenchyma, in addition to spleen lymphoid proliferation heterophyllus and histiocytic infiltrates, in proventriculus lymphoblastic infiltration with congestion of capillaries and small haemorrhages. In samples pathologically altered organs PCR method proved the genome of Marek’s disease virus serotype 1 . Based on these results we concluded that the livestock were sick from Marek’s disease, which is expressed in visceral form.

  9. Diet composition and fish consumption of double-crested cormorants from three St. Lawrence River Colonies in 2013

    Science.gov (United States)

    Johnson, James H.; Farquhar, James F.; Mazzocchi, Irene M.; Bendig, Anne

    2014-01-01

    Double-crested Cormorants (Phalacrocorax auritus) were first observed nesting in the upper St. Lawrence River at Strachan Island in 1992. Cormorants now nest at a number of islands in the Thousand Islands section of the river. Griswold, McNair, and Strachan islands are among the largest colonies in the upper river. Until 2011, nest counts had remained relatively stable, ranging from 200 to 603 nests per colony. However, since 2011 the number of nests at McNair Island have exceeded 700 each year. Although the size of cormorant colonies in the upper St. Lawrence River is smaller than those in the eastern basin of Lake Ontario, the close proximity of islands in the upper river that have colonies may cause a cumulative fish consumption effect similar to a larger colony. Because of increasing numbers of Double-crested Cormorants in the upper St. Lawrence River and the possible effects on fish populations, studies were initiated in 1999 to quantify cormorant diet and fish consumption at the three largest colonies. From 1999 to 2012, these studies have shown that cormorants consumed about 128.6 million fish including 37.5 million yellow perch (Perca flavescens), 17.4 million rock bass (Ambloplites rupestris) and 1.0 million smallmouth bass (Micropterus dolemieu) (Johnson et al. 2012). During this same time period fish assessment studies near some of these islands have shown a major decrease in yellow perch populations (Klindt 2007). This occurrence is known as the halo effect and happens when piscivorous birds deplete local fish populations in areas immediately surrounding the colony (Ashmole 1963). This paper describes the diet and fish consumption of cormorants in the upper St. Lawrence River in 2013.

  10. Discharge coefficient of a rectangular sharp-edged broad-crested weir

    Directory of Open Access Journals (Sweden)

    Zachoval Zbyněk

    2014-06-01

    Full Text Available This paper is concerned with the determination of the relationship for the calculation of the discharge coefficient at free overflow over a rectangular sharp-edged broad-crested weir without lateral contraction. The determination was made on the basis of new measurement in a range of the relative thickness of the weir from 0.12 to 0.30 and newly in a large range of relative height of the weir extremely from 0.24 to 6.8 which greatly expands the application possibilities of low weirs. In addition, the effects of friction and surface tension on the value of the discharge coefficient were evaluated as well as the effect of the relative thickness of the weir. The new equation for discharge coefficient, expressed using the relative height of the weir, was subjected to verification made by an independent laboratory which confirmed its accuracy.

  11. E-cigarette aerosol exposure can cause craniofacial defects in Xenopus laevis embryos and mammalian neural crest cells.

    Science.gov (United States)

    Kennedy, Allyson E; Kandalam, Suraj; Olivares-Navarrete, Rene; Dickinson, Amanda J G

    2017-01-01

    Since electronic cigarette (ECIG) introduction to American markets in 2007, vaping has surged in popularity. Many, including women of reproductive age, also believe that ECIG use is safer than traditional tobacco cigarettes and is not hazardous when pregnant. However, there are few studies investigating the effects of ECIG exposure on the developing embryo and nothing is known about potential effects on craniofacial development. Therefore, we have tested the effects of several aerosolized e-cigarette liquids (e-cigAM) in an in vivo craniofacial model, Xenopus laevis, as well as a mammalian neural crest cell line. Results demonstrate that e-cigAM exposure during embryonic development induces a variety of defects, including median facial clefts and midface hypoplasia in two of e-cigAMs tested e-cigAMs. Detailed quantitative analyses of the facial morphology revealed that nicotine is not the main factor in inducing craniofacial defects, but can exacerbate the effects of the other e-liquid components. Additionally, while two different e-cigAMs can have very similar consequences on facial appearances, there are subtle differences that could be due to the differences in e-cigAM components. Further assessment of embryos exposed to these particular e-cigAMs revealed cranial cartilage and muscle defects and a reduction in the blood supply to the face. Finally, the expression of markers for vascular and cartilage differentiation was reduced in a mammalian neural crest cell line corroborating the in vivo effects. Our work is the first to show that ECIG use could pose a potential hazard to the developing embryo and cause craniofacial birth defects. This emphasizes the need for more testing and regulation of this new popular product.

  12. Lead exposure potentiates predatory attack behavior in the cat.

    Science.gov (United States)

    Li, Wenjie; Han, Shenggao; Gregg, Thomas R; Kemp, Francis W; Davidow, Amy L; Louria, Donald B; Siegel, Allan; Bogden, John D

    2003-07-01

    Epidemiologic studies have demonstrated that environmental lead exposure is associated with aggressive behavior in children; however, numerous confounding variables limit the ability of these studies to establish a causal relationship. The study of aggressive behavior using a validated animal model was used to test the hypothesis that there is a causal relationship between lead exposure and aggression in the absence of confounding variables. We studied the effects of lead exposure on a feline model of aggression: predatory (quiet biting) attack of an anesthetized rat. Five cats were stimulated with a precisely controlled electrical current via electrodes inserted into the lateral hypothalamus. The response measure was the predatory attack threshold current (i.e., the current required to elicit an attack response on 50% of the trials). Blocks of trials were administered in which predatory attack threshold currents were measured three times a week for a total of 6-10 weeks, including before, during, and after lead exposure. Lead was incorporated into cat food "treats" at doses of 50-150 mg/kg/day. Two of the five cats received a second period of lead exposure. Blood lead concentrations were measured twice a week and were cats and increased after the cessation of lead exposure in four of the five cats (Pcat were inversely correlated (r=-0.35 to -0.74). A random-effects mixed model demonstrated a significant (P=0.0019) negative association between threshold current and blood lead concentration. The data of this study demonstrate that lead exposure enhances predatory aggression in the cat and provide experimental support for a causal relationship between lead exposure and aggressive behavior in humans.

  13. Searching for TeV cosmic electrons with the CREST experiment

    International Nuclear Information System (INIS)

    Coutu, S.; Anderson, T.; Bower, C.; Gennaro, J.; Geske, M.; Mueller, D.; Musser, J.; Nutter, S.; Park, N.H.; Schubnell, M.; Tarle, G.; Wakely, S.; Yagi, A.

    2011-01-01

    The Cosmic Ray Electron Synchrotron Telescope (CREST) high-altitude balloon experiment is a pathfinding effort to detect for the first time multi-TeV cosmic-ray electrons. Such would be the markers of nearby cosmic accelerators, as energetic electrons from distant Galactic sources are expected to be depleted by radiative losses during interstellar transport. Electrons will be detected indirectly by the characteristic signature of their geomagnetic synchrotron losses, in the form of a burst of coaligned x-ray photons intersecting the plane of the instrument. Since the primary electron itself need not traverse the payload, an effective detection area is achieved that is several times the nominal 6.4 m 2 instrument. The payload is composed of an array of 1024 BaF2 crystals surrounded by a set of veto scintillator detectors. A long-duration balloon flight in Antarctica is planned for the 2011-12 season.

  14. Searching for TeV cosmic electrons with the CREST experiment

    Energy Technology Data Exchange (ETDEWEB)

    Coutu, S., E-mail: coutu@phys.psu.edu [Department of Physics, Pennsylvania State University, 104 Davey Laboratory, University Park, PA 16802 (United States); Anderson, T. [Department of Physics, Pennsylvania State University, 104 Davey Laboratory, University Park, PA 16802 (United States); Bower, C. [Physics Department, Indiana University, 117 Swain Hall West, Bloomington, IN 47405 (United States); Gennaro, J. [Department of Physics, University of Michigan, Randall Physics Laboratory, 500 E. University Ave, Ann Arbor, MI 48109 (United States); Geske, M. [Department of Physics, Pennsylvania State University, 104 Davey Laboratory, University Park, PA 16802 (United States); Mueller, D. [Enrico Fermi Institute and Department of Physics, University of Chicago, 933 E. 56th St., Chicago, IL 60637 (United States); Musser, J. [Physics Department, Indiana University, 117 Swain Hall West, Bloomington, IN 47405 (United States); Nutter, S. [Department of Physics and Geology, Northern Kentucky University, Highland Heights, KY 41099 (United States); Park, N.H. [Enrico Fermi Institute and Department of Physics, University of Chicago, 933 E. 56th St., Chicago, IL 60637 (United States); Schubnell, M.; Tarle, G. [Department of Physics, University of Michigan, Randall Physics Laboratory, 500 E. University Ave, Ann Arbor, MI 48109 (United States); Wakely, S. [Enrico Fermi Institute and Department of Physics, University of Chicago, 933 E. 56th St., Chicago, IL 60637 (United States); Yagi, A. [Department of Physics, University of Michigan, Randall Physics Laboratory, 500 E. University Ave, Ann Arbor, MI 48109 (United States)

    2011-06-15

    The Cosmic Ray Electron Synchrotron Telescope (CREST) high-altitude balloon experiment is a pathfinding effort to detect for the first time multi-TeV cosmic-ray electrons. Such would be the markers of nearby cosmic accelerators, as energetic electrons from distant Galactic sources are expected to be depleted by radiative losses during interstellar transport. Electrons will be detected indirectly by the characteristic signature of their geomagnetic synchrotron losses, in the form of a burst of coaligned x-ray photons intersecting the plane of the instrument. Since the primary electron itself need not traverse the payload, an effective detection area is achieved that is several times the nominal 6.4 m{sup 2} instrument. The payload is composed of an array of 1024 BaF2 crystals surrounded by a set of veto scintillator detectors. A long-duration balloon flight in Antarctica is planned for the 2011-12 season.

  15. The effect of interior lead hazard controls on children's blood lead concentrations: a systematic evaluation.

    Science.gov (United States)

    Haynes, Erin; Lanphear, Bruce P; Tohn, Ellen; Farr, Nick; Rhoads, George G

    2002-01-01

    Dust control is often recommended to prevent children's exposure to residential lead hazards, but the effect of these controls on children's blood lead concentrations is uncertain. We conducted a systematic review of randomized, controlled trials of low-cost, lead hazard control interventions to determine the effect of lead hazard control on children's blood lead concentration. Four trials met the inclusion criteria. We examined mean blood lead concentration and elevated blood lead concentrations (> or = 10 microg/dL, > or = 15 microg/dL, and > or = 20 microg/dL) and found no significant differences in mean change in blood lead concentration for children by random group assignment (children assigned to the intervention group compared with those assigned to the control group). We found no significant difference between the intervention and control groups in the percentage of children with blood lead > or = 10 microg/dL, 29% versus 32% [odds ratio (OR), 0.85; 95% confidence interval (CI), 0.56-1.3], but there was a significant difference in the percentage of children with blood lead > or = 15 microg/dL between the intervention and control groups, 6% versus 14% (OR, 0.40; 95% CI, 0.21-0.80) and in the percentage of children with blood lead > or = 20 microg/dL between the intervention and control groups, 2% versus 6% (OR, 0.29; 95% CI, 0.10-0.85). We conclude that although low-cost, interior lead hazard control was associated with 50% or greater reduction in the proportion of children who had blood lead concentrations exceeding 15 microg/dL and > or = 20 microg/dL, there was no substantial effect on mean blood lead concentration.

  16. A new technique of "midline anchoring" in spinal cord stimulation dramatically reduces lead migration.

    Science.gov (United States)

    Mironer, Y Eugene; Brown, Christopher; Satterthwaite, John R; Cohen, Mary; Tonder, Lisa M; Grumman, Steve

    2004-01-01

    Spinal cord stimulation (SCS) is a popular method of treatment of chronic pain. Unfortunately, migration of the lead continues to be a serious complication of this therapy. In an attempt to reduce lateral migration of the SCS lead, we performed a retrospective assessment of a new technique of percutaneous lead placement. This new method of "midline anchoring" of the lead using the plica mediana dorsalis was tested against conventional technique in a retrospective study involving 122 trials and 91 implants of SCS over a period of five years. The use of "midline anchoring" resulted in a decrease in lead migration from 23% to 6% after trial insertion and from 24% to 7% after implantation. We conclude that "midline anchoring" of the SCS lead is an effective method of preventing lead migration.

  17. Investigation of the Study Characteristics Affecting Clinical Trial Quality Using the Protocol Deviations Leading to Exclusion of Subjects From the Per Protocol Set Data in Studies for New Drug Application: A Retrospective Analysis.

    Science.gov (United States)

    Kohara, Norihito; Kaneko, Masayuki; Narukawa, Mamoru

    2018-01-01

    The concept of the risk-based approach has been introduced as an effort to secure the quality of clinical trials. In the risk-based approach, identification and evaluation of risk in advance are considered important. For recently completed clinical trials, we investigated the relationship between study characteristics and protocol deviations leading to the exclusion of subjects from Per Protocol Set (PPS) efficacy analysis. New drugs approved in Japan in the fiscal year 2014-2015 were targeted in the research. The reasons for excluding subjects from the PPS efficacy analysis were described in 102 trials out of 492 in the summary of new drug application documents, which was publicly disclosed after the drug's regulatory approval. The author extracted these reasons along with the numbers of the cases and the study characteristics of each clinical trial. Then, the direct comparison, univariate regression analysis, and multivariate regression analysis was carried out based on the exclusion rate. The study characteristics for which exclusion of subjects from the PPS efficacy analysis were frequently observed was multiregional clinical trials in study region; inhalant and external use in administration route; Anti-infective for systemic use; Respiratory system, Dermatologicals, and Nervous system in therapeutic drug under the Anatomical Therapeutic Chemical Classification. In the multivariate regression analysis, the clinical trial variables of inhalant, Respiratory system, or Dermatologicals were selected as study characteristics leading to a higher exclusion rate. The characteristics of the clinical trial that is likely to cause protocol deviations that will affect efficacy analysis were suggested. These studies should be considered for specific attention and priority observation in the trial protocol or its monitoring plan and execution, such as a clear description of inclusion/exclusion criteria in the protocol, development of training materials to site staff, and

  18. Tcf7l1 protects the anterior neural fold from adopting the neural crest fate

    Czech Academy of Sciences Publication Activity Database

    Mašek, Jan; Machoň, Ondřej; Kořínek, Vladimír; Taketo, M.M.; Kozmik, Zbyněk

    2016-01-01

    Roč. 143, č. 12 (2016), s. 2206-2216 ISSN 0950-1991 R&D Projects: GA ČR GAP305/12/2042; GA ČR(CZ) GA14-33952S; GA MŠk(CZ) LK11214; GA MŠk LO1419; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:68378050 Keywords : Tcf/Lef * Wnt dignaling * neural crest * forebrain * mouse * zebrafish Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.843, year: 2016

  19. A new crested pterosaur from the Early Cretaceous of Spain: the first European tapejarid (Pterodactyloidea: Azhdarchoidea.

    Directory of Open Access Journals (Sweden)

    Romain Vullo

    Full Text Available BACKGROUND: The Tapejaridae is a group of unusual toothless pterosaurs characterized by bizarre cranial crests. From a paleoecological point of view, frugivorous feeding habits have often been suggested for one of its included clades, the Tapejarinae. So far, the presence of these intriguing flying reptiles has been unambiguously documented from Early Cretaceous sites in China and Brazil, where pterosaur fossils are less rare and fragmentary than in similarly-aged European strata. METHODOLOGY/PRINCIPAL FINDINGS: Europejara olcadesorum gen. et sp. nov. is diagnosed by a unique combination of characters including an unusual caudally recurved dentary crest. It represents the oldest known member of Tapejaridae and the oldest known toothless pterosaur. The new taxon documents the earliest stage of the acquisition of this anatomical feature during the evolutionary history of the Pterodactyloidea. This innovation may have been linked to the development of new feeding strategies. CONCLUSION/SIGNIFICANCE: The discovery of Europejara in the Barremian of the Iberian Peninsula reveals an earlier and broader global distribution of tapejarids, suggesting a Eurasian origin of this group. It adds to the poorly known pterosaur fauna of the Las Hoyas locality and contributes to a better understanding of the paleoecology of this Konservat-Lagerstätte. Finally, the significance of a probable contribution of tapejarine tapejarids to the early angiosperm dispersal is discussed.

  20. E-cigarette aerosol exposure can cause craniofacial defects in Xenopus laevis embryos and mammalian neural crest cells.

    Directory of Open Access Journals (Sweden)

    Allyson E Kennedy

    Full Text Available Since electronic cigarette (ECIG introduction to American markets in 2007, vaping has surged in popularity. Many, including women of reproductive age, also believe that ECIG use is safer than traditional tobacco cigarettes and is not hazardous when pregnant. However, there are few studies investigating the effects of ECIG exposure on the developing embryo and nothing is known about potential effects on craniofacial development. Therefore, we have tested the effects of several aerosolized e-cigarette liquids (e-cigAM in an in vivo craniofacial model, Xenopus laevis, as well as a mammalian neural crest cell line. Results demonstrate that e-cigAM exposure during embryonic development induces a variety of defects, including median facial clefts and midface hypoplasia in two of e-cigAMs tested e-cigAMs. Detailed quantitative analyses of the facial morphology revealed that nicotine is not the main factor in inducing craniofacial defects, but can exacerbate the effects of the other e-liquid components. Additionally, while two different e-cigAMs can have very similar consequences on facial appearances, there are subtle differences that could be due to the differences in e-cigAM components. Further assessment of embryos exposed to these particular e-cigAMs revealed cranial cartilage and muscle defects and a reduction in the blood supply to the face. Finally, the expression of markers for vascular and cartilage differentiation was reduced in a mammalian neural crest cell line corroborating the in vivo effects. Our work is the first to show that ECIG use could pose a potential hazard to the developing embryo and cause craniofacial birth defects. This emphasizes the need for more testing and regulation of this new popular product.

  1. Lead exposure potentiates predatory attack behavior in the cat

    International Nuclear Information System (INIS)

    Li Wenjie; Han Shenggao; Gregg, T.R.; Kemp, F.W.Francis W.; Davidow, A.L.; Louria, D.B.; Siegel, Allan; Bogden, J.D.

    2003-01-01

    Epidemiologic studies have demonstrated that environmental lead exposure is associated with aggressive behavior in children; however, numerous confounding variables limit the ability of these studies to establish a causal relationship. The study of aggressive behavior using a validated animal model was used to test the hypothesis that there is a causal relationship between lead exposure and aggression in the absence of confounding variables. We studied the effects of lead exposure on a feline model of aggression: predatory (quiet biting) attack of an anesthetized rat. Five cats were stimulated with a precisely controlled electrical current via electrodes inserted into the lateral hypothalamus. The response measure was the predatory attack threshold current (i.e., the current required to elicit an attack response on 50% of the trials). Blocks of trials were administered in which predatory attack threshold currents were measured three times a week for a total of 6-10 weeks, including before, during, and after lead exposure. Lead was incorporated into cat food 'treats' at doses of 50-150 mg/kg/day. Two of the five cats received a second period of lead exposure. Blood lead concentrations were measured twice a week and were <1, 21-77, and <20 μg/dL prior to, during, and after lead exposure, respectively. The predatory attack threshold decreased significantly during initial lead exposure in three of five cats and increased after the cessation of lead exposure in four of the five cats (P<0.01). The predatory attack thresholds and blood lead concentrations for each cat were inversely correlated (r=-0.35 to -0.74). A random-effects mixed model demonstrated a significant (P=0.0019) negative association between threshold current and blood lead concentration. The data of this study demonstrate that lead exposure enhances predatory aggression in the cat and provide experimental support for a causal relationship between lead exposure and aggressive behavior in humans

  2. A career at the interface of cell and developmental biology: a view from the crest.

    Science.gov (United States)

    Bronner, Marianne E

    2012-11-01

    Just as neural crest cells migrate great distances through the embryo, my journey has taken me from a childhood in a distant land to a career as a biologist. My mentoring relationships have shaped not only the careers of my trainees, but also the trajectory of my own science. One of the most satisfying aspects of mentoring comes from helping to empower the next generation of scientists to do more tomorrow than is possible today. This, together with a passion for discovery and learning new things, motivates me and makes science such a rewarding career.

  3. Feeding behavior and activity budget of the southern yellow-cheeked crested gibbons (Nomascus gabriellae) in a lowland tropical forest.

    Science.gov (United States)

    Bach, Thanh H; Chen, Jin; Hoang, Minh D; Beng, Kingsly C; Nguyen, Van T

    2017-08-01

    The southern yellow-cheeked crested gibbon (Nomascus gabriellae), an endangered species native to Vietnam and Cambodia, lives exclusively in undisturbed tropical forests and depends primarily on ripe fruit for food. Although this species is highly threatened, its ecology and conservation status remain relatively unknown. In order to understand how this heavily frugivorous primate adapts to the seasonal fluctuation of fruit resources in the forest, we collected feeding behavior and ranging activity data on one group of southern yellow-cheeked crested gibbons in Cat Tien National Park, Vietnam, over 1-year period. We compared these data to information on phenological patterns at the site gleaned during a prior study. We found that the gibbons gathered most of their food from 69 different plant species and also consumed insects and bird eggs. Fruits were the main dietary item (43.3%), followed by leaves (38.4%), flowers (11.6%), and other plant parts (6.0%). A significant seasonal shift in diet was observed; fruit generally dominated the diet in the rainy season and leaves in the dry season. The gibbons often started daily activities very early (05:10 am) in the morning and also ended quite early (16:45 pm) in the afternoon. Socializing was concentrated in the early morning, feeding had a bimodal pattern of high activity levels in mid-morning and mid-afternoon, and resting was most intense at the earliest and latest hours of the day and at midday, with proportionally less time used for traveling at these times. Averaged over the annual cycle, the gibbons spent 45% of their time feeding, 31.9% resting, 14.1% traveling, and 9.0% socializing. The percentage of time allocated to different activities varied significantly across months and between the dry and rainy seasons. Monthly variation in the activity budget was strongly related to changes in diet. In the rainy season, when the gibbons ate a higher percentage of fruit, they decreased their feeding time, while

  4. A study on multifrequency scintillations near the EIA crest of the Indian zone

    Science.gov (United States)

    Chakraborty, S. K.; Chatterjee, S.; Jana, Debasis

    2017-10-01

    Occurrence features of ionospheric scintillations at S band (2492.028 MHz) are reported for the first time. The same have been explored in the context of scintillations at VHF (250.650 MHz) and L5 (1176.45 MHz) bands. Observations were carried out during the period April-December, 2015 at Raja Peary Mohan College Centre (RPMC: 22.66° N, 88.4° E), located near the equatorial ionization anomaly (EIA) crest of the Indian longitude zone. Mostly weak (<10 dB), short duration, slow fading rate with shallower slope power spectra characterize the S band scintillations compared to VHF and L5 band. In the severe scintillation conditions of VHF frequent loss of lock in L5 channel is reflected. Fade depth of 4.2 ± 1.3 dB and fade rate ∼9 fades/minute at S band mostly precede the loss of lock at L5 channel. A good correspondence between fade rates at multi frequency band is reflected irrespective of phases of scintillation. Spectral analysis reveals weak scattering is the dominating mechanism for scintillation at S band while VHF and L5 band scintillations are mostly attributed to multiple scattering. The estimated threshold coherence length of <23 m at VHF may be suggested to be a good indicator for occurrence of L5 and S band scintillations. Occurrence of simultaneous multi-satellite multi-frequency scintillations leads to speculation over the failsafe navigation using available IRNSS constellation. The results are discussed in terms of existing theory of evolution, structure and dynamics of electron density irregularities in the low latitude region.

  5. Crest Factor Reduction for OFDM Using Selective Subcarrier Degradation

    Institute of Scientific and Technical Information of China (English)

    R. Neil Braithwaite

    2011-01-01

    This paper describes a crest factor reduction (CFR) method that reduces peaks in the time domain by modifying selected data subcarriers within an OFDM signal. The data subcarriers selected for modification vary with each symbol interval and are limited to those subcarriers whose aata elements are mapped onto the outer boundary of the constellation. In the proposed method, a set of peaks are identified within an OFDM symbol interval. Data subcarriers whose data element has a positive or negative correlation with the set peak are selected. For a subcarrier with an outer element and a significant positive correlation, a bit error (reversal) is intentionally introduced. This moves the data element to the opposite side of the constellation. Outer elements on negatively-correlatea subcarriers are increased in magnitude along the real or imaginary axis. Experimental results show that selecting the correct subcarriers for bit reversals and outward enhancements reduces the peak-to-average power ratio (PAPR) of the OFDM signal to a target value and limits in-band degradation measured by bit error rate (BER) and error vector magnitude (EVM).

  6. Conditional deletion of AP-2β in mouse cranial neural crest results in anterior segment dysgenesis and early-onset glaucoma

    Directory of Open Access Journals (Sweden)

    Vanessa B. Martino

    2016-08-01

    Full Text Available Anterior segment dysgenesis (ASD encompasses a group of developmental disorders in which a closed angle phenotype in the anterior chamber of the eye can occur and 50% of patients develop glaucoma. Many ASDs are thought to involve an inappropriate patterning and migration of the periocular mesenchyme (POM, which is derived from cranial neural crest cells (NCCs and mesoderm. Although, the mechanism of this disruption is not well understood, a number of transcriptional regulatory molecules have previously been implicated in ASDs. Here, we investigate the function of the transcription factor AP-2β, encoded by Tfap2b, which is expressed in NCCs and their derivatives. Wnt1-Cre-mediated conditional deletion of Tfap2b in NCCs resulted in post-natal ocular defects typified by opacity. Histological data revealed that the conditional AP-2β NCC knockout (KO mutants exhibited dysgenesis of multiple structures in the anterior segment of the eye including defects in the corneal endothelium, corneal stroma, ciliary body and disruption in the iridocorneal angle with adherence of the iris to the cornea. We further show that this phenotype leads to a significant increase in intraocular pressure and a subsequent loss of retinal ganglion cells and optic nerve degeneration, features indicative of glaucoma. Overall, our findings demonstrate that AP-2β is required in the POM for normal development of the anterior segment of the eye and that the AP-2β NCC KO mice might serve as a new and exciting model of ASD and glaucoma that is fully penetrant and with early post-natal onset.

  7. Osteosclerotic metaphyseal dysplasia: a skeletal dysplasia that may mimic lead poisoning in a child with hypotonia and seizures

    International Nuclear Information System (INIS)

    Mennel, Emilie A.; John, Susan D.

    2003-01-01

    We report the case of a 23-month-old male with hypotonia, developmental delay, and complex seizures. Radiographs revealed profound sclerosis of the metaphyses and epiphyses of the long and short bones in the extremities, with a unique pattern of distribution. Sclerosis also involved the anterior ribs, iliac crests, talus, and calcaneus. The skull and vertebral bodies appeared unaffected. Blood lead levels were normal. We believe that this constellation of clinical and radiographic abnormalities closely resembles osteosclerotic metaphyseal dysplasia (OMD) due to an autosomal recessive defect. Characteristic skeletal findings were instrumental in determining the diagnosis. OMD is a very rare sclerosing bone disorder, first described in 1993. The syndrome is characterized clinically by developmental delay of a progressive nature, hypotonia, elevated alkaline phosphatase, and late-onset spastic paraplegia. We encountered a young child with these neurologic symptoms who displayed sclerotic metaphyseal changes on hand radiographs obtained to determine the bone age. Lead poisoning, a known cause of metaphyseal sclerosis, was initially suspected. Careful analysis of the metaphyseal bone changes helped to distinguish this bone dysplasia from lead poisoning and other causes of metaphyseal sclerosis. (orig.)

  8. Clinical trials in nuclear medicine: Present and future

    International Nuclear Information System (INIS)

    Chaumet-Riffaud, P.; Cachin, F.; Couturier, O.; Desruet, M.D.; Kraeber-Bodere, F.; Talbot, J.N.; Vuillez, J.P.

    2009-01-01

    The particular status of radiopharmaceuticals, together with the positioning of nuclear medicine in multidisciplinary approach of oncology, lead to real difficulties for conception, validation and granting of clinical trials which are necessary for demonstrating clinical interest of new compounds, for diagnosis as well as for therapeutic use. This article is a presentation of some recent clinical trials conducted in nuclear medicine in France, showing its dynamism but also pointing out some encountered difficulties. These experiences could lead to reflexion in order to improve the clinical research performances, taking into account a scientific and regulatory context more and more constraining. (authors)

  9. Simultaneous occurrence of Salmonella arizonae in a sulfur crested cockatoo (Cacatua galerita galerita) and iguanas.

    Science.gov (United States)

    Orós, J; Rodríguez, J L; Fernández, A; Herráez, P; Espinosa de los Monteros, A; Jacobson, E R

    1998-01-01

    A case of fatal hepatitis in a captive sulfur crested cockatoo (Cacatua galerita galerita) in which Salmonella arizonae was microbiologically and immunohistochemically detected is described. The death of the cockatoo was closely related to the arrival of a group of 10 green iguanas (Iguana iguana) at a pet shop, and no previous clinical signs were observed in the cockatoo. The most important lesion observed at necropsy of the cockatoo was a multifocal necrotic hepatitis. Salmonella arizonae was isolated from the liver of the cockatoo and was detected immunohistochemically mainly around the edges of necrotic foci. Four iguanas died 3 days later showing a severe enteritis, and Salmonella arizonae was isolated from these lesions. The importance of quarantine and, because of pathogens such as Salmonella, the need to house reptiles at a distance from avian species, mainly psittacids, are reinforced. This is the first report of Salmonella arizonae infection in a cockatoo.

  10. Chronic prenatal lead exposure impairs long-term memory in day old chicks.

    Science.gov (United States)

    Zhong, Zhaoming; Zhang, Chunxiao; Rizak, Joshua D; Cui, Yonghua; Xu, Shiqing; Che, Yi

    2010-05-26

    Environmental exposure to lead during developmental stages has been established as a potential cause of intellectual deficits. The high susceptibility of rapidly developing fetal and infant brains to external factors suggests that impairment of later cognitive functions may arise from relatively minor prenatal exposure to environmental lead levels. In this study, we used the one-trial passive avoidance learning paradigm with day old chicks to evaluate memory function and memory consolidation in response to prenatal lead exposure. Lead acetate (5.5mg/kg, 11mg/kg, 16.5mg/kg) was administered daily from E9 to E16 via direct injection into the airspace in chick eggs. Higher doses of lead acetate (11mg/kg, 16.5mg/kg) administration had significant effects on the hatching success (23.4 and 17, respectively) and hatch weight ( approximately 10% decrease) of chicks when compared to equivalent treatments of sodium acetate (11mg/kg, 16.5mg/kg) (plong-term memory after 120min following training in the one-trial passive avoidance learning task (pmemory processes. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  11. Competition between items in working memory leads to forgetting.

    Science.gov (United States)

    Lewis-Peacock, Jarrod A; Norman, Kenneth A

    2014-12-18

    Switching attention from one thought to the next propels our mental lives forward. However, it is unclear how this thought-juggling affects our ability to remember these thoughts. Here we show that competition between the neural representations of pictures in working memory can impair subsequent recognition of those pictures. We use pattern classifiers to decode functional magnetic resonance imaging (fMRI) data from a retro-cueing task where participants juggle two pictures in working memory. Trial-by-trial fluctuations in neural dynamics are predictive of performance on a surprise recognition memory test: trials that elicit similar levels of classifier evidence for both pictures (indicating close competition) are associated with worse memory performance than trials where participants switch decisively from thinking about one picture to the other. This result is consistent with the non-monotonic plasticity hypothesis, which predicts that close competition can trigger weakening of memories that lose the competition, leading to subsequent forgetting.

  12. Foraging plasticity in seabirds: A non-invasive study of the diet of greater crested terns breeding in the Benguela region

    Science.gov (United States)

    2018-01-01

    Marine predators, such as seabirds, are useful indicators of marine ecosystem functioning. In particular, seabird diet may reflect variability in food-web composition due to natural or human-induced environmental change. Diet monitoring programmes, which sample diet non-invasively, are valuable aids to conservation and management decision-making. We investigated the diet of an increasing population of greater crested terns Thalasseus bergii in the Western Cape, South Africa, during three successive breeding seasons (2013 to 2015), when populations of other seabirds feeding on small pelagic schooling fish in the region were decreasing. Breeding greater crested terns carry prey in their bills, so we used an intensive photo-sampling method to record their diet with little disturbance. We identified 24,607 prey items from at least 47 different families, with 34 new prey species recorded. Fish dominated the diet, constituting 94% of prey by number, followed by cephalopods (3%), crustaceans (2%) and insects (1%). The terns mainly targeted surface-schooling Clupeiformes, with anchovy Engraulis encrasicolus the most abundant prey in all three breeding seasons (65% overall). Prey composition differed significantly between breeding stages and years, with anchovy most abundant at the start of the breeding season, becoming less frequent as the season progressed. The proportion of anchovy in the diet also was influenced by environmental factors; anchovy occurred more frequently with increasing wind speeds and was scarce on foggy days, presumably because terns rely in part on social facilitation to locate anchovy schools. The application of this intensive and non-invasive photo-sampling method revealed an important degree of foraging plasticity for this seabird within a context of locally reduced food availability, suggesting that, unlike species that specialise on a few high-quality prey, opportunistic seabirds may be better able to cope with reductions in the abundance of

  13. Abundance of Harpy and Crested Eagles from a reservoir-impact area in the Low- and Mid-Xingu River

    Directory of Open Access Journals (Sweden)

    TM. Sanaiotti

    Full Text Available Abstract In the Brazilian Amazon, two monospecific genera, the Harpy Eagle and Crested Eagle have low densities and are classified by IUCN as Near Threatened due to habitat loss, deforestation, habitat degradation and hunting. In this study, we evaluate occurrence of these large raptors using the environmental surveys database from Belo Monte Hydroelectric Power Plant. Integrating the dataset from two methods, we plotted a distribution map along the Xingu River, including records over a 276-km stretch of river. Terrestrial surveys (RAPELD method were more efficient for detecting large raptors than standardized aquatic surveys, although the latter were complementary in areas without modules. About 53% of the records were obtained during activities of wildlife rescue/flushing, vegetation suppression or in transit. Between 2012 and 2014, four Harpy Eagles were removed from the wild; two shooting victims, one injured by collision with power lines and one hit by a vehicle. Also, seven nests were mapped. The mean distance between Harpy Eagle records was 15 km along the river channel, with a mean of 20 km between nests near the channel, which allowed us to estimate 20 possible pairs using the alluvial forest, riverine forest and forest fragments. Territories of another ten pairs will probably be affected by inundation of the Volta Grande channel, which is far from the main river. The average distance between Crested Eagle records was 16 km along the river channel. The only nest found was 1.3 km away from a Harpy Eagle nest. The remnant forests are under threat of being replaced by cattle pastures, so we recommend that permanently protected riparian vegetation borders (APP be guaranteed, and that forest fragments within 5 km of the river be conserved to maintain eagle populations.

  14. Stent-protected angioplasty versus carotid endarterectomy in patients with carotid artery stenosis: meta-analysis of randomized trial data

    International Nuclear Information System (INIS)

    Wiesmann, Martin; Schoepf, Veronika; Brueckmann, Hartmut; Jansen, Olav

    2008-01-01

    Stent-protected angioplasty of carotid artery stenosis may be an alternative to surgical endarterectomy. Results published so far are indecisive, with evidence both in favour of and against this procedure. After the recent publication of two large European multicentre trials (SPACE and EVA-3S) almost 3,000 patients have been included in randomized studies. For this report, we therefore conducted a systematic review of randomized studies that compared endovascular treatment with surgery for carotid stenosis. We evaluated seven trials including 2,973 patients. In our meta-analysis endovascular treatment seemed to carry a slightly higher risk for stroke or death within 30 days after the procedure as compared with surgery (8.2% vs. 6.2%; p = 0.04; OR 1.35), whereas the rates of disabling stroke or death within 30 days did not differ significantly (p = 0.47; n.s.). On the other hand, surgery carried a significantly higher risk for cranial nerve palsy (4.7% vs. 0.2%; p < 0.0001; OR 0.17) and myocardial infarction (2.3% vs. 0.9%; p = 0.03; OR 0.37). Long-term effects of both methods still need to be evaluated. Two other large multicentre trials (ICSS and CREST) are ongoing. Results of these studies will increase the database to about 7,000 randomized patients. Future meta-analyses should then allow definitive treatment recommendations. (orig.)

  15. Lead pollution of road-side vegetation

    Energy Technology Data Exchange (ETDEWEB)

    Quinche, J P; Zuber, R; Bovay, E

    1969-01-01

    In Switzerland, investigations have been made in 1967/1968 concerning the distribution of lead issued from the antiknocking additive of petrol. Observations show that the deposits in meadows in the immediate surrounding (first meter) of roads and highways with high traffic density were especially high (50-100 ppm in dry matter). The pollution is still perceptible even as far as 50 meters from the road. Moreover, during the summer (July and August), a second zone of high lead accumulation (more than 100 ppm) was detected 50 to 100 m from the road, particularly along the highways. This probably is caused by certain climatic conditions and the increase of traffic volume. With regard to fruits, only the downy species (e.g. apricots, peaches) retain some quantities of lead on their skin. Vegetables with large leaves, e.g. lettuce, spinach, and particularly vegetables with definite dissected foliage, such as fennel and parsley, may accumulate relatively high quantities of lead. According to some authors, up to 50 percent of these deposits may be eliminated by washing with water. Conversely, root vegetables (e.g. carrots, onions) do not show a perceptible lead contamination. Likewise the flesh of fruits is not markedly polluted by lead. Trials with foddering milk cows using hay harvested along a highway are not yet analyzed. The results from these trials should permit determining the proportion of lead which remains in the tissues (meat etc.) or passes over into the milk.

  16. CREST-Snow Field Experiment: analysis of snowpack properties using multi-frequency microwave remote sensing data

    Directory of Open Access Journals (Sweden)

    T. Y. Lakhankar

    2013-02-01

    Full Text Available The CREST-Snow Analysis and Field Experiment (CREST-SAFE was carried out during January–March 2011 at the research site of the National Weather Service office, Caribou, ME, USA. In this experiment dual-polarized microwave (37 and 89 GHz observations were accompanied by detailed synchronous observations of meteorology and snowpack physical properties. The objective of this long-term field experiment was to improve understanding of the effect of changing snow characteristics (grain size, density, temperature under various meteorological conditions on the microwave emission of snow and hence to improve retrievals of snow cover properties from satellite observations. In this paper we present an overview of the field experiment and comparative preliminary analysis of the continuous microwave and snowpack observations and simulations. The observations revealed a large difference between the brightness temperature of fresh and aged snowpack even when the snow depth was the same. This is indicative of a substantial impact of evolution of snowpack properties such as snow grain size, density and wetness on microwave observations. In the early spring we frequently observed a large diurnal variation in the 37 and 89 GHz brightness temperature with small depolarization corresponding to daytime snowmelt and nighttime refreeze events. SNTHERM (SNow THERmal Model and the HUT (Helsinki University of Technology snow emission model were used to simulate snowpack properties and microwave brightness temperatures, respectively. Simulated snow depth and snowpack temperature using SNTHERM were compared to in situ observations. Similarly, simulated microwave brightness temperatures using the HUT model were compared with the observed brightness temperatures under different snow conditions to identify different states of the snowpack that developed during the winter season.

  17. Neural crest contribution to lingual mesenchyme, epithelium and developing taste papillae and taste buds.

    Science.gov (United States)

    Liu, Hong-Xiang; Komatsu, Yoshihiro; Mishina, Yuji; Mistretta, Charlotte M

    2012-08-15

    The epithelium of mammalian tongue hosts most of the taste buds that transduce gustatory stimuli into neural signals. In the field of taste biology, taste bud cells have been described as arising from "local epithelium", in distinction from many other receptor organs that are derived from neurogenic ectoderm including neural crest (NC). In fact, contribution of NC to both epithelium and mesenchyme in the developing tongue is not fully understood. In the present study we used two independent, well-characterized mouse lines, Wnt1-Cre and P0-Cre that express Cre recombinase in a NC-specific manner, in combination with two Cre reporter mouse lines, R26R and ZEG, and demonstrate a contribution of NC-derived cells to both tongue mesenchyme and epithelium including taste papillae and taste buds. In tongue mesenchyme, distribution of NC-derived cells is in close association with taste papillae. In tongue epithelium, labeled cells are observed in an initial scattered distribution and progress to a clustered pattern between papillae, and within papillae and early taste buds. This provides evidence for a contribution of NC to lingual epithelium. Together with previous reports for the origin of taste bud cells from local epithelium in postnatal mouse, we propose that NC cells migrate into and reside in the epithelium of the tongue primordium at an early embryonic stage, acquire epithelial cell phenotypes, and undergo cell proliferation and differentiation that is involved in the development of taste papillae and taste buds. Our findings lead to a new concept about derivation of taste bud cells that include a NC origin. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Distinct functional and temporal requirements for zebrafish Hdac1 during neural crest-derived craniofacial and peripheral neuron development.

    Directory of Open Access Journals (Sweden)

    Myron S Ignatius

    Full Text Available The regulation of gene expression is accomplished by both genetic and epigenetic means and is required for the precise control of the development of the neural crest. In hdac1(b382 mutants, craniofacial cartilage development is defective in two distinct ways. First, fewer hoxb3a, dlx2 and dlx3-expressing posterior branchial arch precursors are specified and many of those that are consequently undergo apoptosis. Second, in contrast, normal numbers of progenitors are present in the anterior mandibular and hyoid arches, but chondrocyte precursors fail to terminally differentiate. In the peripheral nervous system, there is a disruption of enteric, DRG and sympathetic neuron differentiation in hdac1(b382 mutants compared to wildtype embryos. Specifically, enteric and DRG-precursors differentiate into neurons in the anterior gut and trunk respectively, while enteric and DRG neurons are rarely present in the posterior gut and tail. Sympathetic neuron precursors are specified in hdac1(b382 mutants and they undergo generic neuronal differentiation but fail to undergo noradrenergic differentiation. Using the HDAC inhibitor TSA, we isolated enzyme activity and temporal requirements for HDAC function that reproduce hdac1(b382 defects in craniofacial and sympathetic neuron development. Our study reveals distinct functional and temporal requirements for zebrafish hdac1 during neural crest-derived craniofacial and peripheral neuron development.

  19. Distinct functional and temporal requirements for zebrafish Hdac1 during neural crest-derived craniofacial and peripheral neuron development.

    Science.gov (United States)

    Ignatius, Myron S; Unal Eroglu, Arife; Malireddy, Smitha; Gallagher, Glen; Nambiar, Roopa M; Henion, Paul D

    2013-01-01

    The regulation of gene expression is accomplished by both genetic and epigenetic means and is required for the precise control of the development of the neural crest. In hdac1(b382) mutants, craniofacial cartilage development is defective in two distinct ways. First, fewer hoxb3a, dlx2 and dlx3-expressing posterior branchial arch precursors are specified and many of those that are consequently undergo apoptosis. Second, in contrast, normal numbers of progenitors are present in the anterior mandibular and hyoid arches, but chondrocyte precursors fail to terminally differentiate. In the peripheral nervous system, there is a disruption of enteric, DRG and sympathetic neuron differentiation in hdac1(b382) mutants compared to wildtype embryos. Specifically, enteric and DRG-precursors differentiate into neurons in the anterior gut and trunk respectively, while enteric and DRG neurons are rarely present in the posterior gut and tail. Sympathetic neuron precursors are specified in hdac1(b382) mutants and they undergo generic neuronal differentiation but fail to undergo noradrenergic differentiation. Using the HDAC inhibitor TSA, we isolated enzyme activity and temporal requirements for HDAC function that reproduce hdac1(b382) defects in craniofacial and sympathetic neuron development. Our study reveals distinct functional and temporal requirements for zebrafish hdac1 during neural crest-derived craniofacial and peripheral neuron development.

  20. Crested wheatgrass-cheatgrass seedling competition in a mixed-density design

    Science.gov (United States)

    Francis, Mark G.; Pyke, David A.

    1996-01-01

    Plant competition experiments have historically used designs that are difficult to interpret due to confounding problems. Recently, designs based on a 'response function' approach have been proposed and tested in various plant mixture settings. For this study, 3 species were used that are important in current revegetation practices in the Intermountain West. 'Nordan' (Agropyron desertorum [Fish. ex Link] Shult.) and 'Hycrest' (A. cristatum [L.] Gaertn. x desertorum) crested wheatgrass are commonly-used revegetation species on rangelands susceptible to cheatgrass (Bromus tectorum L.) invasion, although little quantitative data exist that compare their competitive abilities. We evaluated the competitive ability of Hycrest and Nordan seedlings in 2-species mixtures with cheatgrass in a greenhouse study. Linear and nonlinear models were developed for a range of densities (130- 520 seeds m-2) for each species to predict median above-ground biomass and tiller numbers and to further test the usefulness of this design for evaluating species to rehabilitate rangelands. In both experiments, increasing Hycrest and Nordan densities reduced their own biomass and tiller production while increasing Hycrest densities reduced cheatgrass biomass and tiller production. Nordan did not affect cheatgrass biomass and tiller production. However, increasing cheatgrass densities reduced Hycrest and Nordan biomass and tiller production, and its own biomass and tiller production. The competition index i.e. substitution rate, indicated that Hycrest seedlings were better competitors with cheatgrass than Nordan, although in all mixtures, cheatgrass plants were the superior competitors. Further field research using this design, where environmental inputs are less optimal and diverse, is needed to validate these results and to further evaluate the use of this approach in examining effects of intra- and interspecific competition.

  1. TEC variability near northern EIA crest and comparison with IRI model

    Science.gov (United States)

    Aggarwal, Malini

    2011-10-01

    Monthly median values of hourly total electron content (TEC) is obtained with GPS at a station near northern anomaly crest, Rajkot (geog. 22.29°N, 70.74°E; geomag. 14.21°N, 144.9°E) to study the variability of low latitude ionospheric behavior during low solar activity period (April 2005 to March 2006). The TEC exhibit characteristic features like day-to-day variability, semiannual anomaly and noon bite out. The observed TEC is compared with latest International Reference Ionosphere (IRI) - 2007 model using options of topside electron density, NeQuick, IRI01-corr and IRI-2001 by using both URSI and CCIR coefficients. A good agreement of observed and predicted TEC is found during the daytime with underestimation at other times. The predicted TEC by NeQuick and IRI01-corr is closer to the observed TEC during the daytime whereas during nighttime and morning hours, IRI-2001 shows lesser discrepancy in all seasons by both URSI and CCIR coefficients.

  2. An imbalance in cluster sizes does not lead to notable loss of power in cross-sectional, stepped-wedge cluster randomised trials with a continuous outcome.

    Science.gov (United States)

    Kristunas, Caroline A; Smith, Karen L; Gray, Laura J

    2017-03-07

    The current methodology for sample size calculations for stepped-wedge cluster randomised trials (SW-CRTs) is based on the assumption of equal cluster sizes. However, as is often the case in cluster randomised trials (CRTs), the clusters in SW-CRTs are likely to vary in size, which in other designs of CRT leads to a reduction in power. The effect of an imbalance in cluster size on the power of SW-CRTs has not previously been reported, nor what an appropriate adjustment to the sample size calculation should be to allow for any imbalance. We aimed to assess the impact of an imbalance in cluster size on the power of a cross-sectional SW-CRT and recommend a method for calculating the sample size of a SW-CRT when there is an imbalance in cluster size. The effect of varying degrees of imbalance in cluster size on the power of SW-CRTs was investigated using simulations. The sample size was calculated using both the standard method and two proposed adjusted design effects (DEs), based on those suggested for CRTs with unequal cluster sizes. The data were analysed using generalised estimating equations with an exchangeable correlation matrix and robust standard errors. An imbalance in cluster size was not found to have a notable effect on the power of SW-CRTs. The two proposed adjusted DEs resulted in trials that were generally considerably over-powered. We recommend that the standard method of sample size calculation for SW-CRTs be used, provided that the assumptions of the method hold. However, it would be beneficial to investigate, through simulation, what effect the maximum likely amount of inequality in cluster sizes would be on the power of the trial and whether any inflation of the sample size would be required.

  3. Modeling initiation of Ewing sarcoma in human neural crest cells.

    Directory of Open Access Journals (Sweden)

    Cornelia von Levetzow

    2011-04-01

    Full Text Available Ewing sarcoma family tumors (ESFT are aggressive bone and soft tissue tumors that express EWS-ETS fusion genes as driver mutations. Although the histogenesis of ESFT is controversial, mesenchymal (MSC and/or neural crest (NCSC stem cells have been implicated as cells of origin. For the current study we evaluated the consequences of EWS-FLI1 expression in human embryonic stem cell-derived NCSC (hNCSC. Ectopic expression of EWS-FLI1 in undifferentiated hNCSC and their neuro-mesenchymal stem cell (hNC-MSC progeny was readily tolerated and led to altered expression of both well established as well as novel EWS-FLI1 target genes. Importantly, whole genome expression profiling studies revealed that the molecular signature of established ESFT is more similar to hNCSC than any other normal tissue, including MSC, indicating that maintenance or reactivation of the NCSC program is a feature of ESFT pathogenesis. Consistent with this hypothesis, EWS-FLI1 induced hNCSC genes as well as the polycomb proteins BMI-1 and EZH2 in hNC-MSC. In addition, up-regulation of BMI-1 was associated with avoidance of cellular senescence and reversible silencing of p16. Together these studies confirm that, unlike terminally differentiated cells but consistent with bone marrow-derived MSC, NCSC tolerate expression of EWS-FLI1 and ectopic expression of the oncogene initiates transition to an ESFT-like state. In addition, to our knowledge this is the first demonstration that EWS-FLI1-mediated induction of BMI-1 and epigenetic silencing of p16 might be critical early initiating events in ESFT tumorigenesis.

  4. New developments in the conduct and management of multi-center trials

    DEFF Research Database (Denmark)

    Gluud, C; Sørensen, T I

    1995-01-01

    There is an urgent need for the performance of more, better designed, and better managed randomized clinical trials. After visits to 43 leading organizations and units involved in clinical trials in Europe and North America during 1993, the way of conducting randomized clinical trials was analyzed...... and data management systems). By employing such developments, randomized clinical trials can run much more efficiently. This facilitates faster and better answers to the questions addressed by randomized clinical trials, thereby also making them more ethical....

  5. Resurrection of Bronchocela burmana Blanford, 1878 for the Green Crested Lizard (Squamata, Agamidae of southern Myanmar

    Directory of Open Access Journals (Sweden)

    George R. Zug

    2017-02-01

    Full Text Available Recent fieldwork in southern Tanintharyi revealed the presence of a small Green Crested Lizard in the wet evergreen forest. We generated mtDNA sequence data (ND2 that demonstrates that this population’s nearest relative is Bronchocela rayaensis Grismer et al., 2015 of Pulau Langkawi, northwestern Peninsular Malaysia and Phuket Island. Morphologically the Burmese Bronchocela shares many features with B. rayaensis, which potentially would make this recently described Thai-Malay species a synonym of Bronchocela burmana Blanford, 1878; however, we interpret the genetic and morphological differences to reflect evolutionary divergence and recommend the recognition of both species.

  6. Gene array analysis of neural crest cells identifies transcription factors necessary for direct conversion of embryonic fibroblasts into neural crest cells

    Directory of Open Access Journals (Sweden)

    Tsutomu Motohashi

    2016-03-01

    Full Text Available Neural crest cells (NC cells are multipotent cells that emerge from the edge of the neural folds and migrate throughout the developing embryo. Although the gene regulatory network for generation of NC cells has been elucidated in detail, it has not been revealed which of the factors in the network are pivotal to directing NC identity. In this study we analyzed the gene expression profile of a pure NC subpopulation isolated from Sox10-IRES-Venus mice and investigated whether these genes played a key role in the direct conversion of Sox10-IRES-Venus mouse embryonic fibroblasts (MEFs into NC cells. The comparative molecular profiles of NC cells and neural tube cells in 9.5-day embryos revealed genes including transcription factors selectively expressed in developing trunk NC cells. Among 25 NC cell-specific transcription factor genes tested, SOX10 and SOX9 were capable of converting MEFs into SOX10-positive (SOX10+ cells. The SOX10+ cells were then shown to differentiate into neurons, glial cells, smooth muscle cells, adipocytes and osteoblasts. These SOX10+ cells also showed limited self-renewal ability, suggesting that SOX10 and SOX9 directly converted MEFs into NC cells. Conversely, the remaining transcription factors, including well-known NC cell specifiers, were unable to convert MEFs into SOX10+ NC cells. These results suggest that SOX10 and SOX9 are the key factors necessary for the direct conversion of MEFs into NC cells.

  7. Application of INAA in the assessment of selected elements in cancellous bone of human iliac crest

    International Nuclear Information System (INIS)

    Zaichick, V.

    2007-01-01

    The effect of age and sex was investigated on the concentration of chemical elements in intact cancellous bone of iliac crest of 74 relatively healthy, 15-55 years old women (n = 29) and men (n = 45). Concentrations of Ca, Cl, K, Mg, Mn, Na, P, and Sr in bone samples were determined by instrumental neutron activation analysis using short-lived radionuclides. Mean values (M±S.E.M.) of the mass fraction of the investigated elements (on dry weight basis) for female and male all together were: 127±4 g/kg, 1620±80 mg/kg, 1310±70 mg/kg, 1550±50 mg/kg, <0.32±0.02 mg/kg, 4240±110 mg/kg, 61.8±1.8 g/kg, and 235±18 mg/kg, respectively. The statistically significant (≤0.05) decrease of Ca, Mg, and P concentrations in the iliac cancellous bone with age was found only for women. Sex-related comparison has shown that the mean values of Mg mass fractions in male bone samples were less than in female ones. (author)

  8. Phase 3 Oncology Clinical Trials in South Africa: Experimentation or Therapeutic Misconception?

    Science.gov (United States)

    Malan, Tina; Moodley, Keymanthri

    2016-02-01

    Although clinical research in oncology is vital to improve current understanding of cancer and to validate new treatment options, voluntary informed consent is a critical component. Oncology research participants are a particularly vulnerable population; hence, therapeutic misconception often leads to ethical and legal challenges. We conducted a qualitative study administering semi-structured questionnaires on 29 adult, Phase 3, oncology clinical trial participants at three different private oncology clinical trial sites in South Africa. A descriptive content analysis was performed to identify perceptions of these participants regarding Phase 3 clinical trials. We found that most participants provided consent to be included in the trial for self-benefit. More than half of the participants had a poor understanding of Phase 3 clinical trials, and almost half the participants believed the clinical trial did not pose any significant risk to them. The word "hope" was used frequently by participants, displaying clear optimism with regard to the clinical trial and its outcome. This indicated that therapeutic misconception does occur in the South African oncology research setting and has the potential to lead to underestimation of the risks of a Phase 3 clinical trial. Emphasizing the experimental nature of a clinical trial during the consent process is critical to address therapeutic misconception in oncology research. © The Author(s) 2016.

  9. Big Data in Designing Clinical Trials: Opportunities and Challenges.

    Science.gov (United States)

    Mayo, Charles S; Matuszak, Martha M; Schipper, Matthew J; Jolly, Shruti; Hayman, James A; Ten Haken, Randall K

    2017-01-01

    Emergence of big data analytics resource systems (BDARSs) as a part of routine practice in Radiation Oncology is on the horizon. Gradually, individual researchers, vendors, and professional societies are leading initiatives to create and demonstrate use of automated systems. What are the implications for design of clinical trials, as these systems emerge? Gold standard, randomized controlled trials (RCTs) have high internal validity for the patients and settings fitting constraints of the trial, but also have limitations including: reproducibility, generalizability to routine practice, infrequent external validation, selection bias, characterization of confounding factors, ethics, and use for rare events. BDARS present opportunities to augment and extend RCTs. Preliminary modeling using single- and muti-institutional BDARS may lead to better design and less cost. Standardizations in data elements, clinical processes, and nomenclatures used to decrease variability and increase veracity needed for automation and multi-institutional data pooling in BDARS also support ability to add clinical validation phases to clinical trial design and increase participation. However, volume and variety in BDARS present other technical, policy, and conceptual challenges including applicable statistical concepts, cloud-based technologies. In this summary, we will examine both the opportunities and the challenges for use of big data in design of clinical trials.

  10. Big Data in Designing Clinical Trials: Opportunities and Challenges

    Directory of Open Access Journals (Sweden)

    Charles S. Mayo

    2017-08-01

    Full Text Available Emergence of big data analytics resource systems (BDARSs as a part of routine practice in Radiation Oncology is on the horizon. Gradually, individual researchers, vendors, and professional societies are leading initiatives to create and demonstrate use of automated systems. What are the implications for design of clinical trials, as these systems emerge? Gold standard, randomized controlled trials (RCTs have high internal validity for the patients and settings fitting constraints of the trial, but also have limitations including: reproducibility, generalizability to routine practice, infrequent external validation, selection bias, characterization of confounding factors, ethics, and use for rare events. BDARS present opportunities to augment and extend RCTs. Preliminary modeling using single- and muti-institutional BDARS may lead to better design and less cost. Standardizations in data elements, clinical processes, and nomenclatures used to decrease variability and increase veracity needed for automation and multi-institutional data pooling in BDARS also support ability to add clinical validation phases to clinical trial design and increase participation. However, volume and variety in BDARS present other technical, policy, and conceptual challenges including applicable statistical concepts, cloud-based technologies. In this summary, we will examine both the opportunities and the challenges for use of big data in design of clinical trials.

  11. Recent clinical trials in valvular heart disease.

    Science.gov (United States)

    Kiss, Daniel; Anwaruddin, Saif

    2017-07-01

    With widespread adoption of transcatheter aortic valve replacement, there has been a change in the approach to management of valvular heart disease. New interest has taken hold in transcatheter therapies for valvular heart disease, as well as research into pathophysiology and progression of disease. Additionally, several key trials have further refined our understanding of surgical management of valvular heart disease. This review will elucidate recent clinical trial data leading to changes in practice. There have been several landmark trials expanding the indications for transcatheter aortic valve replacement. Additionally, although still early, trials are beginning to demonstrate the feasibility and safety of transcatheter mitral valves. Options for transcatheter management of right-sided valvular disease continue to evolve, and these are areas of active investigation. The emergence of novel therapies for valvular heart disease has expanded the management options available, allowing physicians to better individualize treatment of patients with valvular heart disease. This review will focus on the recent (within 2 years) trials in this field of interest.

  12. Molecular detection of bacteria in the families Rickettsiaceae and Anaplasmataceae in northern crested caracaras (Caracara cheriway)

    Science.gov (United States)

    Erwin, John A.; Fitak, Robert R.; Dwyer, James F.; Morrison, Joan L.; Culver, Melanie

    2016-01-01

    Bacterial pathogens of the families Anaplasmataceae and Rickettsiaceae are often spread to humans or other animals from bites from infected arthropod hosts. Recently, an increasing number of studies have implicated migratory birds in the circulation of these pathogens through the spread of arthropod vectors. However, few studies have examined the potential for resident bird populations to serve as reservoirs for these zoonoses. In this study, we used nested PCRs of the GroESL and 17 kDa genes to screen for Anaplasmataceae and Rickettsiaceae, respectively, in a resident population of the northern crested caracara (Caracara cheriway) from Florida (n = 55). Additionally, a small number (n = 6) of captive individuals from Texas were included. We identified one individual (1.64%) positive for Rickettsia felis and one (1.64%) positive for Ehrlichia chaffeensis; both these individuals were from Florida. Presence of these pathogens demonstrates that these birds are potential hosts; however, the low prevalence of infections suggests that these populations likely do not function as an ecological reservoir.

  13. Bmps and id2a act upstream of Twist1 to restrict ectomesenchyme potential of the cranial neural crest.

    Directory of Open Access Journals (Sweden)

    Ankita Das

    Full Text Available Cranial neural crest cells (CNCCs have the remarkable capacity to generate both the non-ectomesenchyme derivatives of the peripheral nervous system and the ectomesenchyme precursors of the vertebrate head skeleton, yet how these divergent lineages are specified is not well understood. Whereas studies in mouse have indicated that the Twist1 transcription factor is important for ectomesenchyme development, its role and regulation during CNCC lineage decisions have remained unclear. Here we show that two Twist1 genes play an essential role in promoting ectomesenchyme at the expense of non-ectomesenchyme gene expression in zebrafish. Twist1 does so by promoting Fgf signaling, as well as potentially directly activating fli1a expression through a conserved ectomesenchyme-specific enhancer. We also show that Id2a restricts Twist1 activity to the ectomesenchyme lineage, with Bmp activity preferentially inducing id2a expression in non-ectomesenchyme precursors. We therefore propose that the ventral migration of CNCCs away from a source of Bmps in the dorsal ectoderm promotes ectomesenchyme development by relieving Id2a-dependent repression of Twist1 function. Together our model shows how the integration of Bmp inhibition at its origin and Fgf activation along its migratory route would confer temporal and spatial specificity to the generation of ectomesenchyme from the neural crest.

  14. An experimental evaluation of joint electrical resistance on power lead thermal performance

    International Nuclear Information System (INIS)

    Datskov, V.I.; Demko, J.A.; Augustynowicz, S.D.; Hutton, R.D.

    1994-01-01

    The amount of electrical resistance in braze joints is not known for certain. In addition the annealing processes that occurs during a braze or solder operation can change the residual resistivity ratio (RRR) of the copper. The change in the electrical resistivity of samples of copper because of exposure to conditions that a high current lead would see during a brazing operation were experimentally investigated. A sample was taken from a manufacturing and brazing trial of the high current power leads for the Superconducting Super Collider (SSC), and from oxygen free high conductivity copper (OFHC) 101 rod similar to that used in the trial. The samples were heated under conditions that a current lead would undergo during the brazing process. Measurements were made of the electrical resistance of the copper specimens and across a braze joint in the manufacturing trial sample for temperatures ranging from liquid helium to room temperature. A prototype of the SSC high current lead is shown. This lead was fabricated from 5 sections that were brazed together. Some results for the measured residual resistivity ratio (RRR) along this lead are given

  15. Impaired Cellular Immunity in the Murine Neural Crest Conditional Deletion of Endothelin Receptor-B Model of Hirschsprung's Disease.

    Directory of Open Access Journals (Sweden)

    Ankush Gosain

    Full Text Available Hirschsprung's disease (HSCR is characterized by aganglionosis from failure of neural crest cell (NCC migration to the distal hindgut. Up to 40% of HSCR patients suffer Hirschsprung's-associated enterocolitis (HAEC, with an incidence that is unchanged from the pre-operative to the post-operative state. Recent reports indicate that signaling pathways involved in NCC migration may also be involved in the development of secondary lymphoid organs. We hypothesize that gastrointestinal (GI mucosal immune defects occur in HSCR that may contribute to enterocolitis. EdnrB was deleted from the neural crest (EdnrBNCC-/- resulting in mutants with defective NCC migration, distal colonic aganglionosis and the development of enterocolitis. The mucosal immune apparatus of these mice was interrogated at post-natal day (P 21-24, prior to histological signs of enterocolitis. We found that EdnrBNCC-/- display lymphopenia of their Peyer's Patches, the major inductive site of GI mucosal immunity. EdnrBNCC-/- Peyer's Patches demonstrate decreased B-lymphocytes, specifically IgM+IgDhi (Mature B-lymphocytes, which are normally activated and produce IgA following antigen presentation. EdnrBNCC-/- animals demonstrate decreased small intestinal secretory IgA, but unchanged nasal and bronchial airway secretory IgA, indicating a gut-specific defect in IgA production or secretion. In the spleen, which is the primary source of IgA-producing Mature B-lymphocytes, EdnrBNCC-/- animals display decreased B-lymphocytes, but an increase in Mature B-lymphocytes. EdnrBNCC-/- spleens are also small and show altered architecture, with decreased red pulp and a paucity of B-lymphocytes in the germinal centers and marginal zone. Taken together, these findings suggest impaired GI mucosal immunity in EdnrBNCC-/- animals, with the spleen as a potential site of the defect. These findings build upon the growing body of literature that suggests that intestinal defects in HSCR are not restricted

  16. Channelized lava flows at the East Pacific Rise crest 9°-10°N: the importance of off-axis lava transport in developing the architecture of young oceanic crust

    Science.gov (United States)

    Soule, S.A.; Fornari, D.J.; Perfit, M.R.; Tivey, M.A.; Ridley, W.I.; Schouten, Hans

    2005-01-01

     Submarine lava flows are the building blocks of young oceanic crust. Lava erupted at the ridge axis is transported across the ridge crest in a manner dictated by the rheology of the lava, the characteristics of the eruption, and the topography it encounters. The resulting lava flows can vary dramatically in form and consequently in their impact on the physical characteristics of the seafloor and the architecture of the upper 50–500 m of the oceanic crust. We have mapped and measured numerous submarine channelized lava flows at the East Pacific Rise (EPR) crest 9°–10°N that reflect the high-effusion-rate and high-flow-velocity end-member of lava eruption and transport at mid-ocean ridges. Channel systems composed of identifiable segments 50–1000 m in length extend up to 3 km from the axial summit trough (AST) and have widths of 10–50 m and depths of 2–3 m. Samples collected within the channels are N-MORB with Mg# indicating eruption from the AST. We produce detailed maps of lava surface morphology across the channel surface from mosaics of digital images that show lineated or flat sheets at the channel center bounded by brecciated lava at the channel margins. Modeled velocity profiles across the channel surface allow us to determine flux through the channels from 0.4 to 4.7 × 103m3/s, and modeled shear rates help explain the surface morphology variation. We suggest that channelized lava flows are a primary mechanism by which lava accumulates in the off-axis region (1–3 km) and produces the layer 2A thickening that is observed at fast and superfast spreading ridges. In addition, the rapid, high-volume-flux eruptions necessary to produce channelized flows may act as an indicator of the local magma budget along the EPR. We find that high concentrations of channelized lava flows correlate with local, across-axis ridge morphology indicative of an elevated magma budget. Additionally, in locations where channelized flows are located dominantly to the east

  17. Destruction of intertidal bar morphology during a summer storm surge event: Example of positive morphodynamic feedback

    DEFF Research Database (Denmark)

    Masselink, Gerd; Aagaard, Troels; Kroon, Aart

    2011-01-01

    . The measurements demonstrated an example of positive morphodynamic feedback. Once the bar crest elevation started to decrease because of wave overtopping and sediment transport into the runnel on the rising tide, the bar crest lowered and overwash frequency increased, leading to enhanced crest erosion, even under...

  18. A Comparative Analysis of Recombinant Human Bone Morphogenetic Protein-2 with a Demineralized Bone Matrix versus Iliac Crest Bone Graft for Secondary Alveolar Bone Grafts in Patients with Cleft Lip and Palate: Review of 501 Cases.

    Science.gov (United States)

    Hammoudeh, Jeffrey A; Fahradyan, Artur; Gould, Daniel J; Liang, Fan; Imahiyerobo, Thomas; Urbinelli, Leo; Nguyen, JoAnna T; Magee, William; Yen, Stephen; Urata, Mark M

    2017-08-01

    Alveolar cleft reconstruction using iliac crest bone graft is considered standard of care for children with complete cleft lip and palate at the time of mixed dentition. Harvesting bone may result in donor-site morbidity and additional operating time and length of hospitalization. Recombinant human bone morphogenetic protein (rhBMP)-2 with a demineralized bone matrix is an alternative bone source for alveolar cleft reconstruction. The authors investigated the outcomes of rhBMP-2/demineralized bone matrix versus iliac crest bone graft for alveolar cleft reconstruction by reviewing postoperative surgical complications and cleft closure. A retrospective chart review was conducted for 258 rhBMP-2/demineralized bone matrix procedures (mean follow-up, 2.9 years) and 243 iliac crest bone graft procedures (mean follow-up, 4.1 years) on 414 patients over a 12-year period. The authors compared complications, canine eruption, and alveolar cleft closure between the two groups. In the rhBMP-2/demineralized bone matrix group, one patient required prolonged intubation because of intraoperative airway swelling not thought to be caused by rhBMP-2, 36 reported facial swelling and one required outpatient steroids as treatment, and 12 had dehiscence; however, half of these complications resolved without intervention. Twenty-three of the 228 rhBMP-2/demineralized bone matrix patients and 28 of the 242 iliac crest bone graft patients required repeated surgery for alveolar cleft repair. Findings for canine tooth eruption into the cleft site through the graft were similar between the groups. The rhBMP-2/demineralized bone matrix appears to be an acceptable alternative for alveolar cleft repair. The authors found no increase in serious adverse events with the use of this material. Local complications, such as swelling and minor wound dehiscence, predominantly improved without intervention. Therapeutic, III.

  19. Stephen L. Gans Distinguished Overseas Lecture. The neural crest in pediatric surgery.

    Science.gov (United States)

    Tovar, Juan A

    2007-06-01

    This review highlights the relevance of the neural crest (NC) as a developmental control mechanism involved in several pediatric surgical conditions and the investigative interest of following some of its known signaling pathways. The participation of the NC in facial clefts, ear defects, branchial fistulae and cysts, heart outflow tract and aortic arch anomalies, pigmentary disorders, abnormal enteric innervation, neural tumors, hemangiomas, and vascular anomalies is briefly reviewed. Then, the literature on clinical and experimental esophageal atresia-tracheoesophageal fistula (EA-TEF) and congenital diaphragmatic hernia (CDH) is reviewed for the presence of associated NC defects. Finally, some of the molecular signaling pathways involved in both conditions (sonic hedgehog, Hox genes, and retinoids) are summarized. The association of facial, cardiovascular, thymic, parathyroid, and C-cell defects together with anomalies of extrinsic and intrinsic esophageal innervation in babies and/or animals with both EA-TEF and CDH strongly supports the hypothesis that NC is involved in the pathogenesis of these malformative clusters. On the other hand, both EA-TEF and CDH are observed in mice mutant for genes involved in the previously mentioned signaling pathways. The investigation of NC-related molecular pathogenic pathways involved in malformative associations like EA-TEF and CDH that are induced by chromosomal anomalies, chemical teratogens, and engineered mutations is a promising way of clarifying why and how some pediatric surgical conditions occur. Pediatric surgeons should be actively involved in these investigations.

  20. In vitro cementoblast-like differentiation of postmigratory neural crest-derived p75+ stem cells with dental follicle cell conditioned medium

    International Nuclear Information System (INIS)

    Wen, Xiujie; Liu, Luchuan; Deng, Manjing; Liu, Rui; Zhang, Li; Nie, Xin

    2015-01-01

    Cranial neural crest-derived cells (CNCCs) play important role in epithelial–mesenchymal interactions during tooth morphogenesis. However, the heterogeneity of CNCCs and their tendency to spontaneously differentiate along smooth muscle or osteoblast lineages in vitro limit further understanding of their biological properties. We studied the differentiation properties of isolated rat embryonic postmigratory CNCCs, expressing p75 neurotrophin receptor (p75NTR). These p75NTR positive (p75 + ) CNCCs, isolated using fluorescence activated cell sorter, exhibited fibroblast-like morphology and characteristics of mesenchymal stem cells. Incubation of p75 + CNCCs in dental follicle cell conditioned medium (DFCCM) combined with dentin non-collagenous proteins (dNCPs), altered their morphological features to cementoblast-like appearance. These cells also showed low proliferative activity, high ALP activity and significantly increased calcified nodule formation. Markers related to mineralization or specific to cementoblast lineage were highly expressed in dNCPs/DFCCM-treated p75 + cells, suggesting their differentiation along cementoblast-like lineage. p75 + stem cells selected from postmigratory CNCCs represent a pure stem cell population and could be used as a stem cell model for in vitro studies due to their intrinsic ability to differentiate to neuronal cells and transform from neuroectoderm to ectomesenchyme. They can provide a potential stem cell resource for tooth engineering studies and help to further investigate mechanisms of epithelial–mesenchymal interactions in tooth morphogenesis. - Highlights: • Cranial neural crest-derived cells (CNCCs) take part in tooth morphogenesis. • positive (p75 + ) CNCCs are fibroblast-like and resemble mesenchymal stem cells. • p75 + CNCCs in dental follicle cell medium (DFCCM/dNCP) appear like cementoblasts. • DFCCM/dNCP-treated p75 + cells express cementoblast specific mineralization markers. • p75 + cells are pure stem

  1. Influence of implant neck design on facial bone crest dimensions in the esthetic zone analyzed by cone beam CT: a comparative study with a 5-to-9-year follow-up.

    Science.gov (United States)

    Chappuis, Vivianne; Bornstein, Michael M; Buser, Daniel; Belser, Urs

    2016-09-01

    To examine the influence of two different neck designs on facial bone crest dimensions in esthetic single implant sites after a 5-to-9-year follow-up analyzed by cone beam computed tomography (CBCT). Sixty-one patients with an implant-borne single crown following early implant placement in the esthetic zone were enrolled. The test group consisted of a bone level (BL) neck design exhibiting a hydrophilic micro-rough surface combined with a platform-switching interface (PS) (n = 20). The control group comprised a soft tissue level (STL) neck design exhibiting a hydrophobic machined surface with a matching butt-joint interface (n = 41). Standardized clinical, radiologic, and esthetic parameters were applied. The facial bone crest dimensions were assessed by CBCT. Soft tissue parameters and pink esthetic scores yielded no significant differences between the two designs. Major differences were only observed at the implant shoulder level. The height of the facial bone crest for the BL design was located 0.2 mm above the implant shoulder level, whereas for the STL design, its location was 1.6 mm below. The width of the peri-implant saucer-like bone defect was reduced by 40% for the BL implant design. No differences were observed 2 mm below the shoulder level. The results of this comparative study suggest better crestal bone stability on the facial aspect of single implant sites in the esthetic zone for a BL design with a platform-switching concept when compared with STL implants with a butt-joint interface. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Development and psychometric testing of a Clinical Reasoning Evaluation Simulation Tool (CREST) for assessing nursing students' abilities to recognize and respond to clinical deterioration.

    Science.gov (United States)

    Liaw, Sok Ying; Rashasegaran, Ahtherai; Wong, Lai Fun; Deneen, Christopher Charles; Cooper, Simon; Levett-Jones, Tracy; Goh, Hongli Sam; Ignacio, Jeanette

    2018-03-01

    The development of clinical reasoning skills in recognising and responding to clinical deterioration is essential in pre-registration nursing education. Simulation has been increasingly used by educators to develop this skill. To develop and evaluate the psychometric properties of a Clinical Reasoning Evaluation Simulation Tool (CREST) for measuring clinical reasoning skills in recognising and responding to clinical deterioration in a simulated environment. A scale development with psychometric testing and mixed methods study. Nursing students and academic staff were recruited at a university. A three-phase prospective study was conducted. Phase 1 involved the development and content validation of the CREST; Phase 2 included the psychometric testing of the tool with 15 second-year and 15 third-year nursing students who undertook the simulation-based assessment; Phase 3 involved the usability testing of the tool with nine academic staff through a survey questionnaire and focus group discussion. A 10-item CREST was developed based on a model of clinical reasoning. A content validity of 0.93 was obtained from the validation of 15 international experts. The construct validity was supported as the third-year students demonstrated significantly higher (preasoning scores than the second-year students. The concurrent validity was also supported with significant positive correlations between global rating scores and almost all subscale scores, and the total scores. The predictive validity was supported with an existing tool. The internal consistency was high with a Cronbach's alpha of 0.92. A high inter-rater reliability was demonstrated with an intraclass correlation coefficient of 0.88. The usability of the tool was rated positively by the nurse educators but the need to ease the scoring process was highlighted. A valid and reliable tool was developed to measure the effectiveness of simulation in developing clinical reasoning skills for recognising and responding to

  3. The monocortical window (MCW): a modified split-crest technique adopting ligature osteosynthesis.

    Science.gov (United States)

    Contessi, Marcello

    2013-01-01

    Split-crest procedures performed with ultrasonic devices have proven to be a viable and effective surgical treatment when the alveolar ridge shows forms of resorption in thickness while its height remains virtually unchanged. However, in the case of stiff, type 1, corticalized mandibular bone, it may be very difficult or even impossible to have any elasticity and lateral augmentation in between the split bone walls. Furthermore, a complete detachment of the outer lamellae may also occur during expansion maneuvers or during implant insertion. This study describes the use of a steel-wire ligature osteosynthesis technique to give primary stability both to the expanded cortical window and to the implants themselves when they have none at all. This osteosynthesis is simple, quick, safe, and bone-saving in force delivery. It is also extremely cheap as well as being effective in obtaining ridge expansion, bone regeneration, and implant positioning in an all-in-one procedure. This article describes the foundations in the literature as well as new elements in the technique. Three short case studies are used by way of example.

  4. Human harvest, climate change and their synergistic effects drove the Chinese Crested Tern to the brink of extinction

    Directory of Open Access Journals (Sweden)

    Shuihua Chen

    2015-07-01

    Full Text Available Synergistic effect refers to simultaneous actions of separate factors which have a greater total effect than the sum of the individual factor effects. However, there has been a limited knowledge on how synergistic effects occur and individual roles of different drivers are not often considered. Therefore, it becomes quite challenging to manage multiple threatening processes simultaneously in order to mitigate biodiversity loss. In this regard, our hypothesis is, if the traits actually play different roles in the synergistic interaction, conservation efforts could be made more effectively. To understand the synergistic effect and test our hypothesis, we examined the processes associated with the endangerment of critically endangered Chinese Crested Tern (Thalasseus bernsteini, whose total population number was estimated no more than 50. Through monitoring of breeding colonies and investigations into causative factors, combined with other data on human activities, we found that widespread human harvest of seabird eggs and increasing frequency of typhoons are the major factors that threatened the Chinese Crested Tern. Furthermore, 28 percent of breeding failures were due to the synergistic effects in which egg harvest-induced renestings suffered the higher frequent typhoons. In such combined interactions, the egg harvest has clearly served as a proximal factor for the population decline, and the superimposition of enhanced typhoon activity further accelerated the species toward imminent extinction. Our findings suggest that species endangerment, on one hand, should be treated as a synergistic process, while conservation efforts, on the other hand, should focus principally on combatting the threat that triggers synergistic effects.

  5. Antiviral lead compounds from marine sponges

    KAUST Repository

    Sagar, Sunil

    2010-10-11

    Marine sponges are currently one of the richest sources of pharmacologically active compounds found in the marine environment. These bioactive molecules are often secondary metabolites, whose main function is to enable and/or modulate cellular communication and defense. They are usually produced by functional enzyme clusters in sponges and/or their associated symbiotic microorganisms. Natural product lead compounds from sponges have often been found to be promising pharmaceutical agents. Several of them have successfully been approved as antiviral agents for clinical use or have been advanced to the late stages of clinical trials. Most of these drugs are used for the treatment of human immunodeficiency virus (HIV) and herpes simplex virus (HSV). The most important antiviral lead of marine origin reported thus far is nucleoside Ara-A (vidarabine) isolated from sponge Tethya crypta. It inhibits viral DNA polymerase and DNA synthesis of herpes, vaccinica and varicella zoster viruses. However due to the discovery of new types of viruses and emergence of drug resistant strains, it is necessary to develop new antiviral lead compounds continuously. Several sponge derived antiviral lead compounds which are hopedto be developed as future drugs are discussed in this review. Supply problems are usually the major bottleneck to the development of these compounds as drugs during clinical trials. However advances in the field of metagenomics and high throughput microbial cultivation has raised the possibility that these techniques could lead to the cost-effective large scale production of such compounds. Perspectives on biotechnological methods with respect to marine drug development are also discussed. 2010 by the authors; licensee MDPI.

  6. How does iliac crest bone marrow biopsy compare with imaging in the detection of bone metastases in small cell lung cancer?

    International Nuclear Information System (INIS)

    Perrin-Resche, I.; Bizais, Y.; Buhe, T.; Fiche, M.

    1993-01-01

    Iliac crest bone marrow biopsy (BMB) has often been used as the gold standard for the detection of bone marrow metastases in small cell lung cancer (SCLC). However, it is likely to lead to numerous false-negative results. For this reason, we compared the results of bone scintigraphy (BS), magnetic resonance imaging (MRI), and BMB in 48 sequential patients affected with pathologically confirmed SCLC (47 were evaluable; mean age, 58.4 years). The three procedures were carried out within 1 week, no treatment being performed during this period. Whole-body scans and spot views were obtained in the anterior and posterior projections. For MRI, only the thoracolumbar spine, the sternum and the pelvis were scanned, using spin-echo T1-weighted sequences, resulting in an acquisition time of less than 45 min. Only five BMBs were rated as positive. In these cases, both BS and MRI were also positive. The other 42 biopsies were negative. Among them, in ten cases both BS and MRI were positive. In 21 cases, both BS and MRI were negative. In five cases MRI was positive while BS was negative. Finally, in six cases MRI was negative whilst BS was positive. In most cases in which either BS or MRI was positive, follow-up scans confirmed the initial findings. This study suggests that BMB is more invasive and less sensitive than BS or MRI in detecting bone metastases. MRI seems to be more sensitive than BS in detecting small spinal or pelvic metastases. Whole-body bone scintigraphy is more sensitive in detecting skull, costal or peripheral metastases. BS and MRI should be used in combination and may replace BMB in the detection of bone metastases in SCLC. (orig.)

  7. Leader Cells Define Directionality of Trunk, but Not Cranial, Neural Crest Cell Migration

    Directory of Open Access Journals (Sweden)

    Jo Richardson

    2016-05-01

    Full Text Available Collective cell migration is fundamental for life and a hallmark of cancer. Neural crest (NC cells migrate collectively, but the mechanisms governing this process remain controversial. Previous analyses in Xenopus indicate that cranial NC (CNC cells are a homogeneous population relying on cell-cell interactions for directional migration, while chick embryo analyses suggest a heterogeneous population with leader cells instructing directionality. Our data in chick and zebrafish embryos show that CNC cells do not require leader cells for migration and all cells present similar migratory capacities. In contrast, laser ablation of trunk NC (TNC cells shows that leader cells direct movement and cell-cell contacts are required for migration. Moreover, leader and follower identities are acquired before the initiation of migration and remain fixed thereafter. Thus, two distinct mechanisms establish the directionality of CNC cells and TNC cells. This implies the existence of multiple molecular mechanisms for collective cell migration.

  8. The influence of geographical location, host maturity and sex on intestinal helminth communities of the double-crested cormorant Phalacrocorax auritus from the eastern United States.

    Science.gov (United States)

    Sheehan, K L; Hanson-Dorr, K C; Dorr, B S; Yarrow, G K; Johnson, R J

    2017-09-01

    Here the intestinal helminth infracommunities of 218 double-crested cormorants (Phalacrocorax auritus) from 11 locations in Alabama, Minnesota, Mississippi and Vermont are documented. Trematode infections were present in 98% of hosts; 65% of cormorants carried cestode infections, 4% were infected with acanthocephalans and 66% had nematode intestinal parasites. Parasite infracommunities of hosts collected on wintering grounds had higher richness and diversity than did birds collected on breeding grounds. Differences in parasite richness and diversity between male and female P. auritus were also detected, but not between immature and mature bird hosts. Parasite intensity did not differ by sex, maturity, or between breeding and wintering season. The most common parasite was Drepanocephalus auritus (spathans), which is recognized as a disease agent that negatively impacts the catfish aquaculture industry in the US. Echinochasmus sp. in double-crested cormorants is documented for the first time in the United States. We suggest that the differences observed among parasite infracommunities could be associated with the foraging distances travelled by P. auritus during breeding and wintering seasons, which is limited by allocation of parental care during the breeding season.

  9. A comparison of single-lead atrial pacing with dual-chamber pacing in sick sinus syndrome

    DEFF Research Database (Denmark)

    Nielsen, Jens Cosedis; Thomsen, Poul Erik B; Højberg, Søren

    2011-01-01

    In patients with sick sinus syndrome, bradycardia can be treated with a single-lead pacemaker or a dual-chamber pacemaker. Previous trials have revealed that pacing modes preserving atrio-ventricular synchrony are superior to single-lead ventricular pacing, but it remains unclear if there is any ...

  10. Determination of Sight Distance on a Combined Crest and Circular Curve in a Three Dimensional Space

    Directory of Open Access Journals (Sweden)

    Chiu Liu, PhD, PE, PTOE

    2012-06-01

    Full Text Available The sight distance (SD on a two-dimensional (2-d curve, namely, a vertical curve or a horizontal curve, has been well understood and documented for roadway geometric design in literature. In reality, three-dimensional (3-d curves can be found along ramps, connectors, and often mountain roads. The sight distance on these 3-d curves, which may vary with driver's location, has not been tackled in literature on an exact analytic setting. By integrating human-vehicle-roadway interaction, the formulas for computing the SD on a 3-d curve are derived the first time on an analytic framework. The crest curve SD that has been used in various literatures, can be deduced from these derived formulas as special limiting cases. Practitioners can easily apply theses user-friendly formulas or equations on a Microsoft Excel spread sheet to calculate 3-d SD on a roadway with sufficient roadside clearance. In addition, this framework can be extended easily to cope with various scenarios in which obstacles partially blocking driver's sight are present in a roadway environment.

  11. Anatomy and histochemistry of spread-wing posture in birds. I. Wing drying posture in the double-crested cormorant, Phalacrocorax auritus.

    Science.gov (United States)

    Meyers, Ron A

    1997-07-01

    Spread-wing postures of birds often have been studied with respect to the function of behavior, but ignored with regard to the mechanism by which the birds accomplish posture. The double-crested cormorant, Phalacrocorax auritus, was used as a model for this study of spread-wing posture. Those muscles capable of positioning and maintaining the wing in extension and protraction were assayed histochemically for the presence of slow (postural) muscle fibers. Within the forelimb of Phalacrocorax, Mm. coracobrachialis cranialis, pectoralis thoracicus (cranial portion), deltoideus minor, triceps scapularis, and extensor metacarpi radialis pars dorsalis and ventralis were found to contain populations of slow-twitch or slow-tonic muscle fibers. These slow fibers in the above muscles are considered to function during spread-wing posture in this species. J Morphol 233:67-76, 1997. © 1997 Wiley-Liss, Inc. Copyright © 1997 Wiley-Liss, Inc.

  12. In vitro cementoblast-like differentiation of postmigratory neural crest-derived p75{sup +} stem cells with dental follicle cell conditioned medium

    Energy Technology Data Exchange (ETDEWEB)

    Wen, Xiujie; Liu, Luchuan; Deng, Manjing; Liu, Rui; Zhang, Li; Nie, Xin, E-mail: dr.xinnie@gmail.com

    2015-09-10

    Cranial neural crest-derived cells (CNCCs) play important role in epithelial–mesenchymal interactions during tooth morphogenesis. However, the heterogeneity of CNCCs and their tendency to spontaneously differentiate along smooth muscle or osteoblast lineages in vitro limit further understanding of their biological properties. We studied the differentiation properties of isolated rat embryonic postmigratory CNCCs, expressing p75 neurotrophin receptor (p75NTR). These p75NTR positive (p75{sup +}) CNCCs, isolated using fluorescence activated cell sorter, exhibited fibroblast-like morphology and characteristics of mesenchymal stem cells. Incubation of p75{sup +} CNCCs in dental follicle cell conditioned medium (DFCCM) combined with dentin non-collagenous proteins (dNCPs), altered their morphological features to cementoblast-like appearance. These cells also showed low proliferative activity, high ALP activity and significantly increased calcified nodule formation. Markers related to mineralization or specific to cementoblast lineage were highly expressed in dNCPs/DFCCM-treated p75{sup +} cells, suggesting their differentiation along cementoblast-like lineage. p75{sup +} stem cells selected from postmigratory CNCCs represent a pure stem cell population and could be used as a stem cell model for in vitro studies due to their intrinsic ability to differentiate to neuronal cells and transform from neuroectoderm to ectomesenchyme. They can provide a potential stem cell resource for tooth engineering studies and help to further investigate mechanisms of epithelial–mesenchymal interactions in tooth morphogenesis. - Highlights: • Cranial neural crest-derived cells (CNCCs) take part in tooth morphogenesis. • positive (p75{sup +}) CNCCs are fibroblast-like and resemble mesenchymal stem cells. • p75{sup +} CNCCs in dental follicle cell medium (DFCCM/dNCP) appear like cementoblasts. • DFCCM/dNCP-treated p75{sup +} cells express cementoblast specific mineralization

  13. Leading coordinate analysis of reaction pathways in proton chain transfer: Application to a two-proton transfer model for the green fluorescent protein

    International Nuclear Information System (INIS)

    Wang Sufan; Smith, Sean C.

    2006-01-01

    The 'leading coordinate' approach to computing an approximate reaction pathway, with subsequent determination of the true minimum energy profile, is applied to a two-proton chain transfer model based on the chromophore and its surrounding moieties within the green fluorescent protein (GFP). Using an ab initio quantum chemical method, a number of different relaxed energy profiles are found for several plausible guesses at leading coordinates. The results obtained for different trial leading coordinates are rationalized through the calculation of a two-dimensional relaxed potential energy surface (PES) for the system. Analysis of the 2-D relaxed PES reveals that two of the trial pathways are entirely spurious, while two others contain useful information and can be used to furnish starting points for successful saddle-point searches. Implications for selection of trial leading coordinates in this class of proton chain transfer reactions are discussed, and a simple diagnostic function is proposed for revealing whether or not a relaxed pathway based on a trial leading coordinate is likely to furnish useful information

  14. Chemistry of unsaturated zone gases sampled in open boreholes at the crest of Yucca Mountain, Nevada: Data and basic concepts of chemical and physical processes in the mountain

    Science.gov (United States)

    Thorstenson, Donald C.; Weeks, Edwin P.; Haas, Herbert; Busenberg, Eurybiades; Plummer, Niel; Peters, Charles A.

    1998-01-01

    Boreholes open to the unsaturated zone at the crest of Yucca Mountain, Nevada, were variously sampled for CO2 (including 13C and 14C), CH4, N2, O2, Ar, CFC-11, CFC-12, and CFC-113 from 1986 to 1993. Air enters the mountain in outcrops, principally on the eastern slope, is enriched in CO2by mixing with soil gas, and is advected to the mountain crest, where it returns to the atmosphere. The CFC data indicate that travel times of the advecting gas in the shallow Tiva Canyon hydrogeologic unit are ≤5 years. The 14C activities are postbomb to depths of 100 m, indicating little retardation of 14CO2 in the shallow flow systems. The 14C activities from 168 to 404 m in the Topopah Spring hydrogeologic unit are 85–90 pMC at borehole USW-UZ6. The CFC data show that the drilling of USW-UZ6 in 1984 has altered the natural system by providing a conduit through the Paintbrush Nonwelded unit, allowing flow from Topopah Spring outcrops in Solitario Canyon on the west to USW-UZ6, upward in the borehole through the Paintbrush, to the shallow Tiva Canyon flow systems, and out of the mountain.

  15. Effects of wheat-flour biscuits fortified with iron and EDTA, alone and in combination, on blood lead concentration, iron status, and cognition in children: a double-blind randomized controlled trial.

    Science.gov (United States)

    Bouhouch, Raschida R; El-Fadeli, Sana; Andersson, Maria; Aboussad, Abdelmounaim; Chabaa, Laila; Zeder, Christophe; Kippler, Maria; Baumgartner, Jeannine; Sedki, Azzedine; Zimmermann, Michael B

    2016-11-01

    Lead is a common neurotoxicant and its absorption may be increased in iron deficiency (ID). Thus, iron fortification to prevent ID in populations is a promising lead mitigation strategy. Two common fortificants are ferrous sulfate (FeSO 4 ) and ferric sodium EDTA (NaFeEDTA). EDTA can chelate iron and lead. Our study objective was to determine the effects of iron and EDTA, alone and in combination, on blood lead (BPb) concentration, iron status, and cognition. In this 2 × 2 factorial, double-blind placebo-controlled trial, 457 lead-exposed Moroccan children were stratified by school and grade and randomly assigned to consume biscuits (6 d/wk at school) containing 1) ∼8 mg Fe as FeSO 4 , 2) ∼8 mg Fe as NaFeEDTA that contained ∼41 mg EDTA, 3) ∼41 mg EDTA as sodium EDTA (Na 2 EDTA), or 4) placebo for 28 wk. The primary outcome was BPb concentration; secondary outcomes were iron status and cognitive outcomes from subtests of the Kaufman Assessment Battery for Children and the Hopkins Verbal Learning Test. These outcomes were measured at baseline and endpoint. All data were analyzed by intention-to-treat. The adjusted geometric mean BPb concentration at baseline was 4.3 μg/dL (95% CI: 4.2, 4.3 μg/dL), and at endpoint these values were 3.3 μg/dL (95% CI: 3.1, 3.5 μg/dL) for FeSO 4 , 2.9 μg/dL (95% CI: 2.7, 3.0 μg/dL) for NaFeEDTA, 3.3 μg/dL (95% CI: 3.1, 3.5 μg/dL) for EDTA, and 3.7 μg/dL (95% CI: 3.5, 3.9 μg/dL) for placebo. We found an effect of iron (P = 0.009) and EDTA (P = 0.012) for reduced BPb concentrations at endpoint, but no iron × EDTA interaction. Iron fortification improved iron status, but there were no positive effects of iron or EDTA on cognitive test scores. Food fortification with iron and EDTA additively reduces BPb concentrations. Our findings suggest that NaFeEDTA should be the iron fortificant of choice in lead-exposed populations. This trial was registered at clinicaltrials.gov as NCT01573013. © 2016 American Society for

  16. Heterogeneity in avian richness-environment relationships along the Pacific Crest Trail

    Directory of Open Access Journals (Sweden)

    Michael C. McGrann

    2014-12-01

    Full Text Available Predictions of the responses of montane bird communities to climate change generally presuppose that species and assemblages hold constant relationships to temperature across large study regions. However, comparative studies of avian communities exploring the factors that currently shape species richness patterns rarely analyze relationships across neighboring ecological regions of the same mountain chain. Evaluations of the intrinsic regional differences in species-environment relationships are needed to better inform expectations of how bird communities may be affected by future climate change. In this study, we evaluated the relative importance of three environmental factors (temperature, precipitation, and net primary productivity in structuring avian richness patterns along a continuous mega-transect. We followed the route of the Pacific Crest Trail (PCT (32.58° N to 42.00° N, ranging in elevation from 365 to 4020 m on the California cordillera and completed avian point counts on 3578 systematically established survey plots. We divided this mega-transect into five sections, which corresponded to distinct ecological regions along the mountain chain. Regions differed both for elevation-richness patterns, exhibiting linear and unimodal trends, and for model-supported environmental drivers of patterns, with some richness-environment correlations changing sign across adjacent regions. These results were robust to sampling bias, regional species availability, and spatial autocorrelation. Although seasonal variation in avian movements may have limited influence on our results, we conclude that intrinsic regional environments affect bird species richness differently in each of these sections on the PCT, thus creating region-specific species-environment relationships. Appreciation of regional environmental heterogeneity will only increase in light of forecasted climate change, where regional predictions often diverge greatly from global trends

  17. ADAM13 Induces Cranial Neural Crest by Cleaving Class B Ephrins and Regulating Wnt Signaling

    Science.gov (United States)

    Wei, Shuo; Xu, Guofeng; Bridges, Lance C.; Williams, Phoebe; White, Judith M.; DeSimone, Douglas W.

    2010-01-01

    SUMMARY The cranial neural crest (CNC) are multipotent embryonic cells that contribute to craniofacial structures and other cells and tissues of the vertebrate head. During embryogenesis, CNC is induced at the neural plate boundary through the interplay of several major signaling pathways. Here we report that the metalloproteinase activity of ADAM13 is required for early induction of CNC in Xenopus. In both cultured cells and X. tropicalis embryos, membrane-bound Ephrins (Efns) B1 and B2 were identified as substrates for ADAM13. ADAM13 upregulates canonical Wnt signaling and early expression of the transcription factor snail2, whereas EfnB1 inhibits the canonical Wnt pathway and snail2 expression. We propose that by cleaving class B Efns, ADAM13 promotes canonical Wnt signaling and early CNC induction. PMID:20708595

  18. Zebrafish msxB, msxC and msxE function together to refine the neural-nonneural border and regulate cranial placodes and neural crest development.

    Science.gov (United States)

    Phillips, Bryan T; Kwon, Hye-Joo; Melton, Colt; Houghtaling, Paul; Fritz, Andreas; Riley, Bruce B

    2006-06-15

    The zebrafish muscle segment homeobox genes msxB, msxC and msxE are expressed in partially overlapping domains in the neural crest and preplacodal ectoderm. We examined the roles of these msx genes in early development. Disrupting individual msx genes causes modest variable defects, whereas disrupting all three produces a reproducible severe phenotype, suggesting functional redundancy. Neural crest differentiation is blocked at an early stage. Preplacodal development begins normally, but placodes arising from the msx expression domain later show elevated apoptosis and are reduced in size. Cell proliferation is normal in these tissues. Unexpectedly, Msx-deficient embryos become ventralized by late gastrulation whereas misexpression of msxB dorsalizes the embryo. These effects appear to involve Distal-less (Dlx) protein activity, as loss of dlx3b and dlx4b suppresses ventralization in Msx-depleted embryos. At the same time, Msx-depletion restores normal preplacodal gene expression to dlx3b-dlx4b mutants. These data suggest that mutual antagonism between Msx and Dlx proteins achieves a balance of function required for normal preplacodal differentiation and placement of the neural-nonneural border.

  19. Outcome Measures for Clinical Trials in Down Syndrome.

    Science.gov (United States)

    Esbensen, Anna J; Hooper, Stephen R; Fidler, Deborah; Hartley, Sigan L; Edgin, Jamie; d'Ardhuy, Xavier Liogier; Capone, George; Conners, Frances A; Mervis, Carolyn B; Abbeduto, Leonard; Rafii, Michael; Krinsky-McHale, Sharon J; Urv, Tiina

    2017-05-01

    Increasingly individuals with intellectual and developmental disabilities, including Down syndrome, are being targeted for clinical trials. However, a challenge exists in effectively evaluating the outcomes of these new pharmacological interventions. Few empirically evaluated, psychometrically sound outcome measures appropriate for use in clinical trials with individuals with Down syndrome have been identified. To address this challenge, the National Institutes of Health (NIH) assembled leading clinicians and scientists to review existing measures and identify those that currently are appropriate for trials; those that may be appropriate after expansion of age range addition of easier items, and/or downward extension of psychometric norms; and areas where new measures need to be developed. This article focuses on measures in the areas of cognition and behavior.

  20. Internal Occipital Crest Misalignment with Internal Occipital Protuberance: A Case Report of Posterior Cranial Fossa Anatomic Variations

    Science.gov (United States)

    Kim, Jae Ha

    2016-01-01

    During gross anatomy head and neck laboratory session, one dissection group observed an abnormal anatomic variation in the posterior cranial fossa of a 94-year-old male cadaver. The internal occipital crest was not aligned with internal occipital protuberance and groove for superior sagittal sinus. It seemed that the internal occipital protuberance was shifted significantly to the right side. As a result the skull was overly stretched in order to connect with the internal occipital ridge. These internal skull variations of occipital bone landmarks can influence the location of adjacent dural venous sinuses and possibly influence cerebrospinal fluid flow. Similar anatomical anomalies have been attributed to presence of hydrocephalus and abnormalities in cisterna magna. PMID:27648322

  1. Spinicauda sumatrana sp. nov. (Nematoda: Heterakidae) from Ludeking's Crested Dragon, Lophocalotes ludekingi (Agamidae), from the Bukit Barisan Range of Sumatra.

    Science.gov (United States)

    Bursey, Charles R; Goldberg, Stephen R; Harvey, Michael B

    2017-09-26

    Spinicauda sumatrana sp. nov. is described from the large intestine of Ludeking's Crested Dragon, Lophocalotes ludekingi (Agamidae) from the Bukit Barisan Range of Sumatra. The new species is assigned to Spinicauda based on the presence of off-set lips in both male and female and a ventrally directed sucker combined with the absence of caudal alae in males. It is the 17th species assigned to the genus and differs from all congeners in the combination of spicule length, presence of a gubernaculum, presence of a tail filament and fourteen pairs of caudal papillae.

  2. Identifying Variations in Hydraulic Conductivity on the East River at Crested Butte, CO

    Science.gov (United States)

    Ulmer, K. N.; Malenda, H. F.; Singha, K.

    2016-12-01

    Slug tests are a widely used method to measure saturated hydraulic conductivity, or how easily water flows through an aquifer, by perturbing the piezometric surface and measuring the time the local groundwater table takes to re-equilibrate. Saturated hydraulic conductivity is crucial to calculating the speed and direction of groundwater movement. Therefore, it is important to document data variance from in situ slug tests. This study addresses two potential sources of data variability: different users and different types of slug used. To test for user variability, two individuals slugged the same six wells with water multiple times at a stream meander on the East River near Crested Butte, CO. To test for variations in type of slug test, multiple water and metal slug tests were performed at a single well in the same meander. The distributions of hydraulic conductivities of each test were then tested for variance using both the Kruskal-Wallis test and the Brown-Forsythe test. When comparing the hydraulic conductivity distributions gathered by the two individuals, we found that they were statistically similar. However, we found that the two types of slug tests produced hydraulic conductivity distributions for the same well that are statistically dissimilar. In conclusion, multiple people should be able to conduct slug tests without creating any considerable variations in the resulting hydraulic conductivity values, but only a single type of slug should be used for those tests.

  3. Comparison of the diagenetic and reservoir quality evolution between the anticline crest and flank of an Upper Jurassic carbonate gas reservoir, Abu Dhabi, United Arab Emirates

    Science.gov (United States)

    Morad, Daniel; Nader, Fadi H.; Gasparrini, Marta; Morad, Sadoon; Rossi, Carlos; Marchionda, Elisabetta; Al Darmaki, Fatima; Martines, Marco; Hellevang, Helge

    2018-05-01

    This petrographic, stable isotopic and fluid inclusion microthermometric study of the Upper Jurassic limestones of an onshore field, Abu Dhabi, United Arab Emirates (UAE) compares diagenesis in flanks and crest of the anticline. The results revealed that the diagenetic and related reservoir quality evolution occurred during three phases, including: (i) eogenesis to mesogenesis 1, during which reservoir quality across the field was either deteriorated or preserved by calcite cementation presumably derived from marine or evolved marine pore waters. Improvement of reservoir quality was due to the formation of micropores by micritization of allochems and creation of moldic/intragranular pores by dissolution of peloids and skeletal fragments. (ii) Obduction of Oman ophiolites and formation of the anticline of the studied field was accompanied by cementation by saddle dolomite and blocky calcite. High homogenization temperatures (125-175 °C) and high salinity (19-26 wt% NaCl eq) of the fluid inclusions, negative δ18OVPDB values (-7.7 to -2.9‰), saddle shape of dolomite, and the presence of exotic cements (i.e. fluorite and sphalerite) suggest that these carbonates were formed by flux of hot basinal brines, probably related to this tectonic compression event. (iii) Mesogenesis 2 during subsidence subsequent to the obduction event, which resulted in extensive stylolitization and cementation by calcite. This calcite cement occluded most of the remaining moldic and inter-/intragranular pores of the flank limestones (water zone) whereas porosity was preserved in the crest. This study contributes to: (1) our understanding of differences in the impact of diagenesis on reservoir quality evolution in flanks and crests of anticlines, i.e. impact of hydrocarbon emplacement on diagenesis, and (2) relating various diagenetic processes to burial history and tectonic events of foreland basins in the Arabian Gulf area and elsewhere.

  4. Power analysis of trials with multilevel data

    CERN Document Server

    Moerbeek, Mirjam

    2015-01-01

    Power Analysis of Trials with Multilevel Data covers using power and sample size calculations to design trials that involve nested data structures. The book gives a thorough overview of power analysis that details terminology and notation, outlines key concepts of statistical power and power analysis, and explains why they are necessary in trial design. It guides you in performing power calculations with hierarchical data, which enables more effective trial design.The authors are leading experts in the field who recognize that power analysis has attracted attention from applied statisticians i

  5. Contribution of lead in wine to the total dietary intake of lead in humans with and without a meal

    International Nuclear Information System (INIS)

    Gulson, B.L.; Gray, B.; Mizon, K.J.; Patison, N.

    2000-01-01

    We have undertaken a case-control study using high precision lead isotopes to evaluate the contribution to blood lead when a normal quantity of wine is consumed with a meal and compared this with consumption under fasting conditions. White wine dosed with a 207 Pb tracer was consumed with a meal by a male subject and blood, urine and faeces monitored for up to four months. In addition to the spiked wine, the male subject and a female control subject residing in the same household consumed approximately equal proportions of unspiked red and white wine from the same vintage and vineyard over the four months. On a succeeding occasion, the male subject consumed 207 Pb-spiked wine under fasting conditions. As the 207 Pb/ 204 Pb ratio in blood and urine prior to the experiment was 15.48 compared with a value of 355 in the doped wine, changes in the 207 Pb/ 204 Pb ratio would be easily discernible. Over the four months of the trial, the results confirmed that there is a minimal uptake of lead from vine when consumed with food

  6. A Human Neural Crest Stem Cell-Derived Dopaminergic Neuronal Model Recapitulates Biochemical Abnormalities in GBA1 Mutation Carriers

    Directory of Open Access Journals (Sweden)

    Shi-Yu Yang

    2017-03-01

    Full Text Available Numerically the most important risk factor for the development of Parkinson's disease (PD is the presence of mutations in the glucocerebrosidase GBA1 gene. In vitro and in vivo studies show that GBA1 mutations reduce glucocerebrosidase (GCase activity and are associated with increased α-synuclein levels, reflecting similar changes seen in idiopathic PD brain. We have developed a neural crest stem cell-derived dopaminergic neuronal model that recapitulates biochemical abnormalities in GBA1 mutation-associated PD. Cells showed reduced GCase protein and activity, impaired macroautophagy, and increased α-synuclein levels. Advantages of this approach include easy access to stem cells, no requirement to reprogram, and retention of the intact host genome. Treatment with a GCase chaperone increased GCase protein levels and activity, rescued the autophagic defects, and decreased α-synuclein levels. These results provide the basis for further investigation of GCase chaperones or similar drugs to slow the progression of PD.

  7. Zebrafish Adar2 Edits the Q/R site of AMPA receptor Subunit gria2α transcript to ensure normal development of nervous system and cranial neural crest cells.

    Directory of Open Access Journals (Sweden)

    I-Chen Li

    Full Text Available BACKGROUND: Adar2 deaminates selective adenosines to inosines (A-to-I RNA editing in the double-stranded region of nuclear transcripts. Although the functions of mouse Adar2 and its biologically most important substrate gria2, encoding the GluA2 subunit of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor, have been extensively studied, the substrates and functions of zebrafish Adar2 remain elusive. METHODS/PRINCIPAL FINDINGS: Expression of Adar2 was perturbed in the adar2 morphant (adar2MO, generated by antisense morpholio oligonucleotides. The Q/R editing of gria2α was reduced in the adar2MO and was enhanced by overexpression of Adar2, demonstrating an evolutionarily conserved activity between zebrafish and mammalian Adar2 in editing the Q/R site of gria2. To delineate the role of Q/R editing of gria2α in the developmental defects observed in the adar2MO, the Q/R editing of gria2α was specifically perturbed in the gria2αQRMO, generated by a morpholio oligonucleotide complementary to the exon complementary sequence (ECS required for the Q/R editing. Analogous to the adar2-deficient and Q/R-editing deficient mice displaying identical neurological defects, the gria2αQRMO and adar2MO displayed identical developmental defects in the nervous system and cranial cartilages. Knockdown p53 abolished apoptosis and partially suppressed the loss of spinal cord motor neurons in these morphants. However, reducing p53 activity neither replenished the brain neuronal populations nor rescued the developmental defects. The expressions of crestin and sox9b in the neural crest cells were reduced in the adar2MO and gria2αQRMO. Overexpressing the edited GluA2αR in the adar2MO restored normal expressions of cresting and sox9b. Moreover, overexpressing the unedited GluA2αQ in the wild type embryos resulted in reduction of crestin and sox9b expressions. These results argue that an elevated GluA2αQ level is sufficient for generating the

  8. Online visual feedback during error-free channel trials leads to active unlearning of movement dynamics: evidence for adaptation to trajectory prediction errors.

    Directory of Open Access Journals (Sweden)

    Angel Lago-Rodriguez

    2016-09-01

    Full Text Available Prolonged exposure to movement perturbations leads to creation of motor memories which decay towards previous states when the perturbations are removed. However, it remains unclear whether this decay is due only to a spontaneous and passive recovery of the previous state. It has recently been reported that activation of reinforcement-based learning mechanisms delays the onset of the decay. This raises the question whether other motor learning mechanisms may also contribute to the retention and/or decay of the motor memory. Therefore, we aimed to test whether mechanisms of error-based motor adaptation are active during the decay of the motor memory. Forty-five right-handed participants performed point-to-point reaching movements under an external dynamic perturbation. We measured the expression of the motor memory through error-clamped (EC trials, in which lateral forces constrained movements to a straight line towards the target. We found greater and faster decay of the motor memory for participants who had access to full online visual feedback during these EC trials (Cursor group, when compared with participants who had no EC feedback regarding movement trajectory (Arc group. Importantly, we did not find between-group differences in adaptation to the external perturbation. In addition, we found greater decay of the motor memory when we artificially increased feedback errors through the manipulation of visual feedback (Augmented-Error group. Our results then support the notion of an active decay of the motor memory, suggesting that adaptive mechanisms are involved in correcting for the mismatch between predicted movement trajectories and actual sensory feedback, which leads to greater and faster decay of the motor memory.

  9. Are neural crest stem cells the missing link between hematopoietic and neurogenic niches?

    Directory of Open Access Journals (Sweden)

    Cécile eCoste

    2015-06-01

    Full Text Available Hematopoietic niches are defined as cellular and molecular microenvironments that regulate hematopoietic stem cell (HSC function together with stem cell autonomous mechanisms. Many different cell types have been characterized as contributors to the formation of HSC niches, such as osteoblasts, endothelial cells, Schwann cells, and mesenchymal progenitors. These mesenchymal progenitors have themselves been classified as CXC chemokine ligand (CXCL12-abundant reticular (CAR cells, stem cell factor expressing cells, or nestin-positive mesenchymal stem cells (MSCs, which have been recently identified as neural crest-derived cells (NCSCs. Together, these cells are spatially associated with HSCs and believed to provide appropriate microenvironments for HSC self-renewal, differentiation, mobilization and hibernation both by cell-to-cell contact and soluble factors. Interestingly, it appears that regulatory pathways governing the hematopoietic niche homeostasis are operating in the neurogenic niche as well. Therefore, this review paper aims to compare both the regulation of hematopoietic and neurogenic niches, in order to highlight the role of NCSCs and nervous system components in the development and the regulation of the hematopoietic system.

  10. Are neural crest stem cells the missing link between hematopoietic and neurogenic niches?

    Science.gov (United States)

    Coste, Cécile; Neirinckx, Virginie; Gothot, André; Wislet, Sabine; Rogister, Bernard

    2015-01-01

    Hematopoietic niches are defined as cellular and molecular microenvironments that regulate hematopoietic stem cell (HSC) function together with stem cell autonomous mechanisms. Many different cell types have been characterized as contributors to the formation of HSC niches, such as osteoblasts, endothelial cells, Schwann cells, and mesenchymal progenitors. These mesenchymal progenitors have themselves been classified as CXC chemokine ligand (CXCL) 12-abundant reticular (CAR) cells, stem cell factor expressing cells, or nestin-positive mesenchymal stem cells (MSCs), which have been recently identified as neural crest-derived cells (NCSCs). Together, these cells are spatially associated with HSCs and believed to provide appropriate microenvironments for HSC self-renewal, differentiation, mobilization and hibernation both by cell-cell contact and soluble factors. Interestingly, it appears that regulatory pathways governing the hematopoietic niche homeostasis are operating in the neurogenic niche as well. Therefore, this review paper aims to compare both the regulation of hematopoietic and neurogenic niches, in order to highlight the role of NCSCs and nervous system components in the development and the regulation of the hematopoietic system.

  11. Size does matter - Intraspecific variation of feeding mechanics in the crested newt Triturus dobrogicus (Kiritzescu, 1903)

    Science.gov (United States)

    Kucera, Florian; Beisser, Christian J.; Lemell, Patrick

    2018-03-01

    Many studies have yet been conducted on suction feeding in aquatic salamander species. Within the Salamandridae, the crested newt Triturus dobrogicus (Kiritzescu, 1903), occurring from the Austrian Danube floodplains to the Danube Delta, was not subject of investigations so far. The present study examines the kinematics of aquatic suction feeding in this species by means of high-speed videography. Recordings of five individuals of different size and sex while feeding on bloodworms were conducted, in order to identify potential discrepancies among individuals and sizes. Five coordinate points were digitized from recordings of prey capture and twelve time- and velocity-determined variables were evaluated. All specimens follow a typical inertial suction feeding process, where rapid hyoid depression expands the buccal cavity. Generated negative pressure within the buccal cavity causes influx of water along with the prey item into the mouth. Results demonstrate higher distance values and angles for gape in individuals with smaller size. In addition, hyoid depression is maximized in smaller individuals. While Triturus dobrogicus resembles a typical inertial suction feeder in its functional morphology, intraspecific differences could be found regarding the correlation of different feeding patterns and body size.

  12. System upgrade and its complications in patients with a single lead atrial pacemaker

    DEFF Research Database (Denmark)

    Kirkfeldt, Rikke Esberg; Andersen, Henning Rud; Nielsen, Jens Cosedis

    2013-01-01

    To investigate the indications for system upgrade with single lead atrial pacing (AAIR), complications associated with these re-interventions, and possible predictors for system upgrade among patients included in the Danish Multicenter Randomized Trial on AAIR vs. dual-chamber pacing (DDDR) in si...

  13. Early effects of zoledronic acid and teriparatide on bone microarchitecture, remodeling and collagen crosslinks: comparison between iliac crest and lumbar vertebra in ewes.

    Science.gov (United States)

    Portero-Muzy, N R; Chavassieux, P M; Bouxsein, M L; Gineyts, E; Garnero, P; Chapurlat, R D

    2012-10-01

    Iliac crest bone biopsies are used to assess the mechanism of action of drug treatments, yet there are little data comparing this site to sites prone to fracture. The purpose of this study was to compare the delay and the amplitude of responses to treatment in two different bone sites. The short-term effects of zoledronic acid and teriparatide on microarchitecture, collagen crosslinks and bone remodeling were evaluated in iliac crest and lumbar vertebrae. Aged ewes (n=8/gr) received either vehicle (CTRL) or a single injection of zoledronic acid (ZOL, 10mg) or daily injections of teriparatide (TPTD, 20 μg/d) for 3 months. Blood samples were collected monthly for assessing bone turnover markers. At the end of the study, a transiliac bone biopsy (IC) and L1 lumbar vertebrae (LV1) were collected to assess bone microarchitecture; pyridinoline (PYD), deoxypyridinoline (DPD), pentosidine (PEN) content, static and dynamic parameters of bone remodeling. In CTRL, Tb-BV/TV was significantly higher in LV1 than IC (psALP (p<0.001) and sCTX (p<0.001) were observed in the ZOL-group whereas in TPTD-group, after transient increases, they returned to baseline values. When compared to their respective CTRL, ZOL induced significant increases in Tb.BV/TV, Conn.D, Tb.N and Tb.Sp, in IC but not in LV1. Regardless of the site, ZOL markedly depressed the bone turnover: The static parameters of bone formation significantly decreased and the diminution of MS/BS, BFR/BS and Ac.f varied from -94 to -98% vs CTRL (p<0.01 to 0.001). It was associated with a diminution of the DPD content and the PYD/DPD ratio mainly in IC cortices. In contrast, after 3 months, TPTD did not modify the 3D structure and microarchitecture in IC and LV1, except a trend of higher Conn.D in IC, compared to IC-CTRL. TPTD treatment induced a significant increase in cortical porosity in LV1 (p<0.05) when compared to LV1-CTRL. Static parameters of bone formation and resorption were augmented in both sites, significantly

  14. The neuro-glial properties of adipose-derived adult stromal (ADAS) cells are not regulated by Notch 1 and are not derived from neural crest lineage.

    Science.gov (United States)

    Wrage, Philip C; Tran, Thi; To, Khai; Keefer, Edward W; Ruhn, Kelly A; Hong, John; Hattangadi, Supriya; Treviño, Isaac; Tansey, Malú G

    2008-01-16

    We investigated whether adipose-derived adult stromal (ADAS) are of neural crest origin and the extent to which Notch 1 regulates their growth and differentiation. Mouse ADAS cells cultured in media formulated for neural stem cells (NSC) displayed limited capacity for self-renewal, clonogenicity, and neurosphere formation compared to NSC from the subventricular zone in the hippocampus. Although ADAS cells expressed Nestin, GFAP, NSE and Tuj1 in vitro, exposure to NSC differentiation supplements did not induce mature neuronal marker expression. In contrast, in mesenchymal stem cell (MSC) media, ADAS cells retained their ability to proliferate and differentiate beyond 20 passages and expressed high levels of Nestin. In neuritizing cocktails, ADAS cells extended processes, downregulated Nestin expression, and displayed depolarization-induced Ca(2+) transients but no spontaneous or evoked neural network activity on Multi-Electrode Arrays. Deletion of Notch 1 in ADAS cell cultures grown in NSC proliferation medium did not significantly alter their proliferative potential in vitro or the differentiation-induced downregulation of Nestin. Co-culture of ADAS cells with fibroblasts that stably expressed the Notch ligand Jagged 1 or overexpression of the Notch intracellular domain (NICD) did not alter ADAS cell growth, morphology, or cellular marker expression. ADAS cells did not display robust expression of neural crest transcription factors or genes (Sox, CRABP2, and TH); and lineage tracing analyses using Wnt1-Cre;Rosa26R-lacZ or -EYFP reporter mice confirmed that fewer than 2% of the ADAS cell population derived from a Wnt1-positive population during development. In summary, although media formulations optimized for MSCs or NSCs enable expansion of mouse ADAS cells in vitro, we find no evidence that these cells are of neural crest origin, that they can undergo robust terminal differentiation into functionally mature neurons, and that Notch 1 is likely to be a key

  15. Apophyseal Ossification of the Iliac Crest in Forensic Age Estimation: Computed Tomography Standards for Modern Australian Subadults.

    Science.gov (United States)

    Lottering, Nicolene; Alston-Knox, Clair L; MacGregor, Donna M; Izatt, Maree T; Grant, Caroline A; Adam, Clayton J; Gregory, Laura S

    2017-03-01

    This study contrasts the ontogeny of the iliac crest apophysis using conventional radiography and multislice computed tomography (MSCT), providing probabilistic information for age estimation of modern Australian subadults. Retrospective abdominopelvic MSCT data acquired from 524 Australian individuals aged 7-25 and surveillance radiographs of adolescent idiopathic scoliosis patients included in the Paediatric Spine Research Group Progression Study (n = 531) were assessed. Ossification scoring of pseudo-radiographs and three-dimensional (3D) volume-rendered reconstructions using Risser (1958) quantitative descriptors indicate discrepancies in age estimates, stage allocation, and conflicting morphological progression. To mitigate visualization limitations associated with two-dimensional radiographs, we provide and validate a modified 3D-MSCT scoring tier of ossification, demonstrating complete fusion between 17.3-19.2 and 17.1-20.1 years in males and females. Legal demarcation for doli incapax presumption and age of majority (18 years) can be achieved using probability estimates from a fitted cumulative probit model for apophyseal fusion using the recalibrated standards. © 2016 American Academy of Forensic Sciences.

  16. Field performance of wood-burning and coal-burning appliances in Crested Butte during the 1989-90 heating season. Final report

    International Nuclear Information System (INIS)

    Jaasma, D.R.; Champion, M.R.; Gundappa, M.

    1991-10-01

    The field performance of woodburning and coalburning appliances in and around Crested Butte, CO, has been evaluated. Measurements included particulate matter (PM), carbon monoxide (CO), and weekly average burn rates. Woodburning appliances included conventional airtight stoves, EPA-certified catalytic stoves, and EPA-certified noncatalytic stoves. Compared to the emissions measured from conventional stoves, the certified stoves reduced PM emission factors (g/kg) by 53% and CO emission factors by 49%. Coalburning appliances included a commercial scale boiler, a residential stoker, and hand-fired coalstove. The coalburning appliances were compared to conventional woodstoves on a grams of pollutant per joule of heat output basis. The automatically stoked coal appliances reduced PM and CO emissions by roughly 84% and 85%, respectively. The hand-fired stove was cleaner than expected, reducing PM by 55% and CO by 27%

  17. Hematological alterations and splenic T lymphocyte polarization at the crest of snake venom induced acute kidney injury in adult male mice.

    Science.gov (United States)

    Nasim, Farhat; Das, Sreyasi; Mishra, Roshnara; Mishra, Raghwendra

    2017-08-01

    Snake venom induced acute kidney injury (SAKI) is of great clinical relevance in tropical countries. Involvement of T cell, a key mediator of AKI and its remission, is least explored in SAKI. In the present study the in vivo hematological alterations and associated splenic T cell polarization is probed in order to investigate the immune response at the crest of Russell's viper venom (RVV) induced AKI in experimental murine model. Based on a dose and time kinetic study intra muscular injection dose of 20 μg RVV/100 gm body weight of mice and incubation period of 60 h was selected for induction of SAKI. Renal involvement in SAKI group was confirmed from oliguria, significantly elevated urinary microprotein (p < 0.001), decreased urinary creatinine (p = 0.003) and creatinine clearance (p < 0.001) compared to control. Hematological analyses revealed a significant neutrophilic leukocytosis (p < 0.001) associated with a reduced lymphocyte percentage (p < 0.001) favoring a state of acute inflammation in SAKI group. Immunophenotyping study of splenocytes showed a significant decrease in CD4 + /CD8 + ratio (p < 0.001) with a significant increase in regulatory (CD25 + FoxP3 + ) helper and cytotoxic subset of T cell (p < 0.001). Significant increase in IL-10+ regulatory helper and cytotoxic T cell (p < 0.001) further confirmed the internal milieu favoring immunosuppression. Apart from these the CD25 - FoxP3 + reservoir regulatory T cells were also found to be significantly elevated in SAKI group compared to that of control (p < 0.001). Taken together, the results of the present study clearly indicated a state of acute inflammation and splenic T cell polarization towards regulatory subset at the crest of SAKI. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. E-cadherin is required for cranial neural crest migration in Xenopus laevis.

    Science.gov (United States)

    Huang, Chaolie; Kratzer, Marie-Claire; Wedlich, Doris; Kashef, Jubin

    2016-03-15

    The cranial neural crest (CNC) is a highly motile and multipotent embryonic cell population, which migrates directionally on defined routes throughout the embryo, contributing to facial structures including cartilage, bone and ganglia. Cadherin-mediated cell-cell adhesion is known to play a crucial role in the directional migration of CNC cells. However, migrating CNC co-express different cadherin subtypes, and their individual roles have yet to be fully explored. In previous studies, the expression of individual cadherin subtypes has been analysed using different methods with varying sensitivities, preventing the direct comparison of expression levels. Here, we provide the first comprehensive and comparative analysis of the expression of six cadherin superfamily members during different phases of CNC cell migration in Xenopus. By applying a quantitative RT-qPCR approach, we can determine the copy number and abundance of each expressed cadherin through different phases of CNC migration. Using this approach, we show for the first time expression of E-cadherin and XB/C-cadherin in CNC cells, adding them as two new members of cadherins co-expressed during CNC migration. Cadherin co-expression during CNC migration in Xenopus, in particular the constant expression of E-cadherin, contradicts the classical epithelial-mesenchymal transition (EMT) model postulating a switch in cadherin expression. Loss-of-function experiments further show that E-cadherin is required for proper CNC cell migration in vivo and also for cell protrusion formation in vitro. Knockdown of E-cadherin is not rescued by co-injection of other classical cadherins, pointing to a specific function of E-cadherin in mediating CNC cell migration. Finally, through reconstitution experiments with different E-cadherin deletion mutants in E-cadherin morphant embryos, we demonstrate that the extracellular domain, but not the cytoplasmic domain, of E-cadherin is sufficient to rescue CNC cell migration in vivo

  19. SOXE neofunctionalization and elaboration of the neural crest during chordate evolution

    Science.gov (United States)

    Tai, Andrew; Cheung, Martin; Huang, Yong-Heng; Jauch, Ralf; Bronner, Marianne E.; Cheah, Kathryn S. E.

    2016-01-01

    During chordate evolution, two genome-wide duplications facilitated acquisition of vertebrate traits, including emergence of neural crest cells (NCCs), in which neofunctionalization of the duplicated genes are thought to have facilitated development of craniofacial structures and the peripheral nervous system. How these duplicated genes evolve and acquire the ability to specify NC and their derivatives are largely unknown. Vertebrate SoxE paralogues, most notably Sox9/10, are essential for NC induction, delamination and lineage specification. In contrast, the basal chordate, amphioxus, has a single SoxE gene and lacks NC-like cells. Here, we test the hypothesis that duplication and divergence of an ancestral SoxE gene may have facilitated elaboration of NC lineages. By using an in vivo expression assay to compare effects of AmphiSoxE and vertebrate Sox9 on NC development, we demonstrate that all SOXE proteins possess similar DNA binding and homodimerization properties and can induce NCCs. However, AmphiSOXE is less efficient than SOX9 in transactivation activity and in the ability to preferentially promote glial over neuronal fate, a difference that lies within the combined properties of amino terminal and transactivation domains. We propose that acquisition of AmphiSoxE expression in the neural plate border led to NCC emergence while duplication and divergence produced advantageous mutations in vertebrate homologues, promoting elaboration of NC traits. PMID:27734831

  20. Early response to sibutramine in patients not meeting current label criteria: preliminary analysis of SCOUT lead-in period

    DEFF Research Database (Denmark)

    Caterson, Ian; Coutinho, Walmir; Finer, Nick

    2010-01-01

    The Sibutramine Cardiovascular Outcomes (SCOUT) trial protocol defines a patient population predominantly outside current European Union label criteria. This article explores responses to sibutramine during the 6-week, single-blind, lead-in period between patients who conformed to the label...... requirements ("conformers") and those who did not ("nonconformers"). SCOUT is an ongoing, randomized, double-blind, placebo-controlled outcome trial in overweight/obese patients at high risk of a cardiovascular event. In total, 10,742 patients received sibutramine and weight management during the lead...... with sibutramine confirms its good tolerability and efficacy in patients who meet current label criteria. Preliminary data from high-risk patients for whom sibutramine is currently contraindicated suggest a low discontinuation rate and few serious adverse events but confirmation from the SCOUT outcome data...

  1. Characteristics of cancer patients participating in presurgical lifestyle intervention trials exploring effects on tumor biology

    Directory of Open Access Journals (Sweden)

    John A. Dasher

    2017-12-01

    Conclusion: Similar to other clinical trials, lack of time is a leading barrier to enrollment, and travel/distance appears to be a greater barrier for women in presurgical studies. Larger presurgical lifestyle intervention trials will require tailored strategies to enhance recruitment.

  2. The combined effects of developmental lead and ethanol exposure on hippocampus dependent spatial learning and memory in rats: Role of oxidative stress.

    Science.gov (United States)

    Soleimani, Elham; Goudarzi, Iran; Abrari, Kataneh; Lashkarbolouki, Taghi

    2016-10-01

    Either developmental lead or ethanol exposure can impair learning and memory via induction of oxidative stress, which results in neuronal damage. we examined the effect of combined exposure with lead and ethanol on spatial learning and memory in offspring and oxidative stress in hippocampus. Rats were exposed to lead (0.2% in drinking water) or ethanol (4 g/kg) either individually or in combination in 5th day gestation through weaning. On postnatal days (PD) 30, rats were trained with six trials per day for 6 consecutive days in the water maze. On day 37, a probe test was done. Also, oxidative stress markers in the hippocampus were also evaluated. Results demonstrated that lead + ethanol co-exposed rats exhibited higher escape latency during training trials and reduced time spent in target quadrant, higher escape location latency and average proximity in probe trial test. There was significant decrease in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities and increase of malondialdehyde (MDA) levels in hippocampus of animals co-exposed to lead and ethanol compared with their individual exposures. We suggest that maternal consumption of ethanol during lead exposure has pronounced detrimental effects on memory, which may be mediated by oxidative stress. Copyright © 2016. Published by Elsevier Ltd.

  3. Derivation of corneal endothelial cell-like cells from rat neural crest cells in vitro.

    Directory of Open Access Journals (Sweden)

    Chengqun Ju

    Full Text Available The aim of this study was to investigate the feasibility of inducing rat neural crest cells (NCC to differentiate to functional corneal endothelial cell (CEC-like cells in vitro. Rat NCC were induced with adult CEC-derived conditioned medium. Immunofluorescence, flow cytometry and real time RT-PCR assay were used to detect expression of the corneal endothelium differentiation marker N-cadherin and transcription factors FoxC1 and Pitx2. CFDA SE-labeled CEC-like cells were transplanted to the corneal endothelium of a rat corneal endothelium deficiency model, and an eye-down position was maintained for 24 hours to allow cell attachment. The animals were observed for as long as 2 months after surgery and underwent clinical and histological examination. Spindle-like NCC turned to polygonal CEC-like after induction and expressed N-cadherin, FoxC1, Pitx2, zonula occludens-1 and sodium-potassium pump Na(+/K(+ ATPase. The corneas of the experimental group were much clearer than those of the control group and the mean corneal thickness in the experimental group was significantly less than in the control group7, 14, 21 and 28 days after surgery. Confocal microscopy through focusing and histological analysis confirmed that green fluorescence-positive CEC-like cells formed a monolayer covering the Descemet's membrane in the experimental group. In conclusion, CEC-like cells derived from NCCs displayed characters of native CEC, and the induction protocol provides guidance for future human CEC induction from NCC.

  4. Safety and efficacy of dual-lead thalamic deep brain stimulation for patients with treatment-refractory multiple sclerosis tremor: a single-centre, randomised, single-blind, pilot trial.

    Science.gov (United States)

    Oliveria, Seth F; Rodriguez, Ramon L; Bowers, Dawn; Kantor, Daniel; Hilliard, Justin D; Monari, Erin H; Scott, Bonnie M; Okun, Michael S; Foote, Kelly D

    2017-09-01

    Efficacy in previous studies of surgical treatments of refractory multiple sclerosis tremor using lesioning or deep brain stimulation (DBS) has been variable. The aim of this study was to investigate the safety and efficacy of dual-lead thalamic DBS (one targeting the ventralis intermedius-ventralis oralis posterior nucleus border [the VIM lead] and one targeting the ventralis oralis anterior-ventralis oralis posterior border [the VO lead]) for the treatment of multiple sclerosis tremor. We did a single centre, single-blind, prospective, randomised pilot trial at the University of Florida Center for Movement Disorders and Neurorestoration clinic (Gainesville, FL, USA). We recruited adult patients with a clinical diagnosis of multiple sclerosis tremor refractory to previous medical therapy. Before surgery to implant both leads, we randomly assigned patients (1:1) to receive 3 months of optimised single-lead DBS-either VIM or VO. We did the randomisation with a computer-generated sequence, using three blocks of four patients, and independent members of the Center did the assignment. Patients and all clinicians other than the DBS programming nurse were masked to the choice of lead. Patients underwent surgery 1 month after their baseline visit for implantation of the dual lead DBS system. A pulse generator and two extension cables were implanted in a second surgery 3-4 weeks later. Patients then received an initial 3-month period of continuous stimulation of either the VIM or VO lead followed by blinded safety assessment of their tremor with the Tolosa-Fahn-Marin Tremor Rating Scale (TRS) during optimised VIM or VO lead stimulation at the end of the 3 months. After this visit, both leads were activated in all patients for an additional 3 months, and optimally programmed during serial visits as dictated by a prespecified programming algorithm. At the 6-month follow-up visit, TRS score was measured, and mood and psychological batteries were administered under four

  5. Standards for reporting randomized controlled trials in neurosurgery.

    Science.gov (United States)

    Kiehna, Erin N; Starke, Robert M; Pouratian, Nader; Dumont, Aaron S

    2011-02-01

    The Consolidated Standards for Reporting of Trials (CONSORT) criteria were published in 1996 to standardize the reporting and improve the quality of clinical trials. Despite having been endorsed by major medical journals and shown to improve the quality of reported trials, neurosurgical journals have yet to formally adopt these reporting criteria. The purpose of this study is to evaluate the quality and reporting of randomized controlled trials (RCTs) in neurosurgery and the factors that may affect the quality of reported trials. The authors evaluated all neurosurgical RCTs published in 2006 and 2007 in the principal neurosurgical journals (Journal of Neurosurgery; Neurosurgery; Surgical Neurology; Journal of Neurology, Neurosurgery, and Psychiatry; and Acta Neurochirurgica) and in 3 leading general medical journals (Journal of the American Medical Association, Lancet, and the New England Journal of Medicine). Randomized controlled trials that addressed operative decision making or the treatment of neurosurgical patients were included in this analysis. The RCT quality was evaluated using the Jadad score and the CONSORT checklist. In 2006 and 2007, 27 RCTs relevant to intracranial neurosurgery were reported. Of these trials, only 59% had a Jadad score ≥ 3. The 3 major medical journals all endorsed the CONSORT guidelines, while none of the neurosurgical journals have adopted these guidelines. Randomized controlled trials published in the 3 major medical journals had a significantly higher mean CONSORT score (mean 41, range 39-44) compared with those published in neurosurgical journals (mean 26.4, range 17-38; p journals (mean 3.42, range 2-5) than neurosurgical journals (mean 2.45, range 1-5; p = 0.05). Despite the growing volume of RCTs in neurosurgery, the quality of reporting of these trials remains suboptimal, especially in the neurosurgical journals. Improved awareness of the CONSORT guidelines by journal editors, reviewers, and authors of these papers could

  6. rhBMP-2 for posterolateral instrumented lumbar fusion: a multicenter prospective randomized controlled trial.

    Science.gov (United States)

    Hurlbert, R John; Alexander, David; Bailey, Stewart; Mahood, James; Abraham, Ed; McBroom, Robert; Jodoin, Alain; Fisher, Charles

    2013-12-01

    Multicenter randomized controlled trial. To evaluate the effect of recombinant human bone morphogenetic protein (rhBMP-2) on radiographical fusion rate and clinical outcome for surgical lumbar arthrodesis compared with iliac crest autograft. In many types of spinal surgery, radiographical fusion is a primary outcome equally important to clinical improvement, ensuring long-term stability and axial support. Biologic induction of bone growth has become a commonly used adjunct in obtaining this objective. We undertook this study to objectify the efficacy of rhBMP-2 compared with traditional iliac crest autograft in instrumented posterolateral lumbar fusion. Patients undergoing 1- or 2-level instrumented posterolateral lumbar fusion were randomized to receive either autograft or rhBMP-2 for their fusion construct. Clinical and radiographical outcome measures were followed for 2 to 4 years postoperatively. One hundred ninety seven patients were successfully randomized among the 8 participating institutions. Adverse events attributable to the study drug were not significantly different compared with controls. However, the control group experienced significantly more graft-site complications as might be expected. 36-Item Short Form Health Survey, Oswestry Disability Index, and leg/back pain scores were comparable between the 2 groups. After 4 years of follow-up, radiographical fusion rates remained significantly higher in patients treated with rhBMP-2 (94%) than those who received autograft (69%) (P = 0.007). The use of rhBMP-2 for instrumented posterolateral lumbar surgery significantly improves the chances of radiographical fusion compared with the use of autograft. However, there is no associated improvement in clinical outcome within a 4-year follow-up period. These results suggest that use of rhBMP-2 should be considered in cases where lumbar arthrodesis is of primary concern.

  7. An empirical model of ionospheric total electron content (TEC) near the crest of the equatorial ionization anomaly (EIA)

    Science.gov (United States)

    Hajra, Rajkumar; Chakraborty, Shyamal Kumar; Tsurutani, Bruce T.; DasGupta, Ashish; Echer, Ezequiel; Brum, Christiano G. M.; Gonzalez, Walter D.; Sobral, José Humberto Andrade

    2016-07-01

    We present a geomagnetic quiet time (Dst > -50 nT) empirical model of ionospheric total electron content (TEC) for the northern equatorial ionization anomaly (EIA) crest over Calcutta, India. The model is based on the 1980-1990 TEC measurements from the geostationary Engineering Test Satellite-2 (ETS-2) at the Haringhata (University of Calcutta, India: 22.58° N, 88.38° E geographic; 12.09° N, 160.46° E geomagnetic) ionospheric field station using the technique of Faraday rotation of plane polarized VHF (136.11 MHz) signals. The ground station is situated virtually underneath the northern EIA crest. The monthly mean TEC increases linearly with F10.7 solar ionizing flux, with a significantly high correlation coefficient (r = 0.89-0.99) between the two. For the same solar flux level, the TEC values are found to be significantly different between the descending and ascending phases of the solar cycle. This ionospheric hysteresis effect depends on the local time as well as on the solar flux level. On an annual scale, TEC exhibits semiannual variations with maximum TEC values occurring during the two equinoxes and minimum at summer solstice. The semiannual variation is strongest during local noon with a summer-to-equinox variability of ~50-100 TEC units. The diurnal pattern of TEC is characterized by a pre-sunrise (0400-0500 LT) minimum and near-noon (1300-1400 LT) maximum. Equatorial electrodynamics is dominated by the equatorial electrojet which in turn controls the daytime TEC variation and its maximum. We combine these long-term analyses to develop an empirical model of monthly mean TEC. The model is validated using both ETS-2 measurements and recent GNSS measurements. It is found that the present model efficiently estimates the TEC values within a 1-σ range from the observed mean values.

  8. An empirical model of ionospheric total electron content (TEC near the crest of the equatorial ionization anomaly (EIA

    Directory of Open Access Journals (Sweden)

    Hajra Rajkumar

    2016-01-01

    Full Text Available We present a geomagnetic quiet time (Dst > −50 nT empirical model of ionospheric total electron content (TEC for the northern equatorial ionization anomaly (EIA crest over Calcutta, India. The model is based on the 1980–1990 TEC measurements from the geostationary Engineering Test Satellite-2 (ETS-2 at the Haringhata (University of Calcutta, India: 22.58° N, 88.38° E geographic; 12.09° N, 160.46° E geomagnetic ionospheric field station using the technique of Faraday rotation of plane polarized VHF (136.11 MHz signals. The ground station is situated virtually underneath the northern EIA crest. The monthly mean TEC increases linearly with F10.7 solar ionizing flux, with a significantly high correlation coefficient (r = 0.89–0.99 between the two. For the same solar flux level, the TEC values are found to be significantly different between the descending and ascending phases of the solar cycle. This ionospheric hysteresis effect depends on the local time as well as on the solar flux level. On an annual scale, TEC exhibits semiannual variations with maximum TEC values occurring during the two equinoxes and minimum at summer solstice. The semiannual variation is strongest during local noon with a summer-to-equinox variability of ~50–100 TEC units. The diurnal pattern of TEC is characterized by a pre-sunrise (0400–0500 LT minimum and near-noon (1300–1400 LT maximum. Equatorial electrodynamics is dominated by the equatorial electrojet which in turn controls the daytime TEC variation and its maximum. We combine these long-term analyses to develop an empirical model of monthly mean TEC. The model is validated using both ETS-2 measurements and recent GNSS measurements. It is found that the present model efficiently estimates the TEC values within a 1-σ range from the observed mean values.

  9. Measuring behavioral responses of sea turtles, saltwater crocodiles, and crested terns to drone disturbance to define ethical operating thresholds.

    Science.gov (United States)

    Bevan, Elizabeth; Whiting, Scott; Tucker, Tony; Guinea, Michael; Raith, Andrew; Douglas, Ryan

    2018-01-01

    Drones are being increasingly used in innovative ways to enhance environmental research and conservation. Despite their widespread use for wildlife studies, there are few scientifically justified guidelines that provide minimum distances at which wildlife can be approached to minimize visual and auditory disturbance. These distances are essential to ensure that behavioral and survey data have no observer bias and form the basis of requirements for animal ethics and scientific permit approvals. In the present study, we documented the behaviors of three species of sea turtle (green turtles, Chelonia mydas, flatback turtles, Natator depressus, hawksbill turtles, Eretmochelys imbricata), saltwater crocodiles (Crocodylus porosus), and crested terns (Thalasseus bergii) in response to a small commercially available (1.4 kg) multirotor drone flown in Northern Territory and Western Australia. Sea turtles in nearshore waters off nesting beaches or in foraging habitats exhibited no evasive behaviors (e.g. rapid diving) in response to the drone at or above 20-30 m altitude, and at or above 10 m altitude for juvenile green and hawksbill turtles foraging on shallow, algae-covered reefs. Adult female flatback sea turtles were not deterred by drones flying forward or stationary at 10 m altitude when crawling up the beach to nest or digging a body pit or egg chamber. In contrast, flyovers elicited a range of behaviors from crocodiles, including minor, lateral head movements, fleeing, or complete submergence when a drone was present below 50 m altitude. Similarly, a colony of crested terns resting on a sand-bank displayed disturbance behaviors (e.g. flight response) when a drone was flown below 60 m altitude. The current study demonstrates a variety of behavioral disturbance thresholds for diverse species and should be considered when establishing operating conditions for drones in behavioral and conservation studies.

  10. Measuring behavioral responses of sea turtles, saltwater crocodiles, and crested terns to drone disturbance to define ethical operating thresholds

    Science.gov (United States)

    Whiting, Scott; Tucker, Tony; Guinea, Michael; Raith, Andrew; Douglas, Ryan

    2018-01-01

    Drones are being increasingly used in innovative ways to enhance environmental research and conservation. Despite their widespread use for wildlife studies, there are few scientifically justified guidelines that provide minimum distances at which wildlife can be approached to minimize visual and auditory disturbance. These distances are essential to ensure that behavioral and survey data have no observer bias and form the basis of requirements for animal ethics and scientific permit approvals. In the present study, we documented the behaviors of three species of sea turtle (green turtles, Chelonia mydas, flatback turtles, Natator depressus, hawksbill turtles, Eretmochelys imbricata), saltwater crocodiles (Crocodylus porosus), and crested terns (Thalasseus bergii) in response to a small commercially available (1.4 kg) multirotor drone flown in Northern Territory and Western Australia. Sea turtles in nearshore waters off nesting beaches or in foraging habitats exhibited no evasive behaviors (e.g. rapid diving) in response to the drone at or above 20–30 m altitude, and at or above 10 m altitude for juvenile green and hawksbill turtles foraging on shallow, algae-covered reefs. Adult female flatback sea turtles were not deterred by drones flying forward or stationary at 10 m altitude when crawling up the beach to nest or digging a body pit or egg chamber. In contrast, flyovers elicited a range of behaviors from crocodiles, including minor, lateral head movements, fleeing, or complete submergence when a drone was present below 50 m altitude. Similarly, a colony of crested terns resting on a sand-bank displayed disturbance behaviors (e.g. flight response) when a drone was flown below 60 m altitude. The current study demonstrates a variety of behavioral disturbance thresholds for diverse species and should be considered when establishing operating conditions for drones in behavioral and conservation studies. PMID:29561901

  11. Yield, SDG lignan, cadmium, lead, oil and protein contents of linseed (Linum usitatissimum L. cultivated in trials and at different farm conditions in the south-western part of Finland

    Directory of Open Access Journals (Sweden)

    Marketta Saastamoinen

    2013-06-01

    Full Text Available Linseed varieties were studied in variety trials and under farm conditions in south-western Finland in the years 2007−2010. The variation in yield, oil, protein, SDG lignan, cadmium and lead contents were studied in 8 oil and 2 fibre linseed varieties. Genotypic, environmental and genotype x environment interaction variance estimates were calculated. Fibre varieties ‘Belinka’ and ‘Martta’ had higher protein and lower oil contents than oil linseed varieties.The SDG lignan contents of linseed varieties varied between 3635−9560 mg kg-1. Rather high genotypic variance was found in yield, oil, protein and SDG lignan contents. Variety ‘Laser’ had lower SDG lignan content. ‘Abacus’, ‘Helmi’ and ‘Martta’ had the highest SDG lignan contents. Variation in cadmium and lead contents were caused by environmental effects. The highest cadmium contents, 0.82−1.69 mg kg-1, were found in soils fertilized by wastewater sludge about 20 years ago and at fields with low bottom soil pH (4.1−4.5.

  12. CREST : a computer program for the calculation of composition dependent self-shielded cross-sections

    International Nuclear Information System (INIS)

    Kapil, S.K.

    1977-01-01

    A computer program CREST for the calculation of the composition and temperature dependent self-shielded cross-sections using the shielding factor approach has been described. The code includes the editing and formation of the data library, calculation of the effective shielding factors and cross-sections, a fundamental mode calculation to generate the neutron spectrum for the system which is further used to calculate the effective elastic removal cross-sections. Studies to explore the sensitivity of reactor parameters to changes in group cross-sections can also be carried out by using the facility available in the code to temporarily change the desired constants. The final self-shielded and transport corrected group cross-sections can be dumped on cards or magnetic tape in a suitable form for their direct use in a transport or diffusion theory code for detailed reactor calculations. The program is written in FORTRAN and can be accommodated in a computer with 32 K work memory. The input preparation details, sample problem and the listing of the program are given. (author)

  13. Randomized controlled trials in dentistry: common pitfalls and how to avoid them.

    Science.gov (United States)

    Fleming, Padhraig S; Lynch, Christopher D; Pandis, Nikolaos

    2014-08-01

    Clinical trials are used to appraise the effectiveness of clinical interventions throughout medicine and dentistry. Randomized controlled trials (RCTs) are established as the optimal primary design and are published with increasing frequency within the biomedical sciences, including dentistry. This review outlines common pitfalls associated with the conduct of randomized controlled trials in dentistry. Common failings in RCT design leading to various types of bias including selection, performance, detection and attrition bias are discussed in this review. Moreover, methods of minimizing and eliminating bias are presented to ensure that maximal benefit is derived from RCTs within dentistry. Well-designed RCTs have both upstream and downstream uses acting as a template for development and populating systematic reviews to permit more precise estimates of treatment efficacy and effectiveness. However, there is increasing awareness of waste in clinical research, whereby resource-intensive studies fail to provide a commensurate level of scientific evidence. Waste may stem either from inappropriate design or from inadequate reporting of RCTs; the importance of robust conduct of RCTs within dentistry is clear. Optimal reporting of randomized controlled trials within dentistry is necessary to ensure that trials are reliable and valid. Common shortcomings leading to important forms or bias are discussed and approaches to minimizing these issues are outlined. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Can we identify non-stationary dynamics of trial-to-trial variability?

    Directory of Open Access Journals (Sweden)

    Emili Balaguer-Ballester

    Full Text Available Identifying sources of the apparent variability in non-stationary scenarios is a fundamental problem in many biological data analysis settings. For instance, neurophysiological responses to the same task often vary from each repetition of the same experiment (trial to the next. The origin and functional role of this observed variability is one of the fundamental questions in neuroscience. The nature of such trial-to-trial dynamics however remains largely elusive to current data analysis approaches. A range of strategies have been proposed in modalities such as electro-encephalography but gaining a fundamental insight into latent sources of trial-to-trial variability in neural recordings is still a major challenge. In this paper, we present a proof-of-concept study to the analysis of trial-to-trial variability dynamics founded on non-autonomous dynamical systems. At this initial stage, we evaluate the capacity of a simple statistic based on the behaviour of trajectories in classification settings, the trajectory coherence, in order to identify trial-to-trial dynamics. First, we derive the conditions leading to observable changes in datasets generated by a compact dynamical system (the Duffing equation. This canonical system plays the role of a ubiquitous model of non-stationary supervised classification problems. Second, we estimate the coherence of class-trajectories in empirically reconstructed space of system states. We show how this analysis can discern variations attributable to non-autonomous deterministic processes from stochastic fluctuations. The analyses are benchmarked using simulated and two different real datasets which have been shown to exhibit attractor dynamics. As an illustrative example, we focused on the analysis of the rat's frontal cortex ensemble dynamics during a decision-making task. Results suggest that, in line with recent hypotheses, rather than internal noise, it is the deterministic trend which most likely underlies

  15. Skeletogenic fate of zebrafish cranial and trunk neural crest.

    Directory of Open Access Journals (Sweden)

    Erika Kague

    Full Text Available The neural crest (NC is a major contributor to the vertebrate craniofacial skeleton, detailed in model organisms through embryological and genetic approaches, most notably in chick and mouse. Despite many similarities between these rather distant species, there are also distinct differences in the contribution of the NC, particularly to the calvariae of the skull. Lack of information about other vertebrate groups precludes an understanding of the evolutionary significance of these differences. Study of zebrafish craniofacial development has contributed substantially to understanding of cartilage and bone formation in teleosts, but there is currently little information on NC contribution to the zebrafish skeleton. Here, we employ a two-transgene system based on Cre recombinase to genetically label NC in the zebrafish. We demonstrate NC contribution to cells in the cranial ganglia and peripheral nervous system known to be NC-derived, as well as to a subset of myocardial cells. The indelible labeling also enables us to determine NC contribution to late-forming bones, including the calvariae. We confirm suspected NC origin of cartilage and bones of the viscerocranium, including cartilages such as the hyosymplectic and its replacement bones (hymandibula and symplectic and membranous bones such as the opercle. The cleithrum develops at the border of NC and mesoderm, and as an ancestral component of the pectoral girdle was predicted to be a hybrid bone composed of both NC and mesoderm tissues. However, we find no evidence of a NC contribution to the cleithrum. Similarly, in the vault of the skull, the parietal bones and the caudal portion of the frontal bones show no evidence of NC contribution. We also determine a NC origin for caudal fin lepidotrichia; the presumption is that these are derived from trunk NC, demonstrating that these cells have the ability to form bone during normal vertebrate development.

  16. Cleanliness of disposable vs nondisposable electrocardiography lead wires in children.

    Science.gov (United States)

    Addison, Nancy; Quatrara, Beth; Letzkus, Lisa; Strider, David; Rovnyak, Virginia; Syptak, Virginia; Fuzy, Lisa

    2014-09-01

    Mediastinitis costs hospitals thousands of dollars a year and increases the incidence of patient morbidity and mortality. No studies have been done to evaluate adenosine triphosphate (ATP) counts on disposable and nondisposable electrocardiography (ECG) lead wires in pediatric patients. To compare the cleanliness of disposable and nondisposable ECG lead wires in postoperative pediatric cardiac surgery patients by measuring the quantity of ATP (in relative luminescence units [RLUs]). ATP levels correlate with microbial cell counts and are used by institutions to assess hospital equipment and cleanliness. A prospective, randomized trial was initiated with approval from the institutional review board. Verbal consent was obtained from the parents/guardians for each patient. Trained nurses performed ATP swabs on the right and left upper ECG cables on postoperative days 1, 2, and 3. This study enrolled 51 patients. The disposable ECG lead wire ATP count on postoperative day 1 (median, 157 RLUs) was significantly lower (P disposable ECG lead wires (median, 200 RLUs) was also lower (P = .06) than the count for the nondisposable ECG lead wires (median, 453 RLUs). Results of this study support the use of disposable ECG lead wires in postoperative pediatric cardiac surgery patients for at least the first 48 hours as a direct strategy to reduce the ATP counts on ECG lead wires. ©2014 American Association of Critical-Care Nurses.

  17. Fibronectin promotes differentiation of neural crest progenitors endowed with smooth muscle cell potential

    International Nuclear Information System (INIS)

    Costa-Silva, Bruno; Coelho da Costa, Meline; Melo, Fernanda Rosene; Neves, Cynara Mendes; Alvarez-Silva, Marcio; Calloni, Giordano Wosgrau; Trentin, Andrea Goncalves

    2009-01-01

    The neural crest (NC) is a model system used to investigate multipotency during vertebrate development. Environmental factors control NC cell fate decisions. Despite the well-known influence of extracellular matrix molecules in NC cell migration, the issue of whether they also influence NC cell differentiation has not been addressed at the single cell level. By analyzing mass and clonal cultures of mouse cephalic and quail trunk NC cells, we show for the first time that fibronectin (FN) promotes differentiation into the smooth muscle cell phenotype without affecting differentiation into glia, neurons, and melanocytes. Time course analysis indicated that the FN-induced effect was not related to massive cell death or proliferation of smooth muscle cells. Finally, by comparing clonal cultures of quail trunk NC cells grown on FN and collagen type IV (CLIV), we found that FN strongly increased both NC cell survival and the proportion of unipotent and oligopotent NC progenitors endowed with smooth muscle potential. In contrast, melanocytic progenitors were prominent in clonogenic NC cells grown on CLIV. Taken together, these results show that FN promotes NC cell differentiation along the smooth muscle lineage, and therefore plays an important role in fate decisions of NC progenitor cells

  18. Size does matter – Intraspecific variation of feeding mechanics in the crested newt Triturus dobrogicus (Kiritzescu, 1903

    Directory of Open Access Journals (Sweden)

    Kucera Florian

    2018-03-01

    Full Text Available Many studies have yet been conducted on suction feeding in aquatic salamander species. Within the Salamandridae, the crested newt Triturus dobrogicus (Kiritzescu, 1903, occurring from the Austrian Danube floodplains to the Danube Delta, was not subject of investigations so far. The present study examines the kinematics of aquatic suction feeding in this species by means of high-speed videography. Recordings of five individuals of different size and sex while feeding on bloodworms were conducted, in order to identify potential discrepancies among individuals and sizes. Five coordinate points were digitized from recordings of prey capture and twelve time- and velocity-determined variables were evaluated. All specimens follow a typical inertial suction feeding process, where rapid hyoid depression expands the buccal cavity. Generated negative pressure within the buccal cavity causes influx of water along with the prey item into the mouth. Results demonstrate higher distance values and angles for gape in individuals with smaller size. In addition, hyoid depression is maximized in smaller individuals. While Triturus dobrogicus resembles a typical inertial suction feeder in its functional morphology, intraspecific differences could be found regarding the correlation of different feeding patterns and body size.

  19. Dataset of TWIST1-regulated genes in the cranial mesoderm and a transcriptome comparison of cranial mesoderm and cranial neural crest

    Directory of Open Access Journals (Sweden)

    Heidi Bildsoe

    2016-12-01

    Full Text Available This article contains data related to the research article entitled “Transcriptional targets of TWIST1 in the cranial mesoderm regulate cell-matrix interactions and mesenchyme maintenance” by Bildsoe et al. (2016 [1]. The data presented here are derived from: (1 a microarray-based comparison of sorted cranial mesoderm (CM and cranial neural crest (CNC cells from E9.5 mouse embryos; (2 comparisons of transcription profiles of head tissues from mouse embryos with a CM-specific loss-of-function of Twist1 and control mouse embryos collected at E8.5 and E9.5; (3 ChIP-seq using a TWIST1-specific monoclonal antibody with chromatin extracts from TWIST1-expressing MDCK cells, a model for a TWIST1-dependent mesenchymal state.

  20. The CYTONOX trial

    DEFF Research Database (Denmark)

    Gade, Christina; Mikus, Gerd; Christensen, Hanne Rolighed

    2016-01-01

    INTRODUCTION: In Denmark, it is estimated that 3-5% of children are obese. Obesity is associated with pathophysiological alterations that may lead to alterations in the pharmacokinetics of drugs. In adults, obesity was found to influence important drug-metabolising enzyme pathways. The impact...... of obesity-related alterations on drug metabolism and its consequences for drug dosing remains largely unknown in both children and adults. An altered drug metabolism may contribute significantly to therapeutic failure or toxicity. The aim of this trial is to investigate the in vivo activity of CYP3A4, CYP2E......1 and CYP1A2 substrates in obese versus non-obese children. METHODS: The CYTONOX trial is an open-label explorative pharmacokinetic trial. We intend to include 50 obese and 50 non-obese children. The primary end points are: in vivo clearance of CYP3A4, CYP2E1 and CYP1A2 substrates, which...

  1. Periodontal treatment to improve glycaemic control in diabetic patients: study protocol of the randomized, controlled DIAPERIO trial.

    Science.gov (United States)

    Vergnes, Jean-Noel; Arrivé, Elise; Gourdy, Pierre; Hanaire, Hélène; Rigalleau, Vincent; Gin, Henri; Sédarat, Cyril; Dorignac, Georges; Bou, Christophe; Sixou, Michel; Nabet, Cathy

    2009-08-02

    Periodontitis is a common, chronic inflammatory disease caused by gram-negative bacteria leading to destruction of tissues supporting the teeth. Epidemiological studies have consistently shown increased frequency, extent and severity of periodontitis among diabetic adults. More recently, some controlled clinical trials have also suggested that periodontal treatment could improve glycaemic control in diabetic patients. However current evidence does not provide sufficient information on which to confidently base any clinical recommendations. The main objective of this clinical trial is to assess whether periodontal treatment could lead to a decrease in glycated haemoglobin levels in metabolically unbalanced diabetic patients suffering from chronic periodontitis. The DIAPERIO trial is an open-label, 13-week follow-up, randomized, controlled trial. The total target sample size is planned at 150 participants, with a balanced (1:1) treatment allocation (immediate treatment vs delayed treatment). Periodontal treatment will include full mouth non-surgical scaling and root planing, systemic antibiotherapy, local antiseptics (chlorhexidine 0.12%) and oral health instructions. The primary outcome will be the difference in change of HbA1c between the two groups after the 13-weeks' follow-up. Secondary outcomes will be the difference in change of fructosamine levels and quality of life between the two groups. The DIAPERIO trial will provide insight into the question of whether periodontal treatment could lead to an improvement in glycaemic control in metabolically unbalanced diabetic patients suffering from periodontitis. The results of this trial will help to provide evidence-based recommendations for clinicians and a draft framework for designing national health policies. Current Controlled Trials ISRCTN15334496.

  2. Tissue stiffening coordinates morphogenesis by triggering collective cell migration in vivo.

    Science.gov (United States)

    Barriga, Elias H; Franze, Kristian; Charras, Guillaume; Mayor, Roberto

    2018-02-22

    Collective cell migration is essential for morphogenesis, tissue remodelling and cancer invasion. In vivo, groups of cells move in an orchestrated way through tissues. This movement involves mechanical as well as molecular interactions between cells and their environment. While the role of molecular signals in collective cell migration is comparatively well understood, how tissue mechanics influence collective cell migration in vivo remains unknown. Here we investigated the importance of mechanical cues in the collective migration of the Xenopus laevis neural crest cells, an embryonic cell population whose migratory behaviour has been likened to cancer invasion. We found that, during morphogenesis, the head mesoderm underlying the cephalic neural crest stiffens. This stiffening initiates an epithelial-to-mesenchymal transition in neural crest cells and triggers their collective migration. To detect changes in their mechanical environment, neural crest cells use mechanosensation mediated by the integrin-vinculin-talin complex. By performing mechanical and molecular manipulations, we show that mesoderm stiffening is necessary and sufficient to trigger neural crest migration. Finally, we demonstrate that convergent extension of the mesoderm, which starts during gastrulation, leads to increased mesoderm stiffness by increasing the cell density underneath the neural crest. These results show that convergent extension of the mesoderm has a role as a mechanical coordinator of morphogenesis, and reveal a link between two apparently unconnected processes-gastrulation and neural crest migration-via changes in tissue mechanics. Overall, we demonstrate that changes in substrate stiffness can trigger collective cell migration by promoting epithelial-to-mesenchymal transition in vivo. More broadly, our results raise the idea that tissue mechanics combines with molecular effectors to coordinate morphogenesis.

  3. An inter-laboratory trial of the unified BARGE bioaccessibility method for arsenic, cadmium and lead in soil

    International Nuclear Information System (INIS)

    Wragg, Joanna; Cave, Mark; Basta, Nick; Brandon, Esther; Casteel, Stan; Denys, Sebastien; Gron, Christian; Oomen, Agnes; Reimer, Kenneth; Tack, Karine; Van de Wiele, Tom

    2011-01-01

    The Bioaccessibility Research Group of Europe (BARGE) has carried out an inter-laboratory trial of a proposed harmonised in vitro physiologically based ingestion bioaccessibility procedure for soils, called the Unified BARGE Method (UBM). The UBM includes an initial saliva phase and simulated stomach and intestine compartments. The trial involved the participation of seven laboratories (five European and two North American) providing bioaccessibility data for As (11 samples), Cd (9 samples) and Pb (13 samples) using soils with in vivo relative bioavailability data measured using a swine model. The results of the study were compared with benchmark criteria for assessing the suitability of the UBM to provide data for human health risk assessments. Mine waste and slag soils containing high concentrations of As caused problems of poor repeatability and reproducibility which were alleviated when the samples were run at lower soil to solution ratios. The study showed that the UBM met the benchmark criteria for both the stomach and stomach and intestine phase for As. For Cd, three out of four criteria were met for the stomach phase but only one for the stomach and intestine phase. For Pb two, out of four criteria were met for the stomach phase and none for the stomach and intestine phase. However, the study recommends tighter control of pH in the stomach phase extraction to improve between-laboratory variability, more reproducible in vivo validation data and that a follow up inter-laboratory trial should be carried out.

  4. An inter-laboratory trial of the unified BARGE bioaccessibility method for arsenic, cadmium and lead in soil

    Energy Technology Data Exchange (ETDEWEB)

    Wragg, Joanna [British Geological Survey, Nottingham (United Kingdom); Cave, Mark, E-mail: mrca@bgs.ac.uk [British Geological Survey, Nottingham (United Kingdom); Basta, Nick [School of Environment and Natural Resources, Ohio State University, Columbus, OH, 43210-1085 (United States); Brandon, Esther [National Institute for Public Health and the Environment, Bilthoven (Netherlands); Casteel, Stan [College of Veterinary Medicine, University of Missouri, 65205 (United States); Denys, Sebastien [INERIS, Parc Technologique Alata, Verneuil-en-Halatte (France); Gron, Christian [DHI Water Environment Health, Horsholm (Denmark); Oomen, Agnes [National Institute for Public Health and the Environment, Bilthoven (Netherlands); Reimer, Kenneth [Environmental Sciences Group, Royal Military College of Canada, Kingston, Ontario (Canada); Tack, Karine [INERIS, Parc Technologique Alata, Verneuil-en-Halatte (France); Van de Wiele, Tom [Laboratory of Microbial Ecology and Technology, University of Ghent, Ghent (Belgium)

    2011-09-01

    The Bioaccessibility Research Group of Europe (BARGE) has carried out an inter-laboratory trial of a proposed harmonised in vitro physiologically based ingestion bioaccessibility procedure for soils, called the Unified BARGE Method (UBM). The UBM includes an initial saliva phase and simulated stomach and intestine compartments. The trial involved the participation of seven laboratories (five European and two North American) providing bioaccessibility data for As (11 samples), Cd (9 samples) and Pb (13 samples) using soils with in vivo relative bioavailability data measured using a swine model. The results of the study were compared with benchmark criteria for assessing the suitability of the UBM to provide data for human health risk assessments. Mine waste and slag soils containing high concentrations of As caused problems of poor repeatability and reproducibility which were alleviated when the samples were run at lower soil to solution ratios. The study showed that the UBM met the benchmark criteria for both the stomach and stomach and intestine phase for As. For Cd, three out of four criteria were met for the stomach phase but only one for the stomach and intestine phase. For Pb two, out of four criteria were met for the stomach phase and none for the stomach and intestine phase. However, the study recommends tighter control of pH in the stomach phase extraction to improve between-laboratory variability, more reproducible in vivo validation data and that a follow up inter-laboratory trial should be carried out.

  5. Phytoextraction trials of cadmium and lead contaminated soil using ...

    African Journals Online (AJOL)

    Study on the phytoextraction of cadmium (Cd) and lead (Pb) artificially contaminated soil using 3 weed species (Ageratum conyzoides, Syndrella nodiflora and Cleome rutidosperma) was carried out at the Centre for Ecological Studies, University of Port Harcourt. A Randomized Complete Block Design consisting of 2 sets of ...

  6. Mexican-American perspectives on participation in clinical trials: A qualitative study

    Directory of Open Access Journals (Sweden)

    Mariana Arevalo

    2016-12-01

    Full Text Available Clinical trials are essential to advancing knowledge to reduce disease morbidity and mortality; however, ethnic and racial minorities remain under-represented in those studies. We explored knowledge and perceptions of clinical trials among Mexican-Americans in Texas. We conducted focus groups (N = 128 stratified by gender, language preference, and geographical location. This paper presents four emergent, primary themes: 1 knowledge and understanding of clinical trials, 2 fears and concerns about participating, 3 perceived benefits of participating, and 4 incentives to participate. Results suggest that lack of knowledge and understanding of clinical trials leads to misunderstanding about research, including fears and lack of trust. Participants indicated that fears related to perceived experimentation, harm, immigration status, and lack of clinical trial opportunities within their communities were barriers to participation. On the other hand, free healthcare access, helping family members in the future, and monetary incentives could facilitate participation. We also found differences across themes by language, gender, and place of residence. Findings from our study could inform the development of interventions to enhance recruitment of Mexican-American participants into clinical trials.

  7. Evaluation of home lead remediation in an Australian mining community.

    Science.gov (United States)

    Boreland, F; Lesjak, M; Lyle, D

    2009-12-20

    In 1994 a comprehensive program was established to reduce children's blood lead levels in Broken Hill, NSW, Australia. Home remediation (abatement of lead hazards in a child's home) was included as part of a case management strategy for children with blood lead levels >or=15 microg/dL. Children with blood lead levels >or=30 microg/dL were offered immediate home remediation. Children with blood lead levels of 15-29 microg/dL were allocated to 'immediate' or 'delayed' home remediation; a subset of these participated in a randomized controlled trial (RCT) to evaluate the effectiveness of home remediation for reducing blood lead levels. One hundred and seventeen children received home remediation. One hundred and thirteen returned for follow-up blood tests, 88 of whom participated in the RCT. On average children's blood lead levels decreased by 1.7 microg/dL (10%) in the 6 months after remediation and by 2.2 microg/dL (13%) in the 6-12 months after remediation. However, remediation did not significantly change the rate of decline in blood lead levels (P=0.609). There was no evidence of association between change in children's blood lead levels and changes in lead loading in their homes. The results are consistent with the published literature, which suggests that home remediation does not reduce children's exposure to lead sufficiently to cause a moderate or greater decrease in their blood lead level. In communities where lead is widely dispersed, the study suggests that it is important to assess potential sources and pathways by which children are exposed to lead when developing an intervention plan, and the need for multiple interventions to effectively reduce blood lead levels. The findings reinforce the ongoing need for rigorous epidemiological evaluation of lead management programs to improve the evidence base, and for effective primary prevention to avoid children being exposed to lead in the first place.

  8. Two-Stage Surgical Management of Multilevel Symptomatic Thoracic Haemangioma Using Ethanol and Iliac Crest Bone Graft

    Science.gov (United States)

    Brahmajoshyula, Venkatramana; Mayi, Shivanand; Teegala, Suman

    2014-01-01

    This article presents a 56-year-old obese female who presented with back pain and progressive weakness in her lower limbs for three months. She was bed-ridden for one week before reporting to our hospital. Plain radiographs showed vertical striations in multiple vertebrae classical of haemangioma. Magnetic resonance imaging (MRI) spine revealed multiple thoracic and lumbar vertebral haemangiomas. Extra osseous extension of haemangioma at T12 was causing spinal cord compression. Two-stage surgery was performed with absolute alcohol (ethanol) injection followed by pedicle screw fixation and decompression with tricortical iliac crest bone graft into the vertebral body. Postoperatively rapid neurological improvement was seen. After three weeks, she could walk independently. One year later, computed tomography showed complete incorporation of bone graft and maintained vertebral body height. MRI showed complete resolution of the cord edema at T12. These findings indicated diminished vascularity of the tumor. PMID:25187869

  9. [What can we expect from clinical trials in psychiatry?

    Science.gov (United States)

    Marsot, A; Boucherie, Q; Kheloufi, F; Riff, C; Braunstein, D; Dupouey, J; Guilhaumou, R; Zendjidjian, X; Bonin-Guillaume, S; Fakra, E; Guye, M; Jirsa, V; Azorin, J-M; Belzeaux, R; Adida, M; Micallef, J; Blin, O

    2016-12-01

    Clinical trials in psychiatry allow to build the regulatory dossiers for market authorization but also to document the mechanism of action of new drugs, to build pharmacodynamics models, evaluate the treatment effects, propose prognosis, efficacy or tolerability biomarkers and altogether to assess the impact of drugs for patient, caregiver and society. However, clinical trials have shown some limitations. Number of recent dossiers failed to convince the regulators. The clinical and biological heterogeneity of psychiatric disorders, the pharmacokinetic and pharmacodynamics properties of the compounds, the lack of translatable biomarkers possibly explain these difficulties. Several breakthrough options are now available: quantitative system pharmacology analysis of drug effects variability, pharmacometry and pharmacoepidemiology, Big Data analysis, brain modelling. In addition to more classical approaches, these opportunities lead to a paradigm change for clinical trials in psychiatry. © L’Encéphale, Paris, 2016.

  10. Clinical trials in dentistry in India: Analysis from trial registry.

    Science.gov (United States)

    Gowri, S; Kannan, Sridharan

    2017-01-01

    Evidence-based practice requires clinical trials to be performed. In India, if any clinical trial has to be performed, it has to be registered with clinical trial registry of India. Studies have shown that the report of clinical trials is poor in dentistry. Hence, the present study has been conducted to assess the type and trends of clinical trials being undertaken in dentistry in India over a span of 6 years. All the clinical trials which were registered with the Central Trial Registry of India (CTRI) (www.ctri.nic.in) from January 1, 2007 to March 3, 2014 were evaluated using the keyword "dental." Following information were collected for each of the clinical trials obtained from the search; number of centres (single center/multicentric), type of the institution undertaking the research (government/private/combined), study (observational/interventional), study design (randomized/single blinded/double-blinded), type of health condition, type of participants (healthy/patients), sponsors (academia/commercial), phase of clinical trial (Phase 1/2/3/4), publication details (published/not published), whether it was a postgraduate thesis or not and prospective or retrospective registration of clinical trials, methodological quality (method of randomization, allocation concealment). Descriptive statistics was used for analysis of various categories. Trend analysis was done to assess the changes over a period of time. The search yielded a total of 84 trials of which majority of them were single centered. Considering the study design more than half of the registered clinical trials were double-blinded (47/84 [56%]). With regard to the place of conducting a trial, most of the trials were planned to be performed in private hospitals (56/84 [66.7%]). Most (79/84, 94.1%) of the clinical trials were interventional while only 5/84 (5.9%) were observational. Majority (65/84, 77.4%) of the registered clinical trials were recruiting patients while the rest were being done in healthy

  11. Leading Wave Amplitude of a Tsunami

    Science.gov (United States)

    Kanoglu, U.

    2015-12-01

    Okal and Synolakis (EGU General Assembly 2015, Geophysical Research Abstracts-Vol. 17-7622) recently discussed that why the maximum amplitude of a tsunami might not occur for the first wave. Okal and Synolakis list observations from 2011 Japan tsunami, which reached to Papeete, Tahiti with a fourth wave being largest and 72 min later after the first wave; 1960 Chilean tsunami reached Hilo, Hawaii with a maximum wave arriving 1 hour later with a height of 5m, first wave being only 1.2m. Largest later waves is a problem not only for local authorities both in terms of warning to the public and rescue efforts but also mislead the public thinking that it is safe to return shoreline or evacuated site after arrival of the first wave. Okal and Synolakis considered Hammack's (1972, Ph.D. Dissertation, Calif. Inst. Tech., 261 pp., Pasadena) linear dispersive analytical solution with a tsunami generation through an uplifting of a circular plug on the ocean floor. They performed parametric study for the radius of the plug and the depth of the ocean since these are the independent scaling lengths in the problem. They identified transition distance, as the second wave being larger, regarding the parameters of the problem. Here, we extend their analysis to an initial wave field with a finite crest length and, in addition, to a most common tsunami initial wave form of N-wave as presented by Tadepalli and Synolakis (1994, Proc. R. Soc. A: Math. Phys. Eng. Sci., 445, 99-112). We compare our results with non-dispersive linear shallow water wave results as presented by Kanoglu et al. (2013, Proc. R. Soc. A: Math. Phys. Eng. Sci., 469, 20130015), investigating focusing feature. We discuss the results both in terms of leading wave amplitude and tsunami focusing. Acknowledgment: The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no 603839 (Project ASTARTE - Assessment, Strategy and Risk

  12. Geometric interpretation of the ratio of overall diameter to rim crest diameter for lunar and terrestrial craters.

    Science.gov (United States)

    Siegal, B. S.; Wickman, F. E.

    1973-01-01

    An empirical linear relationship has been established by Pike (1967) between the overall diameter and the rim crest diameter for rimmed, flat-floored as well as bowl-shaped, lunar and terrestrial craters formed by impact and explosion. A similar relationship for experimentally formed fluidization craters has been established by Siegal (1971). This relationship is examined in terms of the geometry of the crater and the slope angles of loose materials. The parameter varies from 1.40 to 1.65 and is found to be dependent on mean interior flat floor radius, exterior and interior rim slope angles, angle of aperture of the crater cone, and the volume fraction of crater void accounted for in the rim. The range of the observed parameter can be understood in terms of simple crater geometry by realistic values of the five parameters.

  13. The SWI/SNF BAF-A complex is essential for neural crest development.

    Science.gov (United States)

    Chandler, Ronald L; Magnuson, Terry

    2016-03-01

    Growing evidence indicates that chromatin remodeler mutations underlie the pathogenesis of human neurocristopathies or disorders that affect neural crest cells (NCCs). However, causal relationships among chromatin remodeler subunit mutations and NCC defects remain poorly understood. Here we show that homozygous loss of ARID1A-containing, SWI/SNF chromatin remodeling complexes (BAF-A) in NCCs results in embryonic lethality in mice, with mutant embryos succumbing to heart defects. Strikingly, monoallelic loss of ARID1A in NCCs led to craniofacial defects in adult mice, including shortened snouts and low set ears, and these defects were more pronounced following homozygous loss of ARID1A, with the ventral cranial bones being greatly reduced in size. Early NCC specification and expression of the BRG1 NCC target gene, PLEXINA2, occurred normally in the absence of ARID1A. Nonetheless, mutant embryos displayed incomplete conotruncal septation of the cardiac outflow tract and defects in the posterior pharyngeal arteries, culminating in persistent truncus arteriosus and agenesis of the ductus arteriosus. Consistent with this, migrating cardiac NCCs underwent apoptosis within the circumpharyngeal ridge. Our data support the notion that multiple, distinct chromatin remodeling complexes govern genetically separable events in NCC development and highlight a potential pathogenic role for NCCs in the human BAF complex disorder, Coffin-Siris Syndrome. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. The Tendency of the Crest Factor Helps Detect Nascent Events; Electronic Circuit, Software and Applications to Signals from Diverse Fields

    Directory of Open Access Journals (Sweden)

    Núñez-Pérez Ricardo Francisco

    2014-04-01

    Full Text Available Within the signal analysis techniques in the time domain, the crest factor (CF is undoubtedly one of the most simple and fast to implement using electronic circuits and/or software. That's why it has been used reliably to care for machinery and to evaluate the quality of supply. One of the major manufacturers of instruments for these purposes is Bruel and Kjaer and defines the crest factor of voltage or repetitive current signal as the ratio of the peak level and its rms value during a certain period of time. In this paper, we try to find out experimentally the potential of CF and their tendency to detect the nascent and evolution of events in various fields of knowledge, either by generating it with a developed electronic circuit, or with calculations, through routines that are performed with the programs DADISP and LabVIEW. The results are validated and checked for all the above factors and trends through a comparison between them and the proposed features and specifications. The results were acceptable so that the tools were applied to detect early faults in electrical machines, to identify chaosity differences between the circuits with these dynamics, to detect abnormal respiratory distress or rales in patients and to detect harmful distortions in the electrical current, all this based on simulations and measurements for each of the 4 cases studied. Other CF original applications proposed are: a control of chaos in electronic circuits that stir/ mix industrial processes and b correct the power factor of non-linear and inductive loads. A medium-term study and use a CF that considers the maximum signal peak to peak is contemplated, and it is thought that it can improve event detection

  15. Influence of reported study design characteristics on intervention effect estimates from randomized, controlled trials

    DEFF Research Database (Denmark)

    Savović, Jelena; Jones, Hayley E; Altman, Douglas G

    2012-01-01

    bias and increases in between-trial heterogeneity were driven primarily by trials with subjective outcomes, with little evidence of bias in trials with objective and mortality outcomes. This study is limited by incomplete trial reporting, and findings may be confounded by other study design...... characteristics. Bias associated with study design characteristics may lead to exaggeration of intervention effect estimates and increases in between-trial heterogeneity in trials reporting subjectively assessed outcomes....

  16. Participant recruitment and retention in longitudinal preconception randomized trials: lessons learnt from the Calcium And Pre-eclampsia (CAP) trial.

    Science.gov (United States)

    Lawrie, Theresa A; Betrán, Ana Pilar; Singata-Madliki, Mandisa; Ciganda, Alvaro; Hofmeyr, G Justus; Belizán, José M; Purnat, Tina Dannemann; Manyame, Sarah; Parker, Catherine; Cormick, Gabriela

    2017-10-26

    The preconception period has the potential to influence pregnancy outcomes and randomized controlled trials (RCTs) are needed to evaluate a variety of potentially beneficial preconception interventions. However, RCTs commencing before pregnancy have significant participant recruitment and retention challenges. The Calcium And Pre-eclampsia trial (CAP trial) is a World Health Organization multi-country RCT of calcium supplementation commenced before pregnancy to prevent recurrent pre-eclampsia in which non-pregnant participants are recruited and followed up until childbirth. This sub-study explores recruitment methods and preconception retention of participants of the CAP trial to inform future trials. Recruiters at the study sites in Argentina, South Africa and Zimbabwe completed post-recruitment phase questionnaires on recruitment methods used. Qualitative data from these questionnaires and quantitative data on pre-pregnancy trial visit attendance and pregnancy rates up to September 2016 are reported in this paper. RStudio (Version 0.99.903 https://www.rstudio.org ) statistical software was used for summary statistics. Between July 2011 and 8 September 2016, 1354 women with previous pre-eclampsia were recruited. Recruitment took 2 years longer than expected and was facilitated mainly through medical record/register and maternity ward/clinic-based strategies. Recruiters highlighted difficulties associated with inadequate medical records, redundant patient contact details, and follow-up of temporarily ineligible women as some of the challenges faced. Whilst the attendance rates at pre-pregnancy visits were high (78% or more), visits often occurred later than scheduled. Forty-five percent of participants became pregnant (614/1354), 33.5% (454/1354) within 1 year of randomization. In preconception trials, both retrospective and prospective methods are useful for recruiting eligible women with certain conditions. However, these are time-consuming in low

  17. Occipital cephalocele with neural crest remnants? Radiological and pathological findings in a newborn boy.

    Science.gov (United States)

    Arishima, Hidetaka; Neishi, Hiroyuki; Kikuta, Ken-Ichiro

    2016-06-01

    A cephalocele is a congenital anomaly involving the herniation of intracranial tissue from a skull defect. The sac containing the central nervous system (CNS) with the ventricle system is called the encephalocystocele. An atretic cephalocele is thought to be an abortive form of cephalocele, and the essential nature is still controversial. Here, we report the case of a newborn boy with an occipital cephalocele containing a small cystic component which was composed of ependymal cells and the immature CNS tissue. A newborn boy was admitted to our hospital because of an occipital mass, which was about 2.5 cm in diameter, located at the posterior midline, and covered with alopetic skin without CSF leakage. He had a cleft palate. Magnetic resonance imaging (MRI) clearly showed an occipital cephalocele with a tiny cystic component connecting to the subarachnoid space. MRI also showed mild hydrocephalus, hypoplasia of the corpus callosum and tentorium cerebelli, dropping down of the bilateral occipital lobes and vermicular agenesis. We performed the extirpation of the subscalp module under general anesthesia and histologically examined the resected mass. On immunohistopathological examination, most part of the subscalp module was fibrous tissue with numerous vessels and meningeal origin cells. In a small part of the innermost layer, we found a small island consisting of CNS tissue and a tiny cyst lined with a single layer of ependymal cells. Based on radiological and immunohistopathological findings, we speculate that the cystic component at the base of the nodule seems to correspond to neural crest remnants but not to true herniation of the brain and cerebral ventricles.

  18. Ultrastructural study of liver and lead tissue concentrations in young mallard ducks (Anas platyrhynchos) after ingestion of single lead shot.

    Science.gov (United States)

    Pineau, Alain; Fauconneau, Bernard; Plouzeau, Eric; Fernandez, Béatrice; Quellard, Nathalie; Levillain, Pierre; Guillard, Olivier

    2017-01-01

    Lead (Pb) represents a serious threat to wildlife and ecosystems. The aim of this study was to examine the subcellular effects of dietary Pb pellet ingestion on mallard (Anas platyrhynchos) livers. After ingestion of a single Pb shot (LS4 size class: 0.177 ± 0.03 g) in 41 mallard ducks (22 males and 19 females) versus 10 controls (5 males and 5 females), all 7-week old, a morphologic study was conducted by TEM (transmission electron microscopy) of liver at the subcellular level. The results in treated mallards showed at a magnification of 2500 X that hepatic parenchyma was altered as evidenced by intralysosomal electron-dense deposits, which are compatible with Pb deposits. Further, at a higher magnification (15,000 X) in both genders, deterioration of mitochondria was observed in which the crests and, to a lesser extent, outer membrane were lysed. While the rough endoplasmic reticulum was fragmented, intracytoplasmic electron-dense material compatible with Pb deposits was maximally visible, thereby underscoring the deeply destructive effect of this metal on the subcellular architecture of the liver. In addition, applying an optimized and validated method in a clean room using electrothermal atomic absorption spectrophotometer (ETAAS) with Zeeman background correction, the objective was to improve and refine certain indispensable measurements pertaining to Pb impregnation in tissues other than liver such as kidneys, bones, and feathers of mallards. Data demonstrated show that compared with controls, Pb accumulation increases significantly, not only in the liver (3-fold), but also in the bones and the feathers (14-fold). No significant difference was noted between males and females. Bearing in mind the marked subcellular toxicity attributed to Pb, this study reinforces present-day arguments advocating limitation of game consumption.

  19. Coastal defence through low crested breakwater structures: jumping out of the frying pan into the fire?

    Science.gov (United States)

    Munari, Cristina; Corbau, Corinne; Simeoni, Umberto; Mistri, Michele

    2011-08-01

    The Adriatic coast of Punta Marina (Ravenna) is protected by 3-km long low crested breakwater structures (LCSs). Through a 3-years long multidisciplinar study, we assessed the impact of such defensive structures on environmental and biological condition. LCSs create pools where conditions are very different from the surrounding nearshore system. Mechanical disturbance by currents and waves varied greatly in intensity and frequency between seaward and landward sides of the structures. Sedimentary budget was positive at the landward side, but it was due to a gain on the seafloor and not on the emerged beach. The budget at seaward was negative. LCSs determine differences in benthic assemblages, alter the seasonal pattern of communities, and modify seasonal fluctuations of animal assemblages. Landward sheltered areas can be seen as "lagoonal island" surrounded by a "sea of marine habitat". Differences in ecological quality status, obtained through M-AMBI, are due to the sum of these factors. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. CpG plus radiotherapy: a review of preclinical works leading to clinical trial

    Energy Technology Data Exchange (ETDEWEB)

    Mason, Kathy A.; Hunter, Nancy R., E-mail: kmason@mdanderson.org [Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States)

    2012-08-14

    Studies performed three decades ago in our laboratory supported the hypothesis that radiation efficacy may be augmented by bacterial extracts that stimulate non-specific systemic antitumor immune responses. Application to the clinic was halted by unacceptable side effects and toxicities resulting from exposure to whole bacterial pathogens. Later scientific advances demonstrated that DNA isolated from bacteria was immunostimulatory and could be reproduced with synthetic oligodeoxynucleotides (ODNs), thus fueling the transition from bugs to drugs. Unmethylated CpG motifs within bacterial DNA induce activation of Toll-like receptor 9 and subsequently activate antigen-specific cellular immune responses. CpG ODNs have demonstrated favorable toxicity profiles in phase I clinical trials. We showed that this potent immunoadjuvant can be used in combination with radiation therapy to enhance local and systemic responses of several murine tumors. Studies demonstrated that enhanced tumor response is mediated in part by the host immune system. Antitumor efficacy was diminished in immunocompromised mice. Animals cured by combination of radiation and CpG ODN were resistant to subsequent tumor rechallenge. This body of work contributes to our understanding of the dynamic interplay between tumor irradiation and the host immune system and may facilitate translation to clinical trials.

  1. CpG plus radiotherapy: a review of preclinical works leading to clinical trial

    International Nuclear Information System (INIS)

    Mason, Kathy A.; Hunter, Nancy R.

    2012-01-01

    Studies performed three decades ago in our laboratory supported the hypothesis that radiation efficacy may be augmented by bacterial extracts that stimulate non-specific systemic antitumor immune responses. Application to the clinic was halted by unacceptable side effects and toxicities resulting from exposure to whole bacterial pathogens. Later scientific advances demonstrated that DNA isolated from bacteria was immunostimulatory and could be reproduced with synthetic oligodeoxynucleotides (ODNs), thus fueling the transition from bugs to drugs. Unmethylated CpG motifs within bacterial DNA induce activation of Toll-like receptor 9 and subsequently activate antigen-specific cellular immune responses. CpG ODNs have demonstrated favorable toxicity profiles in phase I clinical trials. We showed that this potent immunoadjuvant can be used in combination with radiation therapy to enhance local and systemic responses of several murine tumors. Studies demonstrated that enhanced tumor response is mediated in part by the host immune system. Antitumor efficacy was diminished in immunocompromised mice. Animals cured by combination of radiation and CpG ODN were resistant to subsequent tumor rechallenge. This body of work contributes to our understanding of the dynamic interplay between tumor irradiation and the host immune system and may facilitate translation to clinical trials.

  2. Anterior cervical discectomy and fusion with "mini-invasive" harvesting of iliac crest graft versus polyetheretherketone (PEEK) cages: a retrospective outcome analysis.

    Science.gov (United States)

    Spallone, A; Marchione, P; Li Voti, P; Ferrante, L; Visocchi, M

    2014-12-01

    Limited outcome data suggested a minimal evidence for better clinical and radiographic outcome of polyetheretherketone cages compared with bone grafts in the anterior cervical discectomy and fusion. We proposed a "mini-invasive" surgical technique for harvesting iliac crest grafts that provides bicortical autografts of sufficient size to be used in multilevel cervical procedures and is not associated with long-term significant donor site pain. All patients undergoing discectomy and fusion during a three years period were consecutively extracted from computer database and retrospectively evaluated by means of telephonic interview, independently from surgical procedure (iliac crest autograph or prosthesis). Two procedure-blinded neurologists retrieved baseline clinical-demographic data and pre-surgical scores of routinely performed scales for pain and functional abilities. Afterwards, a third blinded neurologist performed clinical follow up by a semi-structured interview including Verbal Analog Scale for pain and Neck Disability Scale for discomfort. 80 patients out of 115 selected cases completed the follow up. 40 patients had been treated by mini-invasive bone graft harvesting and 40 with PEEK cages for cervical fusion. VAS for both neck and arm pain were significantly reduced within groups. Patients did not complaint any significant pain and/or paraesthesias at donor site from the first week after intervention. Neck Disability Scale was significantly lower at the end of follow up in both groups. "Miniinvasive" bicortical autografts is a less invasive, inexpensive technique to harvest iliac graft that may produce a reduced amount of general and local donor-site complications without outcome differences with prosthetic cages. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

  3. In vivo x-ray fluorescence of bone lead in the study of human lead metabolism: Serum lead, whole blood lead, bone lead, and cumulative exposure

    International Nuclear Information System (INIS)

    Cake, K.M.; Chettle, D.R.; Webber, C.E.; Gordon, C.L.

    1995-01-01

    Traditionally, clinical studies of lead's effect on health have relied on blood lead levels to indicate lead exposure. However, this is unsatisfactory because blood lead levels have a half-life of approximately 5 weeks, and thus reflect recent exposure. Over 90% of the lead body burden is in bone, and it is thought to have a long residence time, thus implying that measurements of bone lead reflect cumulative exposure. So, measurements of bone lead are useful in understanding the long-term health effects of lead. Ahlgren reported the first noninvasive measurements of bone lead in humans, where γ-rays from 57 Co were used to excite the K series x-rays of lead. The lead detection system at McMaster University uses a 109 Cd source which is positioned at the center of the detector face (HPGe) and a near backscatter (∼160 degrees) geometry. This arrangement allows great flexibility, since one can sample lead in a range of different bone sites due to a robust normalization technique which eliminates the need to correct for bone geometry, thickness of overlying tissue, and other related factors. The effective radiation dose to an adult during an x-ray fluorescence bone lead measurement is extremely low, being 35 nSv. This paper addresses the issue of how bone, whole blood, and serum lead concentrations can be related in order to understand a person's lead exposure history

  4. Right on Post-trial Access to Investigational Treatment

    Directory of Open Access Journals (Sweden)

    Dmytro Lurye

    2018-03-01

    On this base, the author offered to provide in the legislation of Ukraine requirements to inform in advance subjects about the presence or absence of post-trial access and to evaluate these provisions by ethics committees before and at the end of all trials in order to determine its real need in each individual case. The scope of the right on post-trial access to investigational treatment must be reasonably weighed in order to avoid, on the one hand, becoming an excessive stimulus for the subjects, and, on the other hand, not leading to a situation where on such regulation conducting of clinical trials in the country will no longer be appropriate.

  5. Factors influencing participation of psychiatry inpatients in clinical trials.

    Science.gov (United States)

    Mopuru, Nandeeshwar Reddy; Jose, Sam Padamadan; Viswanath, Biju; Kumar, C Naveen; Math, Suresh Bada; Thirthalli, Jagadisha

    2018-02-01

    Serious concerns have arisen in recent years regarding the unethical and illegal practices resorted to during clinical trials. Clinical trials in psychiatry are further complicated by issues such as 'validity of consent' and 'decision making capacity' of patients. This study was planned to explore the factors determining patient participation in clinical trials. A random sample of 123 consenting psychiatry inpatients were provided the information and consent-form of a hypothetical clinical drug trial. They were interviewed regarding their decision, the decision maker and factors that led to the decision. Family members tended to be the decision makers when patients were females, had low-income, were from rural background or had severe illnesses. Anticipated side effects and not wanting to interfere with existing treatment were the common reasons for refusal to participate while hope of betterment of the patient and benefit to humanity were cited for consent. The educated, urban, affluent class had more awareness regarding unethical trials and tended to be mistrustful of the medical community leading to higher rates of non-participation. Those who were adherent with ongoing treatment were also unwilling to participate. The lesser educated, low-income patients and rural domicile patients on the other hand had lesser awareness regarding clinical trials, trusted doctors and were more likely to participate. A good doctor-patient relationship, detailed explanations and clarification regarding the study and its conduct, and building awareness regarding clinical trials among vulnerable groups is necessary to ensure a valid consent involving no coercion, removal of prejudices, and ethical conduct of trials. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Robustness assessments are needed to reduce bias in meta-analyses that include zero-event randomized trials

    DEFF Research Database (Denmark)

    Keus, F; Wetterslev, J; Gluud, C

    2009-01-01

    of statistical method on inference. RESULTS: In seven meta-analyses of seven outcomes from 15 trials, there were zero-event trials in 0 to 71.4% of the trials. We found inconsistency in significance in one of seven outcomes (14%; 95% confidence limit 0.4%-57.9%). There was also considerable variability......OBJECTIVES: Meta-analysis of randomized trials with binary data can use a variety of statistical methods. Zero-event trials may create analytic problems. We explored how different methods may impact inferences from meta-analyses containing zero-event trials. METHODS: Five levels of statistical...... methods are identified for meta-analysis with zero-event trials, leading to numerous data analyses. We used the binary outcomes from our Cochrane review of randomized trials of laparoscopic vs. small-incision cholecystectomy for patients with symptomatic cholecystolithiasis to illustrate the influence...

  7. Spatiotemporal height variations of large-scale bedforms in the Grådyb tidal inlet channel (Denmark): a case study on coastal system impact

    DEFF Research Database (Denmark)

    Ernstsen, Verner Brandbyge; Lefebvre, Alice; Bartholdy, Jesper

    2011-01-01

    material, potentially leading to lowering of the crests. Potentially, this lead to a decreasing strength of the reverse flows within the recirculation cell in the lee of the bedforms, reducing reverse flow erosivity, and resulting in accretion of the troughs. With the scour hole refilled in 2008...

  8. Protocol of the Definition for the Assessment of Time-to-event Endpoints in CANcer trials (DATECAN) project: formal consensus method for the development of guidelines for standardised time-to-event endpoints' definitions in cancer clinical trials.

    Science.gov (United States)

    Bellera, Carine A; Pulido, Marina; Gourgou, Sophie; Collette, Laurence; Doussau, Adélaïde; Kramar, Andrew; Dabakuyo, Tienhan Sandrine; Ouali, Monia; Auperin, Anne; Filleron, Thomas; Fortpied, Catherine; Le Tourneau, Christophe; Paoletti, Xavier; Mauer, Murielle; Mathoulin-Pélissier, Simone; Bonnetain, Franck

    2013-03-01

    In randomised phase III cancer clinical trials, the most objectively defined and only validated time-to-event endpoint is overall survival (OS). The appearance of new types of treatments and the multiplication of lines of treatment have resulted in the use of surrogate endpoints for overall survival such as progression-free survival (PFS), or time-to-treatment failure. Their development is strongly influenced by the necessity of reducing clinical trial duration, cost and number of patients. However, while these endpoints are frequently used, they are often poorly defined and definitions can differ between trials which may limit their use as primary endpoints. Moreover, this variability of definitions can impact on the trial's results by affecting estimation of treatments' effects. The aim of the Definition for the Assessment of Time-to-event Endpoints in CANcer trials (DATECAN) project is to provide recommendations for standardised definitions of time-to-event endpoints in randomised cancer clinical trials. We will use a formal consensus methodology based on experts' opinions which will be obtained in a systematic manner. Definitions will be independently developed for several cancer sites, including pancreatic, breast, head and neck and colon cancer, as well as sarcomas and gastrointestinal stromal tumours (GISTs). The DATECAN project should lead to the elaboration of recommendations that can then be used as guidelines by researchers participating in clinical trials. This process should lead to a standardisation of the definitions of commonly used time-to-event endpoints, enabling appropriate comparisons of future trials' results. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Evaluating Protocol Lifecycle Time Intervals in HIV/AIDS Clinical Trials

    Science.gov (United States)

    Schouten, Jeffrey T.; Dixon, Dennis; Varghese, Suresh; Cope, Marie T.; Marci, Joe; Kagan, Jonathan M.

    2014-01-01

    Background Identifying efficacious interventions for the prevention and treatment of human diseases depends on the efficient development and implementation of controlled clinical trials. Essential to reducing the time and burden of completing the clinical trial lifecycle is determining which aspects take the longest, delay other stages, and may lead to better resource utilization without diminishing scientific quality, safety, or the protection of human subjects. Purpose In this study we modeled time-to-event data to explore relationships between clinical trial protocol development and implementation times, as well as identify potential correlates of prolonged development and implementation. Methods We obtained time interval and participant accrual data from 111 interventional clinical trials initiated between 2006 and 2011 by NIH’s HIV/AIDS Clinical Trials Networks. We determined the time (in days) required to complete defined phases of clinical trial protocol development and implementation. Kaplan-Meier estimates were used to assess the rates at which protocols reached specified terminal events, stratified by study purpose (therapeutic, prevention) and phase group (pilot/phase I, phase II, and phase III/ IV). We also examined several potential correlates to prolonged development and implementation intervals. Results Even though phase grouping did not determine development or implementation times of either therapeutic or prevention studies, overall we observed wide variation in protocol development times. Moreover, we detected a trend toward phase III/IV therapeutic protocols exhibiting longer developmental (median 2 ½ years) and implementation times (>3years). We also found that protocols exceeding the median number of days for completing the development interval had significantly longer implementation. Limitations The use of a relatively small set of protocols may have limited our ability to detect differences across phase groupings. Some timing effects

  10. The effect of the publication of a major clinical trial in a high impact journal on clinical practise: the ORACLE Trial experience.

    Science.gov (United States)

    Kenyon, Sara; Taylor, David J

    2002-12-01

    To estimate the short term effect of the publication of a major clinical trial on clinical practise. Questionnaire survey of clinical practise. UK. All maternity units in the UK. A self-administered questionnaire completed by lead consultants on delivery suite of maternity units. Changes in antibiotic prescription. Within six months of publication, approximately 50% of maternity units had changed their guidelines for the care of women with preterm prelabour rupture of the fetal membranes. Publication of a major clinical trial does impact on clinical practise but the impact is heterogeneous in terms of time and consistency.

  11. Sequential Multiple Assignment Randomized Trials: An Opportunity for Improved Design of Stroke Reperfusion Trials.

    Science.gov (United States)

    Meurer, William J; Seewald, Nicholas J; Kidwell, Kelley

    2017-04-01

    Modern clinical trials in stroke reperfusion fall into 2 categories: alternative systemic pharmacological regimens to alteplase and "rescue" endovascular approaches using targeted thrombectomy devices and/or medications delivered directly for persistently occluded vessels. Clinical trials in stroke have not evaluated how initial pharmacological thrombolytic management might influence subsequent rescue strategy. A sequential multiple assignment randomized trial (SMART) is a novel trial design that can test these dynamic treatment regimens and lead to treatment guidelines that more closely mimic practice. To characterize a SMART design in comparison to traditional approaches for stroke reperfusion trials. We conducted a numerical simulation study that evaluated the performance of contrasting acute stroke clinical trial designs of both initial reperfusion and rescue therapy. We compare a SMART design where the same patients are followed through initial reperfusion and rescue therapy within 1 trial to a standard phase III design comparing 2 reperfusion treatments and a separate phase II futility design of rescue therapy in terms of sample size, power, and ability to address particular research questions. Traditional trial designs can be well powered and have optimal design characteristics for independent treatment effects. When treatments, such as the reperfusion and rescue therapies, may interact, commonly used designs fail to detect this. A SMART design, with similar sample size to standard designs, can detect treatment interactions. The use of SMART designs to investigate effective and realistic dynamic treatment regimens is a promising way to accelerate the discovery of new, effective treatments for stroke. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  12. Development and degeneration of dorsal root ganglia in the absence of the HMG-domain transcription factor Sox10

    DEFF Research Database (Denmark)

    Sonnenberg-Riethmacher, Eva; Miehe, Michaela; Stolt, Claus C.

    2001-01-01

    neurogenesis seemed initially normal. A degeneration of motoneurons and sensory neurons occurred later in development. The mechanism that leads to the dramatic effects on the neural crest derived cell lineages in the dorsal root ganglia (DRG), however, has not been examined up to now. Here, we provide...... a detailed analysis of proliferation and apoptosis in the DRG during the time of their generation and lineage segregation (between E 9.5 and E 11.5). We show that both increased apoptosis as well as decreased proliferation of neural crest cells contribute to the observed hypomorphism....

  13. Significance of grooming behavior in two polygynous groups of western black crested gibbons: Implications for understanding social relationships among immigrant and resident group members.

    Science.gov (United States)

    Guan, Zhen-Hua; Huang, Bei; Ning, Wen-He; Ni, Qing-Yong; Sun, Guo-Zheng; Jiang, Xue-Long

    2013-12-01

    In primates, grooming is considered among the most common behaviors for maintaining social bonds; however, to date, few studies have examined grooming behavior in gibbon species in detail. We used both a 5-min interval scan method and social network analysis to study grooming in two groups of polygynous western black-crested gibbon (Nomascus concolor) in Wuliang Mountain, Central Yunnan, China. Individuals in both groups spent little time in social grooming (1.45% and 1.97% of active time). We compared the two groups' grooming networks and found that the group that maintained a more stable social unit had a more complex grooming network while the group with new immigrants had a grooming network characterized by fewer grooming pairs. Females in both groups played important roles in the grooming network. A newly immigrant female spent the most time grooming others and chose the resident adult female as her main adult grooming partner. Other females from both groups chose the adult male as their primary grooming partner (except their offspring). A sub-adult male who had resided in his natal group for 2 years after maturing into an adult also groomed more and was at the center of the network. This male finally replaced the breeding male in his group 3 years after our data collection period ended. We hypothesize that the immigrant female and the resident young adult male engaged in more extensive grooming interactions as a behavioral strategy to gain tolerance from long-term residents. Our results suggest that female gibbons in polygynous groups actively cooperate in maintaining social relationships rather than co-exist through tolerance or avoidance. Our observations indicate that grooming networks in crested gibbons reflect individual dynamics and partly support the social cohesion hypothesis for primate grooming. In this regard, we suggest that changes in gibbon grooming networks can be used to predict social change. © 2013 Wiley Periodicals, Inc.

  14. Sex-biased disruptive behaviour in breeding crested penguins

    OpenAIRE

    Poisbleau, M.; Demongin, L.; Eens, M.; Quillfeldt, P.

    2013-01-01

    Colonial breeding is common in seabirds, and may provide individuals with benefits such as increased protection from predators by joint defence, improved information exchange and enhanced access to mates. However, the presence of large numbers of individuals in breeding colonies may also lead to interference, especially where conspecific behaviour disrupts the normal chick-rearing routine. Using standardised video recordings, we describe and quantify for the first time such disruptive behavio...

  15. Shape and Dimensions of Ripples

    DEFF Research Database (Denmark)

    Jacobsen, Niels Gjøl

    and the general conclusion is that sharp crested ripples is thought unlikely to become stable under oscillatory flow due to the large increase in bed shear stresses because of the rapid contraction of the flow around the crest. Further, a dynamically moving ripple crest is investigated. The key focus...... are the recirculation zone and its penetration into the main flow. This will be compared to the period averaged bed shear stress. An analysis of the bed load transport, both as a transport capacity in the phase resolved space and an analysis of possible stable ripples is conducted. This leads to some stable ripples...

  16. Use of crowdsourcing for cancer clinical trial development.

    Science.gov (United States)

    Leiter, Amanda; Sablinski, Tomasz; Diefenbach, Michael; Foster, Marc; Greenberg, Alex; Holland, John; Oh, William K; Galsky, Matthew D

    2014-10-01

    Patient and physician awareness and acceptance of trials and patient ineligibility are major cancer clinical trial accrual barriers. Yet, trials are typically conceived and designed by small teams of researchers with limited patient input. We hypothesized that through crowdsourcing, the intellectual and creative capacity of a large number of researchers, clinicians, and patients could be harnessed to improve the clinical trial design process. In this study, we evaluated the feasibility and utility of using an internet-based crowdsourcing platform to inform the design of a clinical trial exploring an antidiabetic drug, metformin, in prostate cancer. Over a six-week period, crowd-sourced input was collected from 60 physicians/researchers and 42 patients/advocates leading to several major (eg, eligibility) and minor modifications to the clinical trial protocol as originally designed. Crowdsourcing clinical trial design is feasible, adds value to the protocol development process, and may ultimately improve the efficiency of trial conduct. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. The blind leading the blind: use and misuse of blinding in randomized controlled trials.

    Science.gov (United States)

    Miller, Larry E; Stewart, Morgan E

    2011-03-01

    The use of blinding strengthens the credibility of randomized controlled trials (RCTs) by minimizing bias. However, there is confusion surrounding the definition of blinding as well as the terms single, double, and triple blind. It has been suggested that these terms should be discontinued due to their broad misinterpretation. We recommend that, instead of abandoning the use of these terms, explicit definitions of blinding should be adopted. We address herein the concept of blinding, propose standard definitions for the consistent use of these terms, and detail when different types of blinding should be utilized. Standardizing the definition of blinding and utilizing proper blinding methods will improve the quality and clarity of reporting in RCTs. Copyright © 2010 Elsevier Inc. All rights reserved.

  18. Association between funding, risk of bias, and outcome of randomised controlled trials in oral and maxillofacial surgery

    NARCIS (Netherlands)

    Oomens, M.A.E.M.; Lazzari, S.; Heymans, M.W.; Forouzanfar, T.

    2016-01-01

    The influence of funding on the main outcome of a random control trial (RCT) is important, as it could potentially lead to bias towards industry, and results that are too optimistic. We investigated the association between funding, the published outcome, and the risk of bias in trials in oral and

  19. Placebo effect in clinical trial design for irritable bowel syndrome.

    Science.gov (United States)

    Shah, Eric; Pimentel, Mark

    2014-04-30

    Ongoing efforts to improve clinical trial design in irritable bowel syndrome have been hindered by high placebo response rates and ineffective outcome measures. We assessed established strategies to minimize placebo effect as well as the various ap-proaches to placebo effect which can affect trial design. These include genetic markers such as catechol-O-methyltransferase, opioidergic and dopaminergic neurobiologic theory, pre-cebo effect centered on expectancy theory, and side effect unblinding grounded on conditioning theory. We reviewed endpoints used in the study of IBS over the past decade including adequate relief and subjective global relief, emphasizing their weaknesses in fully evaluating the IBS condition, specifically their motility effects based on functional net value and relative benefit-harm based on dropouts due to adverse events. The focus of this review is to highlight ongoing efforts to improve clinical trial design which can lead to better outcomes in a real-world setting.

  20. Lead deposit on vegetation growing along highways traveled by automobiles. Milk cow feeding experiments with hay contaminated with lead

    Energy Technology Data Exchange (ETDEWEB)

    Bovay, E

    1971-03-01

    Measurements conducted in Switzerland from 1967 through 1970 revealed that vegetation growing along highways contained lead in concentrations in excess of 100 ppm. Although the amounts of lead in vegetation rapidly decrease with distance from the highway, lead can be detected up to a distance of about 100 M. The rate and extent of dispersion of lead particles depended on seasonal orographic and/or meteorological conditions. Lead retention by different plant organs is governed by their nature and composition. Plants with large hairy leaves or leaves with a rough surface accumulate much more lead than plants with smooth leaves. From 35-65% of the plant tissue lead content can be removed by thorough washing, an indication that the contamination consists for the most part in a surface deposit. But plant roots growing in lead-contaminated soil absorb the element, even if present in a relatively insoluble form. In spite of these observations, no symptoms of plant disease or a decrease in crop yield has been noted. High tightly growing hedges of perennials (pine or fir) markedly reduce the dispersion of exhaust gases. Feeding trials with mild cows involving hay harvested along highways demonstrated that a high percentage of the lead ingested with the fodder was eliminated. Some organs like bones, kidneys, and the liver accumulated large quantities of lead (up to 21-fold quantities). After four weeks on the contaminated hay, the lead content in milk quadrupled. The cows ingested 1300 mg lead daily with contaminated fodder containing 99 ppm Pb. Toxic symptoms in cattle and horses do not appear until an ingestion level of about 2200 mg Pb/day is reached. 36 references.

  1. Trial Sequential Analysis in systematic reviews with meta-analysis

    Directory of Open Access Journals (Sweden)

    Jørn Wetterslev

    2017-03-01

    Full Text Available Abstract Background Most meta-analyses in systematic reviews, including Cochrane ones, do not have sufficient statistical power to detect or refute even large intervention effects. This is why a meta-analysis ought to be regarded as an interim analysis on its way towards a required information size. The results of the meta-analyses should relate the total number of randomised participants to the estimated required meta-analytic information size accounting for statistical diversity. When the number of participants and the corresponding number of trials in a meta-analysis are insufficient, the use of the traditional 95% confidence interval or the 5% statistical significance threshold will lead to too many false positive conclusions (type I errors and too many false negative conclusions (type II errors. Methods We developed a methodology for interpreting meta-analysis results, using generally accepted, valid evidence on how to adjust thresholds for significance in randomised clinical trials when the required sample size has not been reached. Results The Lan-DeMets trial sequential monitoring boundaries in Trial Sequential Analysis offer adjusted confidence intervals and restricted thresholds for statistical significance when the diversity-adjusted required information size and the corresponding number of required trials for the meta-analysis have not been reached. Trial Sequential Analysis provides a frequentistic approach to control both type I and type II errors. We define the required information size and the corresponding number of required trials in a meta-analysis and the diversity (D2 measure of heterogeneity. We explain the reasons for using Trial Sequential Analysis of meta-analysis when the actual information size fails to reach the required information size. We present examples drawn from traditional meta-analyses using unadjusted naïve 95% confidence intervals and 5% thresholds for statistical significance. Spurious conclusions in

  2. A key role for poly(ADP-ribose polymerase 3 in ectodermal specification and neural crest development.

    Directory of Open Access Journals (Sweden)

    Michèle Rouleau

    2011-01-01

    Full Text Available The PARP family member poly(ADP-ribose polymerase 3 (PARP3 is structurally related to the well characterized PARP1 that orchestrates cellular responses to DNA strand breaks and cell death by the synthesis of poly(ADP-ribose. In contrast to PARP1 and PARP2, the functions of PARP3 are undefined. Here, we reveal critical functions for PARP3 during vertebrate development.We have used several in vitro and in vivo approaches to examine the possible functions of PARP3 as a transcriptional regulator, a function suggested from its previously reported association with several Polycomb group (PcG proteins. We demonstrate that PARP3 gene occupancy in the human neuroblastoma cell line SK-N-SH occurs preferentially with developmental genes regulating cell fate specification, tissue patterning, craniofacial development and neurogenesis. Addressing the significance of this association during zebrafish development, we show that morpholino oligonucleotide-directed inhibition of parp3 expression in zebrafish impairs the expression of the neural crest cell specifier sox9a and of dlx3b/dlx4b, the formation of cranial sensory placodes, inner ears and pectoral fins. It delays pigmentation and severely impedes the development of the median fin fold and tail bud.Our findings demonstrate that Parp3 is crucial in the early stages of zebrafish development, possibly by exerting its transcriptional regulatory functions as early as during the specification of the neural plate border.

  3. From randomised trials to rational practice.

    Science.gov (United States)

    van Gijn, J

    2005-01-01

    From the age of Enlightenment onwards, philosophical thinking has become increasingly influenced by empiricism: observations lead to theories, but experiments are needed to put the reasoning to the test. However, it was not until the middle of the 20th century that well-designed experiments were at last introduced in medical treatment, in the form of randomised controlled clinical trials. This design is now standard in medicine, but in everyday practice a multitude of management decisions must still be taken without good evidence. There are several reasons for this: there may not be a trial at all or only a single trial; trial results may be equivocal; patients may be different from those enrolled in trials; new procedures require practice, or a trial may not be feasible. 'Logical reasoning', with all its fallacies, is still required - not only to fill the gaps in empirical knowledge but also to interpret existing evidence and to plan new trials. In fact, the generation of new knowledge is a continuous, cyclical process in which newly gained insights in pathophysiology give rise to new therapeutic experiments, the results of which generate fresh hypotheses, and so on. Compassion, curiosity and doubt are the essential forces that keep the cycle moving. Conversely, the progress is slowed down by present-day legalism, which distorts investigator accountability and patient autonomy. Copyright (c) 2005 S. Karger AG, Basel.

  4. Older cancer patients in cancer clinical trials are underrepresented. Systematic literature review of almost 5000 meta- and pooled analyses of phase III randomized trials of survival from breast, prostate and lung cancer.

    Science.gov (United States)

    Dunn, Cita; Wilson, Andrew; Sitas, Freddy

    2017-12-01

    Older people represent increasing proportions of the population with cancer. To understand the representivity of cancer treatments in older people, we performed a systematic literature review using PRISMA guidelines of the age distribution of clinical trial participants for three leading cancer types, namely breast, prostate, and lung. We used PubMed to identify articles detailing meta or pooled-analyses of phase III, randomised controlled trials (RCTs) of survival for breast, prostate and lung cancer, published ≤5 years from 2016. We compared the age distribution of participants to that of these cancers for "More developed regions". 4993 potential papers were identified, but only three papers on breast cancer, three on lung cancer, and none on prostate cancer presented the age distribution of their participants. Except for one paper of breast cancer, participants ≥70 years in all other papers were underrepresented. We recommend the age distribution of patients be clearly reported in all clinical trials, as per guidelines. Clinical trials ought to be more representative of the populations most affected by the disease for which treatments are being tested. This should lead to better knowledge of effectiveness of treatments and better translation of trial results to optimal care of older cancer patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Therapeutics discovery: From bench to first in-human trials.

    Science.gov (United States)

    Al-Hujaily, Ensaf M; Khatlani, Tanvir; Alehaideb, Zeyad; Ali, Rizwan; Almuzaini, Bader; Alrfaei, Bahauddeen M; Iqbal, Jahangir; Islam, Imadul; Malik, Shuja; Marwani, Bader A; Massadeh, Salam; Nehdi, Atef; Alsomaie, Barrak; Debasi, Bader; Bushnak, Ibraheem; Noibi, Saeed; Hussain, Syed; Wajid, Wahid Abdul; Armand, Jean-Pierre; Gul, Sheraz; Oyarzabal, Julen; Rais, Rana; Bountra, Chas; Alaskar, Ahmed; Knawy, Bander Al; Boudjelal, Mohamed

    2018-03-01

    The 'Therapeutics discovery: From bench to first in-human trials' conference, held at the King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard Health Affairs (MNGHA), Kingdom of Saudi Arabia (KSA) from October 10-12, 2017, provided a unique opportunity for experts worldwide to discuss advances in drug discovery and development, focusing on phase I clinical trials. It was the first event of its kind to be hosted at the new research center, which was constructed to boost drug discovery and development in the KSA in collaboration with institutions, such as the Academic Drug Discovery Consortium in the United States of America (USA), Structural Genomics Consortium of the University of Oxford in the United Kingdom (UK), and Institute of Materia Medica of the Chinese Academy of Medical Sciences in China. The program was divided into two parts. A pre-symposium day took place on October 10, during which courses were conducted on clinical trials, preclinical drug discovery, molecular biology and nanofiber research. The attendees had the opportunity for one-to-one meetings with international experts to exchange information and foster collaborations. In the second part of the conference, which took place on October 11 and 12, the clinical trials pipeline, design and recruitment of volunteers, and economic impact of clinical trials were discussed. The Saudi Food and Drug Administration presented the regulations governing clinical trials in the KSA. The process of preclinical drug discovery from small molecules, cellular and immunologic therapies, and approaches to identifying new targets were also presented. The recommendation of the conference was that researchers in the KSA must invest more fund, talents and infrastructure to lead the region in phase I clinical trials and preclinical drug discovery. Diseases affecting the local population, such as Middle East Respiratory Syndrome and resistant bacterial infections, represent the optimal

  6. Delamination of neural crest cells requires transient and reversible Wnt inhibition mediated by Dact1/2.

    Science.gov (United States)

    Rabadán, M Angeles; Herrera, Antonio; Fanlo, Lucia; Usieto, Susana; Carmona-Fontaine, Carlos; Barriga, Elias H; Mayor, Roberto; Pons, Sebastián; Martí, Elisa

    2016-06-15

    Delamination of neural crest (NC) cells is a bona fide physiological model of epithelial-to-mesenchymal transition (EMT), a process that is influenced by Wnt/β-catenin signalling. Using two in vivo models, we show that Wnt/β-catenin signalling is transiently inhibited at the time of NC delamination. In attempting to define the mechanism underlying this inhibition, we found that the scaffold proteins Dact1 and Dact2, which are expressed in pre-migratory NC cells, are required for NC delamination in Xenopus and chick embryos, whereas they do not affect the motile properties of migratory NC cells. Dact1/2 inhibit Wnt/β-catenin signalling upstream of the transcriptional activity of T cell factor (TCF), which is required for EMT to proceed. Dact1/2 regulate the subcellular distribution of β-catenin, preventing β-catenin from acting as a transcriptional co-activator to TCF, yet without affecting its stability. Together, these data identify a novel yet important regulatory element that inhibits β-catenin signalling, which then affects NC delamination. © 2016. Published by The Company of Biologists Ltd.

  7. Mitochondrial disease patient motivations and barriers to participate in clinical trials.

    Directory of Open Access Journals (Sweden)

    Zarazuela Zolkipli-Cunningham

    Full Text Available Clinical treatment trials are increasingly being designed in primary mitochondrial disease (PMD, a phenotypically and genetically heterogeneous collection of inherited multi- system energy deficiency disorders that lack effective therapy. We sought to identify motivating factors and barriers to clinical trial participation in PMD.A survey study was conducted in two independent mitochondrial disease subject cohorts. A discovery cohort invited subjects with well-defined biochemical or molecularly- confirmed PMD followed at a single medical center (CHOP, n = 30/67 (45% respondents. A replication cohort included self-identified PMD subjects in the Rare Disease Clinical Research Network (RDCRN national contact registry (n = 290/1119 (26% respondents. Five-point Likert scale responses were analyzed using descriptive and quantitative statistics. Experienced and prioritized symptoms for trial participation, and patient attitudes toward detailed aspects of clinical trial drug features and study design.PMD subjects experienced an average of 16 symptoms. Muscle weakness, chronic fatigue, and exercise intolerance were the lead symptoms encouraging trial participation. Motivating trial design factors included a self-administered study drug; vitamin, antioxidant, natural or plant-derivative; pills; daily treatment; guaranteed treatment access during and after study; short travel distances; and late-stage (phase 3 participation. Relative trial participation barriers included a new study drug; discontinuation of current medications; disease progression; daily phlebotomy; and requiring participant payment. Treatment trial type or design preferences were not influenced by population age (pediatric versus adult, prior research trial experience, or disease severity.These data are the first to convey clear PMD subject preferences and priorities to enable improved clinical treatment trial design that cuts across the complex diversity of disease. Partnering with rare

  8. Avoiding Internal Capsule Stimulation With a New Eight-Channel Steering Deep Brain Stimulation Lead.

    Science.gov (United States)

    van Dijk, Kees J; Verhagen, Rens; Bour, Lo J; Heida, Ciska; Veltink, Peter H

    2017-10-15

    Novel deep brain stimulation (DBS) lead designs are currently entering the market, which are hypothesized to provide a way to steer the stimulation field away from neural populations responsible for side effects and towards populations responsible for beneficial effects. The objective of this study is to assess the performances of a new eight channel steering-DBS lead and compare this with a conventional cylindrical contact (CC) lead. The two leads were evaluated in a finite element electric field model combined with multicompartment neuron and axon models, representing the internal capsule (IC) fibers and subthalamic nucleus (STN) cells. We defined the optimal stimulation setting as the configuration that activated the highest percentage of STN cells, without activating any IC fibers. With this criterion, we compared monopolar stimulation using a single contact of the steering-DBS lead and CC lead, on three locations and four orientations of the lead. In addition, we performed a current steering test case by dividing the current over two contacts with the steering-DBS lead in its worst-case orientation. In most cases, the steering-DBS lead is able to stimulate a significantly higher percentage of STN cells compared to the CC lead using single contact stimulation or using a two contact current steering protocol when there is approximately a 1 mm displacement of the CC lead. The results also show that correct placement and orientation of the lead in the target remains an important aspect in achieving the optimal stimulation outcome. Currently, clinical trials are set up in Europe with a similar design as the steering-DBS lead. Our results illustrate the importance of the orientation of the new steering-DBS lead in avoiding side effects induced by stimulation of IC fibers. Therefore, in clinical trials sufficient attention should be paid to implanting the steering DBS-lead in the most effective orientation. © 2017 International Neuromodulation Society.

  9. Neural crest stem cell multipotency requires Foxd3 to maintain neural potential and repress mesenchymal fates.

    Science.gov (United States)

    Mundell, Nathan A; Labosky, Patricia A

    2011-02-01

    Neural crest (NC) progenitors generate a wide array of cell types, yet molecules controlling NC multipotency and self-renewal and factors mediating cell-intrinsic distinctions between multipotent versus fate-restricted progenitors are poorly understood. Our earlier work demonstrated that Foxd3 is required for maintenance of NC progenitors in the embryo. Here, we show that Foxd3 mediates a fate restriction choice for multipotent NC progenitors with loss of Foxd3 biasing NC toward a mesenchymal fate. Neural derivatives of NC were lost in Foxd3 mutant mouse embryos, whereas abnormally fated NC-derived vascular smooth muscle cells were ectopically located in the aorta. Cranial NC defects were associated with precocious differentiation towards osteoblast and chondrocyte cell fates, and individual mutant NC from different anteroposterior regions underwent fate changes, losing neural and increasing myofibroblast potential. Our results demonstrate that neural potential can be separated from NC multipotency by the action of a single gene, and establish novel parallels between NC and other progenitor populations that depend on this functionally conserved stem cell protein to regulate self-renewal and multipotency.

  10. The reporting quality of randomized controlled trials in orthodontics.

    Science.gov (United States)

    Lempesi, Evangelia; Koletsi, Despina; Fleming, Padhraig S; Pandis, Nikolaos

    2014-06-01

    Accurate trial reporting facilitates evaluation and better use of study results. The objective of this article is to investigate the quality of reporting of randomized controlled trials (RCTs) in leading orthodontic journals, and to explore potential predictors of improved reporting. The 50 most recent issues of 4 leading orthodontic journals until November 2013 were electronically searched. Reporting quality assessment was conducted using the modified CONSORT statement checklist. The relationship between potential predictors and the modified CONSORT score was assessed using linear regression modeling. 128 RCTs were identified with a mean modified CONSORT score of 68.97% (SD = 11.09). The Journal of Orthodontics (JO) ranked first in terms of completeness of reporting (modified CONSORT score 76.21%, SD = 10.1), followed by American Journal of Orthodontics and Dentofacial Orthopedics (AJODO) (73.05%, SD = 10.1). Journal of publication (AJODO: β = 10.08, 95% CI: 5.78, 14.38; JO: β = 16.82, 95% CI: 11.70, 21.94; EJO: β = 7.21, 95% CI: 2.69, 11.72 compared to Angle), year of publication (β = 0.98, 95% CI: 0.28, 1.67 for each additional year), region of authorship (Europe: β = 5.19, 95% CI: 1.30, 9.09 compared to Asia/other), statistical significance (significant: β = 3.10, 95% CI: 0.11, 6.10 compared to non-significant) and methodologist involvement (involvement: β = 5.60, 95% CI: 1.66, 9.54 compared to non-involvement) were all significant predictors of improved modified CONSORT scores in the multivariable model. Additionally, median overall Jadad score was 2 (IQR = 2) across journals, with JO (median = 3, IQR = 1) and AJODO (median = 3, IQR = 2) presenting the highest score values. The reporting quality of RCTs published in leading orthodontic journals is considered suboptimal in various CONSORT areas. This may have a bearing in trial result interpretation and use in clinical decision making and evidence- based orthodontic treatment interventions. Copyright

  11. The effect of supplementation with vitamin A on serum and liver concentrations in Puerto Rican crested toads (Peltophryne lemur) and its lack of impact on brown skin disease.

    Science.gov (United States)

    Dutton, Christopher; Lentini, Andrew; Berkvens, Charlene; Crawshaw, Graham

    2014-01-01

    "Brown skin disease" (BSD) is a clinical syndrome of dysecdysis, chronic weight loss and death, previously reported in Puerto Rican crested toads (Peltophryne lemur). Although vitamin A deficiency has been suggested, its cause remains unknown and multiple treatments have failed to prevent or reverse the condition. This study compared the efficacy of vitamin A supplementation, administered in different forms and by different routes, in 48 captive born Puerto Rican crested toads fed from metamorphosis on gut-loaded, dusted, commercially raised crickets. Forty-five toads started to show clinical signs of BSD at 9 months of age; all toads were treated orally with an oil-based vitamin A formulation twice weekly for 2 months but continued to deteriorate. Two treatment groups were then compared: Animals in one group (n=19) received 2 IU injectable vitamin A (Aquasol-A) per gram bodyweight subcutaneously twice weekly for 3 months with no change in diet. Toads in the other group (n=22) received a single oral dose of vitamins A, D3 , and E, and were fed on earthworms and crickets gut-loaded with produce and a finely-ground alfalfa-based pellet, dusted with the same vitamin/mineral supplement. All affected animals developed severe BSD equally and died during, or were euthanized at the end of, the treatment regimen, with no clinical improvement. Animals supplemented with Aquasol-A had significantly higher liver vitamin A concentrations compared with the other treatment group, whereas serum retinol concentrations showed no significant difference. Vitamin A supplementation does not appear a successful treatment once BSD symptoms have developed. © 2014 Wiley Periodicals, Inc.

  12. Does intensive management improve remission rates in patients with intermediate rheumatoid arthritis? (the TITRATE trial): study protocol for a randomised controlled trial.

    Science.gov (United States)

    Martin, Naomi H; Ibrahim, Fowzia; Tom, Brian; Galloway, James; Wailoo, Allan; Tosh, Jonathan; Lempp, Heidi; Prothero, Louise; Georgopoulou, Sofia; Sturt, Jackie; Scott, David L

    2017-12-08

    Uncontrolled active rheumatoid arthritis can lead to increasing disability and reduced quality of life over time. 'Treating to target' has been shown to be effective in active established disease and also in early disease. However, there is a lack of nationally agreed treatment protocols for patients with established rheumatoid arthritis who have intermediate disease activity. This trial is designed to investigate whether intensive management of disease leads to a greater number of remissions at 12 months. Levels of disability and quality of life, and acceptability and cost-effectiveness of the intervention will also be examined. The trial is a 12-month, pragmatic, randomised, open-label, two-arm, parallel-group, multicentre trial undertaken at specialist rheumatology centres across England. Three hundred and ninety-eight patients with established rheumatoid arthritis will be recruited. They will currently have intermediate disease activity (disease activity score for 28 joints assessed using an erythrocyte sedimentation rate of 3.2 to 5.1 with at least three active joints) and will be taking at least one disease-modifying anti-rheumatic drug. Participants will be randomly selected to receive intensive management or standard care. Intensive management will involve monthly clinical reviews with a specialist health practitioner, where drug treatment will be optimised and an individualised treatment support programme delivered based on several principles of motivational interviewing to address identified problem areas, such as pain, fatigue and adherence. Standard care will follow standard local pathways and will be in line with current English guidelines from the National Institute for Health and Clinical Excellence. Patients will be assessed initially and at 6 and 12 months through self-completed questionnaires and clinical evaluation. The trial will establish whether the known benefits of intensive treatment strategies in active rheumatoid arthritis are also seen

  13. Prevalence and reporting of recruitment, randomisation and treatment errors in clinical trials: A systematic review.

    Science.gov (United States)

    Yelland, Lisa N; Kahan, Brennan C; Dent, Elsa; Lee, Katherine J; Voysey, Merryn; Forbes, Andrew B; Cook, Jonathan A

    2018-06-01

    Background/aims In clinical trials, it is not unusual for errors to occur during the process of recruiting, randomising and providing treatment to participants. For example, an ineligible participant may inadvertently be randomised, a participant may be randomised in the incorrect stratum, a participant may be randomised multiple times when only a single randomisation is permitted or the incorrect treatment may inadvertently be issued to a participant at randomisation. Such errors have the potential to introduce bias into treatment effect estimates and affect the validity of the trial, yet there is little motivation for researchers to report these errors and it is unclear how often they occur. The aim of this study is to assess the prevalence of recruitment, randomisation and treatment errors and review current approaches for reporting these errors in trials published in leading medical journals. Methods We conducted a systematic review of individually randomised, phase III, randomised controlled trials published in New England Journal of Medicine, Lancet, Journal of the American Medical Association, Annals of Internal Medicine and British Medical Journal from January to March 2015. The number and type of recruitment, randomisation and treatment errors that were reported and how they were handled were recorded. The corresponding authors were contacted for a random sample of trials included in the review and asked to provide details on unreported errors that occurred during their trial. Results We identified 241 potentially eligible articles, of which 82 met the inclusion criteria and were included in the review. These trials involved a median of 24 centres and 650 participants, and 87% involved two treatment arms. Recruitment, randomisation or treatment errors were reported in 32 in 82 trials (39%) that had a median of eight errors. The most commonly reported error was ineligible participants inadvertently being randomised. No mention of recruitment, randomisation

  14. Spine device clinical trials: design and sponsorship.

    Science.gov (United States)

    Cher, Daniel J; Capobianco, Robyn A

    2015-05-01

    Multicenter prospective randomized clinical trials represent the best evidence to support the safety and effectiveness of medical devices. Industry sponsorship of multicenter clinical trials is purported to lead to bias. To determine what proportion of spine device-related trials are industry-sponsored and the effect of industry sponsorship on trial design. Analysis of data from a publicly available clinical trials database. Clinical trials of spine devices registered on ClinicalTrials.gov, a publicly accessible trial database, were evaluated in terms of design, number and location of study centers, and sample size. The relationship between trial design characteristics and study sponsorship was evaluated using logistic regression and general linear models. One thousand six hundred thrity-eight studies were retrieved from ClinicalTrials.gov using the search term "spine." Of the 367 trials that focused on spine surgery, 200 (54.5%) specifically studied devices for spine surgery and 167 (45.5%) focused on other issues related to spine surgery. Compared with nondevice trials, device trials were far more likely to be sponsored by the industry (74% vs. 22.2%, odds ratio (OR) 9.9 [95% confidence interval 6.1-16.3]). Industry-sponsored device trials were more likely multicenter (80% vs. 29%, OR 9.8 [4.8-21.1]) and had approximately four times as many participating study centers (pdevices not sponsored by the industry. Most device-related spine research is industry-sponsored. Multicenter trials are more likely to be industry-sponsored. These findings suggest that previously published studies showing larger effect sizes in industry-sponsored vs. nonindustry-sponsored studies may be biased as a result of failure to take into account the marked differences in design and purpose. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Relationship between macular pigment and visual function in subjects with early age-related macular degeneration.

    Science.gov (United States)

    Akuffo, Kwadwo Owusu; Nolan, John M; Peto, Tunde; Stack, Jim; Leung, Irene; Corcoran, Laura; Beatty, Stephen

    2017-02-01

    To investigate the relationship between macular pigment (MP) and visual function in subjects with early age-related macular degeneration (AMD). 121 subjects with early AMD enrolled as part of the Central Retinal Enrichment Supplementation Trial (CREST; ISRCTN13894787) were assessed using a range of psychophysical measures of visual function, including best corrected visual acuity (BCVA), letter contrast sensitivity (CS), mesopic and photopic CS, mesopic and photopic glare disability (GD), photostress recovery time (PRT), reading performance and subjective visual function, using the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25). MP was measured using customised heterochromatic flicker photometry. Letter CS, mesopic and photopic CS, photopic GD and mean reading speed were each significantly (p0.05, for all). MP relates positively to many measures of visual function in unsupplemented subjects with early AMD. The CREST trial will investigate whether enrichment of MP influences visual function among those afflicted with this condition. ISRCTN13894787. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  16. Comparison of GPS derived TEC with the TEC predicted by IRI 2012 model in the southern Equatorial Ionization Anomaly crest within the Eastern Africa region

    Science.gov (United States)

    Sulungu, Emmanuel D.; Uiso, Christian B. S.; Sibanda, Patrick

    2018-04-01

    We have compared the TEC obtained from the IRI-2012 model with the GPS derived TEC data recorded within southern crest of the EIA in the Eastern Africa region using the monthly means of the 5 international quiet days for equinoxes and solstices months for the period of 2012 - 2013. GPS-derived TEC data have been obtained from the Africa array and IGS network of ground based dual-frequency GPS receivers from four stations (Kigali (1.95°S, 30.09°E; Geom. Lat. 11.63°S), Malindi (2.99°S, 40.19°E; Geom. Lat. 12.42°S), Mbarara (0.60°S, 30.74°E; Geom. Lat. 10.22°S) and Nairobi (1.22°S, 36.89°E; Geom. Lat. 10.69°S)) located within the EIA crest in this region. All the three options for topside Ne of IRI-2012 model and ABT-2009 for bottomside thickness have been used to compute the IRI TEC. Also URSI coefficients were considered in this study. These results are compared with the TEC estimated from GPS measurements. Correlation Coefficients between the two sets of data, the Root-Mean Square Errors (RMSE) of the IRI-TEC from the GPS-TEC, and the percentage RMSE of the IRI-TEC from the GPS-TEC have been computed. Our general results show that IRI-2012 model with all three options overestimates the GPS-TEC for all seasons and at all stations, and IRI-2001 overestimates GPS-TEC more compared with other options. IRI-Neq and IRI-01-corr are closely matching in most of the time. The observation also shows that, GPS TEC are underestimated by TEC from IRI model during noon hours, especially during equinoctial months. Further, GPS-TEC values and IRI-TEC values using all the three topside Ne options show very good correlation (above 0.8). On the other hand, the TEC using IRI-Neq and IRI-01- corr had smaller deviations from the GPS-TEC compared to the IRI-2001.

  17. Differentiation of neural crest stem cells from nasal mucosa into motor neuron-like cells.

    Science.gov (United States)

    Bagher, Zohreh; Kamrava, Seyed Kamran; Alizadeh, Rafieh; Farhadi, Mohammad; Absalan, Moloud; Falah, Masoumeh; Faghihi, Faezeh; Zare-Sadeghi, Arash; Komeili, Ali

    2018-05-25

    Cell transplantation is a potential therapeutic approach for repairing neuropathological and neurodegenerative disorders of central nervous system by replacing the degenerated cells with new ones. Among a variety of stem cell candidates to provide these new cells, olfactory ectomesenchymal stem cells (OE-MSCs) have attracted a great attention due to their neural crest origin, easy harvest, high proliferation, and autologous transplantation. Since there is no report on differentiation potential of these cells into motor neuron-like cells, we evaluated this potential using Real-time PCR, flowcytometry and immunocytochemistry after the treatment with differentiation cocktail containing retinoic acid and Sonic Hedgehog. Immunocytochemistry staining of the isolated OE-MSCs demonstrated their capability to express nestin and vimentin, as the two markers of primitive neuroectoderm. The motor neuron differentiation of OE-MSCs resulted in changing their morphology into bipolar cells with high expression of motor neuron markers of ChAT, Hb-9 and Islet-1 at the level of mRNA and protein. Consequently, we believe that the OE-MSCs have great potential to differentiate into motor neuron-like cells and can be an ideal stem cell source for the treatment of motor neuron-related disorders of central nervous system. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Lead in teeth from lead-dosed goats: Microdistribution and relationship to the cumulative lead dose

    International Nuclear Information System (INIS)

    Bellis, David J.; Hetter, Katherine M.; Jones, Joseph; Amarasiriwardena, Dula; Parsons, Patrick J.

    2008-01-01

    Teeth are commonly used as a biomarker of long-term lead exposure. There appear to be few data, however, on the content or distribution of lead in teeth where data on specific lead intake (dose) are also available. This study describes the analysis of a convenience sample of teeth from animals that were dosed with lead for other purposes, i.e., a proficiency testing program for blood lead. Lead concentration of whole teeth obtained from 23 animals, as determined by atomic absorption spectrometry, varied from 0.6 to 80 μg g -1 . Linear regression of whole tooth lead (μg g -1 ) on the cumulative lead dose received by the animal (g) yielded a slope of 1.2, with r 2 =0.647 (p -1 , were found in circumpulpal dentine. Linear regression of circumpulpal lead (μg g -1 ) on cumulative lead dose (g) yielded a slope of 23 with r 2 =0.961 (p=0.0001). The data indicated that whole tooth lead, and especially circumpulpal lead, of dosed goats increased linearly with cumulative lead exposure. These data suggest that circumpulpal dentine is a better biomarker of cumulative lead exposure than is whole tooth lead, at least for lead-dosed goats

  19. Establishing HIV treatment as prevention in the HIV Prevention Trials Network 052 randomized trial: an ethical odyssey.

    Science.gov (United States)

    Cohen, Myron S; McCauley, Marybeth; Sugarman, Jeremy

    2012-06-01

    Obtaining the definitive data necessary to determine the safety and efficacy of using antiretroviral treatment (ART) to reduce the sexual transmission of HIV in heterosexual couples encountered an array of ethical challenges that threatened to compromise HIV Prevention Trials Network (HPTN) 052, the multinational clinical trial addressing this issue that has profound public health implications. To describe and analyze the major ethical challenges faced in HPTN 052. The ethical issues and modifications of HPTN 052 in response to these issues were cataloged by the principal investigator, the lead coordinator, and the ethicist working on the trial. The major ethical issues that were unique to the trial were then described and analyzed in light of the published literature as well as guidances and policies. The ethical challenges that must be addressed in many clinical trials, such as those related to obtaining informed consent and making provisions for ancillary care, are not described. When HPTN 052 was being designed, ethical questions emerged related to the relevance of the research question itself given data from observational research and a range of beliefs about the appropriate means of preventing and treating HIV infection and AIDS. Furthermore, ethical challenges were faced regarding site selection since there was a scientific need to conduct the research in settings where HIV incidence was high, but alternatives to study participation should be available. As in most HIV-prevention research, ethical questions surrounded the determination of the appropriate prevention package for all of those enrolled. During the course of the trial, guidance documents and policies emerged that were of direct relevance to the research questions, calling for a balancing of concerns for the research subjects and trial integrity. When the study results were made public, there was a need to ensure access to the treatment shown to be effective that in some cases differed from the

  20. Maximising the value of combining qualitative research and randomised controlled trials in health research: the QUAlitative Research in Trials (QUART) study--a mixed methods study.

    Science.gov (United States)

    O'Cathain, Alicia; Thomas, Kate J; Drabble, Sarah J; Rudolph, Anne; Goode, Jackie; Hewison, Jenny

    2014-06-01

    Researchers sometimes undertake qualitative research with randomised controlled trials (RCTs) of health interventions. To systematically explore how qualitative research is being used with trials and identify ways of maximising its value to the trial aim of providing evidence of effectiveness of health interventions. A sequential mixed methods study with four components. (1) Database search of peer-reviewed journals between January 2008 and September 2010 for articles reporting the qualitative research undertaken with specific trials, (2) systematic search of database of registered trials to identify studies combining qualitative research and trials, (3) survey of 200 lead investigators of trials with no apparent qualitative research and (4) semistructured telephone interviews with 18 researchers purposively sampled from the first three methods. Qualitative research was undertaken with at least 12% of trials. A large number of articles reporting qualitative research undertaken with trials (n=296) were published between 2008 and 2010. A total of 28% (82/296) of articles reported qualitative research undertaken at the pre-trial stage and around one-quarter concerned drugs or devices. The articles focused on 22 aspects of the trial within five broad categories. Some focused on more than one aspect of the trial, totalling 356 examples. The qualitative research focused on the intervention being trialled (71%, 254/356), the design and conduct of the trial (15%, 54/356), the outcomes of the trial (1%, 5/356), the measures used in the trial (3%, 10/356), and the health condition in the trial (9%, 33/356). The potential value of the qualitative research to the trial endeavour included improving the external validity of trials and facilitating interpretation of trial findings. This value could be maximised by using qualitative research more at the pre-trial stage and reporting findings with explicit attention to the implications for the trial endeavour. During interviews

  1. The neural crest is a source of mesenchymal stem cells with specialized hematopoietic stem cell niche function.

    Science.gov (United States)

    Isern, Joan; García-García, Andrés; Martín, Ana M; Arranz, Lorena; Martín-Pérez, Daniel; Torroja, Carlos; Sánchez-Cabo, Fátima; Méndez-Ferrer, Simón

    2014-09-25

    Mesenchymal stem cells (MSCs) and osteolineage cells contribute to the hematopoietic stem cell (HSC) niche in the bone marrow of long bones. However, their developmental relationships remain unclear. In this study, we demonstrate that different MSC populations in the developing marrow of long bones have distinct functions. Proliferative mesoderm-derived nestin(-) MSCs participate in fetal skeletogenesis and lose MSC activity soon after birth. In contrast, quiescent neural crest-derived nestin(+) cells preserve MSC activity, but do not generate fetal chondrocytes. Instead, they differentiate into HSC niche-forming MSCs, helping to establish the HSC niche by secreting Cxcl12. Perineural migration of these cells to the bone marrow requires the ErbB3 receptor. The neonatal Nestin-GFP(+) Pdgfrα(-) cell population also contains Schwann cell precursors, but does not comprise mature Schwann cells. Thus, in the developing bone marrow HSC niche-forming MSCs share a common origin with sympathetic peripheral neurons and glial cells, and ontogenically distinct MSCs have non-overlapping functions in endochondrogenesis and HSC niche formation.

  2. Conducting clinical trials in Singapore.

    Science.gov (United States)

    Woo, K T

    1999-04-01

    All clinical trials in Singapore will now have to conform to the Medicines (Clinical Trials) Amended Regulations 1998 and the Singapore Good Clinical Practice (GCP) Guidelines 1998. The Medical Clinical Research Committee (MCRC) has been established to oversee the conduct of clinical drug trials in Singapore and together with the legislations in place, these will ensure that clinical trials conducted in Singapore are properly controlled and the well-being of trial subjects are safe guarded. All clinical drug trials require a Clinical Trial Certificate from the MCRC before the trial can proceed. The hospital ethics committee (EC) vets the application for a trial certificate before it is sent to MCRC. The drug company sponsoring the trial has to indemnify the trial investigators and the hospital for negligence arising from the trial. The MCRC, apart from ensuring the safety of trial subjects, has to provide continuing review of the clinical trial and monitors adverse events in the course of the trial. The EC will conduct continuing review of clinical trials. When a non-drug clinical trial is carried out, the EC will ensure that the proposed protocol addresses ethical concerns and meets regulatory requirements for such trials. There is great potential for pharmaceutical Research & Development (R&D) in Singapore. We must develop our skills and infrastructure in clinical trials to enable Singapore to be a regional hub for R&D of drugs in Asia.

  3. Development and pilot evaluation of Native CREST-a Cancer Research Experience and Student Training program for Navajo undergraduate students.

    Science.gov (United States)

    Hughes, Christine A; Bauer, Mark C; Horazdovsky, Bruce F; Garrison, Edward R; Patten, Christi A; Petersen, Wesley O; Bowman, Clarissa N; Vierkant, Robert A

    2013-03-01

    The Mayo Clinic Cancer Center and Diné College received funding for a 4-year collaborative P20 planning grant from the National Cancer Institute in 2006. The goal of the partnership was to increase Navajo undergraduates' interest in and commitment to biomedical coursework and careers, especially in cancer research. This paper describes the development, pilot testing, and evaluation of Native CREST (Cancer Research Experience and Student Training), a 10-week cancer research training program providing mentorship in a Mayo Clinic basic science or behavioral cancer research lab for Navajo undergraduate students. Seven Native American undergraduate students (five females, two males) were enrolled during the summers of 2008-2011. Students reported the program influenced their career goals and was valuable to their education and development. These efforts may increase the number of Native American career scientists developing and implementing cancer research, which will ultimately benefit the health of Native American people.

  4. The Apathy in Dementia Methylphenidate Trial 2 (ADMET 2): study protocol for a randomized controlled trial.

    Science.gov (United States)

    Scherer, Roberta W; Drye, Lea; Mintzer, Jacobo; Lanctôt, Krista; Rosenberg, Paul; Herrmann, Nathan; Padala, Prasad; Brawman-Mintzer, Olga; Burke, William; Craft, Suzanne; Lerner, Alan J; Levey, Allan; Porsteinsson, Anton; van Dyck, Christopher H

    2018-01-18

    Alzheimer's disease (AD) is characterized not only by cognitive and functional decline, but also often by the presence of neuropsychiatric symptoms. Apathy, which can be defined as a lack of motivation, is one of the most prevalent neuropsychiatric symptoms in AD and typically leads to a worse quality of life and greater burden for caregivers. Treatment options for apathy in AD are limited, but studies have examined the use of the amphetamine, methylphenidate. The Apathy in Dementia Methylphenidate Trial (ADMET) found that treatment of apathy in AD with methylphenidate was associated with significant improvement in apathy in two of three outcome measures, some evidence of improvement in global cognition, and minimal adverse events. However, the trial only enrolled 60 participants who were followed for only 6 weeks. A larger, longer-lasting trial is required to confirm these promising findings. The Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) is a phase III, placebo-controlled, masked, 6-month, multi-center, randomized clinical trial targeted to enroll 200 participants with AD and apathy. Participants are randomly assigned 1:1 to 20 mg methylphenidate per day prepared as four over-encapsulated tablets or to matching placebo. The primary outcomes include (1) the mean difference in the Neuropsychiatric Inventory Apathy subscale scores measured as change from baseline to 6 months, and (2) the odds of having a given rating or better on the modified AD Cooperative Study Clinical Global Impression of Change ratings at month 6 compared with the baseline rating. Other outcomes include change in cognition, safety, and cost-effectiveness measured at monthly follow-up visits up to 6 months. Given the prevalence of apathy in AD and its impact on both patients and caregivers, an intervention to alleviate apathy would be of great benefit to society. ADMET 2 follows on the promising results from the original ADMET to evaluate the efficacy of methylphenidate as a

  5. Collaborative translational research leading to multicenter clinical trials in Duchenne muscular dystrophy: the Cooperative International Neuromuscular Research Group (CINRG).

    Science.gov (United States)

    Escolar, Diana M; Henricson, Erik K; Pasquali, Livia; Gorni, Ksenija; Hoffman, Eric P

    2002-10-01

    Progress in the development of rationally based therapies for Duchenne muscular dystrophy has been accelerated by encouraging multidisciplinary, multi-institutional collaboration between basic science and clinical investigators in the Cooperative International Research Group. We combined existing research efforts in pathophysiology by a gene expression profiling laboratory with the efforts of animal facilities capable of conducting high-throughput drug screening and toxicity testing to identify safe and effective drug compounds that target different parts of the pathophysiologic cascade in a genome-wide drug discovery approach. Simultaneously, we developed a clinical trial coordinating center and an international network of collaborating physicians and clinics where those drugs could be tested in large-scale clinical trials. We hope that by bringing together investigators at these facilities and providing the infrastructure to support their research, we can rapidly move new bench discoveries through animal model screening and into therapeutic testing in humans in a safe, timely and cost-effective setting.

  6. Evaluation of the Correlation of (He Distance Between the Alveolar Crest and Cementoenamel Junction Inpreiapical. Bitewing and Panoramic Radiographs with its Actual Distance

    Directory of Open Access Journals (Sweden)

    J. Yazdani

    2005-02-01

    Full Text Available Statement of Problem: In spite of the limitations of Radiography, diagnosing of periodontal diseases without having accurate radiographs is inadequate because it provides a visible image of the supporting bone to the clinician and works as a fixed measure of the supporting bone during the study.Purpose: The aim of this study is to compare the precision of preiapical, bitewings and panoramicradiographs in determining the distance between the alveolar crest (AC and cementoenamel junction (CEJ of teeth. Materials and Methods: Statistically this is a survey study in which 120 interproximal surfaces of teeth were measured during surgery by periodontal probing and recorded as the actual measurement. Then 40 sites underwent bitewing, 40 sites preapical and 40 others panoramic radiography and the distance of CEJ up to the alveolar crest of bone was measured on them by periodontal probe and recorded. Then each group was analyzed separately and the Pearson's correlation coefficient was examined for the data.Results: The results of this study showed that when the thickness of the remaining bone in a millimeter limit is important for (he surgeon, the bitewing radiography has a prime importance, but when bone loss ismoderate, the panoramic radiography showing %89 of the cases close to the actual measure, can be acceptable. On the other hand, in anterior sites for determining the bone alteration, preiapical radiography with a 0.93 correlation coefficient is superior to the panoramic radiography with a correlation coefficient of 0.72 and we suggest it for examining the changes of bone in these sites. Conclusion: whenever the bone alteration is moderate or severe, it seems that, bitewing radiography is of particular importance, but when the bone loss is little, panoramic radiography can be used and there is no needto put the patient on unnecessary radiation.

  7. Diet shift of double-crested cormorants in eastern Lake Ontario associated with the expansion of the invasive round goby

    Science.gov (United States)

    Johnson, James H.; Ross, Robert M.; McCullough, Russell D.; Mathers, Alastair

    2010-01-01

    The proliferation of the invasive round goby (Apollonia melanostoma) in the Great Lakes has caused shifts in the trophic ecology in some areas. We examined the diet of double-crested cormorants (Phalacrocorax auritas) prior to, and immediately after, round goby population expansion at two colonies, Pigeon and Snake Islands, in eastern Lake Ontario from 1999 to 2007. Cormorant diet was determined from the examination of 10,167 pellets collected over the nine-year period. By the second year round gobies were found in the diet (2002 at Snake Island and 2003 at Pigeon Island) they were the main species consumed by cormorants at each colony. The dominance of round goby in cormorant diets had a significant effect on both daily fish consumption and seasonal trends in fish consumption compared to the pre-goby years. Seasonal differences that were observed during the pre-goby years were lost once gobies became the main diet component of cormorants. The rapid switch to a benthic prey such as round goby, from a largely limnetic fish diet demonstrates the adaptive foraging ability of cormorants. Round goby may act as a buffer for yellow perch and smallmouth bass, two sport fish impacted by cormorant predation in eastern Lake Ontario.

  8. Epigenetic control of skull morphogenesis by histone deacetylase 8

    OpenAIRE

    Haberland, Michael; Mokalled, Mayssa H.; Montgomery, Rusty L.; Olson, Eric N.

    2009-01-01

    Histone deacetylases (Hdacs) are transcriptional repressors with crucial roles in mammalian development. Here we provide evidence that Hdac8 specifically controls patterning of the skull by repressing a subset of transcription factors in cranial neural crest cells. Global deletion of Hdac8 in mice leads to perinatal lethality due to skull instability, and this is phenocopied by conditional deletion of Hdac8 in cranial neural crest cells. Hdac8 specifically represses the aberrant expression of...

  9. [Early clinical trials in paediatric oncology in Spain: a nationwide perspective].

    Science.gov (United States)

    Bautista, Francisco; Gallego, Soledad; Cañete, Adela; Mora, Jaume; Díaz de Heredia, Cristina; Cruz, Ofelia; Fernández, José María; Rives, Susana; Berlanga, Pablo; Hladun, Raquel; Juan Ribelles, Antonio; Madero, Luis; Ramírez, Manuel; Fernández Delgado, Rafael; Pérez-Martínez, Antonio; Mata, Cristina; Llort, Anna; Martín Broto, Javier; Cela, María Elena; Ramírez, Gema; Sábado, Constantino; Acha, Tomás; Astigarraga, Itziar; Sastre, Ana; Muñoz, Ascensión; Guibelalde, Mercedes; Moreno, Lucas

    2017-09-01

    Cancer is the leading cause of death between the first year of life and adolescence, and some types of diseases are still a major challenge in terms of cure. There is, therefore, a major need for new drugs. Recent findings in cancer biology open the door to the development of targeted therapies against individual molecular changes, as well as immunotherapy. Promising results in adult anti-cancer drug development have not yet been translated into paediatric clinical practice. A report is presented on the activity in early paediatric oncology trials (phase I-II) in Spain. All members of the Spanish Society of Paediatric Haematology Oncology (SEHOP) were contacted in order to identify early clinical trials in paediatric cancer opened between 2005 and 2015. A total of 30 trials had been opened in this period: 21 (70%) in solid tumours, and 9 (30%) in malignant haemopathies. A total of 212 patients have been enrolled. The majority was industry sponsored (53%). Since 2010, four centres have joined the international consortium of Innovative Therapies for Children with Cancer (ITCC), which has as its aim to develop novel therapies for paediatric tumours. A significant number of new studies have opened since 2010, improving the treatment opportunities for our children. Results of recently closed trials show the contribution of Spanish investigators, the introduction of molecularly targeted agents, and their benefits. The activity in clinical trials has increased in the years analysed. The SEHOP is committed to develop and participate in collaborative academic trials, in order to help in the advancement and optimisation of existing therapies in paediatric cancer. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. FGF8 signaling sustains progenitor status and multipotency of cranial neural crest-derived mesenchymal cells in vivo and in vitro

    Science.gov (United States)

    Shao, Meiying; Liu, Chao; Song, Yingnan; Ye, Wenduo; He, Wei; Yuan, Guohua; Gu, Shuping; Lin, Congxin; Ma, Liang; Zhang, Yanding; Tian, Weidong; Hu, Tao; Chen, YiPing

    2015-01-01

    The cranial neural crest (CNC) cells play a vital role in craniofacial development and regeneration. They are multi-potent progenitors, being able to differentiate into various types of tissues. Both pre-migratory and post-migratory CNC cells are plastic, taking on diverse fates by responding to different inductive signals. However, what sustains the multipotency of CNC cells and derivatives remains largely unknown. In this study, we present evidence that FGF8 signaling is able to sustain progenitor status and multipotency of CNC-derived mesenchymal cells both in vivo and in vitro. We show that augmented FGF8 signaling in pre-migratory CNC cells prevents cell differentiation and organogenesis in the craniofacial region by maintaining their progenitor status. CNC-derived mesenchymal cells with Fgf8 overexpression or control cells in the presence of exogenous FGF8 exhibit prolonged survival, proliferation, and multi-potent differentiation capability in cell cultures. Remarkably, exogenous FGF8 also sustains the capability of CNC-derived mesenchymal cells to participate in organogenesis such as odontogenesis. Furthermore, FGF8-mediated signaling strongly promotes adipogenesis but inhibits osteogenesis of CNC-derived mesenchymal cells in vitro. Our results reveal a specific role for FGF8 in the maintenance of progenitor status and in fate determination of CNC cells, implicating a potential application in expansion and fate manipulation of CNC-derived cells in stem cell-based craniofacial regeneration. PMID:26243590

  11. Does Wrist Arthrodesis With Structural Iliac Crest Bone Graft After Wide Resection of Distal Radius Giant Cell Tumor Result in Satisfactory Function and Local Control?

    Science.gov (United States)

    Wang, Tao; Chan, Chung Ming; Yu, Feng; Li, Yuan; Niu, Xiaohui

    2017-03-01

    Many techniques have been described for reconstruction after distal radius resection for giant cell tumor with none being clearly superior. The favored technique at our institution is total wrist fusion with autogenous nonvascularized structural iliac crest bone graft because it is structurally robust, avoids the complications associated with obtaining autologous fibula graft, and is useful in areas where bone banks are not available. However, the success of arthrodesis and the functional outcomes with this approach, to our knowledge, have only been limitedly reported. (1) What is the success of union of these grafts and how long does it take? (2) How effective is the technique in achieving tumor control? (3) What complications occur with this type of arthrodesis? (4) What are the functional results of wrist arthrodesis by this technique for treating giant cell tumor of the distal radius? Between 2005 and 2013, 48 patients were treated for biopsy-confirmed Campanacci Grade III giant cell tumor of the distal radius. Of those, 39 (81% [39 of 48]) were treated with wrist arthrodesis using autogenous nonvascularized iliac crest bone graft. Of those, 27 (69% [27 of 39]) were available for followup at a minimum of 24 months (mean, 45 months; range, 24-103 months). During that period, the general indications for this approach were Campanacci Grade III and estimated resection length of 8 cm or less. Followup included clinical and radiographic assessment and functional assessment using the Disabilities of the Arm, Shoulder and Hand (DASH) score, the Musculoskeletal Tumor Society (MSTS) score, grip strength, and range of motion at every followup by the treating surgeon and his team. All functional results were from the latest followup of each patient. Union of the distal junction occurred at a mean of 4 months (± 2 months) and union of the proximal junction occurred at a mean of 9 months (± 5 months). Accounting for competing events, at 12 months, the rate of proximal

  12. Regulating clinical trials in India: the economics of ethics.

    Science.gov (United States)

    Porter, Gerard

    2017-07-09

    The relationship between the ethical standards for the governance of clinical trials and market forces can be complex and problematic. This article uses India as a case study to explore this nexus. From the mid-2000s, India became a popular destination for foreign-sponsored clinical trials. The Indian government had sought to both attract clinical trials and ensure these would be run in line with internationally accepted ethical norms. Reports of controversial medical research, however, triggered debate about the robustness and suitability of India's regulatory system. In response to civil society pressure and interventions by the Supreme Court, the Indian government proposed additional measures aimed at strengthening protections for clinical trial participants. Whilst the reforms can be seen as a victory for human rights activists, they have also been criticised as being overly burdensome for sponsors. Indeed, their announcement prompted an exodus of clinical trials from India. Fearful of losing business to 'rival' countries, the Indian government is revisiting some of its proposals. The Indian example suggests that research ethics frameworks and national policies for economic development are increasingly intertwined. Host countries are in theory free to improve the lot of research participants, but doing so may make them appear less attractive to foreign sponsors, who can simply shift their activities to more industry-friendly jurisdictions. Although these economic pressures are unlikely to lead to a regulatory 'race to the bottom', they may limit host countries' ability to enact socially desirable reforms. © 2017 John Wiley & Sons Ltd.

  13. Current perspectives in fragment-based lead discovery (FBLD)

    Science.gov (United States)

    Lamoree, Bas; Hubbard, Roderick E.

    2017-01-01

    It is over 20 years since the first fragment-based discovery projects were disclosed. The methods are now mature for most ‘conventional’ targets in drug discovery such as enzymes (kinases and proteases) but there has also been growing success on more challenging targets, such as disruption of protein–protein interactions. The main application is to identify tractable chemical startpoints that non-covalently modulate the activity of a biological molecule. In this essay, we overview current practice in the methods and discuss how they have had an impact in lead discovery – generating a large number of fragment-derived compounds that are in clinical trials and two medicines treating patients. In addition, we discuss some of the more recent applications of the methods in chemical biology – providing chemical tools to investigate biological molecules, mechanisms and systems. PMID:29118093

  14. Single lead atrial vs. dual chamber pacing in sick sinus syndrome

    DEFF Research Database (Denmark)

    Brandt, Niels H; Kirkfeldt, Rikke Esberg; Nielsen, Jens Cosedis

    2017-01-01

    Aims The DANPACE trial randomized patients with sick sinus syndrome (SSS) to single lead atrial (AAIR) or dual chamber (DDDR) pacemaker (PM). After 5 years follow-up, no difference in overall survival, stroke or heart failure (HF) was observed, whereas risk of atrial fibrillation (AF) and PM...... This register-based long-term follow-up study indicates that there is no difference in mortality among patients with SSS randomized to AAIR or DDDR pacing, even with very long follow-up. Nor is there any difference in risk of AF hospitalization, stroke or HF. The higher rate of pacing mode-change to DDDR...

  15. Digital pathology in nephrology clinical trials, research, and pathology practice.

    Science.gov (United States)

    Barisoni, Laura; Hodgin, Jeffrey B

    2017-11-01

    In this review, we will discuss (i) how the recent advancements in digital technology and computational engineering are currently applied to nephropathology in the setting of clinical research, trials, and practice; (ii) the benefits of the new digital environment; (iii) how recognizing its challenges provides opportunities for transformation; and (iv) nephropathology in the upcoming era of kidney precision and predictive medicine. Recent studies highlighted how new standardized protocols facilitate the harmonization of digital pathology database infrastructure and morphologic, morphometric, and computer-aided quantitative analyses. Digital pathology enables robust protocols for clinical trials and research, with the potential to identify previously underused or unrecognized clinically useful parameters. The integration of digital pathology with molecular signatures is leading the way to establishing clinically relevant morpho-omic taxonomies of renal diseases. The introduction of digital pathology in clinical research and trials, and the progressive implementation of the modern software ecosystem, opens opportunities for the development of new predictive diagnostic paradigms and computer-aided algorithms, transforming the practice of renal disease into a modern computational science.

  16. Person mobility in the design and analysis of cluster-randomized cohort prevention trials.

    Science.gov (United States)

    Vuchinich, Sam; Flay, Brian R; Aber, Lawrence; Bickman, Leonard

    2012-06-01

    Person mobility is an inescapable fact of life for most cluster-randomized (e.g., schools, hospitals, clinic, cities, state) cohort prevention trials. Mobility rates are an important substantive consideration in estimating the effects of an intervention. In cluster-randomized trials, mobility rates are often correlated with ethnicity, poverty and other variables associated with disparity. This raises the possibility that estimated intervention effects may generalize to only the least mobile segments of a population and, thus, create a threat to external validity. Such mobility can also create threats to the internal validity of conclusions from randomized trials. Researchers must decide how to deal with persons who leave study clusters during a trial (dropouts), persons and clusters that do not comply with an assigned intervention, and persons who enter clusters during a trial (late entrants), in addition to the persons who remain for the duration of a trial (stayers). Statistical techniques alone cannot solve the key issues of internal and external validity raised by the phenomenon of person mobility. This commentary presents a systematic, Campbellian-type analysis of person mobility in cluster-randomized cohort prevention trials. It describes four approaches for dealing with dropouts, late entrants and stayers with respect to data collection, analysis and generalizability. The questions at issue are: 1) From whom should data be collected at each wave of data collection? 2) Which cases should be included in the analyses of an intervention effect? and 3) To what populations can trial results be generalized? The conclusions lead to recommendations for the design and analysis of future cluster-randomized cohort prevention trials.

  17. Prevention of abdominal wound infection (PROUD trial, DRKS00000390: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Heger Ulrike

    2011-11-01

    Full Text Available Abstract Background Wound infection affects a considerable portion of patients after abdominal operations, increasing health care costs and postoperative morbidity and affecting quality of life. Antibacterial coating has been suggested as an effective measure to decrease postoperative wound infections after laparotomies. The INLINE metaanalysis has recently shown the superiority of a slowly absorbable continuous suture for abdominal closure; with PDS plus® such a suture has now been made available with triclosan antibacterial coating. Methods/Design The PROUD trial is designed as a randomised, controlled, observer, surgeon and patient blinded multicenter superiority trial with two parallel groups and a primary endpoint of wound infection during 30 days after surgery. The intervention group will receive triclosan coated polydioxanone sutures, whereas the control group will receive the standard polydioxanone sutures; abdominal closure will otherwise be standardized in both groups. Statistical analysis is based on intention-to-treat population via binary logistic regression analysis, the total sample size of n = 750 is sufficient to ensure alpha = 5% and power = 80%, an interim analysis will be carried out after data of 375 patients are available. Discussion The PROUD trial will yield robust data to determine the effectiveness of antibacterial coating in one of the standard sutures for abdominal closure and potentially lead to amendment of current guidelines. The exploration of clinically objective parameters as well as quality of life holds immediate relevance for clinical management and the pragmatic trial design ensures high external validity. Trial Registration The trial protocol has been registered with the German Clinical Trials Register (DRKS00000390.

  18. Prospective evaluation of chronic pain associated with posterior autologous iliac crest bone graft harvest and its effect on postoperative outcome

    Directory of Open Access Journals (Sweden)

    Wang David A

    2009-05-01

    Full Text Available Abstract Background Autogenous Iliac Crest Bone Graft (ICBG has been the "gold standard" for spinal fusion. However, bone graft harvest may lead to complications, such as chronic pain, numbness, and poor cosmesis. The long-term impact of these complications on patient function and well-being has not been established but is critical in determining the value of expensive bone graft substitutes such as recombinant bone morphogenic protein. We thus aimed to investigate the long-term complications of ICBG. Our second aim was to evaluate the psychometric properties of a new measure of ICBG morbidity that would be useful for appropriately gauging spinal surgery outcomes. Methods Prospective study of patients undergoing spinal fusion surgery with autologous ICBG. The SF-36v2, Oswestry Disability Index, and a new 14-item follow-up questionnaire addressing persistent pain, functional limitation, and cosmesis were administered with an 83% response rate. Multiple regression analyses examined the independent effect of ICBG complications on physical and mental health and disability. Results The study population included 170 patients with a mean age of 51.1 years (SD = 12.2 and balanced gender (48% male. Lumbar fusion patients predominated (lumbar = 148; cervical n = 22. At 3.5 years mean follow-up, 5% of patients reported being bothered by harvest site scar appearance, 24% reported harvest site numbness, and 13% reported the numbness as bothersome. Harvest site pain resulted in difficulty with household chores (19%, recreational activity (18%, walking (16%, sexual activity (16%, work activity (10%, and irritation from clothing (9%. Multivariate regression analyses revealed that persistent ICBG complications 3.5 years post-surgery were associated with significantly worse disability and showed a trend association with worse physical health, after adjusting for age, workers' compensation status, surgical site pain, and arm or leg pain. There was no association

  19. Prospective evaluation of chronic pain associated with posterior autologous iliac crest bone graft harvest and its effect on postoperative outcome.

    Science.gov (United States)

    Schwartz, Carolyn E; Martha, Julia F; Kowalski, Paulette; Wang, David A; Bode, Rita; Li, Ling; Kim, David H

    2009-05-29

    Autogenous Iliac Crest Bone Graft (ICBG) has been the "gold standard" for spinal fusion. However, bone graft harvest may lead to complications, such as chronic pain, numbness, and poor cosmesis. The long-term impact of these complications on patient function and well-being has not been established but is critical in determining the value of expensive bone graft substitutes such as recombinant bone morphogenic protein. We thus aimed to investigate the long-term complications of ICBG. Our second aim was to evaluate the psychometric properties of a new measure of ICBG morbidity that would be useful for appropriately gauging spinal surgery outcomes. Prospective study of patients undergoing spinal fusion surgery with autologous ICBG. The SF-36v2, Oswestry Disability Index, and a new 14-item follow-up questionnaire addressing persistent pain, functional limitation, and cosmesis were administered with an 83% response rate. Multiple regression analyses examined the independent effect of ICBG complications on physical and mental health and disability. The study population included 170 patients with a mean age of 51.1 years (SD = 12.2) and balanced gender (48% male). Lumbar fusion patients predominated (lumbar = 148; cervical n = 22). At 3.5 years mean follow-up, 5% of patients reported being bothered by harvest site scar appearance, 24% reported harvest site numbness, and 13% reported the numbness as bothersome. Harvest site pain resulted in difficulty with household chores (19%), recreational activity (18%), walking (16%), sexual activity (16%), work activity (10%), and irritation from clothing (9%). Multivariate regression analyses revealed that persistent ICBG complications 3.5 years post-surgery were associated with significantly worse disability and showed a trend association with worse physical health, after adjusting for age, workers' compensation status, surgical site pain, and arm or leg pain. There was no association between ICBG complications and mental health in

  20. The recruitment of patients to trials in head and neck cancer: a qualitative study of the EaStER trial of treatments for early laryngeal cancer.

    Science.gov (United States)

    Hamilton, D W; de Salis, I; Donovan, J L; Birchall, M

    2013-08-01

    We aimed to investigate the factors contributing to poor recruitment to the EaStER trial "Early Stage glottic cancer: Endoscopic excision or Radiotherapy" feasibility study. We performed a prospective qualitative assessment of the EaStER trial at three centres to investigate barriers to recruitment and implement changes. Methods used included semi-structured interviews, focus groups and audio-recordings of recruitment encounters. First, surgeons and recruiters did not all accept the primary outcome as the rationale for the trial. Surgeons did not always adhere to the trial eligibility criteria leading to variations between centres in the numbers of "eligible" patients. Second, as both treatments were considered equally successful, recruiters and patients focused on the pragmatics of the different trial arms, favouring surgery over radiotherapy. The lack of equipoise was reflected in the way recruiters presented trial information. Third, patient views, beliefs and preferences were not fully elicited or addressed by recruiters. Fourth, in some centres, logistical issues made trial participation difficult. This qualitative research identified several major issues that explained recruitment difficulties. While there was insufficient time to address these in the EaStER trial, several factors would need to be addressed to launch further RCTs in head and neck cancer. These include the need for clear ongoing agreement among recruiting clinicians regarding details in the study protocol; an understanding of the logistical issues hindering recruitment at individual centres; and training recruiters to enable them to explain the need for randomisation and the rationale for the RCT to patients.