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Sample records for vivo investigative protocol

  1. An in vivo investigative protocol for HDR prostate brachytherapy using urethral and rectal thermoluminescence dosimetry

    International Nuclear Information System (INIS)

    Toye, Warren; Das, Ram; Kron, Tomas; Franich, Rick; Johnston, Peter; Duchesne, Gillian

    2009-01-01

    Purpose: To develop an in vivo dosimetry based investigative action level relevant for a corrective protocol for HDR brachytherapy boost treatment. Methods and materials: The dose delivered to points within the urethra and rectum was measured using TLD in vivo dosimetry in 56 patients. Comparisons between the urethral and rectal measurements and TPS calculations showed differences, which are related to the relative position of the implant and TLD trains, and allowed shifts of implant position relative to the prostate to be estimated. Results and conclusions: Analysis of rectal dose measurements is consistent with implant movement, which was previously only identified with the urethral data. Shift corrected doses were compared with results from the TPS. Comparison of peak doses to the urethra and rectum has been assessed against the proposed corrective protocol to limit overdosing these critical structures. An initial investigative level of 20% difference between measured and TPS peak dose was established, which corresponds to 1/3 of patients which was practical for the caseload. These patients were assessed resulting in corrective action being applied for one patient. Multiple triggering for selective investigative action is outlined. The use of a single in vivo measurement in the first fraction optimizes patient benefit at acceptable cost.

  2. In-vivo optical investigation of psoriasis

    Science.gov (United States)

    Kapsokalyvas, Dimitrios; Cicchi, Riccardo; Bruscino, Nicola; Alfieri, Domenico; Massi, Daniela; Lotti, Torello; Pavone, Francesco S.

    2011-03-01

    Psoriasis is an autoimmune disease of the skin characterized by hyperkeratosis, hyperproliferation of the epidermis, inflammatory cell accumulation and increased dilatation of dermal papillary blood vessels. Cases of psoriasis were investigated in vivo with optical means in order to evaluate the potential of in vivo optical biopsy. A Polarization Multispectral Dermoscope was employed for the macroscopic observation. Features such as the 'dotted' blood vessels pattern was observed with high contrast. The average size of dot vessels in Psoriasis was measured to be 974 μm2 which is much higher compared to healthy skin. High resolution image sections of the epidermis and the dermis were produced with a custom made Multiphoton Microscope. Imaging extended from the surface of the lesion down to the papillary dermis, at a depth of 200 μm. In the epidermis, a characteristic morphology of the stratum corneum found only in Psoriasis was revealed. Additionally, the cytoplasmic area of the cells in the stratum spinosum layer was found to be smaller than normal. In the dermis the morphological features were more pronounced, where the elongated dermal papillae dominated the papillary layer. Their length exceeds 100μm, which is a far greater value compared to that of healthy skin. These in vivo observations are consistent with the ex vivo histopathological observations, supporting both the applicability and potentiality of multispectral dermoscopy and multiphoton microscopy in the field of in vivo optical investigation and biopsy of skin.

  3. In vivo cellular imaging using fluorescent proteins - Methods and Protocols

    Directory of Open Access Journals (Sweden)

    M. Monti

    2012-12-01

    Full Text Available The discovery and genetic engineering of fluorescent proteins has revolutionized cell biology. What was previously invisible to the cell often can be made visible with the use of fluorescent proteins. With this words, Robert M. Hoffman introduces In vivo Cellular Imaging Using Fluorescent proteins, the eighteen chapters book dedicated to the description of how fluorescence proteins have changed the way to analyze cellular processes in vivo. Modern researches aim to study new and less invasive methods able to follow the behavior of different cell types in different biological contexts: for example, how cancer cells migrate or how they respond to different therapies. Also, in vivo systems can help researchers to better understand animal embryonic development so as how fluorescence proteins may be used to monitor different processes in living organisms at the molecular and cellular level.

  4. Investigations on renal organic and inorganic solutes, in vivo

    International Nuclear Information System (INIS)

    Wolff, S.D.

    1989-01-01

    A basic question in renal physiology is how do the cells of the renal medulla survive the high concentrations of sodium chloride and urea which occur with antidiuresis. The problem is two-fold: (1) urea, being highly permeable to cell membranes, should enter the cell and adversely affect protein function; and (2) inorganic ions, being in much higher concentration extracellularly than intracellularly should dehydrate the cell. If these organic solutes exist in response to high concentrations of sodium chloride and urea, then their content should vary with diuretic state. Two protocols were developed to test the validity of this hypothesis. The first protocol used 31 P-NMR in vivo to monitor GPC content before, during, and after acute diuresis in an exteriorized rabbit kidney model. Changes in sodium distribution and tissue structure were monitored dynamically with 23 Na- and 1 H-NMR imaging, respectively. The second protocol used HPLC to quantitate each of the four organic solutes in renal inner medullary homogenates. Here, the effect of diuretic state and acute diuresis on organic solute content was assessed

  5. In-vivo morphologic and spectroscopic investigation of Psoriasis

    Science.gov (United States)

    Kapsokalyvas, Dimitrios; Cicchi, Riccardo; Bruscino, Nicola; Alfieri, Domenico; Massi, Daniela; Lotti, Torello; Pavone, Francesco S.

    2011-07-01

    Psoriasis is an autoimmune disease of the skin characterized by hyperkeratosis, hyperproliferation of the epidermis, inflammatory cell accumulation and increased dilatation of dermal papillary blood vessels. Cases of psoriasis were investigated in vivo with optical means in order to evaluate the potential of in vivo optical biopsy. A Polarization Multispectral Dermoscope was employed for the macroscopic observation. Features such as the 'dotted' blood vessels pattern was observed with high contrast. High resolution image sections of the epidermis and the dermis were produced with a custom made Multiphoton Microscope. Imaging extended from the surface of the lesion down to the papillary dermis, at a depth of 200 μm. In the epidermis, a characteristic morphology of the stratum corneum found only in Psoriasis was revealed. Additionally, the cytoplasmic area of the cells in the stratum spinosum layer was found to be smaller than normal. In the dermis the morphological features were more pronounced, where the elongated dermal papillae dominated the papillary layer. Their length exceeds 100μm, which is a far greater value compared to that of healthy skin. These in vivo observations are consistent with the ex vivo histopathological observations, supporting both the applicability and potentiality of multispectral dermoscopy and multiphoton microscopy in the field of in vivo optical investigation and biopsy of skin.

  6. Freesurfer cortical normative data for adults using Desikan-Killiany-Tourville and ex vivo protocols.

    Science.gov (United States)

    Potvin, Olivier; Dieumegarde, Louis; Duchesne, Simon

    2017-08-01

    We recently built normative data for FreeSurfer morphometric estimates of cortical regions using its default atlas parcellation (Desikan-Killiany or DK) according to individual and scanner characteristics. We aimed to produced similar normative values for Desikan-Killianny-Tourville (DKT) and ex vivo-based labeling protocols, as well as examine the differences between these three atlases. Surfaces, thicknesses, and volumes of cortical regions were produced using cross-sectional magnetic resonance scans from the same 2713 healthy individuals aged 18-94 years as used in the reported DK norms. Models predicting regional cortical estimates of each hemisphere were produced using age, sex, estimated intracranial volume (eTIV), scanner manufacturer and magnetic field strength (MFS) as predictors. The DKT and DK models generally included the same predictors and produced similar R 2 . Comparison between DK, DKT, ex vivo atlases normative cortical measures showed that the three protocols generally produced similar normative values. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Two in-vivo protocols for testing virucidal efficacy of handwashing and hand disinfection.

    Science.gov (United States)

    Steinmann, J; Nehrkorn, R; Meyer, A; Becker, K

    1995-01-01

    Whole-hands and fingerpads of seven volunteers were contaminated with poliovirus type 1 Sabin strain in order to evaluate virucidal efficacy of different forms of handwashing and handrub with alcohols and alcohol-based disinfectants. In the whole-hand protocol, handwashing with unmedicated soap for 5 min and handrubbing with 80% ethanol yielded a log reduction factor (RF) of > 2, whereas the log RF by 96.8% ethanol exceeded 3.2. With the fingerpad model ethanol produced a greater log RF than iso- or n-propanol. Comparing five commercial hand disinfectants and a chlorine solution (1.0% chloramine T-solution) for handrub, Desderman and Promanum, both composed of ethanol, yielded log RFs of 2.47 and 2.26 respectively after an application time of 60 s, similar to 1.0% chloramine T-solution (log RF of 2.28). Autosept, Mucasept, and Sterillium, based on n-propanol and/or isopropanol, were found to be significantly less effective (log RFs of 1.16, 1.06 and 1.52 respectively). A comparison of a modified whole-hand and the fingerpad protocol with Promanum showed similar results with the two systems suggesting both models are suitable for testing the in-vivo efficacy of handwashing agents and hand disinfectants which are used without any water.

  8. Samples and Sampling Protocols for Scientific Investigations | Joel ...

    African Journals Online (AJOL)

    ... from sampling, through sample preparation, calibration to final measurement and reporting. This paper, therefore offers useful information on practical guidance on sampling protocols in line with best practice and international standards. Keywords: Sampling, sampling protocols, chain of custody, analysis, documentation ...

  9. Immunosuppression for in vivo research: state-of-the-art protocols and experimental approaches

    Institute of Scientific and Technical Information of China (English)

    Rita Diehl; Fabienne Ferrara; Claudia Müller; Antje Y Dreyer; Damian D McLeod; Stephan Fricke; Johannes Boltze

    2017-01-01

    Almost every experimental treatment strategy using non-autologous cell,tissue or organ transplantation is tested in small and large animal models before clinical translation.Because these strategies require immunosuppression in most cases,immunosuppressive protocols are a key element in transplantation experiments.However,standard immunosuppressive protocols are often applied without detailed knowledge regarding their efficacy within the particular experimental setting and in the chosen model species.Optimization of such protocols is pertinent to the translation of experimental results to human patients and thus warrants further investigation.This review summarizes current knowledge regarding immunosuppressive drug classes as well as their dosages and application regimens with consideration of species-specific drug metabolization and side effects.It also summarizes contemporary knowledge of novel immunomodulatory strategies,such as the use of mesenchymal stem cells or antibodies.Thus,this review is intended to serve as a state-of-the-art compendium for researchers to refine applied experimental immunosuppression and immunomodulation strategies to enhance the predictive value of preclinical transplantation studies.

  10. Comparison of Diffusion MRI Acquisition Protocols for the In Vivo Characterization of the Mouse Spinal Cord: Variability Analysis and Application to an Amyotrophic Lateral Sclerosis Model.

    Science.gov (United States)

    Figini, Matteo; Scotti, Alessandro; Marcuzzo, Stefania; Bonanno, Silvia; Padelli, Francesco; Moreno-Manzano, Victoria; García-Verdugo, José Manuel; Bernasconi, Pia; Mantegazza, Renato; Bruzzone, Maria Grazia; Zucca, Ileana

    2016-01-01

    Diffusion-weighted Magnetic Resonance Imaging (dMRI) has relevant applications in the microstructural characterization of the spinal cord, especially in neurodegenerative diseases. Animal models have a pivotal role in the study of such diseases; however, in vivo spinal dMRI of small animals entails additional challenges that require a systematical investigation of acquisition parameters. The purpose of this study is to compare three acquisition protocols and identify the scanning parameters allowing a robust estimation of the main diffusion quantities and a good sensitivity to neurodegeneration in the mouse spinal cord. For all the protocols, the signal-to-noise and contrast-to noise ratios and the mean value and variability of Diffusion Tensor metrics were evaluated in healthy controls. For the estimation of fractional anisotropy less variability was provided by protocols with more diffusion directions, for the estimation of mean, axial and radial diffusivity by protocols with fewer diffusion directions and higher diffusion weighting. Intermediate features (12 directions, b = 1200 s/mm2) provided the overall minimum inter- and intra-subject variability in most cases. In order to test the diagnostic sensitivity of the protocols, 7 G93A-SOD1 mice (model of amyotrophic lateral sclerosis) at 10 and 17 weeks of age were scanned and the derived diffusion parameters compared with those estimated in age-matched healthy animals. The protocols with an intermediate or high number of diffusion directions provided the best differentiation between the two groups at week 17, whereas only few local significant differences were highlighted at week 10. According to our results, a dMRI protocol with an intermediate number of diffusion gradient directions and a relatively high diffusion weighting is optimal for spinal cord imaging. Further work is needed to confirm these results and for a finer tuning of acquisition parameters. Nevertheless, our findings could be important for the

  11. Experimental investigation of quantum communication protocols in higher dimensions

    International Nuclear Information System (INIS)

    Groeblacher, S.; Stuetz, M.; Vaziri, A.; Jennewein, T.; Zeilinger, A.

    2005-01-01

    Full text: Higher dimensional quantum systems, such as qutrits, offer unique possibilities for quantum communication. In particular, quantum key distribution may be realized with a higher security margin than with qubit systems. We plan to demonstrate quantum cryptography with entangled photonic qutrits based on orbital angular momentum (OAM). Therefore we test various methods of manipulating and transforming OAM states of photons, which is required for the implementation of quantum communication protocols. (author)

  12. Modified Scoring, Traditional Item Analysis, and Sato's Caution Index Used To Investigate the Reading Recall Protocol.

    Science.gov (United States)

    Deville, Craig W.; Chalhoub-Deville, Micheline

    A study demonstrated the utility of item analyses to investigate which items function well or poorly in a second language reading recall protocol instrument. Data were drawn from a larger study of 56 learners of German as a second language at various proficiency levels. Pausal units of scored recall protocols were analyzed using both classical…

  13. Investigating a reduced size real-time transport protocol for low-bandwidth networks

    CSIR Research Space (South Africa)

    Kakande, JN

    2011-09-01

    Full Text Available in this work as RTP-Lite, requires investigation. A cyclical approach to compression of the RTP headers was used with different compression cycle patterns for Transmission Control Protocol (TCP) and User Datagram Protocol (UDP) transport. Measurements over...

  14. Development and utilization of an ex vivo bromodeoxyuridine local lymph node assay protocol for assessing potential chemical sensitizers.

    Science.gov (United States)

    Williams, W C; Copeland, C; Boykin, E; Quell, S J; Lehmann, D M

    2015-01-01

    The murine local lymph node assay (LLNA) is widely used to identify chemicals that may cause allergic contact dermatitis. Exposure to a dermal sensitizer results in proliferation of local lymph node T cells, which has traditionally been measured by in vivo incorporation of [(3) H]methyl thymidine. A more recent non-isotopic variation of the assay utilizes bromodeoxyuridine (BrdU) incorporation in vivo. To further improve the utility of this assay, we developed an ex vivo BrdU labeling procedure eliminating the need for in vivo injections. The results of this assay correctly identified a strong sensitizer (i.e., trimellitic anhydride) as well as weak/moderate sensitizers (i.e., eugenol, cinnamaldehyde and hexylcinnaminic aldehyde). As anticipated, neither non-sensitizers isopropanol and lactic acid nor the false negative chemical nickel II sulfate hexahydrate induced a positive threshold response in the assay. The results of this assay are in close agreement with those of the in vivo LLNA:BrdU-enzyme-linked immunosorbent assay labeling procedure. We also used the ex vivo BrdU LLNA procedure to evaluate ammonium hexachloroplatinate, ammonium tetrachloroplatinate and cis-diamminedichloroplatinum(II) and the assay correctly identified them as sensitizers based on the calculation of EC2 values. We conclude that this ex vivo BrdU labeling method offers predictive capacity comparable to previously established LLNA protocols while eliminating animal injections and the use of radioisotope. Published 2014. This article is a U.S. Government work and is in the public domain in the USA. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  15. Investigation into Practical Implementations of a Zero Knowledge Protocol.

    Energy Technology Data Exchange (ETDEWEB)

    Marleau, Peter [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Krentz-Wee, Rebecca E. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-02-01

    In recent years, the concept of Zero Knowledge Protocols (ZKP) as a useful approach to nuclear warhead verification has become increasingly popular. Several implementations of ZKP have been proposed, driving technology development toward proof of concept demonstrations. Whereas proposed implementations seem to fall within the general class of template-based techniques, all physical implementations of ZKPs proposed to date have a complication: once the instrumentation is prepared, it is no longer authenticatable; the instrument physically contains sensitive information. In this work we explore three different concepts that may offer more authenticatable and practical ZKP implementations and evaluate the sensitive information that may be at risk when doing so: sharing a subset of detector counts in a preloaded image (with spatial information removed), real-time image subtraction, and a new concept, CONfirmation using a Fast-neutron Imaging Detector with Anti-image NULL-positive Time Encoding (CONFIDANTE). CONFIDANTE promises to offer an almost ideal implementation of ZKP: a positive result is indicated by a constant rate at all times enabling the monitoring party the possibility of full access to the instrument before, during, and after confirmation. A prototype of CONFIDANTE was designed, built, and its performance evaluated in a series of measurements of several objects including a set of plutonium dioxide Hemispheres. Very encouraging results proving feasibility are presented. 1 Rebecca is currently a graduate student in Nuclear Engineering at UC Berkeley

  16. Ex vivo sentinel lymph node investigation in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Antônio Hilário Alves Freitas

    2013-01-01

    Full Text Available Introduction: In Brazil, about 26,000 cases of colorectal cancer are diagnosed per year. Pa- tients considered at the early stage of disease (without lymph node evolve with tumor relapse or recurrence in up to a quarter of cases, probably due to understaging. Objective: Research on ex vivo sentinel lymph node in patients with colorectal adenocarcinoma. Materials and methods: We studied 37 patients who underwent curative surgical resection. The marker used to identify lymph nodes was patent blue dye injected into the peritu- moral submucosa of the open surgical specimen immediately after its removal from the abdominal cavity. Results: Ex vivo identification of sentinel lymph node with marker occurred in 13 (35.1% patients. The sensitivity was 40% and 60% false negative. The detailed histological examina- tion of sentinel lymph nodes with multilevel section and immunohistochemistry showed metastasis in one (4.3% individual, considered ultra-staging. Conclusion: The ex vivo identification of sentinel lymph node had questionable benefits, and worse results when include patients with rectal cancer. Restaging of one patient was possible after multilevel section and immunohistochemistry of the sentinel lymph node, but more research is needed to evaluate the role of micrometastases in patients with colorectal cancer. Resumo: Introdução: No Brasil, a cada ano são diagnosticados cerca de 26.000 casos de câncer colorre- tal. Pacientes com estadiamento considerado inicial, sem linfonodo metastático, evoluem com recorrência ou recidiva do tumor em até um quarto dos casos, por provável subesta- diamento. Objetivo: pesquisar sobre linfonodo-sentinela ex vivo em pacientes com adeno- carcinoma colorretal. Objetivo: Foram estudados 37 pacientes, submetidos à cirurgia oncológica com ressecção caráter curativo. O marcador de linfonodos utilizado foi o corante azul patente, injetado na submucosa peritumoral da peça cirúrgica aberta imediatamente

  17. Investigating Long-Term Monitoring Protocols in support of Quivira NWR Habitat Objectives

    Data.gov (United States)

    Department of the Interior — The project purpose is to investigate long-term monitoring protocols in support of Quivira NWR habitat objectives as described in the Refuge’s recently approved CCP...

  18. Study protocol for a multicenter investigation of reablement in Norway.

    Science.gov (United States)

    Langeland, Eva; Langland, Eva; Tuntland, Hanne; Førland, Oddvar; Aas, Eline; Folkestad, Bjarte; Jacobsen, Frode F; Kjeken, Ingvild

    2015-09-15

    Reablement is a promising new rehabilitation model, which is being implemented in some Western countries to meet current and future needs for home-based services. There is a need for further investigation of the effects of reablement among community-dwelling adults in terms of clinical and economic outcomes. This study will investigate the effectiveness of reablement in home-dwelling adults compared with standard treatment in terms of daily activities, physical functioning, health-related quality of life, coping, mental health, use of health care services, and costs. The study is a multicenter controlled trial. In total, 44 Norwegian municipalities will participate, including eight municipalities as a control group. For three municipalities with two zones, one will be assigned to the control group and the other to the intervention group. The experimental group will be offered reablement and the control group standard treatment. The sample will comprise approximately 750 participants. People will be eligible if they are home-dwelling adults, understand Norwegian, and have functional decline. Participants will be assessed at baseline, and after 10 weeks, 6 months, and 12 months. The primary outcome will be activity and participation measured by the Canadian Occupational Performance Measure. Physical functioning will be measured by the Short Physical Performance Battery and health-related quality of life by the European Quality of Life Scale. Coping will be measured by the Sense of Coherence questionnaire and mental health by the Mental Health Continuum Short Form. Costs will be generated based on registered working hours in different professions. Data analyses will be performed according to intention to treat. Univariate analysis of covariance will be used to investigate differences between the groups at baseline and the end of intervention. The data will be organized into two levels using a multilevel structure, i.e., individuals and municipalities, which will be

  19. Imaging techniques and investigation protocols in pediatric emergency imaging

    International Nuclear Information System (INIS)

    Scharitzer, M.; Hoermann, M.; Puig, S.; Prokop, M.

    2002-01-01

    Paediatric emergencies demand a quick and efficient radiological investigation with special attention to specific adjustments related to patient age and radiation protection. Imaging modalities are improving rapidly and enable to diagnose childhood diseases and injuries more quickly, accurately and safely. This article provides an overview of imaging techniques adjusted to the age of the child and an overview of imaging strategies of common paediatric emergencies. Optimising the imaging parameters (digital radiography, different screen-film systems, exposure specifications) allows for substantial reduction of radiation dose. Spiral- and multislice-CT reduce scan time and enable a considerable reduction of radiation exposure if scanning parameters (pitch setting, tube current) are properly adjusted. MRI is still mainly used for neurological or spinal emergencies despite the advent of fast imaging sequences. The radiologist's task is to select an appropriate imaging strategy according to expected differential diagnosis and to adjust the imaging techniques to the individual patient. (orig.) [de

  20. Ex vivo investigation of magnetically targeted drug delivery system

    International Nuclear Information System (INIS)

    Yoshida, Y.; Fukui, S.; Fujimoto, S.; Mishima, F.; Takeda, S.; Izumi, Y.; Ohtani, S.; Fujitani, Y.; Nishijima, S.

    2007-01-01

    In conventional systemic drug delivery the drug is administered by intravenous injection; it then travels to the heart from where it is pumped to all regions of the body. When the drug is aimed at a small target region, this method is extremely inefficient and leads to require much larger doses than those being necessary. In order to overcome this problem a number of targeted drug delivery methods are developed. One of these, magnetically targeted drug delivery system (MT-DDS) will be a promising way, which involves binding a drug to small biocompatible magnetic particles, injecting these into the blood stream and using a high gradient magnetic field to pull them out of suspension in the target region. In the present paper, we describe an ex vivo experimental work. It is also reported that navigation and accumulation test of the magnetic particles in the Y-shaped glass tube was performed in order to examine the threshold of the magnetic force for accumulation. It is found that accumulation of the magnetic particles was succeeded in the blood vessel when a permanent magnet was placed at the vicinity of the blood vessel. This result indicates the feasibility of the magnetically drug targeting in the blood vessel

  1. Histo-FISH protocol to detect bacterial compositions and biofilms formation in vivo.

    Science.gov (United States)

    Madar, M; Slizova, M; Czerwinski, J; Hrckova, G; Mudronova, D; Gancarcikova, S; Popper, M; Pistl, J; Soltys, J; Nemcova, R

    2015-01-01

    The study of biofilm function in vivo in various niches of the gastrointestinal tract (GIT) is rather limited. It is more frequently used in in vitro approaches, as an alternative to the studies focused on formation mechanisms and function of biofilms, which do not represent the actual in vivo complexity of microbial structures. Additionally, in vitro tests can sometimes lead to unreliable results. The goal of this study was to develop a simple approach to detect bacterial populations, particularly Lactobacillus and Bifidobacterium in biofilms, in vivo by the fluorescent in situ hybridisation (FISH) method. We standardised a new Histo-FISH method based on specific fluorochrome labelling probes which are able to detect Lactobacillus spp. and Bifidobacterium spp. within biofilms on the mucosal surface of the GIT embedded in paraffin in histological slices. This method is also suitable for visualisation of bacterial populations in the GIT internal content. Depending on the labelling probes, the Histo-FISH method has the potential to detect other probiotic strains or pathogenic bacteria. This original approach permits us to analyse bacterial colonisation processes as well as biofilm formation in stomach and caecum of BALB/c and germ-free mice.

  2. An Individualized, Perception-Based Protocol to Investigate Human Physiological Responses to Cooling

    Science.gov (United States)

    Coolbaugh, Crystal L.; Bush, Emily C.; Galenti, Elizabeth S.; Welch, E. Brian; Towse, Theodore F.

    2018-01-01

    Cold exposure, a known stimulant of the thermogenic effects of brown adipose tissue (BAT), is the most widely used method to study BAT physiology in adult humans. Recently, individualized cooling has been recommended to standardize the physiological cold stress applied across participants, but critical experimental details remain unclear. The purpose of this work was to develop a detailed methodology for an individualized, perception-based protocol to investigate human physiological responses to cooling. Participants were wrapped in two water-circulating blankets and fitted with skin temperature probes to estimate BAT activity and peripheral vasoconstriction. We created a thermoesthesia graphical user interface (tGUI) to continuously record the subject's perception of cooling and shivering status during the cooling protocol. The protocol began with a 15 min thermoneutral phase followed by a series of 10 min cooling phases and concluded when sustained shivering (>1 min duration) occurred. Researchers used perception of cooling feedback (tGUI ratings) to manually adjust and personalize the water temperature at each cooling phase. Blanket water temperatures were recorded continuously during the protocol. Twelve volunteers (ages: 26.2 ± 1.4 years; 25% female) completed a feasibility study to evaluate the proposed protocol. Water temperature, perception of cooling, and shivering varied considerably across participants in response to cooling. Mean clavicle skin temperature, a surrogate measure of BAT activity, decreased (−0.99°C, 95% CI: −1.7 to −0.25°C, P = 0.16) after the cooling protocol, but an increase in supraclavicular skin temperature was observed in 4 participants. A strong positive correlation was also found between thermoesthesia and peripheral vasoconstriction (ρ = 0.84, P < 0.001). The proposed individualized, perception-based protocol therefore has potential to investigate the physiological responses to cold stress applied across populations with

  3. Aging of monolithic zirconia dental prostheses: Protocol for a 5-year prospective clinical study using ex vivo analyses.

    Science.gov (United States)

    Koenig, Vinciane; Wulfman, Claudine P; Derbanne, Mathieu A; Dupont, Nathalie M; Le Goff, Stéphane O; Tang, Mie-Leng; Seidel, Laurence; Dewael, Thibaut Y; Vanheusden, Alain J; Mainjot, Amélie K

    2016-12-15

    Recent introduction of computer-aided design/computer-aided manufacturing (CAD/CAM) monolithic zirconia dental prostheses raises the issue of material low thermal degradation (LTD), a well-known problem with zirconia hip prostheses. This phenomenon could be accentuated by masticatory mechanical stress. Until now zirconia LTD process has only been studied in vitro . This work introduces an original protocol to evaluate LTD process of monolithic zirconia prostheses in the oral environment and to study their general clinical behavior, notably in terms of wear. 101 posterior monolithic zirconia tooth elements (molars and premolars) are included in a 5-year prospective clinical trial. On each element, several areas between 1 and 2 mm 2 (6 on molars, 4 on premolars) are determined on restoration surface: areas submitted or non-submitted to mastication mechanical stress, glazed or non-glazed. Before prosthesis placement, ex vivo analyses regarding LTD and wear are performed using Raman spectroscopy, SEM imagery and 3D laser profilometry. After placement, restorations are clinically evaluated following criteria of the World Dental Federation (FDI), complemented by the analysis of fracture clinical risk factors. Two independent examiners perform the evaluations. Clinical evaluation and ex vivo analyses are carried out after 6 months and then each year for up to 5 years. For clinicians and patients, the results of this trial will justify the use of monolithic zirconia restorations in dental practice. For researchers, the originality of a clinical study including ex vivo analyses of material aging will provide important data regarding zirconia properties.Trial registration: ClinicalTrials.gov Identifier: NCT02150226.

  4. Quinoid radio-toxin (QRT) induced metabolic changes in mice: An ex vivo and in vivo EPR investigation

    Science.gov (United States)

    Ibragimova, M.I.; Petukhov, V.Yu.; Zheglov, E.P.; Khan, N.; Hou, H.; Swartz, H.M.; Konjukhov, G.V.; Nizamov, R.N.

    2013-01-01

    Radio-toxins are toxic metabolites produced by ionizing irradiation and have toxic effects similar to those caused by direct irradiation. We have investigated the effect of a quinoid radio-toxin (QRT) obtained from γ-irradiated potato tuber on various organs in mice using ex vivo and in vivo EPR spectroscopy. Results indicate a decrease in the activity of ribonucleotide reductase enzyme in spleen of mice treated with 0.2 mg QRT. A dose of 2 mg QRT was fatal to mice within 45–60 min of treatment. Nitrosyl hemoglobin complexes α-(Fe2+–NO)α-(Fe2+)β-(Fe2+)2 were detected from spleen, blood, liver, kidney, heart, and lung tissue samples of mice treated with lethal doses of QRT. A significant decrease of pO2 in liver and brain was observed after administration of QRT at the lethal dose. The time of the appearance of the nitrosyl hemoglobin complex and its intensity varied with the dose of QRT and the type of tissue. These results indicate that the effect of the QRT is more prominent in spleen and to a lesser extent in liver and blood. The QRT action at the lethal doses resulted in an increased hypoxia over time with disruption of compensatory adaptive response. The results indicate similar outcome of QRT as observed with γ-irradiation. PMID:18230367

  5. Primary stability of a hybrid self-tapping implant compared to a cylindrical non-self-tapping implant with respect to drilling protocols in an ex vivo model.

    Science.gov (United States)

    Toyoshima, Takeshi; Wagner, Wilfried; Klein, Marcus Oliver; Stender, Elmar; Wieland, Marco; Al-Nawas, Bilal

    2011-03-01

    Modifications of implant design have been intending to improve primary stability. However, little is known about investigation of a hybrid self-tapping implant on primary stability. The aims of this study were to evaluate the primary stability of two hybrid self-tapping implants compared to one cylindrical non-self-tapping implant, and to elucidate the relevance of drilling protocols on primary stability in an ex vivo model. Two types of hybrid self-tapping implants (Straumann® Bone Level implant [BL], Straumann® Tapered Effect implant [TE]) and one type of cylindrical non-self-tapping implant (Straumann® Standard Plus implant [SP]) were investigated in the study. In porcine iliac cancellous bones, 10 implants each were inserted either using standard drilling or under-dimensioned drilling protocol. The evaluation of implant-bone interface stability was carried out by records of maximum insertion torque, the Periotest® (Siemens, Bensheim, Germany), the resonance frequency analysis (RFA), and the push-out test. In each drilling group, the maximum insertion torque values of BL and TE were significantly higher than SP (p=.014 and p=.047, respectively). In each group, the Periotest values of TE were significantly lower than SP (p=.036 and p=.033, respectively). The Periotest values of BL and TE were significantly lower in the group of under-dimensioned drilling than standard drilling (p=.002 and p=.02, respectively). In the RFA, no statistical significances were found in implants between two groups and between implants in each group. In each group, the push-out values of BL and TE were significantly higher than SP (p=.006 and p=.049, respectively). Hybrid self-tapping implants could achieve a high primary stability which predicts them for use in low-density bone. However, there is still a debate to clarify the influence of under-dimensioned drilling on primary stability. © 2009, Copyright the Authors. Journal Compilation © 2011, Wiley Periodicals, Inc.

  6. Cheating and Anti-Cheating in Gossip-Based Protocol: An Experimental Investigation

    Science.gov (United States)

    Xiao, Xin; Shi, Yuanchun; Tang, Yun; Zhang, Nan

    During recent years, there has been a rapid growth in deployment of gossip-based protocol in many multicast applications. In a typical gossip-based protocol, each node acts as dual roles of receiver and sender, independently exchanging data with its neighbors to facilitate scalability and resilience. However, most of previous work in this literature seldom considered cheating issue of end users, which is also very important in face of the fact that the mutual cooperation inherently determines overall system performance. In this paper, we investigate the dishonest behaviors in decentralized gossip-based protocol through extensive experimental study. Our original contributions come in two-fold: In the first part of cheating study, we analytically discuss two typical cheating strategies, that is, intentionally increasing subscription requests and untruthfully calculating forwarding probability, and further evaluate their negative impacts. The results indicate that more attention should be paid to defending cheating behaviors in gossip-based protocol. In the second part of anti-cheating study, we propose a receiver-driven measurement mechanism, which evaluates individual forwarding traffic from the perspective of receivers and thus identifies cheating nodes with high incoming/outgoing ratio. Furthermore, we extend our mechanism by introducing reliable factor to further improve its accuracy. The experiments under various conditions show that it performs quite well in case of serious cheating and achieves considerable performance in other cases.

  7. Hepatic Metabolism of Perfluorinated Carboxylic Acids and Polychlorotrifluoroethylene: A Nuclear Magnetic Resonance Investigation in Vivo

    Science.gov (United States)

    1994-01-05

    Goecke, L. Narayanan, and B. M. Jarnot. "Effects of Perfluoro-n- octanoic Acid , Perfluoro-n-decanoic Acid , and Clofibrate on Hepatic Phosphorus L...Carboxylic Acids and 4Polychiorotrifluoroethylene: A Nuclear Magnetic Resonance G-AFOSR-90-0148 Investigation in Vivo ,IIC 6. AUTHOR(S a Nicholas V. Reo...Maxim um 200 words) This report outlines our research progress regarding toxicological investigations of perifluoro- n-octanoic acid (PFOA) and

  8. Investigating nurse practitioners in the private sector: a theoretically informed research protocol.

    Science.gov (United States)

    Adams, Margaret; Gardner, Glenn; Yates, Patsy

    2017-06-01

    To report a study protocol and the theoretical framework normalisation process theory that informs this protocol for a case study investigation of private sector nurse practitioners. Most research evaluating nurse practitioner service is focused on public, mainly acute care environments where nurse practitioner service is well established with strong structures for governance and sustainability. Conversely, there is lack of clarity in governance for emerging models in the private sector. In a climate of healthcare reform, nurse practitioner service is extending beyond the familiar public health sector. Further research is required to inform knowledge of the practice, operational framework and governance of new nurse practitioner models. The proposed research will use a multiple exploratory case study design to examine private sector nurse practitioner service. Data collection includes interviews, surveys and audits. A sequential mixed method approach to analysis of each case will be conducted. Findings from within-case analysis will lead to a meta-synthesis across all four cases to gain a holistic understanding of the cases under study, private sector nurse practitioner service. Normalisation process theory will be used to guide the research process, specifically coding and analysis of data using theory constructs and the relevant components associated with those constructs. This article provides a blueprint for the research and describes a theoretical framework, normalisation process theory in terms of its flexibility as an analytical framework. Consistent with the goals of best research practice, this study protocol will inform the research community in the field of primary health care about emerging research in this field. Publishing a study protocol ensures researcher fidelity to the analysis plan and supports research collaboration across teams. © 2016 John Wiley & Sons Ltd.

  9. Protocols for the Investigation of Information Processing in Human Assessment of Fundamental Movement Skills.

    Science.gov (United States)

    Ward, Brodie J; Thornton, Ashleigh; Lay, Brendan; Rosenberg, Michael

    2017-01-01

    Fundamental movement skill (FMS) assessment remains an important tool in classifying individuals' level of FMS proficiency. The collection of FMS performances for assessment and monitoring has remained unchanged over the last few decades, but new motion capture technologies offer opportunities to automate this process. To achieve this, a greater understanding of the human process of movement skill assessment is required. The authors present the rationale and protocols of a project in which they aim to investigate the visual search patterns and information extraction employed by human assessors during FMS assessment, as well as the implementation of the Kinect system for FMS capture.

  10. Hepatic Metabolism of Perfluorinated Carboxylic Acids: A Nuclear Magnetic Resonance Investigation in Vivo

    Science.gov (United States)

    1995-01-17

    Reo, C. M. Goecke, L. Narayanan, and B. M. Jarnot. "Effects of Perfluoro-n- octanoic Acid , Perfluoro-n-decanoic Acid , and Clofibrate on Hepatic...SUBTITLE 7C 5. FUNDING NUMBERS" Hepatic Metabolism of Perfluorinated Carboxylic Acids : A Nuclear Magnetic Resonance Investigation in Vivo G-AFOSR-90-0148 6...octanoic acid (PFOA) and perfluoro-n-decanoic acid (PFDA). These Air Force chemicals belong to a class of CU’. compounds known as peroxisome

  11. Investigation of in-vivo skin autofluorescence lifetimes under long-term cw optical excitation

    International Nuclear Information System (INIS)

    Lihachev, A; Ferulova, I; Vasiljeva, K; Spigulis, J

    2014-01-01

    The main results obtained during the last five years in the field of laser-excited in-vivo human skin photobleaching effects are presented. The main achievements and results obtained, as well as methods and experimental devices are briefly described. In addition, the impact of long-term 405-nm cw low-power laser excitation on the skin autofluorescence lifetime is experimentally investigated. (laser biophotonics)

  12. In vivo evaluation of an anti-PSMA antibody conjugated with varying numbers of biotin molecules in a pretargeting protocol

    International Nuclear Information System (INIS)

    Wilbur, D.S.; Hamlin, D.K.; Quinn, J.; Vessella, R.L.

    2003-01-01

    An investigation has been conducted to determine the effect of varying the number of biotin molecules conjugated with an anti-PSMA antibody (mAb) as part of our studies to optimize biotinylated antibodies and radiolabeled streptavidin in pretargeting protocols for Targeted Radionuclide Therapy of prostate cancer. In the investigation, the anti-PSMA antibody 107-1A4 was biotinylated with varying amounts of biotinamidocaproate N-hydroxysuccinimide ester. This procedure resulted in obtaining 107-1A4 with 2.3, 4.5, and 6.8 biotin conjugated as measured by the standard HABA assay. The biotinylated 107-1A4 was radioiodinated and was evaluated in a pretargeting protocol in athymic mice bearing LNCaP human tumor xenografts. In the protocol, 50 μg biotinylated [ 125 I]107-1A4 was injected, followed 48h later by 25 μg of avidin for blood clearance, and 1h after that 20 μg of radiolabeled succinylated recombinant streptavidin ([ 13 1I]sSAv) was administered. The tumor localization and tissue distribution was evaluated at 24, 48, and 72h post [ 131 I]sSAv injection. With 2.3 biotin/mAb, an approximate 1:1 molar ratio (4-5 pmol/g) of sSAv/mAb was obtained at all three time points. With 4.5 biotin/mAb, a 1:1 ratio was observed at 24h, but approx. 2: 1 was observed at 48 and 72h pi. With 6.8 biotin/mAb, sSAv/mAb ratios of approximately 1.5:1; 2:1; and 3:1 were obtained at 24, 48, and 72h pi respectively. The amount of sSAv localized in the tumor was nearly the same (4-5 pmol/g) when 107-1A4 had 2.3 or 4.5 biotin conjugated, but decreased to 3-4.5 pmol/g with 6.8 biotin conjugated. Because the highest levels of co-localized sSAv was found with the lowest number of biotin conjugates, the observed differences in ratios of sSAv/mAb may be best explained as differences in internalization, and degradation of mAb and protease resistant sSAv. In duplicate experiments, similar results were obtained with biotinylated 107-1A4 F(ab') 2 , but not with an mAb to a non-internalizing antigen

  13. Dual-energy CT for the characterization of urinary calculi: In vitro and in vivo evaluation of a low-dose scanning protocol

    International Nuclear Information System (INIS)

    Thomas, C.; Patschan, O.; Nagele, U.; Stenzl, A.; Ketelsen, D.; Tsiflikas, I.; Reimann, A.; Brodoefel, H.; Claussen, C.; Kopp, A.; Heuschmid, M.; Schlemmer, H.P.; Buchgeister, M.

    2009-01-01

    The efficiency and radiation dose of a low-dose dual-energy (DE) CT protocol for the evaluation of urinary calculus disease were evaluated. A low-dose dual-source DE-CT renal calculi protocol (140 kV, 46 mAs; 80 kV, 210 mAs) was derived from the single-energy (SE) CT protocol used in our institution for the detection of renal calculi (120 kV, 75 mAs). An Alderson-Rando phantom was equipped with thermoluminescence dosimeters and examined by CT with both protocols. The effective doses were calculated. Fifty-one patients with suspected or known urinary calculus disease underwent DE-CT. DE analysis was performed if calculi were detected using a dedicated software tool. Results were compared to chemical analysis after invasive calculus extraction. An effective dose of 3.43 mSv (male) and 5.30 mSv (female) was measured in the phantom for the DE protocol (vs. 3.17/4.57 mSv for the SE protocol). Urinary calculi were found in 34 patients; in 28 patients, calculi were removed and analyzed (23 patients with calcified calculi, three with uric acid calculi, one with 2,8-dihyxdroxyadenine-calculi, one patient with a mixed struvite calculus). DE analysis was able to distinguish between calcified and non-calcified calculi in all cases. In conclusion, dual-energy urinary calculus analysis is effective also with a low-dose protocol. The protocol tested in this study reliably identified calcified urinary calculi in vivo. (orig.)

  14. Dual-energy CT for the characterization of urinary calculi: In vitro and in vivo evaluation of a low-dose scanning protocol.

    Science.gov (United States)

    Thomas, C; Patschan, O; Ketelsen, D; Tsiflikas, I; Reimann, A; Brodoefel, H; Buchgeister, M; Nagele, U; Stenzl, A; Claussen, C; Kopp, A; Heuschmid, M; Schlemmer, H-P

    2009-06-01

    The efficiency and radiation dose of a low-dose dual-energy (DE) CT protocol for the evaluation of urinary calculus disease were evaluated. A low-dose dual-source DE-CT renal calculi protocol (140 kV, 46 mAs; 80 kV, 210 mAs) was derived from the single-energy (SE) CT protocol used in our institution for the detection of renal calculi (120 kV, 75 mAs). An Alderson-Rando phantom was equipped with thermoluminescence dosimeters and examined by CT with both protocols. The effective doses were calculated. Fifty-one patients with suspected or known urinary calculus disease underwent DE-CT. DE analysis was performed if calculi were detected using a dedicated software tool. Results were compared to chemical analysis after invasive calculus extraction. An effective dose of 3.43 mSv (male) and 5.30 mSv (female) was measured in the phantom for the DE protocol (vs. 3.17/4.57 mSv for the SE protocol). Urinary calculi were found in 34 patients; in 28 patients, calculi were removed and analyzed (23 patients with calcified calculi, three with uric acid calculi, one with 2,8-dihyxdroxyadenine-calculi, one patient with a mixed struvite calculus). DE analysis was able to distinguish between calcified and non-calcified calculi in all cases. In conclusion, dual-energy urinary calculus analysis is effective also with a low-dose protocol. The protocol tested in this study reliably identified calcified urinary calculi in vivo.

  15. Dual-energy CT for the characterization of urinary calculi: In vitro and in vivo evaluation of a low-dose scanning protocol

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, C. [University of Tuebingen, Department of Diagnostic and Interventional Radiology, Tuebingen (Germany); Department of Diagnostic and Interventional Radiology, Tuebingen (Germany); Patschan, O.; Nagele, U.; Stenzl, A. [University of Tuebingen, Department of Urology, Tuebingen (Germany); Ketelsen, D.; Tsiflikas, I.; Reimann, A.; Brodoefel, H.; Claussen, C.; Kopp, A.; Heuschmid, M.; Schlemmer, H.P. [University of Tuebingen, Department of Diagnostic and Interventional Radiology, Tuebingen (Germany); Buchgeister, M. [University of Tuebingen, Medical Physics, Department of Radiation Oncology, Tuebingen (Germany)

    2009-06-15

    The efficiency and radiation dose of a low-dose dual-energy (DE) CT protocol for the evaluation of urinary calculus disease were evaluated. A low-dose dual-source DE-CT renal calculi protocol (140 kV, 46 mAs; 80 kV, 210 mAs) was derived from the single-energy (SE) CT protocol used in our institution for the detection of renal calculi (120 kV, 75 mAs). An Alderson-Rando phantom was equipped with thermoluminescence dosimeters and examined by CT with both protocols. The effective doses were calculated. Fifty-one patients with suspected or known urinary calculus disease underwent DE-CT. DE analysis was performed if calculi were detected using a dedicated software tool. Results were compared to chemical analysis after invasive calculus extraction. An effective dose of 3.43 mSv (male) and 5.30 mSv (female) was measured in the phantom for the DE protocol (vs. 3.17/4.57 mSv for the SE protocol). Urinary calculi were found in 34 patients; in 28 patients, calculi were removed and analyzed (23 patients with calcified calculi, three with uric acid calculi, one with 2,8-dihyxdroxyadenine-calculi, one patient with a mixed struvite calculus). DE analysis was able to distinguish between calcified and non-calcified calculi in all cases. In conclusion, dual-energy urinary calculus analysis is effective also with a low-dose protocol. The protocol tested in this study reliably identified calcified urinary calculi in vivo. (orig.)

  16. Two-photon excited fluorescence microscopy application for ex vivo investigation of ocular fundus samples

    Science.gov (United States)

    Peters, Sven; Hammer, Martin; Schweitzer, Dietrich

    2011-07-01

    Two-photon excited fluorescence (TPEF) imaging of ocular tissue has recently become a promising tool in ophthalmology for diagnostic and research purposes. The feasibility and the advantages of TPEF imaging, namely deeper tissue penetration and improved high-resolution imaging of microstructures, have been demonstrated lately using human ocular samples. The autofluorescence properties of endogenous fluorophores in ocular fundus tissue are well known from spectrophotometric analysis. But fluorophores, especially when it comes to fluorescence lifetime, typically display a dependence of their fluorescence properties on local environmental parameters. Hence, a more detailed investigation of ocular fundus autofluorescence ideally in vivo is of utmost interest. The aim of this study is to determine space-resolved the stationary and time-resolved fluorescence properties of endogenous fluorophores in ex vivo porcine ocular fundus samples by means of two-photon excited fluorescence spectrum and lifetime imaging microscopy (FSIM/FLIM). By our first results, we characterized the autofluorescence of individual anatomical structures of porcine retina samples excited at 760 nm. The fluorescence properties of almost all investigated retinal layers are relatively homogenous. But as previously unknown, ganglion cell bodies show a significantly shorter fluorescence lifetime compared to the adjacent mueller cells. Since all retinal layers exhibit bi-exponential autofluorescence decays, we were able to achieve a more precise characterization of fluorescence properties of endogenous fluorophores compared to a present in vivo FLIM approach by confocal scanning laser ophthalmoscope (cSLO).

  17. In vivo reactive neural plasticity investigation by means of correlative two photon: electron microscopy

    Science.gov (United States)

    Allegra Mascaro, A. L.; Cesare, P.; Sacconi, L.; Grasselli, G.; Mandolesi, G.; Maco, B.; Knott, G.; Huang, L.; De Paola, V.; Strata, P.; Pavone, F. S.

    2013-02-01

    In the adult nervous system, different populations of neurons correspond to different regenerative behavior. Although previous works showed that olivocerebellar fibers are capable of axonal regeneration in a suitable environment as a response to injury1, we have hitherto no details about the real dynamics of fiber regeneration. We set up a model of singularly axotomized climbing fibers (CF) to investigate their reparative properties in the adult central nervous system (CNS) in vivo. Time lapse two-photon imaging has been combined to laser nanosurgery2, 3 to define a temporal pattern of the degenerative event and to follow the structural rearrangement after injury. To characterize the damage and to elucidate the possible formation of new synaptic contacts on the sprouted branches of the lesioned CF, we combined two-photon in vivo imaging with block face scanning electron microscopy (FIB-SEM). Here we describe the approach followed to characterize the reactive plasticity after injury.

  18. Provesicular granisetron hydrochloride buccal formulations: in vitro evaluation and preliminary investigation of in vivo performance.

    Science.gov (United States)

    Ahmed, Sami; El-Setouhy, Doaa Ahmed; El-Latif Badawi, Alia Abd; El-Nabarawi, Mohamed Ahmed

    2014-08-18

    Granisetron hydrochloride (granisetron) is a potent antiemetic that has been proven to be effective in acute and delayed emesis in cancer chemotherapy. Granisetron suffers from reduced oral bioavailability (≈60%) due to hepatic metabolism. In this study the combined advantage of provesicular carriers and buccal drug delivery has been explored aiming to sustain effect and improve bioavailability of granisetron via development of granisetron provesicular buccoadhesive tablets with suitable quality characteristics (hardness, drug content, in vitro release pattern, exvivo bioadhesion and in vivo bioadhesion behavior). Composition of the reconstituted niosomes from different prepared provesicular carriers regarding type of surfactant used and cholesterol concentration significantly affected both entrapment efficiency (%EE) and vesicle size. Span 80 proniosome-derived niosomes exhibited higher encapsulation efficiency and smaller particle size than those derived from span 20. Also, the effect of %EE and bioadhesive polymer type on in vitro drug release and in vivo performance of buccoadhesive tablets was investigated. Based on achievement of required in vitro release pattern (20-30% at 2h, 40-65% at 6h and 80-95% at 12h), in vivo swelling behavior, and in vivo adhesion time (>14 h) granisetron formulation (F19, 1.4 mg) comprising HPMC:carbopol 974P (7:3) and maltodextrin coated with the vesicular precursors span 80 and cholesterol (9:1) was chosen for in vivo study. In vivo pharmacokinetic study revealed higher bioavailability of buccal formulation relative to conventional oral formulation of granisetron (AUC0-∞ is 89.97 and 38.18 ng h/ml for buccal and oral formulation, respectively). A significantly lower and delayed Cmax (12.09±4.47 ng/ml, at 8h) was observed after buccal application compared to conventional oral tablet (31.66±10.15 ng/ml, at 0.5 h). The prepared provesicular buccoadhesive tablet of granisetron (F19) might help bypass hepatic first

  19. Quantitative Comparison of 21 Protocols for Labeling Hippocampal Subfields and Parahippocampal Cortical Subregions in In Vivo MRI: Towards Developing a Harmonized Segmentation Protocol

    DEFF Research Database (Denmark)

    Yushkevich, Paul A.; Amaral, Robert S.C.; Augustinack, Jean C.

    2015-01-01

    Objective: An increasing number of human in vivo magnetic resonance imaging (MRI) studies have focused on examining the structure and function of the subfields of the hippocampal formation (the dentate gyrus, CA fields 1 − 3, and the subiculum) and subregions of the parahippocampal gyrus...

  20. In Vivo Investigation of Breast Cancer Progression by Use of an Internal Control1

    Science.gov (United States)

    Baeten, John; Haller, Jodi; Shih, Helen; Ntziachristos, Vasilis

    2009-01-01

    Optical imaging of breast cancer has been considered for detecting functional and molecular characteristics of diseases in clinical and preclinical settings. Applied to laboratory research, photonic investigations offer a highly versatile tool for preclinical imaging and drug discovery. A particular advantage of the optical method is the availability of multiple spectral bands for performing imaging. Herein, we capitalize on this feature to demonstrate how it is possible to use different wavelengths to offer internal controls and significantly improve the observation accuracy in molecular imaging applications. In particular, we show the independent in vivo detection of cysteine proteases along with tumor permeability and interstitial volume measurements using a dual-wavelength approach. To generate results with a view toward clinically geared studies, a transgenic Her2/neu mouse model that spontaneously developed mammary tumors was used. In vivo findings were validated against conventional ex vivo tests such as histology and Western blot analyses. By correcting for biodistribution parameters, the dual-wavelength method increases the accuracy of molecular observations by separating true molecular target from probe biodistribution. As such, the method is highly appropriate for molecular imaging studies where often probe delivery and target presence are not independently assessed. On the basis of these findings, we propose the dual-wavelength/normalization approach as an essential method for drug discovery and preclinical imaging studies. PMID:19242603

  1. In Vitro and In Vivo Investigation of the Angiogenic Effects of Liraglutide during Islet Transplantation.

    Directory of Open Access Journals (Sweden)

    Allan Langlois

    Full Text Available This study investigated the angiogenic properties of liraglutide in vitro and in vivo and the mechanisms involved, with a focus on Hypoxia Inducible Factor-1α (HIF-1α and mammalian target of rapamycin (mTOR.Rat pancreatic islets were incubated in vitro with 10 μmol/L of liraglutide (Lira for 12, 24 and 48 h. Islet viability was studied by fluorescein diacetate/propidium iodide staining and their function was assessed by glucose stimulation. The angiogenic effect of liraglutide was determined in vitro by the measure of vascular endothelial growth factor (VEGF secretion using enzyme-linked immunosorbent assay and by the evaluation of VEGF and platelet-derived growth factor-α (PDGFα expression with quantitative polymerase chain reaction technic. Then, in vitro and in vivo, angiogenic property of Lira was evaluated using immunofluorescence staining targeting the cluster of differentiation 31 (CD31. To understand angiogenic mechanisms involved by Lira, HIF-1α and mTOR activation were studied using western blotting. In vivo, islets (1000/kg body-weight were transplanted into diabetic (streptozotocin Lewis rats. Metabolic control was assessed for 1 month by measuring body-weight gain and fasting blood glucose.Islet viability and function were respectively preserved and enhanced (p<0.05 with Lira, versus control. Lira increased CD31-positive cells, expression of VEGF and PDGFα (p<0.05 after 24 h in culture. Increased VEGF secretion versus control was also observed at 48 h (p<0.05. Moreover, Lira activated mTOR (p<0.05 signalling pathway. In vivo, Lira improved vascular density (p<0.01, body-weight gain (p<0.01 and reduced fasting blood glucose in transplanted rats (p<0.001.The beneficial effects of liraglutide on islets appeared to be linked to its angiogenic properties. These findings indicated that glucagon-like peptide-1 analogues could be used to improve transplanted islet revascularisation.

  2. Investigation of optimal scanning protocol for X-ray computed tomography polymer gel dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Sellakumar, P. [Bangalore Institute of Oncology, 44-45/2, II Cross, RRMR Extension, Bangalore 560 027 (India)], E-mail: psellakumar@rediffmail.com; James Jebaseelan Samuel, E. [School of Science and Humanities, VIT University, Vellore 632 014 (India); Supe, Sanjay S. [Department of Radiation Physics, Kidwai Memorial Institute of Oncology, Hosur Road, Bangalore 560 027 (India)

    2007-11-15

    X-ray computed tomography is one of the potential tool used to evaluate the polymer gel dosimeters in three dimensions. The purpose of this study is to investigate the factors which affect the image noise for X-ray CT polymer gel dosimetry. A cylindrical water filled phantom was imaged with single slice Siemens Somatom Emotion CT scanner. The imaging parameters like tube voltage, tube current, slice scan time, slice thickness and reconstruction algorithm were varied independently to study the dependence of noise on each other. Reductions of noise with number of images to be averaged and spatial uniformity of the image were also investigated. Normoxic polymer gel PAGAT was manufactured and irradiated using Siemens Primus linear accelerator. The radiation induced change in CT number was evaluated using X-ray CT scanner. From this study it is clear that image noise is reduced with increase in tube voltage, tube current, slice scan time, slice thickness and also reduced with increasing the number of images averaged. However to reduce the tube load and total scan time, it was concluded that tube voltage of 130 kV, tube current of 200 mA, scan time of 1.5 s, slice thickness of 3 mm for high dose gradient and 5 mm for low dose gradient were optimal scanning protocols for this scanner. Optimum number of images to be averaged was concluded to be 25 for X-ray CT polymer gel dosimetry. Choice of reconstruction algorithm was also critical. From the study it is also clear that CT number increase with imaging tube voltage and shows the energy dependency of polymer gel dosimeter. Hence for evaluation of polymer gel dosimeters with X-ray CT scanner needs the optimization of scanning protocols to reduce the image noise.

  3. On Designing Thermal-Aware Localized QoS Routing Protocol for in-vivo Sensor Nodes in Wireless Body Area Networks

    OpenAIRE

    Monowar, Muhammad Mostafa; Bajaber, Fuad

    2015-01-01

    In this paper, we address the thermal rise and Quality-of-Service (QoS) provisioning issue for an intra-body Wireless Body Area Network (WBAN) having in-vivo sensor nodes. We propose a thermal-aware QoS routing protocol, called TLQoS, that facilitates the system in achieving desired QoS in terms of delay and reliability for diverse traffic types, as well as avoids the formation of highly heated nodes known as hotspot(s), and keeps the temperature rise along the network to an acceptable level....

  4. A unique in vivo approach for investigating antimicrobial materials utilizing fistulated animals

    Science.gov (United States)

    Berean, Kyle J.; Adetutu, Eric M.; Zhen Ou, Jian; Nour, Majid; Nguyen, Emily P.; Paull, David; McLeod, Jess; Ramanathan, Rajesh; Bansal, Vipul; Latham, Kay; Bishop-Hurley, Greg J.; McSweeney, Chris; Ball, Andrew S.; Kalantar-Zadeh, Kourosh

    2015-06-01

    Unique in vivo tests were conducted through the use of a fistulated ruminant, providing an ideal environment with a diverse and vibrant microbial community. Utilizing such a procedure can be especially invaluable for investigating the performance of antimicrobial materials related to human and animal related infections. In this pilot study, it is shown that the rumen of a fistulated animal provides an excellent live laboratory for assessing the properties of antimicrobial materials. We investigate microbial colonization onto model nanocomposites based on silver (Ag) nanoparticles at different concentrations into polydimethylsiloxane (PDMS). With implantable devices posing a major risk for hospital-acquired infections, the present study provides a viable solution to understand microbial colonization with the potential to reduce the incidence of infection through the introduction of Ag nanoparticles at the optimum concentrations. In vitro measurements were also conducted to show the validity of the approach. An optimal loading of 0.25 wt% Ag is found to show the greatest antimicrobial activity and observed through the in vivo tests to reduce the microbial diversity colonizing the surface.

  5. Microfluidic biofunctionalisation protocols to form multi-valent interactions for cell rolling and phenotype modification investigations

    KAUST Repository

    Perozziello, Gerardo

    2013-07-01

    In this study, we propose a fast, simple method to biofunctionalise microfluidic systems for cellomic investigations based on micro-fluidic protocols. Many available processes either require expensive and time-consuming protocols or are incompatible with the fabrication of microfluidic systems. Our method differs from the existing since it is applicable to an assembled system, uses few microlitres of reagents and it is based on the use of microbeads. The microbeads have specific surface moieties to link the biomolecules and couple cell receptors. Furthermore, the microbeads serve as arm spacer and offer the benefit of the multi-valent interaction. Microfluidics was adapted together with topology and biochemistry surface modifications to offer the microenvironment for cellomic studies. Based on this principle, we exploit the streptavidin-biotin interaction to couple antibodies to the biofunctionalised microfluidic environment within 5 h using 200 μL of reagents and biomolecules. We selected the antibodies able to form complexes with the MHC class I (MHC-I) molecules present on the cell membrane and involved in the immune surveillance. To test the microfluidic system, tumour cell lines (RMA) were rolled across the coupled antibodies to recognise and strip MHC-I molecules. As result, we show that cell rolling performed inside a microfluidic chamber functionalised with beads and the opportune antibody facilitate the removal of MHC class I molecules. We showed that the level of median fluorescent intensity of the MHC-I molecules is 300 for cells treated in a not biofunctionalised surface. It decreased to 275 for cells treated in a flat biofunctionalised surface and to 250 for cells treated on a surface where biofunctionalised microbeads were immobilised. The cells with reduced expression of MHC-I molecules showed, after cytotoxicity tests, susceptibility 3.5 times higher than normal cells. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Use of a standardized JaCVAM in vivo rat comet assay protocol to assess the genotoxicity of three coded test compounds; ampicillin trihydrate, 1,2-dimethylhydrazine dihydrochloride, and N-nitrosodimethylamine.

    Science.gov (United States)

    McNamee, J P; Bellier, P V

    2015-07-01

    As part of the Japanese Center for the Validation of Alternative Methods (JaCVAM)-initiative international validation study of the in vivo rat alkaline comet assay (comet assay), our laboratory examined ampicillin trihydrate (AMP), 1,2-dimethylhydrazine dihydrochloride (DMH), and N-nitrosodimethylamine (NDA) using a standard comet assay validation protocol (v14.2) developed by the JaCVAM validation management team (VMT). Coded samples were received by our laboratory along with basic MSDS information. Solubility analysis and range-finding experiments of the coded test compounds were conducted for dose selection. Animal dosing schedules, the comet assay processing and analysis, and statistical analysis were conducted in accordance with the standard protocol. Based upon our blinded evaluation, AMP was not found to exhibit evidence of genotoxicity in either the rat liver or stomach. However, both NDA and DMH were observed to cause a significant increase in % tail DNA in the rat liver at all dose levels tested. While acute hepatoxicity was observed for these compounds in the high dose group, in the investigators opinion there were a sufficient number of consistently damaged/measurable cells at the medium and low dose groups to judge these compounds as genotoxic. There was no evidence of genotoxicity from either NDA or DMH in the rat stomach. In conclusion, our laboratory observed increased DNA damage from two blinded test compounds in rat liver (later identified as genotoxic carcinogens), while no evidence of genotoxicity was observed for the third blinded test compound (later identified as a non-genotoxic, non-carcinogen). This data supports the use of a standardized protocol of the in vivo comet assay as a cost-effective alternative genotoxicity assay for regulatory testing purposes. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

  7. In Vitro and In Vivo Investigation of the Angiogenic Effects of Liraglutide during Islet Transplantation

    Science.gov (United States)

    Langlois, Allan; Mura, Carole; Bietiger, William; Seyfritz, Elodie; Dollinger, Camille; Peronet, Claude; Maillard, Elisa; Pinget, Michel; Jeandidier, Nathalie; Sigrist, Séverine

    2016-01-01

    Introduction This study investigated the angiogenic properties of liraglutide in vitro and in vivo and the mechanisms involved, with a focus on Hypoxia Inducible Factor-1α (HIF-1α) and mammalian target of rapamycin (mTOR). Materials and Methods Rat pancreatic islets were incubated in vitro with 10 μmol/L of liraglutide (Lira) for 12, 24 and 48 h. Islet viability was studied by fluorescein diacetate/propidium iodide staining and their function was assessed by glucose stimulation. The angiogenic effect of liraglutide was determined in vitro by the measure of vascular endothelial growth factor (VEGF) secretion using enzyme-linked immunosorbent assay and by the evaluation of VEGF and platelet-derived growth factor-α (PDGFα) expression with quantitative polymerase chain reaction technic. Then, in vitro and in vivo, angiogenic property of Lira was evaluated using immunofluorescence staining targeting the cluster of differentiation 31 (CD31). To understand angiogenic mechanisms involved by Lira, HIF-1α and mTOR activation were studied using western blotting. In vivo, islets (1000/kg body-weight) were transplanted into diabetic (streptozotocin) Lewis rats. Metabolic control was assessed for 1 month by measuring body-weight gain and fasting blood glucose. Results Islet viability and function were respectively preserved and enhanced (p<0.05) with Lira, versus control. Lira increased CD31-positive cells, expression of VEGF and PDGFα (p<0.05) after 24 h in culture. Increased VEGF secretion versus control was also observed at 48 h (p<0.05). Moreover, Lira activated mTOR (p<0.05) signalling pathway. In vivo, Lira improved vascular density (p<0.01), body-weight gain (p<0.01) and reduced fasting blood glucose in transplanted rats (p<0.001). Conclusion The beneficial effects of liraglutide on islets appeared to be linked to its angiogenic properties. These findings indicated that glucagon-like peptide-1 analogues could be used to improve transplanted islet revascularisation

  8. Feasibility study of Raman spectroscopy for investigating the mouse retina in vivo

    Science.gov (United States)

    Manna, Suman K.; de Oliveira, Marcos A. S.; Zhang, Pengfei; Maleppat, Ratheesh K.; Chang, Che-Wei; Pugh, Edward N.; Chan, James W.; Zawadzki, Robert J.

    2018-02-01

    The use of Raman spectroscopy in biochemistry has been very successful, particularly because of its ability to identify elementary chemical species. However, application of this spectroscopic technique for in vivo assessment is often limited by autofluorescence, which make detection of Raman signatures difficult. The mouse eye has been used as an optical testbed for investigation of a variety of disease models and therapeutic pathways. Implementation of in vivo Raman spectroscopy in mice retina would be valuable but needs to be examined in context of the intrinsic auto-fluorescence artifact and potential light damage if high probing beam powers were used. To evaluate feasibility, a Raman system was built on a custom SLO/OCT platform allowing mouse positioning and morphological data acquisition along with the Raman signal from a desired retinal eccentricity. The performance of the Raman system was first assessed with a model eye consisting of polystyrene in the image plane (retina), using excitation wavelengths of 488 nm, 561 nm, and 785 nm to determine whether auto-fluorescence would be reduced at longer wavelengths. To improve the SNR, the combined system is featured with the optical compatibility for these three excitations such that their corresponding spectra from a typical region of interest can be acquired consecutively during single imaging run. Our results include emission spectra acquired over 10 s with excitation energy less than 160 J.s-1.m-2 for all wavelengths and corresponding retinal morphology for different mouse strains including WT, BALB/c and ABCA4-/-.

  9. Caval filter implantation under MRI control - experimental in vitro and in vivo investigations

    International Nuclear Information System (INIS)

    Neuerburg, J.; Buecker, A.; Adam, G.; Leenen, M.; Guenther, R.W.; Hurtak, M.S.W.

    1997-01-01

    Purpose: An instrument has been developed for the introduction of caval filters which can be used with MRI; it has been investigated in in vitro and in in vivo experiments. Material and method: The ferromagnetic components of a commercially available instrument for the femoral introduction of the MR-eye TM Tulip IVC filter were changed for similar, non-ferromagnetic parts and the lock and dilator marked with dysprosium oxide rings. The instrument was used in a flow phantom and in animal experiments (two domestic pigs) in order to insert filters under MRI control on a 1.5 T Philips Gyroscan with integrated mobile digital subtraction angiography. Results: Both in vitro and in vivo, the introducer, catheter and caval filter could be identified by MRI and positioned under MRI control. The position of the filter as indicated by MRI corresponded with radiological and macroscopic findings in all cases (5 phantoms, 2 pigs). Conclusion: The early experimental results indicate that percutaneous introduction of caval filters with placement under MRI control is possible. (orig.) [de

  10. Utilizing nonlinear optical microscopy to investigate the development of early cancer in nude mice in vivo

    Science.gov (United States)

    Wang, Chun-Chin; Li, Feng-Chieh; Lin, Sung-Jan; Lo, Wen; Dong, Chen-Yuan

    2007-07-01

    In this investigation, we used in vivo nonlinear optical microscopy to image normal and carcinogen DMBA treated skin tissues of nude mice. We acquired two-photon autofluroescence and second harmonic generation (SHG) images of the skin tissue, and applied the ASI (Autofluorescence versus SHG Index) to the resulting image. This allows us to visualize and quantify the interaction between mouse skin cells and the surrounding connective tissue. We found that as the imaging depth increases, ASI has a different distribution in the normal and the treated skin tissues. Since the DMBA treated skin eventually became squamous cell carcinoma (SCC), our results show that the physiological changes to mouse skin en route to become cancer can be effectively tracked by multiphoton microscopy. We envision this approach to be effective in studying tumor biology and tumor treatment procedures.

  11. Development and Utilization of an Ex Vivo Bromodeoxyuridine Local Lymph Node Assay (LLNA) Protocol for Assessing Potential Chemical Sensitizers

    Science.gov (United States)

    The murine local lymph node assay (LLNA) is widely used to identify chemicals that may cause allergic contact dermatitis. Exposure to a dermal sensitizer results in proliferation of local lymph node T cells, which has traditionally been measured by in vivo incorporation of [3H]m...

  12. Multi-omic investigations of mouse liver subjected to simulated spaceflight freezing and storage protocols

    Data.gov (United States)

    National Aeronautics and Space Administration — This study compares standard laboratory protocols for tissue freezing and storage with a simulation of the delayed processing of liver specimens and long-term...

  13. Prion structure investigated in situ, ex vivo, and in vitro by FTIR spectroscopy

    Science.gov (United States)

    Kneipp, Janina; Miller, Lisa M.; Spassov, Sashko; Sokolowski, Fabian; Lasch, Peter; Beekes, Michael; Naumann, Dieter

    2004-07-01

    Syrian hamster nervous tissue was investigated by FTIR microspectroscopy with conventional and synchrotron infrared light sources. Various tissue structures from the cerebellum and medulla oblongata of scrapie-infected and control hamsters were investigated at a spatial resolution of 50 μm. Single neurons in dorsal root ganglia of scrapie-infected hamsters were analyzed by raster scan mapping at 6 μm spatial resolution. These measurements enabled us to (i) scrutinize structural differences between infected and non-infected tissue and (ii) analyze for the first time the distribution of different protein structures in situ within single nerve cells. Single nerve cells exhibited areas of increased β-sheet content, which co-localized consistently with accumulations of the pathological prion protein (PrPSc). Spectral data were also obtained from purified, partly proteinase K digested PrPSc isolated from scrapie-infected nervous tissue of hamsters to elucidate similarities/dissimilarities between prion structure in situ and ex vivo. A further comparison is drawn to the recombinant Syrian hamster prion protein SHaPrP90-232, whose in vitro transition from the predominantly a-helical isoform to β-sheet rich oligomeric structures was also investigated by FTIR spectroscopy.

  14. An investigation into current protocols and radiographer opinions on contrast extravasation in Irish CT departments

    International Nuclear Information System (INIS)

    Cleary, N.; McNulty, J.P.; Foley, S.J.; Kelly, E.

    2017-01-01

    Background: Iodinated contrast extravasation is a serious complication associated with intravenous administration in radiology. Departmental protocols and the radiographer's approach on both prevention techniques and treatment will affect the prevalence of extravasation, and the eventual outcome for the patient when it does occur. Aims: To examine contrast extravasation protocols in place in Irish CT departments for alignment with European Society of Urogenital Radiology (ESUR) Guidelines (2014); to establish radiographer's opinions on contrast extravasation; and to examine radiographer adherence to protocols. Methods: Contrast extravasation protocols from a purposively selected sample of CT departments across Ireland (n = 6) were compared to ESUR guidelines, followed by an online survey of CT radiographers practicing in the participating centres. Results: All participating CT departments (n = 5) had written protocols in place. High risk patients, such as elderly or unconscious, were identified in most protocols, however, children were mentioned in just one protocol and obese patients were not specified in any. The response rate of CT radiographers was 23% (n = 24). 58% (n = 14) of respondents indicated that contrast extravasation was more likely during CTA examinations. While high levels of confidence in managing extravasation were reported, suggested treatment approaches, and confidence in same, was more variable. Clinical workload in CT departments was also identified as a factor impacting on patient care and management. Conclusion: While contrast extravasation protocols were generally in line with ESUR Guidelines, high risk patients may not be getting sufficient attention. More radiographer awareness of patient monitoring needs, particularly in busy departments with a heavy workload may also reduce extravasation risk, and improve management of same. - Highlights: • Irish protocols on contrast extravasation are generally in line with

  15. Aging of monolithic zirconia dental prostheses: Protocol for a 5-year prospective clinical study using ex vivo analyses

    OpenAIRE

    Koenig, Vinciane; Wulfman, Claudine P.; Derbanne, Mathieu A.; Dupont, Nathalie M.; Le Goff, Stéphane O.; Tang, Mie-Leng; Seidel, Laurence; Dewael, Thibaut Y.; Vanheusden, Alain J.; Mainjot, Amélie K.

    2016-01-01

    Background: Recent introduction of computer-aided design/computer-aided manufacturing (CAD/CAM) monolithic zirconia dental prostheses raises the issue of material low thermal degradation (LTD), a well-known problem with zirconia hip prostheses. This phenomenon could be accentuated by masticatory mechanical stress. Until now zirconia LTD process has only been studied in vitro. This work introduces an original protocol to evaluate LTD process of monolithic zirconia prostheses in the oral enviro...

  16. IN VIVO EVIDENCE OF FREE RADICAL FORMATION AFTER ASBESTOS INSTILLATION: AN ESR SPIN TRAPPING INVESTIGATION

    Science.gov (United States)

    It has been postulated that the in vivo toxicity of asbestos results from its catalysis of free radical generation. We examined in vivo radical production using electron spin resonance (ESR) coupled with the spin trap alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone (4-POBN); 180 d...

  17. Standardization of a Videofluoroscopic Swallow Study Protocol to Investigate Dysphagia in Dogs.

    Science.gov (United States)

    Harris, R A; Grobman, M E; Allen, M J; Schachtel, J; Rawson, N E; Bennett, B; Ledyayev, J; Hopewell, B; Coates, J R; Reinero, C R; Lever, T E

    2017-03-01

    Videofluoroscopic swallow study (VFSS) is the gold standard for diagnosis of dysphagia in veterinary medicine but lacks standardized protocols that emulate physiologic feeding practices. Age impacts swallow function in humans but has not been evaluated by VFSS in dogs. To develop a protocol with custom kennels designed to allow free-feeding of 3 optimized formulations of contrast media and diets that address limitations of current VFSS protocols. We hypothesized that dogs evaluated by a free-feeding VFSS protocol would show differences in objective swallow metrics based on age. Healthy juvenile, adult, and geriatric dogs (n = 24). Prospective, experimental study. Custom kennels were developed to maintain natural feeding behaviors during VFSS. Three food consistencies (thin liquid, pureed food, and dry kibble) were formulated with either iohexol or barium to maximize palatability and voluntary prehension. Dogs were evaluated by 16 swallow metrics and compared across age groups. Development of a standardized VFSS protocol resulted in successful collection of swallow data in healthy dogs. No significant differences in swallow metrics were observed among age groups. Substantial variability was observed in healthy dogs when evaluated under these physiologic conditions. Features typically attributed to pathologic states, such as gastric reflux, were seen in healthy dogs. Development of a VFSS protocol that reflects natural feeding practices may allow emulation of physiology resulting in clinical signs of dysphagia. Age did not result in significant changes in swallow metrics, but additional studies are needed, particularly in light of substantial normal variation. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  18. A pilot audit of a protocol for ambulatory investigation of predicted low-risk patients with possible pulmonary embolism.

    Science.gov (United States)

    McDonald, A H; Murphy, R

    2011-09-01

    Patients with possible pulmonary embolism (PE) commonly present to acute medical services. Research has led to the identification of low-risk patients suitable for ambulatory management. We report on a protocol designed to select low-risk patients for ambulatory investigation if confirmatory imaging is not available that day. The protocol was piloted in the Emergency Department and Medical Assessment Area at the Royal Infirmary of Edinburgh. We retrospectively analysed electronic patient records in an open observational audit of all patients managed in the ambulatory arm over five months of use. We analysed 45 patients' records. Of these, 91.1% required imaging to confirm or refute PE, 62.2% received a computed tomography pulmonary angiogram (CTPA). In 25% of patients, PE was confirmed with musculoskeletal pain (22.7%), and respiratory tract infection (15.9%) the next most prevalent diagnoses. Alternative diagnoses was provided by CTPA in 32% of cases. We identified no adverse events or readmissions but individualised follow-up was not attempted. The data from this audit suggests this protocol can be applied to select and manage low-risk patients suitable for ambulatory investigation of possible PE. A larger prospective comparative study would be required to accurately define the safety and effectiveness of this protocol.

  19. Investigation of a pulsed current annealing method in reusing MOSFET dosimeters for in vivo IMRT dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Guang-Wen; Qi, Zhen-Yu, E-mail: qizhy@sysucc.org.cn; Deng, Xiao-Wu [Department of Radiation Oncology, Sun Yat-Sen University Cancer Center and State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060 (China); Rosenfeld, Anatoly [Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW 2522 (Australia)

    2014-05-15

    Purpose: To explore the feasibility of pulsed current annealing in reusing metal oxide semiconductor field-effect transistor (MOSFET) dosimeters forin vivo intensity modulated radiation therapy (IMRT) dosimetry. Methods: Several MOSFETs were irradiated atd{sub max} using a 6 MV x-ray beam with 5 V on the gate and annealed with zero bias at room temperature. The percentage recovery of threshold voltage shift during multiple irradiation-annealing cycles was evaluated. Key dosimetry characteristics of the annealed MOSFET such as the dosimeter's sensitivity, reproducibility, dose linearity, and linearity of response within the dynamic range were investigated. The initial results of using the annealed MOSFETs for IMRT dosimetry practice were also presented. Results: More than 95% of threshold voltage shift can be recovered after 24-pulse current continuous annealing in 16 min. The mean sensitivity degradation was found to be 1.28%, ranging from 1.17% to 1.52%, during multiple annealing procedures. Other important characteristics of the annealed MOSFET remained nearly consistent before and after annealing. Our results showed there was no statistically significant difference between the annealed MOSFETs and their control samples in absolute dose measurements for IMRT QA (p = 0.99). The MOSFET measurements agreed with the ion chamber results on an average of 0.16% ± 0.64%. Conclusions: Pulsed current annealing provides a practical option for reusing MOSFETs to extend their operational lifetime. The current annealing circuit can be integrated into the reader, making the annealing procedure fully automatic.

  20. In vivo laser scanning microscopic investigation of the decontamination of hazardous substances from the human skin

    International Nuclear Information System (INIS)

    Lademann, J; Patzelt, A; Schanzer, S; Richter, H; Sterry, W; Gross, I; Menting, K H; Frazier, L; Antoniou, C

    2010-01-01

    The stimulation of the penetration of topically applied substances into the skin is a topic of intensive dermatological and pharmacological research. In this context, it was found that in addition to the intercellular penetration, the follicular penetration also represents an efficient penetration pathway. The hair follicles act as a long-term reservoir for topically applied substances. They are surrounded by all important target structures, such as blood capillaries, stem and dendritic cells. Therefore, the hair follicles, as well as the skin, need to be protected from hazardous substances. The traditional method of decontamination after respective accidental contacts consists of an intensive washing of the skin. However, during this mechanical procedure, the substances can be pushed even deeper into the hair follicles. In the present study, absorbent materials were applied to remove a fluorescent model substance from the skin without inducing mechanical stress. The results were compared to the decontamination effects obtained by intensive washing. Investigations were performed by means of in vivo laser scanning microscopy (LSM). The comparison revealed that decontamination with absorbent materials is more effective than decontamination with washing processes

  1. Investigation of a pulsed current annealing method in reusing MOSFET dosimeters for in vivo IMRT dosimetry.

    Science.gov (United States)

    Luo, Guang-Wen; Qi, Zhen-Yu; Deng, Xiao-Wu; Rosenfeld, Anatoly

    2014-05-01

    To explore the feasibility of pulsed current annealing in reusing metal oxide semiconductor field-effect transistor (MOSFET) dosimeters for in vivo intensity modulated radiation therapy (IMRT) dosimetry. Several MOSFETs were irradiated at d(max) using a 6 MV x-ray beam with 5 V on the gate and annealed with zero bias at room temperature. The percentage recovery of threshold voltage shift during multiple irradiation-annealing cycles was evaluated. Key dosimetry characteristics of the annealed MOSFET such as the dosimeter's sensitivity, reproducibility, dose linearity, and linearity of response within the dynamic range were investigated. The initial results of using the annealed MOSFETs for IMRT dosimetry practice were also presented. More than 95% of threshold voltage shift can be recovered after 24-pulse current continuous annealing in 16 min. The mean sensitivity degradation was found to be 1.28%, ranging from 1.17% to 1.52%, during multiple annealing procedures. Other important characteristics of the annealed MOSFET remained nearly consistent before and after annealing. Our results showed there was no statistically significant difference between the annealed MOSFETs and their control samples in absolute dose measurements for IMRT QA (p = 0.99). The MOSFET measurements agreed with the ion chamber results on an average of 0.16% ± 0.64%. Pulsed current annealing provides a practical option for reusing MOSFETs to extend their operational lifetime. The current annealing circuit can be integrated into the reader, making the annealing procedure fully automatic.

  2. Investigation of a pulsed current annealing method in reusing MOSFET dosimeters for in vivo IMRT dosimetry

    International Nuclear Information System (INIS)

    Luo, Guang-Wen; Qi, Zhen-Yu; Deng, Xiao-Wu; Rosenfeld, Anatoly

    2014-01-01

    Purpose: To explore the feasibility of pulsed current annealing in reusing metal oxide semiconductor field-effect transistor (MOSFET) dosimeters forin vivo intensity modulated radiation therapy (IMRT) dosimetry. Methods: Several MOSFETs were irradiated atd max using a 6 MV x-ray beam with 5 V on the gate and annealed with zero bias at room temperature. The percentage recovery of threshold voltage shift during multiple irradiation-annealing cycles was evaluated. Key dosimetry characteristics of the annealed MOSFET such as the dosimeter's sensitivity, reproducibility, dose linearity, and linearity of response within the dynamic range were investigated. The initial results of using the annealed MOSFETs for IMRT dosimetry practice were also presented. Results: More than 95% of threshold voltage shift can be recovered after 24-pulse current continuous annealing in 16 min. The mean sensitivity degradation was found to be 1.28%, ranging from 1.17% to 1.52%, during multiple annealing procedures. Other important characteristics of the annealed MOSFET remained nearly consistent before and after annealing. Our results showed there was no statistically significant difference between the annealed MOSFETs and their control samples in absolute dose measurements for IMRT QA (p = 0.99). The MOSFET measurements agreed with the ion chamber results on an average of 0.16% ± 0.64%. Conclusions: Pulsed current annealing provides a practical option for reusing MOSFETs to extend their operational lifetime. The current annealing circuit can be integrated into the reader, making the annealing procedure fully automatic

  3. A Think-Aloud Protocols Investigation of Dictionary Processing Strategies among Saudi EFL Students

    Science.gov (United States)

    Alhaysony, Maha

    2012-01-01

    This paper aims to examine qualitatively how Saudi EFL female students look-up word meanings in their dictionaries while reading. We aimed to identify and describe the look-up strategies used by these students. The subjects of the study were ten third-year English major students. A think-aloud protocol was used in order to gain insights into the…

  4. Investigation of spatial resolution characteristics of an in vivo microcomputed tomography system

    Energy Technology Data Exchange (ETDEWEB)

    Ghani, Muhammad U. [Center for Biomedical engineering and School of Electrical and Computer Engineering, University of Oklahoma, Norman, OK 73019 (United States); Zhou, Zhongxing [Center for Biomedical engineering and School of Electrical and Computer Engineering, University of Oklahoma, Norman, OK 73019 (United States); School of Precision and Optoelectronics Engineering, Tianjin University, Tianjin 300072 (China); Ren, Liqiang; Wong, Molly; Li, Yuhua; Zheng, Bin [Center for Biomedical engineering and School of Electrical and Computer Engineering, University of Oklahoma, Norman, OK 73019 (United States); Yang, Kai [Department of Radiology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114 (United States); Liu, Hong, E-mail: liu@ou.edu [Center for Biomedical engineering and School of Electrical and Computer Engineering, University of Oklahoma, Norman, OK 73019 (United States)

    2016-01-21

    The spatial resolution characteristics of an in vivo microcomputed tomography (CT) system was investigated in the in-plane (x–y), cross plane (z) and projection imaging modes. The microCT system utilized in this study employs a flat panel detector with a 127 µm pixel pitch, a microfocus x-ray tube with a focal spot size ranging from 5–30 µm, and accommodates three geometric magnifications (M) of 1.72, 2.54 and 5.10. The in-plane modulation transfer function (MTF) curves were measured as a function of the number of projections, geometric magnification (M), detector binning and reconstruction magnification (M{sub Recon}). The in plane cutoff frequency (10% MTF) ranged from 2.31 lp/mm (M=1.72, 2×2 binning) to 12.56 lp/mm (M=5.10, 1×1 binning) and a bar pattern phantom validated those measurements. A slight degradation in the spatial resolution was observed when comparing the image reconstruction with 511 and 918 projections, whose effect was visible at the lower frequencies. Small value of M{sub Recon} has little or no impact on the in-plane spatial resolution owning to a stable system. Large value of M{sub Recon} has implications on the spatial resolution and it was evident when comparing the bar pattern images reconstructed with M{sub Recon}=1.25 and 2.5. The cross plane MTF curves showed that the spatial resolution increased as the slice thickness decreased. The cutoff frequencies in the projection imaging mode yielded slightly higher values as compared to the in-plane and cross plane modes at all the geometric magnifications (M). At M=5.10, the cutoff resolution of the projection and cross plane on an ultra-high contrast resolution bar chip phantom were 14.9 lp/mm and 13–13.5 lp/mm. Due to the finite focal spot size of the x-ray tube, the detector blur and the reconstruction kernel functions, the system's spatial resolution does not reach the limiting spatial resolution as defined by the Nyquist's detector criteria with an ideal point source

  5. In Vivo and In Silico Investigation Into Mechanisms of Frequency Dependence of Repolarization Alternans in Human Ventricular Cardiomyocytes.

    Science.gov (United States)

    Zhou, Xin; Bueno-Orovio, Alfonso; Orini, Michele; Hanson, Ben; Hayward, Martin; Taggart, Peter; Lambiase, Pier D; Burrage, Kevin; Rodriguez, Blanca

    2016-01-22

    Repolarization alternans (RA) are associated with arrhythmogenesis. Animal studies have revealed potential mechanisms, but human-focused studies are needed. RA generation and frequency dependence may be determined by cell-to-cell variability in protein expression, which is regulated by genetic and external factors. To characterize in vivo RA in human and to investigate in silico using human models, the ionic mechanisms underlying the frequency-dependent differences in RA behavior identified in vivo. In vivo electrograms were acquired at 240 sites covering the epicardium of 41 patients at 6 cycle lengths (600-350 ms). In silico investigations were conducted using a population of biophysically detailed human models incorporating variability in protein expression and calibrated using in vivo recordings. Both in silico and in vivo, 2 types of RA were identified, with Fork- and Eye-type restitution curves, based on RA persistence or disappearance, respectively, at fast pacing rates. In silico simulations show that RA are strongly correlated with fluctuations in sarcoplasmic reticulum calcium, because of strong release and weak reuptake. Large L-type calcium current conductance is responsible for RA disappearance at fast frequencies in Eye-type (30% larger in Eye-type versus Fork-type; Psilico, 2 types of RA are identified, with RA persistence/disappearance as frequency increases. In silico, L-type calcium current and Na(+)/Ca(2+) exchanger current determine RA human cell-to-cell differences through intracellular and sarcoplasmic reticulum calcium regulation. © 2015 The Authors.

  6. In vivo immunogenicity of bovine bone removed by a novel decellularization protocol based on supercritical carbon dioxide.

    Science.gov (United States)

    You, Ling; Weikang, Xu; Lifeng, Yang; Changyan, Liang; Yongliang, Lin; Xiaohui, Wei; Bin, Xu

    2018-05-04

    Trauma or infections associated critical bone defects lead to a huge economic burden in the healthcare system worldwide. Recent advances in tissue engineering have led to potential new strategies for the repair, replacement, and regeneration of bone defects, especially in biomaterials and decellularization protocols from xenogenic tissues. However, the complexity in bone structure and mechanical environment limits the synthesis of artificial bone with biomaterials. Thus, the purpose of our study is to develop a natural bone scaffold with great immunocompatibility. We combined decellularization techniques base on SC-CO 2 to decellularize bovine bone. In order to study the immune response of mice to materials, the histology, spleen index, immune cells contents and in vitro proliferative performance, cytokine and immunoglobulin light chain expression of mice were characterized. Compared with the fresh bone group, the immune responses of decellularized group were significantly reduced. In conclusion, decellularization via this method can achieve a decellularized scaffold with great immunocompatibility. Our findings suggest the potential of using decellularized BB as a scaffold for bone bioengineering.

  7. A Monte Carlo investigation of contaminant electrons due to a novel in vivo transmission detector

    International Nuclear Information System (INIS)

    Asuni, G; Jensen, J M; McCurdy, B M C

    2011-01-01

    A novel transmission detector (IBA Dosimetry, Germany) developed as an IMRT quality assurance tool, intended for in vivo patient dose measurements, is studied here. The goal of this investigation is to use Monte Carlo techniques to characterize treatment beam parameters in the presence of the detector and to compare to those of a plastic block tray (a frequently used clinical device). Particular attention is paid to the impact of the detector on electron contamination model parameters of two commercial dose calculation algorithms. The linac head together with the COMPASS transmission detector (TRD) was modeled using BEAMnrc code. To understand the effect of the TRD on treatment beams, the contaminant electron fluence, energy spectra, and angular distributions at different SSDs were analyzed for open and non-open (i.e. TRD and block tray) fields. Contaminant electrons in the BEAMnrc simulations were separated according to where they were created. Calculation of surface dose and the evaluation of contributions from contaminant electrons were performed using the DOSXYZnrc user code. The effect of the TRD on contaminant electrons model parameters in Eclipse AAA and Pinnacle 3 dose calculation algorithms was investigated. Comparisons of the fluence of contaminant electrons produced in the non-open fields versus open field show that electrons created in the non-open fields increase at shorter SSD, but most of the electrons at shorter SSD are of low energy with large angular spread. These electrons are out-scattered or absorbed in air and contribute less to surface dose at larger SSD. Calculated surface doses with the block tray are higher than those with the TRD. Contribution of contaminant electrons to dose in the buildup region increases with increasing field size. The additional contribution of electrons to surface dose increases with field size for TRD and block tray. The introduction of the TRD results in a 12% and 15% increase in the Gaussian widths used in the

  8. Zoonoses action plan Salmonella monitoring programme: an investigation of the sampling protocol.

    Science.gov (United States)

    Snary, E L; Munday, D K; Arnold, M E; Cook, A J C

    2010-03-01

    The Zoonoses Action Plan (ZAP) Salmonella Programme was established by the British Pig Executive to monitor Salmonella prevalence in quality-assured British pigs at slaughter by testing a sample of pigs with a meat juice enzyme-linked immunosorbent assay for antibodies against group B and C(1) Salmonella. Farms were assigned a ZAP level (1 to 3) depending on the monitored prevalence, and ZAP 2 or 3 farms were required to act to reduce the prevalence. The ultimate goal was to reduce the risk of human salmonellosis attributable to British pork. A mathematical model has been developed to describe the ZAP sampling protocol. Results show that the probability of assigning a farm the correct ZAP level was high, except for farms that had a seroprevalence close to the cutoff points between different ZAP levels. Sensitivity analyses identified that the probability of assigning a farm to the correct ZAP level was dependent on the sensitivity and specificity of the test, the number of batches taken to slaughter each quarter, and the number of samples taken per batch. The variability of the predicted seroprevalence was reduced as the number of batches or samples increased and, away from the cutoff points, the probability of being assigned the correct ZAP level increased as the number of batches or samples increased. In summary, the model described here provided invaluable insight into the ZAP sampling protocol. Further work is required to understand the impact of the program for Salmonella infection in British pig farms and therefore on human health.

  9. Investigation of allergenicity of some cosmetic mixtures by using ex vivo local lymph node assay-BrdU endpoints.

    Science.gov (United States)

    Ulker, Ozge Cemiloglu; Kaymak, Yesim; Karakaya, Asuman

    2014-01-01

    Balsam of Peru and fragrance mix are commonly used in cosmetic products. Allergy to fragrance is the most common cause of cosmetic contact dermatitis. In the present study, ex vivo local lymph node assay-5-bromo-2'-deoxyuridine (LLNA-BrdU) was used to evaluate the dermal sensitization potential of these cosmetic mixtures. The stimulation index values and estimated concentration (EC3) values were calculated and the potency classification was found for each mixture. At the same time, in order to measure the irritant effect without having to use additional animals, a combination of ex vivo LLNA-BrdU and the irritancy assay was conducted. Th1 [interleukin (IL)-2, interferon-γ] and Th2 cytokine (IL-4, IL-5) releases from lymph node cell culture were investigated as non-radioactive endpoints. According to the results of ex vivo LLNA-BrdU assays, EC3 values were found to be 3.09% (moderate) for balsam of Peru and 4.44% (moderate) for fragrance mix. Cytokine analysis results indicate that both Th1 and Th2 cytokines are involved in the regulation of murine contact allergy and can be considered as useful endpoints. In conclusion, according to our results, fragrance mix and balsam of Peru can be considered as moderate sensitizers; however, in high concentrations, both of them have irritation properties. The cytokines investigated can be considered as the endpoints of the ex vivo LLNA-BrdU assay. © 2014 S. Karger AG, Basel.

  10. Feasibility of a Research Protocol to Investigate the Effect of the TherapressureTM Program Using Salivary Cortisol

    Directory of Open Access Journals (Sweden)

    Scott Weeks

    2016-04-01

    Full Text Available Background: There is an absence of high quality research to support the use of the Therapressure ProgramTM. This pilot study aimed at developing appropriate research protocols to investigate the effectiveness of the Therapressure ProgramTM on the stress response in children with sensory overresponsivity. Method: A one-group pre-test/post-test repeated measures design was conducted using a convenience sample. Six children (6-8 years of age with sensory overresponsivity received 14 consecutive days of the Therapressure ProgramTM by their parents at home. Parents concurrently collected salivary cortisol samples from their children. Results: Children with sensory overresponsivity displayed both hyper- and hypo-cortisolism at baseline. All of the children’s cortisol levels shifted toward a normative range after intervention. Aspects have been identified related to the data collection protocol. Conclusion: When testing children with sensory overresponsivity who are constantly activating their stress response system, we raise awareness of the need to check for both hyper- and hypo-cortisolism during statistical analysis. Preliminary pilot data may also show modulation of sympathetic arousal following the intervention. Further research is warranted and recommendations are made related to data collection protocols.

  11. On Designing Thermal-Aware Localized QoS Routing Protocol for in-vivo Sensor Nodes in Wireless Body Area Networks

    Directory of Open Access Journals (Sweden)

    Muhammad Mostafa Monowar

    2015-06-01

    Full Text Available In this paper, we address the thermal rise and Quality-of-Service (QoS provisioning issue for an intra-body Wireless Body Area Network (WBAN having in-vivo sensor nodes. We propose a thermal-aware QoS routing protocol, called TLQoS, that facilitates the system in achieving desired QoS in terms of delay and reliability for diverse traffic types, as well as avoids the formation of highly heated nodes known as hotspot(s, and keeps the temperature rise along the network to an acceptable level. TLQoS exploits modular architecture wherein different modules perform integrated operations in providing multiple QoS service with lower temperature rise. To address the challenges of highly dynamic wireless environment inside the human body. TLQoS implements potential-based localized routing that requires only local neighborhood information. TLQoS avoids routing loop formation as well as reduces the number of hop traversal exploiting hybrid potential, and tuning a configurable parameter. We perform extensive simulations of TLQoS, and the results show that TLQoS has significant performance improvements over state-of-the-art approaches.

  12. On Designing Thermal-Aware Localized QoS Routing Protocol for in-vivo Sensor Nodes in Wireless Body Area Networks.

    Science.gov (United States)

    Monowar, Muhammad Mostafa; Bajaber, Fuad

    2015-06-15

    In this paper, we address the thermal rise and Quality-of-Service (QoS) provisioning issue for an intra-body Wireless Body Area Network (WBAN) having in-vivo sensor nodes. We propose a thermal-aware QoS routing protocol, called TLQoS, that facilitates the system in achieving desired QoS in terms of delay and reliability for diverse traffic types, as well as avoids the formation of highly heated nodes known as hotspot(s), and keeps the temperature rise along the network to an acceptable level. TLQoS exploits modular architecture wherein different modules perform integrated operations in providing multiple QoS service with lower temperature rise. To address the challenges of highly dynamic wireless environment inside the human body. TLQoS implements potential-based localized routing that requires only local neighborhood information. TLQoS avoids routing loop formation as well as reduces the number of hop traversal exploiting hybrid potential, and tuning a configurable parameter. We perform extensive simulations of TLQoS, and the results show that TLQoS has significant performance improvements over state-of-the-art approaches.

  13. In Vitro and In Vivo Investigation of the Potential of Amorphous Microporous Silica as a Protein Delivery Vehicle

    Directory of Open Access Journals (Sweden)

    Amol Chaudhari

    2013-01-01

    Full Text Available Delivering growth factors (GFs at bone/implant interface needs to be optimized to achieve faster osseointegration. Amorphous microporous silica (AMS has a potential to be used as a carrier and delivery platform for GFs. In this work, adsorption (loading and release (delivery mechanism of a model protein, bovine serum albumin (BSA, from AMS was investigated in vitro as well as in vivo. In general, strong BSA adsorption to AMS was observed. The interaction was stronger at lower pH owing to favorable electrostatic interaction. In vitro evaluation of BSA release revealed a peculiar release profile, involving a burst release followed by a 6 h period without appreciable BSA release and a further slower release later. Experimental data supporting this observation are discussed. Apart from understanding protein/biomaterial (BSA/AMS interaction, determination of in vivo protein release is an essential aspect of the evaluation of a protein delivery system. In this regard micropositron emission tomography (μ-PET was used in an exploratory experiment to determine in vivo BSA release profile from AMS. Results suggest stronger in vivo retention of BSA when adsorbed on AMS. This study highlights the possible use of AMS as a controlled protein delivery platform which may facilitate osseointegration.

  14. In vitro and in vivo investigations of targeted chemotherapy with magnetic nanoparticles

    International Nuclear Information System (INIS)

    Alexiou, Christoph; Jurgons, Roland; Schmid, Roswitha; Hilpert, Andrea; Bergemann, Christian; Parak, Fritz; Iro, Heinrich

    2005-01-01

    Magnetic drug targeting is a local drug delivery system. Electromicroscopic pictures document the ferrofluid enrichment in the intracellular space in vitro. In vivo experiments were performed in VX2 tumor-bearing rabbits using magnetic nanoparticles bound to mitoxantrone. High-pressure liquid chromatography (HPLC) analyses after magnetic drug targeting showed an increasing concentration of the chemotherapeutic agent in the tumor region compared to regular systemic chemotherapy

  15. A Novel Ex Vivo Model to Investigate the Underlying Mechanisms in Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Emanuele Brai

    2017-09-01

    Full Text Available Currently there is no widely accepted animal model reproducing the full pathological profile of Alzheimer’s disease (AD, since the basic mechanisms of neurodegeneration are still poorly understood. We have proposed that the interaction between the α7 nicotinic acetylcholine receptor (α7-nAChR and a recently discovered toxic peptide, cleaved from the acetylcholinesterase (AChE C-terminus, could account for the aberrant processes occurring in AD. In this article we describe a new application on ex vivo model procedure, which combines the advantages of both in vivo and in vitro preparations, to study the effects of the AChE-derived peptide on the rat basal forebrain (BF. Western blot analysis showed that the levels of α7-nAChR, p-Tau and Aβ are differentially expressed upon the AChE-peptide administration, in a selective site-dependent manner. In conclusion, this methodology demonstrates the action of a novel peptide in triggering an AD-like phenotype and proposes a new ex vivo approach for manipulating and monitoring neurochemical processes contributing to neurodegeneration, in a time-dependent and site-specific manner.

  16. "Rinse and trickle": a protocol for TEM preparation and investigation of inorganic fibers from biological material.

    Science.gov (United States)

    Vigliaturo, Ruggero; Capella, Silvana; Rinaudo, Caterina; Belluso, Elena

    2016-07-01

    The purpose of this work is to define a sample preparation protocol that allows inorganic fibers and particulate matter extracted from different biological samples to be characterized morphologically, crystallographically and chemically by transmission electron microscopy-energy dispersive spectroscopy (TEM-EDS). The method does not damage or create artifacts through chemical attacks of the target material. A fairly rapid specimen preparation is applied with the aim of performing as few steps as possible to transfer the withdrawn inorganic matter onto the TEM grid. The biological sample is previously digested chemically by NaClO. The salt is then removed through a series of centrifugation and rinse cycles in deionized water, thus drastically reducing the digestive power of the NaClO and concentrating the fibers for TEM analysis. The concept of equivalent hydrodynamic diameter is introduced to calculate the settling velocity during the centrifugation cycles. This technique is applicable to lung tissues and can be extended to a wide range of organic materials. The procedure does not appear to cause morphological damage to the fibers or modify their chemistry or degree of crystallinity. The extrapolated data can be used in interdisciplinary studies to understand the pathological effects caused by inorganic materials.

  17. Investigating And Evaluating Of Network Failures And Performance Over Distributed WAN In Application Protocol Layer

    Directory of Open Access Journals (Sweden)

    Enoch Okoh Kofi

    2015-08-01

    Full Text Available The Experiment was done to find out network failures and application performance relationship over distributed Wide Area Net WAN. In order to access related application over the cloud there must be an internet connectivity which will help the respective workstations to access the remote server for applications being deployed over the network. Bandwidth improvement helps in reducing utilization over the network and it also helps in improving Application Efficiency of these Applications in terms of Response Time. Routers were configured under Enhance Interior Gateway Routing Protocol EIGRP to reduce utilization and to ensure load sharing over the network. Three scenarios were modeled and their performance efficiency was evaluated. A modeled computer Network with and without a fail Router under different scenarios and such Network was simulated with emphasis on the Application Performance. The Experiment was done for fifty workstations under three scenarios and these three scenarios were accessed and evaluated on experimental basis using Riverbed modeler to show the Effect of Application Network performance. The performance results show that increasing the bandwidth reduces utilization and also with the failure of one communication bandwidth users can still access Network Application with a minimal cost.

  18. Isolation of hydroxytyrosol from olive leaves extract, radioiodination and investigation of bioaffinity using in vivo/in vitro methods

    Energy Technology Data Exchange (ETDEWEB)

    Ozkan, M.; Biber Muftuler, F.Z.; Kilcar, A. Yurt; Medine, E.I.; Unak, P. [Ege Univ., Izmir (Turkey). Dept. of Nuclear Applications

    2013-11-01

    It is known that medicinal plants like olive have biological activities due to their flavonoid content such as olueropein, tyrosol, hydroxytyrosol etc. In current study, hydroxytrosol (HT) which is one of the major phenolic compounds in olive, olive leaves and olive oil, was isolated after methanol extraction and purification of olive leaves which are grown in the northern Anatolia region of Turkey. The isolated HT was radiolabeled with {sup 131}I ({sup 131}I-HT) and the bioaffinity of this radiolabeled component of olive leaves extract was investigated by using in vivo/in vitro methods. It was found that HT could be radiolabeled with {sup 131}I in yields of 95.6 {+-} 4.4% (n = 8), and in vivo studies showed that {sup 131}I-HT is taken up by urinary bladder, stomach, small intestine, large intestine, breast and prostate. Significant incorporation of activity was observed in cell lines via in vitro studies. (orig.)

  19. An investigation on in vitro and in vivo antimicrobial properties of the antidepressant: amitriptyline hydrochloride

    Directory of Open Access Journals (Sweden)

    Anurup Mandal

    2010-10-01

    Full Text Available The antidepressant drug amitriptyline hydrochloride was obtained in a dry powder form and was screened against 253 strains of bacteria which included 72 Gram positive and 181 Gram negative bacteria and against 5 fungal strains. The minimum inhibitory concentration (MIC was determined by inoculating a loopful of an overnight peptone water culture of the organism on nutrient agar plates containing increasing concentrations of amitriptyline hydrochloride (0, 10 µg/mL, 25 µg/mL, 50 µg/mL, 100 µg/mL, 200 µg/mL. Amitriptyline hydrochloride exhibited significant action against both Gram positive and Gram negative bacteria at 25-200 µg/mL. In the in vivo studies it was seen that amitriptyline hydrochloride at a concentration of 25 µg/g and 30 µg/g body weight of mouse offered significant protection to Swiss strain of white mice when challenged with 50 median lethal dose (MLD of a virulent strain of Salmonella typhimurium NCTC 74. The in vivo data were highly significant (p<0.001 according to the chi-square test.

  20. Terbinafine hydrochloride nanovesicular gel: In vitro characterization, ex vivo permeation and clinical investigation.

    Science.gov (United States)

    AbdelSamie, Sara M; Kamel, Amany O; Sammour, Omaima A; Ibrahim, Shady M

    2016-06-10

    In this work, nanovesicular chitosan gels were prepared for dermal delivery of terbinafine hydrochloride (TBN HCl). Ethosomes and vesicles containing different types of penetration enhancers (PEs) viz. Terpenes (cineole and limonene), labrasol and transcutol were developed. The prepared vesicles were evaluated for physical characteristics as well as skin interaction. The selected vesicles were incorporated into chitosan gel. An in vivo animal study was done on rat induced superficial Candida infection model. Moreover, randomized double blind clinical study was done on patients to compare the effect of the selected nanovesicular gel against the market product. Results showed the formation of nearly spherical, mostly deformable vesicular systems with size range of 95.5-530nm, zeta potential range of -0.1 to 15mV and entrapment efficiency range of 20-96.7%. Penetration enhancer vesicles (PEVs) prepared with 4% limonene (ELI4) showed the highest percent of drug deposition in the skin (53%) and the highest local accumulation efficiency value (35.3). In vivo animal study showed that the lowest fungal burden produced with ELI4 chitosan gel. Clinical studies showed cure rate of 86% within 7days treatment in case of limonene nanovesicular gel compared to 20% for market product (Lamisil® cream). Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Toward a standardized investigation protocol in sudden unexpected deaths in infancy in South Africa: a multicenter study of medico-legal investigation procedures and outcomes.

    Science.gov (United States)

    du Toit-Prinsloo, Lorraine; Dempers, Johan; Verster, Janette; Hattingh, Christa; Nel, Hestelle; Brandt, V D; Jordaan, Joyce; Saayman, Gert

    2013-09-01

    South Africa manifests a socio-economic dichotomy that shows features of both a developed and developing country. As a result of this, areas exist where a lack of resources and expertise prevents the implementation of a highly standardized protocol for the investigation of sudden and unexpected deaths in infants (SUDI). Although the medico-legal mortuaries attached to academic centers have the capacity to implement standardized protocols, a previous study conducted at two large medico-legal mortuaries indicated otherwise. This study also revealed that the exact number and incidence of sudden infant death syndrome (SIDS) cases was unknown. These findings prompted a multicenter study of the medico-legal investigation procedures and outcomes in five academic centers in South Africa. A retrospective case audit was conducted for a 5-year period (2005-2009) at medico-legal laboratories attached to universities in Bloemfontein, Cape Town-Tygerberg, Durban, Johannesburg, and Pretoria. The total case load as well as the total number of infants younger than 1 year of age admitted to these mortuaries was documented. The case files on all infants younger than 1 year of age who were admitted as sudden and unexpected or unexplained deaths were included in the study population. Data collected on the target population included demographic details, the nature and scope of the post-mortem examinations, as well as the final outcome (cause of death). A total case load of 80,399 cases were admitted to the mortuaries over the 5 year period with a total of 3,295 (6.5 %) infants. In the infant group, 591 (0.7 %) died from non-natural causes and 2,704 (3.3 %) cases of sudden, unexpected and/or unexplained deaths in infants were admitted and included in the detailed case analysis study. One hundred and ninety-nine babies were between 0 and 7 days of age and 210 babies between 8 and 30 days. The remaining 2,295 infants were between 1 month and 12 months of age. Death scene investigation was

  2. Prolonged Helium Postconditioning Protocols during Early Reperfusion Do Not Induce Cardioprotection in the Rat Heart In Vivo: Role of Inflammatory Cytokines

    Directory of Open Access Journals (Sweden)

    Gezina Tanya Mei Ling Oei

    2015-01-01

    Full Text Available Postconditioning of myocardial tissue employs short cycles of ischemia or pharmacologic agents during early reperfusion. Effects of helium postconditioning protocols on infarct size and the ischemia/reperfusion-induced immune response were investigated by measurement of protein and mRNA levels of proinflammatory cytokines. Rats were anesthetized with S-ketamine (150 mg/kg and diazepam (1.5 mg/kg. Regional myocardial ischemia/reperfusion was induced; additional groups inhaled 15, 30, or 60 min of 70% helium during reperfusion. Fifteen minutes of helium reduced infarct size from 43% in control to 21%, whereas 30 and 60 minutes of helium inhalation led to an infarct size of 47% and 39%, respectively. Increased protein levels of cytokine-induced neutrophil chemoattractant (CINC-3 and interleukin-1 beta (IL-1β were found after 30 or 60 min of helium inhalation, in comparison to control. 30 min of helium increased mRNA levels of CINC-3, IL-1β, interleukin 6 (IL-6, and tumor necrosis factor alpha (TNF-α in myocardial tissue not directly subjected to ischemia/reperfusion. These results suggest that the effectiveness of the helium postconditioning protocol is very sensitive to duration of noble gas application. Additionally, helium was associated with higher levels of inflammatory cytokines; however, it is not clear whether this is causative of nature or part of an epiphenomenon.

  3. In vitro and in vivo investigation of matrix metalloproteinase expression in metastatic tumor models

    Energy Technology Data Exchange (ETDEWEB)

    Sprague, Jennifer E. [Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110 (United States); Li Wenping [Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110 (United States); Liang Kexian [Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110 (United States); Achilefu, Samuel [Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110 (United States); Anderson, Carolyn J. [Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110 (United States)]. E-mail: andersoncj@wustl.edu

    2006-02-15

    Introduction: Overexpression of matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, has been correlated with poor prognosis in several cancer types including lung, colon and breast. Noninvasive detection of MMP expression might allow physicians to better determine when more aggressive cancer therapy is appropriate. The peptide CTT (CTTHWGFTLC) was identified as a selective inhibitor of MMP-2/9 that inhibits the growth of MDA-MB-435 human breast cancer xenografts. Methods: CTT was conjugated with the bifunctional chelator DOTA (1,4,7,10-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid) for radiolabeling with {sup 64}Cu (t {sub 1/2}=12.7 h, 17.4% {beta}{sup +}, 39% {beta}{sup -}), a radionuclide suitable for positron emission tomography (PET). In vitro affinity was determined in a fluorogenic substrate assay. Tumor gelatinase targeting was evaluated in both biodistribution and microPET imaging studies. Results: Cu(II)-DOTA-CTT inhibited hMMP-2 (EC{sub 5}=8.7 {mu}M) and mMMP-9 (EC{sub 5}=18.2 {mu}M) with similar affinity to CTT (hMMP-2 EC{sub 5}=13.2 {mu}M; mMMP-9 EC{sub 5}=11.0 {mu}M). In biodistribution and microPET imaging studies, {sup 64}Cu-DOTA-CTT was taken up by MMP-2/9-positive B16F10 murine melanoma tumors. Subsequently, imaging studies using {sup 64}Cu-DOTA-CTT were performed on MDA-MB-435 tumor-bearing mice. With zymography, tumor MMP-2/9 expression in this model was shown to be inconsistent, resulting in microPET detection of the MDA-MB-435 tumor in only 1 of 24 imaged mice. Following limited imaging success, {sup 64}Cu-DOTA-CTT was shown to have poor in vivo stability. Conclusions: Despite some evidence for selective uptake of {sup 64}Cu-DOTA-CTT by gelatinase-expressing tumors, the low affinity for MMP-2 and MMP-9 and in vivo instability make this an inadequate radioligand for in vivo tumor evaluation.

  4. In vitro and in vivo investigation of matrix metalloproteinase expression in metastatic tumor models

    International Nuclear Information System (INIS)

    Sprague, Jennifer E.; Li Wenping; Liang Kexian; Achilefu, Samuel; Anderson, Carolyn J.

    2006-01-01

    Introduction: Overexpression of matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, has been correlated with poor prognosis in several cancer types including lung, colon and breast. Noninvasive detection of MMP expression might allow physicians to better determine when more aggressive cancer therapy is appropriate. The peptide CTT (CTTHWGFTLC) was identified as a selective inhibitor of MMP-2/9 that inhibits the growth of MDA-MB-435 human breast cancer xenografts. Methods: CTT was conjugated with the bifunctional chelator DOTA (1,4,7,10-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid) for radiolabeling with 64 Cu (t 1/2 =12.7 h, 17.4% β + , 39% β - ), a radionuclide suitable for positron emission tomography (PET). In vitro affinity was determined in a fluorogenic substrate assay. Tumor gelatinase targeting was evaluated in both biodistribution and microPET imaging studies. Results: Cu(II)-DOTA-CTT inhibited hMMP-2 (EC 5 =8.7 μM) and mMMP-9 (EC 5 =18.2 μM) with similar affinity to CTT (hMMP-2 EC 5 =13.2 μM; mMMP-9 EC 5 =11.0 μM). In biodistribution and microPET imaging studies, 64 Cu-DOTA-CTT was taken up by MMP-2/9-positive B16F10 murine melanoma tumors. Subsequently, imaging studies using 64 Cu-DOTA-CTT were performed on MDA-MB-435 tumor-bearing mice. With zymography, tumor MMP-2/9 expression in this model was shown to be inconsistent, resulting in microPET detection of the MDA-MB-435 tumor in only 1 of 24 imaged mice. Following limited imaging success, 64 Cu-DOTA-CTT was shown to have poor in vivo stability. Conclusions: Despite some evidence for selective uptake of 64 Cu-DOTA-CTT by gelatinase-expressing tumors, the low affinity for MMP-2 and MMP-9 and in vivo instability make this an inadequate radioligand for in vivo tumor evaluation

  5. Using Think-Aloud Protocols to Investigate Secondary School Chemistry Teachers' Misconceptions about Chemical Equilibrium

    Science.gov (United States)

    Cheung, Derek

    2009-01-01

    Secondary school chemistry teachers' understanding of chemical equilibrium was investigated through interviews using the think-aloud technique. The interviews were conducted with twelve volunteer chemistry teachers in Hong Kong. Their teaching experience ranged from 3 to 18 years. They were asked to predict what would happen to the equilibrium…

  6. In Vivo Investigation of Escitalopram’s Allosteric Site on the Serotonin Transporter

    Science.gov (United States)

    Murray, Karen E.; Ressler, Kerry J.; Owens, Michael J.

    2015-01-01

    Escitalopram is a commonly prescribed antidepressant of the selective serotonin reuptake inhibitor class. Clinical evidence and mapping of the serotonin transporter (SERT) identified that escitalopram, in addition to its binding to a primary uptake-blocking site, is capable of binding to the SERT via an allosteric site that is hypothesized to alter escitalopram’s kinetics at the SERT. The studies reported here examined the in vivo role of the SERT allosteric site in escitalopram action. A knockin mouse model that possesses an allosteric-null SERT was developed. Autoradiographic studies indicated that the knockin protein was expressed at a lower density than endogenous mouse SERT (approximately 10–30% of endogenous mouse SERT), but the knockin mice are a viable tool to study the allosteric site. Microdialysis studies in the ventral hippocampus found no measurable decrease in extracellular serotonin response after local escitalopram challenge in mice without the allosteric site compared to mice with the site (p = 0.297). In marble burying assays there was a modest effect of the absence of the allosteric site, with a larger systemic dose of escitalopram (10-fold) necessary for the same effect as in mice with intact SERT (p = 0.023). However, there was no effect of the allosteric site in the tail suspension test. Together these data suggest that there may be a regional specificity in the role of the allosteric site. The lack of a robust effect overall suggests that the role of the allosteric site for escitalopram on the SERT may not produce meaningful in vivo effects. PMID:26621784

  7. Investigation of anticancer potential of hypophyllanthin and phyllanthin against breast cancer by in vitro and in vivo methods

    Directory of Open Access Journals (Sweden)

    Madhukiran Parvathaneni

    2014-02-01

    Full Text Available Objective: To investigate the in vitro and in vivo anticancer activities of hypophyllanthin and phyllanthin isolated from Phyllanthus amarus Schum & Thonn against breast cancer. Methods: In vitro anticancer activity was evaluated against two cell lines (MCF-7 and MDAMB-231 using MTT assay. In vivo anticancer activity was tested using Sprague-Dawley rats with N-methyl-N-nitrosourea induced mammary cancer. Results: In vitro studies demonstrated a dose-dependent inhibitory effect on cell growth with IC50 values of (35.18依1.48 µg/mL (hypophyllanthin and (32.51依0.95 µg/mL (phyllanthin for MCF-7; (38.74 依1.24 (hypophyllanthin and (32.2依1.17 (phyllanthin for MDA-MB-231 breast cancer cell lines. Tumor weights per group at doses of 5 and 10 mg/kg/day for hypophyllanthin (12.82 and 12.06 g and phyllanthin (11.95 and 8.87 g treated groups were significantly (P<0.001 lower than untreated N-methyl-N-nitrosourea group (35.85. Conclusions: Results of the present research work indicated that the isolated lignan compounds, hypophyllanthin and phyllanthin showed significant anticancer activities against breast cancer, in vitro and in vivo.

  8. Investigation of complexes with bone affinity using the In vivo generator system 166 Dy/166 Ho

    International Nuclear Information System (INIS)

    Pedraza L, M.

    2006-01-01

    The importance of this original research lies in the fact that it has proven that the [ 166 Dy]Dy/ 166 Ho-EDTMP in vivo generator system is a stable complex that can be used as a therapeutic radiopharmaceutical. Multiple myeloma and other hematological malignancies have been treated by myeloablative radiotherapy/chemotherapy and subsequent stem cell transplantation. Bone-seeking radiopharmaceuticals such as 166 Ho-DOTMP or 153 Sm-DTMP, have been proposed for delivering ablative radiation doses to marrow in multiple myeloma and other hematological malignancies or have shown excellent results in palliative bone metastasis pain therapy, respectively. As lanthanides have similar chemical characteristics the phosphonate with bone affinity (EDTMP) labeled with Dy/Ho can be used for marrow ablation while causing minimal irradiation to normal organs. This in vivo generator system has not been previously reported. The aim of this research was to label EDTMP (ethylene diamine tetramethylene phosphonate) with 166 Dy/ 166 Ho; to evaluate the in vitro and in vivo stability of both 166 Dy-EDTMP and 166 Ho-EDTMP complexes when the daughter 166 Ho is formed as a dysprosium decay product; to determine the bone marrow cytotoxic and genotoxic effect in mice and to evaluate, by histopathology, the myeloablative potential of the [ 166 Dy]Dy/ 166 Ho-EDTMP in vivo generator system. 166 Dy was obtained by neutron irradiation of enriched 164 Dy 2 O 3 in a TRIGA Mark III reactor. Labeling was carried out in an aqueous phosphate medium at pH 8.0 by addition of 166 DyCl 3 to EDTMP at a molar ratio 1:1.75, with >99 % radiochemical purity, as determined by thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC). In vitro studies demonstrated that 166 Dy/ 166 Ho-EDTMP is unstable after dilution in saline but stable in human serum with no translocation of the daughter nucleus subsequent to β decay of 166 Dy, which could release free 166 Ho 3+ . Biodistribution in mice

  9. Quantum driving of a two level system: quantum speed limit and superadiabatic protocols – an experimental investigation

    International Nuclear Information System (INIS)

    Malossi, N; Arimondo, E; Ciampini, D; Mannella, R; Bason, M G; Viteau, M; Morsch, O

    2013-01-01

    A fundamental requirement in quantum information processing and in many other areas of science is the capability of precisely controlling a quantum system by preparing a quantum state with the highest fidelity and/or in the fastest possible way. Here we present an experimental investigation of a two level system, characterized by a time-dependent Landau-Zener Hamiltonian, aiming to test general and optimal high-fidelity control protocols. The experiment is based on a Bose-Einstein condensate (BEC) loaded into an optical lattice, then accelerated, which provides a high degree of control over the experimental parameters. We implement generalized Landau-Zener sweeps, comparing them with the well-known linear Landau-Zener sweep. We drive the system from an initial state to a final state with fidelity close to unity in the shortest possible time (quantum brachistochrone), thus reaching the ultimate speed limit imposed by quantum mechanics. On the opposite extreme of the quantum control spectrum, the aim is not to minimize the total transition time but to maximize the adiabaticity during the time-evolution, the system being constrained to the adiabatic ground state at any time. We implement such transitionless superadiabatic protocols by an appropriate transformation of the Hamiltonian parameters. This transformation is general and independent of the physical system.

  10. Study protocol: a randomized controlled trial investigating the effects of a psychosexual training program for adolescents with autism spectrum disorder.

    Science.gov (United States)

    Visser, Kirsten; Greaves-Lord, Kirstin; Tick, Nouchka T; Verhulst, Frank C; Maras, Athanasios; van der Vegt, Esther J M

    2015-08-28

    Previous research shows that adolescents with autism spectrum disorder (ASD) run several risks in their psychosexual development and that these adolescents can have limited access to reliable information on puberty and sexuality, emphasizing the need for specific guidance of adolescents with ASD in their psychosexual development. Few studies have investigated the effects of psychosexual training programs for adolescents with ASD and to date no randomized controlled trials are available to study the effects of psychosexual interventions for this target group. The randomized controlled trial (RCT) described in this study protocol aims to investigate the effects of the Tackling Teenage Training (TTT) program on the psychosexual development of adolescents with ASD. This parallel clinical trial, conducted in the South-West of the Netherlands, has a simple equal randomization design with an intervention and a waiting-list control condition. Two hundred adolescents and their parents participate in this study. We assess the participants in both conditions using self-report as well as parent-report questionnaires at three time points during 1 year: at baseline (T1), post-treatment (T2), and for follow-up (T3). To our knowledge, the current study is the first that uses a randomized controlled design to study the effects of a psychosexual training program for adolescents with ASD. It has a number of methodological strengths, namely a large sample size, a wide range of functionally relevant outcome measures, the use of multiple informants, and a standardized research and intervention protocol. Also some limitations of the described study are identified, for instance not making a comparison between two treatment conditions, and no use of blinded observational measures to investigate the ecological validity of the research results. Dutch Trial Register NTR2860. Registered on 20 April 2011.

  11. An Investigation into the Prediction of in Vivo Clearance for a Range of Flavin-containing Monooxygenase Substrates.

    Science.gov (United States)

    Jones, Barry C; Srivastava, Abhishek; Colclough, Nicola; Wilson, Joanne; Reddy, Venkatesh Pilla; Amberntsson, Sara; Li, Danxi

    2017-10-01

    Flavin-containing monooxygenases (FMO) are metabolic enzymes mediating the oxygenation of nucleophilic atoms such as nitrogen, sulfur, phosphorus, and selenium. These enzymes share similar properties to the cytochrome P450 system but can be differentiated through heat inactivation and selective substrate inhibition by methimazole. This study investigated 10 compounds with varying degrees of FMO involvement to determine the nature of the correlation between human in vitro and in vivo unbound intrinsic clearance. To confirm and quantify the extent of FMO involvement six of the compounds were investigated in human liver microsomal (HLM) in vitro assays using heat inactivation and methimazole substrate inhibition. Under these conditions FMO contribution varied from 21% (imipramine) to 96% (itopride). Human hepatocyte and HLM intrinsic clearance (CL int ) data were scaled using standard methods to determine the predicted unbound intrinsic clearance (predicted CL int u ) for each compound. This was compared with observed unbound intrinsic clearance (observed CL int u ) values back calculated from human pharmacokinetic studies. A good correlation was observed between the predicted and observed CL int u using hepatocytes ( R 2 = 0.69), with 8 of the 10 compounds investigated within or close to a factor of 2. For HLM the in vitro-in vivo correlation was maintained ( R 2 = 0.84) but the accuracy was reduced with only 3 out of 10 compounds falling within, or close to, twofold. This study demonstrates that human hepatocytes and HLM can be used with standard scaling approaches to predict the human in vivo clearance for FMO substrates. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  12. Investigations of the post-IR IRSL protocol applied to single K-feldspar grains from fluvial sediment samples

    International Nuclear Information System (INIS)

    Nian, Xiaomei; Bailey, Richard M.; Zhou, Liping

    2012-01-01

    The post-IR IRSL protocol with single K-feldspar grains was applied to three samples taken from a fluvial sedimentary sequence at the archaeological site of the Dali Man, Shaanxi Province, China. K-feldspar coarse grains were extracted for measurement. Approximately 30–40% of the grains were sufficiently bright to measure, and after application of rejection criteria based on signal strength, recuperation, recycling ratio and saturation dose, ∼10–15% of the grains were used for D e calculation. The relationship of signal decay rate and form of D e (t) with the recovery dose were investigated. The dose recovery ratios of the samples after initial bleaching with the four different light sources were within uncertainties of unity. No anomalous fading was observed. The over-dispersion of the recovered dose and D e values were similar, suggesting neither incomplete resetting of the post-IR IRSL signals nor spatially heterogeneous dose rates significantly affected the natural dose estimates. The values of D e obtained with the single K-feldspar grain post-IR IRSL protocol were in the range ∼400–490 Gy. Combining all of the measured single-grain signals for each of the individual samples (into a ‘synthetic single aliquot’) increased the D e estimates to the range ∼700–900 Gy, suggesting that the grains screened-out by the rejection criteria may have the potential to cause palaeodose over-estimation, although this finding requires a more extensive investigation. Thermally transferred signals were found in the single K-feldspar grains post-IR IRSL protocol, and the proportion of thermally transferred signal to test-dose OSL signal (stimulation at 290 °C) from the natural dose was higher than from regenerative doses, and the proportion was grain- and dose-dependent. As such, TT-post-IR IRSL signals at 290 °C have the potential to cause dose underestimation, although this may be reduced by using larger test-dose irradiations. Our study demonstrates

  13. Adaptive Focusing For Ultrasonic Transcranial Brain Therapy: First In Vivo Investigation On 22 Sheep

    Science.gov (United States)

    Pernot, Mathieu; Aubry, Jean-François; Tanter, Mickael; Boch, Anne Laure; Kujas, Michelle; Fink, Mathias

    2005-03-01

    A high power prototype dedicated to trans-skull therapy has been tested in vivo on 22 sheep. The array is made of 300 high power transducers working at 1MHz central frequency and is able to achieve 400 bars at focus in water during five seconds with a 50% percent duty cycle. In the first series of experiments, 10 sheep were treated and sacrificed immediately after treatment. A complete craniotomy was performed on half of the treated animal models in order to get a reference model. On the other half, minimally invasive surgery has been performed: a hydrophone was inserted at a given target location inside the brain through a craniotomy of a few mm2. A time reversal experiment was then conducted through the skull bone with the therapeutic array to treat the targeted point. Thanks to the high power technology of the prototype, trans-skull adaptive treatment could be achieved. In a second series of experiments, 12 animals were divided into three groups and sacrificed respectively one, two or three weeks after treatment. Finally, Magnetic Resonance Imaging and histological examination were performed to confirm tissue damage.

  14. In vitro and in vivo investigation of bisphosphonate-loaded hydroxyapatite particles for peri-implant bone augmentation.

    Science.gov (United States)

    Kettenberger, Ulrike; Luginbuehl, Vera; Procter, Philip; Pioletti, Dominique P

    2017-07-01

    Locally applied bisphosphonates, such as zoledronate, have been shown in several studies to inhibit peri-implant bone resorption and recently to enhance peri-implant bone formation. Studies have also demonstrated positive effects of hydroxyapatite (HA) particles on peri-implant bone regeneration and an enhancement of the anti-resorptive effect of bisphosphonates in the presence of calcium. In the present study, both hydroxyapatite nanoparticles (nHA) and zoledronate were combined to achieve a strong reinforcing effect on peri-implant bone. The nHA-zoledronate combination was first investigated in vitro with a pre-osteoclastic cell assay (RAW 264.7) and then in vivo in a rat model of postmenopausal osteoporosis. The in vitro study confirmed that the inhibitory effect of zoledronate on murine osteoclast precursor cells was enhanced by loading the drug on nHA. For the in vivo investigation, either zoledronate-loaded or pure nHA were integrated in hyaluronic acid hydrogel. The gels were injected in screw holes that had been predrilled in rat femoral condyles before the insertion of miniature screws. Micro-CT-based dynamic histomorphometry and histology revealed an unexpected rapid mineralization of the hydrogel in vivo through formation of granules, which served as scaffold for new bone formation. The delivery of zoledronate-loaded nHA further inhibited a degradation of the mineralized hydrogel as well as a resorption of the peri-implant bone as effectively as unbound zoledronate. Hyaluronic acid with zoledronate-loaded nHA, thanks to its dual effect on inducing a rapid mineralization and preventing resorption, is a promising versatile material for bone repair and augmentation. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  15. A systematic review investigating fatigue, psychological and cognitive impairment following TIA and minor stroke: protocol paper.

    Science.gov (United States)

    Moran, Grace M; Fletcher, Benjamin; Calvert, Melanie; Feltham, Max G; Sackley, Catherine; Marshall, Tom

    2013-09-08

    Approximately 20,000 people have a transient ischemic attack (TIA) and 23,375 have a minor stroke in England each year. Fatigue, psychological and cognitive impairments are well documented post-stroke. Evidence suggests that TIA and minor stroke patients also experience these impairments; however, they are not routinely offered relevant treatment. This systematic review aims to: (1) establish the prevalence of fatigue, anxiety, depression, post-traumatic stress disorder (PTSD) and cognitive impairment following TIA and minor stroke and to investigate the temporal course of these impairments; (2) explore impact on quality of life (QoL), change in emotions and return to work; (3) identify where further research is required and to potentially inform an intervention study. A systematic review of MEDLINE, EMBASE, PsycINFO, CINAHL, Cochrane libraries and grey literature between January 1993 and April 2013 will be undertaken. Two reviewers will conduct screening search results, study selection, data extraction and quality assessment. Studies of adult TIA and minor stroke participants containing any of the outcomes of interest; fatigue, anxiety, depression, PTSD or cognitive impairment will be included. Studies at any time period after TIA/minor stroke, including those with any length of follow-up, will be included to investigate the temporal course of impairments. QoL, change in emotions and return to work will also be documented. The proportion of TIA or minor stroke participants experiencing each outcome will be reported.If appropriate, a meta-analysis will pool results of individual outcomes. Studies will be grouped and analyzed according to their follow-up timeframe into short-term (TIA/minor stroke), medium-term (3 to 12 months) and long term (> 12 months). Sub-analysis of studies with a suitable control group will be conducted. Exploratory sub-analysis of memory and attention domains of cognitive impairment will be conducted. The current treatment goal for TIA and

  16. Pilot Study: Colostomy and Urine Collection Protocol for Investigating Potential Inciting Causes of Hen Diuresis Syndrome.

    Science.gov (United States)

    Jones, Kelli; Turner, Bradley; Brandão, João; Hubbard, Sue Ann; Magee, Danny; Baughman, Brittany; Wills, Robert; Tully, Thomas

    2015-06-01

    Hen diuresis syndrome has emerged over the past 5 yr as a significant cause of mortality in the U.S. broiler breeder industry. The condition affects hens in production and is characterized by transient muscle weakness in the vent region, transient diuresis, and often urate deposits on the skin below the vent. Affected hens are often seen straining to lay an egg, which suggests oviduct contraction is also impaired. Related hen mortality, often reaching 1% or more a week, is believed to be primarily the result of male aggression of the vent region (Turner et al., "Investigating Causes of Excessive Urate Production in Broiler Breeder Hens Associated with Peritonitis and Cannibalism Mortality," Oral Presentation at The American Association of Avian Pathologists Annual Meeting, p. 139, 2010). The exact association between the cause of mortality and this syndrome is unknown, but it may be the consequence of transient partial to full oviduct prolapse, which predisposes or stimulates cannibalism and aggression. Based on unpublished work done prior to this study (Turner et al., ibid.), the evidence suggests the underlying problem is metabolic. We feel that urine collection and analysis is an essential component to understanding this condition. This study serves as a pilot study for future investigations that attempt to identify the nature and cause of the metabolic disturbance through paired urine and serum collection and analysis. For the purpose of this study, a small sample of 10 affected and 10 unaffected birds was used for sample collection. In order to collect pure urine, the birds were surgically colostomized. Colostomy did prove to be a useful means of collecting urine free of feces, and for the purposes of our study it yielded adequate urine samples for analysis. There were statistically relevant urine values observed. Affected birds had a higher presence of blood in the urine, a lower uric acid excretion rate (mg/hr), higher concentration (mEq/L) of urine Na+, and

  17. A retrospective cohort study to investigate fatigue, psychological or cognitive impairment after TIA: protocol paper.

    Science.gov (United States)

    Moran, Grace M; Calvert, Melanie; Feltham, Max G; Ryan, Ronan; Marshall, Tom

    2015-05-03

    Transient ischaemic attack (TIA) is defined by short-lasting, stroke-like symptoms, and is recognised as a medical emergency. Symptoms are assumed to completely resolve, and treatment is focused on secondary stroke/TIA prevention. However, evidence suggests that patients with TIA may experience ongoing residual impairments, which they do not receive therapy for as standard practice. TIA-induced sequelae could impact on patients' quality of life and ability to return to work or social activities. We aim to investigate whether TIA is associated with subsequent consultation for fatigue, psychological or cognitive impairment in primary care. A retrospective open cohort study of patients with first-ever TIA and matched controls. Relevant data will be extracted from The Health Improvement Network (THIN) database, an anonymised primary care database which includes data for over 12 million patients and covers approximately 6% of the UK population. Outcomes will be the first consultation for fatigue, anxiety, depression, post-traumatic stress disorder or cognitive impairment. Principal analysis will use Kaplan-Meier survivor functions to estimate time to first consultation, with log-rank tests to compare TIA and control patients. Cox proportional hazard models will predict the effect of demographic and patient characteristics on time to first consultation. Approval was granted by a THIN Scientific Review Committee (ref: 14-008). The study's findings will be published in a peer-reviewed journal and disseminated at national and international conferences and through social media. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  18. Imaging techniques and investigation protocols in pediatric emergency imaging; Aufnahmetechnik und Untersuchungsprotokolle beim paediatrischen Notfall

    Energy Technology Data Exchange (ETDEWEB)

    Scharitzer, M.; Hoermann, M.; Puig, S.; Prokop, M. [Universitaetsklinik fuer Radiodiagnostik, Wien (Austria)

    2002-03-01

    Paediatric emergencies demand a quick and efficient radiological investigation with special attention to specific adjustments related to patient age and radiation protection. Imaging modalities are improving rapidly and enable to diagnose childhood diseases and injuries more quickly, accurately and safely. This article provides an overview of imaging techniques adjusted to the age of the child and an overview of imaging strategies of common paediatric emergencies. Optimising the imaging parameters (digital radiography, different screen-film systems, exposure specifications) allows for substantial reduction of radiation dose. Spiral- and multislice-CT reduce scan time and enable a considerable reduction of radiation exposure if scanning parameters (pitch setting, tube current) are properly adjusted. MRI is still mainly used for neurological or spinal emergencies despite the advent of fast imaging sequences. The radiologist's task is to select an appropriate imaging strategy according to expected differential diagnosis and to adjust the imaging techniques to the individual patient. (orig.) [German] Das akut erkrankte Kind erfordert eine rasche radiologische Abklaerung mit besonderer Beruecksichtung der geaenderten Untersuchungsparameter bei gleichzeitig hohem Anspruch an den Strahlenschutz. Hochaufloesende Schallkoepfe, Multislice-CT und schnelle MR-Sequenzen erlauben eine bessere Anpassung der Untersuchungsmethoden an die Beduerfnisse in der Kinderradiologie. Ziel dieses Artikels ist eine Uebersicht ueber die verschiedenen radiologischen Untersuchungstechniken sowie deren Anpassung an kindliche Anforderungen und die Angabe von Untersuchungsalgorithmen der haeufigsten paediatrischen Notfaelle. In der Projektionsradiographie erlaubt die Optimierung der Aufnahmetechnik (digitale Radiographie, unterschiedliche Klassen von Film-Folien-Systemen, Belichtungsparameter) eine deutliche Reduktion der Strahlendosis bei diagnostisch ausreichender Qualitaet. Spiral- oder

  19. Investigation of soil potentially contaminated by monazite processing by-products: case study and suggestion for protocol

    International Nuclear Information System (INIS)

    Briquet, Claudia

    2006-01-01

    This work describes a characterization of soil potentially contaminated by monazite chemical processing residues. For case study it was selected a country area of Sao Paulo State, containing a monazite processing by-product depository. The main objective was to evaluate the soil contamination in an area of approximately 18,000 m 2 and esteem the total effective dose equivalent. During the development of this work, it was verified necessity of an investigation protocol, in order to standardize actions of regulatory authorities. A survey of the applicable legislation was carried out, as a tool to support decision making process. The methodology was based on the 'Manual de Gerenciamento de Areas Contaminadas' of CETESB (2001 a), a national document to guide studies of contaminated areas. It was also considered the 'Multi Agency Radiation Survey and Site Manual Investigation - MARSSIM' (2000), a U.S. government document that provides a nationally consensus approach to conduct investigations at potentially contaminated sites. The developed activities had been divided in three general stages: data-collecting and information on the place, identification of soil contamination and its distribution until the depth of 3 meters and evaluation of the associated dose. The evaluation of the radiological impact was carried out considering the worst-case use scenario (most restrictive future use), standing out that the final decision fits to the Brazilian National Nuclear Energy Commission - CNEN. CNEN's scope of responsibility includes determining the site release criteria and the cleanup necessity. (author)

  20. Investigations on the visco-elastic behaviour of a human healthy heel pad: in vivo compression tests and numerical analysis

    DEFF Research Database (Denmark)

    Matteoli, Sara; Fontanella, Chiara G.; Carniel, Emanuele L.

    2013-01-01

    The aim of this study was to investigate the viscoelastic behaviour of the human heel pad by comparing the stress–relaxation curves obtained from a compression device used on an in vivo heel pad with those obtained from a threedimensional computer-based subject-specific heel pad model subjected...... numerical analyses were performed to interpret the mechanical response of heel tissues, with loading conditions and displacement rate in agreement with experimental tests. The heel tissues showed a non-linear, viscoelastic behaviour described by characteristic hysteretic curves, stress......–relaxation and viscous recovery phenomena. The reliability of the investigations was validated by the interpretation of the mechanical response of heel tissues under the application of three pistons with diameter of 15, 20 and 40 mm, at the same displacement rate of about 1.7 mm/s. The maximum and minimum relative...

  1. Contribution to the investigation of the p53 in vivo and in vitro trans-activation activity

    International Nuclear Information System (INIS)

    Meiller, A.

    2004-03-01

    Among the body's defence mechanisms, the programmed cellular death or apoptosis is an important safeguard way which allows the body to get rid of the injured cells before they acquire steady genetic modifications leading to an anarchistic multiplication. As p53 tumor suppressor gene plays a predominant role within this process, this research report first presents the p53 protein, its structure, its activities as a transcription factor, its modifications and the implications on its functional activities, its biological activities, and describes the p53 intracellular rate regulation and the use of this protein in radiology, particularly in 'in vivo' investigations on irradiated mice. It also presents the p53 family. Then, the author reports experimental investigations on possible other genes which could be trans-activated by p53. A gene is identified as a new target gene. She also demonstrates a new p53 activation path induced by another member of the p53 family, the p73 alpha protein

  2. Investigating the correlation between in vivo absorption and in vitro release of fenofibrate from lipid matrix particles in biorelevant medium.

    Science.gov (United States)

    Borkar, Nrupa; Xia, Dengning; Holm, René; Gan, Yong; Müllertz, Anette; Yang, Mingshi; Mu, Huiling

    2014-01-23

    Lipid matrix particles (LMP) may be used as better carriers for poorly water-soluble drugs than liquid lipid carriers because of reduced drug mobilization in the formulations. However, the digestion process of solid lipid particles and their effect on the absorption of poorly water-soluble drugs are not fully understood. This study aimed at investigating the effect of particle size of LMP on drug release in vitro as well as absorption in vivo in order to get a better understanding on the effect of degradation of lipid particles on drug solubilisation and absorption. Fenofibrate, a model poorly water-soluble drug, was incorporated into LMP in this study using probe ultrasound sonication. The resultant LMP were characterised in terms of particle size, size distribution, zeta potential, entrapment efficiency, in vitro lipolysis and in vivo absorption in rat model. LMP of three different particle sizes i.e. approximately 100 nm, 400 nm, and 10 μm (microparticles) were produced with high entrapment efficiencies. The in vitro lipolysis study showed that the recovery of fenofibrate in the aqueous phase for 100 nm and 400 nm LMP was significantly higher (pmicroparticles>control. In summary, the present study demonstrated the particle size dependence of bioavailability of fenofibrate loaded LMP in rat model which correlates well with the in vitro drug release performed in the biorelevant medium. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Fat emulsions based on structured lipids (1,3-specific triglycerides): an investigation of the in vivo fate.

    Science.gov (United States)

    Hedeman, H; Brøndsted, H; Müllertz, A; Frokjaer, S

    1996-05-01

    Structured lipids (1,3-specific triglycerides) are new chemical entities made by enzymatic transesterification of the fatty acids in the 1,3 positions of the triglyceride. The purpose of this study is to characterize structured lipids with either short chain fatty acids or medium chain fatty acids in the 1,3 positions with regard to their hydrophobicity, and investigate the in vivo fate in order to evaluate the potential of structured lipids as core material in fat emulsions used as parenteral drug delivery system. The lipids were characterized by employing reversed phase high performance liquid chromatography. The biodistribution of radioactively labeled emulsions was studied in rats. By employing high performance liquid chromatography a rank order of the hydrophobicities of the lipids could be given, with the triglycerides containing long chain fatty acids being the most hydrophobic and the structured lipid with short chain fatty acids in the 1,3 positions the least. When formulated as fat emulsions, the emulsion based on structured lipids with short fatty acids in the 1,3 positions was removed slower from the general blood circulation compared to emulsions based on lipids with long chain fatty acids in the 1,3 positions. The type of core material influences the in vivo circulation time of fat emulsions.

  4. SIC, an intracerebral radiosensitive probe for in vivo neuropharmacology investigations in small laboratory animals: theoretical considerations and practical characteristics

    Science.gov (United States)

    Pain, F.; Laniece, P.; Mastrippolito, R.; Charon, Y.; Comar, D.; Leviel, V.; Pujol, J. F.; Valentin, L.

    2000-02-01

    Although high-resolution tomographs provide a new approach that strongly simplifies the measurement of in vivo tracer biodistribution and kinetics in small animals, they suffer from an important drawback: the need for animal anesthesia or immobilization, which restricts the neurophysiological investigations. Furthermore, quantitative in vivo experiments realized on the brain sometimes only require a simple measurement of the radioactivity achieved on a few local points and do not necessarily imply the use of a tomograph, which is a detector of high cost. These constraints led the authors to develop an interacerebral /spl beta/ sensitive probe, sonde intracerebrate (SIC) (French acronym of intracerebral probe) that will allow chronic measurements of the neurophysiological activity in awake and unrestrained small animals. The volume to which the probe is sensitive and the noise contributions to the relevant signal have been evaluated through Monte Carlo simulations. Characterizations of a first prototype based on a small piece of scintillating fiber (500-/spl mu/m diameter and 1-mm length) fused to a same diameter optical fiber coupled in turn to a photomultiplier are also presented. A first configuration of the detector is finally proposed.

  5. Tracheal anastomosis with the diode laser and fibrin tissue adhesive: an in vitro and in vivo investigation.

    Science.gov (United States)

    Gleich, L L; Wang, Z; Pankratov, M M; Aretz, H T; Shapshay, S M

    1995-05-01

    Absorbable sutures have been advocated for tracheal anastomosis to reduce fibrosis and foreign body reaction leading to recurrent stenosis. Fibrin tissue adhesive (FTA) and diode laser welding with indocyanine green-dyed fibrinogen were evaluated in tracheal anastomosis to reduce the number of sutures and to improve healing. In vitro studies demonstrated strong anastomoses with a combination of laser welding and FTA with minimal tissue damage. In a controlled in vivo study, circumferential resections of canine tracheas were repaired with laser welding and FTA augmented with a few stay sutures. These anastomoses had less fibrosis and tissue damage than anastomoses in control animals repaired with sutures alone. This study supports investigation of laser welding and FTA in human beings for tracheal anastomosis and other procedures in which suturing may be difficult.

  6. Investigation on the in vivo σ peceptor locating roperty of 125I-4-(N-benzylpiperidin)-4-iodo-phenylsulfonamide

    International Nuclear Information System (INIS)

    Zhang Chunli; Wang Rongfu; Fu Zhanli; Liu Qiaoping; Liu Boli

    2004-01-01

    Tributylstannane precursor of the ligand is synthesized, characterized and labeled with 125 I by oxidative radioiododestannylation methods. To investigate the a receptor affinity and the suitability for tumor guiding diagnosis and guiding therapy of 125 I-4-(N-benzylpiperidin)-4-iodo- phenylsulfonamide in vivo, 443 kBq/(0.2 μg) of the labeled ligand is injected into mice bearing H22, S180 and EAC tumor, respectively, and their biodistribution is measured. The results show that high uptake is obtained in liver, spleen, heart, lung, kidney, small intestine in which σ receptors are present as well as in H22 and EAC tumor. In the blocking study using haloperidol, coinjection with haloperidol reduced the uptake in heart, lung and spleen but no inhibition is showed in tumor. The higher T/NT values of tumor to brain and muscle are obtained, 6.98 at 2 hours postinjection of tumor to muscle is the highest. (authors)

  7. Pharmacokinetics of linezolid in bone tissue investigated by in vivo microdialysis

    DEFF Research Database (Denmark)

    Stolle, L.B.; Plock, N.; Joukhadar, C.

    2008-01-01

    Pharmacokinetics of unbound anti-infectives in bone is difficult to characterize. The aim of this study was to assess the feasibility of the microdialysis technique to cancellous bone for single dose pharmacokinetic investigations of the anti-infective linezolid. Serial bone biopsies (left tibia......) and microdialysate samples (right tibia: 2 catheters) as well as plasma and bone marrow samples were obtained from 10 pigs. The concentrations of linezolid reached bacteriostatic levels in plasma, bone marrow, bone biopsies and microdialysates. With the use of microdialysis we here present the first results...... for unbound linezolid bone penetration. Unbound linezolid concentrations in bone obtained by microdialysis were lower than might have been expected from previous bone biopsy studies. To achieve effective concentrations (24 h) for susceptible organisms the chosen dose of linezolid might not be sufficient...

  8. Phytochemical and in vitro and in vivo biological investigation on the antihypertensive activity of mango leaves (Mangifera indica L.).

    Science.gov (United States)

    Ronchi, Silas Nascimento; Brasil, Girlandia Alexandre; do Nascimento, Andrews Marques; de Lima, Ewelyne Miranda; Scherer, Rodrigo; Costa, Helber B; Romão, Wanderson; Boëchat, Giovanna Assis Pereira; Lenz, Dominik; Fronza, Marcio; Bissoli, Nazaré Souza; Endringer, Denise Coutinho; de Andrade, Tadeu Uggere

    2015-10-01

    The aim of this study was to investigate the antihypertensive effect of leaves Mangifera indica L. using in vitro and in vivo assays. The ethanol extract of leaves of M. indica was fractionated to dichloromethanic, n-butyl alcohol and aqueous fractions. The chemical composition of ethanolic extract and dichloromethanic fraction were evaluated by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Antioxidant activity was evaluated in the DPPH scavenging activity assay. Angiotensin-converting enzyme (ACE) inhibitory activity was investigated using in vitro and in vivo assays. The chronic antihypertensive assay was performed in spontaneously hypertensive rats (SHRs) and Wistar rats treated with enalapril (10 mg/kg), dichloromethanic fraction (100 mg/kg; twice a day) or vehicle control for 30 days. The baroreflex sensitivity was evaluated through the use of sodium nitroprusside and phenylephrine. Cardiac hypertrophy was evaluated by morphometric analysis. The dichloromethanic fraction exhibited the highest flavonoid, total phenolic content and high antioxidant activity. Dichloromethanic fraction elicited ACE inhibitory activity in vitro (99 ± 8%) similar to captopril. LC-MS/MS analysis revealed the presence of ferulic acid (48.3 ± 0.04 µg/g) caffeic acid (159.8 ± 0.02 µg/g), gallic acid (142.5 ± 0.03 µg/g), apigenin (11.0 ± 0.01 µg/g) and quercetin (203.3 ± 0.05 µg/g). The chronic antihypertensive effects elicited by dichloromethanic fraction were similar to those of enalapril, and the baroreflex sensitivity was normalized in SHR. Plasma ACE activity and cardiac hypertrophy were comparable with animals treated with enalapril. Dichloromethanic fraction of M. indica presented an antihypertensive effect, most likely by ACE inhibition, with benefits in baroreflex sensitivity and cardiac hypertrophy. Altogether, the results of the present study suggest that the dichloromethanic fraction of M. indica leaves may have potential as a promoting

  9. An Experimental and Finite Element Protocol to Investigate the Transport of Neutral and Charged Solutes across Articular Cartilage.

    Science.gov (United States)

    Arbabi, Vahid; Pouran, Behdad; Zadpoor, Amir A; Weinans, Harrie

    2017-04-23

    Osteoarthritis (OA) is a debilitating disease that is associated with degeneration of articular cartilage and subchondral bone. Degeneration of articular cartilage impairs its load-bearing function substantially as it experiences tremendous chemical degradation, i.e. proteoglycan loss and collagen fibril disruption. One promising way to investigate chemical damage mechanisms during OA is to expose the cartilage specimens to an external solute and monitor the diffusion of the molecules. The degree of cartilage damage (i.e. concentration and configuration of essential macromolecules) is associated with collisional energy loss of external solutes while moving across articular cartilage creates different diffusion characteristics compared to healthy cartilage. In this study, we introduce a protocol, which consists of several steps and is based on previously developed experimental micro-Computed Tomography (micro-CT) and finite element modeling. The transport of charged and uncharged iodinated molecules is first recorded using micro-CT, which is followed by applying biphasic-solute and multiphasic finite element models to obtain diffusion coefficients and fixed charge densities across cartilage zones.

  10. In vitro and in vivo investigations into the biocompatibility of diamond-like carbon (DLC) coatings for orthopedic applications.

    Science.gov (United States)

    Allen, M; Myer, B; Rushton, N

    2001-05-01

    Diamond-like carbon (DLC) shows great promise as a durable, wear- and corrosion-resistant coating for biomedical implants. The effects of DLC coatings on the musculoskeletal system have not been investigated in detail. In this study, DLC coatings were deposited on polystyrene 24-well tissue culture plates by fast-atom bombardment from a hexane precursor. Two osteoblast-like cell lines were cultured on uncoated and DLC-coated plates for periods of up to 72 h. The effects of DLC coatings on cellular metabolism were investigated by measuring the production of three osteoblast-specific marker proteins: alkaline phosphatase, osteocalcin, and type I collagen. There was no evidence that the presence of the DLC coating had any adverse effect on any of the parameters measured in this study. In a second series of experiments, DLC-coated cobalt-chromium cylinders were implanted in intramuscular locations in rats and in transcortical sites in sheep. Histologic analysis of specimens retrieved 90 days after surgery showed that the DLC-coated specimens were well tolerated in both sites. These data indicate that DLC coatings are biocompatible in vitro and in vivo, and further investigations into their long-term biological and tribological performance are now warranted. Copyright 2001 John Wiley & Sons, Inc.

  11. 44Sc for labeling of DOTA- and NODAGA-functionalized peptides: preclinical in vitro and in vivo investigations.

    Science.gov (United States)

    Domnanich, Katharina A; Müller, Cristina; Farkas, Renata; Schmid, Raffaella M; Ponsard, Bernard; Schibli, Roger; Türler, Andreas; van der Meulen, Nicholas P

    2017-01-01

    Recently, 44 Sc (T 1/2  = 3.97 h, Eβ + av  = 632 keV, I = 94.3 %) has emerged as an attractive radiometal candidate for PET imaging using DOTA-functionalized biomolecules. The aim of this study was to investigate the potential of using NODAGA for the coordination of 44 Sc. Two pairs of DOTA/NODAGA-derivatized peptides were investigated in vitro and in vivo and the results obtained with 44 Sc compared with its 68 Ga-labeled counterparts.DOTA-RGD and NODAGA-RGD, as well as DOTA-NOC and NODAGA-NOC, were labeled with 44 Sc and 68 Ga, respectively. The radiopeptides were investigated with regard to their stability in buffer solution and under metal challenge conditions using Fe 3+ and Cu 2+ . Time-dependent biodistribution studies and PET/CT imaging were performed in U87MG and AR42J tumor-bearing mice. Both RGD- and NOC-based peptides with a DOTA chelator were readily labeled with 44 Sc and 68 Ga, respectively, and remained stable over at least 4 half-lives of the corresponding radionuclide. In contrast, the labeling of NODAGA-functionalized peptides with 44 Sc was more challenging and the resulting radiopeptides were clearly less stable than the DOTA-derivatized matches. 44 Sc-NODAGA peptides were clearly more susceptible to metal challenge than 44 Sc-DOTA peptides under the same conditions. Instability of 68 Ga-labeled peptides was only observed if they were coordinated with a DOTA in the presence of excess Cu 2+ . Biodistribution data of the 44 Sc-labeled peptides were largely comparable with the data obtained with the 68 Ga-labeled counterparts. It was only in the liver tissue that the uptake of 68 Ga-labeled DOTA compounds was markedly higher than for the 44 Sc-labeled version and this was also visible on PET/CT images. The 44 Sc-labeled NODAGA-peptides showed a similar tissue distribution to those of the DOTA peptides without any obvious signs of in vivo instability. Although DOTA revealed to be the preferred chelator for stable coordination of 44

  12. Enhanced oral bioavailability of fenofibrate using polymeric nanoparticulated systems: physicochemical characterization and in vivo investigation

    Directory of Open Access Journals (Sweden)

    Yousaf AM

    2015-03-01

    Full Text Available Abid Mehmood Yousaf,1 Dong Wuk Kim,1 Yu-Kyoung Oh,2 Chul Soon Yong,3 Jong Oh Kim,3 Han-Gon Choi11College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, 2College of Pharmacy, Seoul National University, Seoul, 3College of Pharmacy, Yeungnam University, Gyongsan, South KoreaBackground: The intention of this research was to prepare and compare various solubility-enhancing nanoparticulated systems in order to select a nanoparticulated formulation with the most improved oral bioavailability of poorly water-soluble fenofibrate.Methods: The most appropriate excipients for different nanoparticulated preparations were selected by determining the drug solubility in 1% (w/v aqueous solutions of each carrier. The polyvinylpyrrolidone (PVP nanospheres, hydroxypropyl-β-cyclodextrin (HP-β-CD nanocorpuscles, and gelatin nanocapsules were formulated as fenofibrate/PVP/sodium lauryl sulfate (SLS, fenofibrate/HP-β-CD, and fenofibrate/gelatin at the optimized weight ratios of 2.5:4.5:1, 1:4, and 1:8, respectively. The three solid-state products were achieved using the solvent-evaporation method through the spray-drying technique. The physicochemical characterization of these nanoparticles was accomplished by powder X-ray diffraction, differential scanning calorimetry, scanning electron microscopy, and Fourier-transform infrared spectroscopy. Their physicochemical properties, aqueous solubility, dissolution rate, and pharmacokinetics in rats were investigated in comparison with the drug powder.Results: Among the tested carriers, PVP, HP-β-CD, gelatin, and SLS showed better solubility and were selected as the most appropriate constituents for various nanoparticulated systems. All of the formulations significantly improved the aqueous solubility, dissolution rate, and oral bioavailability of fenofibrate compared to the drug powder. The drug was present in the amorphous form in HP-β-CD nanocorpuscles; however, in

  13. A new bi-layered scaffold for osteochondral tissue regeneration: In vitro and in vivo preclinical investigations

    Energy Technology Data Exchange (ETDEWEB)

    Sartori, M. [Laboratory of Biocompatibility, Technological Innovations and Advanced Therapies, Rizzoli Orthopedic Institute, Bologna (Italy); Pagani, S., E-mail: stefania.pagani@ior.it [Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute, Bologna (Italy); Ferrari, A. [Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute, Bologna (Italy); Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna (Italy); Costa, V.; Carina, V. [Innovative Technology Platform for Tissue Engineering, Theranostic and Oncology, Rizzoli Orthopedic Institute, Palermo (Italy); Figallo, E. [Fin-Ceramica Faenza SpA, Faenza, Ravenna (Italy); Maltarello, M.C. [Laboratory of Musculoskeletal Cell Biology, Rizzoli Orthopedic Institute, Bologna (Italy); Martini, L.; Fini, M. [Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute, Bologna (Italy); Giavaresi, G. [Innovative Technology Platform for Tissue Engineering, Theranostic and Oncology, Rizzoli Orthopedic Institute, Palermo (Italy)

    2017-01-01

    Current treatments for acute or degenerative chondral and osteochondral lesions are in need of improvement, as these types of injuries lead to disability and worsen the quality of life in a high percentage of patients. The aim of this study was to develop a new bi-layered scaffold for osteochondral tissue regeneration through a “biomimetic” and “bioinspired” approach. For chondral regeneration, the scaffold was realized with an organic compound (type I collagen), while for the regeneration of the subchondral layer, bioactive magnesium-doped hydroxyapatite (Mg/HA) crystals were co-precipitated with the organic component of the scaffold. The entire scaffold structure was stabilized with a cross-linking agent, highly reactive bis-epoxyde (1,4-butanediol diglycidyl ether – BDDGE 1 wt%). The developed scaffold was then characterized for its physico-chemical characteristics. Its structure and adhesion strength between the integrated layers were investigated. At the same time, in vitro cell culture studies were carried out to examine the ability of chondral and bone scaffold layers to separately support adhesion, proliferation and differentiation of human mesenchymal stem cells (hMSCs) into chondrocytes and osteoblasts, respectively. Moreover, an in vivo study with nude mice, transplanted with osteochondral scaffolds plain or engineered with undifferentiated hMSCs, was also set up with 4 and 8-week time points. The results showed that chondral and bone scaffold layers represented biocompatible scaffolds able to sustain hMSCs attachment and proliferation. Moreover, the association of scaffold stimuli and differentiation medium, induced hMSCs chondrogenic and osteogenic differentiation and deposition of extracellular matrix (ECM). The ectopic implantation of the engineered osteochondral scaffolds indicated that hMSCs were able to colonize the osteochondral scaffold in depth. The scaffold appeared permissive to tissue growth and penetration, ensuring the diffusion

  14. Redundant systematic reviews on the same topic in surgery: a study protocol for a meta-epidemiological investigation.

    Science.gov (United States)

    Katsura, Morihiro; Kuriyama, Akira; Tada, Masafumi; Yamamoto, Kazumichi; Furukawa, Toshi A

    2017-08-21

    We are witnessing an explosive increase in redundant and overlapping publications of systematic reviews and meta-analyses (SRs/MAs) on the same topic, which often present conflicting results and interpretations, in the current medical literature. They represent wasted efforts on the part of investigators and peer reviewers and may confuse and possibly mislead clinicians and policymakers. Here, we present a protocol for a meta-epidemiological investigation to describe how often there are overlapping SRs/MAs on the same topic, to assess the quality of these multiple publications, and to investigate the causes of discrepant results between multiple SRs/MAs in the field of major surgery. We will use MEDLINE/PubMed to identify all SRs/MAs of randomised controlled trials (RCTs) published in 2015 regarding major surgical interventions. After identifying the 'benchmark' SRs/MAs published in 2015, a process of screening in MEDLINE will be carried out to identify the previous SRs/MAs of RCTs on the same topic that were published within 5 years of the 'benchmark' SRs/MAs. We will tabulate the number of previous SRs/MAs on the same topic of RCTs, and then describe their variations in numbers of RCTs included, sample sizes, effect size estimates and other characteristics. We will also assess the differences in quality of each SR/MA using A Measurement Tool to Assess Systematic Reviews (AMSTAR) score. Finally, we will investigate the potential reasons to explain the discrepant results between multiple SRs/MAs. No formal ethical approval and informed consent are required because this study will not collect primary individual data. The intended audiences of the findings include clinicians, healthcare researchers and policymakers. We will publish our findings as a scientific report in a peer-reviewed journal. In PROSPERO CRD42017059077, March 2017. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial

  15. Investigation of in vivo potential of scorpion venom against skin tumorigenesis in mice via targeting markers associated with cancer development

    Directory of Open Access Journals (Sweden)

    Al Asmari AK

    2016-10-01

    Full Text Available Abdulrahman K Al Asmari, Abdul Quaiyoom Khan Research Centre, Prince Sultan Military Medical City, Riyadh, Saudi Arabia Abstract: Cancer is the leading cause of morbidity and mortality all over the world in spite of the advances made in its management. In this study, we investigated the in vivo antitumorigenic potential of the venom obtained from a medically important scorpion species Leiurus quinquestriatus on chemically induced skin cancer in mice. Animals were divided into five groups, with 13 animals in each group. All the treatments were given topically on the shaved dorsal surface of the skin. Animals in Group 1 received vehicle only (0.2 mL acetone. Moreover, 7,12-dimethylbenz[a]anthracene (DMBA, 400 nmol per mouse was applied to all the animals in the remaining four groups. After 1 week, different concentrations of venom (17.5 µg, 35 µg, and 52.5 µg per animal were applied to each animal in the Groups III–V. Thirty minutes after the application of venom, croton oil was applied on the same position where venom was administered to the animals of Groups III–V. Animals in Group II were treated as the positive control (without venom and received croton oil as in Groups III–V. The findings of this study revealed that venom extract of L. quinquestriatus inhibits DMBA + croton oil-induced mouse skin tumor incidence and tumor multiplicity. Venom treatment also decreased the expression of proinflammatory cytokines. Immunohistochemistry results showed a downregulation of the expression of molecular markers such as Ki-67, nuclear factor kappa-B, cyclooxygenase-2, B-cell lymphoma-2, and vascular endothelial growth factor, in venom-treated animals. Our findings suggest that the venom of L. quinquestriatus possesses in vivo anticancer potential and may be used in the development of anticancer molecules. Keywords: Leiurus quinquestriatus, skin cancer, apoptosis, immunosuppression

  16. Ho:YAG laser in reshaping tracheal cartilage: a pilot investigation using ex vivo porcine and rabbit cartilage

    Science.gov (United States)

    Lam, Anthony; Protsenko, Dmitry E.; Carbone, Nicholas; Li, Chao; Jackson, Ryan; Wong, Brian J.

    2004-07-01

    Stenotic, collapsed, and flow-restricted tracheal airways may result from blunt trauma, chronic infection, and the prolonged endotracheal intubation. This pilot investigation characterizes the degree of shape change produced by Ho:YAG laser (λ=2.12 μm) irradiation of rabbit and pig trachea tissue as a function of laser dosimetry and application protocol. Force displacement curves were generated using fresh lagomorph and porcine tracheal cartilage rings secured in a modified single beam cantilever geometry. These specimens were then irradiated for varying amounts of time and power with the objective of straightening these curved specimens. The degree of shape change was documented photographically. Force and surface temperature were monitored. Confocal microscopy was then used in combination a vital staine ("live-dead assay") to determine the level of viability of straightened cartilage for selected exposure time-power pairs. Laser Cartilage Reshaping of the trachea may provide a new method to treat severe tracheal injuries without the need for classic open surgical techniques. This pilot investigation is the first step toward demonstrating the feasibility of this technique. Long-term, the design of stents combined with laser irradiation may provide a means to alter tracheal shape.

  17. In vitro and in vivo investigations on bone regeneration potential of laminated hydroxyapatite/gelatin nanocomposite scaffold along with DBM

    Energy Technology Data Exchange (ETDEWEB)

    Tavakol, Shima [School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Department of Medical Nanotechnology (Iran, Islamic Republic of); Ragerdi Kashani, Iraj [School of Medicine, Tehran University of Medical Sciences, Department of Anatomy (Iran, Islamic Republic of); Azami, Mahmood [School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Department of Tissue Engineering (Iran, Islamic Republic of); Khoshzaban, Ahad [Tehran University of Medical Sciences, Iranian Tissue Bank Research and Preparation Center (Iran, Islamic Republic of); Tavakol, Behnaz [Kashan University of Medical Sciences, Department of Medicine (Iran, Islamic Republic of); Kharrazi, Sharmin [School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Department of Medical Nanotechnology (Iran, Islamic Republic of); Ebrahimi, Somayeh [University of Tarbiat Moallem, Department of Biology, Faculty of Sciences (Iran, Islamic Republic of); Rezayat Sorkhabadi, Seyed Mahdi, E-mail: sh_tavakol@razi.tums.ac.ir [School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Department of Medical Nanotechnology (Iran, Islamic Republic of)

    2012-12-15

    Bone regeneration ability of a scaffold strongly depends on its structure and the size of its components. In this study, a nanostructured scaffold was designed for bone repair using nano hydroxyapatite (nHA) (8-16 nm Multiplication-Sign 50-80 nm) and gelatin (GEL) as main components. In vitro investigations of calcium matrix deposition and gene expression of the seeded cells for this scaffold, demineralized bone matrix (DBM), scaffold plus DBM, and the control group were carried out. Bone regeneration in rat calvarium with critical defect size after 1, 4, and 8 weeks post implantation was investigated. The calcium matrix depositions by the osteoblast and RUNX2, ALP, osteonectin, and osteocalcin gene expression in scaffold were more significant than in other groups. Histomorphometry analysis confirmed in vitro results. In vitro and in vivo bone regeneration were least in scaffold plus DBM group. Enhanced effects in scaffold could be attributed to the shape and size of nHA particles and good architecture of the scaffold. Reduction of bone regeneration might be due to tight bonding of BMPs and nHA particles in the third group. Results obtained from this study confirmed that nano-scale size of the main components and the scaffold architecture (pore diameter, interconnectivity pores, etc.) have significant effects on bone regeneration ability of the scaffold and are important parameters in designing a temporary bone substitute.

  18. In vitro and in vivo investigations on bone regeneration potential of laminated hydroxyapatite/gelatin nanocomposite scaffold along with DBM

    International Nuclear Information System (INIS)

    Tavakol, Shima; Ragerdi Kashani, Iraj; Azami, Mahmood; Khoshzaban, Ahad; Tavakol, Behnaz; Kharrazi, Sharmin; Ebrahimi, Somayeh; Rezayat Sorkhabadi, Seyed Mahdi

    2012-01-01

    Bone regeneration ability of a scaffold strongly depends on its structure and the size of its components. In this study, a nanostructured scaffold was designed for bone repair using nano hydroxyapatite (nHA) (8–16 nm × 50–80 nm) and gelatin (GEL) as main components. In vitro investigations of calcium matrix deposition and gene expression of the seeded cells for this scaffold, demineralized bone matrix (DBM), scaffold plus DBM, and the control group were carried out. Bone regeneration in rat calvarium with critical defect size after 1, 4, and 8 weeks post implantation was investigated. The calcium matrix depositions by the osteoblast and RUNX2, ALP, osteonectin, and osteocalcin gene expression in scaffold were more significant than in other groups. Histomorphometry analysis confirmed in vitro results. In vitro and in vivo bone regeneration were least in scaffold plus DBM group. Enhanced effects in scaffold could be attributed to the shape and size of nHA particles and good architecture of the scaffold. Reduction of bone regeneration might be due to tight bonding of BMPs and nHA particles in the third group. Results obtained from this study confirmed that nano-scale size of the main components and the scaffold architecture (pore diameter, interconnectivity pores, etc.) have significant effects on bone regeneration ability of the scaffold and are important parameters in designing a temporary bone substitute.

  19. Estimation of radiation dose to patients from 18 FDG whole body PET/CT investigations using dynamic PET scan protocol

    Directory of Open Access Journals (Sweden)

    Aruna Kaushik

    2015-01-01

    Full Text Available Background & objectives: There is a growing concern over the radiation exposure of patients from undergoing 18FDG PET/CT (18F-fluorodeoxyglucose positron emission tomography/computed tomography whole body investigations. The aim of the present study was to study the kinetics of 18FDG distributions and estimate the radiation dose received by patients undergoing 18FDG whole body PET/CT investigations. Methods: Dynamic PET scans in different regions of the body were performed in 49 patients so as to measure percentage uptake of 18FDG in brain, liver, spleen, adrenals, kidneys and stomach. The residence time in these organs was calculated and radiation dose was estimated using OLINDA software. The radiation dose from the CT component was computed using the software CT-Expo and measured using computed tomography dose index (CTDI phantom and ionization chamber. As per the clinical protocol, the patients were refrained from eating and drinking for a minimum period of 4 h prior to the study. Results: The estimated residence time in males was 0.196 h (brain, 0.09 h (liver, 0.007 h (spleen, 0.0006 h (adrenals, 0.013 h (kidneys and 0.005 h (stomach whereas it was 0.189 h (brain, 0.11 h (liver, 0.01 h (spleen, 0.0007 h (adrenals, 0.02 h (kidneys and 0.004 h (stomach in females. The effective dose was found to be 0.020 mSv/MBq in males and 0.025 mSv/MBq in females from internally administered 18FDG and 6.8 mSv in males and 7.9 mSv in females from the CT component. For an administered activity of 370 MBq of 18FDG, the effective dose from PET/CT investigations was estimated to be 14.2 mSv in males and 17.2 mSv in females. Interpretation & conclusions: The present results did not demonstrate significant difference in the kinetics of 18FDG distribution in male and female patients. The estimated PET/CT doses were found to be higher than many other conventional diagnostic radiology examinations suggesting that all efforts should be made to clinically justify and

  20. Estimation of radiation dose to patients from (18) FDG whole body PET/CT investigations using dynamic PET scan protocol.

    Science.gov (United States)

    Kaushik, Aruna; Jaimini, Abhinav; Tripathi, Madhavi; D'Souza, Maria; Sharma, Rajnish; Mondal, Anupam; Mishra, Anil K; Dwarakanath, Bilikere S

    2015-12-01

    There is a growing concern over the radiation exposure of patients from undergoing 18FDG PET/CT (18F-fluorodeoxyglucose positron emission tomography/computed tomography) whole body investigations. The aim of the present study was to study the kinetics of 18FDG distributions and estimate the radiation dose received by patients undergoing 18FDG whole body PET/CT investigations. Dynamic PET scans in different regions of the body were performed in 49 patients so as to measure percentage uptake of 18FDG in brain, liver, spleen, adrenals, kidneys and stomach. The residence time in these organs was calculated and radiation dose was estimated using OLINDA software. The radiation dose from the CT component was computed using the software CT-Expo and measured using computed tomography dose index (CTDI) phantom and ionization chamber. As per the clinical protocol, the patients were refrained from eating and drinking for a minimum period of 4 h prior to the study. The estimated residence time in males was 0.196 h (brain), 0.09 h (liver), 0.007 h (spleen), 0.0006 h (adrenals), 0.013 h (kidneys) and 0.005 h (stomach) whereas it was 0.189 h (brain), 0.11 h (liver), 0.01 h (spleen), 0.0007 h (adrenals), 0.02 h (kidneys) and 0.004 h (stomach) in females. The effective dose was found to be 0.020 mSv/MBq in males and 0.025 mSv/MBq in females from internally administered 18FDG and 6.8 mSv in males and 7.9 mSv in females from the CT component. For an administered activity of 370 MBq of 18FDG, the effective dose from PET/CT investigations was estimated to be 14.2 mSv in males and 17.2 mSv in females. The present results did not demonstrate significant difference in the kinetics of 18FDG distribution in male and female patients. The estimated PET/CT doses were found to be higher than many other conventional diagnostic radiology examinations suggesting that all efforts should be made to clinically justify and carefully weigh the risk-benefit ratios prior to every 18FDG whole body PET

  1. 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

  2. Monitoring of implanted stem cell migration in vivo: A highly resolved in vivo magnetic resonance imaging investigation of experimental stroke in rat

    Science.gov (United States)

    Hoehn, Mathias; Küstermann, Ekkehard; Blunk, James; Wiedermann, Dirk; Trapp, Thorsten; Wecker, Stefan; Föcking, Melanie; Arnold, Heinz; Hescheler, Jürgen; Fleischmann, Bernd K.; Schwindt, Wolfram; Bührle, Christian

    2002-01-01

    In vivo monitoring of stem cells after grafting is essential for a better understanding of their migrational dynamics and differentiation processes and of their regeneration potential. Migration of endogenous or grafted stem cells and neurons has been described in vertebrate brain, both under normal conditions from the subventricular zone along the rostral migratory stream and under pathophysiological conditions, such as degeneration or focal cerebral ischemia. Those studies, however, relied on invasive analysis of brain sections in combination with appropriate staining techniques. Here, we demonstrate the observation of cell migration under in vivo conditions, allowing the monitoring of the cell dynamics within individual animals, and for a prolonged time. Embryonic stem (ES) cells, constitutively expressing the GFP, were labeled by a lipofection procedure with a MRI contrast agent and implanted into rat brains. Focal cerebral ischemia had been induced 2 weeks before implantation of ES cells into the healthy, contralateral hemisphere. MRI at 78-μm isotropic spatial resolution permitted the observation of the implanted cells with high contrast against the host tissue, and was confirmed by GFP registration. During 3 weeks, cells migrated along the corpus callosum to the ventricular walls, and massively populated the borderzone of the damaged brain tissue on the hemisphere opposite to the implantation sites. Our results indicate that ES cells have high migrational dynamics, targeted to the cerebral lesion area. The imaging approach is ideally suited for the noninvasive observation of cell migration, engraftment, and morphological differentiation at high spatial and temporal resolution. PMID:12444255

  3. Investigation of the in vivo antioxidative activity of Cynara scolymus (artichoke) leaf extract in the streptozotocin-induced diabetic rat.

    Science.gov (United States)

    Magielse, Joanna; Verlaet, Annelies; Breynaert, Annelies; Keenoy, Begoña Manuel Y; Apers, Sandra; Pieters, Luc; Hermans, Nina

    2014-01-01

    The in vivo antioxidant activity of a quantified leaf extract of Cynara scolymus (artichoke) was studied. The aqueous artichoke leaf extract (ALE), containing 1.5% caffeoylquinic acid with chlorogenic acid being most abundant (0.30%), and luteolin-7-O-glucoside as major flavonoid (0.15%), was investigated by evaluating the effect on different oxidative stress biomarkers, after 3 wk oral supplementation in the streptozotocin-induced diabetic rat model. Apart from two test groups (0.2 g ALE/kg BW/day and 1 g ALE/kg BW/day, where BW is body weight), a healthy control group, untreated oxidative stress group, and vitamin E treated group (positive control) were included. A 0.2 g/kg BW/day of ALE decreased oxidative stress: malondialdehyde and 8-hydroxydeoxyguanosine levels significantly diminished, whereas erythrocyte glutathione levels significantly increased. A 1.0 g/kg BW/day ALE did not show higher antioxidant activity. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. PLGA nanoparticles introduction into mitoxantrone-loaded ultrasound-responsive liposomes: In vitro and in vivo investigations.

    Science.gov (United States)

    Xin, Yuxuan; Qi, Qi; Mao, Zhenmin; Zhan, Xiaoping

    2017-08-07

    A novel ultrasound-responsive liposomal system for tumor targeting was prepared in order to increase the antitumor efficacy and decrease serious side effects. In this paper, PLGA nanoparticles were used ultrasound-responsive agents instead of conventional microbubbles. The PLGA-nanoparticles were prepared by an emulsion solvent evaporation method. The liposomes were prepared by a lipid film hydration method. Particle size, zeta potential, encapsulation efficiency and drug loading capacity of the liposomes were studied by light scattering analysis and dialysis. Transmission electron microscopy (TEM) and atomic force microscope (AFM) were used to investigate the morphology of liposomes. The release in vitro was carried out in the pH 7.4 phosphate buffer solutions, as a result, liposome L3 encapsulating PLGA-nanoparticles displayed good stability under simulative physiological conditions and quickly responsive release under the ultrasound. The release in vivo was carried out on the rats, as a result, liposome L3 showed higher bioavailability than traditional intravenous injectable administration, and liposome L3 showed higher elimination ratio after stimulation by ultrasound than L3 without stimulation. Thus, the novel ultrasound-responsive liposome encapsulating PLGA-nanoparticles has a potential to be developed as a new drug delivery system for anti-tumor drug. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Investigation of the effect of hydration on dermal collagen in ex vivo human skin tissue using second harmonic generation microscopy

    Science.gov (United States)

    Samatham, Ravikant; Wang, Nicholas K.; Jacques, Steven L.

    2016-02-01

    Effect of hydration on the dermal collagen structure in human skin was investigated using second harmonic generation microscopy. Dog ears from the Mohs micrographic surgery department were procured for the study. Skin samples with subject aged between 58-90 years old were used in the study. Three dimensional Multiphoton (Two-photon and backward SHG) control data was acquired from the skin samples. After the control measurement, the skin tissue was either soaked in deionized water for 2 hours (Hydration) or kept at room temperature for 2 hours (Desiccation), and SHG data was acquired. The data was normalized for changes in laser power and detector gain. The collagen signal per unit volume from the dermis was calculated. The desiccated skin tissue gave higher backward SHG compared to respective control tissue, while hydration sample gave a lower backward SHG. The collagen signal decreased with increase in hydration of the dermal collagen. Hydration affected the packing of the collagen fibrils causing a change in the backward SHG signal. In this study, the use of multiphoton microscopy to study the effect of hydration on dermal structure was demonstrated in ex vivo tissue.

  6. Hemocyte responses of Dreissena polymorpha following a short-term in vivo exposure to titanium dioxide nanoparticles: Preliminary investigations

    Energy Technology Data Exchange (ETDEWEB)

    Couleau, Nicolas; Techer, Didier [Universite de Lorraine, Laboratoire des Interactions Ecotoxicologie, Biodiversite, Ecosystemes (LIEBE), CNRS UMR 7146, IUT Thionville-Yutz, Espace Cormontaigne, Yutz, F-57970 (France); Pagnout, Christophe [Universite de Lorraine, Laboratoire des Interactions Ecotoxicologie, Biodiversite, Ecosystemes (LIEBE), UMR 7146, Campus Bridoux, rue du General Delestraint, Metz, F-57070 (France); International Consortium for the Environmental Implications of Nanotechnology, iCEINT, http://www.i-ceint.org (France); Jomini, Stephane [Universite de Lorraine, Laboratoire des Interactions Ecotoxicologie, Biodiversite, Ecosystemes (LIEBE), UMR 7146, Campus Bridoux, rue du General Delestraint, Metz, F-57070 (France); Foucaud, Laurent; Laval-Gilly, Philippe; Falla, Jairo [Universite de Lorraine, Laboratoire des Interactions Ecotoxicologie, Biodiversite, Ecosystemes (LIEBE), CNRS UMR 7146, IUT Thionville-Yutz, Espace Cormontaigne, Yutz, F-57970 (France); Bennasroune, Amar, E-mail: amar.bennasroune@univ-metz.fr [Universite de Lorraine, Laboratoire des Interactions Ecotoxicologie, Biodiversite, Ecosystemes (LIEBE), CNRS UMR 7146, IUT Thionville-Yutz, Espace Cormontaigne, Yutz, F-57970 (France)

    2012-11-01

    The widespread use of titanium-based nanoparticles and their environmental release may pose a significant risk to aquatic organisms within freshwater ecosystems. Suspension-feeder invertebrates like bivalve molluscs represent a unique target group for nanoparticle toxicology. The aim of this work was to investigate the short-term responses of Dreissena polymorpha hemocytes after in vivo exposure to titanium dioxide nanoparticles (TiO{sub 2} NP). For this purpose, freshwater mussels were exposed to P25 TiO{sub 2} NP at the concentrations of 0.1, 1, 5 and 25 mg/L during 24 h. Viability, phagocytosis activity and mitogen activated protein kinase (MAPK) phosphorylation level of ERK 1/2 and p38 in hemocytes extracted from exposed mussels were compared to those from control specimens. Results demonstrated an inhibition of the phagocytosis activity after exposure to TiO{sub 2} NP at 0.1 and 1 mg/L. Similar trends, albeit less pronounced, were reported for higher concentrations of NP. Transmission electron microscopy showed for the first time the internalization of TiO{sub 2} NP into Dreissena polymorpha hemocytes. Besides, exposure to NP increased the ERK 1/2 phosphorylation levels in all treatments. Concerning the phosphorylation level of p38, only exposures to 5 and 25 mg/L of NP induced significant p38 activation in comparison to that of the control. Finally, these short-term effects observed at environmentally relevant concentrations highlighted the need for further studies concerning ecotoxicological evaluation of nanoparticle release into an aquatic environment. -- Highlights: Black-Right-Pointing-Pointer Phagocytosis inhibition at TiO{sub 2} NP exposure concentrations of 0.1 and 1 mg/L. Black-Right-Pointing-Pointer Internalization of TiO{sub 2} NP in freshwater mussel hemocytes. Black-Right-Pointing-Pointer Increased phosphorylation level of p38 and ERK 1/2 after in vivo exposure to TiO{sub 2} NP.

  7. Antioxidant activity of omega-3 derivatives and their delivery via nanocages and nanocones: DFT and experimental in vivo investigation.

    Science.gov (United States)

    Najafi, Houshang; Changizi-Ashtiyani, Saeed; Najafi, Meysam

    2017-10-28

    The antioxidant properties of omega-3 were investigated via experimental in vivo and theoretical methods. For experimental evaluation, oxidative stress was induced by 30 min bilateral renal ischemia and 24 h of reperfusion in male Sprague Dawley rats. The oxidative stress was evaluated through measuring malondialdehyde (MDA) and ferric reducing/antioxidant power (FRAP) levels in renal tissue. In theoretical methods, the reaction enthalpies of antioxidant mechanisms of omega-3 were calculated and the effects of NHMe, OMe, OH, Cl, and Me substituents on its antioxidant activity were investigated. Moreover, the omega-3 delivery potential by carbon and boron nitride nanocages and naocones were evaluated. The experimental results showed that omega-3 administration decreases MDA and increases FRAP levels after their changes by ischemia/reperfusion. Theoretical results indicated that NHMe and OMe substituents can significantly improve the antioxidant activity of omega-3. Also, boron nitride nanocone (BNNC) has higher |∆E ad | values, so it has higher potential for omega-3 delivery. Taken together, the new findings presented here indicate that omega-3 has anti-oxidative properties and NHMe and OMe substituents can improve its antioxidant activity. Moreover, adsorption of omega-3 on the surface of the studied nanostructures was exothermic, and BNNC with higher |∆Ead| values has higher potential for omega-3 delivery. Graphical abstract The interaction and adsorption of BNNC with omega-3 is exothermic and experimentally possible from the energetic viewpoint, so the BNNC with higher |∆E ad | and |∆G ad | values has higher potential for omega-3 delivery.

  8. PET imaging with copper-64 as a tool for real-time in vivo investigations of the necessity for crosslinking of polymeric micelles in nanomedicine

    DEFF Research Database (Denmark)

    Jensen, Andreas Tue Ingemann; Binderup, Tina; Ek, Pramod Kumar

    2017-01-01

    crosslinking is necessary for efficient drug delivery. We used PET imaging with 64Cu to demonstrate general methodology for real-time in vivo investigations of micelle stability. Triblock copolymers with 4-methylcoumarin cores of ABC-type (PEG-PHEMA-PCMA) were functionalized in the handle region (PHEMA...... was quantified by ROI analysis on PET images and ex vivo counting. It was observed that CL and nonCL showed limited differences in biodistribution from each other, whereas both differed markedly from control (free 64Cu). This demonstrated that 4-methylcoumarin core micelles may form micelles that are stable...

  9. Assessment of cerebrospinal fluid system dynamics : novel infusion protocol, mathematical modelling and parameter estimation for hydrocephalus investigations

    OpenAIRE

    Andersson, Kennet

    2011-01-01

    Patients with idiopathic normal pressure hydrocephalus (INPH) have a disturbance in the cerebrospinal fluid (CSF) system. The treatment is neurosurgical – a shunt is placed in the CSF system. The infusion test is used to assess CSF system dynamics and to aid in the selection of patients that will benefit from shunt surgery. The infusion test can be divided into three parts: a mathematical model, an infusion protocol and a parameter estimation method. A non-linear differential equation is used...

  10. What the drivers do and do not tell you: using verbal protocol analysis to investigate driver behaviour in emergency situations.

    Science.gov (United States)

    Banks, Victoria A; Stanton, Neville A; Harvey, Catherine

    2014-01-01

    Although task analysis of pedestrian detection can provide us with useful insights into how a driver may behave in emergency situations, the cognitive elements of driver decision-making are less well understood. To assist in the design of future Advanced Driver Assistance Systems, such as Autonomous Emergency Brake systems, it is essential that the cognitive elements of the driving task are better understood. This paper uses verbal protocol analysis in an exploratory fashion to uncover the thought processes underlying behavioural outcomes represented by hard data collected using the Southampton University Driving Simulator.

  11. Persistent Luminescence Nanophosphor Involved Near-Infrared Optical Bioimaging for Investigation of Foodborne Probiotics Biodistribution in Vivo: A Proof-of-Concept Study.

    Science.gov (United States)

    Liu, Yaoyao; Liu, Jing-Min; Zhang, Dongdong; Ge, Kun; Wang, Peihua; Liu, Huilin; Fang, Guozhen; Wang, Shuo

    2017-09-20

    Probiotics has attracted great attention in food nutrition and safety research field, but thus far there are limited analytical techniques for visualized and real-time monitoring of the probiotics when they are ingested in vivo. Herein, the optical bioimaging technique has been introduced for investigation of foodborne probiotics biodistribution in vivo, employing the near-infrared (NIR) emitting persistent luminescence nanophosphors (PLNPs) of Cr 3+ -doped zinc gallogermanate (ZGGO) as the contrast nanoprobes. The ultrabrightness, super long afterglow, polydispersed size, low toxicity, and excellent photostability and biocompatibility of PLNPs were demonstrated to be qualified as a tracer for labeling probiotics via antibody (anti-Gram positive bacteria LTA antibody) recognition as well as contrast agent for long-term bioimaging the probiotics. In vivo optical bioimaging assay showed that the LTA antibody functionalized ZGGO nanoprobes that could be efficiently tagged to the probiobics were successfully applied for real-time monitoring and nondamaged probing of the biodistribution of probiotics inside the living body after oral administration. This work presents a proof-of-concept that exploited the bioimaging methodology for real-time and nondamaged researching the foodborne probiotics behaviors in vivo, which would open up a novel way of food safety detection and nutrition investigation.

  12. PET imaging with copper-64 as a tool for real-time in vivo investigations of the necessity for cross-linking of polymeric micelles in nanomedicine.

    Science.gov (United States)

    Jensen, Andreas I; Binderup, Tina; Ek, Pramod Kumar; Grandjean, Constance E; Rasmussen, Palle H; Kjaer, Andreas; Andresen, Thomas L

    2017-06-30

    Polymeric micelles in nanomedicine are often cross-linked to prevent disintegration in vivo. This typically requires clinically problematic chemicals or laborious procedures. In addition, cross-linking may interfere with advanced release strategies. Despite this, it is often not investigated whether cross-linking is necessary for efficient drug delivery. We used positron emission tomography (PET) imaging with 64 Cu to demonstrate general methodology for real-time in vivo investigations of micelle stability. Triblock copolymers with 4-methylcoumarin cores of ABC-type (PEG-PHEMA-PCMA) were functionalized in the handle region (PHEMA) with CB-TE2A chelators. Polymeric micelles were formed by dialysis and one half was core cross-linked (CL) by UV light and the other half was not (nonCL). Both CL and nonCL were radiolabeled with 64 Cu and compared in vivo in tumor-bearing mice, with free 64 Cu as control. Accumulation in relevant organs was quantified by region of interest analysis on PET images and ex vivo counting. It was observed that CL and nonCL showed limited differences in biodistribution from each other, whereas both differed markedly from control (free 64 Cu). This demonstrated that 4-methylcoumarin core micelles may form micelles that are stable in circulation even without cross-linking. The methodology presented here where individual unimers are radiolabeled is applicable to a wide range of polymeric micelle types. Copyright © 2017 John Wiley & Sons, Ltd.

  13. Comparison of conventional twist drill protocol and piezosurgery for implant insertion: an ex vivo study on different bone types.

    Science.gov (United States)

    Sagheb, Keyvan; Kumar, Vinay V; Azaripour, Adriano; Walter, Christian; Al-Nawas, Bilal; Kämmerer, Peer W

    2017-02-01

    The aim of this ex vivo study was to compare implant insertion procedures using piezosurgery and conventional drilling in different qualities of bone. Implant bed preparation time, generated heat, and primary implant stability were analyzed. Fresh ex vivo porcine bone block samples (cancellous, mixed, and cortical bone) were obtained. The bone quality was quantified by ultrasound transmission velocity (UTV). Each bone sample received three implants of the same diameter using each of the techniques of piezosurgery and conventional twist drills. Time for preparation was taken and the temperature while performing the osteotomy was measured using infrared spectroscopy. The primary implant stability after osteotomy was measured using resonance frequency analysis (RFA) and extrusion torque (ET). ANOVA with post hoc Tukey test was carried out to compare the values for the three different groups. The UTV values strongly correlated with the density of the bone samples. There was a significant increase in time (threefold, P piezosurgery group. Piezosurgery and conventional implant bed drilling procedure do have similar mechanical outcomes regarding primary stability with high RFA values, but the preparation does need more time for piezosurgery group, so that piezosurgery might be a valuable tool in only very specific cases for implant bed preparation. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Quality assessment in in vivo NMR spectroscopy: V. Multicentre evaluation of prototype test objects and protocols for performance assessment in small bore MRS equipment

    DEFF Research Database (Denmark)

    Howe, F.A.; Canese, R; Podo, F

    1995-01-01

    This paper reports the results of multicentre studies aimed at designing, constructing, and evaluating prototype test objects for performance assessment in small-bore MRS systems, by utilizing the test protocols already proposed by the EEC COMAC-BME Concerted Action for clinical MRS equipment...... using ISIS as volume localization sequence in 31P MRS. The results suggested the interest of adopting some of these prototypes for improving the comparison of spectroscopy data obtained from different sites, for providing useful means of quality assurance in experimental MRS, and facilitating....... Three classes of test objects were considered: (1) a multicompartment test object for 31P MRS measurements performed with slice-selective sequences; (2) a two-compartment test object for volume-selection 1H MRS; and (3) two-compartment test objects for assessing the performance of experimental systems...

  15. A Preliminary Investigation of the Long-Term Outcome of the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders

    Science.gov (United States)

    Bullis, Jacqueline R.; Fortune, Meghan R.; Farchione, Todd J.; Barlow, David H.

    2014-01-01

    Objective To conduct a preliminary examination of long-term outcomes on a broad range of affective disorder symptoms treated with a newly developed intervention: The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP). Method Maintenance of treatment gains at long-term follow-up (LTFU) were explored in patients (n = 15, mean age = 32.27; 60% female) who completed a clinical trial of the UP. Results Treatment gains observed at 6-month follow-up (6MFU) on measures of clinical severity, general symptoms of depression and anxiety, and a measure of symptom interference in daily functioning were largely maintained 12 months later (at an average of 18 months posttreatment), and any significant changes from 6MFU to LTFU reflected small increases in symptoms that remained, on average, in the subclinical range. Conclusions These findings provide the first initial support for the durability of broad treatment gains following transdiagnostic treatment. PMID:25113056

  16. The Resin-Embedded Cornea Prepared Via Rapid Processing Protocol : A Good Histomorphometric Target for Clinical Investigation in Ophthalmology and Optometry

    Science.gov (United States)

    Cheah, Pike See; Mohidin, Norhani; Mohd Ali, Bariah; Maung, Myint; Latif, Azian Abdul

    2008-01-01

    This study illustrates and quantifies the changes on corneal tissue between the paraffin-embedded and resin-embedded blocks and thus, selects a better target in investigational ophthalmology and optometry via light microscopy. Corneas of two cynomolgus monkeys (Macaca fascicularis) were used in this study. The formalin-fixed cornea was prepared in paraffin block via the conventional tissue processing protocol (4-day protocol) and stained with haematoxylin and eosin. The glutaraldehyde-fixed cornea was prepared in resin block via the rapid and modified tissue processing procedure (1.2-day protocol) and stained with toluidine blue. The paraffin-embedded sample exhibits various undesired tissue damage and artifact such as thinner epithelium (due to the substantial volumic extraction from the tissue), thicker stroma layer (due to the separation of lamellae and the presence of voids) and the distorted endothelium. In contrast, the resin-embedded corneal tissue has demonstrated satisfactory corneal ultrastructural preservation. The rapid and modified tissue processing method for preparing the resin-embedded is particularly beneficial to accelerate the microscopic evaluation in ophthalmology and optometry. PMID:22570589

  17. The Functional Task Test (FTT): An Interdisciplinary Testing Protocol to Investigate the Factors Underlying Changes in Astronaut Functional Performance

    Science.gov (United States)

    Bloomberg, J. J.; Lawrence, E. L.; Arzeno, N. M.; Buxton, R. E.; Feiveson, A. H.; Kofman, I. S.; Lee, S. M. C.; Mulavara, A. P.; Peters, B. T.; Platts. S. H.; hide

    2011-01-01

    Exposure to space flight causes adaptations in multiple physiological systems including changes in sensorimotor, cardiovascular, and neuromuscular systems. These changes may affect a crewmember s ability to perform critical mission tasks immediately after landing on a planetary surface. The overall goal of this project is to determine the effects of space flight on functional tests that are representative of high priority exploration mission tasks and to identify the key underlying physiological factors that contribute to decrements in performance. To achieve this goal we developed an interdisciplinary testing protocol (Functional Task Test, FTT) that evaluates both astronaut functional performance and related physiological changes. Functional tests include ladder climbing, hatch opening, jump down, manual manipulation of objects and tool use, seat egress and obstacle avoidance, recovery from a fall and object translation tasks. Physiological measures include assessments of postural and gait control, dynamic visual acuity, fine motor control, plasma volume, orthostatic intolerance, upper- and lower-body muscle strength, power, endurance, control, and neuromuscular drive. Crewmembers perform this integrated test protocol before and after short (Shuttle) and long-duration (ISS) space flight. Data are collected on two sessions before flight, on landing day (Shuttle only) and 1, 6 and 30 days after landing. Preliminary results from both Shuttle and ISS crewmembers indicate decrement in performance of the functional tasks after both short and long-duration space flight. On-going data collection continues to improve the statistical power required to map changes in functional task performance to alterations in physiological systems. The information obtained from this study will be used to design and implement countermeasures that specifically target the physiological systems most responsible for the altered functional performance associated with space flight.

  18. Ablation of clinically relevant kidney tissue volumes by high-intensity focused ultrasound: Preliminary results of standardized ex-vivo investigations.

    Science.gov (United States)

    Häcker, Axel; Peters, Kristina; Knoll, Thomas; Marlinghaus, Ernst; Alken, Peter; Jenne, Jürgen W; Michel, Maurice Stephan

    2006-11-01

    To investigate strategies to achieve confluent kidney-tissue ablation by high-intensity focused ultrasound (HIFU). Our model of the perfused ex-vivo porcine kidney was used. Tissue ablation was performed with an experimental HIFU device (Storz Medical, Kreuzlingen, Switzerland). Lesion-to-lesion interaction was investigated by varying the lesion distance (5 to 2.5 mm), generator power (300, 280, and 260 W), cooling time (10, 20, and 30 seconds), and exposure time (4, 3, and 2 seconds). The lesion rows were analyzed grossly and by histologic examination (hematoxylin-eosin and nicotinamide adenine dinucleotide staining). It was possible to achieve complete homogeneous ablation of a clinically relevant tissue volume but only by meticulous adjustment of the exposure parameters. Minimal changes in these parameters caused changes in lesion formation with holes within the lesions and lesion-to-lesion interaction. Our preliminary results show that when using this new device, HIFU can ablate a large tissue volume homogeneously in perfused ex-vivo porcine tissue under standardized conditions with meticulous adjustment of exposure parameters. Further investigations in vivo are necessary to test whether large tissue volumes can be ablated completely and reliably despite the influence of physiologic tissue and organ movement.

  19. A Simplified Whole-Organ CT Perfusion Technique with Biphasic Acquisition: Preliminary Investigation of Accuracy and Protocol Feasibility in Kidneys.

    Science.gov (United States)

    Yuan, XiaoDong; Zhang, Jing; Quan, ChangBin; Tian, Yuan; Li, Hong; Ao, GuoKun

    2016-04-01

    To determine the feasibility and accuracy of a protocol for calculating whole-organ renal perfusion (renal blood flow [RBF]) and regional perfusion on the basis of biphasic computed tomography (CT), with concurrent dynamic contrast material-enhanced (DCE) CT perfusion serving as the reference standard. This prospective study was approved by the institutional review board, and written informed consent was obtained from all patients. Biphasic CT of the kidneys, including precontrast and arterial phase imaging, was integrated with a first-pass dynamic volume CT protocol and performed and analyzed in 23 patients suspected of having renal artery stenosis. The perfusion value derived from biphasic CT was calculated as CT number enhancement divided by the area under the arterial input function and compared with the DCE CT perfusion data by using the paired t test, correlation analysis, and Bland-Altman plots. Correlation analysis was made between the RBF and the extent of renal artery stenosis. All postprocessing was independently performed by two observers and then averaged as the final result. Mean ± standard deviation biphasic and DCE CT perfusion data for RBF were 425.62 mL/min ± 124.74 and 419.81 mL/min ± 121.13, respectively (P = .53), and for regional perfusion they were 271.15 mL/min per 100 mL ± 82.21 and 266.33 mL/min per 100 mL ± 74.40, respectively (P = .31). Good correlation and agreement were shown between biphasic and DCE CT perfusion for RBF (r = 0.93; ±10% variation from mean perfusion data [P < .001]) and for regional perfusion (r = 0.90; ±13% variation from mean perfusion data [P < .001]). The extent of renal artery stenosis was negatively correlated with RBF with biphasic CT perfusion (r = -0.81, P = .012). Biphasic CT perfusion is clinically feasible and provides perfusion data comparable to DCE CT perfusion data at both global and regional levels in the kidney. Online supplemental material is available for this article.

  20. Q-ball imaging models: comparison between high and low angular resolution diffusion-weighted MRI protocols for investigation of brain white matter integrity

    Energy Technology Data Exchange (ETDEWEB)

    Caiazzo, Giuseppina; Trojsi, Francesca; Cirillo, Mario; Tedeschi, Gioacchino [MRI Research Center SUN-FISM-Neurological Institute for Diagnosis and Care ' ' Hermitage Capodimonte' ' , Naples (Italy); Second University of Naples, Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Naples (Italy); Esposito, Fabrizio [University of Salerno, Department of Medicine and Surgery, Baronissi (Salerno) (Italy); Maastricht University, Department of Cognitive Neuroscience, Maastricht (Netherlands)

    2016-02-15

    Q-ball imaging (QBI) is one of the typical data models for quantifying white matter (WM) anisotropy in diffusion-weighted MRI (DwMRI) studies. Brain and spinal investigation by high angular resolution DwMRI (high angular resolution imaging (HARDI)) protocols exhibits higher angular resolution in diffusion imaging compared to low angular resolution models, although with longer acquisition times. We aimed to assess the difference between QBI-derived anisotropy values from high and low angular resolution DwMRI protocols and their potential advantages or shortcomings in neuroradiology. Brain DwMRI data sets were acquired in seven healthy volunteers using both HARDI (b = 3000 s/mm{sup 2}, 54 gradient directions) and low angular resolution (b = 1000 s/mm{sup 2}, 32 gradient directions) acquisition schemes. For both sequences, tract of interest tractography and generalized fractional anisotropy (GFA) measures were extracted by using QBI model and were compared between the two data sets. QBI tractography and voxel-wise analyses showed that some WM tracts, such as corpus callosum, inferior longitudinal, and uncinate fasciculi, were reconstructed as one-dominant-direction fiber bundles with both acquisition schemes. In these WM tracts, mean percent different difference in GFA between the two data sets was less than 5 %. Contrariwise, multidirectional fiber bundles, such as corticospinal tract and superior longitudinal fasciculus, were more accurately depicted by HARDI acquisition scheme. Our results suggest that the design of optimal DwMRI acquisition protocols for clinical investigation of WM anisotropy by QBI models should consider the specific brain target regions to be explored, inducing researchers to a trade-off choice between angular resolution and acquisition time. (orig.)

  1. Investigating the in vitro and in vivo angiogenic activity of five Philippine medicinal plants associated with wound healing properties

    International Nuclear Information System (INIS)

    Lacson, Mona Lisa B.; Macahig, Rene Angelo S.; Rojas, Nina Rosario L.

    2015-01-01

    Plants have been used since time immemorial to treat many ailments and speed up healing process. Plant parts and extracts have been traditionally used to heal wounds. Angiogenesis is one of the events associated with wound healing. It is a tightly regulated process of blood vessel formation and an important target for diseases like coronary infarction, ischemia and stroke. Several in vitro and in vivo methods have been developed to assess the angiogenic activity of different compounds. These include the chorio-allantaoic membrane (CAM) assay which uses the egg's gas exchange membrane to assess the angiogenic potential of a substance and the tube formation assay which uses endothelial cells grown in the lab. Aqueous ethanolic extracts of five Philippine medicinal plants associated with wound healing were used in the study. Preliminary phytochemical screening using spray raegents and toxicity test using brine shrimp (Artemia salina) nauplii was done. 10% of the computed LC 5 0 value was used to screen the angiogenic potential of the plant extracts using human umbilical vein endothelial cells (HUVECs) in an in vitro tube formation assay and in vivo chorio-allantoic membrane (CAM) assay. Phorbol myristate (PMA) a known pro-angiogenic compound was used as positive control. Initial phytochemical screening showed that the crude enthanolic extracts of the leaves of the five contain flavonoids, steroids, phenols, saponins, alkanoids, coumarins, anthranoids, anthraquinones, sugars and essential oils. Brine shrimp lethality assay revealed that the plants used were not toxic to Artemia salina nauplii at 1000 μg/mL. In vitro tube formation assay revealed the crude ethanolic extracts of the leaves of M. indica showed the greatest angiogenic activity, closely followed by C. pubescens, T. catappa, A. barbadensis and C. odorata. The effect of the crude ethanolic extracts of the plants on blood vessel formation in the in vivo CAM model showed A. barbadensis with the highest

  2. Investigation of in vivo toxicity of hydroxylamine sulfate and the efficiency of intoxication treatment by α-tocopherol acetate and methylene blue.

    Science.gov (United States)

    Prodanchuk, Mykola G; Tsatsakis, Aristidis M; Prodanchuk, Georgiy M; Tsakalof, Andreas K

    2013-11-01

    Investigation of hydroxylamine sulfate toxicity mechanism in vivo and estimation of α-tocopherol acetate and methylene blue efficiency in poisoning treatments. In vivo experiments were conducted on 102 Wistar Han rats. The experiments investigated the hematotoxic and oxidative stress effects of hydroxylamine sulfate in acute and subacute toxicity treatment of animals. Electron Spin Resonance was used for quantitative determination of blood and liver tissue parameters alterations after intoxication. The osmotic fragility of erythrocytes, lipid peroxidation intensity and level of SH-groups in liver of rats were determined by established biochemical assays. Hydroxylamine sulfate cause an acute hematotoxicity and oxidative stress in vivo as demonstrated by the appearance of free oxidized iron in blood, reduced glutathione content and increased lipid peroxidation in liver. The experimental studies showed the formation of Hb-NO, MetHb in erythrocytes and as well of stable complex of reduced iron (Fe(2+)) with hydroxylamine sulfate. Methylene blue treatment does not reduce the Hb-NO or MetHb levels in intoxicated animals while administration of α-tocopherol acetate reduces substantially lipid peroxidation. Oxidative stress is a key mechanism of acute hematotoxicity caused by hydroxylamine sulfate. Methylene blue is not suitable antidote in case of hydroxylamine intoxication. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. A new in vivo model using a dorsal skinfold chamber to investigate microcirculation and angiogenesis in diabetic wounds

    Directory of Open Access Journals (Sweden)

    Langer, Stefan

    2016-02-01

    Full Text Available Introduction: Diabetes mellitus describes a dysregulation of glucose metabolism due to improper insulin secretion, reduced insulin efficacy or both. It is a well-known fact that diabetic patients are likely to suffer from impaired wound healing, as diabetes strongly affects tissue angiogenesis. Until now, no satisfying in vivo murine model has been established to analyze the dynamics of angiogenesis during diabetic wound healing. To help understand the pathophysiology of diabetes and its effect on angiogenesis, a novel in vivo murine model was established using the skinfold chamber in mice.Materials and Methods: Mutant diabetic mice (db; wildtype mice ( and laboratory BALB/c mice were examined. They were kept in single cages with access to laboratory chow with an 12/12 hour day/night circle. Lesions of the panniculus muscle (Ø 2 mm were created in the center of the transparent window chamber and the subsequent muscular wound healing was then observed for a period of 22 days. Important analytic parameters included vessel diameter, red blood cell velocity, vascular permeability, and leakage of muscle capillaries and post capillary venules. The key parameters were functional capillary density (FCD and angiogenesis positive area (APA.Results: We established a model which allows high resolution in vivo imaging of functional angiogenesis in diabetic wounds. As expected, db mice showed impaired wound closure (day 22 compared to wounds of BALB/c or WT mice (day 15. FCD was lower in diabetic mice compared to WT and BALB/c during the entire observation period. The dynamics of angiogenesis also decreased in db mice, as reflected by the lowest APA levels. Significant variations in the skin buildup were observed, with the greatest skin depth in db mice. Furthermore, in db mice, the dermis:subcutaneous ratio was highly shifted towards the subcutaneous layers as opposed to WT or BALB/c mice.Conclusion: Using this new in vivo model of the skinfold chamber, it

  4. A blinded randomised placebo-controlled trial investigating the efficacy of morphine analgesia for procedural pain in infants: Trial protocol.

    Science.gov (United States)

    Slater, Rebeccah; Hartley, Caroline; Moultrie, Fiona; Adams, Eleri; Juszczak, Ed; Rogers, Richard; Norman, Jane E; Patel, Chetan; Stanbury, Kayleigh; Hoskin, Amy; Green, Gabrielle

    2016-11-15

    Infant pain has both immediate and long-term negative consequences, yet in clinical practice it is often undertreated. To date, few pain-relieving drugs have been tested in infants. Morphine is a potent analgesic that provides effective pain relief in adults, but there is inconclusive evidence for its effectiveness in infants. The purpose of this study is to establish whether oral morphine provides effective analgesia for procedural pain in infants. A blinded, placebo-controlled, parallel-group randomized, phase II, clinical trial will be undertaken to determine whether morphine sulphate administered orally prior to clinically-required retinopathy of prematurity (ROP) screening and heel lancing provides effective analgesia. 
156 infants between 34 and 42 weeks' gestational age who require a clinical heel lance and ROP screening on the same test occasion will be included in the trial. Infants will be randomised to receive either a single dose of morphine sulphate (100 μg/kg) or placebo. Each infant will be monitored for 48 hours and safety data will be collected during the 24 hours following drug administration. The primary outcome will be the Premature Infant Pain Profile-revised (PIPP-R) score 30 seconds after ROP screening. The co-primary outcome will be the magnitude of nociceptive-specific brain activity evoked by a clinically-required heel lance. Infant clinical stability will be assessed by comparing the number of episodes of bradycardia, tachycardia, desaturation and apnoea, and changes in respiratory support requirements in the 24-hour periods before and after the clinical intervention. In addition, drug safety will be assessed by considering the occurrence of apnoeic and hypotensive episodes requiring intervention in the 24-hour period following drug administration. This study has been published as an Accepted Protocol Summary by The Lancet .

  5. Study protocol: a randomised controlled trial investigating the effect of a healthy lifestyle intervention for people with severe mental disorders

    Directory of Open Access Journals (Sweden)

    Castle David

    2011-01-01

    Full Text Available Abstract Background The largest single cause of death among people with severe mental disorders is cardiovascular disease (CVD. The majority of people with schizophrenia and bipolar disorder smoke and many are also overweight, considerably increasing their risk of CVD. Treatment for smoking and other health risk behaviours is often not prioritized among people with severe mental disorders. This protocol describes a study in which we will assess the effectiveness of a healthy lifestyle intervention on smoking and CVD risk and associated health behaviours among people with severe mental disorders. Methods/Design 250 smokers with a severe mental disorder will be recruited. After completion of a baseline assessment and an initial face-to-face intervention session, participants will be randomly assigned to either a multi-component intervention for smoking cessation and CVD risk reduction or a telephone-based minimal intervention focusing on smoking cessation. Randomisation will be stratified by site (Newcastle, Sydney, Melbourne, Australia, Body Mass Index (BMI category (normal, overweight, obese and type of antipsychotic medication (typical, atypical. Participants will receive 8 weekly, 3 fortnightly and 6 monthly sessions delivered face to face (typically 1 hour or by telephone (typically 10 minutes. Assessments will be conducted by research staff blind to treatment allocation at baseline, 15 weeks, and 12-, 18-, 24-, 30- and 36-months. Discussion This study will provide comprehensive data on the effect of a healthy lifestyle intervention on smoking and CVD risk among people with severe mental disorders. If shown to be effective, this intervention can be disseminated to treating clinicians using the treatment manuals. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR identifier: ACTRN12609001039279

  6. Sevoflurane-induced Preconditioning Impact of Protocol and Aprotinin Administration on Infarct Size and Endothelial Nitric-Oxide Synthase Phosphorylation in the Rat Heart In Vivo

    NARCIS (Netherlands)

    Fräßdorf, Jan; Huhn, Ragnar; Weber, Nina C.; Ebel, Dirk; Wingert, Nadja; Preckel, Benedikt; Toma, Octavian; Schlack, Wolfgang; Hollmann, Markus W.

    2010-01-01

    Background Sevoflurane induces preconditioning (SevoPC) 1 he effect of aprotinin and the involvement of endothelial nitric-oxide synthase (NOS) on SevoPC are unknown We investigated (1) whether SevoPC is strengthened by multiple preconditioning cycles (2) whether SevoPC is blocked by aprotinin, and

  7. Investigating the correlation between in vivo absorption and in vitro release of fenofibrate from lipid matrix particles in biorelevant medium

    DEFF Research Database (Denmark)

    Borkar, Nrupa Nitin; Xia, Dengning; Holm, René

    2014-01-01

    Lipid matrix particles (LMP) may be used as better carriers for poorly water-soluble drugs than liquid lipid carriers because of reduced drug mobilization in the formulations. However, the digestion process of solid lipid particles and their effect on the absorption of poorly water-soluble drugs......-soluble drug, was incorporated into LMP in this study using probe ultrasound sonication. The resultant LMP were characterised in terms of particle size, size distribution, zeta potential, entrapment efficiency, in vitro lipolysis and in vivo absorption in rat model. LMP of three different particle sizes i.......e. approximately 100 nm, 400 nm, and 10 μm (microparticles) were produced with high entrapment efficiencies. The in vitro lipolysis study showed that the recovery of fenofibrate in the aqueous phase for 100 nm and 400 nm LMP was significantly higher (p

  8. In vivo crystalline lens measurements with novel swept-source optical coherent tomography: an investigation on variability of measurement

    Science.gov (United States)

    Shoji, Takuhei; Kato, Naoko; Ishikawa, Sho; Ibuki, Hisashi; Yamada, Norihiro; Kimura, Itaru; Shinoda, Kei

    2017-01-01

    Objective To evaluate the reproducibility of in vivo crystalline lens measurements obtained by novel commercially available swept-source (SS) optical coherence tomography (OCT) specifically designed for anterior segment imaging. Methods and analysis One eye from each of 30 healthy subjects was randomly selected using the CASIA2 (Tomey, Nagoya, Japan) in two separate visits within a week. Each eye was imaged twice. After image scanning, the anterior and posterior lens curvatures and lens thickness were calculated automatically by the CASIA2 built-in program at 0 dioptre (D) (static), −1 D, −3 D and −5 D accommodative stress. The intraobserver and intervisit reproducibility coefficient (RC) and intraclass correlation coefficient (ICC) were calculated. Results The intraobserver and intervisit RCs ranged from 0.824 to 1.254 mm and 0.789 to 0.911 mm for anterior lens curvature, from 0.276 to 0.299 mm and 0.221 to 0.270 mm for posterior lens curvature and from 0.065 to 0.094 mm and 0.054 to 0.132 mm for lens thickness, respectively. The intraobserver and intervisit ICCs ranged from 0.831 to 0.865 and 0.828 to 0.914 for anterior lens curvature, from 0.832 to 0.898 and 0.840 to 0.933 for posterior lens curvature and from 0.980 to 0.992 and 0.942 to 0.995 for lens thickness. High ICC values were observed for each measurement regardless of accommodative stress. RCs in younger subjects tended to be larger than those in older subjects. Conclusions This novel anterior segment SS-OCT instrument produced reliable in vivo crystalline lens measurement with good repeatability and reproducibility regardless of accommodation stress. PMID:29354706

  9. Investigating Postsecondary Self-Regulated Learning Instructional Practices: The Development of the Self-Regulated Learning Observation Protocol

    Science.gov (United States)

    Hoops, Leah D.; Yu, Shirley L.; Wang, Qianqian; Hollyer, Virginia L.

    2016-01-01

    Promoting students' self-regulated learning (SRL) is one way to improve postsecondary student success. However, few studies have investigated the instructional practices of postsecondary instructors that may support students' SRL. This study sought to fill this gap. An undergraduate mathematics course was observed to determine instruction utilized…

  10. Bioremediation protocols

    National Research Council Canada - National Science Library

    Sheehan, David

    1997-01-01

    ..., .. . . . . .. ,. . . .. . . . . . . . .. . . . . .. . . .. . .. 3 2 Granular Nina Sludge Christiansen, Consortia lndra for Bioremediation, M. Mathrani, and Birgitte K. Ahring . 23 PART II PROTOCOLS...

  11. The in vivo pharmacokinetics, tissue distribution and excretion investigation of mesaconine in rats and its in vitro intestinal absorption study using UPLC-MS/MS.

    Science.gov (United States)

    Liu, Xiuxiu; Tang, Minghai; Liu, Taohong; Wang, Chunyan; Tang, Qiaoxin; Xiao, Yaxin; Yang, Ruixin; Chao, Ruobing

    2017-12-27

    1. Mesaconine, an ingredient from Aconitum carmichaelii Debx., has been proven to have cardiac effect. For further development and better pharmacological elucidation, the in vivo process and intestinal absorptive behavior of mesaconine should be investigated comprehensively. 2. An ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantitation of mesaconine in rat plasma, tissue homogenates, urine and feces to investigate the in vivo pharmacokinetic profiles, tissue distribution and excretion. The intestinal absorptive behavior of mesaconine was investigated using in vitro everted rat gut sac model. 3. Mesaconine was well distributed in tissues and a mass of unchanged form was detected in feces. It was difficultly absorbed into blood circulatory system after oral administration. The insufficient oral bioavailability of mesaconine may be mainly attributed to its low intestinal permeability due to a lack of lipophilicity. The absorption of mesaconine in rat's intestine is a first-order process with the passive diffusion mechanism.

  12. Investigation of cis-trans isomer dependent dermatotoxicokinetics of UV filter ethylhexyl methoxycinnamate through stratum corneum in vivo.

    Science.gov (United States)

    Sharma, Anežka; Bányiová, Katarína; Vrana, Branislav; Justan, Ivan; Čupr, Pavel

    2017-11-01

    2-Ethylhexyl methoxycinnamate (EHMC) is one of the most used ultraviolet filters in personal care products. It undergoes cis/trans isomerization in sunlight, and there is limited toxicological understanding of the effects of the cis-isomer. It is known that two geometric isomers of one compound can have different physico-chemical properties and effects. However, there are no studies focusing on toxicokinetics of EHMC isomerization products to compare their potential difference in dermal exposure to cis-EHMC and trans-EHMC due to the difference in their dermatotoxicokinetics. In this study, dermal absorption of the parental trans-EHMC and its cis isomer was studied. A commercially available sunscreen lotion containing trans-EHMC and spiked with laboratory-prepared cis-EHMC was locally applied on the forearm skin of two volunteers. After 8 h of skin exposure, the stratum corneum (SC) layer was removed by tape stripping. The removed thickness of the SC was determined spectrophotometrically using a total protein assay. The concentration of both isomers in the removed SC was measured by HPLC-DAD. A new diffusion and permeability coefficient of both EHMC isomers in SC were determined by Fick's second law of diffusion in vivo. The difference in dermatotoxicokinetic parameters between the two isomers was not statistically significant. However, separate toxicological studies of isomeric forms and the determination of their dermatotoxicokinetic parameters are crucial for refinement of human risk assessment.

  13. Pediatric suppositories of sulpiride solid dispersion for treatment of Tourette syndrome: in vitro and in vivo investigations.

    Science.gov (United States)

    Zidan, Ahmed S; Emam, Sherif E; Shehata, Tamer M; Ghazy, Fakhr-eldin S

    2015-06-01

    Pharmaceutical development was adopted in the current study to propose a pediatric rectal formulation of sulpiride as a substitute to the available oral or parenteral formulations in the management of Tourette syndrome (TS). The goal was to formulate a product that is easy to use, stable, and highly bioavailable and to achieve a rapid clinical efficacy. Towards this aim, sulpiride solid dispersion (SD) with tartaric acid at a weight ratio of 1:0.25 was incorporated into different suppository bases, namely witepsol W25, witepsol H15, witepsol E75, suppocire NA, suppocire A, glycerogelatin, and polyethylene glycols. The formulae were evaluated in vitro using different pharmacotechnical methods such as visual, melting, weight and content uniformities, drug release, differential scanning calorimetry (DSC), Fourier transform infrared (FTIR), and X-ray diffraction (XRD) analyses. In vivo bioavailability was also assessed in rabbits to compare the bioavailability of either raw sulpiride-incorporated or its SD-incorporated witepsol H15-based suppositories to its oral suspension (reference). Sulpiride SD-incorporated witepsol H15 formulation showed acceptable in vitro characteristics with a bioavailability of 117% relative to oral dosing, which excel that in humans (27% after dosing of oral product). In addition, the proposed formula not only passed the 6-month stability study but also proposed a promising scale-up approach. Hence, it showed a great potential for pediatric product development to manage TS in rural areas.

  14. An investigation into the depth of penetration of low level laser therapy through the equine tendon in vivo

    Directory of Open Access Journals (Sweden)

    Ryan Teresa

    2007-05-01

    Full Text Available Abstract Low level laser therapy (LLLT is frequently used in the treatment of wounds, soft tissue injury and in pain management. The exact penetration depth of LLLT in human tissue remains unspecified. Similar uncertainty regarding penetration depth arises in treating animals. This study was designed to test the hypothesis that transmission of LLLT in horses is increased by clipping the hair and/or by cleaning the area to be treated with alcohol, but is unaffected by coat colour. A LLLT probe (810 nm, 500 mW was applied to the medial aspect of the superficial flexor tendon of seventeen equine forelimbs in vivo. A light sensor was applied to the lateral aspect, directly opposite the laser probe to measure the amount of light transmitted. Light transmission was not affected by individual horse, coat colour or leg. However, it was associated with leg condition (F = 4.42, p = 0.0032. Tendons clipped dry and clipped and cleaned with alcohol, were both associated with greater transmission of light than the unprepared state. Use of alcohol without clipping was not associated with an increase in light transmission. These results suggest that, when applying laser to a subcutaneous structure in the horse, the area should be clipped and cleaned beforehand.

  15. Fast Track Characterization of Highly Radioactive Waste Pits Combining Off-the-Shelf Robotics with Innovative Investigation Protocols

    International Nuclear Information System (INIS)

    Chabeuf, Jean-Michel; Boya, Didier

    2008-01-01

    The investigation and characterization of radioactive waste pits and effluent storage tanks represents a substantial and challenging step in the overall decommissioning programme launched by AREVA NC in 1998 on the site of Marcoule on behalf of the French Atomic Energy commission. Physical ,radiological and regulatory constraints, combined with a tight schedule, have lead our teams to use proven conventional instrumentation and robotics in innovative configurations . One such investigation, conducted on a particularly challenging radioactive effluent storage pit, is described below. The 'H' pit is a stainless steel clad concrete cavity, located in the second basement of the de-cladding building of Marcoule site. It was used for forty years as buffer storage for high activity effluents and has a length of 5 meters, a width of 3 meters , a height of 2.5 meters, and is topped by lead plates over 5 cm thick and The bottom of the cavity is covered with a layer of mud containing mainly graphite, diatoms and resins. The mud level ranges from about 20 centimeters to over 50 centimeters. The overall mud volume is around 2.4 cubic meters. Ambient dose rates above the lead plates exceed 10 mSv/h. The main purpose of our investigation was to characterize the muds for future recovery and conditioning prior to decontaminating the pit. The history of the pit together with the varying mud altimetry lead us to believe that sedimentation had probably occurred throughout the years. We thus decided to combine dose rate measurements using IF104 probes, gamma spectroscopy with CdTe probes and sample collections at different depths to ensure the representativeness and full characterization of the muds. Poor access, ambient dose rates have lead us to conceive a robotic arm, mounted on an shaft which can be modified to fit a wide range of pits and tanks. Custom built robotic tools with maximum manoeuvrability generally involve costs and delays far exceeding our purposes. SIT, a French

  16. The application of a rodent-based Morris water maze (MWM) protocol to an investigation of age-related differences in human spatial learning.

    Science.gov (United States)

    Zhong, Jimmy Y; Magnusson, Kathy R; Swarts, Matthew E; Clendinen, Cherita A; Reynolds, Nadjalisse C; Moffat, Scott D

    2017-12-01

    The current study applied a rodent-based Morris water maze (MWM) protocol to an investigation of search performance differences between young and older adult humans. To investigate whether similar age-related decline in search performance could be seen in humans based on the rodent-based protocol, we implemented a virtual MWM (vMWM) that has characteristics similar to those of the MWM used in previous studies of spatial learning in mice. Through the use of a proximity to platform measure, robust differences were found between healthy young and older adults in search performance. After dividing older adults into good and poor performers based on a median split of their corrected cumulative proximity values, the age effects in place learning were found to be largely related to search performance differences between the young and poor-performing older adults. When compared with the young, poor-performing older adults exhibited significantly higher proximity values in 83% of 24 place trials and overall in the probe trials that assessed spatial learning in the absence of the hidden platform. In contrast, good-performing older adults exhibited patterns of search performance that were comparable with that of the younger adults in most place and probe trials. Taken together, our findings suggest that the low search accuracy in poor-performing older adults stemmed from potential differences in strategy selection, differences in assumptions or expectations of task demands, as well as possible underlying functional and/or structural changes in the brain regions involved in vMWM search performance. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  17. An investigation of somatosensory profiles in work related upper limb disorders: a case-control observational study protocol.

    LENUS (Irish Health Repository)

    Moloney, Niamh

    2010-01-01

    BACKGROUND: Work related upper limb disorders constitute 45% of all occupational diseases and are a significant public health problem. A subgroup, non specific arm pain (NSAP), remains elusive in terms of understanding its pathophysiological mechanisms with its diagnosis based on the absence of specific clinical findings. One commonly proposed theory is that a neural tissue disorder is the primary dysfunction in NSAP and findings from previous studies lend some support to this theory. However, it is not clear if changes identified are simply a consequence of ongoing pain rather than due to specific neural changes. The presence of neuropathic pain has been investigated in several other musculoskeletal conditions but currently, there is no specific diagnostic tool or gold standard which permits an unequivocal diagnosis of neuropathic pain. The purpose of this study is to further describe the somatosensory profiles in patients with NSAP and to compare these profiles to a group of patients with MRI confirmed cervical radiculopathy who have been previously classified as having neuropathic pain. METHODS\\/DESIGN: Three groups of participants will be investigated: Groups 1 and 2 will be office workers with either NSAP or cervical radiculopathy and Group 3 will be a control group of non office workers without upper limb pain. Participants will undergo a clinical assessment, pain questionnaires (LANSS, Short Form McGill, DASH and TSK) and quantitative sensory testing comprising thermal detection and pain thresholds, vibration thresholds and pressure pain thresholds. DISCUSSION: The spectrum of clinically suspected neuropathic pain ranges from more obvious conditions such as trigeminal neuralgia to those with vague signs of nerve disorder such as NSAP. A thorough description of the somatosensory profiles of NSAP patients and a comparison with a more defined group of patients with evidence of neuropathic pain will help in the understanding of underlying neurophysiology in

  18. Experimental protocol of a randomized controlled clinical trial investigating exercise, subclinical atherosclerosis, and walking mobility in persons with multiple sclerosis.

    Science.gov (United States)

    Griffith, Garett; Klaren, Rachel E; Motl, Robert W; Baynard, Tracy; Fernhall, Bo

    2015-03-01

    This randomized controlled trial (RCT) will investigate the effects of a home-based aerobic exercise training regimen (i.e., cycle ergometry) on subclinical atherosclerosis and walking mobility in persons with multiple sclerosis (MS) and minimal disability. This RCT will recruit 54 men and women who have an Expanded Disability Status Scale characteristic of the 1st stage of MS (i.e., 0-4.0) to participate in a 3 month exercise or stretching intervention, with assessments of subclinical atherosclerosis and walking mobility conducted at baseline, week 6 (midpoint), and week 12 (conclusion) of the program. The exercise intervention will consist of 3 days/week of cycling, with a gradual increase of duration followed by an increase in intensity across the 3 month period. The attention-control condition will incorporate stretching activities and will require the same contact time commitment as the exercise condition. Both study groups will participate in weekly video chat sessions with study personnel in order to monitor and track program adherence. Primary outcomes will consist of assessments of vascular structure and function, as well as several walking tasks. Additional outcomes will include questionnaires, cardiorespiratory fitness assessment, and a 1-week free-living physical activity assessment. This investigation will increase understanding of the role of aerobic exercise as part of a treatment plan for managing subclinical atherosclerosis and improving walking mobility persons in the 1st stage of MS. Overall, this study design has the potential to lead to effective aerobic exercise intervention strategies for this population and improve program adherence. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. An investigation of somatosensory profiles in work related upper limb disorders: a case-control observational study protocol

    Directory of Open Access Journals (Sweden)

    Hall Toby

    2010-01-01

    Full Text Available Abstract Background Work related upper limb disorders constitute 45% of all occupational diseases and are a significant public health problem. A subgroup, non specific arm pain (NSAP, remains elusive in terms of understanding its pathophysiological mechanisms with its diagnosis based on the absence of specific clinical findings. One commonly proposed theory is that a neural tissue disorder is the primary dysfunction in NSAP and findings from previous studies lend some support to this theory. However, it is not clear if changes identified are simply a consequence of ongoing pain rather than due to specific neural changes. The presence of neuropathic pain has been investigated in several other musculoskeletal conditions but currently, there is no specific diagnostic tool or gold standard which permits an unequivocal diagnosis of neuropathic pain. The purpose of this study is to further describe the somatosensory profiles in patients with NSAP and to compare these profiles to a group of patients with MRI confirmed cervical radiculopathy who have been previously classified as having neuropathic pain. Methods/Design Three groups of participants will be investigated: Groups 1 and 2 will be office workers with either NSAP or cervical radiculopathy and Group 3 will be a control group of non office workers without upper limb pain. Participants will undergo a clinical assessment, pain questionnaires (LANSS, Short Form McGill, DASH and TSK and quantitative sensory testing comprising thermal detection and pain thresholds, vibration thresholds and pressure pain thresholds. Discussion The spectrum of clinically suspected neuropathic pain ranges from more obvious conditions such as trigeminal neuralgia to those with vague signs of nerve disorder such as NSAP. A thorough description of the somatosensory profiles of NSAP patients and a comparison with a more defined group of patients with evidence of neuropathic pain will help in the understanding of underlying

  20. Study protocol: the empirical investigation of methods to correct for measurement error in biobanks with dietary assessment

    Directory of Open Access Journals (Sweden)

    Masson Lindsey F

    2011-10-01

    Full Text Available Abstract Background The Public Population Project in Genomics (P3G is an organisation that aims to promote collaboration between researchers in the field of population-based genomics. The main objectives of P3G are to encourage collaboration between researchers and biobankers, optimize study design, promote the harmonization of information use in biobanks, and facilitate transfer of knowledge between interested parties. The importance of calibration and harmonisation of methods for environmental exposure assessment to allow pooling of data across studies in the evaluation of gene-environment interactions has been recognised by P3G, which has set up a methodological group on calibration with the aim of; 1 reviewing the published methodological literature on measurement error correction methods with assumptions and methods of implementation; 2 reviewing the evidence available from published nutritional epidemiological studies that have used a calibration approach; 3 disseminating information in the form of a comparison chart on approaches to perform calibration studies and how to obtain correction factors in order to support research groups collaborating within the P3G network that are unfamiliar with the methods employed; 4 with application to the field of nutritional epidemiology, including gene-diet interactions, ultimately developing a inventory of the typical correction factors for various nutrients. Methods/Design Systematic review of (a the methodological literature on methods to correct for measurement error in epidemiological studies; and (b studies that have been designed primarily to investigate the association between diet and disease and have also corrected for measurement error in dietary intake. Discussion The conduct of a systematic review of the methodological literature on calibration will facilitate the evaluation of methods to correct for measurement error and the design of calibration studies for the prospective pooling of

  1. Integrated in silico and in vivo approaches to investigate effects of BDE-99 mediated by the nuclear receptors on developing zebrafish.

    Science.gov (United States)

    Zhang, Li; Jin, Yaru; Han, Zhihua; Liu, Hongling; Shi, Laihao; Hua, Xiaoxue; Doering, Jon A; Tang, Song; Giesy, John P; Yu, Hongxia

    2018-03-01

    One of the most abundant polybrominated diphenyl ethers (PBDEs) is 2,2',4,4',5-pentabromodiphenyl ether (BDE-99), which persists and potentially bioaccumulates in aquatic wildlife. Previous studies in mammals have shown that BDE-99 affects development and disrupts certain endocrine functions through signaling pathways mediated by nuclear receptors. However, fewer studies have investigated the potential of BDE-99 to interact with nuclear receptors in aquatic vertebrates such as fish. In the present study, interactions between BDE-99 and nuclear receptors were investigated by in silico and in vivo approaches. This PBDE was able to dock into the ligand-binding domain of zebrafish aryl hydrocarbon receptor 2 (AhR2) and pregnane X receptor (PXR). It had a significant effect on the transcriptional profiles of genes associated with AhR or PXR. Based on the developed cytoscape of all zebrafish genes, it was also inferred that AhR and PXR could interact via cross-talk. In addition, both the in silico and in vivo approaches found that BDE-99 affected peroxisome proliferator-activated receptor alpha (PPARα), glucocorticoid receptor, and thyroid receptor. Collectively, our results demonstrate for the first time detailed in silico evidence that BDE-99 can bind to and interact with zebrafish AhR and PXR. These findings can be used to elaborate the molecular mechanism of BDE-99 and guide more objective environmental risk assessments. Environ Toxicol Chem 2018;37:780-787. © 2017 SETAC. © 2017 SETAC.

  2. A cluster randomised controlled trial to investigate the effectiveness and cost effectiveness of the 'Girls Active' intervention: a study protocol.

    Science.gov (United States)

    Edwardson, C L; Harrington, D M; Yates, T; Bodicoat, D H; Khunti, K; Gorely, T; Sherar, L B; Edwards, R T; Wright, C; Harrington, K; Davies, M J

    2015-06-04

    Despite the health benefits of physical activity, data from the UK suggest that a large proportion of adolescents do not meet the recommended levels of moderate-to-vigorous physical activity (MVPA). This is particularly evident in girls, who are less active than boys across all ages and may display a faster rate of decline in physical activity throughout adolescence. The 'Girls Active' intervention has been designed by the Youth Sport Trust to target the lower participation rates observed in adolescent girls. 'Girls Active' uses peer leadership and marketing to empower girls to influence decision making in their school, develop as role models and promote physical activity to other girls. Schools are provided with training and resources to review their physical activity, sport and PE provision, culture and practices to ensure they are relevant and attractive to adolescent girls. This study is a two-arm cluster randomised controlled trial (RCT) aiming to recruit 20 secondary schools. Clusters will be randomised at the school level (stratified by school size and proportion of Black and Minority Ethnic (BME) pupils) to receive either the 'Girls Active' intervention or carry on with usual practice (1:1). The 20 secondary schools will be recruited from state secondary schools within the Midlands area. We aim to recruit 80 girls aged 11-14 years in each school. Data will be collected at three time points; baseline and seven and 14 months after baseline. Our primary aim is to investigate whether 'Girls Active' leads to higher objectively measured (GENEActiv) moderate-to-vigorous physical activity in adolescent girls at 14 months after baseline assessment compared to the control group. Secondary outcomes include other objectively measured physical activity variables, adiposity, physical activity-related psychological factors and the cost-effectiveness of the 'Girls Active' intervention. A thorough process evaluation will be conducted during the course of the intervention

  3. Quantitation of dopamine transporter blockade by methylphenidate: first in vivo investigation using [123I]FP-CIT and a dedicated small animal SPECT

    International Nuclear Information System (INIS)

    Nikolaus, Susanne; Wirrwar, Andreas; Antke, Christina; Arkian, Shahram; Mueller, Hans-Wilhelm; Larisch, Rolf; Schramm, Nils

    2005-01-01

    The aim of this study was to investigate the feasibility of assessing dopamine transporter binding after treatment with methylphenidate in the rat using a recently developed high-resolution small animal single-photon emission computed tomograph (TierSPECT) and [ 123 I]FP-CIT. [ 123 I]FP-CIT was administered intravenously 1 h after intraperitoneal injection of methylphenidate (10 mg/kg) or vehicle. Animals underwent scanning 2 h after radioligand administration. The striatum was identified by superimposition of [ 123 I]FP-CIT scans with bone metabolism and perfusion scans obtained with 99m Tc-DPD and 99m Tc-tetrofosmin, respectively. As these tracers do not pass the blood-brain barrier, their distribution permits the identification of extracerebral anatomical landmarks such as the orbitae and the harderian glands. The cerebellum was identified by superimposing [ 123 I]FP-CIT scans with images of brain perfusion obtained with 99m Tc-HMPAO. Methylphenidate-treated animals and vehicle-treated animals yielded striatal equilibrium ratios (V '' 3 ) of 0.24±0.26 (mean ± SD) and 1.09±0.42, respectively (ttest, two-tailed, p '' 3 values amounted to 0.05±0.28 (methylphenidate) and 0.3±0.39 (saline, p=0.176). This first in vivo study of rat dopamine transporter binding after pre-treatment with methylphenidate showed a mean reduction of 78% in striatal [ 123 I]FP-CIT accumulation. The results can be interpreted in terms of a pharmacological blockade in the rat striatum and show that in vivo quantitation of dopamine transporter binding is feasible with [ 123 I]FP-CIT and the TierSPECT. This may be of future relevance for in vivo investigations on rat models of attention deficit/hyperactivity disorder. Furthermore, our findings suggest that investigations in other animal models, e.g. of Parkinson's and Huntington's disease, may be feasible using SPECT radioligands and small animal imaging systems. (orig.)

  4. Quantitation of dopamine transporter blockade by methylphenidate: first in vivo investigation using [{sup 123}I]FP-CIT and a dedicated small animal SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Nikolaus, Susanne; Wirrwar, Andreas; Antke, Christina; Arkian, Shahram; Mueller, Hans-Wilhelm; Larisch, Rolf [Heinrich-Heine University, Clinic of Nuclear Medicine, Duesseldorf (Germany); Schramm, Nils [Research Center Juelich, Central Laboratory for Electronics, Juelich (Germany)

    2005-03-01

    The aim of this study was to investigate the feasibility of assessing dopamine transporter binding after treatment with methylphenidate in the rat using a recently developed high-resolution small animal single-photon emission computed tomograph (TierSPECT) and [{sup 123}I]FP-CIT. [{sup 123}I]FP-CIT was administered intravenously 1 h after intraperitoneal injection of methylphenidate (10 mg/kg) or vehicle. Animals underwent scanning 2 h after radioligand administration. The striatum was identified by superimposition of [{sup 123}I]FP-CIT scans with bone metabolism and perfusion scans obtained with {sup 99m}Tc-DPD and {sup 99m}Tc-tetrofosmin, respectively. As these tracers do not pass the blood-brain barrier, their distribution permits the identification of extracerebral anatomical landmarks such as the orbitae and the harderian glands. The cerebellum was identified by superimposing [{sup 123}I]FP-CIT scans with images of brain perfusion obtained with {sup 99m}Tc-HMPAO. Methylphenidate-treated animals and vehicle-treated animals yielded striatal equilibrium ratios (V''{sub 3}) of 0.24{+-}0.26 (mean {+-} SD) and 1.09{+-}0.42, respectively (ttest, two-tailed, p<0.0001). Cortical V''{sub 3} values amounted to 0.05{+-}0.28 (methylphenidate) and 0.3{+-}0.39 (saline, p=0.176). This first in vivo study of rat dopamine transporter binding after pre-treatment with methylphenidate showed a mean reduction of 78% in striatal [{sup 123}I]FP-CIT accumulation. The results can be interpreted in terms of a pharmacological blockade in the rat striatum and show that in vivo quantitation of dopamine transporter binding is feasible with [{sup 123}I]FP-CIT and the TierSPECT. This may be of future relevance for in vivo investigations on rat models of attention deficit/hyperactivity disorder. Furthermore, our findings suggest that investigations in other animal models, e.g. of Parkinson's and Huntington's disease, may be feasible using SPECT radioligands and

  5. Comparative in Vivo Investigation of Intrathecal and Intracerebroventricular Administration with Melanocortin Ligands MTII and AGRP into Mice.

    Science.gov (United States)

    Adank, Danielle N; Lunzer, Mary M; Lensing, Cody J; Wilber, Stacey L; Gancarz, Amy M; Haskell-Luevano, Carrie

    2018-02-21

    Central administration of melanocortin ligands has been used as a critical technique to study energy homeostasis. While intracerebroventricular (ICV) injection is the most commonly used method during these investigations, intrathecal (IT) injection can be equally efficacious for the central delivery of ligands. Importantly, intrathecal administration can optimize exploration of melanocortin receptors in the spinal cord. Herein, we investigate comparative IT and ICV administration of two melanocortin ligands, the synthetic MTII (Ac-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-NH 2 ) MC4R agonist and agouti-related peptide [AGRP(87-132)] MC4R inverse agonist/antagonist, on the same batch of age-matched mice in TSE metabolic cages undergoing a nocturnal satiated paradigm. To our knowledge, this is the first study to test how central administration of these ligands directly to the spinal cord affects energy homeostasis. Results showed, as expected, that MTII IT administration caused a decrease in food and water intake and an overall negative energy balance without affecting activity. As anticipated, IT administration of AGRP caused weight gain, increase of food/water intake, and increase respiratory exchange ratio (RER). Unexpectantly, the prolonged activity of AGRP was notably shorter (2 days) compared to mice given ICV injections of the same concentrations in previous studies (7 days or more).1-4 It appears that IT administration results in a more sensitive response that may be a good approach for testing synthetic compound potency values ranging in nanomolar to high micromolar in vitro EC 50 values. Indeed, our investigation reveals that the spine influences a different melanocortin response compared to the brain for the AGRP ligand. This study indicates that IT administration can be a useful technique for future metabolic studies using melanocortin ligands and highlights the importance of exploring the role of melanocortin receptors in the spinal cord.

  6. Implantation of a novel biologic and hybridized tissue engineered bioimplant in large tendon defect: an in vivo investigation.

    Science.gov (United States)

    Oryan, Ahmad; Moshiri, Ali; Parizi, Abdolhamid Meimandi; Maffulli, Nicola

    2014-02-01

    Surgical reconstruction of large Achilles tendon defects is technically demanding. There is no standard method, and tissue engineering may be a valuable option. We investigated the effects of 3D collagen and collagen-polydioxanone sheath (PDS) implants on a large tendon defect model in rabbits. Ninety rabbits were divided into three groups: control, collagen, and collagen-PDS. In all groups, 2 cm of the left Achilles tendon were excised and discarded. A modified Kessler suture was applied to all injured tendons to retain the gap length. The control group received no graft, the treated groups were repaired using the collagen only or the collagen-PDS prostheses. The bioelectrical characteristics of the injured areas were measured at weekly intervals. The animals were euthanized at 60 days after the procedure. Gross, histopathological and ultrastructural morphology and biophysical characteristics of the injured and intact tendons were investigated. Another 90 pilot animals were also used to investigate the inflammatory response and mechanism of graft incorporation during tendon healing. The control tendons showed severe hyperemia and peritendinous adhesion, and the gastrocnemius muscle of the control animals showed severe atrophy and fibrosis, with a loose areolar connective tissue filling the injured area. The tendons receiving either collagen or collagen-PDS implants showed lower amounts of peritendinous adhesion, hyperemia and muscle atrophy, and a dense tendon filled the defect area. Compared to the control tendons, application of collagen and collagen-PDS implants significantly improved water uptake, water delivery, direct transitional electrical current and tissue resistance to direct transitional electrical current. Compared to the control tendons, both prostheses showed significantly increased diameter, density and alignment of the collagen fibrils and maturity of the tenoblasts at ultrastructure level. Both prostheses influenced favorably tendon healing

  7. Disruption of in vivo chronic lymphocytic leukemia tumor-microenvironment interactions by ibrutinib - findings from an investigator initiated phase 2 study

    DEFF Research Database (Denmark)

    Niemann, Carsten U; Herman, Sarah E M; Maric, Irina

    2016-01-01

    PURPOSE: Chronic lymphocytic leukemia (CLL) cells depend on microenvironmental interactions for proliferation and survival that are at least partially mediated through B cell receptor (BCR) signaling. Ibrutinib, a Bruton's tyrosine kinase inhibitor, disrupts BCR signaling and leads to the egress...... of tumor cells from the microenvironment. While the on-target effects on CLL cells are well defined, the impact on the microenvironment is less well studied. We therefore sought to characterize the in vivo effects of ibrutinib on the tumor microenvironment. EXPERIMENTAL DESIGN: Patients received single...... agent ibrutinib on an investigator-initiated phase 2 trial. Serial blood and tissue samples were collected pre-treatment and during treatment. Changes in cytokine levels, cellular subsets and microenvironmental interactions were assessed. RESULTS: Serum levels of key chemokines and inflammatory...

  8. Biochemical investigations of the effect of NaF on mammalian cells. 2. Influence on biosynthesis of nucleic acids and proteins in mouse spleen cells ''in vivo''

    Energy Technology Data Exchange (ETDEWEB)

    Klein, W; Kocsis, F; Altmann, H

    1974-10-01

    The influence of NaF on the biosynthesis of nucleic acids and proteins was studied ''in vivo'' with ''Swiss mice''. Using a fluoride concentration of 0.4 ..mu..g/g no effect on DNA-repair appeared within 12 weeks, while DNA-, RNA- and protein-synthesis were suppressed after 10 weeks. Fluoride in a concentration of 3.5 ..mu..g/g gives a nearly complete inhibition of DNA-repair after 10 weeks, while DNA-, RNA- and protein-synthesis were suppressed to various degrees from week 2 until week 12. The phosphorylation of DNA- and RNA-precursors indicated results comparable to both synthesis, but investigating the particular kinase-steps of the phosphorylation, no specific effect on one of them can be localized significantly. (auth)

  9. In-vivo laser induced urethral stricture animal model for investigating the potential of LDR-brachytherapy

    Science.gov (United States)

    Sroka, Ronald; Lellig, Katja; Bader, Markus; Stief, Christian; Weidlich, Patrick; Wechsel, G.; Assmann, Walter; Becker, R.; Fedorova, O.; Khoder, Wael

    2015-02-01

    Purpose: Treatment of urethral strictures is a major challenge in urology. For investigation of different treatment methods an animal model was developed by reproducible induction of urethral strictures in rabbits to mimic the human clinical situation. By means of this model the potential of endoluminal LDR brachytherapy using β-irradiation as prophylaxis of recurrent urethral strictures investigated. Material and Methods: A circumferential urethral stricture was induced by energy deposition using laser light application (wavelength λ=1470 nm, 10 W, 10 s, applied energy 100 J) in the posterior urethra of anaesthetized New Zealand White male rabbits. The radial light emitting fiber was introduced by means of a children resectoscope (14F). The grade of urethral stricture was evaluated in 18 rabbits using videourethroscopy and urethrography at day 28 after stricture induction. An innovative catheter was developed based on a β-irradiation emitting foil containing 32P, which was wrapped around the application system. Two main groups (each n=18) were separated. The "internal urethrotomy group" received after 28days of stricture induction immediately after surgical urethrotomy of the stricture the radioactive catheter for one week in a randomized, controlled and blinded manner. There were 3 subgroups with 6 animals each receiving 0 Gy, 15 Gy and 30 Gy. In contrast animals from the "De Nuovo group" received directly after the stricture induction (day 0) the radioactive catheter also for the duration of one week divided into the same dose subgroups. In order to determine the radiation tolerance of the urethral mucosa, additional animals without any stricture induction received a radioactive catheter applying a total dose of 30 Gy (n=2) and 15 Gy (n=1). Cystourethrography and endoscopic examination of urethra were performed on all operation days for monitoring treatment progress. Based on these investigation a classification of the stricture size was performed and

  10. Investigation of left and right lateral fluid percussion injury in C57BL6/J mice: In vivo functional consequences.

    Science.gov (United States)

    Schurman, Lesley D; Smith, Terry L; Morales, Anthony J; Lee, Nancy N; Reeves, Thomas M; Phillips, Linda L; Lichtman, Aron H

    2017-07-13

    Although rodent models of traumatic brain injury (TBI) reliably produce cognitive and motor disturbances, behavioral characterization resulting from left and right hemisphere injuries remains unexplored. Here we examined the functional consequences of targeting the left versus right parietal cortex in lateral fluid percussion injury, on Morris water maze (MWM) spatial memory tasks (fixed platform and reversal) and neurological motor deficits (neurological severity score and rotarod). In the MWM fixed platform task, right lateral injury produced a small delay in acquisition rate compared to left. However, injury to either hemisphere resulted in probe trial deficits. In the MWM reversal task, left-right performance deficits were not evident, though left lateral injury produced mild acquisition and probe trial deficits compared to sham controls. Additionally, left and right injury produced similar neurological motor task deficits, impaired righting times, and lesion volumes. Injury to either hemisphere also produced robust ipsilateral, and modest contralateral, morphological changes in reactive microglia and astrocytes. In conclusion, left and right lateral TBI impaired MWM performance, with mild fixed platform acquisition rate differences, despite similar motor deficits, histological damage, and glial cell reactivity. Thus, while both left and right lateral TBI produce cognitive deficits, laterality in mouse MWM learning and memory merits consideration in the investigation of TBI-induced cognitive consequences. Copyright © 2017. Published by Elsevier B.V.

  11. THE BIAS (BULLYING IN SICILIAN SCHOOL PILOT STUDY: INVESTIGATING THE PREVALENCE OF BULLYING IN SCHOOL OF PALERMO CITY. A RESEARCH STUDY PROTOCOL.

    Directory of Open Access Journals (Sweden)

    Claudio Costantino

    2017-12-01

    Full Text Available Bullying in school, being a serious threat to physical and emotional health of children and adolescents all over the world, represents an important public health issue. In Italy, since 2007, the Italian Ministry of Education promotes activities to fight against and to prevent bullying in schools of all levels and, at the same time, also Health Authorities are trying to implement effective social-health responses. However, to date, the lack of consistent data, from national to local level, that could help in describing the problem in a proper manner, does not allow a systematic bullying surveillance and so also measuring the effectiveness of the public health strategy that could be implemented. The Bias pilot study’s aim is to evaluate the prevalence of bullying in a sample of schools in the city of Palermo, the largest in Sicily, and to investigate its characteristics in relation to different types of school. Finally, the Bias study aim to evaluate the feasibility of alternative methods for the detection of the prevalence of bullying phenomenon in schools. Here we present the research protocol and the questionnaires that will be used.

  12. Investigation of in vivo PIXE effect within superficial tumor model of high-Z metalnanoplatform for PIXE-based proton therapy

    International Nuclear Information System (INIS)

    Kim, Jong Ki; Seo, Seung Jun; Lee, Ju Hong

    2010-04-01

    Metallic nanoparticles (MNP) are able to release localized X-ray when activated with high energy proton beam by particle induced X-ray emissions (PIXE) effect. The exploitation of this phenomenon in the therapeutic irradiation of tumors has been investigated. PIXE-based X-ray emission directed at CT-26 tumor cells in vitro, when administered with either gold (average diameter, 2 nm and 13 nm) or iron (average diameter, 14 nm) nanoparticles, increased with MNP solution concentration over the range of 0.1-2 mg/mL. With irradiation by 45-MeV proton therapy (PT) beam, higher concentrations had a decreased cell survival fraction. An in vivo study with tumor regression assay demonstrated significant tumor dose enhancement, thought to be result of the PIXE effect when compared to conventional PT without MNP using a 45 MeV proton beam (p<0.01). These effects were observed for gold and iron MNP, injected in doses of 100-300mg/kg body weight into CT-26 mouse tumor models via tail vein. A therapeutic effective MNP concentration range, in vivo,was estimated at 30-79 μg/g tissue for both gold and iron nanoparticles. The tumor dose enhancement may compensate for an increase in entrance dose associated with conventional PT when treating large, solid tumors with a spread out Bragg peak (SOBP) technique. The use of combined high energy Bragg peak PT with PIXE generated by MNP, or PIXE alone may result in new treatment options for infiltrative metastatic tumors and other diffuse inflammatory diseases

  13. Ex vivo investigation of ocular tissue distribution following intravitreal administration of connexin43 mimetic peptide using the microdialysis technique and LC-MS/MS.

    Science.gov (United States)

    Bisht, Rohit; Mandal, Abhirup; Rupenthal, Ilva D; Mitra, Ashim K

    2016-12-01

    This study aimed to develop and evaluate an ex vivo eye model for intravitreal drug sampling and tissue distribution of connexin43 mimetic peptide (Cx43MP) following intravitreal injection using the microdialysis technique and LC-MS/MS. An LC-MS/MS method was developed, validated, and applied for quantification of Cx43MP in ocular tissues. Microdialysis probes were calibrated for in vitro recovery studies. Bovine eyes were fixed in a customized eye holder and after intravitreal injection of Cx43MP, microdialysis probes were implanted in the vitreous body. Vitreous samples were collected at particular time intervals over 24 h. Moreover, 24 and 48 h after intravitreal injection ocular tissues were collected, processed, and analyzed for Cx43MP concentrations using LC-MS/MS. The LC-MS/MS method showed good linearity (r 2  = 0.9991). The mean percent recovery for lower (LQC), medium (MQC), and higher quality control (HQC) (0.244, 3.906, and 125 μg/mL) was found to be 83.83, 84.92, and 94.52, respectively, with accuracy ranges between 96 and 99 % and limits of detection (LOD) and quantification (LOQ) of 0.122 and 0.412 μg/mL. The in vitro recovery of the probes was found to be over 80 %. As per microdialysis sample analysis, the Cx43MP concentration was found to increase slowly in the vitreous body up to 16 h and thereafter declined. After 48 h, the Cx43MP concentration was higher in vitreous, cornea, and retina compared to lens, iris, and aqueous humor. This ex vivo model may therefore be a useful tool to investigate intravitreal kinetics and ocular disposition of therapeutic molecules after intravitreal injection.

  14. In vivo and in vitro animal investigation of the effect of a mixture of herbal extracts from Tribulus terrestris and Cornus officinalis on penile erection.

    Science.gov (United States)

    Kam, Sung Chul; Do, Jung Mo; Choi, Jae Hwi; Jeon, Byeong Tak; Roh, Gu Seob; Hyun, Jae Seog

    2012-10-01

    Herbal preparations have long been used as folk remedies for erectile dysfunction (ED). This study examined the effects of Tribulus terrestris and Cornus officinalis extracts on relaxation of the smooth muscle of the corpus cavernosum (CC), their mechanisms of action, and the effects of oral administration of a mixture of the herbal extracts on penile erection. The relaxation effects and the mechanisms of action of T. terrestris extract, C. officinalis extract, and the mixture of both extracts on the rabbit CC were investigated in an organ bath. To evaluate whether the relaxation response of the CC shown in an organ bath occurs in vivo, intracavernous pressure (ICP) was calculated in rats after oral administration for a month. Additionally, adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3', 5'-cyclic monophosphate (cGMP) in the CC were measured using immunoassay. Smooth muscle relaxation was expressed as the percent decrease in precontraction induced by phenylephrine. ICP was assessed in rats after the oral administration of a mixture of both extracts for 1 month and changes in cGMP and cAMP concentrations were measured based on the concentration of the mixture of both extracts. T. terrestris extract, C. officinalis extract, and the mixture of both extracts showed concentration-dependent relaxation effects of the CC. In both the endothelium-removed group and N(G)-nitro-L-arginine methyl ester pretreatment group, T. terrestris extract inhibited relaxation. ICP measured after oral administration of the extract mixture for a month was higher than that measured in the control group, and a significant increase in cAMP was observed in the mixture group. T. terrestris extract and C. officinalis extract exhibited concentration-dependent relaxation in an organ bath. In the in vivo study of the extract mixture, ICP and cAMP was significantly potentiated. Accordingly, the mixture of T. terrestris extract and C. officinalis extract may improve erectile function.

  15. An investigation into the nutritional status of patients receiving an Enhanced Recovery After Surgery (ERAS) protocol versus standard care following Oesophagectomy.

    Science.gov (United States)

    Benton, Katie; Thomson, Iain; Isenring, Elisabeth; Mark Smithers, B; Agarwal, Ekta

    2018-06-01

    Enhanced Recovery After Surgery (ERAS) protocols have been effectively expanded to various surgical specialities including oesophagectomy. Despite nutrition being a key component, actual nutrition outcomes and specific guidelines are lacking. This cohort comparison study aims to compare nutritional status and adherence during implementation of a standardised post-operative nutritional support protocol, as part of ERAS, compared to those who received usual care. Two groups of patients undergoing resection of oesophageal cancer were studied. Group 1 (n = 17) underwent oesophagectomy between Oct 2014 and Nov 2016 during implementation of an ERAS protocol. Patients in group 2 (n = 16) underwent oesophagectomy between Jan 2011 and Dec 2012 prior to the implementation of ERAS. Demographic, nutritional status, dietary intake and adherence data were collected. Ordinal data was analysed using independent t tests, and categorical data using chi-square tests. There was no significant difference in nutrition status, dietary intake or length of stay following implementation of an ERAS protocol. Malnutrition remained prevalent in both groups at day 42 post surgery (n = 10, 83% usual care; and n = 9, 60% ERAS). A significant difference was demonstrated in adherence with earlier initiation of oral free fluids (p nutrition protocol, within an ERAS framework, results in earlier transition to oral intake; however, malnutrition remains prevalent post surgery. Further large-scale studies are warranted to examine individualised decision-making regarding nutrition support within an ERAS protocol.

  16. In vivo charge injection limits increased after 'unsafe' stimulation

    DEFF Research Database (Denmark)

    Meijs, Suzan; Sørensen, Søren; Rechendorff, Kristian

    2015-01-01

    was not observed with any of the stimulation protocols and no tissue damage was observed for the 20 mA – 200 Hz stimulation group. This indicates that the ‘safe potential window’ may not be applicable in vivo, as no damage was done stimulating with 20 mA at 200 Hz, while damage was done using the same current......The effect of unsafe stimulation on charge injection limits (Qinj) and pulsing capacitance (Cpulse) was investigated. Four stimulation protocols were applied: 20 mA – 200 and 400 Hz, 50 mA – 200 and 400 Hz. Increasing Qinj and Cpulse were observed for all stimulation protocols. Corrosion...

  17. Protocol for a randomised controlled trial investigating the effectiveness of an online e health application for the prevention of Generalised Anxiety Disorder

    Directory of Open Access Journals (Sweden)

    Kenardy Justin

    2010-03-01

    Full Text Available Abstract Background Generalised Anxiety Disorder (GAD is a highly prevalent psychiatric disorder. Effective prevention in young adulthood has the potential to reduce the prevalence of the disorder, to reduce disability and lower the costs of the disorder to the community. The present trial (the WebGAD trial aims to evaluate the effectiveness of an evidence-based online prevention website for GAD. Methods/Design The principal clinical question under investigation is the effectiveness of an online GAD intervention (E-couch using a community-based sample. We examine whether the effect of the intervention can be maximised by either human support, in the form of telephone calls, or by automated support through emails. The primary outcome will be a reduction in symptoms on the GAD-7 in the active arms relative to the non active intervention arms. Discussion The WebGAD trial will be the first to evaluate the use of an internet-based cognitive behavioural therapy (CBT program contrasted with a credible control condition for the prevention of GAD and the first formal RCT evaluation of a web-based program for GAD using community recruitment. In general, internet-based CBT programs have been shown to be effective for the treatment of other anxiety disorders such as Post Traumatic Stress Disorder, Social Phobia, Panic Disorder and stress in clinical trials; however there is no evidence for the use of internet CBT in the prevention of GAD. Given the severe shortage of therapists identified in Australia and overseas, and the low rates of treatment seeking in those with a mental illness, the successful implementation of this protocol has important practical outcomes. If found to be effective, WebGAD will provide those experiencing GAD with an easily accessible, free, evidence-based prevention tool which can be promoted and disseminated immediately. Trial Registration Controlled-trials.com: ISRCTN76298775

  18. An investigation into the role of alcohol in self-harm in rural Sri Lanka: a protocol for a multimethod, qualitative study.

    Science.gov (United States)

    Sørensen, Jane Brandt; Rheinländer, Thilde; Sørensen, Birgitte Refslund; Pearson, Melissa; Agampodi, Thilini; Siribaddana, Sisira; Konradsen, Flemming

    2014-10-07

    Sri Lanka has one of the highest suicide and self-harm rates in the world and although alcohol has been found to be a risk factor for self-harm in Sri Lanka, we know little about the connection between the two. This paper comprises a protocol for a qualitative study investigating alcohol's role in self-harm in rural Sri Lanka at three levels: the individual, community and policy level. The analysis will bring new understanding of the link between alcohol and self-harm in Sri Lanka, drawing on structural, cultural and social concepts. It will equip researchers, health systems and policy makers with vital information for developing strategies to address alcohol-related problems as they relate to self-harm. To capture the complexity of the link between alcohol and self-harm in the Anuradhapura district in the North Central Province in Sri Lanka, qualitative methods will be utilised. Specifically, the data will consist of serial narrative life-story interviews with up to 20 individuals who have non-fatally self-harmed and where alcohol directly or indirectly was involved in the incidence as well as with their significant others; observations in communities and families; six focus group discussions with community members; and key-informant interviews with 15-25 stakeholders who have a stake in alcohol distribution, marketing, policies, prevention and treatment as they relate to self-harm. The study has received ethical approval from the Ethical Review Committee of the Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka. A sensitive data collection technique will be used and ethical issues will be considered throughout the study. The results will be disseminated in scientific peer-reviewed articles in collaboration with Sri Lankan and other international research partners. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  19. Improving implementation of evidence-based practice in mental health service delivery: protocol for a cluster randomised quasi-experimental investigation of staff-focused values interventions.

    Science.gov (United States)

    Williams, Virginia; Oades, Lindsay G; Deane, Frank P; Crowe, Trevor P; Ciarrochi, Joseph; Andresen, Retta

    2013-07-02

    There is growing acceptance that optimal service provision for individuals with severe and recurrent mental illness requires a complementary focus on medical recovery (i.e., symptom management and general functioning) and personal recovery (i.e., having a 'life worth living'). Despite significant research attention and policy-level support, the translation of this vision of healthcare into changed workplace practice continues to elude. Over the past decade, evidence-based training interventions that seek to enhance the knowledge, attitudes, and skills of staff working in the mental health field have been implemented as a primary redress strategy. However, a large body of multi-disciplinary research indicates disappointing rates of training transfer. There is an absence of empirical research that investigates the importance of worker-motivation in the uptake of desired workplace change initiatives. 'Autonomy' is acknowledged as important to human effectiveness and as a correlate of workplace variables like productivity, and wellbeing. To our knowledge, there have been no studies that investigate purposeful and structured use of values-based interventions to facilitate increased autonomy as a means of promoting enhanced implementation of workplace change. This study involves 200 mental health workers across 22 worksites within five community-managed organisations in three Australian states. It involves cluster-randomisation of participants within organisation, by work site, to the experimental (values) condition, or the control (implementation). Both conditions receive two days of training focusing on an evidence-based framework of mental health service delivery. The experimental group receives a third day of values-focused intervention and 12 months of values-focused coaching. Well-validated self-report measures are used to explore variables related to values concordance, autonomy, and self-reported implementation success. Audits of work files and staff work samples

  20. Ex Vivo Expansion of Hematopoietic Stem Cells to Improve Engraftment in Stem Cell Transplantation.

    Science.gov (United States)

    Ko, Kap-Hyoun; Nordon, Robert; O'Brien, Tracey A; Symonds, Geoff; Dolnikov, Alla

    2017-01-01

    The efficient use of hematopoietic stem cells (HSC) for transplantation is often limited by the relatively low numbers of HSC collected. The ex vivo expansion of HSC for clinical use is a potentially valuable and safe approach to increase HSC numbers thereby increasing engraftment and reducing the risk of morbidity from infection. Here, we describe a protocol for the robust ex vivo expansion of human CD34(+) HSC isolated from umbilical cord blood. The protocol described can efficiently generate large numbers of HSC. We also describe a flow cytometry-based method using high-resolution division tracking to characterize the kinetics of HSC growth and differentiation. Utilizing the guidelines discussed, it is possible for investigators to use this protocol as presented or to modify it for their specific needs.

  1. Investigation of phytochemical contents, in vitro antioxidant and antibacterial behavior and in vivo anti-inflammatory potential of Ecballium elaterium methanol fruits extract

    Directory of Open Access Journals (Sweden)

    Samir FELHI

    Full Text Available Abstract Ecballium elaterium species are mostly used as therapeutic agents and food ingredient. The current work was designed to investigate phytochemical contents, antioxidant, antibacterial, and anti-inflammatory properties of methanol fruits extract of Ecballium elaterium. Good antioxidant activity was observed with IC50 values of 156 ± 4 and 377 ± 6 μg/mL for DPPH and ABTS, respectively, and EC50 of 126 ± 4 µg/mL for FRAP assays, which is related with their richness in total phenolic, flavonoid and condensed tannins contents. The results of antibacterial activity showed the effectiveness of methanol extract against Bacillus cereus with value of inhibition zone diameter of 15 ± 0 mm and a MIC and MBC values of 6 ± 0 and 12 ± 0 mg/mL, respectively. The in vivo anti-inflammatory effects have been also studied by carrageenan induced rat paw edema assay and the results revealed that a dose of 75 mg/kg induced a significant inhibition of 66.4% at 2 h. FT-IR spectral data justified the presence of biological functional groups such as ─OH, C─H, C─O, C─C and C=O. These results highlighted the potential using of Ecballium elaterium fruits extract as natural antimicrobial, antioxidant and anti-inflammatory agents for food applications and for the pharmaceutical industry.

  2. Cryptographic Protocols:

    DEFF Research Database (Denmark)

    Geisler, Martin Joakim Bittel

    cryptography was thus concerned with message confidentiality and integrity. Modern cryptography cover a much wider range of subjects including the area of secure multiparty computation, which will be the main topic of this dissertation. Our first contribution is a new protocol for secure comparison, presented...... implemented the comparison protocol in Java and benchmarks show that is it highly competitive and practical. The biggest contribution of this dissertation is a general framework for secure multiparty computation. Instead of making new ad hoc implementations for each protocol, we want a single and extensible...... in Chapter 2. Comparisons play a key role in many systems such as online auctions and benchmarks — it is not unreasonable to say that when parties come together for a multiparty computation, it is because they want to make decisions that depend on private information. Decisions depend on comparisons. We have...

  3. Peer Observations among Faculty in a College of Education: Investigating the Summative and Formative Uses of the Reformed Teaching Observation Protocol (RTOP)

    Science.gov (United States)

    Amrein-Beardsley, Audrey; Osborn Popp, Sharon E.

    2012-01-01

    Teacher educators piloted the use of the Reformed Teaching Observation Protocol (RTOP), a peer observation instrument associated with increases in learning in science and mathematics teacher education courses. Faculty participants received a series of trainings in RTOP use and rated each other's teaching during multiple peer observations. The…

  4. Investigating the burden of antibiotic resistance in ethnic minority groups in high-income countries: protocol for a systematic review and meta-analysis.

    Science.gov (United States)

    Lishman, Hannah; Aylin, Paul; Alividza, Vivian; Castro-Sanchez, Enrique; Chatterjee, Anuja; Mariano, Victor; Johnson, Alan P; Jeraj, Samir; Costelloe, Céire

    2017-12-11

    Antibiotic resistance (ABR) is an urgent problem globally, with overuse and misuse of antibiotics being one of the main drivers of antibiotic-resistant infections. There is increasing evidence that the burden of community-acquired infections such as urinary tract infections and bloodstream infections (both susceptible and resistant) may differ by ethnicity, although the reasons behind this relationship are not well defined. It has been demonstrated that socioeconomic status and ethnicity are often highly correlated with each other; however, it is not yet known whether accounting for deprivation completely explains any discrepancy seen in infection risk. There have currently been no systematic reviews summarising the evidence for the relationship between ethnicity and antibiotic resistance or prescribing. This protocol will outline how we will conduct this systematic literature review and meta-analysis investigating whether there is an association between patient ethnicity and (1) risk of antibiotic-resistant infections or (2) levels of antibiotic prescribing in high-income countries. We will search PubMed/MEDLINE, EMBASE, Global Health, Scopus and CINAHL using MESH terms where applicable. Two reviewers will conduct title/abstract screening, data extraction and quality assessment independently. The Critical Appraisal Skills Programme (CASP) checklist will be used for cohort and case-control studies, and the Cochrane collaboration's risk of bias tool will be used for randomised control trials, if they are included. Meta-analyses will be performed by calculating the minority ethnic group to majority ethnic group odds ratios or risk ratios for each study and presenting an overall pooled odds ratio for the two outcomes. The Grading of Recommendations, Assessments, Development and Evaluation (GRADE) approach will be used to assess the overall quality of the body of evidence. In this systematic review and meta-analysis, we will aim to collate the available evidence of

  5. A study protocol of a randomised controlled trial to investigate if a community based strength training programme improves work task performance in young adults with Down syndrome

    Directory of Open Access Journals (Sweden)

    Taylor Nicholas F

    2010-03-01

    Full Text Available Abstract Background Muscle strength is important for young people with Down syndrome as they make the transition to adulthood, because their workplace activities typically emphasise physical rather than cognitive skills. Muscle strength is reduced up to 50% in people with Down syndrome compared to their peers without disability. Progressive resistance training improves muscle strength and endurance in people with Down syndrome. However, there is no evidence on whether it has an effect on work task performance or physical activity levels. The aim of this study is to investigate if a student-led community-based progressive resistance training programme can improve these outcomes in adolescents and young adults with Down syndrome. Methods A randomised controlled trial will compare progressive resistance training with a control group undertaking a social programme. Seventy adolescents and young adults with Down syndrome aged 14-22 years and mild to moderate intellectual disability will be randomly allocated to the intervention or control group using a concealed method. The intervention group will complete a 10-week, twice a week, student-led progressive resistance training programme at a local community gymnasium. The student mentors will be undergraduate physiotherapy students. The control group will complete an arts/social programme with a student mentor once a week for 90 minutes also for 10 weeks to control for the social aspect of the intervention. Work task performance (box stacking, pail carry, muscle strength (1 repetition maximum for chest and leg press and physical activity (frequency, duration, intensity over 7-days will be assessed at baseline (Week 0, following the intervention (Week 11, and at 3 months post intervention (Week 24 by an assessor blind to group allocation. Data will be analysed using ANCOVA with baseline measures as covariates. Discussion This paper outlines the study protocol for a randomised controlled trial on the

  6. Investigating fractional exhaled nitric oxide (FeNO) in chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap (ACO): a scoping review protocol.

    Science.gov (United States)

    Mostafavi-Pour-Manshadi, Seyed-Mohammad-Yousof; Naderi, Nafiseh; Barrecheguren, Miriam; Dehghan, Abolfazl; Bourbeau, Jean

    2017-12-21

    During the last decade, many articles have been published, including reviews on fractional exhaled nitric oxide (FeNO) use and utility in clinical practice and for monitoring and identifying eosinophilic airway inflammation, especially in asthma, and evaluating corticosteroid responsiveness. However, the exact role of FeNO in patients with chronic obstructive pulmonary disease (COPD) and its ability to distinguish patients with COPD and those having concomitant asthma, that is, asthma-COPD overlap (ACO) is still unclear and needs to be defined. Due to the broad topics of FeNO in chronic airway disease, we undertook a scoping review. The present article describes the protocol of a scoping review of peer-reviewed published literature specific to FeNO in COPD/ACO over the last decade. We used Joanna Briggs Institute Reviewers' Manual scoping review methodology as well as Levac et al 's and Arksey et al 's framework as guides. We searched a variety of databases, including Medline, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, Web of Science, and BioSciences Information Service (BIOSIS) on 29 June 2016. Additional studies will be recognised by exploring the reference list of identified eligible studies. Screening of eligible studies will be independently performed by two reviewers and any disagreement will be solved by the third reviewer. We will analyse the gathered data from article bibliographies and abstracts. To investigate the body of published studies regarding the role of FeNO in patients with COPD and its usefulness in the clinical setting, a scoping review can be used as a modern and pioneer model, which does not need ethics approval. By this review, new insights for conducting new research specific to FeNO in COPD/ACO population will emerge. The results of this study will be reported in the scientific meetings and conferences, which aim to provide information to the clinicians, primary care providers and basic

  7. Immunochemical protocols

    National Research Council Canada - National Science Library

    Pound, John D

    1998-01-01

    ... easy and important refinements often are not published. This much anticipated 2nd edition of Immunochemzcal Protocols therefore aims to provide a user-friendly up-to-date handbook of reliable techniques selected to suit the needs of molecular biologists. It covers the full breadth of the relevant established immunochemical methods, from protein blotting and immunoa...

  8. Use of WGS data for investigation of a long-term NDM-1-producing Citrobacter freundii outbreak and secondary in vivo spread of blaNDM-1 to Escherichia coli, Klebsiella pneumoniae and Klebsiella oxytoca

    DEFF Research Database (Denmark)

    Hammerum, Anette M; Hansen, Frank; Linde Nielsen, Hans

    2016-01-01

    Objectives An outbreak of NDM-1-producing Citrobacter freundii and possible secondary in vivo spread of blaNDM-1 to other Enterobacteriaceae were investigated. Methods From October 2012 to March 2015, meropenem-resistant Enterobacteriaceae were detected in 45 samples from seven patients at Aalborg...... of recent travel abroad and the source of the blaNDM-1 plasmid was unknown. Conclusions To our knowledge, this is the first report of an NDM-1-producing C. freundii outbreak and secondary in vivo spread of an IncA/C2 plasmid with blaNDM-1 to other Enterobacteriaceae....

  9. Synthesis and biodistribution of novel magnetic-poly(HEMA-APH) nanopolymer radiolabeled with iodine-131 and investigation its fate in vivo for cancer therapy

    Science.gov (United States)

    Avcıbaşı, Uğur; Avcıbaşı, Nesibe; Akalın, Hilmi Arkut; Ediz, Melis; Demiroğlu, Hasan; Gümüşer, Fikriye Gül; Özçalışkan, Emir; Türkcan, Ceren; Uygun, Deniz Aktaş; Akgöl, Sinan

    2013-10-01

    Herein, we investigated the biological uptake, distribution, and radiopharmaceutical potential of a novel molecule based on 2-hydroxyethyl methacrylate (HEMA) and anilinephtalein (APH) in the metabolism of Albino Wistar rats. In order to achieve this, we synthesized APH using organic synthesis methods and copolymerized APH with HEMA using a common polymerization method, surfactant-free emulsion polymerization. In the presence of Fe3O4 particles, we obtained a new generation magnetic-nano-scale polymer, magnetic-poly(HEMA-APH). This new molecule was chemically identified and approved by several characterization methods using Fourier transform infrared spectroscopy, scanning electron microscope, energy dispersive X-ray spectroscopy, electron spin resonance, atomic force microscope, and Zeta particle-size analysis. To evaluate the biological activity in live metabolism and anti-cancer potential of mag-poly(HEMA-APH), molecule was radioiodinated by a widely used labeling technique, iodogen method, with a gamma diffuser radionuclide, 131I. Thin-layer radiochromatography experiments demonstrated that 131I binded to nanopolymer with the labeling yield of 90 %. Lipophilicity and stability experiments were conducted to determine the condition of cold and labeled mag-poly(HEMA-APH) in rat blood and lipid medium. Results demonstrated that radioiodinated molecule stayed as an intact complex in rat metabolism for 24 h and experimental lipophilicity was determined as 0.12 ± 0.02. In vivo results obtained by imaging and biological distribution experiments indicated that mag-poly(HEMA-APH) labeled with 131I [131I-mag-poly(HEMA-APH)] highly incorporated into tissues of the uterus, the ovarian, the prostate, and the lungs in rat metabolism. Based on these results, it may be evaluated that novel mag-poly(HEMA-APH) molecule labeled with 131I is a compound which has a significant potential for being used as an anti-cancer agent. Certain results can only be obtained whether this

  10. Disruption of in vivo Chronic Lymphocytic Leukemia Tumor-Microenvironment Interactions by Ibrutinib--Findings from an Investigator-Initiated Phase II Study.

    Science.gov (United States)

    Niemann, Carsten U; Herman, Sarah E M; Maric, Irina; Gomez-Rodriguez, Julio; Biancotto, Angelique; Chang, Betty Y; Martyr, Sabrina; Stetler-Stevenson, Maryalice; Yuan, Constance M; Calvo, Katherine R; Braylan, Raul C; Valdez, Janet; Lee, Yuh Shan; Wong, Deanna H; Jones, Jade; Sun, Clare; Marti, Gerald E; Farooqui, Mohammed Z H; Wiestner, Adrian

    2016-04-01

    Chronic lymphocytic leukemia (CLL) cells depend on microenvironmental interactions for proliferation and survival that are at least partially mediated through B-cell receptor (BCR) signaling. Ibrutinib, a Bruton tyrosine kinase inhibitor, disrupts BCR signaling and leads to the egress of tumor cells from the microenvironment. Although the on-target effects on CLL cells are well defined, the impact on the microenvironment is less well studied. We therefore sought to characterize the in vivo effects of ibrutinib on the tumor microenvironment. Patients received single-agent ibrutinib on an investigator-initiated phase II trial. Serial blood and tissue samples were collected pretreatment and during treatment. Changes in cytokine levels, cellular subsets, and microenvironmental interactions were assessed. Serum levels of key chemokines and inflammatory cytokines decreased significantly in patients on ibrutinib. Furthermore, ibrutinib treatment decreased circulating tumor cells and overall T-cell numbers. Most notably, a reduced frequency of the Th17 subset of CD4(+)T cells was observed concurrent with reduced expression of activation markers and PD-1 on T cells. Consistent with direct inhibition of T cells, ibrutinib inhibited Th17 differentiation of murine CD4(+)T cells in vitro Finally, in the bone marrow microenvironment, we found that ibrutinib disaggregated the interactions of macrophages and CLL cells, inhibited secretion of CXCL13, and decreased the chemoattraction of CLL cells. In conjunction with inhibition of BCR signaling, these changes in the tumor microenvironment likely contribute to the antitumor activity of ibrutinib and may impact the efficacy of immunotherapeutic strategies in patients with CLL. See related commentary by Bachireddy and Wu, p. 1547. ©2015 American Association for Cancer Research.

  11. Disruption of in vivo chronic lymphocytic leukemia tumor-microenvironment interactions by ibrutinib – findings from an investigator initiated phase 2 study

    Science.gov (United States)

    Niemann, Carsten U.; Herman, Sarah E. M.; Maric, Irina; Gomez-Rodriguez, Julio; Biancotto, Angelique; Chang, Betty Y.; Martyr, Sabrina; Stetler-Stevenson, Maryalice; Yuan, Constance; Calvo, Katherine R.; Braylan, Raul C.; Valdez, Janet; Lee, Yuh Shan; Wong, Deanna H.; Jones, Jade; Sun, Clare C. L.; Marti, Gerald E.; Farooqui, Mohammed Z.; Wiestner, Adrian

    2016-01-01

    Purpose Chronic lymphocytic leukemia (CLL) cells depend on microenvironmental interactions for proliferation and survival that are at least partially mediated through B cell receptor (BCR) signaling. Ibrutinib, a Bruton’s tyrosine kinase inhibitor, disrupts BCR signaling and leads to the egress of tumor cells from the microenvironment. While the on-target effects on CLL cells are well defined, the impact on the microenvironment is less well studied. We therefore sought to characterize the in vivo effects of ibrutinib on the tumor microenvironment. Experimental Design Patients received single agent ibrutinib on an investigator-initiated phase 2 trial. Serial blood and tissue samples were collected pre-treatment and during treatment. Changes in cytokine levels, cellular subsets and microenvironmental interactions were assessed. Results Serum levels of key chemokines and inflammatory cytokines decreased significantly in patients on ibrutinib. Further, ibrutinib treatment decreased circulating tumor cells and overall T cell numbers. Most notably, a reduced frequency of the Th17 subset of CD4+ T cells was observed concurrent with reduced activation markers and expression of PD-1 on T cells. Consistent with direct inhibition of T cells, ibrutinib inhibited Th17 differentiation of murine CD4+ T cells in vitro. Lastly, in the bone marrow microenvironment, we found that ibrutinib disaggregated the interactions of macrophages and CLL cells, inhibited secretion of CXCL13 and decreased the chemoattraction of CLL cells. Conclusions In conjunction with inhibition of BCR signaling, these changes in the tumor microenvironment likely contribute to the anti-tumor activity of ibrutinib and may impact the efficacy of immunotherapeutic strategies in patients with CLL. PMID:26660519

  12. Investigation of 3′-debenzoyl-3′-(3-([124I]-iodobenzoyl))paclitaxel analog as a radio-tracer to study multidrug resistance in vivo

    International Nuclear Information System (INIS)

    Sajjad, M.; Riaz, U.; Yao, R.; Bernacki, R.J.; Abouzied, M.; Erb, D.A.; Chaudhary, N.D.; Veith, J.M.; Georg, G.I.; Nabi, H.A.

    2012-01-01

    A study was carried out to identify a suitable radioactive paclitaxel analog and to use it to investigate tumor multidrug resistance in vivo. 3′-Debenzoyl-3′-(3-([ 124 I]-iodobenzoyl))paclitaxel was prepared by aromatic iodination of 3′-debenzoyl-3′-(3-trimethylstannylbenzoyl)paclitaxel. Uptake of the labeled paclitaxel analog in nude mice bearing tumor with the paclitaxel sensitive cancer cell lines MCF7 and MDA-435/LCC6(WT), and multidrug resistant cell lines NCI/ADR-RES and MDA-435/LCC6(MDR), was studied. There was no difference in drug level between the sensitive and resistant MDA-435/LCC6 tumors at 6 h post-injection. However, at 6 h, there was a significant increase in drug level for the MCF7 tumor as compared with the NCI/ADR-RES tumor, presumably due to increased drug retention. At 24 h, drug uptake/retention was significantly higher in both sensitive tumor cell lines as compared to their drug resistant counterparts. Pretreatment of mice with MDR transport modulators, Cyclosporine or tRA 96029, did not increase the level of labeled paclitaxel analog in the drug resistant MDA-435/LCC6(MDR) tumor. On the other hand, at 24 h Cyclosporine apparently increased analog level in the drug sensitive MDA-435/LCC6(WT) tumor, aiding drug imaging studies. - Highlights: ► 3′-Debenzoyl-3′-(3-iodobenzoyl)paclitaxel cytotoxicity was comparable to paclitaxel. ► 3′-Debenzoyl-3′-(3-([ 124 I]-iodobenzoyl)paclitaxel was synthesized. ► Uptake of the drug was higher in sensitive tumor compared to the resistant tumor. ► The Pgp-modulators had a positive effect on drug-sensitive tumor. ► The sensitive tumor was visible in images obtained using micoPET.

  13. Investigation of moxifloxacin loaded chitosan–dextran nanoparticles for topical instillation into eye: In-vitro and ex-vivo evaluation

    Science.gov (United States)

    Kaskoos, Raad A.

    2014-01-01

    Introduction: Management of ocular surface disease by conventional formulation is limited by poor residence of drug at cul-de-sac of eye. To overcome this limitation, prolonged released mucoadhesive chitosan (CS)–dextran sulfate (DS) nanoparticles (NPs) were investigated for the prolonged topical ophthalmic delivery of moxifloxacin (Mox). Methods: Formulation was optimized by 3-factors (CS, DS, and Mox concentration), 3-levels (−1, 0, +1) Box-Behnken design. Optimized formulation was characterized for various in-vitro attributes, including particles size, zeta potential, shape and morphology, in-vitro release profile, corneal permeation, corneal retention, ocular tolerance test as well as antimicrobial activity. Results: Average hydrodynamic particle size of statistically optimized formulation was found to be 279.18 ± 15.63 nm with good polydispersity index, 0.367 ± 0.016 and positive zeta potential, +31.23 ± 1.32. NPs showed entrapment efficiency, 72.82 ± 3.6% and transmission electron microscopic analysis revealed a spherical shape of particles. Formulation exhibited biphasic release profile with an initial fast release (≈25% in 1st h) followed by sustained release (≈95% in next 24 h) following Korsmeyer–Peppas model with a nonFickian diffusion process. Mox loaded CS-DS NPs exhibited a significantly higher (P < 0.01), approximately 1.8-fold transcorneal permeation as well as significantly higher corneal retention (P < 0.01), around 4-5-fold when compared to free solution. Developed formulation exhibited safety profile comparable to normal saline, which was revealed by ocular tolerance test (Hen's egg test-chorioallantoic membrane). Mox-CS-DS NPs exhibited significantly high (P < 0.01) antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa. Conclusion: In-vitro and ex-vivo studies revealed that developed formulation could be a potential substitute for prolonged topical ocular delivery. PMID:25426437

  14. Complementarity of magnetic resonance spectroscopy, positron emission tomography and single photon emission tomography for the in vivo investigation of human cardiac metabolism and neurotransmission

    International Nuclear Information System (INIS)

    Syrota, A.; Jehenson, P.

    1991-01-01

    PET is quantitative and very sensitive, and therefore only tracer amounts of molecules need to be injected. It allows neurotransmitters and receptors to be studied and a global view of metabolism to oxygen consumption, glucose and fatty acid utilization to be obtained. SPET also has good sensitivity, but uses gamma-emitting isotopes of heteroatoms. Their longer half-lives allow follow-up for hours or days. MRS is based on stable elements with high or low natural abundance. It has very low sensitivity and only millimolar concentrations of substrates can be detected, but various parts of metabolism can be studied. The in vivo measurement of myocardial concentration of substances has many problems that are common to all three techniques. The complementarity of the techniques is illustrated by their applications to the study of cardiac metabolism. For instance, the energy metabolism can be studied by 31 P-MRS, which detects the high-energy compounds ATP and phosphocreatine, and 13 C-MRS yields information on the tricarboxylic acid cycle activity. PET and SPET allow the utilization of fatty acids, the normal fuels of the heart, to be studied. During ischaemia, PET with 18 F-fluorodeoxyglucose can determine the glucose consumption and 1 H-MRS shows the increase in lactic acid, reflecting anaerobic glycolysis. Comparison of the use of acetate labelled with 11 C for PET or 13 C for MRS shows the potentials and limitations of each technique. Myocardial perfusion can be evaluated directly with various PET tracers or indirectly with thallium 201 or various technetium-99m-labelled tracers by SPET. No MRS marker of perfusion is so far clinically available. Mainly SPET and PET are used clinically for the investigation of ischaemic heart disease as well as cardiomyophathies, but some initial results using 31 P-MRS are being obtained. (orig./MG)

  15. Comparison of In-Vitro and Ex-Vivo Wound Healing Assays for the Investigation of Diabetic Wound Healing and Demonstration of a Beneficial Effect of a Triterpene Extract.

    Directory of Open Access Journals (Sweden)

    Christopher Ueck

    Full Text Available Diabetes mellitus is a frequent cause for chronic, difficult-to-treat wounds. New therapies for diabetic wounds are urgently needed and in-vitro or ex-vivo test systems are essential for the initial identification of new active molecules. The aim of this study is to compare in-vitro and ex-vivo test systems for their usability for early drug screening and to investigate the efficacy of a birch bark triterpene extract (TE that has been proven ex-vivo and clinically to accelerate non-diabetic wound healing (WH, in a diabetic context. We investigated in-vitro models for diabetic WH, i.e. scratch assays with human keratinocytes from diabetic donors or cultured under hyperglycaemic conditions and a newly developed porcine ex-vivo hyperglycaemic WH model for their potential to mimic delayed diabetic WH and for the influence of TE in these test systems. We show that keratinocytes from diabetic donors often fail to exhibit significantly delayed WH. For cells under hyperglycaemic conditions significant decrease is observed but is influenced by choice of medium and presence of supplements. Also, donor age plays a role. Interestingly, hyperglycaemic effects are mainly hyperosmolaric effects in scratch assays. Ex-vivo models under hyperglycaemic conditions show a clear and substantial decrease of WH, and here both glucose and hyperosmolarity effects are involved. Finally, we provide evidence that TE is also beneficial for ex-vivo hyperglycaemic WH, resulting in significantly increased length of regenerated epidermis to 188±16% and 183±11% (SEM; p<0.05 compared to controls when using two different TE formulations. In conclusion, our results suggest that microenvironmental influences are important in WH test systems and that therefore the more complex hyperglycaemic ex-vivo model is more suitable for early drug screening. Limitations of the in-vitro and ex-vivo models are discussed. Furthermore our data recommend TE as a promising candidate for in-vivo

  16. Preparation, characterization, and in vitro and in vivo investigation of chitosan-coated poly (d,l-lactide-co-glycolide nanoparticles for intestinal delivery of exendin-4

    Directory of Open Access Journals (Sweden)

    Wang M

    2013-03-01

    Full Text Available Mengshu Wang,1* Yong Zhang,1* Jiao Feng,1 Tiejun Gu,1 Qingguang Dong,1 Xu Yang,2 Yanan Sun,1 Yongge Wu,1 Yan Chen,1 Wei Kong1 1National Engineering Laboratory for AIDS Vaccine, College of Life Science, Jilin University, Changchun, People’s Republic of China; 2BCHT Biopharm Co, Ltd, Changchun, People’s Republic of China*These authors contributed equally to this workBackground: Exendin-4 is an incretin mimetic agent approved for type 2 diabetes treatment. However, the required frequent injections restrict its clinical application. Here, the potential use of chitosan-coated poly (d,l-lactide-co-glycolide (CS-PLGA nanoparticles was investigated for intestinal delivery of exendin-4.Methods and results: Nanoparticles were prepared using a modified water–oil–water (w/o/w emulsion solvent-evaporation method, followed by coating with chitosan. The physical properties, particle size, and cell toxicity of the nanoparticles were examined. The cellular uptake mechanism and transmembrane permeability were performed in Madin-Darby canine kidney-cell monolayers. Furthermore, in vivo intraduodenal administration of exendin-4-loaded nanoparticles was carried out in rats. The PLGA nanoparticle coating with chitosan led to a significant change in zeta potential, from negative to positive, accompanied by an increase in particle size of ~30 nm. Increases in both the molecular weight and degree of deacetylation of chitosan resulted in an observable increase in zeta potential but no apparent change in the particle size of ~300 nm. Both unmodified PLGA and chitosan-coated nanoparticles showed only slight cytotoxicity. Use of different temperatures and energy depletion suggested that the cellular uptake of both types of nanoparticles was energy-dependent. Further investigation revealed that the uptake of PLGA nanoparticles occurred via caveolin-mediated endocytosis and that of CS-PLGA nanoparticles involved both macropinocytosis and clathrin-mediated endocytosis

  17. Preparation, characterization, and in vitro and in vivo investigation of chitosan-coated poly (d,l-lactide-co-glycolide) nanoparticles for intestinal delivery of exendin-4

    Science.gov (United States)

    Wang, Mengshu; Zhang, Yong; Feng, Jiao; Gu, Tiejun; Dong, Qingguang; Yang, Xu; Sun, Yanan; Wu, Yongge; Chen, Yan; Kong, Wei

    2013-01-01

    Background Exendin-4 is an incretin mimetic agent approved for type 2 diabetes treatment. However, the required frequent injections restrict its clinical application. Here, the potential use of chitosan-coated poly (d,l-lactide-co-glycolide) (CS-PLGA) nanoparticles was investigated for intestinal delivery of exendin-4. Methods and results Nanoparticles were prepared using a modified water–oil–water (w/o/w) emulsion solvent-evaporation method, followed by coating with chitosan. The physical properties, particle size, and cell toxicity of the nanoparticles were examined. The cellular uptake mechanism and transmembrane permeability were performed in Madin-Darby canine kidney-cell monolayers. Furthermore, in vivo intraduodenal administration of exendin-4-loaded nanoparticles was carried out in rats. The PLGA nanoparticle coating with chitosan led to a significant change in zeta potential, from negative to positive, accompanied by an increase in particle size of ~30 nm. Increases in both the molecular weight and degree of deacetylation of chitosan resulted in an observable increase in zeta potential but no apparent change in the particle size of ~300 nm. Both unmodified PLGA and chitosan-coated nanoparticles showed only slight cytotoxicity. Use of different temperatures and energy depletion suggested that the cellular uptake of both types of nanoparticles was energy-dependent. Further investigation revealed that the uptake of PLGA nanoparticles occurred via caveolin-mediated endocytosis and that of CS-PLGA nanoparticles involved both macropinocytosis and clathrin-mediated endocytosis, as evidenced by using endocytic inhibitors. However, under all conditions, CS-PLGA nanoparticles showed a greater potential to be transported into cells, as shown by flow cytometry and confocal microscopy. Transmembrane permeability analysis showed that unmodified and modified PLGA nanoparticles could improve the transport of exendin-4 by up to 8.9- and 16.5-fold, respectively

  18. Investigating the Impact of Hearing Aid Use and Auditory Training on Cognition, Depressive Symptoms, and Social Interaction in Adults With Hearing Loss: Protocol for a Crossover Trial.

    Science.gov (United States)

    Nkyekyer, Joanna; Meyer, Denny; Blamey, Peter J; Pipingas, Andrew; Bhar, Sunil

    2018-03-23

    Sensorineural hearing loss is the most common sensory deficit among older adults. Some of the psychosocial consequences of this condition include difficulty in understanding speech, depression, and social isolation. Studies have shown that older adults with hearing loss show some age-related cognitive decline. Hearing aids have been proven as successful interventions to alleviate sensorineural hearing loss. In addition to hearing aid use, the positive effects of auditory training-formal listening activities designed to optimize speech perception-are now being documented among adults with hearing loss who use hearing aids, especially new hearing aid users. Auditory training has also been shown to produce prolonged cognitive performance improvements. However, there is still little evidence to support the benefits of simultaneous hearing aid use and individualized face-to-face auditory training on cognitive performance in adults with hearing loss. This study will investigate whether using hearing aids for the first time will improve the impact of individualized face-to-face auditory training on cognition, depression, and social interaction for adults with sensorineural hearing loss. The rationale for this study is based on the hypothesis that, in adults with sensorineural hearing loss, using hearing aids for the first time in combination with individualized face-to-face auditory training will be more effective for improving cognition, depressive symptoms, and social interaction rather than auditory training on its own. This is a crossover trial targeting 40 men and women between 50 and 90 years of age with either mild or moderate symmetric sensorineural hearing loss. Consented, willing participants will be recruited from either an independent living accommodation or via a community database to undergo a 6-month intensive face-to-face auditory training program (active control). Participants will be assigned in random order to receive hearing aid (intervention) for

  19. Synthesis and biodistribution of novel magnetic-poly(HEMA-APH) nanopolymer radiolabeled with iodine-131 and investigation its fate in vivo for cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Avc Latin-Small-Letter-Dotless-I bas Latin-Small-Letter-Dotless-I , Ugur, E-mail: uguravcibasi@yahoo.com [Celal Bayar University, Department of Chemistry, Faculty of Arts and Science (Turkey); Avc Latin-Small-Letter-Dotless-I bas Latin-Small-Letter-Dotless-I , Nesibe [Ege University, Ege Higher Vocational School (Turkey); Akal Latin-Small-Letter-Dotless-I n, Hilmi Arkut; Ediz, Melis; Demiroglu, Hasan [Celal Bayar University, Department of Chemistry, Faculty of Arts and Science (Turkey); Guemueser, Fikriye Guel [Celal Bayar University, Department of Nuclear Medicine, Faculty of Medicine (Turkey); Oezcal Latin-Small-Letter-Dotless-I skan, Emir; Tuerkcan, Ceren [Ege University, Department of Biochemistry, Faculty of Science (Turkey); Uygun, Deniz Aktas [Adnan Menderes University, Department of Chemistry, Faculty of Arts and Science (Turkey); Akgoel, Sinan [Ege University, Department of Biochemistry, Faculty of Science (Turkey)

    2013-10-15

    Herein, we investigated the biological uptake, distribution, and radiopharmaceutical potential of a novel molecule based on 2-hydroxyethyl methacrylate (HEMA) and anilinephtalein (APH) in the metabolism of Albino Wistar rats. In order to achieve this, we synthesized APH using organic synthesis methods and copolymerized APH with HEMA using a common polymerization method, surfactant-free emulsion polymerization. In the presence of Fe{sub 3}O{sub 4} particles, we obtained a new generation magnetic-nano-scale polymer, magnetic-poly(HEMA-APH). This new molecule was chemically identified and approved by several characterization methods using Fourier transform infrared spectroscopy, scanning electron microscope, energy dispersive X-ray spectroscopy, electron spin resonance, atomic force microscope, and Zeta particle-size analysis. To evaluate the biological activity in live metabolism and anti-cancer potential of mag-poly(HEMA-APH), molecule was radioiodinated by a widely used labeling technique, iodogen method, with a gamma diffuser radionuclide, {sup 131}I. Thin-layer radiochromatography experiments demonstrated that {sup 131}I binded to nanopolymer with the labeling yield of 90 %. Lipophilicity and stability experiments were conducted to determine the condition of cold and labeled mag-poly(HEMA-APH) in rat blood and lipid medium. Results demonstrated that radioiodinated molecule stayed as an intact complex in rat metabolism for 24 h and experimental lipophilicity was determined as 0.12 {+-} 0.02. In vivo results obtained by imaging and biological distribution experiments indicated that mag-poly(HEMA-APH) labeled with {sup 131}I [{sup 131}I-mag-poly(HEMA-APH)] highly incorporated into tissues of the uterus, the ovarian, the prostate, and the lungs in rat metabolism. Based on these results, it may be evaluated that novel mag-poly(HEMA-APH) molecule labeled with {sup 131}I is a compound which has a significant potential for being used as an anti-cancer agent. Certain

  20. 177Lu-labeled HPMA copolymers utilizing cathepsin B and S cleavable linkers: Synthesis, characterization and preliminary in vivo investigation in a pancreatic cancer model

    International Nuclear Information System (INIS)

    Ogbomo, Sunny M.; Shi, Wen; Wagh, Nilesh K.; Zhou, Zhengyuan; Brusnahan, Susan K.; Garrison, Jered C.

    2013-01-01

    Introduction: A major barrier to the advancement of therapeutic nanomedicines has been the non-target toxicity caused by the accumulation of the drug delivery systems in organs associated with the reticuloendothelial system, particularly the liver and spleen. Herein, we report the development of peptide based metabolically active linkers (MALs) that are enzymatically cleaved by cysteine cathepsin B and S, two proteases highly expressed in the liver and spleen. The overall goal of this approach is to utilize the MALs to lower the non-target retention and toxicity of radiolabeled drug delivery systems, thus resulting in higher diagnostic and radiotherapeutic efficacy. Methods: In this study three MALs (MAL0, MAL1 and MAL2) were investigated. MAL1 and MAL2 are composed of known substrates of cathepsin B and S, respectively, while MAL0 is a non-cleavable control. Both MAL1 and MAL2 were shown to undergo enzymatic cleavage with the appropriate cathepsin protease. Subsequent to conjugation to the HPMA copolymer and radiolabeling with 177 Lu, the peptide–polymer conjugates were renamed 177 Lu-metabolically active copolymers ( 177 Lu-MACs) with the corresponding designations: 177 Lu-MAC0, 177 Lu-MAC1 and 177 Lu-MAC2. Results: In vivo evaluation of the 177 Lu-MACs was performed in an HPAC human pancreatic cancer xenograft mouse model. 177 Lu-MAC1 and 177 Lu-MAC2 demonstrated 3.1 and 2.1 fold lower liver retention, respectively, compared to control ( 177 Lu-MAC0) at 72 h post-injection. With regard to spleen retention, 177 Lu-MAC1 and 177 Lu-MAC2 each exhibited a nearly fourfold lower retention, relative to control, at the 72 h time point. However, the tumor accumulation of the 177 Lu-MAC0 was two to three times greater than 177 Lu-MAC1 and 177 Lu-MAC2 at the same time point. The MAL approach demonstrated the capability of substantially reducing the non-target retention of the 177 Lu-labeled HPMA copolymers. Conclusions: While further studies are needed to optimize the

  1. Evaluation of non-radioactive endpoints of ex vivo local lymph node assay-BrdU to investigate select contact sensitizers.

    Science.gov (United States)

    Ulker, Ozge Cemiloglu; Ates, Ilker; Atak, Aysegul; Karakaya, Asuman

    2013-01-01

    The present study sought to verify the utility of the non-radioactive endpoints LLNA BrdU (5-bromo-2'-deoxyuridine) ex vivo incorporation and cytokine release using auricular lymph node cells isolated from BALB/c mice topically treated with a strong (formaldehyde or p-phenylene-diamine [PPD]), moderate sensitizer (cinnamal), or weak sensitizer (eugenol). Stimulation index (SI) and EC₃ values were calculated for each agent. Based on the results of ex vivo LLNA-BrdU assays, EC₃ values were calculated to be 0.29, 0.09, 1.91, and 16.60% for formaldehyde, PPD, cinnamal, and eugenol, respectively. These results were in good agreement with data from previous standard radioactive LLNA. Cytokine analyses indicated T(H)1 and T(H)2 cytokine involvement in the regulation of murine contact allergy and these could be utilized as endpoints in assessments of contact allergy in mice. In conclusion, the current study provided evidence that the non-radioactive endpoint LLNA BrdU ex vivo incorporation could be of use as a viable alternative approach to assess the skin sensitization potential of test compound with respect to improving animal welfare. This is of particular importance in the case of any laboratory where it might be difficult to handle and/or readily employ radioisotopes. Further studies will be required to confirm--across test agents--the reproducibility as well as the limits of utility of this new ex vivo BrdU method.

  2. Influence of two cultivars of persimmon on atherosclerosis indices in rats fed cholesterol-containing diets: Investigation in vitro and in vivo.

    Science.gov (United States)

    Gorinstein, Shela; Leontowicz, Hanna; Leontowicz, Maria; Jesion, Iwona; Namiesnik, Jacek; Drzewiecki, Jerzy; Park, Yong-Seo; Ham, Kyung-Sik; Giordani, Edgardo; Trakhtenberg, Simon

    2011-01-01

    To assess the influence of two persimmon cultivars on some atherosclerosis indices in rats fed cholesterol (Chol)-containing diets. Persimmon cultivars "Fuyu" and "Jiro" as supplementation to rats' diets were investigated in vitro to compare the contents of their bioactive compounds (polyphenols, flavonoids, flavanols, tannins, carotenoids, and ascorbic acid) and antioxidant potentials. In the in vivo investigation, 36 male Wistar rats were randomly divided into six diet groups, each with six rats: control, control/Fuyu, control/Jiro, Chol, Chol/Fuyu, and Chol/Jiro. During a period of 47 d (42 d of feeding and 5-d adaptation before the experiment) of the trial, rats in the control group were fed a basal diet and two additional control groups (control/Fuyu and control/Jiro) a basal diet plus 5% of lyophilized Fuyu and Jiro, respectively. The Chol, Chol/Fuyu, and Chol/Jiro rat groups were fed a basal diet supplemented with 1% Chol (Chol group) and 1% Chol plus 5% lyophilized Fuyu (Chol/Fuyu group) and plus 5% lyophilized Jiro (Chol/Jiro group), respectively. After completion of the experiment, the rats were anesthetized using Narcotan (halothane) and sacrificed and the atherosclerotic lesions in the aorta were assessed. The obtained results of the investigation of all six groups were compared. Testing of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triacylglycerols, total cholesterol in the liver, electrophoretic patterns of liver tissue, and three-dimensional fluorescence of serum protein fractions was performed. The polyphenols and tannins were significantly higher in the Fuyu cultivar (Pacid) (ABTS) assay (Pcholesterol 19.4% and 9.5%, low-density lipoprotein cholesterol 25.6% and 13.1%, respectively, P<0.05) and hindered the decrease in plasma antioxidant activity versus the Chol group by 40.0% and 16.8% and by 39.6% and 11.3% for the ABTS and 1,1-diphenyl-2-picrylhydrazyl assays, respectively. The atherosclerotic

  3. Study protocol

    DEFF Research Database (Denmark)

    Smith, Benjamin E; Hendrick, Paul; Bateman, Marcus

    2017-01-01

    avoidance behaviours, catastrophising, self-efficacy, sport and leisure activity participation, and general quality of life. Follow-up will be 3 and 6 months. The analysis will focus on descriptive statistics and confidence intervals. The qualitative components will follow a thematic analysis approach....... DISCUSSION: This study will evaluate the feasibility of running a definitive large-scale trial on patients with patellofemoral pain, within the NHS in the UK. We will identify strengths and weaknesses of the proposed protocol and the utility and characteristics of the outcome measures. The results from...... this study will inform the design of a multicentre trial. TRIAL REGISTRATION: ISRCTN35272486....

  4. Evaluating the predictability of the in vitro transfer model and in vivo rat studies as a surrogate to investigate the supersaturation and precipitation behaviour of different Albendazole formulations for humans.

    Science.gov (United States)

    Ruff, Aaron; Holm, René; Kostewicz, Edmund S

    2017-07-15

    The present study investigated the ability of the in vitro transfer model and an in vivo pharmacokinetic study in rats to investigate the supersaturation and precipitation behaviour of albendazole (ABZ) relative to data from a human intestinal aspiration study reported in the literature. Two lipid based formulation systems, a hydroxypropyl-β-cyclodextrin (HPβCD) solution and the addition of a crystallization inhibitor (HPMC-E5) on the behaviour of ABZ was investigated. These formulations were investigated to represent differences in their ability to facilitate supersaturation within the small intestine. Overall, both the in vitro transfer model and the in vivo rat study were able to rank order the formulations (as aqueous suspension±HPMCvivo rat model and the in vitro transfer model could reflect the performance of the ABZ formulations in the human study. Whilst the rat was able to provide information on the overall plasma exposure, through the use of the in vitro transfer model, a more mechanistic understanding of the supersaturation and precipitation behaviour of ABZ using the different formulation strategies, could be attained. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. PASSIVE CAVITATION DETECTION DURING PULSED HIFU EXPOSURES OF EX VIVO TISSUES AND IN VIVO MOUSE PANCREATIC TUMORS

    Science.gov (United States)

    Li, Tong; Chen, Hong; Khokhlova, Tatiana; Wang, Yak-Nam; Kreider, Wayne; He, Xuemei; Hwang, Joo Ha

    2014-01-01

    Pulsed high-intensity focused ultrasound (pHIFU) has been demonstrated to enhance vascular permeability, disrupt tumor barriers and enhance drug penetration into tumor tissue through acoustic cavitation. Monitoring of cavitation activity during pHIFU treatments and knowing the ultrasound pressure levels sufficient to reliably induce cavitation in a given tissue are therefore very important. Here, three metrics of cavitation activity induced by pHIFU and evaluated by confocal passive cavitation detection were introduced: cavitation probability, cavitation persistence and the level of the broadband acoustic emissions. These metrics were used to characterize cavitation activity in several ex vivo tissue types (bovine tongue and liver and porcine adipose tissue and kidney) and gel phantoms (polyacrylamide and agarose) at varying peak-rarefactional focal pressures (1–12 MPa) during the following pHIFU protocol: frequency 1.1 MHz, pulse duration 1 ms, pulse repetition frequency 1 Hz. To evaluate the relevance of the measurements in ex vivo tissue, cavitation metrics were also investigated and compared in the ex vivo and in vivo murine pancreatic tumors that develop spontaneously in transgenic KPC mice and closely recapitulate human disease in their morphology. The cavitation threshold, defined at 50 % cavitation probability, was found to vary broadly among the investigated tissues (within 2.5–10 MPa), depending mostly on the water-lipid ratio that characterizes the tissue composition. Cavitation persistence and the intensity of broadband emissions depended both on tissue structure and lipid concentration. Both the cavitation threshold and broadband noise emission level were similar between ex vivo and in vivo pancreatic tumor tissue. The largest difference between in vivo and ex vivo settings was found in the pattern of cavitation occurrence throughout pHIFU exposure: it was sporadic in vivo, but ex vivo it decreased rapidly and stopped over the first few pulses

  6. Passive cavitation detection during pulsed HIFU exposures of ex vivo tissues and in vivo mouse pancreatic tumors.

    Science.gov (United States)

    Li, Tong; Chen, Hong; Khokhlova, Tatiana; Wang, Yak-Nam; Kreider, Wayne; He, Xuemei; Hwang, Joo Ha

    2014-07-01

    Pulsed high-intensity focused ultrasound (pHIFU) has been shown to enhance vascular permeability, disrupt tumor barriers and enhance drug penetration into tumor tissue through acoustic cavitation. Monitoring of cavitation activity during pHIFU treatments and knowing the ultrasound pressure levels sufficient to reliably induce cavitation in a given tissue are therefore very important. Here, three metrics of cavitation activity induced by pHIFU and evaluated by confocal passive cavitation detection were introduced: cavitation probability, cavitation persistence and the level of the broadband acoustic emissions. These metrics were used to characterize cavitation activity in several ex vivo tissue types (bovine tongue and liver and porcine adipose tissue and kidney) and gel phantoms (polyacrylamide and agarose) at varying peak-rare factional focal pressures (1-12 MPa) during the following pHIFU protocol: frequency 1.1 MHz, pulse duration 1 ms and pulse repetition frequency 1 Hz. To evaluate the relevance of the measurements in ex vivo tissue, cavitation metrics were also investigated and compared in the ex vivo and in vivo murine pancreatic tumors that develop spontaneously in transgenic KrasLSL.G12 D/+; p53 R172 H/+; PdxCretg/+ (KPC) mice and closely re-capitulate human disease in their morphology. The cavitation threshold, defined at 50% cavitation probability, was found to vary broadly among the investigated tissues (within 2.5-10 MPa), depending mostly on the water-lipid ratio that characterizes the tissue composition. Cavitation persistence and the intensity of broadband emissions depended both on tissue structure and lipid concentration. Both the cavitation threshold and broadband noise emission level were similar between ex vivo and in vivo pancreatic tumor tissue. The largest difference between in vivo and ex vivo settings was found in the pattern of cavitation occurrence throughout pHIFU exposure: it was sporadic in vivo, but it decreased rapidly and stopped

  7. Investigation of complexes with bone affinity using the In vivo generator system {sup 166} Dy/{sup 166} Ho; Investigacion de complejos con afinidad osea utilizando el Sistema de Generador in vivo {sup 166} Dy/{sup 166} Ho

    Energy Technology Data Exchange (ETDEWEB)

    Pedraza L, M

    2006-07-01

    The importance of this original research lies in the fact that it has proven that the [{sup 166}Dy]Dy/{sup 166}Ho-EDTMP in vivo generator system is a stable complex that can be used as a therapeutic radiopharmaceutical. Multiple myeloma and other hematological malignancies have been treated by myeloablative radiotherapy/chemotherapy and subsequent stem cell transplantation. Bone-seeking radiopharmaceuticals such as {sup 166}Ho-DOTMP or {sup 153}Sm-DTMP, have been proposed for delivering ablative radiation doses to marrow in multiple myeloma and other hematological malignancies or have shown excellent results in palliative bone metastasis pain therapy, respectively. As lanthanides have similar chemical characteristics the phosphonate with bone affinity (EDTMP) labeled with Dy/Ho can be used for marrow ablation while causing minimal irradiation to normal organs. This in vivo generator system has not been previously reported. The aim of this research was to label EDTMP (ethylene diamine tetramethylene phosphonate) with {sup 166}Dy/{sup 166}Ho; to evaluate the in vitro and in vivo stability of both {sup 166}Dy-EDTMP and {sup 166}Ho-EDTMP complexes when the daughter {sup 166}Ho is formed as a dysprosium decay product; to determine the bone marrow cytotoxic and genotoxic effect in mice and to evaluate, by histopathology, the myeloablative potential of the [{sup 166}Dy]Dy/{sup 166}Ho-EDTMP in vivo generator system. {sup 166}Dy was obtained by neutron irradiation of enriched {sup 164}Dy{sub 2}O{sub 3} in a TRIGA Mark III reactor. Labeling was carried out in an aqueous phosphate medium at pH 8.0 by addition of {sup 166}DyCl{sub 3} to EDTMP at a molar ratio 1:1.75, with >99 % radiochemical purity, as determined by thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC). In vitro studies demonstrated that {sup 166}Dy/{sup 166}Ho-EDTMP is unstable after dilution in saline but stable in human serum with no translocation of the daughter nucleus

  8. Investigation of complexes with bone affinity using the In vivo generator system {sup 166} Dy/{sup 166} Ho; Investigacion de complejos con afinidad osea utilizando el Sistema de Generador in vivo {sup 166} Dy/{sup 166} Ho

    Energy Technology Data Exchange (ETDEWEB)

    Pedraza L, M

    2006-07-01

    The importance of this original research lies in the fact that it has proven that the [{sup 166}Dy]Dy/{sup 166}Ho-EDTMP in vivo generator system is a stable complex that can be used as a therapeutic radiopharmaceutical. Multiple myeloma and other hematological malignancies have been treated by myeloablative radiotherapy/chemotherapy and subsequent stem cell transplantation. Bone-seeking radiopharmaceuticals such as {sup 166}Ho-DOTMP or {sup 153}Sm-DTMP, have been proposed for delivering ablative radiation doses to marrow in multiple myeloma and other hematological malignancies or have shown excellent results in palliative bone metastasis pain therapy, respectively. As lanthanides have similar chemical characteristics the phosphonate with bone affinity (EDTMP) labeled with Dy/Ho can be used for marrow ablation while causing minimal irradiation to normal organs. This in vivo generator system has not been previously reported. The aim of this research was to label EDTMP (ethylene diamine tetramethylene phosphonate) with {sup 166}Dy/{sup 166}Ho; to evaluate the in vitro and in vivo stability of both {sup 166}Dy-EDTMP and {sup 166}Ho-EDTMP complexes when the daughter {sup 166}Ho is formed as a dysprosium decay product; to determine the bone marrow cytotoxic and genotoxic effect in mice and to evaluate, by histopathology, the myeloablative potential of the [{sup 166}Dy]Dy/{sup 166}Ho-EDTMP in vivo generator system. {sup 166}Dy was obtained by neutron irradiation of enriched {sup 164}Dy{sub 2}O{sub 3} in a TRIGA Mark III reactor. Labeling was carried out in an aqueous phosphate medium at pH 8.0 by addition of {sup 166}DyCl{sub 3} to EDTMP at a molar ratio 1:1.75, with >99 % radiochemical purity, as determined by thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC). In vitro studies demonstrated that {sup 166}Dy/{sup 166}Ho-EDTMP is unstable after dilution in saline but stable in human serum with no translocation of the daughter nucleus

  9. Comprehensive multilevel in vivo and in vitro analysis of heart rate fluctuations in mice by ECG telemetry and electrophysiology.

    Science.gov (United States)

    Fenske, Stefanie; Pröbstle, Rasmus; Auer, Franziska; Hassan, Sami; Marks, Vanessa; Pauza, Danius H; Biel, Martin; Wahl-Schott, Christian

    2016-01-01

    The normal heartbeat slightly fluctuates around a mean value; this phenomenon is called physiological heart rate variability (HRV). It is well known that altered HRV is a risk factor for sudden cardiac death. The availability of genetic mouse models makes it possible to experimentally dissect the mechanism of pathological changes in HRV and its relation to sudden cardiac death. Here we provide a protocol that allows for a comprehensive multilevel analysis of heart rate (HR) fluctuations. The protocol comprises a set of techniques that include in vivo telemetry and in vitro electrophysiology of intact sinoatrial network preparations or isolated single sinoatrial node (SAN) cells. In vitro preparations can be completed within a few hours, with data acquisition within 1 d. In vivo telemetric ECG requires 1 h for surgery and several weeks for data acquisition and analysis. This protocol is of interest to researchers investigating cardiovascular physiology and the pathophysiology of sudden cardiac death.

  10. Bioinspired Security Analysis of Wireless Protocols

    DEFF Research Database (Denmark)

    Petrocchi, Marinella; Spognardi, Angelo; Santi, Paolo

    2016-01-01

    work, this paper investigates feasibility of adopting fraglets as model for specifying security protocols and analysing their properties. In particular, we give concrete sample analyses over a secure RFID protocol, showing evolution of the protocol run as chemical dynamics and simulating an adversary...

  11. Investigation on accordance of DNA double-strand break of blood between in vivo and in vitro irradiation using single cell gel electrophoresis

    International Nuclear Information System (INIS)

    Liu Qiang; Jiang Enhai; Li Jin; Tang Weisheng; Wang Zhiquan; Zhao Yongcheng; Fan Feiyue

    2006-01-01

    Objective: To observe the consistency of DNA double-strand break between in vivo and in vitro irradiation, as a prophase study in radiation biodosimetry using single cell gel electrophoresis (SCGE). Methods: Detect DNA double-strand break after whole-body and in vitro radiation in mice lymphocytes using neutral single cell gel electrophoresis. The comet images were processed by CASP software and all the data were analysed by SPSS12.0. Results: There is no difference between in vivo and in vitro irradiation group in HDNA%, TDNA%, CL, TL, TM and OTM. Conclusion: The result of neutral single cell gel electrophoresis shortly after in vitro irradiation can precisely reflect the DNA double-strand break of lymphocytes in whole-body irradiation. (authors)

  12. Plastic occlusion stress test as a model to investigate the effects of skin delipidization on the stratum corneum water holding capacity in vivo.

    Science.gov (United States)

    Berardesca, E; Herbst, R; Maibach, H

    1993-01-01

    The purpose of the study was to develop an in vivo model to study the effects of lipid removal on skin barrier. 16 subjects (age 41 +/- 8) were delipidized in vivo on the volar forearm using respectively ether/acetone (EA; 1:1) and chloroform/methanol (CM; 2:1). A third site served as control. Water holding capacity (WHC) was measured according to the plastic occlusion stress test (POST) procedure: the water desorption curve after removal of the occlusion was recorded in terms of skin surface water loss (SSWL) using an evaporimeter for 30 min. In the central part of the evaporation curve (bound water) the CM-treated site is significantly different from control and EA-treated sites (p rate of water from SC are higher in the CM-treated site (p evaporation of free water. We conclude that polar lipids have a key role in modulating barrier function and WHC of the stratum corneum. The POST can represent a useful in vivo model to study the effects of lipid extraction on skin function.

  13. Beyond protocols

    DEFF Research Database (Denmark)

    Vanderhoeven, Sonia; Branquart, Etienne; Casaer, Jim

    2017-01-01

    Risk assessment tools for listing invasive alien species need to incorporate all available evidence and expertise. Beyond the wealth of protocols developed to date, we argue that the current way of performing risk analysis has several shortcomings. In particular, lack of data on ecological impact...... information on risk and the exploration of improved methods for decision making on biodiversity management. This is crucial for efficient conservation resource allocation and uptake by stakeholders and the public......., transparency and repeatability of assessments as well as the incorporation of uncertainty should all be explicitly considered. We recommend improved quality control of risk assessments through formalized peer review with clear feedback between assessors and reviewers. Alternatively, a consensus building...

  14. In vivo SELEX for Identification of Brain-penetrating Aptamers

    Directory of Open Access Journals (Sweden)

    Congsheng Cheng

    2013-01-01

    Full Text Available The physiological barriers of the brain impair drug delivery for treatment of many neurological disorders. One delivery approach that has not been investigated for their ability to penetrate the brain is RNA-based aptamers. These molecules can impart delivery to peripheral tissues and circulating immune cells, where they act as ligand mimics or can be modified to carry payloads. We developed a library of aptamers and an in vivo evolution protocol to determine whether specific aptamers could be identified that would home to the brain after injection into the peripheral vasculature. Unlike biopanning with recombinant bacteriophage libraries, we found that the aptamer library employed here required more than 15 rounds of in vivo selection for convergence to specific sequences. The aptamer species identified through this approach bound to brain capillary endothelia and penetrated into the parenchyma. The methods described may find general utility for targeting various payloads to the brain.

  15. Study protocol: a randomised controlled trial investigating the effect of exercise training on peripheral blood gene expression in patients with stable angina

    Directory of Open Access Journals (Sweden)

    Crossman David C

    2010-10-01

    Full Text Available Abstract Background Exercise training has been shown to reduce angina and promote collateral vessel development in patients with coronary artery disease. However, the mechanism whereby exercise exerts these beneficial effects is unclear. There has been increasing interest in the use of whole genome peripheral blood gene expression in a wide range of conditions to attempt to identify both novel mechanisms of disease and transcriptional biomarkers. This protocol describes a study in which we will assess the effect of a structured exercise programme on peripheral blood gene expression in patients with stable angina, and correlate this with changes in angina level, anxiety, depression, and exercise capacity. Methods/Design Sixty patients with stable angina will be recruited and randomised 1:1 to exercise training or conventional care. Patients randomised to exercise training will attend an exercise physiology laboratory up to three times weekly for supervised aerobic interval training sessions of one hour in total duration. Patients will undergo assessments of angina, anxiety, depression, and peripheral blood gene expression at baseline, after six and twelve weeks of training, and twelve weeks after formal exercise training ceases. Discussion This study will provide comprehensive data on the effect of exercise training on peripheral blood gene expression in patients with angina. By correlating this with improvement in angina status we will identify candidate peripheral blood transcriptional markers predictive of improvements in angina level in response to exercise training. Trial Registration Clinicaltrials.gov identifier: NCT01147952

  16. Melatonin reduces hypoxic-ischaemic (HI) induced autophagy and apoptosis: An in vivo and in vitro investigation in experimental models of neonatal HI brain injury.

    Science.gov (United States)

    Hu, Yingying; Wang, Zhouguang; Liu, Yanlong; Pan, Shulin; Zhang, Hao; Fang, Mingchu; Jiang, Huai; Yin, Jiayu; Zou, Shuangshuang; Li, Zhenmao; Zhang, Hongyu; Lin, Zhenlang; Xiao, Jian

    2017-07-13

    Melatonin has neuroprotective effects in many diseases, including neonatal hypoxic-ischaemic (HI) brain injury. The purpose of this study was to evaluate the neuroprotective effects of melatonin both in vivo and in vitro and associated molecular mechanisms behind these effects. Postnatal day 7 male and female rat pups were subjected to unilateral HI, melatonin was injected intraperitoneally 1h before HI and an additional six doses were administered at 24h intervals. The pups were sacrificed at 24h and 7 d after HI. Pre-treatment with melatonin significantly reduced brain damage at 7 d after HI, with 15mg/kg melatonin achieving over 30% recovery in tissue loss compared to vehicle-treated animals. Autophagy and apoptotic cell death as indicated by autophagy associated proteins, cleaved caspase 3 and Tunel staining, was significantly inhibited after melatonin treatment in vivo as well as in PC12 cells. Melatonin treatment also significantly increased the GAP43 in the cortex. In conclusion, melatonin treatment reduced neonatal rat brain injury after HI, and this appeared to be related to inhibiting autophagy as well as reducing apoptotic cell death. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Investigation of Functional Activity of Cells in Granulomatous Inflammatory Lesions from Mice with Latent Tuberculous Infection in the New Ex Vivo Model

    Directory of Open Access Journals (Sweden)

    Elena Ufimtseva

    2013-01-01

    Full Text Available The new ex vivo model system measuring functional input of individual granuloma cells to formation of granulomatous inflammatory lesions in mice with latent tuberculous infection has been developed and described in the current study. Monolayer cultures of cells that migrated from individual granulomas were established in the proposed culture settings for mouse spleen and lung granulomas induced by in vivo exposure to BCG vaccine. The cellular composition of individual granulomas was analyzed. The expression of the leukocyte surface markers such as phagocytic receptors CD11b, CD11c, CD14, and CD16/CD32 and the expression of the costimulatory molecules CD80, CD83, and CD86 were tested as well as the production of proinflammatory cytokines (IFNγ and IL-1α and growth factors (GM-CSF and FGFb for cells of individual granulomas. The colocalization of the phagocytic receptors and costimulatory molecules in the surface microdomains of granuloma cells (with and without acid-fast BCG-mycobacteria has also been detected. It was found that some part of cytokine macrophage producers have carried acid-fast mycobacteria. Detected modulation in dynamics of production of pro-inflammatory cytokines, growth factors, and leukocyte surface markers by granuloma cells has indicated continued processes of activation and deactivation of granuloma inflammation cells during the latent tuberculous infection progress in mice.

  18. Investigation of Functional Activity of Cells in Granulomatous Inflammatory Lesions from Mice with Latent Tuberculous Infection in the New Ex Vivo Model

    Science.gov (United States)

    2013-01-01

    The new ex vivo model system measuring functional input of individual granuloma cells to formation of granulomatous inflammatory lesions in mice with latent tuberculous infection has been developed and described in the current study. Monolayer cultures of cells that migrated from individual granulomas were established in the proposed culture settings for mouse spleen and lung granulomas induced by in vivo exposure to BCG vaccine. The cellular composition of individual granulomas was analyzed. The expression of the leukocyte surface markers such as phagocytic receptors CD11b, CD11c, CD14, and CD16/CD32 and the expression of the costimulatory molecules CD80, CD83, and CD86 were tested as well as the production of proinflammatory cytokines (IFNγ and IL-1α) and growth factors (GM-CSF and FGFb) for cells of individual granulomas. The colocalization of the phagocytic receptors and costimulatory molecules in the surface microdomains of granuloma cells (with and without acid-fast BCG-mycobacteria) has also been detected. It was found that some part of cytokine macrophage producers have carried acid-fast mycobacteria. Detected modulation in dynamics of production of pro-inflammatory cytokines, growth factors, and leukocyte surface markers by granuloma cells has indicated continued processes of activation and deactivation of granuloma inflammation cells during the latent tuberculous infection progress in mice. PMID:24198843

  19. A blinded randomised placebo-controlled trial investigating the efficacy of morphine analgesia for procedural pain in infants: Trial protocol [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Rebeccah Slater

    2016-11-01

    Full Text Available Infant pain has both immediate and long-term negative consequences, yet in clinical practice it is often undertreated. To date, few pain-relieving drugs have been tested in infants. Morphine is a potent analgesic that provides effective pain relief in adults, but there is inconclusive evidence for its effectiveness in infants. The purpose of this study is to establish whether oral morphine provides effective analgesia for procedural pain in infants.   A blinded, placebo-controlled, parallel-group randomized, phase II, clinical trial will be undertaken to determine whether morphine sulphate administered orally prior to clinically-required retinopathy of prematurity (ROP screening and heel lancing provides effective analgesia. 
156 infants between 34 and 42 weeks’ gestational age who require a clinical heel lance and ROP screening on the same test occasion will be included in the trial. Infants will be randomised to receive either a single dose of morphine sulphate (100 μg/kg or placebo. Each infant will be monitored for 48 hours and safety data will be collected during the 24 hours following drug administration.   The primary outcome will be the Premature Infant Pain Profile–revised (PIPP-R score 30 seconds after ROP screening. The co-primary outcome will be the magnitude of nociceptive-specific brain activity evoked by a clinically-required heel lance. Infant clinical stability will be assessed by comparing the number of episodes of bradycardia, tachycardia, desaturation and apnoea, and changes in respiratory support requirements in the 24-hour periods before and after the clinical intervention. In addition, drug safety will be assessed by considering the occurrence of apnoeic and hypotensive episodes requiring intervention in the 24-hour period following drug administration. This study has been published as an Accepted Protocol Summary by The Lancet.

  20. Overcoming language barriers in healthcare: A protocol for investigating safe and effective communication when patients or clinicians use a second language.

    Science.gov (United States)

    Meuter, Renata F I; Gallois, Cindy; Segalowitz, Norman S; Ryder, Andrew G; Hocking, Julia

    2015-09-10

    Miscommunication in the healthcare sector can be life-threatening. The rising number of migrant patients and foreign-trained staff means that communication errors between a healthcare practitioner and patient when one or both are speaking a second language are increasingly likely. However, there is limited research that addresses this issue systematically. This protocol outlines a hospital-based study examining interactions between healthcare practitioners and their patients who either share or do not share a first language. Of particular interest are the nature and efficacy of communication in language-discordant conversations, and the degree to which risk is communicated. Our aim is to understand language barriers and miscommunication that may occur in healthcare settings between patients and healthcare practitioners, especially where at least one of the speakers is using a second (weaker) language. Eighty individual interactions between patients and practitioners who speak either English or Chinese (Mandarin or Cantonese) as their first language will be video recorded in a range of in- and out-patient departments at three hospitals in the Metro South area of Brisbane, Australia. All participants will complete a language background questionnaire. Patients will also complete a short survey rating the effectiveness of the interaction. Recordings will be transcribed and submitted to both quantitative and qualitative analyses to determine elements of the language used that might be particularly problematic and the extent to which language concordance and discordance impacts on the quality of the patient-practitioner consultation. Understanding the role that language plays in creating barriers to healthcare is critical for healthcare systems that are experiencing an increasing range of culturally and linguistically diverse populations both amongst patients and practitioners. The data resulting from this study will inform policy and practical solutions for

  1. Investigations of botanicals on food intake, satiety, weight loss and oxidative stress: study protocol of a double-blind, placebo-controlled, crossover study.

    Science.gov (United States)

    Anton, Stephen D; Shuster, Jonathan; Leeuwenburgh, Christiaan

    2011-11-01

    Botanicals represent an important and underexplored source of potential new therapies that may facilitate caloric restriction and thereby may produce long-term weight loss. In particular, one promising botanical that may reduce food intake and body weight by affecting neuroendocrine pathways related to satiety is hydroxycitric acid (HCA) derived from Garcinia cambogia Desr. The objective of this article is to describe the protocol of a clinical trial designed to directly test the effects of Garcinia cambogia-derived HCA on food intake, satiety, weight loss and oxidative stress levels, and to serve as a model for similar trials. A total of 48 healthy, overweight or obese individuals (with a body mass index range of 25.0 to 39.9 kg/m(2)) between the ages of 50 to 70 will participate in this double-blind, placebo-controlled, crossover study designed to examine the effects of two doses of Garcinia cambogia-derived HCA on food intake, satiety, weight loss, and oxidative stress levels. Food intake represents the primary outcome measure and is calculated based on the total calories consumed at breakfast, lunch, and dinner meals during each test meal day. This study can be completed with far fewer subjects than a parallel design. Of the numerous botanical compounds, the compound Garcinia cambogia-derived HCA is selected for testing in the present study because of its potential to safely reduce food intake, body weight, and oxidative stress levels. We will review potential mechanisms of action and safety parameters throughout this clinical trial. ClinicalTrials.gov (Identifier: NCT01238887).

  2. Investigation of the differentiation of ex vivo nerve and fat tissues using laser-induced breakdown spectroscopy (LIBS): Prospects for tissue-specific laser surgery.

    Science.gov (United States)

    Mehari, Fanuel; Rohde, Maximillian; Kanawade, Rajesh; Knipfer, Christian; Adler, Werner; Klämpfl, Florian; Stelzle, Florian; Schmidt, Michael

    2016-10-01

    In the present study, the elemental compositions of fat and nerve tissue during their plasma mediated laser ablation are studied in the context of tissue differentiation for laser surgery applications by using Laser-Induced Breakdown Spectroscopy (LIBS). Tissue samples of porcine fat and nerve were prepared as ex vivo experimental objects. Plasma mediated laser ablation is performed using an Nd : YAG laser in open air and under normal stray light conditions. The performed measurements suggest that the two tissue types show a high similarity in terms of qualitative elemental composition while at the same time revealing a distinct difference in the concentration of the constituent elements. Different analysis approaches are evaluated and discussed to optimize the tissue-differentiation performance of the LIBS approach. Plasma mediated laser tissue ablation. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. In vivo and in situ investigative results of repair and recovery processes during ontogenesis, after X-ray irradiation of bean seeds

    International Nuclear Information System (INIS)

    Koeroesi, F.; Jezierska-Szabo, E.; Szoeke, P.

    1999-01-01

    When exposing plant organs to high doses of ionizing radiation, disorders in growth and development or even lethality may occur. With the aim of modelling this phenomenon, seeds of bean, variety Echo Elit, were irradiated with a 300 Gy dose of X-ray irradiation (120 kV; 4.5 mA). In order to characterize repair and recovery at plant level, the biological production and photosynthetic pigments of the plants during ontogenesis in vivo and changes in their electric capacitance were continuously monitored and recorded via a computer-aided and -controlled data acquisition system. According to the data obtained, the repair in the biosynthesis of photosynthetic pigments will have been completed by the beginning of flowering. It may be assumed from the capacitance measurements made at 11 a.m. According to this postulation the process of repairing X-ray injuries might be finished by the beginning of pod formation without the plants actually recovering. (author)

  4. Quantitative NMR proton spectroscopy in vivo at 1,5 Tesla and possible applications to investigations of brain metabolism of depressive patients

    International Nuclear Information System (INIS)

    Metzler, D.

    1997-12-01

    Using a clinical magnetic resonance imaging/spectroscopy system 22 patients suffering from bipolar disorders and 22 healthy volunteers were examined by localized in vivo proton spectroscopy. The measurements were performed on a 1.5 Tesla whole body scanner of Siemens AG, Magnetom SP 4000, using the standard head coil (CP). For localization a STEAM sequence was used with an echo times TE of 55 ms. A recovery time of 3500 ms was chosen. The number of acquisitions was 256. The spectra were acquired from voxel volumes of 20 x 30 x 20 mm 3 . Three Gaussian presaturation pulses (CHESS) with subsequent dephasing gradients were used for water suppression. After correction for eddy-current effects and Fast-Fourier transformation the intensities of myo-inositol, choline compounds, creatine together with phospho-creatine, and N-acetylaspartate were evaluated from the spectra. The spectra from the frontal brain of depressed patients and controls revealed mInos/Cr ratios of about 0,4 - 0,5. This lies within the range, which is presumed to be the mInos concentration in 1 H-Magnetic Resonance Spectroscopy studies in human brain in vivo. Concerning the total sample (N = 2 x 22) there were no intergroup differences in the present study. Concluding a subsample of subjects younger than 40 years (N = 2 x 10), depressives showed lower mInos levels than controls in the right frontal lobe. The patients showed a significant positive correlation between age and mInos/Cr in the right frontal lobe, while in the left frontal lobe this could be seen only as a trend. In contrast, NAA/Cr decreased with increasing age. There were neither significant differences between sex nor between hemispheres. (author)

  5. Preparation, characterization and investigation of in vitro and in vivo biological properties of strontium-modified calcium phosphate cement for bone defect repair

    Directory of Open Access Journals (Sweden)

    Reza Masaeli

    2015-12-01

    Full Text Available Background and Aims: The aim of this study was to evaluate the invitro and invivo performance of a 3 wt% of strontium additive hydroxyapatite calcium phosphate cements (CPC. Materials and Methods: The prepared calcium phosphate cement was characterized with XRD, FTIR, setting time, STA and in vitro and in vivo biological analyses. The MTT assay ALP activities as in vitro study and radiological and histological examinations as in vivo study between the three groups of 3 wt% Sr-HA/CPC, CPC and control were performed and compared. Data were analyzed using T-test and One-way ANOVA. Results: XRD analysis demonstrated that by increasing the ratio of Powder/Liquid (P/L, the crystallinity of the prepared cement increased. The substitution of strontium instead of calcium in CPC could also alter the crystal structure, including some structural disorder. However, in the CPC with no strontium hydroxyapatite (Sr-HA, no significant increase in the crystallinity was observed. SEM observations revealed CPC with increasing P/L ratio, the formation of hydroxyapatite crystals arising from the interaction of solid and liquid phase of cement was decreased. Also, the addition of Sr within Ca site culminated in a dramatic increase in crystallinity of hydroxyapatite. In vitro biological properties ascertained that addition of 3 wt. % Sr-HA into CPC enhanced MTT assay and ALP activity, which could be due to the presence of strontium ions. The histological study showed that greater remodeling was seen at 4 weeks after implantation when the 3 wt% Sr-HA/CPC was used. Conclusion: The obtained results cleared that CPC can be a potential candidate as a carrier with strontium additives for bone remodeling and regeneration.

  6. Effective conversion of irinotecan to SN-38 after intratumoral drug delivery to an intracranial murine glioma model in vivo. Laboratory investigation.

    Science.gov (United States)

    Wang, Weijun; Ghandi, Alex; Liebes, Leonard; Louie, Stan G; Hofman, Florence M; Schönthal, Axel H; Chen, Thomas C

    2011-03-01

    Irinotecan (CPT-11), a topoisomerase I inhibitor, is a cytotoxic agent with activity against malignant gliomas and other tumors. After systemic delivery, CPT-11 is converted to its active metabolite, SN-38, which displays significantly higher cytotoxic potency. However, the achievement of therapeutically effective plasma levels of CPT-11 and SN-38 is seriously complicated by variables that affect drug metabolism in the liver. Thus the capacity of CPT-11 to be converted to the active SN38 intratumorally in gliomas was addressed. For in vitro studies, 2 glioma cell lines, U87 and U251, were tested to determine the cytotoxic effects of CPT-11 and SN-38 in a dose-dependent manner. In vivo studies were performed by implanting U87 intracranially into athymic/nude mice. For a period of 2 weeks, SN-38, CPT-11, or vehicle was administered intratumorally by means of an osmotic minipump. One series of experiments measured the presence of SN-38 or CPT-11 in the tumor and surrounding brain tissues after 2 weeks' exposure to the drug. In a second series of experiments, after 2 weeks' exposure to the drug, the animals were maintained, in the absence of drug, until death. The survival curves were then calculated. The results show that the animals that had CPT-11 delivered intratumorally by the minipump expressed SN-38 in vivo. Furthermore, both CPT-11 and SN-38 accumulated at higher levels in tumor tissues compared with uninvolved brain. Intratumoral delivery of CPT-11 or SN-38 extended the average survival time of tumor-bearing animals from 22 days to 46 and 65 days, respectively. These results demonstrate that intratumorally administered CPT-11 can be effectively converted to SN-38 and this method of drug delivery is effective in extending the survival time of animals bearing malignant gliomas.

  7. An investigation of the neutron flux in bone-fluorine phantoms comparing accelerator based in vivo neutron activation analysis and FLUKA simulation data

    International Nuclear Information System (INIS)

    Mostafaei, F.; McNeill, F.E.; Chettle, D.R.; Matysiak, W.; Bhatia, C.; Prestwich, W.V.

    2015-01-01

    We have tested the Monte Carlo code FLUKA for its ability to assist in the development of a better system for the in vivo measurement of fluorine. We used it to create a neutron flux map of the inside of the in vivo neutron activation analysis irradiation cavity at the McMaster Accelerator Laboratory. The cavity is used in a system that has been developed for assessment of fluorine levels in the human hand. This study was undertaken to (i) assess the FLUKA code, (ii) find the optimal hand position inside the cavity and assess the effects on precision of a hand being in a non-optimal position and (iii) to determine the best location for our γ-ray detection system within the accelerator beam hall. Simulation estimates were performed using FLUKA. Experimental measurements of the neutron flux were performed using Mn wires. The activation of the wires was measured inside (1) an empty bottle, (2) a bottle containing water, (3) a bottle covered with cadmium and (4) a dry powder-based fluorine phantom. FLUKA was used to simulate the irradiation cavity, and used to estimate the neutron flux in different positions both inside, and external to, the cavity. The experimental results were found to be consistent with the Monte Carlo simulated neutron flux. Both experiment and simulation showed that there is an optimal position in the cavity, but that the effect on the thermal flux of a hand being in a non-optimal position is less than 20%, which will result in a less than 10% effect on the measurement precision. FLUKA appears to be a code that can be useful for modeling of this type of experimental system

  8. Two-photon microscopy imaging of thy1GFP-M transgenic mice: a novel animal model to investigate brain dendritic cell subsets in vivo.

    Directory of Open Access Journals (Sweden)

    Claudia Laperchia

    Full Text Available Transgenic mice expressing fluorescent proteins in specific cell populations are widely used for in vivo brain studies with two-photon fluorescence (TPF microscopy. Mice of the thy1GFP-M line have been engineered for selective expression of green fluorescent protein (GFP in neuronal populations. Here, we report that TPF microscopy reveals, at the brain surface of these mice, also motile non-neuronal GFP+ cells. We have analyzed the behavior of these cells in vivo and characterized in brain sections their immunophenotype.With TPF imaging, motile GFP+ cells were found in the meninges, subarachnoid space and upper cortical layers. The striking feature of these cells was their ability to move across the brain parenchyma, exhibiting evident shape changes during their scanning-like motion. In brain sections, GFP+ cells were immunonegative to antigens recognizing motile cells such as migratory neuroblasts, neuronal and glial precursors, mast cells, and fibroblasts. GFP+ non-neuronal cells exhibited instead the characteristic features and immunophenotype (CD11c and major histocompatibility complex molecule class II immunopositivity of dendritic cells (DCs, and were immunonegative to the microglial marker Iba-1. GFP+ cells were also identified in lymph nodes and blood of thy1GFP-M mice, supporting their identity as DCs. Thus, TPF microscopy has here allowed the visualization for the first time of the motile behavior of brain DCs in situ. The results indicate that the thy1GFP-M mouse line provides a novel animal model for the study of subsets of these professional antigen-presenting cells in the brain. Information on brain DCs is still very limited and imaging in thy1GFP-M mice has a great potential for analyses of DC-neuron interaction in normal and pathological conditions.

  9. A pilot, quasi-experimental, mixed methods investigation into the efficacy of a group psychotherapy intervention for caregivers of outpatients with cancer: the COPE study protocol.

    Science.gov (United States)

    Mahendran, Rathi; Tan, Joyce Yi Siang; Griva, Konstadina; Lim, Haikel Asyraf; Ng, Hui Ying; Chua, Joanne; Lim, Siew Eng; Kua, Ee Heok

    2015-11-19

    Despite the rising trend of cancer prevalence and increase in family caregiving, little attention has been paid to the efficacy of psychosocial interventions among Asian caregiver samples, particularly support groups, given the benefits that have been shown in studies on Western populations. This trial aims to evaluate the effectiveness of a pilot 4-week group psychotherapy for Singaporean family caregivers of patients receiving outpatient care. Facilitated by a clinical psychologist, this intervention is primarily based on the brief integrative psychological therapy with a supportive-expressive intent. Participants will be recruited while they are accompanying their care recipients for outpatient consultations. Since this is a pilot study, a sample size of 120 participants is targeted on the basis of sample sizes of previous studies. The study adopts a quasi-experimental design, as participants are assigned the intervention or control arms based on their availability to attend the intervention. A mixed methods approach is used to evaluate the outcomes of the intervention. A self-administered battery of tests is completed at four time points: baseline, postintervention and follow-up at 1-month and 2-month postinterventions; semi-structured interviews are conducted at baseline and post-intervention. Primary outcomes are quality of life and anxious and depressive symptoms; secondary outcomes are stress and basic psychological needs. Analysis using analysis of covariance would be conducted to determine the effectiveness of the intervention. This study protocol has ethics approval from the National Healthcare Group Domain Specific Review Board (NHG DSRB Ref: 2013/00662). Written informed consent is obtained from every participant. Results will be disseminated through journals and conferences, and will be particularly relevant for clinicians intending to implement similar support groups to address the psychosocial concerns of caregivers, as well as for researchers

  10. Comparison of low- and ultralow-dose computed tomography protocols for quantitative lung and airway assessment.

    Science.gov (United States)

    Hammond, Emily; Sloan, Chelsea; Newell, John D; Sieren, Jered P; Saylor, Melissa; Vidal, Craig; Hogue, Shayna; De Stefano, Frank; Sieren, Alexa; Hoffman, Eric A; Sieren, Jessica C

    2017-09-01

    Quantitative computed tomography (CT) measures are increasingly being developed and used to characterize lung disease. With recent advances in CT technologies, we sought to evaluate the quantitative accuracy of lung imaging at low- and ultralow-radiation doses with the use of iterative reconstruction (IR), tube current modulation (TCM), and spectral shaping. We investigated the effect of five independent CT protocols reconstructed with IR on quantitative airway measures and global lung measures using an in vivo large animal model as a human subject surrogate. A control protocol was chosen (NIH-SPIROMICS + TCM) and five independent protocols investigating TCM, low- and ultralow-radiation dose, and spectral shaping. For all scans, quantitative global parenchymal measurements (mean, median and standard deviation of the parenchymal HU, along with measures of emphysema) and global airway measurements (number of segmented airways and pi10) were generated. In addition, selected individual airway measurements (minor and major inner diameter, wall thickness, inner and outer area, inner and outer perimeter, wall area fraction, and inner equivalent circle diameter) were evaluated. Comparisons were made between control and target protocols using difference and repeatability measures. Estimated CT volume dose index (CTDIvol) across all protocols ranged from 7.32 mGy to 0.32 mGy. Low- and ultralow-dose protocols required more manual editing and resolved fewer airway branches; yet, comparable pi10 whole lung measures were observed across all protocols. Similar trends in acquired parenchymal and airway measurements were observed across all protocols, with increased measurement differences using the ultralow-dose protocols. However, for small airways (1.9 ± 0.2 mm) and medium airways (5.7 ± 0.4 mm), the measurement differences across all protocols were comparable to the control protocol repeatability across breath holds. Diameters, wall thickness, wall area fraction

  11. A Healthy Eating Education Program for Midwives to Investigate and Explore Their Knowledge, Understanding, and Confidence to Support Pregnant Women to Eat Healthily: Protocol for a Mixed-Methods Study.

    Science.gov (United States)

    Othman, Shwikar Mahmoud Etman; Steen, Mary P; Jayasekara, Rasika; Fleet, Julie-Anne

    2018-05-25

    Nutrition and healthy eating behaviors during pregnancy are vitally important for the health of a mother and her developing baby. However, some midwives have reported a lack of evidence-based nutrition knowledge for providing information about healthy eating to women during pregnancy. In this study, the aim is to design and evaluate a healthy eating education program to enhance midwives' knowledge, understanding, and confidence to support pregnant women in South Australia to make healthy eating choices. This mixed-methods study consists of two phases. The first phase, Phase 1, consists of an education program for midwives, "Healthy Eating in Pregnancy," to be delivered through a workshop or webinar. Each midwife will attend one workshop or webinar, which will be approximately two hours in length. This program will be evaluated through pre-, immediate-, and post-educational questionnaires utilizing a website specifically designed for this study. The participants will be midwives who are members of the Australian College of Midwives and the Australian Nursing and Midwives Federation, and users of social media (eg, Facebook and Twitter) residing and employed in South Australia. Phase 2 will consist of semistructured interviews with a purposive sample of midwives. These interviews will be undertaken to gain an in-depth understanding of midwives' views and how confident they feel educating pregnant women after receiving the healthy eating education. Interviews will be face-to-face or conducted by telephone with midwives who have participated in the healthy eating educational program. A systematic review has previously been undertaken to inform this study protocol. This paper describes and discusses the protocol for this mixed-methods study, which will be completed in April 2019. The results from the systematic review suggest that there is clear justification to undertake this mixed-methods study to investigate and explore midwives' knowledge, understanding and

  12. Delivery of disulfiram into breast cancer cells using folate-receptor-targeted PLGA-PEG nanoparticles: in vitro and in vivo investigations.

    Science.gov (United States)

    Fasehee, Hamidreza; Dinarvand, Rassoul; Ghavamzadeh, Ardeshir; Esfandyari-Manesh, Mehdi; Moradian, Hanieh; Faghihi, Shahab; Ghaffari, Seyed Hamidollah

    2016-04-21

    A folate-receptor-targeted poly (lactide-co-Glycolide) (PLGA)-Polyethylene glycol (PEG) nanoparticle is developed for encapsulation and delivery of disulfiram into breast cancer cells. After a comprehensive characterization of nanoparticles, cell cytotoxicity, apoptosis induction, cellular uptake and intracellular level of reactive oxygen species are analyzed. In vivo acute and chronic toxicity of nanoparticles and their efficacy on inhibition of breast cancer tumor growth is studied. The folate-receptor-targeted nanoparticles are internalized into the cells, induce reactive oxygen species formation, induce apoptosis and inhibit cell proliferation more efficiently compared to the untargeted nanoparticles. The acute and toxicity test show the maximum dose of disulfiram equivalent of nanoparticles for intra-venous injection is 6 mg/kg while show significant decrease in the breast cancer tumor growth rate. It is believed that the developed formulation could be used as a potential vehicle for successful delivery of disulfiram, an old and inexpensive drug, into breast cancer cells and other solid tumors.

  13. The synthesis of (R)- and (S)-[N-methyl-11C]β, β-difluoromethamphetamine for the investigation of the binding mechanism of biogenic amines in vivo

    International Nuclear Information System (INIS)

    Gillings, N.M.; Gee, A.D.; Inoue, O.

    1999-01-01

    In an attempt to elucidate the contribution of the extent of nitrogen protonation on the in vivo binding of methamphetamine in the brain, the enantiomers of [N-methyl- 11 C]β,β-difluoroamphetamine (4) were prepared for use in positron emission tomography (PET) studies. Thus, the enantiomers of β,β-difluoroamphetamine were prepared from trans-β-methylstyrene, via bromination, conversion into the azirine, fluorination and resolution as the tartrate salts. (R)- and (S)-β,β-difluoroamphetamine (3) were then each labelled with carbon-11 (t 1/2 =20.4 min) by N-methylation of the corresponding homochiral β,β-difluoroamphetamine with [ 11 C]methyl iodide. The labelled products were each synthesised, purified and formulated in 35 min, starting from [ 11 C]carbon dioxide in 15-16% decay-corrected radiochemical yield, with a radiochemical purity of >99% and specific radioactivity of 50-150 GBq μmol -1 at end of synthesis

  14. Short Review on Quantum Key Distribution Protocols.

    Science.gov (United States)

    Giampouris, Dimitris

    2017-01-01

    Cryptographic protocols and mechanisms are widely investigated under the notion of quantum computing. Quantum cryptography offers particular advantages over classical ones, whereas in some cases established protocols have to be revisited in order to maintain their functionality. The purpose of this paper is to provide the basic definitions and review the most important theoretical advancements concerning the BB84 and E91 protocols. It also aims to offer a summary on some key developments on the field of quantum key distribution, closely related with the two aforementioned protocols. The main goal of this study is to provide the necessary background information along with a thorough review on the theoretical aspects of QKD, concentrating on specific protocols. The BB84 and E91 protocols have been chosen because most other protocols are similar to these, a fact that makes them important for the general understanding of how the QKD mechanism functions.

  15. An in vivo and in vitro investigation of the effect of Aloe vera gel ethanolic extract using animal model with diabetic foot ulcer

    Directory of Open Access Journals (Sweden)

    Mohan Daburkar

    2014-01-01

    Full Text Available Aim: To examine the preventive effect of Aloe vera gel ethanolic extract using diabetic foot ulcer (DFUs protocol in Wistar rats. Materials and Methods: Male Wistar rats were divided into untreated control (Group I, untreated DFUs (Group II, DFUs treated with A. vera gel ethanolic extract (Group III, DFUs treated with topical A. vera gel (Group IV, DFUs treated with A. vera gel ethanolic extract and topical A. vera gel (Group V. The rats in the treatment groups were daily administered the A. vera gel and ethanolic extract for 9 days. Fasting blood glucose levels and percentage of wound ulcer contraction were measured on day 3, 6, and 9. Statistical Analysis used: The results are expressed as a mean ± Standard Error Mean (SEM. Data were analyzed using one-way analysis of variance (ANOVA after Newman-Keuls test. P < 0.05 were considered statistically significant in all cases. Results: Oral administration of A. vera gel ethanolic extract at a dose of 300 mg/kg body weight per day to diabetic rats for a period of 9 days resulted in a significant reduction in fasting blood glucose and a significant improvement in plasma insulin. Topical application of A. vera gel at a dose 30 mg/kg body weight per day to streptozotocin (STZ-induced diabetic rats for a period of 9 days resulted in no change in blood glucose and plasma insulin. Oral administration as well as topical application of A. vera gel ethanolic extract and gel significantly reduced the blood glucose, improved the plasma insulin, and significantly increased DNA and glycosaminoglycans (GAGs to improve the wound ulcer healing as well as the breaking strength on day 9. Conclusions: Present findings provide a scientific rationale for the use of A. vera gel ethanolic extract, and showed that the gel attenuated the diabetic foot wound in rats.

  16. Investigation of continuous effect modifiers in a meta-analysis on higher versus lower PEEP in patients requiring mechanical ventilation--protocol of the ICEM study.

    Science.gov (United States)

    Kasenda, Benjamin; Sauerbrei, Willi; Royston, Patrick; Briel, Matthias

    2014-05-20

    Categorizing an inherently continuous predictor in prognostic analyses raises several critical methodological issues: dependence of the statistical significance on the number and position of the chosen cut-point(s), loss of statistical power, and faulty interpretation of the results if a non-linear association is incorrectly assumed to be linear. This also applies to a therapeutic context where investigators of randomized clinical trials (RCTs) are interested in interactions between treatment assignment and one or more continuous predictors. Our goal is to apply the multivariable fractional polynomial interaction (MFPI) approach to investigate interactions between continuous patient baseline variables and the allocated treatment in an individual patient data meta-analysis of three RCTs (N = 2,299) from the intensive care field. For each study, MFPI will provide a continuous treatment effect function. Functions from each of the three studies will be averaged by a novel meta-analysis approach for functions. We will plot treatment effect functions separately for each study and also the averaged function. The averaged function with a related confidence interval will provide a suitable basis to assess whether a continuous patient characteristic modifies the treatment comparison and may be relevant for clinical decision-making. The compared interventions will be a higher or lower positive end-expiratory pressure (PEEP) ventilation strategy in patients requiring mechanical ventilation. The continuous baseline variables body mass index, PaO2/FiO2, respiratory compliance, and oxygenation index will be the investigated potential effect modifiers. Clinical outcomes for this analysis will be in-hospital mortality, time to death, time to unassisted breathing, and pneumothorax. This project will be the first meta-analysis to combine continuous treatment effect functions derived by the MFPI procedure separately in each of several RCTs. Such an approach requires individual

  17. Early rehabilitation in sepsis: a prospective randomised controlled trial investigating functional and physiological outcomes The i-PERFORM Trial (Protocol Article

    Directory of Open Access Journals (Sweden)

    Kayambu Geetha

    2011-10-01

    Full Text Available Abstract Background Patients with sepsis syndromes in comparison to general intensive care patients can have worse outcomes for physical function, quality of life and survival. Early intensive care rehabilitation can improve the outcome in general Intensive Care Unit (ICU patients, however no investigations have specifically looked at patients with sepsis syndromes. The 'i-PERFORM Trial' will investigate if early targeted rehabilitation is both safe and effective in patients with sepsis syndromes admitted to ICU. Methods/Design A single-centred blinded randomized controlled trial will be conducted in Brisbane, Australia. Participants (n = 252 will include those ≥ 18 years, mechanically ventilated for ≥ 48 hours and diagnosed with a sepsis syndrome. Participants will be randomised to an intervention arm which will undergo an early targeted rehabilitation program according to the level of arousal, strength and cardiovascular stability and a control group which will receive normal care. The primary outcome measures will be physical function tests on discharge from ICU (The Acute Care Index of Function and The Physical Function ICU Test. Health-related quality of life will be measured using the Short Form-36 and the psychological component will be tested using The Hospital Anxiety and Depression Scale. Secondary measures will include inflammatory biomarkers; Interleukin-6, Interleukin-10 and Tumour Necrosis Factor-α, peripheral blood mitochondrial DNA content and lactate, fat free muscle mass, tissue oxygenation and microcirculatory flow. Discussion The 'i-PERFORM Trial' will determine whether early rehabilitation for patients with sepsis is effective at improving patient outcomes with functional and physiological parameters reflecting long and short-term effects of early exercise and the safety in its application in critical illness. Trial Registration Australia and New Zealand Clinical Trials Register (ANZCTR: ACTRN12610000808044

  18. To Investigate the Therapeutic Efforts of the COX-2 Inhibitor NS-398 as a Single Agent, and in Combination with Vitamin D, in Vitro and in Vivo

    National Research Council Canada - National Science Library

    Lee, Yi-Fen

    2008-01-01

    .... We have identified a cross-talk between vitamin D and COX-2 inhibitor, two chemopreventative agents for prostate cancer, and conducted series investigations of their anti-prostate cancer effects...

  19. A systematic review protocol investigating tests for physical or physiological qualities and game-specific skills commonly used in rugby and related sports and their psychometric properties.

    Science.gov (United States)

    Chiwaridzo, Matthew; Ferguson, Gillian D; Smits-Engelsman, Bouwien C M

    2016-07-27

    Scientific focus on rugby has increased over the recent years, providing evidence of the physical or physiological characteristics and game-specific skills needed in the sport. Identification of tests commonly used to measure these characteristics is important for the development of test batteries, which in turn may be used for talent identification and injury prevention programmes. Although there are a number of tests available in the literature to measure physical or physiological variables and game-specific skills, there is limited information available on the psychometric properties of the tests. Therefore, the purpose of this study is to systematically review the literature for tests commonly used in rugby to measure physical or physiological characteristics and rugby-specific skills, documenting evidence of reliability and validity of the identified tests. A systematic review will be conducted. Electronic databases such as Scopus, MEDLINE via EBSCOhost and PubMed, Academic Search Premier, CINAHL and Africa-Wide Information via EBSCOhost will be searched for original research articles published in English from January 1, 1995, to December 31, 2015, using a pre-defined search strategy. The principal investigator will select potentially relevant articles from titles and abstracts. To minimise bias, full text of titles and abstracts deemed potentially relevant will be retrieved and reviewed by two independent reviewers based on the inclusion criteria. Data extraction will be conducted by the principal investigator and verified by two independent reviewers. The Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist will be used to assess the methodological quality of the selected studies. Choosing an appropriate test to be included in the screening test battery should be based on sound psychometric properties of the test available. This systematic review will provide an overview of the tests commonly used in rugby union

  20. Psychotherapy integration under scrutiny: investigating the impact of integrating emotion-focused components into a CBT-based approach: a study protocol of a randomized controlled trial.

    Science.gov (United States)

    Babl, Anna; Grosse Holtforth, Martin; Heer, Sara; Lin, Mu; Stähli, Annabarbara; Holstein, Dominique; Belz, Martina; Egenolf, Yvonne; Frischknecht, Eveline; Ramseyer, Fabian; Regli, Daniel; Schmied, Emma; Flückiger, Christoph; Brodbeck, Jeannette; Berger, Thomas; Caspar, Franz

    2016-11-24

    This currently recruiting randomized controlled trial investigates the effects of integrating components of Emotion-Focused Therapy (EFT) into Psychological Therapy (PT), an integrative form of cognitive-behavioral therapy in a manner that is directly mirroring common integrative practice in the sense of assimilative integration. Aims of the study are to understand how both, an existing therapy approach as well as the elements to be integrated, are affected by the integration and to clarify the role of emotional processing as a mediator of therapy outcome. A total of 130 adults with a diagnosed unipolar depressive, anxiety or adjustment disorder (seeking treatment at a psychotherapy outpatient clinic) are randomized to either treatment as usual (PT) with integrated emotion-focused components (TAU + EFT) or PT (TAU). Primary outcome variables are psychopathology and symptom severity at the end of therapy and at follow up; secondary outcome variables are interpersonal problems, psychological wellbeing, quality of life, attainment of individual therapy goals, and emotional competency. Furthermore, process variables such as the quality of the therapeutic relationship are studied as well as aptitude-treatment interactions. Variables are assessed at baseline, after 8 and 16 sessions, at the end of therapy, after 25 ± 3 sessions, and at 6, 12 and 36 month follow-up. Underlying mechanisms of change are investigated. Statistical analyses will be conducted using the appropriate multilevel approaches, mainly two-level regression and growth analysis. The results of this study will indicate whether the integration of emotion-focused elements into treatment as usual increases the effectiveness of Psychological Therapy. If advantages are found, which may be limited to particular variables or subgroups of patients, recommendations for a systematic integration, and caveats if also disadvantages are detected, can be formulated. On a more abstract level, a cognitive

  1. Labelling, biodistribution and compartmental analysis of N-acetylcysteine labelled with Tc-99m. Comparative investigation with with 99m Tc-MIBI in an in vivo tumoral model

    International Nuclear Information System (INIS)

    Faintuch, Bluma Linkowski

    1997-01-01

    Labelling and biodistribution studies were done with two different ligands, respectively Methoxy isobutyl isonitrile (MIBI) and N-acetylcysteine (NAC), employing Tc-99m as a tracer. The main objective was to assess the pharmacokinetic properties of the second substance, aiming at its possible application in cancer diagnosis. To this purpose an in vivo investigation was done using healthy and tumor-bearing rats with experimental cancer. Images of tumor-bearing rats registered in a scintillation camera indicated that with 99m Tc-MIBI none of the two selected times was adequate for visualization of the cancer mass. In contrast, 99m Tc-NAC permitted clear identification of the humor, four hours after injection. The results have demonstrated that 99m Tc-NAC is a radiopharmaceutical with affinity for cancer tissue and promising for further investigation concerning imaging diagnosis of tumors. (author)

  2. The IGNITE (investigation to guide new insight into translational effectiveness trial: Protocol for a translational study of an evidenced-based wellness program in fire departments

    Directory of Open Access Journals (Sweden)

    MacKinnon David P

    2010-10-01

    Full Text Available Abstract Background Worksites are important locations for interventions to promote health. However, occupational programs with documented efficacy often are not used, and those being implemented have not been studied. The research in this report was funded through the American Reinvestment and Recovery Act Challenge Topic 'Pathways for Translational Research,' to define and prioritize determinants that enable and hinder translation of evidenced-based health interventions in well-defined settings. Methods The IGNITE (investigation to guide new insights for translational effectiveness trial is a prospective cohort study of a worksite wellness and injury reduction program from adoption to final outcomes among 12 fire departments. It will employ a mixed methods strategy to define a translational model. We will assess decision to adopt, installation, use, and outcomes (reach, individual outcomes, and economic effects using onsite measurements, surveys, focus groups, and key informant interviews. Quantitative data will be used to define the model and conduct mediation analysis of each translational phase. Qualitative data will expand on, challenge, and confirm survey findings and allow a more thorough understanding and convergent validity by overcoming biases in qualitative and quantitative methods used alone. Discussion Findings will inform worksite wellness in fire departments. The resultant prioritized influences and model of effective translation can be validated and manipulated in these and other settings to more efficiently move science to service.

  3. The Physical Activity and Redesigned Community Spaces (PARCS Study: Protocol of a natural experiment to investigate the impact of citywide park redesign and renovation

    Directory of Open Access Journals (Sweden)

    Terry T. K. Huang

    2016-11-01

    Full Text Available Abstract Background The built environment plays a critical role in promoting physical activity and health. The association between parks, as a key attribute of the built environment, and physical activity, however, remains inconclusive. This project leverages a natural experiment opportunity to assess the impact of the Community Parks Initiative (CPI, a citywide park redesign and renovation effort in New York City, on physical activity, park usage, psychosocial and mental health, and community wellbeing. Methods The project will use a longitudinal design with matched controls. Thirty intervention park neighborhoods are socio-demographically matched to 20 control park neighborhoods. The study will investigate whether improvements in physical activity, park usage, psychosocial and mental health, and community wellbeing are observed from baseline to 3 years post-renovation among residents in intervention vs. control neighborhoods. Discussion This study represents a rare opportunity to provide robust evidence to further our understanding of the complex relationship between parks and health. Findings will inform future investments in health-oriented urban design policies and offer evidence for addressing health disparities through built environment strategies.

  4. THE COOPERATIVE INTERNATIONAL NEUROMUSCULAR RESEARCH GROUP DUCHENNE NATURAL HISTORY STUDY—A LONGITUDINAL INVESTIGATION IN THE ERA OF GLUCOCORTICOID THERAPY: DESIGN OF PROTOCOL AND THE METHODS USED

    Science.gov (United States)

    McDonald, Craig M.; Henricson, Erik K.; Abresch, R. Ted; Han, Jay J.; Escolar, Diana M.; Florence, Julaine M.; Duong, Tina; Arrieta, Adrienne; Clemens, Paula R.; Hoffman, Eric P.; Cnaan, Avital

    2014-01-01

    Contemporary natural history data in Duchenne muscular dystrophy (DMD) is needed to assess care recommendations and aid in planning future trials. Methods The Cooperative International Neuromuscular Research Group (CINRG) DMD Natural History Study (DMD-NHS) enrolled 340 individuals, aged 2–28 years, with DMD in a longitudinal, observational study at 20 centers. Assessments obtained every 3 months for 1 year, at 18 months, and annually thereafter included: clinical history; anthropometrics; goniometry; manual muscle testing; quantitative muscle strength; timed function tests; pulmonary function; and patient-reported outcomes/ health-related quality-of-life instruments. Results Glucocorticoid (GC) use at baseline was 62% present, 14% past, and 24% GC-naive. In those ≥6 years of age, 16% lost ambulation over the first 12 months (mean age 10.8 years). Conclusions Detailed information on the study methodology of the CINRG DMD-NHS lays the groundwork for future analyses of prospective longitudinal natural history data. These data will assist investigators in designing clinical trials of novel therapeutics. PMID:23677550

  5. Tumorigenic potential of pituitary tumor transforming gene (PTTG in vivo investigated using a transgenic mouse model, and effects of cross breeding with p53 (+/− transgenic mice

    Directory of Open Access Journals (Sweden)

    Fong Miranda Y

    2012-11-01

    Full Text Available Abstract Background Pituitary tumor-transforming gene (PTTG is an oncogene that is overexpressed in variety of tumors and exhibits characteristics of a transforming gene. Previous transgenic mouse models to access the tumorigenic potential in the pituitary and ovary have resulted in dysplasia without formation of visible tumors, possibly due to the insufficient expression of PTTG. PTTG expression level is critical for ovarian tumorigenesis in a xenograft model. Therefore, the tumorigenic function of PTTG in vivo remains unclear. We generated a transgenic mouse that overexpresses PTTG driven by the CMV promoter to determine whether PTTG functions as a transforming oncogene that is capable of initiating tumorigenesis. Methods Transgenic animals were generated by microinjection of PTTG transgene into the male pronucleus of FVB 0.5 day old embryos. Expression levels of PTTG in tissues of transgenic animals were analyzed using an immunohistochemical analysis. H&E staining and immunohistostaining were performed to examine the type of tumor in transgenic and PTTG transgenic/p53+/- animals. Results PTTG transgenic offspring (TgPTTG were monitored for tumor development at various ages. H&E analysis was performed to identify the presence of cancer and hyperplastic conditions verified with the proliferation marker PCNA and the microvessel marker CD31. Immunohistochemistry was performed to determine transgene expression, revealing localization to the epithelium of the fallopian tube, with more generalized expression in the liver, lung, kidney, and spleen. At eight months of age, 2 out of 15 TgPTTG developed ovarian cancer, 2 out of 15 developed benign tumors, 2 out of 15 developed cervical dysplasia, and 3 out of 15 developed adenomyosis of the uterus. At ten months of age, 2 out of 10 TgPTTG developed adenocarcinoma of the ovary, 1 out of 10 developed a papillary serous adenocarcinoma, and 2 out of 10 presented with atypia of ovarian epithelial cells

  6. The Belgian trial with azithromycin for acute COPD exacerbations requiring hospitalization: an investigator-initiated study protocol for a multicenter, randomized, double-blind, placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Vermeersch K

    2016-03-01

    Full Text Available Kristina Vermeersch,1 Maria Gabrovska,2 Griet Deslypere,3 Ingel K Demedts,4 Hans Slabbynck,5 Joseph Aumann,3 Vincent Ninane,2 Geert M Verleden,1 Thierry Troosters,1,6 Kris Bogaerts,7,8 Guy G Brusselle,9 Wim Janssens1 On behalf of the BACE Trial Investigators 1KU Leuven, Laboratory of Respiratory Diseases, Department of Clinical and Experimental Medicine, Faculty of Medicine, Leuven, Belgium; 2Department of Pneumology, Centre Hospitalier Universitaire Saint-Pierre, Brussels, Belgium; 3Department of Pneumology, Jessa Ziekenhuis, Hasselt, Belgium; 4Department of Respiratory Medicine, AZ Delta Roeselare-Menen, Roeselare, Belgium; 5Department of Respiratory Medicine, ZNA Middelheim, Antwerpen, Belgium; 6KU Leuven, Department of Rehabilitation Sciences, Faculty of Kinesiology and Rehabilitation Sciences, Leuven, Belgium; 7KU Leuven, Department of Public Health and Primary Care, I-BioStat, Leuven, Belgium; 8Hasselt University, Hasselt, Belgium; 9Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium Background: Long-term use of macrolide antibiotics is effective to prevent exacerbations in chronic obstructive pulmonary disease (COPD. As risks and side effects of long-term intervention outweigh the benefits in the general COPD population, the optimal dose, duration of treatment, and target population are yet to be defined. Hospitalization for an acute exacerbation (AE of COPD may offer a targeted risk group and an obvious risk period for studying macrolide interventions.Methods/design: Patients with COPD, hospitalized for an AE, who have a smoking history of ≥10 pack-years and had ≥1 exacerbation in the previous year will be enrolled in a multicenter, randomized, double-blind, placebo-controlled trial (NCT02135354. On top of a standardized treatment of systemic corticosteroids and antibiotics, subjects will be randomized to receive either azithromycin or placebo during 3 months, at an uploading dose of 500 mg once a day for

  7. A study protocol to investigate the relationship between dietary fibre intake and fermentation, colon cell turnover, global protein acetylation and early carcinogenesis: the FACT study

    International Nuclear Information System (INIS)

    Corfe, Bernard M; Williams, Elizabeth A; Bury, Jonathan P; Riley, Stuart A; Croucher, Lisa J; Lai, Daphne YL; Evans, Caroline A

    2009-01-01

    A number of studies, notably EPIC, have shown a descrease in colorectal cancer risk associated with increased fibre consumption. Whilst the underlying mechanisms are likely to be multifactorial, production of the short-chain fatty-acid butyrate fro butyratye is frequently cited as a major potential contributor to the effect. Butyrate inhibits histone deacetylases, which work on a wide range of proteins over and above histones. We therefore hypothesized that alterations in the acetylated proteome may be associated with a cancer risk phenotype in the colorectal mucosa, and that such alterations are candidate biomarkers for effectiveness of fibre interventions in cancer prevention. There are two principal arms to this study: (i) a cross-sectional study (FACT OBS) of 90 subjects recruited from gastroenterology clinics and; (ii) an intervention trial in 40 subjects with an 8 week high fibre intervention. In both studies the principal goal is to investigate a link between fibre intake, SCFA production and global protein acetylation. The primary measure is level of faecal butyrate, which it is hoped will be elevated by moving subjects to a high fibre diet. Fibre intakes will be estimated in the cross-sectional group using the EPIC Food Frequency Questionnaire. Subsidiary measures of the effect of butyrate on colon mucosal function and pre-cancerous phenotype will include measures of apoptosis, apoptotic regulators cell cycle and cell division. This study will provide a new level of mechanistic data on alterations in the functional proteome in response to the colon microenvironment which may underwrite the observed cancer preventive effect of fibre. The study may yield novel candidate biomarkers of fibre fermentation and colon mucosal function. Trial Registration Number: ISRCTN90852168

  8. A study protocol to investigate the relationship between dietary fibre intake and fermentation, colon cell turnover, global protein acetylation and early carcinogenesis: the FACT study

    Directory of Open Access Journals (Sweden)

    Croucher Lisa J

    2009-09-01

    Full Text Available Abstract Background A number of studies, notably EPIC, have shown a descrease in colorectal cancer risk associated with increased fibre consumption. Whilst the underlying mechanisms are likely to be multifactorial, production of the short-chain fatty-acid butyrate fro butyratye is frequently cited as a major potential contributor to the effect. Butyrate inhibits histone deacetylases, which work on a wide range of proteins over and above histones. We therefore hypothesized that alterations in the acetylated proteome may be associated with a cancer risk phenotype in the colorectal mucosa, and that such alterations are candidate biomarkers for effectiveness of fibre interventions in cancer prevention. Methods an design There are two principal arms to this study: (i a cross-sectional study (FACT OBS of 90 subjects recruited from gastroenterology clinics and; (ii an intervention trial in 40 subjects with an 8 week high fibre intervention. In both studies the principal goal is to investigate a link between fibre intake, SCFA production and global protein acetylation. The primary measure is level of faecal butyrate, which it is hoped will be elevated by moving subjects to a high fibre diet. Fibre intakes will be estimated in the cross-sectional group using the EPIC Food Frequency Questionnaire. Subsidiary measures of the effect of butyrate on colon mucosal function and pre-cancerous phenotype will include measures of apoptosis, apoptotic regulators cell cycle and cell division. Discussion This study will provide a new level of mechanistic data on alterations in the functional proteome in response to the colon microenvironment which may underwrite the observed cancer preventive effect of fibre. The study may yield novel candidate biomarkers of fibre fermentation and colon mucosal function. Trial Registration Trial Registration Number: ISRCTN90852168

  9. Investigating the organisational impacts of quality improvement: a protocol for a realist evaluation of improvement approaches drawing on the Resource Based View of the Firm.

    Science.gov (United States)

    Burton, Christopher R; Rycroft Malone, Jo; Robert, Glenn; Willson, Alan; Hopkins, Angela

    2014-07-31

    Little is understood about the role of quality improvement in enabling health organisations to survive and thrive in the contemporary context of financial and economic challenges. We will draw on the theoretical foundations of the 'Resource Based View of the Firm' (RBV) to develop insights into why health organisations engage in improvement work, how impacts are conceptualised, and 'what works' in delivering these impacts. Specifically, RBV theorises that the mix and use of resources across different organisations may explain differences in performance. Whether improvement work influences these resources is unclear. Case study research will be conducted across health organisations participating in four approaches to improvement, including: a national improvement programme; a multiorganisational partnership around implementation; an organisational strategy for quality improvement; and a coproduction project designed to enhance the experience of a clinical service from the perspective of patients. Data will comprise in-depth interviews with key informants, observation of key events and documents; analysed within and then across cases. Adopting a realist perspective, the core tenets of RBV will be evaluated as a programme theory, focusing on the interplay between organisational conditions and behavioural or resource responses that are reported through engagement in improvement. The study has been approved by Bangor University Ethics Committee. The investigation will not judge the relative merits of different approaches to healthcare quality improvement. Rather, we will develop unique insights into the organisational consequences, and dependencies of quality improvement, providing an opportunity to add to the explanatory potential of RBV in this and other contexts. In addition to scientific and lay reports of the study findings, research outputs will include a framework for constructing the economic impacts of quality improvement and practical guidance for health

  10. An investigation of the predictors of photoprotection and UVR dose to the face in patients with XP: a protocol using observational mixed methods.

    Science.gov (United States)

    Walburn, Jessica; Sarkany, Robert; Norton, Sam; Foster, Lesley; Morgan, Myfanwy; Sainsbury, Kirby; Araújo-Soares, Vera; Anderson, Rebecca; Garrood, Isabel; Heydenreich, Jakob; Sniehotta, Falko F; Vieira, Rute; Wulf, Hans Christian; Weinman, John

    2017-08-21

    Xeroderma pigmentosum (XP) is a rare genetic condition caused by defective nucleotide excision repair and characterised by skin cancer, ocular and neurological involvement. Stringent ultraviolet protection is the only way to prevent skin cancer. Despite the risks, some patients' photoprotection is poor, with a potentially devastating impact on their prognosis. The aim of this research is to identify disease-specific and psychosocial predictors of photoprotection behaviour and ultraviolet radiation (UVR) dose to the face. Mixed methods research based on 45 UK patients will involve qualitative interviews to identify individuals' experience of XP and the influences on their photoprotection behaviours and a cross-sectional quantitative survey to assess biopsychosocial correlates of these behaviours at baseline. This will be followed by objective measurement of UVR exposure for 21 days by wrist-worn dosimeter and daily recording of photoprotection behaviours and psychological variables for up to 50 days in the summer months. This novel methodology will enable UVR dose reaching the face to be calculated and analysed as a clinically relevant endpoint. A range of qualitative and quantitative analytical approaches will be used, reflecting the mixed methods (eg, cross-sectional qualitative interviews, n-of-1 studies). Framework analysis will be used to analyse the qualitative interviews; mixed-effects longitudinal models will be used to examine the association of clinical and psychosocial factors with the average daily UVR dose; dynamic logistic regression models will be used to investigate participant-specific psychosocial factors associated with photoprotection behaviours. This research has been approved by Camden and King's Cross Research Ethics Committee 15/LO/1395. The findings will be published in peer-reviewed journals and presented at national and international scientific conferences. © Article author(s) (or their employer(s) unless otherwise stated in the text of

  11. Security analysis of session initiation protocol

    OpenAIRE

    Dobson, Lucas E.

    2010-01-01

    Approved for public release; distribution is unlimited The goal of this thesis is to investigate the security of the Session Initiation Protocol (SIP). This was accomplished by researching previously discovered protocol and implementation vulnerabilities, evaluating the current state of security tools and using those tools to discover new vulnerabilities in SIP software. The CVSS v2 system was used to score protocol and implementation vulnerabilities to give them a meaning that was us...

  12. Labelling, biodistribution and compartmental analysis of N-acetylcysteine labelled with Tc-99m. Comparative investigation with with {sup 99m} Tc-MIBI in an in vivo tumoral model; Estudo de marcacao, biodistribuicao e analise compartimental da N-acetil cisteina marcada com Tc-99m. Investigacao comparativa com MIBI-{sup 99m}Tc em modelo tumoral in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Faintuch, Bluma Linkowski

    1997-07-01

    Labelling and biodistribution studies were done with two different ligands, respectively Methoxy isobutyl isonitrile (MIBI) and N-acetylcysteine (NAC), employing Tc-99m as a tracer. The main objective was to assess the pharmacokinetic properties of the second substance, aiming at its possible application in cancer diagnosis. To this purpose an in vivo investigation was done using healthy and tumor-bearing rats with experimental cancer. Images of tumor-bearing rats registered in a scintillation camera indicated that with {sup 99m} Tc-MIBI none of the two selected times was adequate for visualization of the cancer mass. In contrast, {sup 99m} Tc-NAC permitted clear identification of the humor, four hours after injection. The results have demonstrated that {sup 99m} Tc-NAC is a radiopharmaceutical with affinity for cancer tissue and promising for further investigation concerning imaging diagnosis of tumors. (author)

  13. Essential oil of Artemisia vestita exhibits potent in vitro and in vivo antibacterial activity: Investigation of the effect of oil on biofilm formation, leakage of potassium ions and survival curve measurement.

    Science.gov (United States)

    Yang, Chang; Hu, Dong-Hui; Feng, Yan

    2015-10-01

    The aim of the present study was to investigate the chemical composition of the essential oil of Artemisia vestita and to determine the antibacterial activity of the essential oil and its two major components, grandisol and 1,8‑cineole, against certain respiratory infection‑causing bacterial strains, in vitro and in vivo. The chemical composition of the essential oil was analyzed using gas chromatography‑mass spectrometry. A micro‑well dilution method was used to determine the minimum inhibition concentration (MIC) values of the essential oil and its major constituents. A model of Streptococcus pyogenes infection in mice was used to determine its in vivo activities. Lung and blood samples were obtained to assess bacterial cell counts. Toxicity evaluation of the essential oil and its components was completed by performing biochemical analysis of the serum, particularly monitoring aspartate transaminase, alanine transaminase, urea and creatinine. The essential oil exhibited potent antibacterial activity, whereas the two major constituents were less potent. The essential oil exhibited MIC values between 20 and 80 µg/ml, while the values of the two constituents were between 130 and 200 µg/ml. Scanning electron microscopy results demonstrated that the essential oil inhibited biofilm formation and altered its architecture. Survival curves indicated that the essential oil led to a reduction in the viability of different bacteria. The essential oil also induced significant leakage of potassium ions from S. pyogenes. The essential oil (100 µg/mouse) and grandisol (135 µg/mouse) significantly reduced the number of viable bacterial cells in the lungs (Pessential oil or grandisol 135 µg/mouse once or twice each day for 9 days did not produce any toxic effects in the mice. In conclusion, the in vitro and in vivo results suggested that the essential oil of A. vestita and one of its major constituents, grandisol, can significantly inhibit the growth of different

  14. Essential oil of Artemisia vestita exhibits potent in vitro and in vivo antibacterial activity: Investigation of the effect of oil on biofilm formation, leakage of potassium ions and survival curve measurement

    Science.gov (United States)

    YANG, CHANG; HU, DONG-HUI; FENG, YAN

    2015-01-01

    The aim of the present study was to investigate the chemical composition of the essential oil of Artemisia vestita and to determine the antibacterial activity of the essential oil and its two major components, grandisol and 1,8-cineole, against certain respiratory infection-causing bacterial strains, in vitro and in vivo. The chemical composition of the essential oil was analyzed using gas chromatography-mass spectrometry. A micro-well dilution method was used to determine the minimum inhibition concentration (MIC) values of the essential oil and its major constituents. A model of Streptococcus pyogenes infection in mice was used to determine its in vivo activities. Lung and blood samples were obtained to assess bacterial cell counts. Toxicity evaluation of the essential oil and its components was completed by performing biochemical analysis of the serum, particularly monitoring aspartate transaminase, alanine transaminase, urea and creatinine. The essential oil exhibited potent antibacterial activity, whereas the two major constituents were less potent. The essential oil exhibited MIC values between 20 and 80 μg/ml, while the values of the two constituents were between 130 and 200 μg/ml. Scanning electron microscopy results demonstrated that the essential oil inhibited biofilm formation and altered its architecture. Survival curves indicated that the essential oil led to a reduction in the viability of different bacteria. The essential oil also induced significant leakage of potassium ions from S. pyogenes. The essential oil (100 μg/mouse) and grandisol (135 μg/mouse) significantly reduced the number of viable bacterial cells in the lungs (Pessential oil or grandisol 135 μg/mouse once or twice each day for 9 days did not produce any toxic effects in the mice. In conclusion, the in vitro and in vivo results suggested that the essential oil of A. vestita and one of its major constituents, grandisol, can significantly inhibit the growth of different bacterial

  15. Development of an organ-specific insert phantom generated using a 3D printer for investigations of cardiac computed tomography protocols.

    Science.gov (United States)

    Abdullah, Kamarul A; McEntee, Mark F; Reed, Warren; Kench, Peter L

    2018-04-30

    An ideal organ-specific insert phantom should be able to simulate the anatomical features with appropriate appearances in the resultant computed tomography (CT) images. This study investigated a 3D printing technology to develop a novel and cost-effective cardiac insert phantom derived from volumetric CT image datasets of anthropomorphic chest phantom. Cardiac insert volumes were segmented from CT image datasets, derived from an anthropomorphic chest phantom of Lungman N-01 (Kyoto Kagaku, Japan). These segmented datasets were converted to a virtual 3D-isosurface of heart-shaped shell, while two other removable inserts were included using computer-aided design (CAD) software program. This newly designed cardiac insert phantom was later printed by using a fused deposition modelling (FDM) process via a Creatbot DM Plus 3D printer. Then, several selected filling materials, such as contrast media, oil, water and jelly, were loaded into designated spaces in the 3D-printed phantom. The 3D-printed cardiac insert phantom was positioned within the anthropomorphic chest phantom and 30 repeated CT acquisitions performed using a multi-detector scanner at 120-kVp tube potential. Attenuation (Hounsfield Unit, HU) values were measured and compared to the image datasets of real-patient and Catphan ® 500 phantom. The output of the 3D-printed cardiac insert phantom was a solid acrylic plastic material, which was strong, light in weight and cost-effective. HU values of the filling materials were comparable to the image datasets of real-patient and Catphan ® 500 phantom. A novel and cost-effective cardiac insert phantom for anthropomorphic chest phantom was developed using volumetric CT image datasets with a 3D printer. Hence, this suggested the printing methodology could be applied to generate other phantoms for CT imaging studies. © 2018 The Authors. Journal of Medical Radiation Sciences published by John Wiley & Sons Australia, Ltd on behalf of Australian Society of Medical

  16. Herpes simplex virus mutant generation and dual-detection methods for gaining insight into latent/lytic cycles in vivo.

    Science.gov (United States)

    Sawtell, Nancy M; Thompson, Richard L

    2014-01-01

    Two important components to a useful strategy to examine viral gene regulation in vivo are (1) a highly efficient protocol to generate viral mutants that limits undesired mutation and retains full replication competency in vivo and (2) an efficient system to detect and quantify viral promoter activity in rare cells in vivo. Our strategy and protocols for generating, characterizing, and employing HSV viral promoter/reporter mutants in vivo are provided in this two-part chapter.

  17. Investigating the Impact of Hearing Aid Use and Auditory Training on Cognition, Depressive Symptoms, and Social Interaction in Adults With Hearing Loss: Protocol for a Crossover Trial

    Science.gov (United States)

    Meyer, Denny; Blamey, Peter J; Pipingas, Andrew; Bhar, Sunil

    2018-01-01

    Background Sensorineural hearing loss is the most common sensory deficit among older adults. Some of the psychosocial consequences of this condition include difficulty in understanding speech, depression, and social isolation. Studies have shown that older adults with hearing loss show some age-related cognitive decline. Hearing aids have been proven as successful interventions to alleviate sensorineural hearing loss. In addition to hearing aid use, the positive effects of auditory training—formal listening activities designed to optimize speech perception—are now being documented among adults with hearing loss who use hearing aids, especially new hearing aid users. Auditory training has also been shown to produce prolonged cognitive performance improvements. However, there is still little evidence to support the benefits of simultaneous hearing aid use and individualized face-to-face auditory training on cognitive performance in adults with hearing loss. Objective This study will investigate whether using hearing aids for the first time will improve the impact of individualized face-to-face auditory training on cognition, depression, and social interaction for adults with sensorineural hearing loss. The rationale for this study is based on the hypothesis that, in adults with sensorineural hearing loss, using hearing aids for the first time in combination with individualized face-to-face auditory training will be more effective for improving cognition, depressive symptoms, and social interaction rather than auditory training on its own. Methods This is a crossover trial targeting 40 men and women between 50 and 90 years of age with either mild or moderate symmetric sensorineural hearing loss. Consented, willing participants will be recruited from either an independent living accommodation or via a community database to undergo a 6-month intensive face-to-face auditory training program (active control). Participants will be assigned in random order to receive

  18. Vertical Protocol Composition

    DEFF Research Database (Denmark)

    Groß, Thomas; Mödersheim, Sebastian Alexander

    2011-01-01

    The security of key exchange and secure channel protocols, such as TLS, has been studied intensively. However, only few works have considered what happens when the established keys are actually used—to run some protocol securely over the established “channel”. We call this a vertical protocol.......e., that the combination cannot introduce attacks that the individual protocols in isolation do not have. In this work, we prove a composability result in the symbolic model that allows for arbitrary vertical composition (including self-composition). It holds for protocols from any suite of channel and application...

  19. Method for determining transcriptional linkage by means of inhibition of deoxyribonucleic acid transcription by ultraviolet irradiation: evaluation in application to the investigation of in vivo transcription in bacteriophage T7

    International Nuclear Information System (INIS)

    Brautigam, A.R.

    1975-01-01

    A technique is presented for mapping promotor sites that utilizes the introduction of transcription-terminating lesions in DNA through uv irradiation which prevents transcription of genes in proportion to their distance from the promotor. This technique was applied to and evaluated in investigations of the transcriptional linkage of bacteriophage T7. All results substantiate the hypothesis that transcription in vivo does not proceed beyond the first uv lesion encountered in the template DNA and that such premature termination of transcription is the principal effect of the uv irradiation on the transcriptional template function of DNA. UV-induced inhibition of the initiation of transcription is insignificant by comparison. Uv inactivation of expression of individual T7 genes was found to follow pseudo first-order kinetics, allowing a gene-specific uv inactivation cross section to be evaluated for each gene. Promotor locations were inferred from the discontinuity in the numerical values of inactivation cross sections arising at the start of each new unit. By such analysis the bacteriophage T7 genome was found to consist of seven transcription units. In vivo E. coli RNA polymerase transcribes the T7 early region as a single unit from a pomotor region located at the left end of the genome. The T7 late region was found to consist of six transcription units, with promotors located just ahead of genes 1.7, 7, 9, 11, 13 and 17

  20. Investigation of centers sensitive to S1-nuclease in the genoma of the yeast S. cerevisiae after in-vivo exposure to gamma radiation

    International Nuclear Information System (INIS)

    Geigl, E.M.

    1987-09-01

    The structure, distribution and repair of basal damage in DNS after exposure to 60 Co gamma radiation were investigated in S. cerevisiae cells. Small DNS regions with mispaired or unpaired bases of rather high stability were found whose rate of incidence and linear dose dependence appear to be similar to those of double strand breaks. In contrast to double strand breaks, they showed no statistical' distribution pattern across the genoma. Liquid holding experiments showed that centers sensitive to S1-nuclease will be repaired in S. cerevisiae by a combined process of recombination and postreplication repair; the gene products of the genes RAD50 and RAD18 are involved. (orig./AJ) [de

  1. Systematic radiation dose optimization of abdominal dual-energy CT on a second-generation dual-source CT scanner: assessment of the accuracy of iodine uptake measurement and image quality in an in vitro and in vivo investigations.

    Science.gov (United States)

    Schindera, Sebastian T; Zaehringer, Caroline; D'Errico, Luigia; Schwartz, Fides; Kekelidze, Maka; Szucs-Farkas, Zsolt; Benz, Matthias R

    2017-10-01

    To assess the accuracy of iodine quantification in a phantom study at different radiation dose levels with dual-energy dual-source CT and to evaluate image quality and radiation doses in patients undergoing a single-energy and two dual-energy abdominal CT protocols. In a phantom study, the accuracy of iodine quantification (4.5-23.5 mgI/mL) was evaluated using the manufacturer-recommended and three dose-optimized dual-energy protocols. In a patient study, 75 abdomino-pelvic CT examinations were acquired as follows: 25 CT scans with the manufacturer-recommended dual-energy protocol (protocol A); 25 CT scans with a dose-optimized dual-energy protocol (protocol B); and 25 CT scans with a single-energy CT protocol (protocol C). CTDI vol and objective noise were measured. Five readers scored each scan according to six subjective image quality parameters (noise, contrast, artifacts, visibility of small structures, sharpness, overall diagnostic confidence). In the phantom study, differences between the real and measured iodine concentrations ranged from -8.8% to 17.0% for the manufacturer-recommended protocol and from -1.6% to 20.5% for three dose-optimized protocols. In the patient study, the CTDI vol of protocol A, B, and C were 12.5 ± 1.9, 7.5 ± 1.2, and 6.5 ± 1.7 mGycm, respectively (p dual-energy and the single-energy protocol. A dose reduction of 41% is feasible for the manufacturer-recommended, abdominal dual-energy CT protocol, as it maintained the accuracy of iodine measurements and subjective image quality compared to a single-energy protocol.

  2. Preclinical investigation to compare different gadolinium-based contrast agents regarding their propensity to release gadolinium in vivo and to trigger nephrogenic systemic fibrosis-like lesions

    International Nuclear Information System (INIS)

    Sieber, Martin A.; Frenzel, Thomas; Golfier, Sven; Weinmann, Hanns-Joachim; Pietsch, Hubertus; Lengsfeld, Philipp; Schmitt-Willich, Heribert; Siegmund, Fred; Walter, Jakob

    2008-01-01

    Recent reports suggest that nephrogenic systemic fibrosis (NSF) is associated with the administration of gadolinium (Gd)-based contrast agents (GBCAs) and in particular with the stability of the Gd-complex. The aim of this investigation was to compare GBCAs and their potential to trigger NSF. Forty-two healthy male rats received repeated intravenous injections of six different GBCAs at high doses to simulate the exposure seen in patients with severe renal dysfunction. Histopathological and immunohistochemical analysis of the skin was performed, and the concentrations of Gd, zinc and copper were measured in several tissues by inductive coupled plasma atomic emission spectroscopy. Macroscopic and histological skin changes similar to those seen in NSF patients were only observed in rats receiving Omniscan. In addition, very high concentrations of Gd were observed in the animals treated with Omniscan, and, to a lesser extent, in animals treated with OptiMARK. Significantly lower levels of Gd were found after the treatment with ionic linear agents and even less after the treatment with macrocyclic agents. The data in this investigation strongly suggest that the stability of the Gd-complex is a key factor for the development of NSF-like symptoms in this experimental setting. (orig.)

  3. Preclinical investigation to compare different gadolinium-based contrast agents regarding their propensity to release gadolinium in vivo and to trigger nephrogenic systemic fibrosis-like lesions

    Energy Technology Data Exchange (ETDEWEB)

    Sieber, Martin A.; Frenzel, Thomas; Golfier, Sven; Weinmann, Hanns-Joachim; Pietsch, Hubertus [Bayer Schering Pharma AG, TRG Diagnostic Imaging, Berlin (Germany); Lengsfeld, Philipp [Bayer Schering Pharma AG, GMA DG Diagnostic Imaging, Berlin (Germany); Schmitt-Willich, Heribert [Bayer Schering Pharma AG, GDD Diagnostic Imaging, Berlin (Germany); Siegmund, Fred; Walter, Jakob [Bayer Schering Pharma AG, Nonclinical Drug Safety, Berlin (Germany)

    2008-10-15

    Recent reports suggest that nephrogenic systemic fibrosis (NSF) is associated with the administration of gadolinium (Gd)-based contrast agents (GBCAs) and in particular with the stability of the Gd-complex. The aim of this investigation was to compare GBCAs and their potential to trigger NSF. Forty-two healthy male rats received repeated intravenous injections of six different GBCAs at high doses to simulate the exposure seen in patients with severe renal dysfunction. Histopathological and immunohistochemical analysis of the skin was performed, and the concentrations of Gd, zinc and copper were measured in several tissues by inductive coupled plasma atomic emission spectroscopy. Macroscopic and histological skin changes similar to those seen in NSF patients were only observed in rats receiving Omniscan. In addition, very high concentrations of Gd were observed in the animals treated with Omniscan, and, to a lesser extent, in animals treated with OptiMARK. Significantly lower levels of Gd were found after the treatment with ionic linear agents and even less after the treatment with macrocyclic agents. The data in this investigation strongly suggest that the stability of the Gd-complex is a key factor for the development of NSF-like symptoms in this experimental setting. (orig.)

  4. Optimized isolation enables Ex vivo analysis of microglia from various central nervous system regions

    NARCIS (Netherlands)

    De Haas, Alexander H.; Boddeke, Hendricus W. G. M.; Brouwer, Nieske; Biber, Knut

    2007-01-01

    Ex vivo analysis is an accurate and convenient way to study in vivo microglia phenotype and function. However, current microglia isolation protocols for ex vivo analysis show many differences in isolation steps (perfusion, removal of meninges and blood vessels, mechanical dissociation, enzymatic

  5. Sincalide - the final protocol

    International Nuclear Information System (INIS)

    Clarke, E.A.; Notghi, A.; Hesslewood, S.R.; Harding, L.K.

    2002-01-01

    undergoing further investigations. We conclude that 0.6 ngm/kg/minute Sincalide infused over 30 minutes is a satisfactory replacement for CCK and is the protocol we recommend for HIDA studies. (author)

  6. An Investigation into Kyoto Protocol's Clean Development ...

    African Journals Online (AJOL)

    CDM) as a transition mechanism to Kenya's green economy and the contribution of CDM projects towards sustainable development in Kenya. Accordingly, a positive checklist approach to sustainable development indicators was applied as ...

  7. A long-term in vivo investigation on the effects of xenogenous based, electrospun, collagen implants on the healing of experimentally-induced large tendon defects.

    Science.gov (United States)

    Oryan, A; Moshiri, A; Parizi Meimandi, A; Silver, I A

    2013-09-01

    This study was designed to investigate the effect of novel 3-dimensional (3-D) collagen implants on the healing of large, experimentally-induced, tendon-defects in rabbits. Forty mature male white New Zealand rabbits were divided randomly into treated and control groups. Two cm of the left Achilles tendon was excised and the gap was spanned by Kessler suture. In the treated group, a novel 3-D collagen implant was inserted between the cut ends of the tendon. No implant was used in the control group. During the course of the experiment the bioelectrical characteristics of the healing and normal tendons of both groups were investigated weekly. At 120 days post injury (DPI), the tendons were dissected and inspected for gross pathology, examined by transmission and scanning electron microscopy, and their biomechanical properties, percentage dry matter and hydroxyproline concentration assessed. The collagen implant significantly improved the bioelectrical characteristics, gross appearance and tissue alignment of the healed, treated tendons, compared to the healed, control scars. It also significantly increased fibrillogenesis, diameter and density of the collagen fibrils, dry matter content, hydroxyproline concentration, maximum load, stiffness, stress and modulus of elasticity of the treated tendons, as compared to the control tendons. Treatment also significantly decreased peri-tendinous adhesions, and improved the hierarchical organization of the tendon from the collagen fibril to fibre-bundle level. 3-D xenogeneic-based collagen implants induced newly regenerated tissue that was ultrastructurally and biomechanically superior to tissue that was regenerated by natural unassisted healing. This type of bioimplant was biocompatible, biodegradable and appeared suitable for clinical use.

  8. Effect of prophylactic polishing protocols on the surface roughness of esthetic restorative materials.

    Science.gov (United States)

    Neme, A L; Frazier, K B; Roeder, L B; Debner, T L

    2002-01-01

    Many polishing protocols have been evaluated in vitro for their effect on the surface roughness of restorative materials. These results have been useful in establishing protocols for in vivo application. However, limited research has focused on the subsequent care and maintenance of esthetic restorations following their placement. This investigation evaluated the effect of five polishing protocols that could be implemented at recall on the surface roughness of five direct esthetic restorative materials. Specimens (n=25) measuring 8 mm diameter x 3 mm thick were fabricated in an acrylic mold using five light-cured resin-based materials (hybrid composite, microfilled composite, packable composite, compomer and resin-modified glass ionomer). After photopolymerization, all specimens were polished with Sof-Lex Disks to produce an initial (baseline) surface finish. All specimens were then polished with one of five prophylactic protocols (Butler medium paste, Butler coarse paste, OneGloss, SuperBuff or OneGloss & SuperBuff). The average surface roughness of each treated specimen was determined from three measurements with a profilometer (Surface 1). Next, all specimens were brushed 60,000 times at 1.5 Hz using a brush-head force of 2 N on a Manly V-8 cross-brushing machine in a 50:50 (w/w) slurry of toothpaste and water. The surface roughness of each specimen was measured after brushing (Surface 2) followed by re-polishing with one of five protocols, then final surface roughness values were determined (Surface 3). The data were analyzed using repeated measures ANOVA. Significant differences (p=0.05) in surface roughness were observed among restorative materials and polishing protocols. The microfilled and hybrid resin composite yielded significantly rougher surfaces than the other three materials following tooth brushing. Prophylactic polishing protocols can be used to restore a smooth surface on resin-based esthetic restorative materials following simulated tooth

  9. Towards a clinically relevant lentiviral transduction protocol for primary human CD34 hematopoietic stem/progenitor cells.

    Directory of Open Access Journals (Sweden)

    Michelle Millington

    2009-07-01

    Full Text Available Hematopoietic stem cells (HSC, in particular mobilized peripheral blood stem cells, represent an attractive target for cell and gene therapy. Efficient gene delivery into these target cells without compromising self-renewal and multi-potency is crucial for the success of gene therapy. We investigated factors involved in the ex vivo transduction of CD34(+ HSCs in order to develop a clinically relevant transduction protocol for gene delivery. Specifically sought was a protocol that allows for efficient transduction with minimal ex vivo manipulation without serum or other reagents of animal origin.Using commercially available G-CSF mobilized peripheral blood (PB CD34(+ cells as the most clinically relevant target, we systematically examined factors including the use of serum, cytokine combinations, pre-stimulation time, multiplicity of infection (MOI, transduction duration and the use of spinoculation and/or retronectin. A self-inactivating lentiviral vector (SIN-LV carrying enhanced green fluorescent protein (GFP was used as the gene delivery vehicle. HSCs were monitored for transduction efficiency, surface marker expression and cellular function. We were able to demonstrate that efficient gene transduction can be achieved with minimal ex vivo manipulation while maintaining the cellular function of transduced HSCs without serum or other reagents of animal origin.This study helps to better define factors relevant towards developing a standard clinical protocol for the delivery of SIN-LV into CD34(+ cells.

  10. The French dosimetry protocol

    International Nuclear Information System (INIS)

    Dutreix, A.

    1985-01-01

    After a general introduction the protocol is divided in five sections dealing with: determination of the quality of X-ray, γ-ray and electron beams; the measuring instrument; calibration of the reference instrument; determination of the reference absorbed dose in the user's beams; determination of the absorbed dose in water at other points, in other conditions. The French protocol is not essentially different from the Nordic protocol and it is based on the experience gained in using both the American and the Nordic protocols. Therefore, only the main difference with the published protocols are discussed. (Auth.)

  11. The role of three-dimensional pure bovine gelatin scaffolds in tendon healing, modeling, and remodeling: an in vivo investigation with potential clinical value.

    Science.gov (United States)

    Oryan, Ahmad; Sharifi, Pardis; Moshiri, Ali; Silver, Ian A

    2017-09-01

    Large tendon defects involving extensive tissue loss present complex clinical problems. Surgical reconstruction of such injuries is normally performed by transplanting autogenous and allogenous soft tissues that are expected to remodel to mimic a normal tendon. However, the use of grafts has always been associated with significant limitations. Tissue engineering employing artificial scaffolds may provide acceptable alternatives. Gelatin is a hydrolyzed form of collagen that is bioactive, biodegradable, and biocompatible. The present study has investigated the suitability of gelatin scaffold for promoting healing of a large tendon-defect model in rabbits. An experimental model of a large tendon defect was produced by partial excision of the Achilles tendon of the left hind leg in adult rabbits. To standardize and stabilize the length of the tendon defect a modified Kessler core suture was anchored in the sectioned tendon ends. The defects were either left untreated or filled with three-dimensional gelatin scaffold. Before euthanasia 60 days after injury, the progress of healing was evaluated clinically. Samples of healing tendon were harvested at autopsy and evaluated by gross, histopathologic, scanning, and transmission electron microscopy, and by biomechanical testing. The treated animals showed superior weight-bearing and physical activity compared with those untreated, while frequency of peritendinous adhesions around the healing site was reduced. The gelatin scaffold itself was totally degraded and replaced by neo-tendon that morphologically had significantly greater numbers, diameters, density, and maturation of collagen fibrils, fibers, and fiber bundles than untreated tendon scar tissue. It also had mechanically higher ultimate load, yield load, stiffness, maximum stress and elastic modulus, when compared to the untreated tendons. Gelatin scaffold may be a valuable option in surgical reconstruction of large tendon defects.

  12. Protocol Implementation Generator

    DEFF Research Database (Denmark)

    Carvalho Quaresma, Jose Nuno; Probst, Christian W.

    2010-01-01

    Users expect communication systems to guarantee, amongst others, privacy and integrity of their data. These can be ensured by using well-established protocols; the best protocol, however, is useless if not all parties involved in a communication have a correct implementation of the protocol and a...... Generator framework based on the LySatool and a translator from the LySa language into C or Java....... necessary tools. In this paper, we present the Protocol Implementation Generator (PiG), a framework that can be used to add protocol generation to protocol negotiation, or to easily share and implement new protocols throughout a network. PiG enables the sharing, verification, and translation...

  13. A general protocol for the generation of Nanobodies for structural biology

    DEFF Research Database (Denmark)

    Pardon, Els; Laeremans, Toon; Triest, Sarah

    2014-01-01

    There is growing interest in using antibodies as auxiliary tools to crystallize proteins. Here we describe a general protocol for the generation of Nanobodies to be used as crystallization chaperones for the structural investigation of diverse conformational states of flexible (membrane) proteins...... and complexes thereof. Our technology has a competitive advantage over other recombinant crystallization chaperones in that we fully exploit the natural humoral response against native antigens. Accordingly, we provide detailed protocols for the immunization with native proteins and for the selection by phage...... display of in vivo-matured Nanobodies that bind conformational epitopes of functional proteins. Three representative examples illustrate that the outlined procedures are robust, making it possible to solve by Nanobody-assisted X-ray crystallography in a time span of 6-12 months....

  14. Investigation of Combined Action of Food Supplement's and Ionizing Radiation on the Cytogenetic Damage Induction and Ehrlich Ascite Carcinoma Growth on Mice in Vivo

    Science.gov (United States)

    Sorokina, Svetlana; Zaichkina, Svetlana; Dyukina, Alsu; Rozanova, Olga; Balakin, Vladimir; Peleshko, Vladimir; Romanchenko, Sergey; Smirnova, Helena; Aptikaeva, Gella; Shemyakov, Alexander

    In recent ten years one of the major problems of modern radiobiology is the study of radiation protective mechanisms with the help of different substances as well as activation of internal resources of the organism. Internal resources mean such phenomena as hormesis and adaptive response which represent cell or body reaction on low doses of inducing factors and predetermine their further high dose effect resistance. At present special interest is attracted by studies of biological effects of low-dose-rate high-LET radiation because of searching for new types of radiation for more effective cancer therapy and searching for new methods of radiation protection. Since natural biologically active substances have low toxicity and are capable of affecting physiological processes taking place in human’s organism and increasing organism’s natural defense system, the interest to protective means of vegetal origin and search of special food supplements intensifies every year. The purpose of this study is to investigate the combined influence of food supplement, low dose rate high-LET radiation simulating high-altitude flight conditions and X-ray radiations on radiosensitivity, induction of radiation adaptive response (RAR) and growth of Ehrlich ascite carcinoma as well. Experiments were performed with males of SHK mice at the age of two months. The animals were being irradiated with low-dose-rate high-LET radiation with the dose of 11,6 cGy (0,5 cGy/day) behind the concrete shield of the 70 GeV protons accelerator (Protvino). The X-ray irradiation was carried out on the RTH device with a voltage of 200 kV (1 Gy/min; Pushchino). The diet composition included products containing big amount of biologically active substances, such as: soybeam meat, buckwheat, lettuce leaves and drug of cod-liver oil. Four groups of mice were fed with selected products mentioned above during the whole irradiation period of 22 days. The control groups received the same food without irradiation

  15. Mapping in vivo target interaction profiles of covalent inhibitors using chemical proteomics with label-free quantification.

    Science.gov (United States)

    van Rooden, Eva J; Florea, Bogdan I; Deng, Hui; Baggelaar, Marc P; van Esbroeck, Annelot C M; Zhou, Juan; Overkleeft, Herman S; van der Stelt, Mario

    2018-04-01

    Activity-based protein profiling (ABPP) has emerged as a valuable chemical proteomics method to guide the therapeutic development of covalent drugs by assessing their on-target engagement and off-target activity. We recently used ABPP to determine the serine hydrolase interaction landscape of the experimental drug BIA 10-2474, thereby providing a potential explanation for the adverse side effects observed with this compound. ABPP allows mapping of protein interaction landscapes of inhibitors in cells, tissues and animal models. Whereas our previous protocol described quantification of proteasome activity using stable-isotope labeling, this protocol describes the procedures for identifying the in vivo selectivity profile of covalent inhibitors with label-free quantitative proteomics. The optimization of our protocol for label-free quantification methods results in high proteome coverage and allows the comparison of multiple biological samples. We demonstrate our protocol by assessing the protein interaction landscape of the diacylglycerol lipase inhibitor DH376 in mouse brain, liver, kidney and testes. The stages of the protocol include tissue lysis, probe incubation, target enrichment, sample preparation, liquid chromatography-mass spectrometry (LC-MS) measurement, data processing and analysis. This approach can be used to study target engagement in a native proteome and to identify potential off targets for the inhibitor under investigation. The entire protocol takes at least 4 d, depending on the number of samples.

  16. Investigation of the neuroprotective effects of bee-venom acupuncture in a mouse model of Parkinson's disease by using immunohistochemistry and In-vivo 1H magnetic resonance spectroscopy at 9.4 T

    Science.gov (United States)

    Yoon, Moon-Hyun; Lee, Do-Wan; Kim, Hyun-Jin; Chung, Jin-Yeung; Doo, Ah-Reum; Park, Hi-Joon; Kim, Seung-Nam; Choe, Bo-Young

    2013-01-01

    Neuroprotective therapeutics slows down the degeneration process in animal models of Parkinson's disease (PD). The neuronal survival in PD animal models is often measured by using immunohistochemistry. However, dynamic changes in the pathology of the brain cannot be explored with this technique. Application of in-vivo 1H magnetic resonance spectroscopy (1H MRS) can cover this shortcoming, as these techniques are non-invasive and can be repeated over time in the same animal. Thus, the sensitivity of both techniques to measure changes in the PD pathology was explored in an experiment studying the neuroprotective effects of the vigilance enhancer bee-venom (BV) in a mouse model of PD. The mice were pre-treated with 0.02-ml BV administered to the acupuncture point GB34 (Yangneungcheon) once every 3 days for 2 weeks. Three groups were classified as control, MPTP-intoxicated PD model and BV-treated mice. Outer volume suppression combined with the ultra-short echo-time STEAM (TE = 2.2 ms, TM = 20 ms, TR = 5000 ms) was used for localized in-vivo 1H MRS. Based on the 1H MRS spectral analysis, substantial changes of the neurochemical profiles were evaluated in the three investigated groups. In particular, the glutamate complex (Glx)/creatine (Cr) ratio (7.72 ± 1.25) in the PD group was significantly increased compared to that in the control group (3.93 ± 2.21, P = 0.001). Compared to the baseline values, the Glx/Cr ratio of the BV-treated group was significantly decreased 2 weeks after MPTP intoxication (one-way ANOVA, p < 0.05). In conclusion, the present study demonstrated that neurochemical alterations occurred in the three groups and that the neuroprotective effects of the BV acupuncture in a mouse model of PD could be quantified by using immunohistochemistry and 1H MRS.

  17. In Vivo MRI Quantification of Individual Muscle and Organ Volumes for Assessment of Anabolic Steroid Growth Effects

    Science.gov (United States)

    Wu, Ed X.; Tang, Haiying; Tong, Christopher; Heymsfield, Steve B.; Vasselli, Joseph R.

    2015-01-01

    This study aimed to develop a quantitative and in vivo magnetic resonance imaging (MRI) approach to investigate the muscle growth effects of anabolic steroids. A protocol of MRI acquisition on a standard clinical 1.5 Tesla scanner and quantitative image analysis was established and employed to measure the individual muscle and organ volumes in the intact and castrated guinea pigs undergoing a 16-week treatment protocol by two well-documented anabolic steroids, testosterone and nandrolone, via implanted silastic capsules. High correlations between the in vivo MRI and postmortem dissection measurements were observed for shoulder muscle complex (R = 0.86), masseter (R=0.79), temporalis (R=0.95), neck muscle complex (R=0.58), prostate gland and seminal vesicles (R=0.98), and testis (R=0.96). Furthermore, the longitudinal MRI measurements yielded adequate sensitivity to detect the restoration of growth to or towards normal in castrated guinea pigs by replacing circulating steroid levels to physiological or slightly higher levels, as expected. These results demonstrated that quantitative MRI using a standard clinical scanner provides accurate and sensitive measurement of individual muscles and organs, and this in vivo MRI protocol in conjunction with the castrated guinea pig model constitutes an effective platform to investigate the longitudinal and cross-sectional growth effects of other potential anabolic steroids. The quantitative MRI protocol developed can also be readily adapted for human studies on most clinical MRI scanner to investigate the anabolic steroid growth effects, or monitor the changes in individual muscle and organ volume and geometry following injury, strength training, neuromuscular disorders, and pharmacological or surgical interventions. PMID:18241900

  18. In vivo MRI quantification of individual muscle and organ volumes for assessment of anabolic steroid growth effects.

    Science.gov (United States)

    Wu, Ed X; Tang, Haiying; Tong, Christopher; Heymsfield, Steve B; Vasselli, Joseph R

    2008-04-01

    This study aimed to develop a quantitative and in vivo magnetic resonance imaging (MRI) approach to investigate the muscle growth effects of anabolic steroids. A protocol of MRI acquisition on a standard clinical 1.5 T scanner and quantitative image analysis was established and employed to measure the individual muscle and organ volumes in the intact and castrated guinea pigs undergoing a 16-week treatment protocol by two well-documented anabolic steroids, testosterone and nandrolone, via implanted silastic capsules. High correlations between the in vivo MRI and postmortem dissection measurements were observed for shoulder muscle complex (R=0.86), masseter (R=0.79), temporalis (R=0.95), neck muscle complex (R=0.58), prostate gland and seminal vesicles (R=0.98), and testis (R=0.96). Furthermore, the longitudinal MRI measurements yielded adequate sensitivity to detect the restoration of growth to or towards normal in castrated guinea pigs by replacing circulating steroid levels to physiological or slightly higher levels, as expected. These results demonstrated that quantitative MRI using a standard clinical scanner provides accurate and sensitive measurement of individual muscles and organs, and this in vivo MRI protocol in conjunction with the castrated guinea pig model constitutes an effective platform to investigate the longitudinal and cross-sectional growth effects of other potential anabolic steroids. The quantitative MRI protocol developed can also be readily adapted for human studies on most clinical MRI scanner to investigate the anabolic steroid growth effects, or monitor the changes in individual muscle and organ volume and geometry following injury, strength training, neuromuscular disorders, and pharmacological or surgical interventions.

  19. Fosfomycin versus meropenem in bacteraemic urinary tract infections caused by extended-spectrum β-lactamase-producing Escherichia coli (FOREST): study protocol for an investigator-driven randomised controlled trial.

    Science.gov (United States)

    Rosso-Fernández, Clara; Sojo-Dorado, Jesús; Barriga, Angel; Lavín-Alconero, Lucía; Palacios, Zaira; López-Hernández, Inmaculada; Merino, Vicente; Camean, Manuel; Pascual, Alvaro; Rodríguez-Baño, Jesús

    2015-03-31

    Finding therapeutic alternatives to carbapenems in infections caused by extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) is imperative. Although fosfomycin was discovered more than 40 years ago, it was not investigated in accordance with current standards and so is not used in clinical practice except in desperate situations. It is one of the so-called neglected antibiotics of high potential interest for the future. The main objective of this project is to demonstrate the clinical non-inferiority of intravenous fosfomycin with regard to meropenem for treating bacteraemic urinary tract infections (UTI) caused by ESBL-EC. This is a 'real practice' multicentre, open-label, phase III randomised controlled trial, designed to compare the clinical and microbiological efficacy, and safety of intravenous fosfomycin (4 g/6 h) and meropenem (1 g/8 h) as targeted therapy for this infection; a change to oral therapy is permitted after 5 days in both arms, in accordance with predetermined options. The study design follows the latest recommendations for designing trials investigating new options for multidrug-resistant bacteria. Secondary objectives include the study of fosfomycin concentrations in plasma and the impact of both drugs on intestinal colonisation by multidrug-resistant Gram-negative bacilli. Ethical approval was obtained from the Andalusian Coordinating Institutional Review Board (IRB) for Biomedical Research (Referral Ethics Committee), which obtained approval from the local ethics committees at all participating sites in Spain (22 sites). Data will be presented at international conferences and published in peer-reviewed journals. This project is proposed as an initial step in the investigation of an orphan antimicrobial of low cost with high potential as a therapeutic alternative in common infections such as UTI in selected patients. These results may have a major impact on the use of antibiotics and the development of new projects

  20. Near-infrared optical imaging of nucleic acid nanocarriers in vivo.

    Science.gov (United States)

    Rome, Claire; Gravier, Julien; Morille, Marie; Divita, Gilles; Bolcato-Bellemin, Anne-Laure; Josserand, Véronique; Coll, Jean-Luc

    2013-01-01

    Noninvasive, real-time optical imaging methods are well suited to follow the in vivo distribution of nucleic acid nanocarriers, their dissociation, and the resulting gene expression or inhibition. Indeed, most small animal imaging devices perform bioluminescence and fluorescence measurements without moving the animal, allowing a simple, rapid, and cost-effective method of investigation of several parameters at a time, in longitudinal experiments that can last for days or weeks.Here we help the reader in choosing adapted near-infrared (NIR) fluorophores or pairs of fluorophores for Förster resonance energy transfer assays, imaging of reporter genes, as well as nanocarriers for in vivo gene and siRNA delivery. In addition, we present the labeling methods of these macromolecules and of their payload and the protocols to detect them using bioluminescence and NIR fluorescence imaging in mice.

  1. The value of a rapid contrast-enhanced angio-MRI protocol in the detection of head and neck paragangliomas in SDHx mutations carriers: a retrospective study on behalf of the PGL.EVA investigators*

    International Nuclear Information System (INIS)

    Gravel, Guillaume; Hernigou, Anne; Niccoli, Patricia; Rohmer, Vincent; Moulin, Guy; Borson-Chazot, Francoise; Rousset, Pascal; Pasco-Papon, Anne; Marcus, Claude; Dubrulle, Frederique; Gouya, Herve; Bidault, Francois; Dupas, Benoit; Gabrillargues, Jean; Caumont-Prim, Aurore; Gimenez-Roqueplo, Anne-Paule; Halimi, Philippe

    2016-01-01

    To assess the performance of a simplified MRI protocol consisting of a contrast-enhanced three-dimensional MR angiography (CE-MRA) in association with a post-contrast T1-weighted sequence (T1WIV) for the detection of HNPGLs in SDHx mutation carriers. This retrospective sub-study is based on the multicenter PGL.EVA cohort, which prospectively enrolled SDHx mutation carriers from 2005 to 2009; 157 index cases or relatives were included. CE-MRA and the T1WIV images were read solely with knowledge of the clinical data but blind to the diagnosis. Sensitivity, specificity and likelihood ratios for the simplified MRI protocol were compared to the full MRI protocol reading results and to the gold standard status obtained through the consensus of an expert committee. The sensitivity and specificity of the readings of the simplified MRI protocol were, respectively, 88.7 % (95 % CI = 78.1-95.3) and 93.7 % (95 % CI = 86.8-97.7) versus 80.7 % (95 % CI = 68.6-89.6) and 94.7 % (95 % CI = 88.1-98.3) for the readings of the full MRI protocol. The simplified post-contrast MRI with shorter duration (5 to 10 minutes) showed no performance difference compared to the lengthy standard full MRI and can be proposed for the detection of head and neck paragangliomas (HNPGLs) in SDHx mutation carriers. (orig.)

  2. The value of a rapid contrast-enhanced angio-MRI protocol in the detection of head and neck paragangliomas in SDHx mutations carriers: a retrospective study on behalf of the PGL.EVA investigators*

    Energy Technology Data Exchange (ETDEWEB)

    Gravel, Guillaume; Hernigou, Anne [Hopital Europeen Georges Pompidou, Assistance Publique-Hopitaux de Paris, Service de Radiologie, Paris (France); Niccoli, Patricia [Centre Hospitalier Universitaire la Timone, Assistance Publique-Hopitaux de Marseille, Service d' Endocrinologie, Diabete et Maladies Metaboliques, Marseille (France); Rohmer, Vincent [Centre Hospitalier Universitaire d' Angers, Service d' Endocrinologie, Diabetologie, Nutrition, Angers (France); LUNAM Universite, INSERM, U1063, Angers (France); Moulin, Guy [Centre Hospitalier Universitaire la Timone, Assistance Publique-Hopitaux de Marseille, Service de Radiologie, Marseille (France); Borson-Chazot, Francoise [Federation d' Endocrinologie, Hospices civils de Lyon, Groupement Hospitalier Est, Lyon (France); Universite de Lyon, Faculte de Medecine Lyon-Est, Lyon (France); Cancer Research Center of Lyon, INSERM UMR1052, UMR CNRS 5286, Lyon (France); Rousset, Pascal [Hospices civils de Lyon, Groupement Hospitalier Est, Service de Radiologie, Lyon (France); Pasco-Papon, Anne [Centre Hospitalier Universitaire d' Angers, Service de Radiologie, Angers (France); Marcus, Claude [Centre Hospitalo-Universitaire de Reims, Service de Radiologie, Reims (France); Dubrulle, Frederique [Centre Hospitalo-Universitaire de Lille, Service de Radiologie, Lille (France); Gouya, Herve [Hopital Cochin, Assistance Publique-Hopitaux de Paris, Service de Radiologie, Paris (France); Bidault, Francois [Institut Gustave Roussy, Service de Radiologie, Villejuif (France); Dupas, Benoit [Centre Hospitalo-Universitaire de Nantes, Service de Radiologie, Nantes (France); Gabrillargues, Jean [Centre Hospitalo-Universitaire de Clermont-Ferrand, Service de Neuroradiologie, Clermont Ferrand (France); Caumont-Prim, Aurore [Unite d' Epidemiologie et de Recherche Clinique, Assistance Publique-Hopitaux de Paris, Hopital Europeen Georges Pompidou, Paris (France); Centre d' investigation Epidemiologique 4, INSERM, Paris (France); Gimenez-Roqueplo, Anne-Paule [Hopital Europeen Georges Pompidou, Assistance Publique-Hopitaux de Paris, Service de Genetique, Paris (France); Paris Cardiovascular Research Center, INSERM, UMR970, Paris (France); Universite Paris Descartes, Sorbonne Paris Cite, Faculte de Medecine, Paris (France); Halimi, Philippe [Hopital Europeen Georges Pompidou, Assistance Publique-Hopitaux de Paris, Service de Radiologie, Paris (France); Universite Paris Descartes, Sorbonne Paris Cite, Faculte de Medecine, Paris (France)

    2016-06-15

    To assess the performance of a simplified MRI protocol consisting of a contrast-enhanced three-dimensional MR angiography (CE-MRA) in association with a post-contrast T1-weighted sequence (T1WIV) for the detection of HNPGLs in SDHx mutation carriers. This retrospective sub-study is based on the multicenter PGL.EVA cohort, which prospectively enrolled SDHx mutation carriers from 2005 to 2009; 157 index cases or relatives were included. CE-MRA and the T1WIV images were read solely with knowledge of the clinical data but blind to the diagnosis. Sensitivity, specificity and likelihood ratios for the simplified MRI protocol were compared to the full MRI protocol reading results and to the gold standard status obtained through the consensus of an expert committee. The sensitivity and specificity of the readings of the simplified MRI protocol were, respectively, 88.7 % (95 % CI = 78.1-95.3) and 93.7 % (95 % CI = 86.8-97.7) versus 80.7 % (95 % CI = 68.6-89.6) and 94.7 % (95 % CI = 88.1-98.3) for the readings of the full MRI protocol. The simplified post-contrast MRI with shorter duration (5 to 10 minutes) showed no performance difference compared to the lengthy standard full MRI and can be proposed for the detection of head and neck paragangliomas (HNPGLs) in SDHx mutation carriers. (orig.)

  3. Network protocols and sockets

    OpenAIRE

    BALEJ, Marek

    2010-01-01

    My work will deal with network protocols and sockets and their use in programming language C#. It will therefore deal programming network applications on the platform .NET from Microsoft and instruments, which C# provides to us. There will describe the tools and methods for programming network applications, and shows a description and sample applications that work with sockets and application protocols.

  4. In Vivo Investigation of the Safety and Efficacy of Pulsed Dye Laser with Two Spot Sizes in Port-Wine Stain Treatment: A Prospective Side-by-Side Comparison.

    Science.gov (United States)

    Yu, Wenxin; Ying, Hanru; Chen, Yijie; Qiu, Yajing; Chen, Hui; Jin, Yunbo; Yang, Xi; Wang, Tianyou; Ma, Gang; Lin, Xiaoxi

    2017-09-01

    Pulsed dye laser (PDL) with 7 and 10 mm spot sizes is widely used on a regular basis for the treatment of port-wine stain (PWS). No studies have reported on the differences in efficacy outcomes resulting from the use of different laser spot sizes in the treatment of PWS by PDL. Thus, an in vivo investigation into the differences in safety and efficacy of treatment between two spot sizes (7 vs. 10 mm) of PWS by PDL was conducted. A total of 35 PWS patients underwent three treatment sessions by using a 595 nm wavelength PDL (Vbeam ® , Candela Corp) with two laser settings: (1) 7 mm spot size, radiant exposure of 12 J/cm 2 and (2) 10 mm spot size, radiant exposure of 10 J/cm 2 . Cryogen spray cooling and 1.5 msec pulse duration were applied. Therapeutic outcomes were evaluated by visual and chromametric evaluation 3 months after the final treatment. Average blanching rates were 34.03% and 36.51% at sites treated by PDL with 7 and 10 mm laser spot sizes, respectively (p spot sizes were similar. PDL with a 10 mm laser spot size is more efficacious with lower radiant exposure than PDL with a 7 mm spot size; it can also reduce the treatment time.

  5. Current investigations into the genotoxicity of zinc oxide and silica nanoparticles in mammalian models in vitro and in vivo: carcinogenic/genotoxic potential, relevant mechanisms and biomarkers, artifacts, and limitations

    Directory of Open Access Journals (Sweden)

    Kwon JY

    2014-12-01

    Full Text Available Jee Young Kwon,1,* Preeyaporn Koedrith,2,* Young Rok Seo1 1Department of Life Science, Institute of Environmental Medicine, Dongguk University, Seoul, Republic of Korea; 2Faculty of Environment and Resource Studies, Mahidol University, Phuttamonthon District, NakhonPathom, Thailand *These authors contributed equally to this work and should be considered as co-first authors Abstract: Engineered nanoparticles (NPs are widely used in many sectors, such as food, medicine, military, and sport, but their unique characteristics may cause deleterious health effects. Close attention is being paid to metal NP genotoxicity; however, NP genotoxic/carcinogenic effects and the underlying mechanisms remain to be elucidated. In this review, we address some metal and metal oxide NPs of interest and current genotoxicity tests in vitro and in vivo. Metal NPs can cause DNA damage such as chromosomal aberrations, DNA strand breaks, oxidative DNA damage, and mutations. We also discuss several parameters that may affect genotoxic response, including physicochemical properties, widely used assays/end point tests, and experimental conditions. Although potential biomarkers of nanogenotoxicity or carcinogenicity are suggested, inconsistent findings in the literature render results inconclusive due to a variety of factors. Advantages and limitations related to different methods for investigating genotoxicity are described, and future directions and recommendations for better understanding genotoxic potential are addressed. Keywords: carcinogenicity, exposure assessment, genotoxicity, nanoparticles, risk evaluation

  6. How Does Food Taste in Anorexia and Bulimia Nervosa? A Protocol for a Quasi-Experimental, Cross-Sectional Design to Investigate Taste Aversion or Increased Hedonic Valence of Food in Eating Disorders

    Directory of Open Access Journals (Sweden)

    David Garcia-Burgos

    2018-03-01

    Full Text Available Background: Despite on-going efforts to better understand dysregulated eating, the olfactory-gustatory deficits and food preferences in eating disorders (ED, and the mechanisms underlying the perception of and responses to food properties in anorexia nervosa (AN and bulimia nervosa (BN remain largely unknown; both during the course of the illness and compared to healthy populations. It is, therefore, necessary to systematically investigate the gustatory perception and hedonics of taste in patients with AN and BN. To this end, we will examine whether aversions to the taste of high-calorie food is related to the suppression of energy intake in restricting-type AN, and whether an increased hedonic valence of sweet, caloric-dense foods may be part of the mechanisms triggering binge-eating episodes in BN. In addition, the role of cognitions influencing these mechanisms will be examined.Method: In study 1, four mixtures of sweet-fat stimuli will be presented in a sensory two-alternative forced-choice test involving signal detection analysis. In study 2, a full-scale taste reactivity test will be carried out, including psychophysiological and behavioral measures to assess subtle and covert hedonic changes. We will compare the responses of currently-ill AN and BN patients to those who have recovered from AN and BN, and also to those of healthy normal-weight and underweight individuals without any eating disorder pathology.Discussion: If taste response profiles are differentially linked to ED types, then future studies should investigate whether taste responsiveness represents a useful diagnostic measure in the prevention, assessment and treatment of EDs. The expected results on cognitive mechanisms in the top-down processes of food hedonics will complement current models and contribute to the refinement of interventions to change cognitive aspects of taste aversions, to establish functional food preferences and to better manage food cravings associated

  7. How Does Food Taste in Anorexia and Bulimia Nervosa? A Protocol for a Quasi-Experimental, Cross-Sectional Design to Investigate Taste Aversion or Increased Hedonic Valence of Food in Eating Disorders

    Science.gov (United States)

    Garcia-Burgos, David; Maglieri, Sabine; Vögele, Claus; Munsch, Simone

    2018-01-01

    Background: Despite on-going efforts to better understand dysregulated eating, the olfactory-gustatory deficits and food preferences in eating disorders (ED), and the mechanisms underlying the perception of and responses to food properties in anorexia nervosa (AN) and bulimia nervosa (BN) remain largely unknown; both during the course of the illness and compared to healthy populations. It is, therefore, necessary to systematically investigate the gustatory perception and hedonics of taste in patients with AN and BN. To this end, we will examine whether aversions to the taste of high-calorie food is related to the suppression of energy intake in restricting-type AN, and whether an increased hedonic valence of sweet, caloric-dense foods may be part of the mechanisms triggering binge-eating episodes in BN. In addition, the role of cognitions influencing these mechanisms will be examined. Method: In study 1, four mixtures of sweet-fat stimuli will be presented in a sensory two-alternative forced-choice test involving signal detection analysis. In study 2, a full-scale taste reactivity test will be carried out, including psychophysiological and behavioral measures to assess subtle and covert hedonic changes. We will compare the responses of currently-ill AN and BN patients to those who have recovered from AN and BN, and also to those of healthy normal-weight and underweight individuals without any eating disorder pathology. Discussion: If taste response profiles are differentially linked to ED types, then future studies should investigate whether taste responsiveness represents a useful diagnostic measure in the prevention, assessment and treatment of EDs. The expected results on cognitive mechanisms in the top-down processes of food hedonics will complement current models and contribute to the refinement of interventions to change cognitive aspects of taste aversions, to establish functional food preferences and to better manage food cravings associated with binge

  8. How Does Food Taste in Anorexia and Bulimia Nervosa? A Protocol for a Quasi-Experimental, Cross-Sectional Design to Investigate Taste Aversion or Increased Hedonic Valence of Food in Eating Disorders.

    Science.gov (United States)

    Garcia-Burgos, David; Maglieri, Sabine; Vögele, Claus; Munsch, Simone

    2018-01-01

    Background: Despite on-going efforts to better understand dysregulated eating, the olfactory-gustatory deficits and food preferences in eating disorders (ED), and the mechanisms underlying the perception of and responses to food properties in anorexia nervosa (AN) and bulimia nervosa (BN) remain largely unknown; both during the course of the illness and compared to healthy populations. It is, therefore, necessary to systematically investigate the gustatory perception and hedonics of taste in patients with AN and BN. To this end, we will examine whether aversions to the taste of high-calorie food is related to the suppression of energy intake in restricting-type AN, and whether an increased hedonic valence of sweet, caloric-dense foods may be part of the mechanisms triggering binge-eating episodes in BN. In addition, the role of cognitions influencing these mechanisms will be examined. Method: In study 1, four mixtures of sweet-fat stimuli will be presented in a sensory two-alternative forced-choice test involving signal detection analysis. In study 2, a full-scale taste reactivity test will be carried out, including psychophysiological and behavioral measures to assess subtle and covert hedonic changes. We will compare the responses of currently-ill AN and BN patients to those who have recovered from AN and BN, and also to those of healthy normal-weight and underweight individuals without any eating disorder pathology. Discussion: If taste response profiles are differentially linked to ED types, then future studies should investigate whether taste responsiveness represents a useful diagnostic measure in the prevention, assessment and treatment of EDs. The expected results on cognitive mechanisms in the top-down processes of food hedonics will complement current models and contribute to the refinement of interventions to change cognitive aspects of taste aversions, to establish functional food preferences and to better manage food cravings associated with binge

  9. In vivo stem cell transplantation using reduced cell numbers.

    Science.gov (United States)

    Tsutsui, Takeo W

    2015-01-01

    Dental pulp stem cell (DPSC) characterization is essential for regeneration of a dentin/pulp like complex in vivo. This is especially important for identifying the potential of DPSCs to function as stem cells. Previously reported DPSC transplantation methods have used with huge numbers of cells, along with hydroxyapatite/tricalcium phosphate (HA/TCP), gelatin and fibrin, and collagen scaffolds. This protocol describe a transplantation protocol that uses fewer cells and a temperature-responsive cell culture dish.

  10. Lessons learned from vivo-morpholinos: How to avoid vivo-morpholino toxicity

    Science.gov (United States)

    Ferguson, David P.; Dangott, Lawrence J.; Lightfoot, J. Timothy

    2014-01-01

    Vivo-morpholinos are a promising tool for gene silencing. These oligonucleotide analogs transiently silence genes by blocking either translation or pre-mRNA splicing. Little to no toxicity has been reported for vivo-morpholino treatment. However, in a recent study conducted in our lab, treatment of mice with vivo-morpholinos resulted in high mortality rates. We hypothesized that the deaths were the result of oligonucleotide hybridization, causing an increased cationic charge associated with the dendrimer delivery moiety of the vivo-morpholino. The cationic charge increased blood clot formation in whole blood treated with vivo-morpholinos, suggesting that clotting could have caused cardiac arrest in the deceased mice. Therefore, we investigate the mechanism by which some vivo-morpholinos increase mortality rates and propose techniques to alleviate vivo-morpholino toxicity. PMID:24806225

  11. SPIRIT 2013 Statement: defining standard protocol items for clinical trials.

    Science.gov (United States)

    Chan, An-Wen; Tetzlaff, Jennifer M; Altman, Douglas G; Laupacis, Andreas; Gøtzsche, Peter C; Krle A-Jerić, Karmela; Hrobjartsson, Asbjørn; Mann, Howard; Dickersin, Kay; Berlin, Jesse A; Dore, Caroline J; Parulekar, Wendy R; Summerskill, William S M; Groves, Trish; Schulz, Kenneth F; Sox, Harold C; Rockhold, Frank W; Rennie, Drummond; Moher, David

    2015-12-01

    The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol. The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders.

  12. In vivo genotoxic effects of dietary heme iron on rat colon mucosa and ex vivo effects on colon cells monitored by an optimized alkaline comet assay.

    Directory of Open Access Journals (Sweden)

    Océane, C Martin

    2015-04-01

    In conclusion, our results offer a suitable protocol to evaluate genotoxicity on in vivo cryopreserved colon mucosa and on in vitro murine colonic cells, with a middle throughput capacity. This protocol confirms the increase of genotoxicity in rat colon mucosa after an heme-iron diet. Moreover, this protocol enables the demonstration that aldehydes from heme-induced lipoperoxidation are responsible for this increase of genotoxicity.

  13. Topology Discovery Using Cisco Discovery Protocol

    OpenAIRE

    Rodriguez, Sergio R.

    2009-01-01

    In this paper we address the problem of discovering network topology in proprietary networks. Namely, we investigate topology discovery in Cisco-based networks. Cisco devices run Cisco Discovery Protocol (CDP) which holds information about these devices. We first compare properties of topologies that can be obtained from networks deploying CDP versus Spanning Tree Protocol (STP) and Management Information Base (MIB) Forwarding Database (FDB). Then we describe a method of discovering topology ...

  14. Ex-vivo MR Volumetry of Human Brain Hemispheres

    Science.gov (United States)

    Kotrotsou, Aikaterini; Bennett, David A.; Schneider, Julie A.; Dawe, Robert J.; Golak, Tom; Leurgans, Sue E.; Yu, Lei; Arfanakis, Konstantinos

    2013-01-01

    Purpose The aims of this work were to: a) develop an approach for ex-vivo MR volumetry of human brain hemispheres that does not contaminate the results of histopathological examination, b) longitudinally assess regional brain volumes postmortem, and c) investigate the relationship between MR volumetric measurements performed in-vivo and ex-vivo. Methods An approach for ex-vivo MR volumetry of human brain hemispheres was developed. Five hemispheres from elderly subjects were imaged ex-vivo longitudinally. All datasets were segmented. The longitudinal behavior of volumes measured ex-vivo was assessed. The relationship between in-vivo and ex-vivo volumetric measurements was investigated in seven elderly subjects imaged both ante-mortem and postmortem. Results The presented approach for ex-vivo MR volumetry did not contaminate the results of histopathological examination. For a period of 6 months postmortem, within-subject volume variation across time points was substantially smaller than inter-subject volume variation. A close linear correspondence was detected between in-vivo and ex-vivo volumetric measurements. Conclusion Regional brain volumes measured with the presented approach for ex-vivo MR volumetry remain relatively unchanged for a period of 6 months postmortem. Furthermore, the linear relationship between in-vivo and ex-vivo MR volumetric measurements suggests that the presented approach captures information linked to ante-mortem macrostructural brain characteristics. PMID:23440751

  15. Ex vivo MR volumetry of human brain hemispheres.

    Science.gov (United States)

    Kotrotsou, Aikaterini; Bennett, David A; Schneider, Julie A; Dawe, Robert J; Golak, Tom; Leurgans, Sue E; Yu, Lei; Arfanakis, Konstantinos

    2014-01-01

    The aims of this work were to (a) develop an approach for ex vivo MR volumetry of human brain hemispheres that does not contaminate the results of histopathological examination, (b) longitudinally assess regional brain volumes postmortem, and (c) investigate the relationship between MR volumetric measurements performed in vivo and ex vivo. An approach for ex vivo MR volumetry of human brain hemispheres was developed. Five hemispheres from elderly subjects were imaged ex vivo longitudinally. All datasets were segmented. The longitudinal behavior of volumes measured ex vivo was assessed. The relationship between in vivo and ex vivo volumetric measurements was investigated in seven elderly subjects imaged both antemortem and postmortem. This approach for ex vivo MR volumetry did not contaminate the results of histopathological examination. For a period of 6 months postmortem, within-subject volume variation across time points was substantially smaller than intersubject volume variation. A close linear correspondence was detected between in vivo and ex vivo volumetric measurements. Regional brain volumes measured with this approach for ex vivo MR volumetry remain relatively unchanged for a period of 6 months postmortem. Furthermore, the linear relationship between in vivo and ex vivo MR volumetric measurements suggests that this approach captures information linked to antemortem macrostructural brain characteristics. Copyright © 2013 Wiley Periodicals, Inc.

  16. Protocol Fuel Mix reporting

    International Nuclear Information System (INIS)

    2002-07-01

    The protocol in this document describes a method for an Electricity Distribution Company (EDC) to account for the fuel mix of electricity that it delivers to its customers, based on the best available information. Own production, purchase and sale of electricity, and certificates trading are taken into account. In chapter 2 the actual protocol is outlined. In the appendixes additional (supporting) information is given: (A) Dutch Standard Fuel Mix, 2000; (B) Calculation of the Dutch Standard fuel mix; (C) Procedures to estimate and benchmark the fuel mix; (D) Quality management; (E) External verification; (F) Recommendation for further development of the protocol; (G) Reporting examples

  17. Coded Splitting Tree Protocols

    DEFF Research Database (Denmark)

    Sørensen, Jesper Hemming; Stefanovic, Cedomir; Popovski, Petar

    2013-01-01

    This paper presents a novel approach to multiple access control called coded splitting tree protocol. The approach builds on the known tree splitting protocols, code structure and successive interference cancellation (SIC). Several instances of the tree splitting protocol are initiated, each...... instance is terminated prematurely and subsequently iterated. The combined set of leaves from all the tree instances can then be viewed as a graph code, which is decodable using belief propagation. The main design problem is determining the order of splitting, which enables successful decoding as early...

  18. Playing With Population Protocols

    Directory of Open Access Journals (Sweden)

    Xavier Koegler

    2009-06-01

    Full Text Available Population protocols have been introduced as a model of sensor networks consisting of very limited mobile agents with no control over their own movement: A collection of anonymous agents, modeled by finite automata, interact in pairs according to some rules. Predicates on the initial configurations that can be computed by such protocols have been characterized under several hypotheses. We discuss here whether and when the rules of interactions between agents can be seen as a game from game theory. We do so by discussing several basic protocols.

  19. ATM and Internet protocol

    CERN Document Server

    Bentall, M; Turton, B

    1998-01-01

    Asynchronous Transfer Mode (ATM) is a protocol that allows data, sound and video being transferred between independent networks via ISDN links to be supplied to, and interpreted by, the various system protocols.ATM and Internet Protocol explains the working of the ATM and B-ISDN network for readers with a basic understanding of telecommunications. It provides a handy reference to everyone working with ATM who may not require the full standards in detail, but need a comprehensive guide to ATM. A substantial section is devoted to the problems of running IP over ATM and there is some discussion o

  20. In vivo dose verification for photon treatments of head and neck carcinomas using MOSFET dosimeters

    International Nuclear Information System (INIS)

    Tung, C.J.; Wang, L.C.; Wang, H.C.; Lee, C.C.; Chao, T.C.

    2008-01-01

    In vivo dosimetry was performed for the head and neck carcinoma patients during the treatment of a large photon field using MOSFETs. This study followed the protocols recommended by the European Society for Therapeutic Radiology and Oncology. A total of 32 portals belonging to 12 patients were under investigation. Results showed that the deviation between in vivo midline doses and planned target doses was partly due to the manual dose calculations in the treatment planning which used the patient geometric thickness rather than the radiological thickness. Other factors responsible for this deviation included the difficult positioning of MOSFETs on the face mask, the asymmetric positioning of MOSFETs on the left and right sides of the mask, and the asymmetric tissue inhomogeneities with respect to the body midline. To reduce the deviation contributed from these factors, in vivo midline doses were calculated by averaging the results for each bilaterally opposed portals and compared with corresponding planned target doses. This comparison showed that MOSFET dosimeters are suitable for in vivo dosimetry of the present study

  1. Magnesium alloys: predicting in vivo corrosion with in vitro immersion testing.

    Science.gov (United States)

    Walker, Jemimah; Shadanbaz, Shaylin; Kirkland, Nicholas T; Stace, Edward; Woodfield, Tim; Staiger, Mark P; Dias, George J

    2012-05-01

    Magnesium (Mg) and its alloys have been proposed as degradable replacements to commonly used orthopedic biomaterials such as titanium alloys and stainless steel. However, the corrosion of Mg in a physiological environment remains a difficult characteristic to accurately assess with in vitro methods. The aim of this study was to identify a simple in vitro immersion test that could provide corrosion rates similar to those observed in vivo. Pure Mg and five alloys (AZ31, Mg-0.8Ca, Mg-1Zn, Mg-1Mn, Mg-1.34Ca-3Zn) were immersed in either Earle's balanced salt solution (EBSS), minimum essential medium (MEM), or MEM-containing 40 g/L bovine serum albumin (MEMp) for 7, 14, or 21 days before removal and assessment of corrosion by weight loss. This in vitro data was compared to in vivo corrosion rates of the same materials implanted in a subcutaneous environment in Lewis rats for equivalent time points. The results suggested that, for the alloys investigated, the EBSS buffered with sodium bicarbonate provides a rate of degradation comparable to those observed in vivo. In contrast, the addition of components such as (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid) (HEPES), vitamins, amino acids, and albumin significantly increased corrosion rates. Based on these findings, it is proposed that with this in vitro protocol, immersion of Mg alloys in EBSS can be used as a predictor of in vivo corrosion. Copyright © 2012 Wiley Periodicals, Inc.

  2. Analysis of Riboflavin Compounds in the Rabbit Cornea In Vivo.

    Science.gov (United States)

    Hammer, Arthur; Rudaz, Serge; Guinchard, Sylvie; Kling, Sabine; Richoz, Olivier; Hafezi, Farhad

    2016-09-01

    To investigate the composition and concentration of individual riboflavin compounds in the corneal stroma in vivo after soaking with various commercially available riboflavin formulations. Experiments were performed in 26 rabbit corneas in vivo: 24 corneas were soaked with riboflavin formulations for 30 minutes or with 0.9% NaCl for control (n = 2). After treatment, corneas were excised and prepared for ultra-high-pressure liquid chromatography (UHPLC) analysis. Additionally, computational chemical analysis of riboflavin compounds and keratan sulfate were performed. The amount of riboflavin and riboflavin phosphate isomers in cornea decreased by a factor of 10 to 100, when compared to the amount in riboflavin formulations. In particular, we found an inverse relationship in the ratio of riboflavin to riboflavin phosphate isomer concentration between formulations and cornea. The electronegativity and ionization potential of riboflavin and phosphate isomers are different. The inverse relationship observed might be explained by a stronger electronegativity of the phosphate isomers, leading to a stronger repulsion by corneal proteoglycans. Indicating the individual concentration of riboflavin compounds in formulations is more representative than the total riboflavin concentration. Riboflavin formulations and CXL protocols might be improved considering the differences in diffusion and ionization potentials of the different riboflavin compounds.

  3. Simultaneous two-voxel localized 1H-observed 13C-edited spectroscopy for in vivo MRS on rat brain at 9.4 T: Application to the investigation of excitotoxic lesions

    Science.gov (United States)

    Doan, Bich-Thuy; Autret, Gwennhael; Mispelter, Joël; Méric, Philippe; Même, William; Montécot-Dubourg, Céline; Corrèze, Jean-Loup; Szeremeta, Frédéric; Gillet, Brigitte; Beloeil, Jean-Claude

    2009-05-01

    13C spectroscopy combined with the injection of 13C-labeled substrates is a powerful method for the study of brain metabolism in vivo. Since highly localized measurements are required in a heterogeneous organ such as the brain, it is of interest to augment the sensitivity of 13C spectroscopy by proton acquisition. Furthermore, as focal cerebral lesions are often encountered in animal models of disorders in which the two brain hemispheres are compared, we wished to develop a bi-voxel localized sequence for the simultaneous bilateral investigation of rat brain metabolism, with no need for external additional references. Two sequences were developed at 9.4 T: a bi-voxel 1H-( 13C) STEAM-POCE (Proton Observed Carbon Edited) sequence and a bi-voxel 1H-( 13C) PRESS-POCE adiabatically decoupled sequence with Hadamard encoding. Hadamard encoding allows both voxels to be recorded simultaneously, with the same acquisition time as that required for a single voxel. The method was validated in a biological investigation into the neuronal damage and the effect on the Tri Carboxylic Acid cycle in localized excitotoxic lesions. Following an excitotoxic quinolinate-induced localized lesion in the rat cortex and the infusion of U- 13C glucose, two 1H-( 13C) spectra of distinct (4 × 4 × 4 mm 3) voxels, one centred on the injured hemisphere and the other on the contralateral hemisphere, were recorded simultaneously. Two 1H bi-voxel spectra were also recorded and showed a significant decrease in N-acetyl aspartate, and an accumulation of lactate in the ipsilateral hemisphere. The 1H-( 13C) spectra could be recorded dynamically as a function of time, and showed a fall in the glutamate/glutamine ratio and the presence of a stable glutamine pool, with a permanent increase of lactate in the ipsilateral hemisphere. This bi-voxel 1H-( 13C) method can be used to investigate simultaneously both brain hemispheres, and to perform dynamic studies. We report here the neuronal damage and the

  4. Ex vivo-expanded bone marrow CD34(+) for acute myocardial infarction treatment: in vitro and in vivo studies.

    Science.gov (United States)

    Gunetti, Monica; Noghero, Alessio; Molla, Fabiola; Staszewsky, Lidia Irene; de Angelis, Noeleen; Soldo, Annarita; Russo, Ilaria; Errichiello, Edoardo; Frasson, Chiara; Rustichelli, Deborah; Ferrero, Ivana; Gualandris, Anna; Berger, Massimo; Geuna, Massimo; Scacciatella, Paolo; Basso, Giuseppe; Marra, Sebastiano; Bussolino, Federico; Latini, Roberto; Fagioli, Franca

    2011-10-01

    Bone marrow (BM)-derived cells appear to be a promising therapeutic source for the treatment of acute myocardial infarction (AMI). However, the quantity and quality of the cells to be used, along with the appropriate time of administration, still need to be defined. We thus investigated the use of BM CD34(+)-derived cells as cells suitable for a cell therapy protocol (CTP) in the treatment of experimental AMI. The need for a large number of cells was satisfied by the use of a previously established protocol allowing the expansion of human CD34(+) cells isolated from neonatal and adult hematopoietic tissues. We evaluated gene expression, endothelial differentiation potential and cytokine release by BM-derived cells during in vitro culture. Basal and expanded CD34(+) cells were used as a delivery product in a murine AMI model consisting of a coronary artery ligation (CAL). Cardiac function recovery was evaluated after injecting basal or expanded cells. Gene expression analysis of in vitro-expanded cells revealed that endothelial markers were up-regulated during culture. Moreover, expanded cells generated a CD14(+) subpopulation able to differentiate efficiently into VE-cadherin-expressing cells. In vivo, we observed a cardiac function recovery in mice sequentially treated with basal and expanded cells injected 4 h and 7 days after CAL, respectively. Our data suggest that combining basal and expanded BM-derived CD34(+) cells in a specific temporal pattern of administration might represent a promising strategy for a successful cell-based therapy.

  5. Mobile Internet Protocol Analysis

    National Research Council Canada - National Science Library

    Brachfeld, Lawrence

    1999-01-01

    ...) and User Datagram Protocol (UDP). Mobile IP allows mobile computers to send and receive packets addressed with their home network IP address, regardless of the IP address of their current point of attachment on the Internet...

  6. USA-USSR protocol

    CERN Multimedia

    1970-01-01

    On 30 November the USA Atomic Energy Commission and the USSR State Committee for the Utilization of Atomic Energy signed, in Washington, a protocol 'on carrying out of joint projects in the field of high energy physics at the accelerators of the National Accelerator Laboratory (Batavia) and the Institute for High Energy Physics (Serpukhov)'. The protocol will be in force for five years and can be extended by mutual agreement.

  7. Evaluation of the in vivo and ex vivo optical properties in a mouse ear model

    Energy Technology Data Exchange (ETDEWEB)

    Salomatina, E; Yaroslavsky, A N [Wellman Center for Photomedicine, 40 Blossom Street, Boston, MA 02114 (United States)], E-mail: Yaroslav@helix.mgh.harvard.edu

    2008-06-07

    Determination of in vivo optical properties is a challenging problem. Absorption and scattering measured ex vivo are often used for in vivo applications. To investigate the validity of this approach, we have obtained and compared the optical properties of mouse ears in vivo and ex vivo in the spectral range from 370 to 1650 nm. Integrating sphere spectrophotometry in combination with the inverse Monte Carlo technique was employed to determine absorption coefficients, {mu}{sub a}, scattering coefficients, {mu}{sub s}, and anisotropy factors, g. Two groups of mice were used for the study. The first group was measured in vivo and ex vivo within 5-10 min post mortem. The second group was measured in vivo and ex vivo every 24 h for up to 72 h after sacrifice. Between the measurements the tissues were kept at 4 deg. C wrapped in a gauze moistened with saline solution. Then the specimens were frozen at -25 deg. C for 40 min, thawed and measured again. The results indicate that the absorption coefficients determined in vivo and ex vivo within 5-10 min post mortem differed considerably only in the spectral range dominated by hemoglobin. These changes can be attributed to rapid deoxygenation of tissue and blood post mortem. Absorption coefficients determined ex vivo up to 72 h post mortem decreased gradually with time in the spectral regions dominated by hemoglobin and water, which can be explained by the continuing loss of blood. Absorption properties of the frozen-thawed ex vivo tissues showed increase in oxygenation, which is likely caused by the release of hemoglobin from hemolyzed erythrocytes. Scattering of the ex vivo tissues decreased gradually with time in the entire spectral range due to the continuing loss of blood and partial cell damage. Anisotropy factors did not change considerably.

  8. Compiling symbolic attacks to protocol implementation tests

    Directory of Open Access Journals (Sweden)

    Michael Rusinowitch

    2013-07-01

    Full Text Available Recently efficient model-checking tools have been developed to find flaws in security protocols specifications. These flaws can be interpreted as potential attacks scenarios but the feasability of these scenarios need to be confirmed at the implementation level. However, bridging the gap between an abstract attack scenario derived from a specification and a penetration test on real implementations of a protocol is still an open issue. This work investigates an architecture for automatically generating abstract attacks and converting them to concrete tests on protocol implementations. In particular we aim to improve previously proposed blackbox testing methods in order to discover automatically new attacks and vulnerabilities. As a proof of concept we have experimented our proposed architecture to detect a renegotiation vulnerability on some implementations of SSL/TLS, a protocol widely used for securing electronic transactions.

  9. A randomised controlled intervention study investigating the efficacy of carotenoid-rich fruits and vegetables and extra-virgin olive oil on attenuating sarcopenic symptomology in overweight and obese older adults during energy intake restriction: protocol paper

    OpenAIRE

    Villani, Anthony; Wright, Hattie; Slater, Gary; Buckley, Jonathan

    2018-01-01

    Background Weight loss interventions have not been advocated for overweight/obese older adults due to potential loss of skeletal muscle and strength impacting on physical function with potential loss of independence. Carotenoids and polyphenols are inversely associated with sarcopenic symptomology. This paper reports the protocol of a study evaluating the efficacy of a high-protein, energy restricted diet rich in carotenoids and polyphenols on body composition, muscle strength, physical perfo...

  10. Absolute calibration in vivo measurement systems

    International Nuclear Information System (INIS)

    Kruchten, D.A.; Hickman, D.P.

    1991-02-01

    Lawrence Livermore National Laboratory (LLNL) is currently investigating a new method for obtaining absolute calibration factors for radiation measurement systems used to measure internally deposited radionuclides in vivo. Absolute calibration of in vivo measurement systems will eliminate the need to generate a series of human surrogate structures (i.e., phantoms) for calibrating in vivo measurement systems. The absolute calibration of in vivo measurement systems utilizes magnetic resonance imaging (MRI) to define physiological structure, size, and composition. The MRI image provides a digitized representation of the physiological structure, which allows for any mathematical distribution of radionuclides within the body. Using Monte Carlo transport codes, the emission spectrum from the body is predicted. The in vivo measurement equipment is calibrated using the Monte Carlo code and adjusting for the intrinsic properties of the detection system. The calibration factors are verified using measurements of existing phantoms and previously obtained measurements of human volunteers. 8 refs

  11. Detection of Helicobacter pylori in the Gastric Mucosa by Fluorescence In Vivo Hybridization

    DEFF Research Database (Denmark)

    Fontenete, Silvia; Leite, Marina; Figueiredo, Céu

    2017-01-01

    In this chapter, we describe a fluorescence in vivo hybridization (FIVH) protocol, using nucleic acid probes, for the detection of the bacterium Helicobacter pylori in the gastric mucosa of an infected C57BL/6 mouse model. This protocol should be easily extended to other microorganisms not only...

  12. Imaging N-acyl homoserine lactone quorum sensing in vivo

    DEFF Research Database (Denmark)

    Christensen, Louise Dahl; van Gennip, Maria; Jakobsen, Tim Holm

    2011-01-01

    In order to study N-acyl homoserine lactone (AHL)-based quorum sensing in vivo, we present a protocol using an Escherichia coli strain equipped with a luxR-based monitor system, which in the presence of exogenous AHL molecules expresses a green fluorescent protein (GFP). Lungs from mice challenged...

  13. Imaging N-acyl homoserine lactone quorum sensing in vivo

    DEFF Research Database (Denmark)

    Hultqvist, Louise Dahl; Alhede, Maria; Jakobsen, Tim Holm

    2018-01-01

    In order to study N-acyl homoserine lactone (AHL)-based quorum sensing in vivo, we present a protocol using an Escherichia coli strain equipped with a luxR-based monitor system, which in the presence of exogenous AHL molecules expresses a green fluorescent protein (GFP). Lungs from mice challenged...

  14. Abortamento recorrente de causa imunológica: avaliação de um protocolo de investigação e tratamento Recurrent abortion due to immunologic causes: evaluation of an investigation and treatment protocol

    Directory of Open Access Journals (Sweden)

    Ricardo Barini

    1998-03-01

    Full Text Available São apresentados resultados de protocolo de investigação diagnóstica e tratamento do aborto recorrente de causa imunológica. Estima-se que até 60 % das pacientes que não apresentam nenhuma alteração clínica identificável sejam portadoras de perturbações aloimunes associadas ao aborto Uma das alternativas terapêuticas é a imunização com linfócitos do parceiro. Foram revisados os resultados de 116 pacientes seguidas no Departamento de Tocoginecologia da UNICAMP. As mulheres foram avaliadas segundo minucioso protocolo de investigação das causas de aborto recorrente conhecidas (genética, hormonal, uterina e infecciosa, imunológicos auto-imunes (síndrome do anticorpo antifosfolipídico, auto-anticorpos anômalos e aloimunes (prova cruzada por microlinfocitotoxicidade e cultura mista de linfócitos. As que apresentavam prova cruzada negativa e índice de inibição menor que 50% na cultura mista de linfócitos foram tratadas com duas imunizações intradérmicas de concentrado de linfócitos de seus maridos. Foram estimuladas a engravidar se os exames de controle demonstrassem prova cruzada positiva e cultura mista com inibição superior a 50%. Quando este regime não resultou em mudança significativa foram tratadas novamente com concentrado de linfócitos de seus maridos, associado ou não a um doador não-aparentado. Com esta abordagem terapêutica 81% tiveram evolução gestacional favorável .Results on investigation and immune treatment for recurrent abortion are presented. Up to 60% of patients who are free of any clinical identifiable cause for abortion are believed to have alloimmune abnormalities. One of the suggested therapies for this condition is paternal lymphocyte immunization. We present the result of 116 pregnancies followed at the Departamento de Tocoginecologia UNICAMP. Patients were thoroughly evaluated for causes of recurrent abortion mentioned in the literature (genetics, hormones, uterine abnormalities

  15. Investigating the application of motion accelerometers as a sleep monitoring technique and the clinical burden of the intensive care environment on sleep quality: study protocol for a prospective observational study in Australia.

    Science.gov (United States)

    Delaney, Lori J; Currie, Marian J; Huang, Hsin-Chia Carol; Litton, Edward; Wibrow, Bradley; Lopez, Violeta; Haren, Frank Van

    2018-01-21

    prehospital discharge survey regarding patients' perception of sleep quality and disturbing factors using the Little Sleep Questionnaire will be undertaken. Associations between sleep disturbance, noise and light levels, and the frequency of clinical interactions will also be investigated. Sound and luminance levels will be recorded at 1 s epochs via Extech SDL600 and SDL400 monitoring devices. Clinical interactions will be logged via the electronic patient record system Metavision which documents patient monitoring and clinical care. The relevant institutions have approved the study protocol and consent procedures. The findings of the study will contribute to the understanding of sleep disturbance, and the ability to implement sleep monitoring methods within ICUs. Understanding the contribution of a clinical environment on sleep disturbance may provide insight into the need to address clinical environmental issues that may positively influence patient outcomes, and could dispel notions that the environment is a primary factor in sleep disturbance. The research findings will be disseminated via presentations at national and international conferences, proceedings and published articles in peer-reviewed journals. ACTRN12615000945527; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  16. In silico toxicology protocols.

    Science.gov (United States)

    Myatt, Glenn J; Ahlberg, Ernst; Akahori, Yumi; Allen, David; Amberg, Alexander; Anger, Lennart T; Aptula, Aynur; Auerbach, Scott; Beilke, Lisa; Bellion, Phillip; Benigni, Romualdo; Bercu, Joel; Booth, Ewan D; Bower, Dave; Brigo, Alessandro; Burden, Natalie; Cammerer, Zoryana; Cronin, Mark T D; Cross, Kevin P; Custer, Laura; Dettwiler, Magdalena; Dobo, Krista; Ford, Kevin A; Fortin, Marie C; Gad-McDonald, Samantha E; Gellatly, Nichola; Gervais, Véronique; Glover, Kyle P; Glowienke, Susanne; Van Gompel, Jacky; Gutsell, Steve; Hardy, Barry; Harvey, James S; Hillegass, Jedd; Honma, Masamitsu; Hsieh, Jui-Hua; Hsu, Chia-Wen; Hughes, Kathy; Johnson, Candice; Jolly, Robert; Jones, David; Kemper, Ray; Kenyon, Michelle O; Kim, Marlene T; Kruhlak, Naomi L; Kulkarni, Sunil A; Kümmerer, Klaus; Leavitt, Penny; Majer, Bernhard; Masten, Scott; Miller, Scott; Moser, Janet; Mumtaz, Moiz; Muster, Wolfgang; Neilson, Louise; Oprea, Tudor I; Patlewicz, Grace; Paulino, Alexandre; Lo Piparo, Elena; Powley, Mark; Quigley, Donald P; Reddy, M Vijayaraj; Richarz, Andrea-Nicole; Ruiz, Patricia; Schilter, Benoit; Serafimova, Rositsa; Simpson, Wendy; Stavitskaya, Lidiya; Stidl, Reinhard; Suarez-Rodriguez, Diana; Szabo, David T; Teasdale, Andrew; Trejo-Martin, Alejandra; Valentin, Jean-Pierre; Vuorinen, Anna; Wall, Brian A; Watts, Pete; White, Angela T; Wichard, Joerg; Witt, Kristine L; Woolley, Adam; Woolley, David; Zwickl, Craig; Hasselgren, Catrin

    2018-04-17

    The present publication surveys several applications of in silico (i.e., computational) toxicology approaches across different industries and institutions. It highlights the need to develop standardized protocols when conducting toxicity-related predictions. This contribution articulates the information needed for protocols to support in silico predictions for major toxicological endpoints of concern (e.g., genetic toxicity, carcinogenicity, acute toxicity, reproductive toxicity, developmental toxicity) across several industries and regulatory bodies. Such novel in silico toxicology (IST) protocols, when fully developed and implemented, will ensure in silico toxicological assessments are performed and evaluated in a consistent, reproducible, and well-documented manner across industries and regulatory bodies to support wider uptake and acceptance of the approaches. The development of IST protocols is an initiative developed through a collaboration among an international consortium to reflect the state-of-the-art in in silico toxicology for hazard identification and characterization. A general outline for describing the development of such protocols is included and it is based on in silico predictions and/or available experimental data for a defined series of relevant toxicological effects or mechanisms. The publication presents a novel approach for determining the reliability of in silico predictions alongside experimental data. In addition, we discuss how to determine the level of confidence in the assessment based on the relevance and reliability of the information. Copyright © 2018. Published by Elsevier Inc.

  17. Business protocol in integrated Europe

    OpenAIRE

    Pavelová, Nina

    2009-01-01

    The first chapter devotes to definitions of basic terms such as protocol or business protocol, to differences between protocol and etiquette, and between social etiquette and business etiquette. The second chapter focuses on the factors influencing the European business protocol. The third chapter is devoted to the etiquette of business protocol in the European countries. It touches the topics such as punctuality and planning of business appointment, greeting, business cards, dress and appear...

  18. Security Protocols in a Nutshell

    OpenAIRE

    Toorani, Mohsen

    2016-01-01

    Security protocols are building blocks in secure communications. They deploy some security mechanisms to provide certain security services. Security protocols are considered abstract when analyzed, but they can have extra vulnerabilities when implemented. This manuscript provides a holistic study on security protocols. It reviews foundations of security protocols, taxonomy of attacks on security protocols and their implementations, and different methods and models for security analysis of pro...

  19. DNA repair protocols

    DEFF Research Database (Denmark)

    Bjergbæk, Lotte

    In its 3rd edition, this Methods in Molecular Biology(TM) book covers the eukaryotic response to genomic insult including advanced protocols and standard techniques in the field of DNA repair. Offers expert guidance for DNA repair, recombination, and replication. Current knowledge of the mechanisms...... that regulate DNA repair has grown significantly over the past years with technology advances such as RNA interference, advanced proteomics and microscopy as well as high throughput screens. The third edition of DNA Repair Protocols covers various aspects of the eukaryotic response to genomic insult including...... recent advanced protocols as well as standard techniques used in the field of DNA repair. Both mammalian and non-mammalian model organisms are covered in the book, and many of the techniques can be applied with only minor modifications to other systems than the one described. Written in the highly...

  20. Protocol Monitoring Energy Conservation; Protocol Monitoring Energiebesparing

    Energy Technology Data Exchange (ETDEWEB)

    Boonekamp, P.G.M. [ECN Beleidsstudies, Petten (Netherlands); Mannaerts, H. [Centraal Planburea CPB, Den Haag (Netherlands); Tinbergen, W. [Centraal Bureau voor de Statistiek CBS, Den Haag (Netherlands); Vreuls, H.H.J. [Nederlandse onderneming voor energie en milieu Novem, Utrecht (Netherlands); Wesselink, B. [Rijksinstituut voor Volksgezondheid en Milieuhygiene RIVM, Bilthoven (Netherlands)

    2001-12-01

    On request of the Dutch ministry of Economic Affairs five institutes have collaborated to create a 'Protocol Monitoring Energy Conservation', a common method and database to calculate the amount of energy savings realised in past years. The institutes concerned are the Central Bureau of Statistics (CBS), the Netherlands Bureau for Economic Policy Analysis (CPB), the Energy research Centre of the Netherlands (ECN), the National Agency for Energy and Environment (Novem) and the Netherlands Institute of Public Health and the Environment (RIVM). The institutes have agreed upon a clear definition of energy use and energy savings. The demarcation with renewable energy, the saving effects of substitution between energy carriers and the role of import and export of energy have been elaborated. A decomposition method is used to split up the observed change in energy use in a number of effects, on a national and sectoral level. This method includes an analysis of growth effects, effects of structural changes in production and consumption activities and savings on end use or with more efficient conversion processes. To calculate these effects the total energy use is desegregated as much as possible. For each segment a reference energy use is calculated according to the trend in a variable which is supposed to be representative for the use without savings. The difference with the actual energy use is taken as the savings realised. Results are given for the sectors households, industry, agriculture, services and government, transportation and the energy sector; as well as a national figure. A special feature of the protocol method is the application of primary energy use figures in the determination of savings for end users. This means that the use of each energy carrier is increased with a certain amount, according to the conversion losses caused elsewhere in the energy system. The losses concern the base year energy sector and losses abroad for imports of secondary

  1. Human platelet lysate in mesenchymal stromal cell expansion according to a GMP grade protocol: a cell factory experience.

    Science.gov (United States)

    Becherucci, Valentina; Piccini, Luisa; Casamassima, Serena; Bisin, Silvia; Gori, Valentina; Gentile, Francesca; Ceccantini, Riccardo; De Rienzo, Elena; Bindi, Barbara; Pavan, Paola; Cunial, Vanessa; Allegro, Elisa; Ermini, Stefano; Brugnolo, Francesca; Astori, Giuseppe; Bambi, Franco

    2018-05-02

    The use of platelet lysate (PL) for the ex-vivo expansion of mesenchymal stromal/stem cells (MSCs) was initially proposed by Doucet et al. in 2005, as an alternative to animal serum. Moreover, regulatory authorities discourage the use of fetal bovine serum (FBS) or other animal derivatives, to avoid risk of zoonoses and xenogeneic immune reactions. Even if many studies investigated PL composition, there still are some open issues related to its use in ex-vivo MSC expansion, especially according to good manufacturing practice (GMP) grade protocols. As an authorized cell factory, we report our experience using standardized PL produced by Azienda Ospedaliero Universitaria Meyer Transfusion Service for MSC expansion according to a GMP grade clinical protocol. As suggested by other authors, we performed an in-vitro test on MSCs versus MSCs cultured with FBS that still represents the best way to test PL batches. We compared 12 MSC batches cultured with DMEM 5% PL with similar batches cultured with DMEM 10% FBS, focusing on the MSC proliferation rate, MSC surface marker expression, MSC immunomodulatory and differentiation potential, and finally MSC relative telomere length. Results confirmed the literature data as PL increases cell proliferation without affecting the MSC immunophenotype, immunomodulatory potential, differentiation potential and relative telomere length. PL can be considered a safe alternative to FBS for ex-vivo expansion of MSC according to a GMP grade protocol. Our experience confirms the literature data: a large number of MSCs for clinical applications can be obtained by expansion with PL, without affecting the MSC main features. Our experience underlines the benefits of a close collaboration between the PL producers (transfusion service) and the end users (cell factory) in a synergy of skills and experiences that can lead to standardized PL production.

  2. In vitro and in vivo investigation of natural compounds from seed extract of Mucuna pruriens lacking l-DOPA for the treatment of erectile dysfunction.

    Science.gov (United States)

    Duangnin, Natthachai; Phitak, Thanyaluck; Pothacharoen, Peraphan; Kongtawelert, Prachya

    2017-03-01

    To investigate the biological effects of the Mucuna pruriens (M. pruriens) seed extracts that lacked l-DOPA, which was formerly reported as the active ingredient, on erectile dysfunction (ED) both in vitro and in vivo. Seed of M. pruriens plant that cultivated in Mae Taeng District, Chiang Mai Province, Thailand, was collected. Component of its seeds were extracted and isolated into 2 fractions using methanol, polar and nonpolar. Each fraction was investigated for phytochemicals using gas chromatography and mass spectroscopy and was screened for biological activity in vitro using three different cell lines. The most biological active fraction was used to treat both streptozotocin (STZ)-induced diabetes mellitus-erectile dysfunction (DM-ED) male Wistar rats and normal rats (n = 6 per groups) to compare the effect on sexual behavior parameters, including number of intromission, mounting and ejaculation, with that of rats given Sildenafil by individually pairing with their female counterparts. Penile tissues and serums were collected to determine histological structure, related gene expression and biomolecules. The phytochemicals of the polar fraction were possibly catechol and its derivatives plus polyphenols, whereas the nonpolar fraction consisted of lipid derivatives. l-DOPA was not detected in either of the extracts. The polar fraction was able to up-regulate the expression of ED-related genes including eNOS and nNOS in vitro which subsequently promotes nitric oxide production and maintains intracellular cyclic guanosine monophosphate levels. When administrated to DM-ED rats, the polar extract significantly improved all sexual behavior parameters in DM-ED rats compared to untreated group (18.3 ± 1.8 to 10.8 ± 2.9 for intromission, 9.8 ± 2.2 to 5.7 ± 1.3 for mounting, and 1.8 ± 0.6 to 0.2 ± 0.4 for ejaculation). That effect might due to the ability of the extract to stimulate the expression of eNOS and nNOS which results in nitric oxide

  3. Immunocytochemical methods and protocols

    National Research Council Canada - National Science Library

    Javois, Lorette C

    1999-01-01

    ... monoclonal antibodies to study cell differentiation during embryonic development. For a select few disciplines volumes have been published focusing on the specific application of immunocytochemical techniques to that discipline. What distinguished Immunocytochemical Methods and Protocols from earlier books when it was first published four years ago was i...

  4. Critical Response Protocol

    Science.gov (United States)

    Ellingson, Charlene; Roehrig, Gillian; Bakkum, Kris; Dubinsky, Janet M.

    2016-01-01

    This article introduces the Critical Response Protocol (CRP), an arts-based technique that engages students in equitable critical discourse and aligns with the "Next Generation Science Standards" vision for providing students opportunities for language learning while advancing science learning (NGSS Lead States 2013). CRP helps teachers…

  5. Linear Logical Voting Protocols

    DEFF Research Database (Denmark)

    DeYoung, Henry; Schürmann, Carsten

    2012-01-01

    Current approaches to electronic implementations of voting protocols involve translating legal text to source code of an imperative programming language. Because the gap between legal text and source code is very large, it is difficult to trust that the program meets its legal specification. In r...

  6. Principles of Protocol Design

    DEFF Research Database (Denmark)

    Sharp, Robin

    This is a new and updated edition of a book first published in 1994. The book introduces the reader to the principles used in the construction of a large range of modern data communication protocols, as used in distributed computer systems of all kinds. The approach taken is rather a formal one...

  7. Model Additional Protocol

    International Nuclear Information System (INIS)

    Rockwood, Laura

    2001-01-01

    Since the end of the cold war a series of events has changed the circumstances and requirements of the safeguards system. The discovery of a clandestine nuclear weapons program in Iraq, the continuing difficulty in verifying the initial report of Democratic People's Republic of Korea upon entry into force of their safeguards agreement, and the decision of the South African Government to give up its nuclear weapons program and join the Treaty on the Non-Proliferation of Nuclear Weapons have all played a role in an ambitious effort by IAEA Member States and the Secretariat to strengthen the safeguards system. A major milestone in this effort was reached in May 1997 when the IAEA Board of Governors approved a Model Protocol Additional to Safeguards Agreements. The Model Additional Protocol was negotiated over a period of less than a year by an open-ended committee of the Board involving some 70 Member States and two regional inspectorates. The IAEA is now in the process of negotiating additional protocols, State by State, and implementing them. These additional protocols will provide the IAEA with rights of access to information about all activities related to the use of nuclear material in States with comprehensive safeguards agreements and greatly expanded physical access for IAEA inspectors to confirm or verify this information. In conjunction with this, the IAEA is working on the integration of these measures with those provided for in comprehensive safeguards agreements, with a view to maximizing the effectiveness and efficiency, within available resources, the implementation of safeguards. Details concerning the Model Additional Protocol are given. (author)

  8. Computed tomography-based lung nodule volumetry - do optimized reconstructions of routine protocols achieve similar accuracy, reproducibility and interobserver variability to that of special volumetry protocols?

    International Nuclear Information System (INIS)

    Bolte, H.; Riedel, C.; Knoess, N.; Hoffmann, B.; Heller, M.; Biederer, J.; Freitag, S.

    2007-01-01

    Purpose: The aim of this in vitro and ex vivo CT study was to investigate whether the use of a routine thorax protocol (RTP) with optimized reconstruction parameters can provide comparable accuracy, reproducibility and interobserver variability of volumetric analyses to that of a special volumetry protocol (SVP). Materials and Methods: To assess accuracy, 3 polyurethane (PU) spheres (35 HU; diameters: 4, 6 and 10 mm) were examined with a recommended SVP using a multislice CT (collimation 16 x 0.75 mm, pitch 1.25, 20 mAs, slice thickness 1 mm, increment 0.7 mm, medium kernel) and an optimized RTP (collimation 16 x 1.5 mm, pitch 1.25, 100 mAs, reconstructed slice thickness 2 mm, increment 0.4 mm, sharp kernel). For the assessment of intrascan and interscan reproducibility and interobserver variability, 20 artificial small pulmonary nodules were placed in a dedicated ex vivo chest phantom and examined with identical scan protocols. The artificial lesions consisted of a fat-wax-Lipiodol registered mixture. Phantoms and ex vivo lesions were examined afterwards using commercial volumetry software. To describe accuracy the relative deviations from the true volumes of the PU phantoms were calculated. For intrascan and interscan reproducibility and interobserver variability, the 95 % normal range (95 % NR) of relative deviations between two measurements was calculated. Results: For the SVP the achieved relative deviations for the 4, 6 and 10 mm PU phantoms were - 14.3 %, - 12.7 % and - 6.8 % and were 4.5 %, - 0.6 % and - 2.6 %, respectively, for the optimized RTP. SVP showed a 95 % NR of 0 - 1.5 % for intrascan and a 95 % NR of - 10.8 - 2.9 % for interscan reproducibility. The 95 % NR for interobserver variability was - 4.3 - 3.3 %. The optimized RTP achieved a 95 % NR of - 3.1 - 4.3 % for intrascan reproducibility and a 95 % NR of - 7.0 - 3.5 % for interscan reproducibility. The 95 % NR for interobserver variability was - 0.4 - 6.8 %. (orig.)

  9. The in vivo biofilm

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Alhede, Maria; Alhede, Morten

    2013-01-01

    Bacteria can grow and proliferate either as single, independent cells or organized in aggregates commonly referred to as biofilms. When bacteria succeed in forming a biofilm within the human host, the infection often becomes very resistant to treatment and can develop into a chronic state. Biofilms...... have been studied for decades using various in vitro models, but it remains debatable whether such in vitro biofilms actually resemble in vivo biofilms in chronic infections. In vivo biofilms share several structural characteristics that differ from most in vitro biofilms. Additionally, the in vivo...... experimental time span and presence of host defenses differ from chronic infections and the chemical microenvironment of both in vivo and in vitro biofilms is seldom taken into account. In this review, we discuss why the current in vitro models of biofilms might be limited for describing infectious biofilms...

  10. Satellite Communications Using Commercial Protocols

    Science.gov (United States)

    Ivancic, William D.; Griner, James H.; Dimond, Robert; Frantz, Brian D.; Kachmar, Brian; Shell, Dan

    2000-01-01

    NASA Glenn Research Center has been working with industry, academia, and other government agencies in assessing commercial communications protocols for satellite and space-based applications. In addition, NASA Glenn has been developing and advocating new satellite-friendly modifications to existing communications protocol standards. This paper summarizes recent research into the applicability of various commercial standard protocols for use over satellite and space- based communications networks as well as expectations for future protocol development. It serves as a reference point from which the detailed work can be readily accessed. Areas that will be addressed include asynchronous-transfer-mode quality of service; completed and ongoing work of the Internet Engineering Task Force; data-link-layer protocol development for unidirectional link routing; and protocols for aeronautical applications, including mobile Internet protocol routing for wireless/mobile hosts and the aeronautical telecommunications network protocol.

  11. Using critiquing for improving medical protocols : Harder than it seems

    NARCIS (Netherlands)

    Marcos, Mar; Berger, Geert; van Harmelen, Frank; ten Teije, Annette; Roomans, Hugo; Miksch, Silvia

    2001-01-01

    Medical protocols are widely recognised to provide clinicians with high-quality and up-to-date recommendations. A critical condition for this is of course that the protocols themselves are of high quality. In this paper we investigate the use of critiquing for improving the quality of medical

  12. Cost-optimization of the IPv4 zeroconf protocol

    NARCIS (Netherlands)

    Bohnenkamp, H.C.; van der Stok, Peter; Hermanns, H.; Vaandrager, Frits

    2003-01-01

    This paper investigates the tradeoff between reliability and effectiveness for the IPv4 Zeroconf protocol, proposed by Cheshire/Adoba/Guttman in 2002, dedicated to the selfconfiguration of IP network interfaces. We develop a simple stochastic cost model of the protocol, where reliability is measured

  13. Epistemic Protocols for Distributed Gossiping

    Directory of Open Access Journals (Sweden)

    Krzysztof R. Apt

    2016-06-01

    Full Text Available Gossip protocols aim at arriving, by means of point-to-point or group communications, at a situation in which all the agents know each other's secrets. We consider distributed gossip protocols which are expressed by means of epistemic logic. We provide an operational semantics of such protocols and set up an appropriate framework to argue about their correctness. Then we analyze specific protocols for complete graphs and for directed rings.

  14. Symmetric cryptographic protocols

    CERN Document Server

    Ramkumar, Mahalingam

    2014-01-01

    This book focuses on protocols and constructions that make good use of symmetric pseudo random functions (PRF) like block ciphers and hash functions - the building blocks for symmetric cryptography. Readers will benefit from detailed discussion of several strategies for utilizing symmetric PRFs. Coverage includes various key distribution strategies for unicast, broadcast and multicast security, and strategies for constructing efficient digests of dynamic databases using binary hash trees.   •        Provides detailed coverage of symmetric key protocols •        Describes various applications of symmetric building blocks •        Includes strategies for constructing compact and efficient digests of dynamic databases

  15. Data-driven CT protocol review and management—experience from a large academic hospital.

    Science.gov (United States)

    Zhang, Da; Savage, Cristy A; Li, Xinhua; Liu, Bob

    2015-03-01

    Protocol review plays a critical role in CT quality assurance, but large numbers of protocols and inconsistent protocol names on scanners and in exam records make thorough protocol review formidable. In this investigation, we report on a data-driven cataloging process that can be used to assist in the reviewing and management of CT protocols. We collected lists of scanner protocols, as well as 18 months of recent exam records, for 10 clinical scanners. We developed computer algorithms to automatically deconstruct the protocol names on the scanner and in the exam records into core names and descriptive components. Based on the core names, we were able to group the scanner protocols into a much smaller set of "core protocols," and to easily link exam records with the scanner protocols. We calculated the percentage of usage for each core protocol, from which the most heavily used protocols were identified. From the percentage-of-usage data, we found that, on average, 18, 33, and 49 core protocols per scanner covered 80%, 90%, and 95%, respectively, of all exams. These numbers are one order of magnitude smaller than the typical numbers of protocols that are loaded on a scanner (200-300, as reported in the literature). Duplicated, outdated, and rarely used protocols on the scanners were easily pinpointed in the cataloging process. The data-driven cataloging process can facilitate the task of protocol review. Copyright © 2015 American College of Radiology. Published by Elsevier Inc. All rights reserved.

  16. Diplomacy and Diplomatic Protocol

    Directory of Open Access Journals (Sweden)

    Lect. Ph.D Oana Iucu

    2008-12-01

    Full Text Available The present study aims to observe relationships and determining factors between diplomacyand diplomatic protocol as outlined by historical and contextual analyses. The approach is very dynamic,provided that concepts are able to show their richness, antiquity and polyvalence at the level of connotations,semantics, grammatical and social syntax. The fact that this information is up to date determines anattitude of appreciation and a state of positive contamination.

  17. Automatic Validation of Protocol Narration

    DEFF Research Database (Denmark)

    Bodei, Chiara; Buchholtz, Mikael; Degano, Pierpablo

    2003-01-01

    We perform a systematic expansion of protocol narrations into terms of a process algebra in order to make precise some of the detailed checks that need to be made in a protocol. We then apply static analysis technology to develop an automatic validation procedure for protocols. Finally, we...

  18. Dysphonia risk screening protocol

    Directory of Open Access Journals (Sweden)

    Katia Nemr

    2016-03-01

    Full Text Available OBJECTIVE: To propose and test the applicability of a dysphonia risk screening protocol with score calculation in individuals with and without dysphonia. METHOD: This descriptive cross-sectional study included 365 individuals (41 children, 142 adult women, 91 adult men and 91 seniors divided into a dysphonic group and a non-dysphonic group. The protocol consisted of 18 questions and a score was calculated using a 10-cm visual analog scale. The measured value on the visual analog scale was added to the overall score, along with other partial scores. Speech samples allowed for analysis/assessment of the overall degree of vocal deviation and initial definition of the respective groups and after six months, the separation of the groups was confirmed using an acoustic analysis. RESULTS: The mean total scores were different between the groups in all samples. Values ranged between 37.0 and 57.85 in the dysphonic group and between 12.95 and 19.28 in the non-dysphonic group, with overall means of 46.09 and 15.55, respectively. High sensitivity and specificity were demonstrated when discriminating between the groups with the following cut-off points: 22.50 (children, 29.25 (adult women, 22.75 (adult men, and 27.10 (seniors. CONCLUSION: The protocol demonstrated high sensitivity and specificity in differentiating groups of individuals with and without dysphonia in different sample groups and is thus an effective instrument for use in voice clinics.

  19. Dysphonia risk screening protocol

    Science.gov (United States)

    Nemr, Katia; Simões-Zenari, Marcia; da Trindade Duarte, João Marcos; Lobrigate, Karen Elena; Bagatini, Flavia Alves

    2016-01-01

    OBJECTIVE: To propose and test the applicability of a dysphonia risk screening protocol with score calculation in individuals with and without dysphonia. METHOD: This descriptive cross-sectional study included 365 individuals (41 children, 142 adult women, 91 adult men and 91 seniors) divided into a dysphonic group and a non-dysphonic group. The protocol consisted of 18 questions and a score was calculated using a 10-cm visual analog scale. The measured value on the visual analog scale was added to the overall score, along with other partial scores. Speech samples allowed for analysis/assessment of the overall degree of vocal deviation and initial definition of the respective groups and after six months, the separation of the groups was confirmed using an acoustic analysis. RESULTS: The mean total scores were different between the groups in all samples. Values ranged between 37.0 and 57.85 in the dysphonic group and between 12.95 and 19.28 in the non-dysphonic group, with overall means of 46.09 and 15.55, respectively. High sensitivity and specificity were demonstrated when discriminating between the groups with the following cut-off points: 22.50 (children), 29.25 (adult women), 22.75 (adult men), and 27.10 (seniors). CONCLUSION: The protocol demonstrated high sensitivity and specificity in differentiating groups of individuals with and without dysphonia in different sample groups and is thus an effective instrument for use in voice clinics. PMID:27074171

  20. Structural degradation of acrylic bone cements due to in vivo and simulated aging.

    Science.gov (United States)

    Hughes, Kerry F; Ries, Michael D; Pruitt, Lisa A

    2003-05-01

    Acrylic bone cement is the primary load-bearing material used for the attachment of orthopedic devices to adjoining bone. Degradation of acrylic-based cements in vivo results in a loss of structural integrity of the bone-cement-prosthesis interface and limits the longevity of cemented orthopedic implants. The purpose of this study is to investigate the effect of in vivo aging on the structure of the acrylic bone cement and to develop an in vitro artificial aging protocol that mimics the observed degradation. Three sets of retrievals are examined in this study: Palacos brand cement retrieved from hip replacements, and Simplex brand cement retrieved from both hip and knee replacement surgeries. In vitro aging is performed using oxidative and acidic environments on three acrylic-based cements: Palacos, Simplex, and CORE. Gel permeation chromatography (GPC) and Fourier transform infrared spectroscopy (FTIR) are used to examine the evolution of molecular weight and chemical species within the acrylic cements due to both in vivo and simulated aging. GPC analysis indicates that molecular weight is degraded in the hip retrievals but not in the knee retrievals. Artificial aging in an oxidative environment best reproduces this degradation mechanism. FTIR analysis indicates that there exists a chemical evolution within the cement due to in vivo and in vitro aging. These findings are consistent with scission-based degradation schemes in the cement. Based on the results of this study, a pathway for structural degradation of acrylic bone cement is proposed. The findings from this investigation have broad applicability to acrylic-based cements and may provide guidance for the development of new bone cements that resist degradation in the body. Copyright 2003 Wiley Periodicals, Inc.

  1. A customised cold-water immersion protocol favours one-size-fits-all protocols in improving acute performance recovery

    NARCIS (Netherlands)

    Zandvoort, Coen S.; de Zwart, Jelmer R.; van Keeken, Brenda L.; Viroux, Patrick J.F.; Tiemessen, Ivo J.H.

    The purpose of the present study was to investigate whether a customised cold-water immersion (CWIc) protocol was more effective in enhancing acute performance recovery than a one-size-fits-all CWI (CWIs) or active recovery (AR) protocol. On three separate testing days, 10 healthy, physically

  2. Association between in vivo bone formation and ex vivo migratory capacity of human bone marrow stromal cells

    DEFF Research Database (Denmark)

    Andersen, Rikke K.; Zaher, Walid; Larsen, Kenneth Hauberg

    2015-01-01

    INTRODUCTION: There is a clinical need for developing systemic transplantation protocols for use of human skeletal stem cells (also known bone marrow stromal stem cells) (hBMSC) in tissue regeneration. In systemic transplantation studies, only a limited number of hBMSC home to injured tissues...... populations derived from telomerized hBMSC (hBMSC-TERT) with variable ability to form heterotopic bone when implanted subcutaneously in immune deficient mice. In vitro transwell migration assay was used and the in vivo homing ability of transplanted hBMSC to bone fractures in mice was visualized...... suggesting that only a subpopulation of hBMSC possesses "homing" capacity. Thus, we tested the hypothesis that a subpopulation of hBMSC defined by ability to form heterotopic bone in vivo, is capable of homing to injured bone. METHODS: We tested ex vivo and in vivo homing capacity of a number of clonal cell...

  3. Breaking Megrelishvili protocol using matrix diagonalization

    Science.gov (United States)

    Arzaki, Muhammad; Triantoro Murdiansyah, Danang; Adi Prabowo, Satrio

    2018-03-01

    In this article we conduct a theoretical security analysis of Megrelishvili protocol—a linear algebra-based key agreement between two participants. We study the computational complexity of Megrelishvili vector-matrix problem (MVMP) as a mathematical problem that strongly relates to the security of Megrelishvili protocol. In particular, we investigate the asymptotic upper bounds for the running time and memory requirement of the MVMP that involves diagonalizable public matrix. Specifically, we devise a diagonalization method for solving the MVMP that is asymptotically faster than all of the previously existing algorithms. We also found an important counterintuitive result: the utilization of primitive matrix in Megrelishvili protocol makes the protocol more vulnerable to attacks.

  4. Investigation of the biochemical state of paramagnetic ions in vivo using the magnetic field dependence of 1/T1 of tissue protons (NMRD profile): applications to contrast agents for magnetic resonance imaging

    International Nuclear Information System (INIS)

    Koenig, S.H.; Brown, R.D. III; Spiller, M.; Wolf, G.L.

    1988-01-01

    Nuclear magnetic relaxation dispersion (NMRD) profiles of protons are obtained in homogenous aqueous solutions of the paramagnetic ions, Mn 2+ and Gd 3+ and their chelate and macromolecular complexes in vitro, giving information regarding the biochemical state of these ions. Similarly NMRD profiles of protons of excised rabbit tissues containing Mn 2+ and Gd 3+ complexes are obtained. These NMRD profiles are shown to be very useful for determining the fate of potentially useful paramagnetic NMR imaging contrast agents in vivo. (U.K.)

  5. WDM Network and Multicasting Protocol Strategies

    Directory of Open Access Journals (Sweden)

    Pinar Kirci

    2014-01-01

    Full Text Available Optical technology gains extensive attention and ever increasing improvement because of the huge amount of network traffic caused by the growing number of internet users and their rising demands. However, with wavelength division multiplexing (WDM, it is easier to take the advantage of optical networks and optical burst switching (OBS and to construct WDM networks with low delay rates and better data transparency these technologies are the best choices. Furthermore, multicasting in WDM is an urgent solution for bandwidth-intensive applications. In the paper, a new multicasting protocol with OBS is proposed. The protocol depends on a leaf initiated structure. The network is composed of source, ingress switches, intermediate switches, edge switches, and client nodes. The performance of the protocol is examined with Just Enough Time (JET and Just In Time (JIT reservation protocols. Also, the paper involves most of the recent advances about WDM multicasting in optical networks. WDM multicasting in optical networks is given as three common subtitles: Broadcast and-select networks, wavelength-routed networks, and OBS networks. Also, in the paper, multicast routing protocols are briefly summarized and optical burst switched WDM networks are investigated with the proposed multicast schemes.

  6. Orotracheal administration of contrast agents: a new protocol for brain tumor targeting.

    Science.gov (United States)

    Bianchi, Andrea; Moncelet, Damien; Lux, François; Plissonneau, Marie; Rizzitelli, Silvia; Ribot, Emeline Julie; Tassali, Nawal; Bouchaud, Véronique; Tillement, Olivier; Voisin, Pierre; Crémillieux, Yannick

    2015-06-01

    The development of new non-invasive diagnostic and therapeutic approaches is of paramount importance in order to improve the outcome of patients with glioblastoma (GBM). In this work we investigated a completely non-invasive pre-clinical protocol to effectively target and detect brain tumors through the orotracheal route, using ultra-small nanoparticles (USRPs) and MRI. A mouse model of GBM was developed. In vivo MRI acquisitions were performed before and after intravenous or orotracheal administration of the nanoparticles to identify and segment the tumor. The accumulation of the nanoparticles in neoplastic lesions was assessed ex vivo through fluorescence microscopy. Before the administration of contrast agents, MR images allowed the identification of the presence of abnormal brain tissue in 73% of animals. After orotracheal or intravenous administration of USRPs, in all the mice an excellent co-localization of the position of the tumor with MRI and histology was observed. The elimination time of the USRPs from the tumor after the orotracheal administration was approximately 70% longer compared with intravenous injection. MRI and USRPs were shown to be powerful imaging tools able to detect, quantify and longitudinally monitor the development of GBMs. The absence of ionizing radiation and high resolution of MRI, along with the complete non-invasiveness and good reproducibility of the proposed protocol, make this technique potentially translatable to humans. To our knowledge, this is the first time that the advantages of a needle-free orotracheal administration route have been demonstrated for the investigation of the pathomorphological changes due to GBMs. Copyright © 2015 John Wiley & Sons, Ltd.

  7. A Randomized Controlled Trial Investigating the Effects of a Special Extract of Bacopa monnieri (CDRI 08) on Hyperactivity and Inattention in Male Children and Adolescents: BACHI Study Protocol (ANZCTRN12612000827831).

    Science.gov (United States)

    Kean, James D; Kaufman, Jordy; Lomas, Justine; Goh, Antionette; White, David; Simpson, David; Scholey, Andrew; Singh, Hemant; Sarris, Jerome; Zangara, Andrea; Stough, Con

    2015-12-02

    Clinical diagnoses of Attention Deficit Hyperactivity Disorder (ADHD) and the use of prescription medications for its treatment have increased in recent years. Current treatments may involve the administration of amphetamine-type substances, a treatment path many parents are apprehensive to take. Therefore, alternative pharmacological treatments are required. Few nutritional or pharmacological alternatives that reduce ADHD associated symptoms (hyperactivity and inattention) have been subjected to rigorous clinical trials. Bacopa monnieri is a perennial creeping herb. CDRI 08 is a special extract of Bacopa monnieri which has been subjected to hundreds of scientific studies and has been shown in human randomized controlled trials (RCTs) to improve memory, attention, and mood. It is hypothesised that chronic administration of CDRI 08 will improve attention, concentration and behaviour in children with high levels of hyperactivity and/or inattention. This paper reports the protocol for the first 16-week, randomized, placebo-controlled, double-blind, parallel groups trial examining the efficacy and safety of CDRI 08 in male children aged 6-14 years with high levels of inattention and hyperactivity. The primary outcome variable will be the level of hyperactivity and inattention measured by the Conners' Parent Rating Scale (CPRS). Secondary outcome variables include cognition, mood, sleep, and EEG. Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000827831.

  8. A Randomized Controlled Trial Investigating the Effects of a Special Extract of Bacopa monnieri (CDRI 08 on Hyperactivity and Inattention in Male Children and Adolescents: BACHI Study Protocol (ANZCTRN12612000827831

    Directory of Open Access Journals (Sweden)

    James D. Kean

    2015-12-01

    Full Text Available Clinical diagnoses of Attention Deficit Hyperactivity Disorder (ADHD and the use of prescription medications for its treatment have increased in recent years. Current treatments may involve the administration of amphetamine-type substances, a treatment path many parents are apprehensive to take. Therefore, alternative pharmacological treatments are required. Few nutritional or pharmacological alternatives that reduce ADHD associated symptoms (hyperactivity and inattention have been subjected to rigorous clinical trials. Bacopa monnieri is a perennial creeping herb. CDRI 08 is a special extract of Bacopa monnieri which has been subjected to hundreds of scientific studies and has been shown in human randomized controlled trials (RCTs to improve memory, attention, and mood. It is hypothesised that chronic administration of CDRI 08 will improve attention, concentration and behaviour in children with high levels of hyperactivity and/or inattention. This paper reports the protocol for the first 16-week, randomized, placebo-controlled, double-blind, parallel groups trial examining the efficacy and safety of CDRI 08 in male children aged 6–14 years with high levels of inattention and hyperactivity. The primary outcome variable will be the level of hyperactivity and inattention measured by the Conners’ Parent Rating Scale (CPRS. Secondary outcome variables include cognition, mood, sleep, and EEG. Trial registration: Australia and New Zealand Clinical Trials Register (ANZCTR: ACTRN12612000827831.

  9. The correlation of in vivo and ex vivo tissue dielectric properties to validate electromagnetic breast imaging: initial clinical experience

    International Nuclear Information System (INIS)

    Halter, Ryan J; Zhou, Tian; Meaney, Paul M; Hartov, Alex; Barth, Richard J Jr; Rosenkranz, Kari M; Wells, Wendy A; Kogel, Christine A; Borsic, Andrea; Rizzo, Elizabeth J; Paulsen, Keith D

    2009-01-01

    Electromagnetic (EM) breast imaging provides low-cost, safe and potentially a more specific modality for cancer detection than conventional imaging systems. A primary difficulty in validating these EM imaging modalities is that the true dielectric property values of the particular breast being imaged are not readily available on an individual subject basis. Here, we describe our initial experience in seeking to correlate tomographic EM imaging studies with discrete point spectroscopy measurements of the dielectric properties of breast tissue. The protocol we have developed involves measurement of in vivo tissue properties during partial and full mastectomy procedures in the operating room (OR) followed by ex vivo tissue property recordings in the same locations in the excised tissue specimens in the pathology laboratory immediately after resection. We have successfully applied all of the elements of this validation protocol in a series of six women with cancer diagnoses. Conductivity and permittivity gauged from ex vivo samples over the frequency range 100 Hz–8.5 GHz are found to be similar to those reported in the literature. A decrease in both conductivity and permittivity is observed when these properties are gauged from ex vivo samples instead of in vivo. We present these results in addition to a case study demonstrating how discrete point spectroscopy measurements of the tissue can be correlated and used to validate EM imaging studies

  10. Exploring sex differences in the adult zebra finch brain: In vivo diffusion tensor imaging and ex vivo super-resolution track density imaging.

    Science.gov (United States)

    Hamaide, Julie; De Groof, Geert; Van Steenkiste, Gwendolyn; Jeurissen, Ben; Van Audekerke, Johan; Naeyaert, Maarten; Van Ruijssevelt, Lisbeth; Cornil, Charlotte; Sijbers, Jan; Verhoye, Marleen; Van der Linden, Annemie

    2017-02-01

    Zebra finches are an excellent model to study the process of vocal learning, a complex socially-learned tool of communication that forms the basis of spoken human language. So far, structural investigation of the zebra finch brain has been performed ex vivo using invasive methods such as histology. These methods are highly specific, however, they strongly interfere with performing whole-brain analyses and exclude longitudinal studies aimed at establishing causal correlations between neuroplastic events and specific behavioral performances. Therefore, the aim of the current study was to implement an in vivo Diffusion Tensor Imaging (DTI) protocol sensitive enough to detect structural sex differences in the adult zebra finch brain. Voxel-wise comparison of male and female DTI parameter maps shows clear differences in several components of the song control system (i.e. Area X surroundings, the high vocal center (HVC) and the lateral magnocellular nucleus of the anterior nidopallium (LMAN)), which corroborate previous findings and are in line with the clear behavioral difference as only males sing. Furthermore, to obtain additional insights into the 3-dimensional organization of the zebra finch brain and clarify findings obtained by the in vivo study, ex vivo DTI data of the male and female brain were acquired as well, using a recently established super-resolution reconstruction (SRR) imaging strategy. Interestingly, the SRR-DTI approach led to a marked reduction in acquisition time without interfering with the (spatial and angular) resolution and SNR which enabled to acquire a data set characterized by a 78μm isotropic resolution including 90 diffusion gradient directions within 44h of scanning time. Based on the reconstructed SRR-DTI maps, whole brain probabilistic Track Density Imaging (TDI) was performed for the purpose of super resolved track density imaging, further pushing the resolution up to 40μm isotropic. The DTI and TDI maps realized atlas

  11. Desmosomes In Vivo

    Directory of Open Access Journals (Sweden)

    David Garrod

    2010-01-01

    Full Text Available The structure, function, and regulation of desmosomal adhesion in vivo are discussed. Most desmosomes in tissues exhibit calcium-independent adhesion, which is strongly adhesive or “hyperadhesive”. This is fundamental to tissue strength. Almost all studies in culture are done on weakly adhesive, calcium-dependent desmosomes, although hyperadhesion can be readily obtained in confluent cell culture. Calcium dependence is a default condition in vivo, found in wounds and embryonic development. Hyperadhesion appears to be associated with an ordered arrangement of the extracellular domains of the desmosomal cadherins, which gives rise to the intercellular midline identified in ultrastructural studies. This in turn probably depends on molecular order in the desmosomal plaque. Protein kinase C downregulates hyperadhesion and there is preliminary evidence that it may also be regulated by tyrosine kinases. Downregulation of desmosomes in vivo may occur by internalisation of whole desmosomes rather than disassembly. Hyperadhesion has implications for diseases such as pemphigus.

  12. FRENCH PROTOCOL CARDS

    CERN Multimedia

    Division du Personnel

    1999-01-01

    Senior officials, holders of FRENCH PROTOCOL cards (blue cards) due to expire on 31.12.1999, are requested to return these cards and those of family members, for extension to:Bureau des cartes, bâtiment 33.1-025Should the 3 spaces for authentication on the back of the card be full, please enclose 2 passport photographs for a new card.In the case of children aged 14 and over, an attestation of dependency and a school certificate should be returned with the card.Personnel DivisionTel. 79494/74683

  13. FRENCH PROTOCOL CARDS

    CERN Multimedia

    Human Resources Division

    2000-01-01

    Senior officials, holders of FRENCH PROTOCOL cards (blue cards) due to expire on 31.12.2000, are requested to return these cards and those of family members, for extension to: Bureau des cartes, Bât 33.1-009/1-015 Should the three spaces for authentication on the back of the card be full, please enclose two passport photographs for a new card. In the case of children aged 14 and over, an attestation of dependency and a school certificate should be returned with the card.

  14. Distributed Network Protocols

    Science.gov (United States)

    1980-07-01

    MONITORING AGENCY NAME & ADDRESS(II different from Controlting Office) IS. SECURITY CLASS. (of this report) S Office of Naval Research Unclassified...All protocols are extended to networks with changing. topology. S80 8 4 246 DD0I iA 1473 EDITION OF INOV 65 IS OBSOLETE 8 0 24 SECURITY CLASSIFICATION...to the netowrk . f) Each node knows its adjacent links, but not necessarily the identity of its neighbors, i.e. the nodes at the other end of the links

  15. A blinded randomised placebo-controlled trial investigating the efficacy of morphine analgesia for procedural pain in infants: Trial protocol [version 2; referees: 2 approved, 1 approved with reservations

    Directory of Open Access Journals (Sweden)

    Rebeccah Slater

    2017-01-01

    Full Text Available Infant pain has both immediate and long-term negative consequences, yet in clinical practice it is often undertreated. To date, few pain-relieving drugs have been tested in infants. Morphine is a potent analgesic that provides effective pain relief in adults, but there is inconclusive evidence for its effectiveness in infants. The purpose of this study is to establish whether oral morphine provides effective analgesia for procedural pain in infants.   A blinded, placebo-controlled, parallel-group randomized, phase II, clinical trial will be undertaken to determine whether morphine sulphate administered orally prior to clinically-required retinopathy of prematurity (ROP screening and heel lancing provides effective analgesia. 
156 infants between 34 and 42 weeks’ gestational age who require a clinical heel lance and ROP screening on the same test occasion will be included in the trial. Infants will be randomised to receive either a single dose of morphine sulphate (100 μg/kg or placebo. Each infant will be monitored for 48 hours and safety data will be collected during the 24 hours following drug administration.   The primary outcome will be the Premature Infant Pain Profile–revised (PIPP-R score during the 30 second periods after ROP screening. The co-primary outcome will be the magnitude of nociceptive-specific brain activity evoked by a clinically-required heel lance. Infant clinical stability will be assessed by comparing the number of episodes of bradycardia, tachycardia, desaturation and apnoea, and changes in respiratory support requirements in the 24-hour periods before and after the clinical intervention. In addition, drug safety will be assessed by considering the occurrence of apnoeic and hypotensive episodes requiring intervention in the 24-hour period following drug administration. This study has been published as an Accepted Protocol Summary by The Lancet.

  16. Study protocol: a phase III randomised, double-blind, parallel arm, stratified, block randomised, placebo-controlled trial investigating the clinical effect and cost-effectiveness of sertraline for the palliative relief of breathlessness in people with chronic breathlessness.

    Science.gov (United States)

    Watts, Gareth J; Clark, Katherine; Agar, Meera; Davidson, Patricia M; McDonald, Christine; Lam, Lawrence T; Sajkov, Dimitar; McCaffrey, Nicola; Doogue, Matthew; Abernethy, Amy P; Currow, David C

    2016-11-29

    Breathlessness remains a highly prevalent and distressing symptom for many patients with progressive life-limiting illnesses. Evidence-based interventions for chronic breathlessness are limited, and there is an ongoing need for high-quality research into developing management strategies for optimal palliation of this complex symptom. Previous studies have suggested that selective serotonin reuptake inhibitors such as sertraline may have a role in reducing breathlessness. This paper presents the protocol for a large, adequately powered randomised study evaluating the use of sertraline for chronic breathlessness in people with progressive life-limiting illnesses. A total of 240 participants with modified Medical Research Council Dyspnoea Scale breathlessness of level 2 or higher will be randomised to receive either sertraline or placebo for 28 days in this multisite, double-blind study. The dose will be titrated up every 3 days to a maximum of 100 mg daily. The primary outcome will be to compare the efficacy of sertraline with placebo in relieving the intensity of worst breathlessness as assessed by a 0-100 mm Visual Analogue Scale. A number of other outcome measures and descriptors of breathlessness as well as caregiver assessments will also be recorded to ensure adequate analysis of participant breathlessness and to allow an economic analysis to be performed. Participants will also be given the option of continuing blinded treatment until either study data collection is complete or net benefit ceases. Appropriate statistical analysis of primary and secondary outcomes will be used to describe the wealth of data obtained. Ethics approval was obtained at all participating sites. Results of the study will be submitted for publication in peer-reviewed journals and the key findings presented at national and international conferences. ACTRN12610000464066. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a

  17. Radio-marking and in vivo imagery of oligonucleotides

    International Nuclear Information System (INIS)

    Kuehnast, Bertrand

    2000-01-01

    This research thesis is part of activities aimed at the development of new molecules like oligonucleotides. Its first objective was the development and validation of a marking method with fluorine-18 of oligonucleotides for their in-vivo pharmacological assessment with positron emission tomography (PET). Further investigations addressed the use of iodine-125 for oligonucleotide marking purpose. This radio-marking, and in vivo and ex vivo imagery techniques are described, and their potential is highlighted for the pharmacological assessment of different oligonucleotides

  18. Security and SCADA protocols

    International Nuclear Information System (INIS)

    Igure, V. M.; Williams, R. D.

    2006-01-01

    Supervisory control and data acquisition (SCADA) networks have replaced discrete wiring for many industrial processes, and the efficiency of the network alternative suggests a trend toward more SCADA networks in the future. This paper broadly considers SCADA to include distributed control systems (DCS) and digital control systems. These networks offer many advantages, but they also introduce potential vulnerabilities that can be exploited by adversaries. Inter-connectivity exposes SCADA networks to many of the same threats that face the public internet and many of the established defenses therefore show promise if adapted to the SCADA differences. This paper provides an overview of security issues in SCADA networks and ongoing efforts to improve the security of these networks. Initially, a few samples from the range of threats to SCADA network security are offered. Next, attention is focused on security assessment of SCADA communication protocols. Three challenges must be addressed to strengthen SCADA networks. Access control mechanisms need to be introduced or strengthened, improvements are needed inside of the network to enhance security and network monitoring, and SCADA security management improvements and policies are needed. This paper discusses each of these challenges. This paper uses the Profibus protocol as an example to illustrate some of the vulnerabilities that arise within SCADA networks. The example Profibus security assessment establishes a network model and an attacker model before proceeding to a list of example attacks. (authors)

  19. Evaluation of functional erythropoietin receptor status in skeletal muscle in vivo

    DEFF Research Database (Denmark)

    Christensen, Britt; Lundby, Carsten; Jessen, Niels

    2012-01-01

    Background: Erythropoietin receptors have been identified in human skeletal muscle tissue, but downstream signal transduction has not been investigated. We therefore studied in vivo effects of systemic erythropoietin exposure in human skeletal muscle. Methodology/Principal Findings: The protocols...... involved 1) acute effects of a single bolus injection of erythropoietin followed by consecutive muscle biopsies for 1-10 hours, and 2) a separate study with prolonged administration for 16 days with biopsies obtained before and after. The presence of erythropoietin receptors in muscle tissue as well...... as activation of Epo signalling pathways (STAT5, MAPK, Akt, IKK) were analysed by western blotting. Changes in muscle protein profiles after prolonged erythropoietin treatment were evaluated by 2D gel-electrophoresis and mass spectrometry. The presence of the erythropoietin receptor in skeletal muscle...

  20. Evaluation of functional erythropoietin receptor status in skeletal muscle in vivo

    DEFF Research Database (Denmark)

    Christensen, Britt; Lundby, Carsten; Jessen, Niels

    2012-01-01

    as activation of Epo signalling pathways (STAT5, MAPK, Akt, IKK) were analysed by western blotting. Changes in muscle protein profiles after prolonged erythropoietin treatment were evaluated by 2D gel-electrophoresis and mass spectrometry. The presence of the erythropoietin receptor in skeletal muscle......Background: Erythropoietin receptors have been identified in human skeletal muscle tissue, but downstream signal transduction has not been investigated. We therefore studied in vivo effects of systemic erythropoietin exposure in human skeletal muscle. Methodology/Principal Findings: The protocols...... involved 1) acute effects of a single bolus injection of erythropoietin followed by consecutive muscle biopsies for 1-10 hours, and 2) a separate study with prolonged administration for 16 days with biopsies obtained before and after. The presence of erythropoietin receptors in muscle tissue as well...

  1. A non-covalent peptide-based strategy for ex vivo and in vivo oligonucleotide delivery.

    Science.gov (United States)

    Crombez, Laurence; Morris, May C; Heitz, Frederic; Divita, Gilles

    2011-01-01

    The dramatic acceleration in identification of new nucleic acid-based therapeutic molecules such as short interfering RNA (siRNA) and peptide-nucleic acid (PNA) analogues has provided new perspectives for therapeutic targeting of specific genes responsible for pathological disorders. However, the poor cellular uptake of nucleic acids together with the low permeability of the cell membrane to negatively charged molecules remain major obstacles to their clinical development. Several non-viral strategies have been proposed to improve the delivery of synthetic short oligonucleotides both in cultured cells and in vivo. Cell-penetrating peptides constitute very promising tools for non-invasive cellular import of oligonucleotides and analogs. We recently described a non-covalent strategy based on short amphiphatic peptides (MPG8/PEP3) that have been successfully applied ex vivo and in vivo for the delivery of therapeutic siRNA and PNA molecules. PEP3 and MPG8 form stable nanoparticles with PNA analogues and siRNA, respectively, and promote their efficient cellular uptake, independently of the endosomal pathway, into a wide variety of cell lines, including primary and suspension lines, without any associated cytotoxicity. This chapter describes easy-to-handle protocols for the use of MPG-8 or PEP-3-nanoparticle technologies for PNA and siRNA delivery into adherent and suspension cell lines as well as in vivo into cancer mouse models.

  2. A randomised controlled intervention study investigating the efficacy of carotenoid-rich fruits and vegetables and extra-virgin olive oil on attenuating sarcopenic symptomology in overweight and obese older adults during energy intake restriction: protocol paper.

    Science.gov (United States)

    Villani, Anthony; Wright, Hattie; Slater, Gary; Buckley, Jonathan

    2018-01-05

    Weight loss interventions have not been advocated for overweight/obese older adults due to potential loss of skeletal muscle and strength impacting on physical function with potential loss of independence. Carotenoids and polyphenols are inversely associated with sarcopenic symptomology. This paper reports the protocol of a study evaluating the efficacy of a high-protein, energy restricted diet rich in carotenoids and polyphenols on body composition, muscle strength, physical performance and quality of life in overweight and obese older adults. This randomised controlled clinical trial will recruit community-dwelling, healthy overweight and obese older adults (≥60 years) for a 12-week weight loss intervention. Seventy-three participants will be recruited and randomized to an energy restricted (~30% restriction), isocaloric diet (30% protein; 30% carbohydrate; 40% fat) enriched with either: a) 375 g/d of high carotenoid vegetables, 300 g/d high carotenoid fruit, and 40-60 ml extra-virgin olive oil (EVOO); or b) 375 g/d of lower carotenoid vegetables, 300 g/d lower carotenoid fruit, and 40-60 ml Polyunsaturated fatty acid (PUFA) based oil. All participants will receive individual dietary counselling each fortnight for the duration of the study and will be asked to maintain their habitual level of physical activity throughout the study. The primary outcome will be appendicular skeletal muscle (ASM) assessed by dual energy X-ray absorptiometry (DXA). Secondary outcomes will include body weight, fat-free mass (FFM), fat mass (FM), muscle strength (Isometric hand-grip strength), physical performance (Short Physical Performance Battery), physical activity (International Physical Activity Questionnaire) and health related quality of life (SF-36). Outcomes will be measured at baseline and at week 12. The results of this study will provide a novel insight relating to the potential influence of high carotenoid and polyphenol intakes on attenuation of ASM during

  3. Multicentre randomised controlled trial to investigate the usefulness of continuous pneumatic regulation of tracheal cuff pressure for reducing ventilator-associated pneumonia in mechanically ventilated severe trauma patients: the AGATE study protocol.

    Science.gov (United States)

    Marjanovic, Nicolas; Frasca, Denis; Asehnoune, Karim; Paugam, Catherine; Lasocki, Sigismond; Ichai, Carole; Lefrant, Jean-Yves; Leone, Marc; Dahyot-Fizelier, Claire; Pottecher, Julien; Falcon, Dominique; Veber, Benoit; Constantin, Jean-Michel; Seguin, Sabrina; Guénézan, Jérémy; Mimoz, Olivier

    2017-08-07

    Severe trauma represents the leading cause of mortality worldwide. While 80% of deaths occur within the first 24 hours after trauma, 20% occur later and are mainly due to healthcare-associated infections, including ventilator-associated pneumonia (VAP). Preventing underinflation of the tracheal cuff is recommended to reduce microaspiration, which plays a major role in the pathogenesis of VAP. Automatic devices facilitate the regulation of tracheal cuff pressure, and their implementation has the potential to reduce VAP. The objective of this work is to determine whether continuous regulation of tracheal cuff pressure using a pneumatic device reduces the incidence of VAP compared with intermittent control in severe trauma patients. This multicentre randomised controlled and open-label trial will include patients suffering from severe trauma who are admitted within the first 24 hours, who require invasive mechanical ventilation to longer than 48 hours. Their tracheal cuff pressure will be monitored either once every 8 hours (control group) or continuously using a pneumatic device (intervention group). The primary end point is the proportion of patients that develop VAP in the intensive care unit (ICU) at day 28. The secondary end points include the proportion of patients that develop VAP in the ICU, early (≤7 days) or late (>7 days) VAP, time until the first VAP diagnosis, the number of ventilator-free days and antibiotic-free days, the length of stay in the ICU, the proportion of patients with ventilator-associated events and that die during their ICU stay. This protocol has been approved by the ethics committee of Poitiers University Hospital, and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals. Clinical Trials NCT02534974. © Article author(s) (or

  4. [Computerized clinical protocol for occlusion].

    Science.gov (United States)

    Salsench, J; Ferrer, J; Nogueras, J

    1988-11-01

    In making a protocol it is necessary that all members of the team who are going to collect information have the same unity of criterion about the different variables that compose it. The drawing up of this document is as much or more necessary than the protocol itself. In this work we all data collected in the protocol and we give the explanations of each concept.

  5. Static Validation of Security Protocols

    DEFF Research Database (Denmark)

    Bodei, Chiara; Buchholtz, Mikael; Degano, P.

    2005-01-01

    We methodically expand protocol narrations into terms of a process algebra in order to specify some of the checks that need to be made in a protocol. We then apply static analysis technology to develop an automatic validation procedure for protocols. Finally, we demonstrate that these techniques ...... suffice to identify several authentication flaws in symmetric and asymmetric key protocols such as Needham-Schroeder symmetric key, Otway-Rees, Yahalom, Andrew secure RPC, Needham-Schroeder asymmetric key, and Beller-Chang-Yacobi MSR...

  6. PROTOCOL FOR EXAMINATION OF THE INNER CAN CLOSURE WELD REGION FOR 3013 DE CONTAINERS

    Energy Technology Data Exchange (ETDEWEB)

    Mickalonis, J.

    2014-09-16

    The protocol for the examination of the inner can closure weld region (ICCWR) for 3013 DE containers is presented within this report. The protocol includes sectioning of the inner can lid section, documenting the surface condition, measuring corrosion parameters, and storing of samples. This protocol may change as the investigation develops since findings may necessitate additional steps be taken. Details of the previous analyses, which formed the basis for this protocol, are also presented.

  7. Unconditionally Secure Protocols

    DEFF Research Database (Denmark)

    Meldgaard, Sigurd Torkel

    This thesis contains research on the theory of secure multi-party computation (MPC). Especially information theoretically (as opposed to computationally) secure protocols. It contains results from two main lines of work. One line on Information Theoretically Secure Oblivious RAMS, and how....... We construct an oblivious RAM that hides the client's access pattern with information theoretic security with an amortized $\\log^3 N$ query overhead. And how to employ a second server that is guaranteed not to conspire with the first to improve the overhead to $\\log^2 N$, while also avoiding...... they are used to speed up secure computation. An Oblivious RAM is a construction for a client with a small $O(1)$ internal memory to store $N$ pieces of data on a server while revealing nothing more than the size of the memory $N$, and the number of accesses. This specifically includes hiding the access pattern...

  8. Protocols for Scholarly Communication

    CERN Document Server

    Pepe, Alberto; Pepe, Alberto; Yeomans, Joanne

    2007-01-01

    CERN, the European Organization for Nuclear Research, has operated an institutional preprint repository for more than 10 years. The repository contains over 850,000 records of which more than 450,000 are full-text OA preprints, mostly in the field of particle physics, and it is integrated with the library's holdings of books, conference proceedings, journals and other grey literature. In order to encourage effective propagation and open access to scholarly material, CERN is implementing a range of innovative library services into its document repository: automatic keywording, reference extraction, collaborative management tools and bibliometric tools. Some of these services, such as user reviewing and automatic metadata extraction, could make up an interesting testbed for future publishing solutions and certainly provide an exciting environment for e-science possibilities. The future protocol for scientific communication should naturally guide authors towards OA publication and CERN wants to help reach a full...

  9. Nevomelanocytic atypia detection by in vivo reflectance confocal microscopy

    Directory of Open Access Journals (Sweden)

    Ingrida Vaišnorienė

    2014-01-01

    Conclusions: Nevus with histopathologically confirmed nevomelanocytic atypia (dysplastic nevus could not be distinguished from nevus without atypia using analyzed in vivo RCM features of melanocytic atypia. More accurate diagnostics by means of in vivo RCM needs further investigation on reflectance of single and nested cutaneous melanocytes in benign and malignant skin lesions.

  10. The synthesis of (R)- and (S)-[N-methyl-{sup 11}C]{beta}, {beta}-difluoromethamphetamine for the investigation of the binding mechanism of biogenic amines in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Gillings, N.M.; Gee, A.D. [PET Centre, Aarhus University Hospital, Aarhus C (Denmark); Inoue, O. [School of Allied Health Sciences, Osaka University Medical School, Osaka (Japan)

    1999-04-01

    In an attempt to elucidate the contribution of the extent of nitrogen protonation on the in vivo binding of methamphetamine in the brain, the enantiomers of [N-methyl-{sup 11}C]{beta},{beta}-difluoroamphetamine (4) were prepared for use in positron emission tomography (PET) studies. Thus, the enantiomers of {beta},{beta}-difluoroamphetamine were prepared from trans-{beta}-methylstyrene, via bromination, conversion into the azirine, fluorination and resolution as the tartrate salts. (R)- and (S)-{beta},{beta}-difluoroamphetamine (3) were then each labelled with carbon-11 (t{sub 1/2}=20.4 min) by N-methylation of the corresponding homochiral {beta},{beta}-difluoroamphetamine with [{sup 11}C]methyl iodide. The labelled products were each synthesised, purified and formulated in 35 min, starting from [{sup 11}C]carbon dioxide in 15-16% decay-corrected radiochemical yield, with a radiochemical purity of >99% and specific radioactivity of 50-150 GBq {mu}mol{sup -1} at end of synthesis.

  11. Investigation of the In Vitro and In Vivo efficiency of RM-532-105, a 17β-hydroxysteroid dehydrogenase type 3 inhibitor, in LAPC-4 prostate cancer cell and tumor models.

    Directory of Open Access Journals (Sweden)

    Lucie Carolle Kenmogne

    Full Text Available In the fight against androgen-sensitive prostate cancer, the enzyme 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3 is an attractive therapeutic target considering its key role in the formation of androgenic steroids. In this study, we attempted to assess the in vivo efficacy of the compound RM-532-105, an androsterone derivative developed as an inhibitor of 17β-HSD3, in the prostate cancer model of androgen-sensitive LAPC-4 cells xenografted in nude mice. RM-532-105 did not inhibit the tumor growth induced by 4-androstene-3,17-dione (4-dione; rather, the levels of the androgens testosterone (T and dihydrotestosterone (DHT increased within the tumors. In plasma, however, DHT levels increased but T levels did not. In troubleshooting experiments, the non-androgenic potential of RM-532-105 was confirmed by two different assays (LAPC-4 proliferation and androgen receptor transcriptional activity assays. The enzyme 5α-reductase was also revealed to be the predominant enzyme metabolizing 4-dione in LAPC-4 cells, yielding 5α-androstane-3,17-dione and not T. Other 17β-HSDs than 17β-HSD3 seem responsible in the androgen synthesis. From experiments with LAPC-4 cells, we fortuitously came across the interesting finding that 17β-HSD3 inhibitor RM-532-105 is concentrated inside tumors.

  12. Modeling and Verification of the Bitcoin Protocol

    OpenAIRE

    Chaudhary, Kaylash; Fehnker, Ansgar; van de Pol, Jaco; Stoelinga, Marielle

    2015-01-01

    Bitcoin is a popular digital currency for online payments, realized as a decentralized peer-to-peer electronic cash system. Bitcoin keeps a ledger of all transactions; the majority of the participants decides on the correct ledger. Since there is no trusted third party to guard against double spending, and inspired by its popularity, we would like to investigate the correctness of the Bitcoin protocol. Double spending is an important threat to electronic payment systems. Double spending would...

  13. In Vivo Respiratory-Gated Micro-CT Imaging in Small-Animal Oncology Models

    Directory of Open Access Journals (Sweden)

    Dawn Cavanaugh

    2004-01-01

    Full Text Available Micro-computed tomography (micro-CT is becoming an accepted research tool for the noninvasive examination of laboratory animals such as mice and rats, but to date, in vivo scanning has largely been limited to the evaluation of skeletal tissues. We use a commercially available micro-CT device to perform respiratory gated in vivo acquisitions suitable for thoracic imaging. The instrument is described, along with the scan protocol and animal preparation techniques. Preliminary results confirm that lung tumors as small as 1 mm in diameter are visible in vivo with these methods. Radiation dose was evaluated using several approaches, and was found to be approximately 0.15 Gy for this respiratory-gated micro-CT imaging protocol. The combination of high-resolution CT imaging and respiratory-gated acquisitions appears well-suited to serial in vivo scanning.

  14. [Protocols for the health surveillance of fisherman].

    Science.gov (United States)

    Soleo, Leonardo; Cannizzaro, Emanuele; Lovreglio, Piero; Basso, Antonella; D'Errico, Maria Nicolà; Pira, Enrico

    2013-01-01

    To define protocols for health surveillance of workers in the marine fishing sector for specific occupational risk factors, considering the latest and most advanced scientific knowledge. The specific literature was analyzed to identify the occupational risk factors to which fishermen are exposed. Then, for each risk factor a protocol for the relative health checkups and their time schedule was defined. The risk factors to which fishermen are exposed are essentially noise, vibrations, solar and ultraviolet radiation, climatic agents (heat, cold, wind, rain, damp), chemical agents, shifts, work rate, night work, physical strain, stress, manual handling of loads, upper limb repetitive tasks, incongruous postures. The health protocols stipulate the health screening investigations to be carried out in all workers of a homogeneous group, and in-depth diagnostic investigations to be carried out in symptomatic workers. Complementary health investigations must be focused on a functional exploration of the organs specifically exposed to the risk factor. For hearing impairments due to noise exposure, the medico-legal measures with which the occupational health physician must comply, in cases of occupational disease, are indicated.

  15. The UMTS-AKA Protocols for Intelligent Transportation Systems

    Directory of Open Access Journals (Sweden)

    Hwang Min-Shiang

    2009-01-01

    Full Text Available The integration of communication protocols into transport systems is a much adored research area today. Much of seminal work has been reported on the topic of intelligent transportation systems (ITS in the recent years. Many advanced techniques have been garnered to improve online communication and to promote the security, comfort, and efficiency of ITS. Of primary importance to the effective application of ITS is the communication protocol used. A fascinating development is that the yesterday's Global System for Mobile Communication protocol is being replaced by the Universal Mobile Telecommunication System protocol, which is the third-generation mobile technology. This article attempts to identify a suitable communication system for ITS applications. It is impracticable to substantially modify the original UMTS-IMS-AKA protocol which is in practice because it can disturb the operation of the current system, and thus we explore other possibilities through this research. We investigate a novel protocol to make the original UMTS-IMS-AKA protocol compliant with ITS as well as adaptable into the current UMTS protocol.

  16. Corrosion Damage Investigation of Silver-Soldered Stainless Steel Orthodontic Appliances Used in Vivo / Ocena Zniszczeń Korozyjnych Używanych In Vivo Stałych Aparatów Ortodontycznych O Połączeniach Lutowanych Na Bazie Srebra

    Directory of Open Access Journals (Sweden)

    Łępicka M.

    2015-12-01

    Full Text Available Processes of destruction of products used in orthodontic treatment, e.g. fixed orthodontic appliances, microimplants or dental prostheses considerably limit its operational lifetime and comfort and safety of patients. The objective of the research was to evaluate and assess corrosion damage to silver-soldered stainless steel rapid palatal expansion Hyrax devices. Used in vivo for 2 or 6 months, respectively, RPE (rapid palatal expansion devices were analyzed macroscopically and in a scanning electron microscope with an energy X-ray analyzer for signs of corrosion. The evaluated appliances showed discernible differences between the overall condition of the noble solders and the stainless steel elements. The Ag-rich solders were chiefly covered in corrosion pits, whereas stainless steel wires, molar bands and Hyrax screws presented corrosion-free surfaces. What is more, the EDS analysis showed differential element composition of the solders. According to the results, noble materials, such as Ag-rich solders, can corrode in a salivary environment when coupled with stainless steel. The selective leaching processes are observed.

  17. Correlation of In Vivo Versus In Vitro Benchmark Doses (BMDs) Derived From Micronucleus Test Data: A Proof of Concept Study.

    Science.gov (United States)

    Soeteman-Hernández, Lya G; Fellows, Mick D; Johnson, George E; Slob, Wout

    2015-12-01

    In this study, we explored the applicability of using in vitro micronucleus (MN) data from human lymphoblastoid TK6 cells to derive in vivo genotoxicity potency information. Nineteen chemicals covering a broad spectrum of genotoxic modes of action were tested in an in vitro MN test using TK6 cells using the same study protocol. Several of these chemicals were considered to need metabolic activation, and these were administered in the presence of S9. The Benchmark dose (BMD) approach was applied using the dose-response modeling program PROAST to estimate the genotoxic potency from the in vitro data. The resulting in vitro BMDs were compared with previously derived BMDs from in vivo MN and carcinogenicity studies. A proportional correlation was observed between the BMDs from the in vitro MN and the BMDs from the in vivo MN assays. Further, a clear correlation was found between the BMDs from in vitro MN and the associated BMDs for malignant tumors. Although these results are based on only 19 compounds, they show that genotoxicity potencies estimated from in vitro tests may result in useful information regarding in vivo genotoxic potency, as well as expected cancer potency. Extension of the number of compounds and further investigation of metabolic activation (S9) and of other toxicokinetic factors would be needed to validate our initial conclusions. However, this initial work suggests that this approach could be used for in vitro to in vivo extrapolations which would support the reduction of animals used in research (3Rs: replacement, reduction, and refinement). © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology.

  18. Triamcinolone acetonide activates an anti-inflammatory and folate receptor-positive macrophage that prevents osteophytosis in vivo.

    Science.gov (United States)

    Siebelt, Michiel; Korthagen, Nicoline; Wei, Wu; Groen, Harald; Bastiaansen-Jenniskens, Yvonne; Müller, Christina; Waarsing, Jan Hendrik; de Jong, Marion; Weinans, Harrie

    2015-12-05

    Triamcinolone acetonide (TA) is used for osteoarthritis management to reduce pain, and pre-clinical studies have shown that TA limits osteophyte formation. Osteophyte formation is known to be facilitated by synovial macrophage activation. TA injections might influence macrophage activation and subsequently reduce osteophytosis. Although widely applied in clinical care, the mechanism through which TA exerts this effect remains unknown. In this animal study, we investigated the in vivo effects of TA injections on macrophage activation, osteophyte development and joint degeneration. Furthermore, in vitro macrophage differentiation experiments were conducted to further explain working mechanisms of TA effects found in vivo. Osteoarthritis was induced in rat knees using papain injections and a running protocol. Untreated and TA-treated animals were longitudinally monitored for 12 weeks with in vivo micro-computed tomography (μCT) to measure subchondral bone changes. Synovial macrophage activation was measured in vivo using folate receptor β (FRβ)-targeted single-photon emission computed tomography/computed tomography. Articular cartilage was analyzed at 6 and 12 weeks with ex vivo contrast-enhanced μCT and histology. To further explain the outcomes of our in vivo study, TA on macrophages was also studied in vitro. These cultured macrophages were either M1- or M2-activated, and they were analyzed using fluorescence-activated cell sorting for CD163 and FRβ expression as well as for messenger RNA (mRNA) expression of interleukin (IL)-10. Our in vivo study showed that intra-articular injections with TA strongly enhanced FRβ(+) macrophage activation. Despite stimulated macrophage activation, osteophyte formation was fully prevented. There was no beneficial effect of TA against cartilage degradation or subchondral bone sclerosis. In vitro macrophage cultures showed that TA strongly induced monocyte differentiation towards CD163(+) and FRβ(+) macrophages. Furthermore

  19. In vivo and ex vivo characterization of a novel Er fiber laser system for fractional treatment of soft oral tissues

    Science.gov (United States)

    Shatilova, Ksenia; Aloian, Georgii; Karabut, Maria; Ryabova, Valentina; Yaroslavsky, Ilya V.; Altshuler, Gregory

    2018-02-01

    In this work, we present the first histological in vivo and ex vivo study of effects of fractional Er fiber laser (wavelength 1550 nm, peak power 25 W) on keratinized gum and alveolar mucosa for gum regeneration. Biopsy with subsequent NBTC staining was used as primary evaluation technique. Ex vivo, porcine tissue model was used. Effects of pulse energy, beam diameter, and beam divergence were investigated in detail. It has been demonstrated that under optimal conditions columns up to 800 μm in depth could be reliably produced with 130 mJ pulses. Clinically, 2 subjects were treated and 4 punch biopsies were collected. The results were compared with ex vivo data. Both ex vivo and in vivo datasets suggest feasibility of a dental fractional system intended for gum regeneration.

  20. Gene probes: principles and protocols

    National Research Council Canada - National Science Library

    Aquino de Muro, Marilena; Rapley, Ralph

    2002-01-01

    ... of labeled DNA has allowed genes to be mapped to single chromosomes and in many cases to a single chromosome band, promoting significant advance in human genome mapping. Gene Probes: Principles and Protocols presents the principles for gene probe design, labeling, detection, target format, and hybridization conditions together with detailed protocols, accom...

  1. Developing frameworks for protocol implementation

    NARCIS (Netherlands)

    de Barros Barbosa, C.; de barros Barbosa, C.; Ferreira Pires, Luis

    1999-01-01

    This paper presents a method to develop frameworks for protocol implementation. Frameworks are software structures developed for a specific application domain, which can be reused in the implementation of various different concrete systems in this domain. The use of frameworks support a protocol

  2. Incorporating ethical principles into clinical research protocols: a tool for protocol writers and ethics committees.

    Science.gov (United States)

    Li, Rebecca H; Wacholtz, Mary C; Barnes, Mark; Boggs, Liam; Callery-D'Amico, Susan; Davis, Amy; Digilova, Alla; Forster, David; Heffernan, Kate; Luthin, Maeve; Lynch, Holly Fernandez; McNair, Lindsay; Miller, Jennifer E; Murphy, Jacquelyn; Van Campen, Luann; Wilenzick, Mark; Wolf, Delia; Woolston, Cris; Aldinger, Carmen; Bierer, Barbara E

    2016-04-01

    A novel Protocol Ethics Tool Kit ('Ethics Tool Kit') has been developed by a multi-stakeholder group of the Multi-Regional Clinical Trials Center of Brigham and Women's Hospital and Harvard. The purpose of the Ethics Tool Kit is to facilitate effective recognition, consideration and deliberation of critical ethical issues in clinical trial protocols. The Ethics Tool Kit may be used by investigators and sponsors to develop a dedicated Ethics Section within a protocol to improve the consistency and transparency between clinical trial protocols and research ethics committee reviews. It may also streamline ethics review and may facilitate and expedite the review process by anticipating the concerns of ethics committee reviewers. Specific attention was given to issues arising in multinational settings. With the use of this Tool Kit, researchers have the opportunity to address critical research ethics issues proactively, potentially speeding the time and easing the process to final protocol approval. 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/

  3. Repetitive cryotherapy attenuates the in vitro and in vivo mononuclear cell activation response.

    Science.gov (United States)

    Lindsay, Angus; Othman, Mohd Izani; Prebble, Hannah; Davies, Sian; Gieseg, Steven P

    2016-07-01

    What is the central question of this study? Acute and repetitive cryotherapy are routinely used to accelerate postexercise recovery, although the effect on resident immune cells and repetitive exposure has largely been unexplored and neglected. What is the main finding and its importance? Using blood-derived mononuclear cells and semi-professional mixed martial artists, we show that acute and repetitive cryotherapy reduces the in vitro and in vivo T-cell and monocyte activation response whilst remaining independent of the physical performance of elite athletes. We investigated the effect of repetitive cryotherapy on the in vitro (cold exposure) and in vivo (cold water immersion) activation of blood-derived mononuclear cells following high-intensity exercise. Single and repeated cold exposure (5°C) of a mixed cell culture (T cells and monocytes) was investigated using in vitro tissue culture experimentation for total neopterin production (neopterin plus 7,8-dihydroneopterin). Fourteen elite mixed martial art fighters were also randomly assigned to either a cold water immersion (15 min at 10°C) or passive recovery protocol, which they completed three times per week during a 6 week training camp. Urine was collected and analysed for neopterin and total neopterin three times per week, and perceived soreness, fatigue, physical performance (broad jump, push-ups and pull-ups) and training performance were also assessed. Single and repetitive cold exposure significantly (P cryotherapy attenuates in vitro T-cell and monocyte activation. This may explain the disparity in in vivo neopterin and total neopterin between cold water immersion and passive recovery following repetitive exposure during a high-intensity physical impact sport that remains independent of physical performance. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

  4. Quantifying drug-protein binding in vivo

    International Nuclear Information System (INIS)

    Buchholz, B; Bench, G; Keating III, G; Palmblad, M; Vogel, J; Grant, P G; Hillegonds, D

    2004-01-01

    Accelerator mass spectrometry (AMS) provides precise quantitation of isotope labeled compounds that are bound to biological macromolecules such as DNA or proteins. The sensitivity is high enough to allow for sub-pharmacological (''micro-'') dosing to determine macromolecular targets without inducing toxicities or altering the system under study, whether it is healthy or diseased. We demonstrated an application of AMS in quantifying the physiologic effects of one dosed chemical compound upon the binding level of another compound in vivo at sub-toxic doses [4].We are using tissues left from this study to develop protocols for quantifying specific binding to isolated and identified proteins. We also developed a new technique to quantify nanogram to milligram amounts of isolated protein at precisions that are comparable to those for quantifying the bound compound by AMS

  5. Growing old at home – A randomized controlled trial to investigate the effectiveness and cost-effectiveness of preventive home visits to reduce nursing home admissions: study protocol [NCT00644826

    Directory of Open Access Journals (Sweden)

    Riedel-Heller Steffi G

    2008-05-01

    Full Text Available Abstract Background Regarding demographic changes in Germany it can be assumed that the number of elderly and the resulting need for long term care is increasing in the near future. It is not only an individual's interest but also of public concern to avoid a nursing home admission. Current evidence indicates that preventive home visits can be an effective way to reduce the admission rate in this way making it possible for elderly people to stay longer at home than without home visits. As the effectiveness and cost-effectiveness of preventive home visits strongly depends on existing services in the social and health system existing international results cannot be merely transferred to Germany. Therefore it is necessary to investigate the effectiveness and cost-effectiveness of such an intervention in Germany by a randomized controlled trial. Methods The trial is designed as a prospective multi-center randomized controlled trial in the cities of Halle and Leipzig. The trial includes an intervention and a control group. The control group receives usual care. The intervention group receives three additional home visits by non-physician health professionals (1 geriatric assessment, (2 consultation, (3 booster session. The nursing home admission rate after 18 months will be defined as the primary outcome. An absolute risk reduction from a 20% in the control-group to a 7% admission rate in the intervention group including an assumed drop out rate of 30% resulted in a required sample size of N = 320 (n = 160 vs. n = 160. Parallel to the clinical outcome measurement the intervention will be evaluated economically. The economic evaluation will be performed from a society perspective. Discussion To the authors' knowledge for the first time a trial will investigate the effectiveness and cost-effectiveness of preventive home visits for people aged 80 and over in Germany using the design of a randomized controlled trial. Thus, the trial will contribute to

  6. Protocols for Scholarly Communication

    Science.gov (United States)

    Pepe, A.; Yeomans, J.

    2007-10-01

    CERN, the European Organization for Nuclear Research, has operated an institutional preprint repository for more than 10 years. The repository contains over 850,000 records of which more than 450,000 are full-text OA preprints, mostly in the field of particle physics, and it is integrated with the library's holdings of books, conference proceedings, journals and other grey literature. In order to encourage effective propagation and open access to scholarly material, CERN is implementing a range of innovative library services into its document repository: automatic keywording, reference extraction, collaborative management tools and bibliometric tools. Some of these services, such as user reviewing and automatic metadata extraction, could make up an interesting testbed for future publishing solutions and certainly provide an exciting environment for e-science possibilities. The future protocol for scientific communication should guide authors naturally towards OA publication, and CERN wants to help reach a full open access publishing environment for the particle physics community and related sciences in the next few years.

  7. A Novel Methodology for the Simulation of Athletic Tasks on Cadaveric Knee Joints with Respect to In Vivo Kinematics

    Science.gov (United States)

    Bates, Nathaniel A.; Nesbitt, Rebecca J.; Shearn, Jason T.; Myer, Gregory D.; Hewett, Timothy E.

    2015-01-01

    Six degree of freedom (6-DOF) robotic manipulators have simulated clinical tests and gait on cadaveric knees to examine knee biomechanics. However, these activities do not necessarily emulate the kinematics and kinetics that lead to anterior cruciate ligament (ACL) rupture. The purpose of this study was to determine the techniques needed to derive reproducible, in vitro simulations from in vivo skin-marker kinematics recorded during simulated athletic tasks. Input of raw, in vivo, skin-marker-derived motion capture kinematics consistently resulted in specimen failure. The protocol described in this study developed an in-depth methodology to adapt in vivo kinematic recordings into 6-DOF knee motion simulations for drop vertical jumps and sidestep cutting. Our simulation method repeatably produced kinetics consistent with vertical ground reaction patterns while preserving specimen integrity. Athletic task simulation represents an advancement that allows investigators to examine ACL-intact and graft biomechanics during motions that generate greater kinetics, and the athletic tasks are more representative of documented cases of ligament rupture. Establishment of baseline functional mechanics within the knee joint during athletic tasks will serve to advance the prevention, repair and rehabilitation of ACL injuries. PMID:25869454

  8. Investigating the safety and efficacy of naltrexone for anti-psychotic induced weight gain in severe mental illness: study protocol of a double-blind, randomized, placebo-controlled trial.

    Science.gov (United States)

    Tek, Cenk; Guloksuz, Sinan; Srihari, Vinod H; Reutenauer, Erin L

    2013-06-27

    Obesity is a growing health problem leading to high rates of mortality and morbidity in patients with severe mental illness (SMI). The increased rate of obesity is largely attributed to antipsychotic use. The effect of antipsychotic medications on H1 and 5HT2 receptors has been associated with weight gain, but there is also a substantial amount of evidence showing that D2 receptor blockade may be responsible for weight gain by interacting with the dopamine-opioid system. Unfortunately, current available medications for weight loss have limited efficacy in this population. Naltrexone, an opioid receptor antagonist, may be a promising agent to reduce antipsychotic induced weight gain by decreasing food cravings. We aim to investigate the safety and efficacy of two doses of naltrexone (25 mg & 50 mg) versus placebo for weight and health risk reduction in overweight and obese individuals (BMI ≥ 28) with SMI, who gained weight while being treated with antipsychotics. One hundred and forty four patients will be recruited throughout the greater New Haven area. The participants will be randomized to naltrexone 25 mg/day, naltrexone 50 mg/day, or placebo in a 1:1:1 ratio. Participants will be on the study medication for 52 weeks, and assessed weekly for the first 4 weeks and bi-weekly thereafter. The primary outcome measurements are weight reduction and percentage achieving clinically significant weight loss (5% of total body weight). Waist circumference, body mass index, serum lipid profile, fasting glucose, and glycosylated hemoglobin are the secondary outcome measures. The effect of naltrexone on other outcome measurements such as schizophrenia symptoms, depression, dietary consumption, quality of life, cognitive functioning, physical activity, metabolism/inflammation markers, serum leptin, ghrelin, peptide YY, adinopectin, high sensitivity CRP, interleukin 6, interleukin-1B, interleukin-18, and tumor necrosis factor alpha (TNF-α) will be evaluated. The data will be

  9. Investigation of inter-grain critical current density in Bi2Sr2CaCu2O8+δ superconducting wires and its relationship with the heat treatment protocol

    Science.gov (United States)

    Pallecchi, I.; Leveratto, A.; Braccini, V.; Zunino, V.; Malagoli, A.

    2017-09-01

    In this work we investigate the effect of each different heat treatment stage in the fabrication of Bi2Sr2CaCu2O8+δ superconducting wires on intra-grain and inter-grain superconducting properties. We measure magnetic critical temperature T c values and transport critical current density J c at temperatures from 4 K to 40 K and in fields up to 7 T. From an analysis of the temperature dependence of the self-field critical current density J c(T) that takes into account weak link behavior and the proximity effect, we study grain boundary (GB) transparency to supercurrents; we also establish a relationship between GB oxygenation in the different steps of the fabrication process and GB transparency to supercurrents. We find that GB oxygenation starts in the first crystallization stage, but it becomes complete in the plateau at 836 °C and in slow cooling stages and is further enhanced in the prolonged post-annealing step. Such oxygenation makes GBs more conductive, thus improving the inter-grain J c value and temperature dependence. On the other hand, from inspection of the T c values in the framework of the phase diagram dome, we find that grains are already oxygenated in the crystallization step up to the optimal doping, while successive slow cooling and post-annealing treatments further enhance the degree of overdoping, especially if carried out in oxygen atmosphere rather than in air.

  10. Effectiveness of oxaliplatin desensitization protocols.

    Science.gov (United States)

    Cortijo-Cascajares, Susana; Nacle-López, Inmaculada; García-Escobar, Ignacio; Aguilella-Vizcaíno, María José; Herreros-de-Tejada, Alberto; Cortés-Funes Castro, Hernán; Calleja-Hernández, Miguel-Ángel

    2013-03-01

    Hypersensitivity reaction (HSR) to antineoplastic drugs can force doctors to stop treatment and seek other alternatives. These alternatives may be less effective, not as well tolerated and/or more expensive. Another option is to use desensitization protocols that induce a temporary state of tolerance by gradually administering small quantities of the antineoplastic drug until the therapeutic dosage is reached. The aim of this study is to assess the effectiveness of oxaliplatin desensitization protocols. A retrospective observational study was carried out between January 2006 and May 2011. The inclusion criteria were patients undergoing chemotherapy treatment with oxaliplatin who had developed an HSR to the drug and who were candidates for continuing the treatment using a desensitization protocol. The patients' clinical records were reviewed and variables were gathered relating to the patient, the treatment, the HSR, and the desensitization protocol administered. The data were analysed using version 18.0 of the statistics program SPSS. A total of 53 desensitization protocols were administered to 21 patients. In 89 % of these cases, no new reactions occurred while the drug was being administered. New reactions of mild severity only occurred in 11 % of cases, and none of these reactions were severe enough for treatment to be stopped. All patients were able to complete the desensitization protocol. This study confirms that oxaliplatin desensitization protocols are safe and effective and allow patients to continue with the treatment that initially caused an HSR.

  11. Time-dependent recovery of in vivo binding sites after drug dosing: A method for radiotracer evaluation

    International Nuclear Information System (INIS)

    Kilbourn, Michael R.

    1997-01-01

    The recovery of in vivo binding sites for (±)-α-[ 11 C]methoxytetrabenazine, a radioligand for the monoamine vesicular transporter (VMAT2), was determined in mouse brain at various times following a pharmacological dose of tetrabenazine. Concentrations of in vivo radioligand binding sites progressively increased and had reached control values by 8.5 h, and this recovery was consistent with the pharmacokinetics of the competing drug tetrabenazine and its active metabolite, dihydrotetrabenazine. This study demonstrates a simple experimental protocol of using a single dose of a reversible competing drug and time-dependent measurements of in vivo binding of a radioligand. This protocol is suitable for testing the sensitivity of an in vivo radiotracer for measurement of varying concentrations of in vivo binding sites

  12. Automated Verification of Quantum Protocols using MCMAS

    Directory of Open Access Journals (Sweden)

    F. Belardinelli

    2012-07-01

    Full Text Available We present a methodology for the automated verification of quantum protocols using MCMAS, a symbolic model checker for multi-agent systems The method is based on the logical framework developed by D'Hondt and Panangaden for investigating epistemic and temporal properties, built on the model for Distributed Measurement-based Quantum Computation (DMC, an extension of the Measurement Calculus to distributed quantum systems. We describe the translation map from DMC to interpreted systems, the typical formalism for reasoning about time and knowledge in multi-agent systems. Then, we introduce dmc2ispl, a compiler into the input language of the MCMAS model checker. We demonstrate the technique by verifying the Quantum Teleportation Protocol, and discuss the performance of the tool.

  13. Insulin nanocomplexes formed by self-assembly from amine-modified poly(vinyl alcohol)-graft-poly(L-Lactide) for non-invasive mucosal delivery: Preparation, characterization and in vivo investigations

    OpenAIRE

    Simon, Michael

    2006-01-01

    In this work biodegradable DEAPA-PVAL-g-PLLA nanocomplexes were investigated as a colloidal peptide carrier system for non-invasive transmucosal insulin delivery. Chapter 1 describes the basic fundamentals of insulin therapy, current status, problems and future trends. The pathogenesis of diabetes mellitus and the different treatment options are discussed to give an understanding of the necessity for alternative non-invasive ...

  14. Subclass of individual IgA-secreting human lymphocytes. Investigation of in vivo pneumococcal polysaccharide-induced and in vitro mitogen-induced blood B cells by monolayer plaque-forming cell assays

    DEFF Research Database (Denmark)

    Heilmann, C; Barington, T; Sigsgaard, T

    1988-01-01

    The subclass of individual human IgA B cells was investigated by means of monolayer plaque-forming cell assays permitting analysis of all IgA-secreting cells as well as of cells secreting IgA anti-pneumococcal polysaccharide antibody. Center cells were examined by indirect immunofluorescence...

  15. In Vivo Evidence for a Lactate Gradient from Astrocytes to Neurons

    KAUST Repository

    Mä chler, Philipp; Wyss, Matthias  T.; Elsayed, Maha; Stobart, Jillian; Gutierrez, Robin; von  Faber-Castell, Alexandra; Kaelin, Vincens; Zuend, Marc; San  Martí n, Alejandro; Romero-Gó mez, Ignacio; Baeza-Lehnert, Felipe; Lengacher, Sylvain; Schneider, Bernard  L.; Aebischer, Patrick; Magistretti, Pierre J.; Barros, L.  Felipe; Weber, Bruno

    2015-01-01

    Investigating lactate dynamics in brain tissue is challenging, partly because in vivo data at cellular resolution are not available. We monitored lactate in cortical astrocytes and neurons of mice using the genetically encoded FRET sensor Laconic in combination with two-photon microscopy. An intravenous lactate injection rapidly increased the Laconic signal in both astrocytes and neurons, demonstrating high lactate permeability across tissue. The signal increase was significantly smaller in astrocytes, pointing to higher basal lactate levels in these cells, confirmed by a one-point calibration protocol. Trans-acceleration of the monocarboxylate transporter with pyruvate was able to reduce intracellular lactate in astrocytes but not in neurons. Collectively, these data provide in vivo evidence for a lactate gradient from astrocytes to neurons. This gradient is a prerequisite for a carrier-mediated lactate flux from astrocytes to neurons and thus supports the astrocyte-neuron lactate shuttle model, in which astrocyte-derived lactate acts as an energy substrate for neurons. © 2016 Elsevier Inc.

  16. Surgical model pig ex vivo for venous dissection teaching in medical schools.

    Science.gov (United States)

    Tube, Milton Ignacio Carvalho; Spencer-Netto, Fernando Antonio Campelo; Oliveira, Anderson Igor Pereira de; Holanda, Arthur Cesário de; Barros, Bruno Leão Dos Santos; Rezende, Caio Cezar Gomes; Cavalcanti, João Pedro Guerra; Batista, Marília Apolinário; Campos, Josemberg Marins

    2017-02-01

    To investigate a method for development of surgical skills in medical students simulating venous dissection in surgical ex vivo pig model. Prospective, analytical, experimental, controlled study with four stages: selection, theoretical teaching, training and assessment. Sample of 312 students was divided into two groups: Group A - 2nd semester students; Group B - students of 8th semester. The groups were divided into five groups of 12 students, trained two hours per week in the semester. They set up four models to three students in each skill station assisted by a monitor. Teaching protocol emergency procedures training were applied to venous dissection, test goal-discursive and OSATS scale. The pre-test confirmed that the methodology has not been previously applied to the students. The averages obtained in the theoretical evaluation reached satisfactory parameters in both groups. The results of applying OSATS scale showed the best performance in group A compared to group B, however, both groups had satisfactory medium. The method was enough to raise a satisfactory level of skill both groups in venous dissection running on surgical swine ex vivo models.

  17. Identification of a Minimal Peptide Tag for in Vivo and in Vitro Loading of Encapsulin.

    Science.gov (United States)

    Cassidy-Amstutz, Caleb; Oltrogge, Luke; Going, Catherine C; Lee, Antony; Teng, Poh; Quintanilla, David; East-Seletsky, Alexandra; Williams, Evan R; Savage, David F

    2016-06-21

    The encapsulation of enzymes and other proteins within a proteinaceous shell has been observed in many bacteria and archaea, but the function and utility of many such compartments are enigmatic. Efforts to study these functions have been complicated by the size and complexity of traditional protein compartments. One potential system for investigating the effect of compartmentalization is encapsulin, a large and newly discovered class of protein shells that are typically composed of two proteins: a protomer that assembles into the icosahedral shell and a cargo protein packaged inside. Encapsulins are some of the simplest known protein shell systems and readily self-assemble in vivo. Systematic characterization of the effects of compartmentalization requires the ability to load a wide range of cargo proteins. Here, we demonstrate that foreign cargo can be loaded into the encapsulin from Thermotoga maritima both in vivo and in vitro by fusion of the cargo protein with a short C-terminal peptide present in the native cargo. To facilitate biochemical characterization, we also develop a simple and rapid purification protocol and demonstrate the thermal and pH stability of the shell. Efforts to study the biophysical effects of protein encapsulation have been problematic in complex compartments, but the simplicity of assembling and loading encapsulin makes it an ideal system for future experiments exploring the effects of encapsulation on proteins.

  18. In vivo study on the biocompatibility of chitosan-hydroxyapatite film depending on degree of deacetylation.

    Science.gov (United States)

    Jeong, Ki-Jae; Song, Younseong; Shin, Hye-Ri; Kim, Ji Eun; Kim, Jeonghyo; Sun, Fangfang; Hwang, Dae-Youn; Lee, Jaebeom

    2017-06-01

    Chitosan, produced from chitin, is one of the polymers with promising applications in various fields. However, despite diverse research studies conducted on its biocompatibility, its uses are still limited. The main reason is the degree of deacetylation (DOD), which represents the proportion of deacetylated units in the polymer and is directly correlated with its biocompatibility property. In this article, the in vivo biocompatibility of three chitosan-hydroxyapatite composite films composed of chitosan with different DOD values was investigated by traditional biological protocols and novel optical spectroscopic analyses. The DOD of the chitosan obtained from three different manufacturers was estimated and calculated by Raman spectroscopy, Fourier transform infrared spectroscopy, and proton nuclear magnetic resonance spectroscopy. The chitosan with the higher DOD induced a higher incidence of inflammation in skin cells. The amino group density, biodegradability, and crystallinity of chitosan are the three possible factors that need to be considered when determining the biocompatibility of the films for in vivo application, as they led to complicated biological results, resulting in either better or worse inflammation even when using chitosan products with the same DOD. This basic study on the relationship between the DOD and inflammation is valuable for the development of further chitosan-based researches. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1637-1645, 2017. © 2017 Wiley Periodicals, Inc.

  19. In Vivo Evidence for a Lactate Gradient from Astrocytes to Neurons

    KAUST Repository

    Mächler, Philipp

    2015-11-19

    Investigating lactate dynamics in brain tissue is challenging, partly because in vivo data at cellular resolution are not available. We monitored lactate in cortical astrocytes and neurons of mice using the genetically encoded FRET sensor Laconic in combination with two-photon microscopy. An intravenous lactate injection rapidly increased the Laconic signal in both astrocytes and neurons, demonstrating high lactate permeability across tissue. The signal increase was significantly smaller in astrocytes, pointing to higher basal lactate levels in these cells, confirmed by a one-point calibration protocol. Trans-acceleration of the monocarboxylate transporter with pyruvate was able to reduce intracellular lactate in astrocytes but not in neurons. Collectively, these data provide in vivo evidence for a lactate gradient from astrocytes to neurons. This gradient is a prerequisite for a carrier-mediated lactate flux from astrocytes to neurons and thus supports the astrocyte-neuron lactate shuttle model, in which astrocyte-derived lactate acts as an energy substrate for neurons. © 2016 Elsevier Inc.

  20. Deterministic secure communication protocol without using entanglement

    OpenAIRE

    Cai, Qing-yu

    2003-01-01

    We show a deterministic secure direct communication protocol using single qubit in mixed state. The security of this protocol is based on the security proof of BB84 protocol. It can be realized with current technologies.

  1. SIP protocol model for OMNET++

    Directory of Open Access Journals (Sweden)

    Jan Kucerak

    2016-01-01

    Full Text Available The article describes our new SIP protocol implementation for the OMNeT++ simulation framework. OMNeT++ simulation framework provides an extensive support of IP related protocols, nevertheless a working SIP protocol implementation is missing. Real measurements were also done using a SIPp traffic generator and the results are compared to those obtained by our new SIP model. Since this work is a part of bigger project concerned strictly on measuring "first response times" over networks with a faulty transmission links, the actually collected statistics are focused only this way.

  2. Cadmium analysis in vivo

    International Nuclear Information System (INIS)

    Bergman, R.

    1980-12-01

    The report describes the development of a method for in vivo Cd-analysis. The method is based on the analysis of the prompt gamma radiation which is emitted by neutron capture of the isotope Cd113. Different parts of the body can be analysed selectively by neutrons in the interval of 1 to 100 KeV. The results show that the level of Cd in Kidneys can be measured without exceeding the dose of 40 mrad and that only 20% uncertainty is introduced when analysing Cd. The development has been made at the R2 reactor in Studsvik using 25 KeV neutrons. (G.B.)

  3. The HPA photon protocol and proposed electron protocol

    International Nuclear Information System (INIS)

    Pitchford, W.G.

    1985-01-01

    The Hospital Physicists Association (HPA) photon dosimetry protocol has been produced and was published in 1983. Revised values of some components of Csub(lambda) and refinements introduced into the theory in the last few years have enabled new Csub(lambda) values to be produced. The proposed HPA electron protocol is at present in draft form and will be published shortly. Both protocels are discussed. (Auth.)

  4. Study protocol: An investigation of mother-infant signalling during breastfeeding using a randomised trial to test the effectiveness of breastfeeding relaxation therapy on maternal psychological state, breast milk production and infant behaviour and growth.

    Science.gov (United States)

    Shukri, N H M; Wells, J; Mukhtar, F; Lee, M H S; Fewtrell, M

    2017-01-01

    The physiological and psychological signalling between mother and infant during lactation is one of the prominent mother-infant factors that may influence breastfeeding outcomes. The infant can 'signal' his needs through vocalisation, and the mother can respond by allowing or restricting nipple access, which might alter the breast milk composition or volume. This may lead to parent-offspring conflict during the lactation period. Challenging infant behaviour has also been associated with maternal psychological distress, which might affect breastfeeding performance. Most attempts to improve breastfeeding rates focus on providing additional support, yet many aspects of the breastfeeding process are poorly understood. Thus, our objective is to investigate mother-infant signalling during breastfeeding by manipulating maternal psychological state using a relaxation therapy intervention. The study will test the hypothesis that mothers who listen to the therapy will be more relaxed/less stressed and this will favourably alter breast milk composition and/or affect milk volume and hence influence infant outcomes. A randomised controlled trial will be conducted in first-time breastfeeding mothers and their new-born infants. Pregnant mothers will be recruited at antenatal clinics in Selangor, Malaysia, and four home visits will be carried out at 2, 6, 12 and 14 weeks postnatally. Participants will be randomised into a control and an intervention group in the early post-partum period. Mothers from the intervention group will be asked to listen daily to an audio recording with relaxation therapy during breastfeeding. Maternal psychological state, breastfeeding practices and infant behaviour will be assessed using validated questionnaires. Milk volume will be measured using stable isotopes. Breast milk samples will be collected to measure macronutrient content and hormone levels. Anthropometric measurements (weight, length and head circumference) will be performed during all

  5. A single-center randomized, controlled trial investigating the efficacy of a mHealth ECG technology intervention to improve the detection of atrial fibrillation: the iHEART study protocol.

    Science.gov (United States)

    Hickey, Kathleen T; Hauser, Nicole R; Valente, Laura E; Riga, Teresa C; Frulla, Ashton P; Masterson Creber, Ruth; Whang, William; Garan, Hasan; Jia, Haomiao; Sciacca, Robert R; Wang, Daniel Y

    2016-07-16

    Atrial fibrillation is a major public health problem and is the most common cardiac arrhythmia, affecting an estimated 2.7 million Americans. The true prevalence of atrial fibrillation is likely underestimated because episodes are often sporadic; therefore, it is challenging to detect and record an occurrence in a "real world" setting. To date, mobile health tools that promote earlier detection and treatment of atrial fibrillation and improvement in self-management behaviors and knowledge have not been evaluated. This study will be the first to address the epidemic problem of atrial fibrillation with a novel approach utilizing advancements in mobile health electrocardiogram technology to empower patients to actively engage in their healthcare and to evaluate impact on quality of life and quality-adjusted life years. Furthermore, sending a daily electrocardiogram transmission, coupled with receiving educational and motivational text messages aimed at promoting self-management and a healthy lifestyle may improve the management of chronic cardiovascular conditions (e.g., hypertension, diabetes, heart failure, etc.). Therefore, we are currently conducting a randomized controlled trial to assess the efficacy of a mobile health intervention, iPhone® Helping Evaluate Atrial fibrillation Rhythm through Technology (iHEART) versus usual cardiac care. The iHEART study is a single center, prospective, randomized controlled trial. A total of 300 participants with a recent history of atrial fibrillation will be enrolled. Participants will be randomized 1:1 to receive the iHEART intervention, receiving an iPhone® equipped with an AliveCor® Mobile ECG and accompanying Kardia application and behavioral altering motivational text messages or usual cardiac care for 6 months. This will be the first study to investigate the utility of a mobile health intervention in a "real world" setting. We will evaluate the ability of the iHEART intervention to improve the detection and

  6. Study protocol to investigate the effect of a lifestyle intervention on body weight, psychological health status and risk factors associated with disease recurrence in women recovering from breast cancer treatment [ISRCTN08045231

    Directory of Open Access Journals (Sweden)

    Mutrie Nanette

    2006-02-01

    Full Text Available Abstract Background Breast cancer survivors often encounter physiological and psychological problems related to their diagnosis and treatment that can influence long-term prognosis. The aim of this research is to investigate the effects of a lifestyle intervention on body weight and psychological well-being in women recovering from breast cancer treatment, and to determine the relationship between changes in these variables and biomarkers associated with disease recurrence and survival. Methods/design Following ethical approval, a total of 100 patients will be randomly assigned to a lifestyle intervention (incorporating dietary energy restriction in conjunction with aerobic exercise training or normal care control group. Patients randomised to the dietary and exercise intervention will be given individualised healthy eating dietary advice and written information and attend moderate intensity aerobic exercise sessions on three to five days per week for a period of 24 weeks. The aim of this strategy is to induce a steady weight loss of up to 0.5 Kg each week. In addition, the overall quality of the diet will be examined with a view to (i reducing the dietary intake of fat to ~25% of the total calories, (ii eating at least 5 portions of fruit and vegetables a day, (iii increasing the intake of fibre and reducing refined carbohydrates, and (iv taking moderate amounts of alcohol. Outcome measures will include body weight and body composition, psychological health status (stress and depression, cardiorespiratory fitness and quality of life. In addition, biomarkers associated with disease recurrence, including stress hormones, estrogen status, inflammatory markers and indices of innate and adaptive immune function will be monitored. Discussion This research will provide valuable information on the effectiveness of a practical, easily implemented lifestyle intervention for evoking positive effects on body weight and psychological well-being, two

  7. A randomized controlled trial investigating the effect of Pycnogenol and Bacopa CDRI08 herbal medicines on cognitive, cardiovascular, and biochemical functioning in cognitively healthy elderly people: the Australian Research Council Longevity Intervention (ARCLI study protocol (ANZCTR12611000487910

    Directory of Open Access Journals (Sweden)

    Stough Con K

    2012-03-01

    Full Text Available Abstract Background One of the major challenges associated with our ageing population is the increasing incidence of age-associated cognitive decline, which has significant implications for an individual's ability to lead a productive and fulfilling life. In pure economic terms the costs of ageing reflects decreased productivity and engagement with the workforce. The maintenance of brain health underpinning intact cognition is a key factor to maintaining a positive, engaged, and productive lifestyle. In light of this, the role of diet, including supplementation with nutritional and even pharmacological interventions capable of ameliorating the neurocognitive changes that occur with age constitute vital areas of research. Methods In order to reduce cognitive ageing, the ARC longevity intervention (ARCLI was developed to examine the effects of two promising natural pharmacologically active supplements on cognitive performance. ARCLI is a randomized, placebo-controlled, double-blind, 3-arm clinical trial in which 465 participants will be randomized to receive an extract of Bacopa monnieri (CDRI08 300 mg/day, Pycnogenol (150 mg/day, or placebo daily for 12 months. Participants will be tested at baseline and then at 3, 6 and 12 months post-randomization on a wide battery of cognitive, neuropsychological and mood measures, cardiovascular (brachial and aortic systolic and diastolic blood pressures as well as arterial stiffness, biochemical (assays to measure inflammation, oxidative stress and safety as well as genetic assessments (telomere length and several Single Nucleotide Polymorphisms. The primary aim is to investigate the effects of these supplements on cognitive performance. The secondary aims are to explore the time-course of cognitive enhancement as well as potential cardiovascular and biochemical mechanisms underpinning cognitive enhancement over the 12 months of administration. ARCLI will represent one of the largest and most comprehensive

  8. Methods for culturing retinal pigment epithelial cells: a review of current protocols and future recommendations

    Directory of Open Access Journals (Sweden)

    Aaron H Fronk

    2016-07-01

    Full Text Available The retinal pigment epithelium is an important part of the vertebrate eye, particularly in studying the causes and possible treatment of age-related macular degeneration. The retinal pigment epithelium is difficult to access in vivo due to its location at the back of the eye, making experimentation with age-related macular degeneration treatments problematic. An alternative to in vivo experimentation is cultivating the retinal pigment epithelium in vitro, a practice that has been going on since the 1970s, providing a wide range of retinal pigment epithelial culture protocols, each producing cells and tissue of varying degrees of similarity to natural retinal pigment epithelium. The purpose of this review is to provide researchers with a ready list of retinal pigment epithelial protocols, their effects on cultured tissue, and their specific possible applications. Protocols using human and animal retinal pigment epithelium cells, derived from tissue or cell lines, are discussed, and recommendations for future researchers included.

  9. Antibody engineering: methods and protocols

    National Research Council Canada - National Science Library

    Chames, Patrick

    2012-01-01

    "Antibody Engineering: Methods and Protocols, Second Edition was compiled to give complete and easy access to a variety of antibody engineering techniques, starting from the creation of antibody repertoires and efficient...

  10. Implementation of postoperative handoff protocol

    African Journals Online (AJOL)

    Background: Standardised handoff protocols have become necessary patient ... improve the perioperative handoff communications from the cardiac operating theatres to the ICU. ..... as you can imagine, there was push-back to the change.

  11. Redactions in protocols for drug trials: what industry sponsors concealed.

    Science.gov (United States)

    Marquardsen, Mikkel; Ogden, Michelle; Gøtzsche, Peter C

    2018-04-01

    Objective To describe the redactions in contemporary protocols for industry-sponsored randomised drug trials with patient relevant outcomes and to evaluate whether there was a legitimate rationale for the redactions. Design Cohort study. Under the Freedom of Information Act, we requested access to trial protocols approved by a research ethics committee in Denmark from October 2012 to March 2013. We received 17 consecutive protocols, which had been redacted before we got them, and nine protocols without redactions. In five additional cases, the companies refused to let the committees give us access, and in three other cases, documents were missing. Participants Not applicable. Setting Not applicable. Main outcome measure Amount and nature of redactions in 22 predefined key protocol variables. Results The redactions were most widespread in those sections of the protocol where there is empirical evidence of substantial problems with the trustworthiness of published drug trials: data analysis, handling of missing data, detection and analysis of adverse events, definition of the outcomes, interim analyses and premature termination of the study, sponsor's access to incoming data while the study is running, ownership to the data and investigators' publication rights. The parts of the text that were redacted differed widely, both between companies and within the same company. Conclusions We could not identify any legitimate rationale for the redactions. The current mistrust in industry-sponsored drug trials can only change if the industry offers unconditional access to its trial protocols and other relevant documents and data.

  12. Performance analysis of routing protocols for IoT

    Science.gov (United States)

    Manda, Sridhar; Nalini, N.

    2018-04-01

    Internet of Things (IoT) is an arrangement of advancements that are between disciplinary. It is utilized to have compelling combination of both physical and computerized things. With IoT physical things can have personal virtual identities and participate in distributed computing. Realization of IoT needs the usage of sensors based on the sector for which IoT is integrated. For instance, in healthcare domain, IoT needs to have integration with wearable sensors used by patients. As sensor devices produce huge amount of data, often called big data, there should be efficient routing protocols in place. To the extent remote systems is worried there are some current protocols, for example, OLSR, DSR and AODV. It additionally tosses light into Trust based routing protocol for low-power and lossy systems (TRPL) for IoT. These are broadly utilized remote directing protocols. As IoT is developing round the corner, it is basic to investigate routing protocols that and evaluate their execution regarding throughput, end to end delay, and directing overhead. The execution experiences can help in settling on very much educated choices while incorporating remote systems with IoT. In this paper, we analyzed different routing protocols and their performance is compared. It is found that AODV showed better performance than other routing protocols aforementioned.

  13. Data Exchange Protocol in Repsail

    Directory of Open Access Journals (Sweden)

    Gucma Maciej

    2017-12-01

    Full Text Available Article presents implantation and theoretical considerations of data exchange protocol developed for the RepSail project, where main objective was design and building innovative hybrid yacht. One of problems during the design process was improper functioning of data exchange protocols that were available in the commercially available devices to mention navigation purpose NMEA183 or 2000 as well as automation dedicated ones (CAN and similar. Author shows the basis of the dedicated format of exchange for in board devices.

  14. The Groningen protocol: another perspective

    OpenAIRE

    Jotkowitz, A B; Glick, S

    2006-01-01

    The Groningen protocol allows for the euthanasia of severely ill newborns with a hopeless prognosis and unbearable suffering. We understand the impetus for such a protocol but have moral and ethical concerns with it. Advocates for euthanasia in adults have relied on the concept of human autonomy, which is lacking in the case of infants. In addition, biases can potentially influence the decision making of both parents and physicians. It is also very difficult to weigh the element of quality of...

  15. A streamlined ribosome profiling protocol for the characterization of microorganisms

    DEFF Research Database (Denmark)

    Latif, Haythem; Szubin, Richard; Tan, Justin

    2015-01-01

    Ribosome profiling is a powerful tool for characterizing in vivo protein translation at the genome scale, with multiple applications ranging from detailed molecular mechanisms to systems-level predictive modeling. Though highly effective, this intricate technique has yet to become widely used...... in the microbial research community. Here we present a streamlined ribosome profiling protocol with reduced barriers to entry for microbial characterization studies. Our approach provides simplified alternatives during harvest, lysis, and recovery of monosomes and also eliminates several time-consuming steps...

  16. Benzodiazepine receptor binding in vivo with (/sup 3/)-Ro 15-1788

    Energy Technology Data Exchange (ETDEWEB)

    Goeders, N.E.; Kuhar, M.J.

    1985-07-29

    In vivo benzodiazepine receptor binding has generally been studied by ex vivo techniques. In this investigation, the authors identify the conditions where (/sup 3/H)-Ro 15-1788 labels benzodiazepine receptors by true in vivo binding, i.e. where workable specific to nonspecific ratios are obtained in intact tissues without homogenization or washing. (/sup 3/H)-Flunitrazepam and (/sup 3/H)-clonazepam did not exhibit useful in vivo receptor binding. 39 references, 5 figures, 1 table.

  17. EDITORIAL: Nanotechnology in vivo Nanotechnology in vivo

    Science.gov (United States)

    Demming, Anna

    2010-04-01

    -imaging labels [4]. A surface hydroxyl group renders silicon quantum dots soluble in water and the photoluminescence can be made stable with oxygen-passivation. In addition, researchers in Japan have demonstrated how the initially modest yield in the preparation of silicon quantum dots can be improved to tens of milligrams per batch, thus further promoting their application in bio-imaging [5]. In the search for non-toxic quantum dots, researchers at the Amrita Centre for Nanoscience in India have prepared heavy metal-free quantum dot bio-probes based on single phase ZnS [6]. The quantum dots are selectively doped with metals, transition metals and halides to provide tuneable luminescence properties, and they are surface conjugated with folic acid for cancer targeting. The quantum dots were demonstrated to be water-soluble, non-toxic in normal and cancer cell lines, and have bright, tuneable luminescence. So far most of the quantum dots developed for bio-imaging have had excitation and emission wavelengths in the visible spectrum, which is highly absorbed by tissue. This limits imaging with these quantum dots to superficial tissues. This week, researchers in China and the US reported work developing functionalized dots for in vivo tumour vasculature in the infrared part of the spectrum [7]. In addition the quantum dots were functionalised with glycine-aspartic acid (RGD) peptides, which target the vasculature of almost all types of growing tumours, unlike antibody- or aptamer-mediated targeting strategies that are specific to a particular cancer type. In this issue, researchers in China and the US demonstrate a novel type of contrast agent for ultrasonic tumour imaging [8]. Contrast-enhanced ultrasonic tumour imaging extends the diagnostic and imaging capabilities of traditional techniques. The use of nanoparticles as ultrasound contrast agents exploits the presence of open pores in the range of 380 to 780 nm in tumour blood vessels, which enhance the permeability and retention

  18. In vitro-in vivo correlation in skin permeation.

    Science.gov (United States)

    Mohammed, D; Matts, P J; Hadgraft, J; Lane, M E

    2014-02-01

    In vitro skin permeation studies have been used extensively in the development and optimisation of delivery of actives in vivo. However, there are few reported correlations of such in vitro studies with in vivo data. The aim of this study was to investigate the skin permeation of a model active, niacinamide, both in vitro and in vivo. Conventional diffusion cell studies were conducted in human skin to determine niacinamide permeation from a range of vehicles which included dimethyl isosorbide (DMI), propylene glycol (PG), propylene glycol monolaurate (PGML), N-methyl 2-pyrrolidone (NMP), Miglyol 812N® (MG), and mineral oil (MO). Single, binary or ternary systems were examined. The same vehicles were subsequently examined to investigate niacinamide delivery in vivo. For this proof-of-concept study one donor was used for the in vitro studies and one volunteer for the in vivo investigations to minimise biovariability. Analysis of in vitro samples was conducted using HPLC and in vivo uptake of niacinamide was evaluated using Confocal Raman spectroscopy (CRS). The amount of niacinamide permeated through skin in vitro was linearly proportional to the intensity of the niacinamide signal determined in the stratum corneum in vivo. A good correlation was observed between the signal intensities of selected vehicles and niacinamide signal intensity. The findings provide further support for the use of CRS to monitor drug delivery into and across the skin. In addition, the results highlight the critical role of the vehicle and its disposition in skin for effective dermal delivery.

  19. Microstructural imaging of human neocortex in vivo.

    Science.gov (United States)

    Edwards, Luke J; Kirilina, Evgeniya; Mohammadi, Siawoosh; Weiskopf, Nikolaus

    2018-03-24

    The neocortex of the human brain is the seat of higher brain function. Modern imaging techniques, chief among them magnetic resonance imaging (MRI), allow non-invasive imaging of this important structure. Knowledge of the microstructure of the neocortex has classically come from post-mortem histological studies of human tissue, and extrapolations from invasive animal studies. From these studies, we know that the scale of important neocortical structure spans six orders of magnitude, ranging from the size of axonal diameters (microns), to the size of cortical areas responsible for integrating sensory information (centimetres). MRI presents an opportunity to move beyond classical methods, because MRI is non-invasive and MRI contrast is sensitive to neocortical microstructure over all these length scales. MRI thus allows inferences to be made about neocortical microstructure in vivo, i.e. MRI-based in vivo histology. We review recent literature that has applied and developed MRI-based in vivo histology to probe the microstructure of the human neocortex, focusing specifically on myelin, iron, and neuronal fibre mapping. We find that applications such as cortical parcellation (using R 1 maps as proxies for myelin content) and investigation of cortical iron deposition with age (using R 2 * maps) are already contributing to the frontiers of knowledge in neuroscience. Neuronal fibre mapping in the cortex remains challenging in vivo, but recent improvements in diffusion MRI hold promise for exciting applications in the near future. The literature also suggests that utilising multiple complementary quantitative MRI maps could increase the specificity of inferences about neocortical microstructure relative to contemporary techniques, but that further investment in modelling is required to appropriately combine the maps. In vivo histology of human neocortical microstructure is undergoing rapid development. Future developments will improve its specificity, sensitivity, and

  20. In vivo and in vitro testing for selenium and selenium compounds bioavailability assessment in foodstuff.

    Science.gov (United States)

    Moreda-Piñeiro, Jorge; Moreda-Piñeiro, Antonio; Bermejo-Barrera, Pilar

    2017-03-04

    The assessment of selenium and selenium species bioavailability in foodstuff is of special concern on the context of human nutrition. In vivo (human and animal), and in vitro tests are important approaches for estimating the bioavailability of toxic and essential compounds to humans. An overview on in vivo and in vitro bioavailability assays for releasing selenium and selenium species in foodstuffs is summarized. Se and Se species content in a foodstuff critically influence Se bioavailability and bioactivity to humans and animals. Se bioavailability is affected by foodstuff-matrix major composition and minor components. Foodstuffs processing and/or treatments could enhancement or decrease Se bioavailability. Experimental conditions such as the selection of healthy status of examined people (in in vivo humans approaches), the selection of animal model (in vivo animals approaches), or the selection of GI conditions (in in vitro tests) could determines the results. Thus, international standardized protocol for in vivo and in vitro approaches assessment is mandatory.

  1. Capsiate supplementation reduces oxidative cost of contraction in exercising mouse skeletal muscle in vivo.

    Science.gov (United States)

    Yashiro, Kazuya; Tonson, Anne; Pecchi, Émilie; Vilmen, Christophe; Le Fur, Yann; Bernard, Monique; Bendahan, David; Giannesini, Benoît

    2015-01-01

    Chronic administration of capsiate is known to accelerate whole-body basal energy metabolism, but the consequences in exercising skeletal muscle remain very poorly documented. In order to clarify this issue, the effect of 2-week daily administration of either vehicle (control) or purified capsiate (at 10- or 100-mg/kg body weight) on skeletal muscle function and energetics were investigated throughout a multidisciplinary approach combining in vivo and in vitro measurements in mice. Mechanical performance and energy metabolism were assessed strictly non-invasively in contracting gastrocnemius muscle using magnetic resonance (MR) imaging and 31-phosphorus MR spectroscopy (31P-MRS). Regardless of the dose, capsiate treatments markedly disturbed basal bioenergetics in vivo including intracellular pH alkalosis and decreased phosphocreatine content. Besides, capsiate administration did affect neither mitochondrial uncoupling protein-3 gene expression nor both basal and maximal oxygen consumption in isolated saponin-permeabilized fibers, but decreased by about twofold the Km of mitochondrial respiration for ADP. During a standardized in vivo fatiguing protocol (6-min of repeated maximal isometric contractions electrically induced at a frequency of 1.7 Hz), both capsiate treatments reduced oxidative cost of contraction by 30-40%, whereas force-generating capacity and fatigability were not changed. Moreover, the rate of phosphocreatine resynthesis during the post-electrostimulation recovery period remained unaffected by capsiate. Both capsiate treatments further promoted muscle mass gain, and the higher dose also reduced body weight gain and abdominal fat content. These findings demonstrate that, in addition to its anti-obesity effect, capsiate supplementation improves oxidative metabolism in exercising muscle, which strengthen this compound as a natural compound for improving health.

  2. Modeling and Verification of the Bitcoin Protocol

    Directory of Open Access Journals (Sweden)

    Kaylash Chaudhary

    2015-11-01

    Full Text Available Bitcoin is a popular digital currency for online payments, realized as a decentralized peer-to-peer electronic cash system. Bitcoin keeps a ledger of all transactions; the majority of the participants decides on the correct ledger. Since there is no trusted third party to guard against double spending, and inspired by its popularity, we would like to investigate the correctness of the Bitcoin protocol. Double spending is an important threat to electronic payment systems. Double spending would happen if one user could force a majority to believe that a ledger without his previous payment is the correct one. We are interested in the probability of success of such a double spending attack, which is linked to the computational power of the attacker. This paper examines the Bitcoin protocol and provides its formalization as an UPPAAL model. The model will be used to show how double spending can be done if the parties in the Bitcoin protocol behave maliciously, and with what probability double spending occurs.

  3. In vivo biodistribution and biological impact of injected carbon nanotubes using magnetic resonance techniques

    Directory of Open Access Journals (Sweden)

    Achraf Al Faraj

    2011-02-01

    Full Text Available Achraf Al Faraj1,2, Florence Fauvelle3, Nathalie Luciani4, Ghislaine Lacroix5, Michael Levy4, Yannick Crémillieux1, Emmanuelle Canet-Soulas1Université Lyon1, Créatis-LRMN, Lyon, France; 2King Saud University, College of Applied Medical Sciences, Radiological Sciences Department, Riyadh, Kingdom of Saudi Arabia; 3CRSSA, Biophysique Cellulaire et Moléculaire, Laboratoire de RMN, La Tronche, France; 4Université Paris7-Paris Diderot, Matières et Systèmes Complexes, Paris, France; 5Institut National de l’Environnement et des Risques Industriels, Verneuil-en-Halatte, FranceBackground: Single-walled carbon nanotubes (SWCNT hold promise for applications as contrast agents and target delivery carriers in the field of nanomedicine. When administered in vivo, their biodistribution and pharmacological profile needs to be fully characterized. The tissue distribution of carbon nanotubes and their potential impact on metabolism depend on their shape, coating, and metallic impurities. Because standard radiolabeled or fluorescently-labeled pharmaceuticals are not well suited for long-term in vivo follow-up of carbon nanotubes, alternative methods are required.Methods: In this study, noninvasive in vivo magnetic resonance imaging (MRI investigations combined with high-resolution magic angle spinning (HR-MAS, Raman spectroscopy, iron assays, and histological analysis ex vivo were proposed and applied to assess the biodistribution and biological impact of intravenously injected pristine (raw and purified and functionalized SWCNT in a 2-week longitudinal study. Iron impurities allowed raw detection of SWCNT in vivo by susceptibility-weighted MRI.Results: A transitional accumulation in the spleen and liver was observed by MRI. Raman spectroscopy, iron assays, and histological findings confirmed the MRI readouts. Moreover, no acute toxicological effect on the liver metabolic profile was observed using the HR-MAS technique, as confirmed by quantitative real

  4. An Accurate Link Correlation Estimator for Improving Wireless Protocol Performance

    Science.gov (United States)

    Zhao, Zhiwei; Xu, Xianghua; Dong, Wei; Bu, Jiajun

    2015-01-01

    Wireless link correlation has shown significant impact on the performance of various sensor network protocols. Many works have been devoted to exploiting link correlation for protocol improvements. However, the effectiveness of these designs heavily relies on the accuracy of link correlation measurement. In this paper, we investigate state-of-the-art link correlation measurement and analyze the limitations of existing works. We then propose a novel lightweight and accurate link correlation estimation (LACE) approach based on the reasoning of link correlation formation. LACE combines both long-term and short-term link behaviors for link correlation estimation. We implement LACE as a stand-alone interface in TinyOS and incorporate it into both routing and flooding protocols. Simulation and testbed results show that LACE: (1) achieves more accurate and lightweight link correlation measurements than the state-of-the-art work; and (2) greatly improves the performance of protocols exploiting link correlation. PMID:25686314

  5. In Vivo Cytogenetic Studies on Aspartame

    OpenAIRE

    AlSuhaibani, Entissar S.

    2010-01-01

    Aspartame (a-Laspartyl-L-phenylalanine 1-methylester) is a dipeptide low-calorie artificial sweetener that is widely used as a nonnutritive sweetener in foods and drinks. The safety of aspartame and its metabolic breakdown products (phenylalanine, aspartic acid and methanol) was investigated in vivo using chromosomal aberration (CA) test and sister chromatid exchange (SCE) test in the bone marrow cells of mice. Swiss Albino male mice were exposed to aspartame (3.5, 35, 350 mg/kg body weight)....

  6. Computational design of in vivo biomarkers

    International Nuclear Information System (INIS)

    Somogyi, Bálint; Gali, Adam

    2014-01-01

    Fluorescent semiconductor nanocrystals (or quantum dots) are very promising agents for bioimaging applications because their optical properties are superior compared to those of conventional organic dyes. However, not all the properties of these quantum dots suit the stringent criteria of in vivo applications, i.e. their employment in living organisms that might be of importance in therapy and medicine. In our review, we first summarize the properties of an ‘ideal’ biomarker needed for in vivo applications. Despite recent efforts, no such hand-made fluorescent quantum dot exists that may be considered as ‘ideal’ in this respect. We propose that ab initio atomistic simulations with predictive power can be used to design ‘ideal’ in vivo fluorescent semiconductor nanoparticles. We briefly review such ab initio methods that can be applied to calculate the electronic and optical properties of very small nanocrystals, with extra emphasis on density functional theory (DFT) and time-dependent DFT which are the most suitable approaches for the description of these systems. Finally, we present our recent results on this topic where we investigated the applicability of nanodiamonds and silicon carbide nanocrystals for in vivo bioimaging. (topical review)

  7. Monoclonal antibodies technology. Protocols

    International Nuclear Information System (INIS)

    Acevado Castro, B.E.

    1997-01-01

    Full text: Immunization. The first step in preparing useful monoclonal antibodies (MAbs) is to immunize an animal (Balb/c for example) with an appropriate antigen. Methods (only for soluble antigen): Solubilize selected antigen in Phosphate buffer solution (PBS) at pH 7.2-7.4, ideally at a final concentration per animal between 10 to 50 μg/ml. It is recommended that the antigen under consideration be incorporated into the emulsion adjuvants in 1:1 volumetric relation. We commonly use Frend's adjuvant (FA) to prepared immunized solution. The first immunization should be prepared with complete FA, and the another could be prepared with incomplete FA. It is recommended to inject mice with 0.2 ml intraperitoneal (ip) or subcutaneous (sc). Our experience suggests the sc route is the preferred route. A minimum protocol for immunizing mice to generate cells for preparing hybridomas is s follows: immunize sc on day 0, boost sc on day 21, take a trial bleeding on day 26; if antibody titters are satisfactory, boost ip on day 35 with antigen only, and remove the spleen to obtain cells for fusion on day 38. Fusion protocol. The myeloma cell line we are using is X63 Ag8.653. At the moment of fusion myeloma cells need a good viability (at least a 95%). 1. Remove the spleen cells from immunized mice using sterile conditions. An immune spleen should yield between 7 a 10x10 7 nucleated cells. 2. Place the spleen in 20 ml of serum-free RPMI 1640 in a Petri dish. Using a needle and syringe, inject the spleen with medium to distend and disrupt the spleen stroma and free the nucleated cells. 3. Flush the cell suspension with a Pasteur pipet to disperse clumps of cells. 4. Centrifuge the spleen cell suspension at 250g for 10 min. Resuspend the pellet in serum-free RPMI 1640. Determine cell concentration using Neuhabuer chamber. 5. Mix the myeloma cells and spleen cells in a conical 50-ml tube in serum-free RPMI 1640, 1 x10 7 spleen cells to 1x10 6 myeloma cells (ratio 10:1). Centrifuge

  8. Investigation of implementing a synchronization protocol under multiprocessors hierarchical scheduling

    NARCIS (Netherlands)

    Nemati, F.; Behnam, M.; Bril, R.J.

    2009-01-01

    In the multi-core and multiprocessor domain, there has been considerable work done on scheduling techniques assuming that real-time tasks are independent. In practice a typical real-time system usually share logical resources among tasks. However, synchronization in the multiprocessor area has not

  9. A Type Theoretic Investigation of the Verification of Voting Protocols

    DEFF Research Database (Denmark)

    Gustafsson, Daniel

    is correct, and on the other hand we can we trust that the secrecy of the vote is preserved. These seemingly contradictory statements have fuelled new developments in cryptography, but the question remain can we trust these developments? The thesis of my dissertation is that it possible to formalise...... and calculation of probabilities, in particular ∑-types are used as they correspond to summation. Furthermore, I extend the type theory with process algebraic constructions in order to capture attack games as defined by semantic security in cryptography. To type these processes I propose a session type system...

  10. Fusing in vivo and ex vivo NMR sources of information for brain tumor classification

    International Nuclear Information System (INIS)

    Croitor-Sava, A R; Laudadio, T; Sima, D M; Van Huffel, S; Martinez-Bisbal, M C; Celda, B; Piquer, J; Heerschap, A

    2011-01-01

    In this study we classify short echo-time brain magnetic resonance spectroscopic imaging (MRSI) data by applying a model-based canonical correlation analyses algorithm and by using, as prior knowledge, multimodal sources of information coming from high-resolution magic angle spinning (HR-MAS), MRSI and magnetic resonance imaging. The potential and limitations of fusing in vivo and ex vivo nuclear magnetic resonance sources to detect brain tumors is investigated. We present various modalities for multimodal data fusion, study the effect and the impact of using multimodal information for classifying MRSI brain glial tumors data and analyze which parameters influence the classification results by means of extensive simulation and in vivo studies. Special attention is drawn to the possibility of considering HR-MAS data as a complementary dataset when dealing with a lack of MRSI data needed to build a classifier. Results show that HR-MAS information can have added value in the process of classifying MRSI data

  11. Multi-party quantum key agreement protocol secure against collusion attacks

    Science.gov (United States)

    Wang, Ping; Sun, Zhiwei; Sun, Xiaoqiang

    2017-07-01

    The fairness of a secure multi-party quantum key agreement (MQKA) protocol requires that all involved parties are entirely peer entities and can equally influence the outcome of the protocol to establish a shared key wherein no one can decide the shared key alone. However, it is found that parts of the existing MQKA protocols are sensitive to collusion attacks, i.e., some of the dishonest participants can collaborate to predetermine the final key without being detected. In this paper, a multi-party QKA protocol resisting collusion attacks is proposed. Different from previous QKA protocol resisting N-1 coconspirators or resisting 1 coconspirators, we investigate the general circle-type MQKA protocol which can be secure against t dishonest participants' cooperation. Here, t < N. We hope the results of the presented paper will be helpful for further research on fair MQKA protocols.

  12. In vitro-ex vivo correlations between a cell-laden hydrogel and mucosal tissue for screening composite delivery systems.

    Science.gov (United States)

    Blakney, Anna K; Little, Adam B; Jiang, Yonghou; Woodrow, Kim A

    2016-11-01

    Composite delivery systems where drugs are electrospun in different layers and vary the drug stacking-order are posited to affect bioavailability. We evaluated how the formulation characteristics of both burst- and sustained-release electrospun fibers containing three physicochemically diverse drugs: dapivirine (DPV), maraviroc (MVC) and tenofovir (TFV) affect in vitro and ex vivo release. We developed a poly(hydroxyethyl methacrylate) (pHEMA) hydrogel release platform for the rapid, inexpensive in vitro evaluation of burst- and sustained-release topical or dermal drug delivery systems with varying microarchitecture. We investigated properties of the hydrogel that could recapitulate ex vivo release into nonhuman primate vaginal tissue. Using a dimethyl sulfoxide extraction protocol and high-performance liquid chromatography analysis, we achieved >93% recovery from the hydrogels and >88% recovery from tissue explants for all three drugs. We found that DPV loading, but not stacking order (layers of fiber containing a single drug) or microarchitecture (layers with isolated drug compared to all drugs in the same layer) impacted the burst release in vitro and ex vivo. Our burst-release formulations showed a correlation for DPV accumulation between the hydrogel and tissue (R 2 =   0.80), but the correlation was not significant for MVC or TFV. For the sustained-release formulations, the PLGA/PCL content did not affect TFV release in vitro or ex vivo. Incorporation of cells into the hydrogel matrix improved the correlation between hydrogel and tissue explant release for TFV. We expect that this hydrogel-tissue mimic may be a promising preclinical model to evaluate topical or transdermal drug delivery systems with complex microarchitectures.

  13. Observing documentary reading by verbal protocol

    Directory of Open Access Journals (Sweden)

    Fujita Mariangela Spotti Lopes

    2003-01-01

    Full Text Available Verifies the applicability to research on indexers' reading strategies of the process observing technique known as Verbal Protocol or Thinking Aloud. This interpretative-qualitative data collecting technique allows the observation of different kinds of process during the progress of different kinds of tasks. Presents a theoretical investigation into "reading" and into formal methodological procedures to observe reading processes. Describes details of the methodological procedures adopted in five case studies with analysis of samples of data. The project adopted three kinds of parameters for data analysis: theoretical, normative, empirical (derived from observations made in the first case study. The results are compared, and important conclusions regarding documentary reading are drawn.

  14. 2014 Building America House Simulation Protocols

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, E. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Engebrecht-Metzger, C. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Horowitz, S. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Hendron, R. [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2014-03-01

    As BA has grown to include a large and diverse cross-section of the home building and retrofit industries, it has become more important to develop accurate, consistent analysis techniques to measure progress towards the program's goals. The House Simulation Protocol (HSP) document provides guidance to program partners and managers so they can compare energy savings for new construction and retrofit projects. The HSP provides the program with analysis methods that are proven to be effective and reliable in investigating the energy use of advanced energy systems and of entire houses.

  15. 2014 Building America House Simulation Protocols

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, E. [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Engebrecht, C. Metzger [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Horowitz, S. [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Hendron, R. [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2014-03-01

    As Building America has grown to include a large and diverse cross-section of the home building and retrofit industries, it has become more important to develop accurate, consistent analysis techniques to measure progress towards the program's goals. The House Simulation Protocol (HSP) document provides guidance to program partners and managers so they can compare energy savings for new construction and retrofit projects. The HSP provides the program with analysis methods that are proven to be effective and reliable in investigating the energy use of advanced energy systems and of entire houses.

  16. Families of quantum fingerprinting protocols

    Science.gov (United States)

    Lovitz, Benjamin; Lütkenhaus, Norbert

    2018-03-01

    We introduce several families of quantum fingerprinting protocols to evaluate the equality function on two n -bit strings in the simultaneous message passing model. The original quantum fingerprinting protocol uses a tensor product of a small number of O (logn ) -qubit high-dimensional signals [H. Buhrman et al., Phys. Rev. Lett. 87, 167902 (2001), 10.1103/PhysRevLett.87.167902], whereas a recently proposed optical protocol uses a tensor product of O (n ) single-qubit signals, while maintaining the O (logn ) information leakage of the original protocol [J. M. Arazola and N. Lütkenhaus, Phys. Rev. A 89, 062305 (2014), 10.1103/PhysRevA.89.062305]. We find a family of protocols which interpolate between the original and optical protocols while maintaining the O (logn ) information leakage, thus demonstrating a tradeoff between the number of signals sent and the dimension of each signal. There has been interest in experimental realization of the recently proposed optical protocol using coherent states [F. Xu et al., Nat. Commun. 6, 8735 (2015), 10.1038/ncomms9735; J.-Y. Guan et al., Phys. Rev. Lett. 116, 240502 (2016), 10.1103/PhysRevLett.116.240502], but as the required number of laser pulses grows linearly with the input size n , eventual challenges for the long-time stability of experimental setups arise. We find a coherent state protocol which reduces the number of signals by a factor 1/2 while also reducing the information leakage. Our reduction makes use of a simple modulation scheme in optical phase space, and we find that more complex modulation schemes are not advantageous. Using a similar technique, we improve a recently proposed coherent state protocol for evaluating the Euclidean distance between two real unit vectors [N. Kumar et al., Phys. Rev. A 95, 032337 (2017), 10.1103/PhysRevA.95.032337] by reducing the number of signals by a factor 1/2 and also reducing the information leakage.

  17. Cannabinoid antagonist in nanostructured lipid carriers (NLCs): design, characterization and in vivo study

    Energy Technology Data Exchange (ETDEWEB)

    Esposito, Elisabetta; Ravani, Laura [Department of Life Sciences and Biotechnology, University of Ferrara, I-44121 Ferrara (Italy); Drechsler, Markus [BIMF/Soft Matter Electron Microscopy, University of Bayreuth (Germany); Mariani, Paolo [Department of Life and Environmental Sciences and CNISM, Università Politecnica delle Marche, I-60100 Ancona (Italy); Contado, Catia [Department of Chemical and Pharmaceutical Sciences, University of Ferrara, I-44121 Ferrara (Italy); Ruokolainen, Janne [Department of Applied Physics, Aalto University, 00076 Aalto (Finland); Ratano, Patrizia; Campolongo, Patrizia [Department of Physiology and Pharmacology, Sapienza University of Rome, 00185 Roma (Italy); Trezza, Viviana [Department of Science, Roma Tre University, 00146 Roma (Italy); Nastruzzi, Claudio, E-mail: nas@unife.it [Department of Life Sciences and Biotechnology, University of Ferrara, I-44121 Ferrara (Italy); Cortesi, Rita [Department of Life Sciences and Biotechnology, University of Ferrara, I-44121 Ferrara (Italy)

    2015-03-01

    This study describes the preparation, characterization, and in vivo evaluation in rats of nanostructured lipid carriers (NLCs) encapsulating rimonabant (RMN) as prototypical cannabinoid antagonist. A study was conducted in order to optimize NLC production by melt and ultrasonication method. NLCs were prepared by alternatively adding the lipid phase into the aqueous one (direct protocol) or the aqueous phase into the lipid one (reverse protocol). RMN-NLCs have been characterized by cryogenic transmission electron microscopy (cryo-TEM), X-ray, photon correlation spectroscopy (PCS) and sedimentation field flow fractionation (SdFFF). Reverse NLCs were treated with polysorbate 80. RMN release kinetics have been determined in vitro by dialysis method. In vivo RMN biodistribution in rats was evaluated after intranasal (i.n.) administration of reverse RMN-NLC. The reverse protocol enabled to prevent the lost of lipid phase and to achieve higher RMN encapsulation efficacy (EE) with respect to the direct protocol (98% w/w versus 67% w/w). The use of different protocols did not affect NLC morphology and dimensional distribution. An in vitro dissolutive release rate of RMN was calculated. The in vivo data indicate that i.n. administration of RMN by reverse NLC treated with polysorbate 80 increased RMN concentration in the brain with respect to the drug in solution. The nanoencapsulation protocol presented here appears as an optimal strategy to improve the low solubility of cannabinoid compounds in an aqueous system suitable for in vivo administration. - Highlights: • Rimonabant (RMN) can be encapsulated in nanostructured lipid carriers (NLCs). • Nanoencapsulation improves RMN solubility in a stable physiologic aqueous formulation. • RMN is released in vitro from NLC by a controlled dissolutive release modality. • I.n. administration leads to higher RMN concentration in the brain with respect to plasma. • NLC increases RMN concentration in the brain with respect to

  18. In vivo gluten challenge in coeliac disease

    Directory of Open Access Journals (Sweden)

    HJ Ellis

    2001-01-01

    Full Text Available In vivo gluten challenge has been used since the early 1950s to study the role of cereal fractions in celiac disease. While early studies relied on crude indicators of celiac toxicity, the advent of jejunal biopsy and sophisticated immunohistochemical techniques has allowed accurate studies to be performed. Studies to determine the nature of the cereal component that is toxic to patients with celiac disease have concentrated on wheat because of its nutritional importance. A number of in vitro studies indicated the presence of one or more celiac-activating epitopes with the N-terminus of the A-gliadin molecule. In vivo challenge with three synthetic peptides subsequently indicated the toxicity of a peptide corresponding to amino acids 31 to 49 of A-gliadin. In vivo gluten challenge is the gold standard for the assessment of celiac toxicity; however, jejunal biopsy is a relatively invasive procedure, thus, other methods have been investigated. Direct infusion of the rectum with gluten has been shown to result in an increase in mucosal intraepithelial lymphocytes, occurring only in celiac patients. This method has been used to study the celiac toxicity of gliadin subfractions. The in vitro technique of small intestinal biopsy organ culture is also a useful tool and appears to give the same results as in vivo challenge. The importance of tiny amounts of gliadin in the diet, such as that which occurs in wheat starch, has been studied by in vivo challenge; this technique has clarified the position of oats in the gluten-free diet. Several studies suggest that this cereal may be included in the diet of most adult celiac patients. Studies of the transport of gliadin across the enterocyte following ingestion or challenge suggest that gliadin may be metabolized by a different pathway in celiac disease. This could result in an abnormal presentation to the immune system, triggering a pathogenic rather than a tolerogenic response.

  19. The Network Protocol Analysis Technique in Snort

    Science.gov (United States)

    Wu, Qing-Xiu

    Network protocol analysis is a network sniffer to capture data for further analysis and understanding of the technical means necessary packets. Network sniffing is intercepted by packet assembly binary format of the original message content. In order to obtain the information contained. Required based on TCP / IP protocol stack protocol specification. Again to restore the data packets at protocol format and content in each protocol layer. Actual data transferred, as well as the application tier.

  20. Understanding protocol performance: impact of test performance.

    Science.gov (United States)

    Turner, Robert G

    2013-01-01

    This is the second of two articles that examine the factors that determine protocol performance. The objective of these articles is to provide a general understanding of protocol performance that can be used to estimate performance, establish limits on performance, decide if a protocol is justified, and ultimately select a protocol. The first article was concerned with protocol criterion and test correlation. It demonstrated the advantages and disadvantages of different criterion when all tests had the same performance. It also examined the impact of increasing test correlation on protocol performance and the characteristics of the different criteria. To examine the impact on protocol performance when individual tests in a protocol have different performance. This is evaluated for different criteria and test correlations. The results of the two articles are combined and summarized. A mathematical model is used to calculate protocol performance for different protocol criteria and test correlations when there are small to large variations in the performance of individual tests in the protocol. The performance of the individual tests that make up a protocol has a significant impact on the performance of the protocol. As expected, the better the performance of the individual tests, the better the performance of the protocol. Many of the characteristics of the different criteria are relatively independent of the variation in the performance of the individual tests. However, increasing test variation degrades some criteria advantages and causes a new disadvantage to appear. This negative impact increases as test variation increases and as more tests are added to the protocol. Best protocol performance is obtained when individual tests are uncorrelated and have the same performance. In general, the greater the variation in the performance of tests in the protocol, the more detrimental this variation is to protocol performance. Since this negative impact is increased as

  1. The Geneva Protocol of 1925

    International Nuclear Information System (INIS)

    Mc Elroy, R.J.

    1991-01-01

    This paper reports that when President Gerald Ford signed the instruments of ratification for the Geneva Protocol of 1925 on January 22, 1975, a tortured, half-century-long chapter in U.S. arms control policy was brought to a close. Fifty years earlier, at the Geneva Conference for the Control of the International Trade in Arms, Munitions and Implements of War, the United States had played a key role in drafting and reaching agreement on the Protocol for the Prohibition of the Use in War of Asphyxiating, Poisonous or Other Gases and of Bacteriological Methods of Warfare. The protocol, signed by thirty nations, including the United States, on June 17, 1925, prohibits the use in war of asphyxiating, poisonous or other gases, and of all analogous liquids, materials or devices as well as the use of bacteriological methods of warfare

  2. National protocol framework for the inventory and monitoring of bees

    Science.gov (United States)

    Droege, Sam; Engler, Joseph D.; Sellers, Elizabeth A.; Lee O'Brien,

    2016-01-01

    This national protocol framework is a standardized tool for the inventory and monitoring of the approximately 4,200 species of native and non-native bee species that may be found within the National Wildlife Refuge System (NWRS) administered by the U.S. Fish and Wildlife Service (USFWS). However, this protocol framework may also be used by other organizations and individuals to monitor bees in any given habitat or location. Our goal is to provide USFWS stations within the NWRS (NWRS stations are land units managed by the USFWS such as national wildlife refuges, national fish hatcheries, wetland management districts, conservation areas, leased lands, etc.) with techniques for developing an initial baseline inventory of what bee species are present on their lands and to provide an inexpensive, simple technique for monitoring bees continuously and for monitoring and evaluating long-term population trends and management impacts. The latter long-term monitoring technique requires a minimal time burden for the individual station, yet can provide a good statistical sample of changing populations that can be investigated at the station, regional, and national levels within the USFWS’ jurisdiction, and compared to other sites within the United States and Canada. This protocol framework was developed in cooperation with the United States Geological Survey (USGS), the USFWS, and a worldwide network of bee researchers who have investigated the techniques and methods for capturing bees and tracking population changes. The protocol framework evolved from field and lab-based investigations at the USGS Bee Inventory and Monitoring Laboratory at the Patuxent Wildlife Research Center in Beltsville, Maryland starting in 2002 and was refined by a large number of USFWS, academic, and state groups. It includes a Protocol Introduction and a set of 8 Standard Operating Procedures or SOPs and adheres to national standards of protocol content and organization. The Protocol Narrative

  3. The DOMUS study protocol

    DEFF Research Database (Denmark)

    Nordly, Mie; Benthien, Kirstine Skov; Von Der Maase, Hans

    2014-01-01

    be a powerful tool to improve patients' quality of life and support family/caregivers during the disease trajectory. The present study offers a model for achieving optimal delivery of palliative care in the patient's preferred place of care and attempt to clarify challenges. TRIAL REGISTRATION: Clinicaltrials......BACKGROUND: The focus of Specialized Palliative Care (SPC) is to improve care for patients with incurable diseases and their families, which includes the opportunity to make their own choice of place of care and ultimately place of death. The Danish Palliative Care Trial (DOMUS) aims to investigate...... psychological intervention for patients and caregivers at home or b) standard care alone. Inclusion criteria are incurable cancer with no or limited antineoplastic treatment options. DISCUSSION: Programs that facilitate transition from hospital treatment to SPC at home for patients with incurable cancer can...

  4. The Kyoto protocol development; La viabilite du protocole de Kyoto

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, R. [Harvard Univ., Barrow, AK (United States); Guesneris, R. [College de France, 75 - Paris (France)

    2002-04-01

    From the author R. Cooper point of view the Kyoto Protocol is a flawed concept. The reasons for dropping Kyoto are presented in this paper insisting that rejecting Kyoto not means to imply that global climate change is not a serious problem. After a presentation of the US policy facing the Climatic Change, some concluding propositions are proposed. (A.L.B.)

  5. Symbolic Analysis of Cryptographic Protocols

    DEFF Research Database (Denmark)

    Dahl, Morten

    We present our work on using abstract models for formally analysing cryptographic protocols: First, we present an ecient method for verifying trace-based authenticity properties of protocols using nonces, symmetric encryption, and asymmetric encryption. The method is based on a type system...... of Gordon et al., which we modify to support fully-automated type inference. Tests conducted via an implementation of our algorithm found it to be very ecient. Second, we show how privacy may be captured in a symbolic model using an equivalencebased property and give a formal denition. We formalise...

  6. Protocol for Isolation of Primary Human Hepatocytes and Corresponding Major Populations of Non-parenchymal Liver Cells

    Science.gov (United States)

    Pfeiffer, Elisa; Zeilinger, Katrin; Seehofer, Daniel; Damm, Georg

    2016-01-01

    Beside parenchymal hepatocytes, the liver consists of non-parenchymal cells (NPC) namely Kupffer cells (KC), liver endothelial cells (LEC) and hepatic Stellate cells (HSC). Two-dimensional (2D) culture of primary human hepatocyte (PHH) is still considered as the "gold standard" for in vitro testing of drug metabolism and hepatotoxicity. It is well-known that the 2D monoculture of PHH suffers from dedifferentiation and loss of function. Recently it was shown that hepatic NPC play a central role in liver (patho-) physiology and the maintenance of PHH functions. Current research focuses on the reconstruction of in vivo tissue architecture by 3D- and co-culture models to overcome the limitations of 2D monocultures. Previously we published a method to isolate human liver cells and investigated the suitability of these cells for their use in cell cultures in Experimental Biology and Medicine1. Based on the broad interest in this technique the aim of this article was to provide a more detailed protocol for the liver cell isolation process including a video, which will allow an easy reproduction of this technique. Human liver cells were isolated from human liver tissue samples of surgical interventions by a two-step EGTA/collagenase P perfusion technique. PHH were separated from the NPC by an initial centrifugation at 50 x g. Density gradient centrifugation steps were used for removal of dead cells. Individual liver cell populations were isolated from the enriched NPC fraction using specific cell properties and cell sorting procedures. Beside the PHH isolation we were able to separate KC, LEC and HSC for further cultivation. Taken together, the presented protocol allows the isolation of PHH and NPC in high quality and quantity from one donor tissue sample. The access to purified liver cell populations could allow the creation of in vivo like human liver models. PMID:27077489

  7. In vitro and in vivo antioxidant activities of inulin

    OpenAIRE

    Shang, Hong-Mei; Zhou, Hai-Zhu; Yang, Jun-Yan; Li, Ran; Song, Hui; Wu, Hong-Xin

    2018-01-01

    This study was designed to investigate the in vitro and in vivo antioxidant activities of inulin. The in vitro assays demonstrated that the antioxidant activities of inulin, including the DPPH radical scavenging activity, ABTS scavenging activity and ferric reducing power, were weak and significantly lower than those of Vitamin C (P < 0.05). The influence of dietary supplementation with inulin on the antioxidant status of laying hens was evaluated with in vivo antioxidant assays. The results ...

  8. Intermuscular force transmission between human plantarflexor muscles in vivo

    DEFF Research Database (Denmark)

    Bojsen-Møller, Jens; Schwartz, Sidse; Kalliokoski, Kari K

    2010-01-01

    of the present study was to investigate if intermuscular force transmission occurs within and between human plantarflexor muscles in vivo. Seven subjects performed four types of either active contractile tasks or passive joint manipulations: passive knee extension, voluntary isometric plantarflexion, voluntary...... surae muscles was seen during passive hallux extension. Large interindividual differences with respect to deep plantarflexor activation during voluntary contractions were observed. The present results suggest that force may be transmitted between the triceps surae muscles in vivo, while only limited...

  9. A Comprehensive Survey on Hierarchical-Based Routing Protocols for Mobile Wireless Sensor Networks: Review, Taxonomy, and Future Directions

    Directory of Open Access Journals (Sweden)

    Nabil Sabor

    2017-01-01

    Full Text Available Introducing mobility to Wireless Sensor Networks (WSNs puts new challenges particularly in designing of routing protocols. Mobility can be applied to the sensor nodes and/or the sink node in the network. Many routing protocols have been developed to support the mobility of WSNs. These protocols are divided depending on the routing structure into hierarchical-based, flat-based, and location-based routing protocols. However, the hierarchical-based routing protocols outperform the other routing types in saving energy, scalability, and extending lifetime of Mobile WSNs (MWSNs. Selecting an appropriate hierarchical routing protocol for specific applications is an important and difficult task. Therefore, this paper focuses on reviewing some of the recently hierarchical-based routing protocols that are developed in the last five years for MWSNs. This survey divides the hierarchical-based routing protocols into two broad groups, namely, classical-based and optimized-based routing protocols. Also, we present a detailed classification of the reviewed protocols according to the routing approach, control manner, mobile element, mobility pattern, network architecture, clustering attributes, protocol operation, path establishment, communication paradigm, energy model, protocol objectives, and applications. Moreover, a comparison between the reviewed protocols is investigated in this survey depending on delay, network size, energy-efficiency, and scalability while mentioning the advantages and drawbacks of each protocol. Finally, we summarize and conclude the paper with future directions.

  10. The effectiveness of Korean medicine treatment in male patients with infertility: a study protocol for a prospective observational pilot study.

    Science.gov (United States)

    Kim, Kwan-Ii; Jo, Junyoung

    2018-01-01

    Male factor subfertility has increasingly been considered the cause of infertility in couples. Many men with male infertility have sperm problems such as oligozoospermia, asthenozoospermia, or teratozoospermia. Because abnormal semen parameters are idiopathic to some extent, no standard therapy has been established to date. Herbal medicine has been reported to have beneficial properties in the treatment of subfertility, especially in improving semen quality both in vivo and in human studies. Therefore, we intend to investigate the effectiveness and safety of treatment using Korean medicine (KM) for infertile male patients with poor semen quality.This will be a single-center, prospective, case-only observational pilot study. About 20 male patients with infertility who visit Conmaul Hospital of Korean Medicine will be recruited. We will follow the standard treatment protocol, which has shown good results in the treatment of male infertility. The protocol is composed mainly of a 10-week herbal decoction treatment; acupuncture and/or pharmacopuncture are added when needed. Semen samples, quality of life, and the scrotal temperatures of infertile men will be observed before and after the 10-week treatment with KM.The study has received ethical approval from the Public Institutional Review Board (approval number: P01-201708-21-008). The findings will be disseminated to appropriate audiences via peer-reviewed publication and conference presentations. Korean Clinical Trial Registry (CRIS), Republic of Korea: KCT0002611.

  11. Colon cleansing protocol in children: research conditions vs. clinical practice.

    Science.gov (United States)

    Elitsur, Yoram; Balfaqih, Yaslam; Preston, Deborah

    2018-04-01

     Colon preparation rates are the limiting factor for a successful diagnostic colonoscopy in children. Different colon cleansing protocols have been published for use in children. Unfortunately, the applicability of those published research protocols has not been formally evaluated in routine clinical practice. We investigated the success rate of our previously published colon cleansing protocol as utilized in our clinical practice.  This was a retrospective study. In the clinical practice, the colon cleansing protocol included PEG-3350 at a dose of 2 g/kg/day plus Dulcolax (Bisacodyl, Boehringer Ingelheim, TX USA) 5 mg/day for 2 days. Adequate colon preparation was graded between 1 - 5, as previously described, and grade ≥ 4.0 was considered an adequate preparation. Patients were instructed to complete a questionnaire that included PEG-3350 dose, number of stools per day, consistency of each stool, and side effects (vomiting, abdominal pain). Clinical and endoscopic results were compared between the protocol under research conditions and routine practice.  The success rate of the colon preparation in our clinical practice was similar to the results observed under our research protocol (75 % vs. 73.6 %). Moreover, the total number of stools, stool consistency, and the intubation rate of the terminal ileum were also similar. We concluded, that in our experience, the colon cleansing protocol used under research conditions was effective and appropriate for use in routine clinical practice.  We recommend testing each new protocol under the routine conditions of clinical practice to confirm its applicability for general practitioners.

  12. Lack of indirect sensitization in vivo

    International Nuclear Information System (INIS)

    Hetzel, F.W.; Avery, K.; Mensinger, M.; Frinak, S.; Tidwell, C.

    1985-01-01

    The possible utility of respiratory inhibiting drugs as indirect radiation sensitizers has been investigated in both in vitro and in vivo systems. In vitro studies were conducted in V79 monolayer and spheroid cultures examining both respiratory inhibition and radiation survival as end points. These drugs (BCNU, Mustargen and Chlorambucil) were found to be potent respiratory inhibitors and, in the spheroid system, to be effective indirect radiation sensitizers with enhancement ratios of approximately 2.0. In vivo studies with these drugs have also been conducted in a C/sub 3/H mouse MCa tumor system to determine if the same reoxygenation effect observed in spheroids could be demonstrated in the solid tumor system. Detailed microelectrode studies, employing each drug at its LD/sub 10/ level, have been unable to demonstrate any drug induced reoxygenation for any of the drugs tested. Complete details are presented

  13. Ex-vivo machine perfusion for kidney preservation.

    Science.gov (United States)

    Hamar, Matyas; Selzner, Markus

    2018-06-01

    Machine perfusion is a novel strategy to decrease preservation injury, improve graft assessment, and increase organ acceptance for transplantation. This review summarizes the current advances in ex-vivo machine-based kidney preservation technologies over the last year. Ex-vivo perfusion technologies, such as hypothermic and normothermic machine perfusion and controlled oxygenated rewarming, have gained high interest in the field of organ preservation. Keeping kidney grafts functionally and metabolically active during the preservation period offers a unique chance for viability assessment, reconditioning, and organ repair. Normothermic ex-vivo kidney perfusion has been recently translated into clinical practice. Preclinical results suggest that prolonged warm perfusion appears superior than a brief end-ischemic reconditioning in terms of renal function and injury. An established standardized protocol for continuous warm perfusion is still not available for human grafts. Ex-vivo machine perfusion represents a superior organ preservation method over static cold storage. There is still an urgent need for the optimization of the perfusion fluid and machine technology and to identify the optimal indication in kidney transplantation. Recent research is focusing on graft assessment and therapeutic strategies.

  14. Methods of in-vivo mouse lung micro-CT

    Science.gov (United States)

    Recheis, Wolfgang A.; Nixon, Earl; Thiesse, Jacqueline; McLennan, Geoffrey; Ross, Alan; Hoffman, Eric

    2005-04-01

    Micro-CT will have a profound influence on the accumulation of anatomical and physiological phenotypic changes in natural and transgenetic mouse models. Longitudinal studies will be greatly facilitated, allowing for a more complete and accurate description of events if in-vivo studies are accomplished. The purpose of the ongoing project is to establish a feasible and reproducible setup for in-vivo mouse lung micro-computed tomography (μCT). We seek to use in-vivo respiratory-gated μCT to follow mouse models of lung disease with subsequent recovery of the mouse. Methodologies for optimizing scanning parameters and gating for the in-vivo mouse lung are presented. A Scireq flexiVent ventilated the gas-anesthetized mice at 60 breaths/minute, 30 cm H20 PEEP, 30 ml/kg tidal volume and provided a respiratory signal to gate a Skyscan 1076 μCT. Physiologic monitoring allowed the control of vital functions and quality of anesthesia, e.g. via ECG monitoring. In contrary to longer exposure times with ex-vivo scans, scan times for in-vivo were reduced using 35μm pixel size, 158ms exposure time and 18μm pixel size, 316ms exposure time to reduce motion artifacts. Gating via spontaneous breathing was also tested. Optimal contrast resolution was achieved at 50kVp, 200μA, applying an aluminum filter (0.5mm). There were minimal non-cardiac related motion artifacts. Both 35μm and 1μm voxel size images were suitable for evaluation of the airway lumen and parenchymal density. Total scan times were 30 and 65 minutes respectively. The mice recovered following scanning protocols. In-vivo lung scanning with recovery of the mouse delivered reasonable image quality for longitudinal studies, e.g. mouse asthma models. After examining 10 mice, we conclude μCT is a feasible tool evaluating mouse models of lung pathology in longitudinal studies with increasing anatomic detail available for evaluation as one moves from in-vivo to ex-vivo studies. Further developments include automated

  15. Petri Nets in Cryptographic Protocols

    DEFF Research Database (Denmark)

    Crazzolara, Federico; Winskel, Glynn

    2001-01-01

    A process language for security protocols is presented together with a semantics in terms of sets of events. The denotation of process is a set of events, and as each event specifies a set of pre and postconditions, this denotation can be viewed as a Petri net. By means of an example we illustrate...

  16. Improving the DGK comparison protocol

    NARCIS (Netherlands)

    Veugen, P.J.M.

    2012-01-01

    When processing signals in the encrypted domain, homomorphic encryption can be used to enable linear operations on encrypted data. Comparison of encrypted data however requires an additional protocol between the parties and will be relatively expensive. A well-known and frequently used comparison

  17. Performance Evaluation of Security Protocols

    DEFF Research Database (Denmark)

    Bodei, Chiara; Buchholtz, Mikael; Curti, Michele

    2005-01-01

    We use a special operational semantics which drives us in inferring quantitative measures on systems describing cryptographis cryptographic protocols. We assign rates to transitions by only looking at these labels. The rates reflect the distributed architecture running applications and the use...... of possibly different cryptosystems. We then map transition systems to Markov chains and evaluate performance of systems, using standard tools....

  18. Art. 1 Eerste Protocol EVRM

    NARCIS (Netherlands)

    Poelmann, E.

    2014-01-01

    Het recht op bezit is niet in het Europees Verdrag ter bescherming van de rechten van de mens en de fundamentele vrijheden (hierna: EVRM) neergelegd, maar in het Eerste Protocol daarbij (hierna: EP), dat in 1954 in werking is getreden. Het is van belang voor ogen te houden dat de Tweede Wereldoorlog

  19. Bundle Security Protocol for ION

    Science.gov (United States)

    Burleigh, Scott C.; Birrane, Edward J.; Krupiarz, Christopher

    2011-01-01

    This software implements bundle authentication, conforming to the Delay-Tolerant Networking (DTN) Internet Draft on Bundle Security Protocol (BSP), for the Interplanetary Overlay Network (ION) implementation of DTN. This is the only implementation of BSP that is integrated with ION.

  20. Affinity biosensors: techniques and protocols

    National Research Council Canada - National Science Library

    Rogers, Kim R; Mulchandani, Ashok

    1998-01-01

    ..., and government to begin or expand their biosensors research. This volume, Methods in Biotechnology vol. 7: Affinity Biosensors: Techniques and Protocols, describes a variety of classical and emerging transduction technologies that have been interfaced to bioaffinity elements (e.g., antibodies and receptors). Some of the reas...

  1. High Entropy Random Selection Protocols

    NARCIS (Netherlands)

    H. Buhrman (Harry); M. Christandl (Matthias); M. Koucky (Michal); Z. Lotker (Zvi); B. Patt-Shamir; M. Charikar; K. Jansen; O. Reingold; J. Rolim

    2007-01-01

    textabstractIn this paper, we construct protocols for two parties that do not trust each other, to generate random variables with high Shannon entropy. We improve known bounds for the trade off between the number of rounds, length of communication and the entropy of the outcome.

  2. A Student Teamwork Induction Protocol

    Science.gov (United States)

    Kamau, Caroline; Spong, Abigail

    2015-01-01

    Faulty group processes have harmful effects on performance but there is little research about intervention protocols to pre-empt them in higher education. This naturalistic experiment compared a control cohort with an inducted cohort. The inducted cohort attended a workshop, consultations, elected a leader and used tools (a group log and group…

  3. Cognitive Communications Protocols for SATCOM

    Science.gov (United States)

    2017-10-20

    communications protocols for satellite and space communications with possible broad applications in defense, homeland-security as well as consumer ...communications with possible broad applications in defense, homeland-security, and civilian as well as consumer telecommunications. Such cognitive...vulnerable against smart jammers that may attempt to learn the cognitive radios own behavior . In response, our second class of proposed algorithms

  4. In vivo and in vitro investigations on rotenoids from Indigofera ...

    Indian Academy of Sciences (India)

    tribpo

    Laboratory of Plant Physiology and Biochemistry Department of Botany, University of ... different growth stages and analysed for their