Sample records for equivalent count nec

  1. NEMA count-rate evaluation of the first and second generation of the Ecat Exact and Ecat Exact HR family of scanners

    NASA Astrophysics Data System (ADS)

    Eriksson, L.; Wienhard, K.; Eriksson, M.; Casey, M. E.; Knoess, C.; Bruckbauer, T.; Hamill, J.; Mulnix, T.; Vollmar, S.; Bendriem, B.; Heiss, W. D.; Nutt, R.

    2002-06-01

    The first and second generation of the Exact and Exact HR family of scanners has been evaluated in terms of noise equivalent count rate (NEC) and count-rate capabilities. The new National Electrical Manufacturers Association standard was used for the evaluation. In spite of improved electronics and improved count-rate capabilities, the peak NEC was found to be fairly constant between the generations. The results are discussed in terms of the different electronic solutions for the two generations and its implications on system dead time and NEC count-rate capability.

  2. Effective count rates for PET scanners with reduced and extended axial field of view

    NASA Astrophysics Data System (ADS)

    MacDonald, L. R.; Harrison, R. L.; Alessio, A. M.; Hunter, W. C. J.; Lewellen, T. K.; Kinahan, P. E.

    2011-06-01

    We investigated the relationship between noise equivalent count (NEC) and axial field of view (AFOV) for PET scanners with AFOVs ranging from one-half to twice those of current clinical scanners. PET scanners with longer or shorter AFOVs could fulfill different clinical needs depending on exam volumes and site economics. Using previously validated Monte Carlo simulations, we modeled true, scattered and random coincidence counting rates for a PET ring diameter of 88 cm with 2, 4, 6, and 8 rings of detector blocks (AFOV 7.8, 15.5, 23.3, and 31.0 cm). Fully 3D acquisition mode was compared to full collimation (2D) and partial collimation (2.5D) modes. Counting rates were estimated for a 200 cm long version of the 20 cm diameter NEMA count-rate phantom and for an anthropomorphic object based on a patient scan. We estimated the live-time characteristics of the scanner from measured count-rate data and applied that estimate to the simulated results to obtain NEC as a function of object activity. We found NEC increased as a quadratic function of AFOV for 3D mode, and linearly in 2D mode. Partial collimation provided the highest overall NEC on the 2-block system and fully 3D mode provided the highest NEC on the 8-block system for clinically relevant activities. On the 4-, and 6-block systems 3D mode NEC was highest up to ~300 MBq in the anthropomorphic phantom, above which 3D NEC dropped rapidly, and 2.5D NEC was highest. Projected total scan time to achieve NEC-density that matches current clinical practice in a typical oncology exam averaged 9, 15, 24, and 61 min for the 8-, 6-, 4-, and 2-block ring systems, when using optimal collimation. Increasing the AFOV should provide a greater than proportional increase in NEC, potentially benefiting patient throughput-to-cost ratio. Conversely, by using appropriate collimation, a two-ring (7.8 cm AFOV) system could acquire whole-body scans achieving NEC-density levels comparable to current standards within long, but feasible, scan times.

  3. Initial evaluation of the Celesteion large-bore PET/CT scanner in accordance with the NEMA NU2-2012 standard and the Japanese guideline for oncology FDG PET/CT data acquisition protocol version 2.0.

    PubMed

    Kaneta, Tomohiro; Ogawa, Matsuyoshi; Motomura, Nobutoku; Iizuka, Hitoshi; Arisawa, Tetsu; Hino-Shishikura, Ayako; Yoshida, Keisuke; Inoue, Tomio

    2017-10-11

    The goal of this study was to evaluate the performance of the Celesteion positron emission tomography/computed tomography (PET/CT) scanner, which is characterized by a large-bore and time-of-flight (TOF) function, in accordance with the NEMA NU-2 2012 standard and version 2.0 of the Japanese guideline for oncology fluorodeoxyglucose PET/CT data acquisition protocol. Spatial resolution, sensitivity, count rate characteristic, scatter fraction, energy resolution, TOF timing resolution, and image quality were evaluated according to the NEMA NU-2 2012 standard. Phantom experiments were performed using 18 F-solution and an IEC body phantom of the type described in the NEMA NU-2 2012 standard. The minimum scanning time required for the detection of a 10-mm hot sphere with a 4:1 target-to-background ratio, the phantom noise equivalent count (NEC phantom ), % background variability (N 10mm ), % contrast (Q H,10mm ), and recovery coefficient (RC) were calculated according to the Japanese guideline. The measured spatial resolution ranged from 4.5- to 5-mm full width at half maximum (FWHM). The sensitivity and scatter fraction were 3.8 cps/kBq and 37.3%, respectively. The peak noise-equivalent count rate was 70 kcps in the presence of 29.6 kBq mL -1 in the phantom. The system energy resolution was 12.4% and the TOF timing resolution was 411 ps at FWHM. Minimum scanning times of 2, 7, 6, and 2 min per bed position, respectively, are recommended for visual score, noise-equivalent count (NEC) phantom , N 10mm , and the Q H,10mm to N 10mm ratio (QNR) by the Japanese guideline. The RC of a 10-mm-diameter sphere was 0.49, which exceeded the minimum recommended value. The Celesteion large-bore PET/CT system had low sensitivity and NEC, but good spatial and time resolution when compared to other PET/CT scanners. The QNR met the recommended values of the Japanese guideline even at 2 min. The Celesteion is therefore thought to provide acceptable image quality with 2 min/bed position acquisition, which is the most common scan protocol in Japan.

  4. Performance Evaluation of the microPET®—FOCUS-F120

    NASA Astrophysics Data System (ADS)

    Laforest, Richard; Longford, Desmond; Siegel, Stefan; Newport, Danny F.; Yap, Jeffrey

    2007-02-01

    microPETreg-Focus-F120 is the latest model of dedicated small animal PET scanners from CTI-Concorde Microsystems LLC, (Knoxville, TN). This scanner, based on the geometry of the microPET-R4, takes advantage of several detector modifications to the coincidence processing electronics that improve the image resolution, sensitivity, and counting rate performance as compared to the predecessor models. This work evaluates the performance of the Focus-F120 system and shows its improvement over the earlier models. In particular, the spatial resolution is shown to improve from 2.32 to 1.69 mm at 5 mm radial distance and the peak absolute sensitivity increases from 4.1% to 7.1% compared to the microPET-R4. The counting rate capability, expressed in noise equivalent counting rate (NEC-1R), was shown to peak at over 800 kcps at 88 MBq for both systems using a mouse phantom. For this small phantom, the NECR counting rate is limited by the data transmission bandwidth between the scanner and the acquisition console. The rat-like phantom showed peak NEC-1R value at 300 kcps at 140 MBq. Evaluation of image quality and quantitation accuracy was also performed using specially designed phantoms and animal experiments

  5. Optimization of PET instrumentation for brain activation studies

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

    Dahlbom, M.; Cherry, S.R.; Hoffman, E.J.

    By performing cerebral blood flow studies with positron emission tomography (PET), and comparing blood flow images of different states of activation, functional mapping of the brain is possible. The ability of current commercial instruments to perform such studies is investigated in this work, based on a comparison of noise equivalent count (NEC) rates. Differences in the NEC performance of the different scanners in conjunction with scanner design parameters, provide insights into the importance of block design (size, dead time, crystal thickness) and overall scanner design (sensitivity and scatter fraction) for optimizing data from activation studies. The newer scanners with removablemore » septa, operating with 3-D acquisition, have much higher sensitivity, but require new methodology for optimized operation. Only by administering multiple low doses (fractionation) of the flow tracer can the high sensitivity be utilized.« less

  6. PET Timing Performance Measurement Method Using NEMA NEC Phantom

    NASA Astrophysics Data System (ADS)

    Wang, Gin-Chung; Li, Xiaoli; Niu, Xiaofeng; Du, Huini; Balakrishnan, Karthik; Ye, Hongwei; Burr, Kent

    2016-06-01

    When comparing the performance of time-of-flight whole-body PET scanners, timing resolution is one important benchmark. Timing performance is heavily influenced by detector and electronics design. Even for the same scanner design, measured timing resolution is a function of many factors including the activity concentration, geometry and positioning of the radioactive source. Due to lack of measurement standards, the timing resolutions reported in the literature may not be directly comparable and may not describe the timing performance under clinically relevant conditions. In this work we introduce a method which makes use of the data acquired during the standard NEMA Noise-Equivalent-Count-Rate (NECR) measurements, and compare it to several other timing resolution measurement methods. The use of the NEMA NEC phantom, with well-defined dimensions and radioactivity distribution, is attractive because it has been widely accepted in the industry and allows for the characterization of timing resolution across a more relevant range of conditions.

  7. Generation of the Acquisition-Specific NEC (AS-NEC) Curves to Optimize the Injected Dose in 3D18F-FDG Whole Body PET Studies

    NASA Astrophysics Data System (ADS)

    Danna, M.; Lecchi, M.; Bettinardi, V.; Gilardi, M.; Stearns, C.; Lucignani, G.; Fazio, F.

    2006-02-01

    Aim of this work was the implementation and validation, for the Discovery-ST PET/CT (GE Medical Systems) system, of the acquisition-specific noise equivalent counts (AS-NEC) method to establish the amount of tracer to be injected in 3D18F-FDG whole body (WB) PET studies to achieve the peak of the NEC (NEC-p) at the acquisition time. The AS-NEC method uses prompts, delayed events and detector dead-time of a single reference PET scan to calculate the full shape of the NEC curve. The method was implemented using a 3D decay series of the 70 cm NEMA 2001 (line source in a 20 cm diameter solid polyethylene cylinder) phantom and validated with the cylindrical NEMA 1994 (diameter, 20 cm; length, 20 cm) and NEMA 2001 IEC body phantoms. The NEC curves generated by the single frames of the phantom series, using the AS-NEC method, well correlated with the experimental NEC curves proving the validity of the method and the possible application to clinical studies. The AS-NEC model was then retrospectively applied on 40 3D18F-FDG WB studies in a range of body mass index (BMI) between 16 and 30 (kg/m2) (6 under-weight (uw), 18 normal-weight (nw), 16 over-weight (ow)). For each acquisition frame of each patient study, the activity at the acquisition time, corresponding to the NEC-p was identified on the NEC curves. Furthermore, as the NEC curves show a region around the NEC-p with small variations (nearly a plateau), the values of radioactivity corresponding to a reduction of 1%, 3% and 5% with respect to NEC-p were also calculated to assess a possible reduction of the doses to be injected in clinical studies. The results show that the average activities at the acquisition time corresponding to the NEC-p were comparable for the three BMI classes: 336.7 MBq (sd=22.2), 329.3 MBq (sd=33.3), 344.1 MBq (sd=48.1) for uw, nw and ow, respectively. Therefore, the total average NEC-p activity for the three BMI classes was 336.7 MBq (sd=40.7). The mean values of the radioactivity at a reduction of 1%, 3% and 5% with respect to the NEC-p were: 284.9 MBq (sd=40.7), 247.9 MBq (sd=33.3) and 225.7 MBq (sd=29.6) respectively. These results indicate the possibility to use, for the Discovery-ST, a single injection protocol of 448 MBq (for the range of BMI here considered) to have an activity at the acquisition time (after 45 min of uptake) of 336.7 MBq (NEC-p). Nevertheless, the plateau near the NEC-p suggests the possibility to reduce significantly the dose to be injected in clinical studies down to about 330 MBq, while preserving suitable NEC performance (-3%) with respect to the NEC-p. This result was supported by image quality assessment performed on reconstructed images of the NEMA 2001 IEC body phantom.

  8. Optimization and performance evaluation of the microPET II scanner for in vivo small-animal imaging

    NASA Astrophysics Data System (ADS)

    Yang, Yongfeng; Tai, Yuan-Chuan; Siegel, Stefan; Newport, Danny F.; Bai, Bing; Li, Quanzheng; Leahy, Richard M.; Cherry, Simon R.

    2004-06-01

    MicroPET II is a newly developed PET (positron emission tomography) scanner designed for high-resolution imaging of small animals. It consists of 17 640 LSO crystals each measuring 0.975 × 0.975 × 12.5 mm3, which are arranged in 42 contiguous rings, with 420 crystals per ring. The scanner has an axial field of view (FOV) of 4.9 cm and a transaxial FOV of 8.5 cm. The purpose of this study was to carefully evaluate the performance of the system and to optimize settings for in vivo mouse and rat imaging studies. The volumetric image resolution was found to depend strongly on the reconstruction algorithm employed and averaged 1.1 mm (1.4 µl) across the central 3 cm of the transaxial FOV when using a statistical reconstruction algorithm with accurate system modelling. The sensitivity, scatter fraction and noise-equivalent count (NEC) rate for mouse- and rat-sized phantoms were measured for different energy and timing windows. Mouse imaging was optimized with a wide open energy window (150-750 keV) and a 10 ns timing window, leading to a sensitivity of 3.3% at the centre of the FOV and a peak NEC rate of 235 000 cps for a total activity of 80 MBq (2.2 mCi) in the phantom. Rat imaging, due to the higher scatter fraction, and the activity that lies outside of the field of view, achieved a maximum NEC rate of 24 600 cps for a total activity of 80 MBq (2.2 mCi) in the phantom, with an energy window of 250-750 keV and a 6 ns timing window. The sensitivity at the centre of the FOV for these settings is 2.1%. This work demonstrates that different scanner settings are necessary to optimize the NEC count rate for different-sized animals and different injected doses. Finally, phantom and in vivo animal studies are presented to demonstrate the capabilities of microPET II for small-animal imaging studies.

  9. Performance evaluation and optimization of the MiniPET-II scanner

    NASA Astrophysics Data System (ADS)

    Lajtos, Imre; Emri, Miklos; Kis, Sandor A.; Opposits, Gabor; Potari, Norbert; Kiraly, Beata; Nagy, Ferenc; Tron, Lajos; Balkay, Laszlo

    2013-04-01

    This paper presents results of the performance of a small animal PET system (MiniPET-II) installed at our Institute. MiniPET-II is a full ring camera that includes 12 detector modules in a single ring comprised of 1.27×1.27×12 mm3 LYSO scintillator crystals. The axial field of view and the inner ring diameter are 48 mm and 211 mm, respectively. The goal of this study was to determine the NEMA-NU4 performance parameters of the scanner. In addition, we also investigated how the calculated parameters depend on the coincidence time window (τ=2, 3 and 4 ns) and the low threshold settings of the energy window (Elt=250, 350 and 450 keV). Independent measurements supported optimization of the effective system radius and the coincidence time window of the system. We found that the optimal coincidence time window and low threshold energy window are 3 ns and 350 keV, respectively. The spatial resolution was close to 1.2 mm in the center of the FOV with an increase of 17% at the radial edge. The maximum value of the absolute sensitivity was 1.37% for a point source. Count rate tests resulted in peak values for the noise equivalent count rate (NEC) curve and scatter fraction of 14.2 kcps (at 36 MBq) and 27.7%, respectively, using the rat phantom. Numerical values of the same parameters obtained for the mouse phantom were 55.1 kcps (at 38.8 MBq) and 12.3%, respectively. The recovery coefficients of the image quality phantom ranged from 0.1 to 0.87. Altering the τ and Elt resulted in substantial changes in the NEC peak and the sensitivity while the effect on the image quality was negligible. The spatial resolution proved to be, as expected, independent of the τ and Elt. The calculated optimal effective system radius (resulting in the best image quality) was 109 mm. Although the NEC peak parameters do not compare favorably with those of other small animal scanners, it can be concluded that under normal counting situations the MiniPET-II imaging capability assures remarkably good image quality, sensitivity and spatial resolution.

  10. Thymic stromal lymphopoietin expression is increased in nasal epithelial cells of patients with mugwort pollen sensitive-seasonal allergic rhinitis.

    PubMed

    Zhu, Dong-dong; Zhu, Xue-wei; Jiang, Xiao-dan; Dong, Zhen

    2009-10-05

    Excessive expression of thymic stromal lymphopoietin (TSLP) has been demonstrated in asthmatic airway epithelia and in nasal epithelia from animal models of allergic rhinitis (AR), but the evidence of expression of TSLP in nasal epithelial cells (NECs) of patients with AR is lacking. We aimed to investigate the expression of TSLP in NECs of patients with mugwort sensitive-seasonal AR and determine whether it is associated with severity of symptoms and the number of infiltrated eosinophils in nasal mucosa. NECs specimens were obtained by scraping with plastic curettes from the nasal inferior turbinates of patients with mugwort pollen sensitive-seasonal AR (n = 22) and nonallergic controls (n = 11) during last peak mugwort pollen season. The severity of nasal symptom was assessed using a Visual Analog Scale (VAS). In addition, serum mugwort pollen IgE levels were tested from each patient. In situ hybridization (ISH) was performed to test the messenger RNA (mRNA) of TSLP in the NECs. Furthermore, immunohistochemical staining (IHC) was scored to evaluate the expression of TSLP and eosinophil cell count was made by May-Grünwald/Giemsa staining. The correlation between expression of TSLP and all other parameters was analyzed in this study. The mRNA level of TSLP was significantly increased in NECs of patients with AR compared with the nonallergic control group (P < 0.05). In addition, IHC results showed that expression of TSLP in NECs from patients with AR was up-regulated which was correlated with VAS score (r = 0.598; P < 0.05) and nasal eosinophils count (r = 0.702; P < 0.05), but it was unrelated with mugwort pollen specific IgE level. These preliminary findings indicate a potential relationship between TSLP expression, severity of symptoms and nasal eosinophils count in pathogenesis of AR, but TSLP expression did not correlate with mugwort pollen specific IgE level. The elevated expression of TSLP might play a critical role in local atopical responses of AR. In the future, the TSLP has the potential to be one of the most important molecular markers for AR diagnoses and assessment.

  11. Kernel Equating Under the Non-Equivalent Groups With Covariates Design

    PubMed Central

    Bränberg, Kenny

    2015-01-01

    When equating two tests, the traditional approach is to use common test takers and/or common items. Here, the idea is to use variables correlated with the test scores (e.g., school grades and other test scores) as a substitute for common items in a non-equivalent groups with covariates (NEC) design. This is performed in the framework of kernel equating and with an extension of the method developed for post-stratification equating in the non-equivalent groups with anchor test design. Real data from a college admissions test were used to illustrate the use of the design. The equated scores from the NEC design were compared with equated scores from the equivalent group (EG) design, that is, equating with no covariates as well as with equated scores when a constructed anchor test was used. The results indicate that the NEC design can produce lower standard errors compared with an EG design. When covariates were used together with an anchor test, the smallest standard errors were obtained over a large range of test scores. The results obtained, that an EG design equating can be improved by adjusting for differences in test score distributions caused by differences in the distribution of covariates, are useful in practice because not all standardized tests have anchor tests. PMID:29881012

  12. Kernel Equating Under the Non-Equivalent Groups With Covariates Design.

    PubMed

    Wiberg, Marie; Bränberg, Kenny

    2015-07-01

    When equating two tests, the traditional approach is to use common test takers and/or common items. Here, the idea is to use variables correlated with the test scores (e.g., school grades and other test scores) as a substitute for common items in a non-equivalent groups with covariates (NEC) design. This is performed in the framework of kernel equating and with an extension of the method developed for post-stratification equating in the non-equivalent groups with anchor test design. Real data from a college admissions test were used to illustrate the use of the design. The equated scores from the NEC design were compared with equated scores from the equivalent group (EG) design, that is, equating with no covariates as well as with equated scores when a constructed anchor test was used. The results indicate that the NEC design can produce lower standard errors compared with an EG design. When covariates were used together with an anchor test, the smallest standard errors were obtained over a large range of test scores. The results obtained, that an EG design equating can be improved by adjusting for differences in test score distributions caused by differences in the distribution of covariates, are useful in practice because not all standardized tests have anchor tests.

  13. Evaluation of PeneloPET Simulations of Biograph PET/CT Scanners

    NASA Astrophysics Data System (ADS)

    Abushab, K. M.; Herraiz, J. L.; Vicente, E.; Cal-González, J.; España, S.; Vaquero, J. J.; Jakoby, B. W.; Udías, J. M.

    2016-06-01

    Monte Carlo (MC) simulations are widely used in positron emission tomography (PET) for optimizing detector design, acquisition protocols, and evaluating corrections and reconstruction methods. PeneloPET is a MC code based on PENELOPE, for PET simulations which considers detector geometry, acquisition electronics and materials, and source definitions. While PeneloPET has been successfully employed and validated with small animal PET scanners, it required a proper validation with clinical PET scanners including time-of-flight (TOF) information. For this purpose, we chose the family of Biograph PET/CT scanners: the Biograph True-Point (B-TP), Biograph True-Point with TrueV (B-TPTV) and the Biograph mCT. They have similar block detectors and electronics, but a different number of rings and configuration. Some effective parameters of the simulations, such as the dead-time and the size of the reflectors in the detectors, were adjusted to reproduce the sensitivity and noise equivalent count (NEC) rate of the B-TPTV scanner. These parameters were then used to make predictions of experimental results such as sensitivity, NEC rate, spatial resolution, and scatter fraction (SF), from all the Biograph scanners and some variations of them (energy windows and additional rings of detectors). Predictions agree with the measured values for the three scanners, within 7% (sensitivity and NEC rate) and 5% (SF). The resolution obtained for the B-TPTV is slightly better (10%) than the experimental values. In conclusion, we have shown that PeneloPET is suitable for simulating and investigating clinical systems with good accuracy and short computational time, though some effort tuning of a few parameters of the scanners modeled may be needed in case that the full details of the scanners studied are not available.

  14. A phantom design and assessment of lesion detectability in PET imaging

    NASA Astrophysics Data System (ADS)

    Wollenweber, Scott D.; Kinahan, Paul E.; Alessio, Adam M.

    2017-03-01

    The early detection of abnormal regions with increased tracer uptake in positron emission tomography (PET) is a key driver of imaging system design and optimization as well as choice of imaging protocols. Detectability, however, remains difficult to assess due to the need for realistic objects mimicking the clinical scene, multiple lesion-present and lesion-absent images and multiple observers. Fillable phantoms, with tradeoffs between complexity and utility, provide a means to quantitatively test and compare imaging systems under truth-known conditions. These phantoms, however, often focus on quantification rather than detectability. This work presents extensions to a novel phantom design and analysis techniques to evaluate detectability in the context of realistic, non-piecewise constant backgrounds. The design consists of a phantom filled with small solid plastic balls and a radionuclide solution to mimic heterogeneous background uptake. A set of 3D-printed regular dodecahedral `features' were included at user-defined locations within the phantom to create `holes' within the matrix of chaotically-packed balls. These features fill at approximately 3:1 contrast to the lumpy background. A series of signal-known-present (SP) and signal-known-absent (SA) sub-images were generated and used as input for observer studies. This design was imaged in a head-like 20 cm diameter, 20 cm long cylinder and in a body-like 36 cm wide by 21 cm tall by 40 cm long tank. A series of model observer detectability indices were compared across scan conditions (count levels, number of scan replicates), PET image reconstruction methods (with/without TOF and PSF) and between PET/CT scanner system designs using the same phantom imaged on multiple systems. The detectability index was further compared to the noise-equivalent count (NEC) level to characterize the relationship between NEC and observer SNR.

  15. Enhanced colon cancer chemoprevention of curcumin by nanoencapsulation with whey protein.

    PubMed

    Jayaprakasha, Guddadarangavvanahally K; Chidambara Murthy, Kotamballi N; Patil, Bhimanagouda S

    2016-10-15

    To improve bioavailability and enhance colon cancer prevention ability of curcumin, whey protein was used to nanoencapsulate at three different ratios such as 70:30, 50:50 and 35:65 for the first time. The drug loading, entrapment efficiency and structural changes of curcumin was confirmed by quantitative NMR spectroscopy. The nanoparticles prepared using the three ratios had an average diameters of 236.5±8.8, 212±3.4, and 187±11.4nm, as well as zeta (ζ) potentials of -13.1,-9.26, and -4.63mV, respectively, at pH 7.0. The cytotoxicity assay was performed for human colon and prostate cancer (SW480 and LNCap) by MTT assay and results showed significantly higher cytotoxicity of nanoencapsulated curcumin (NEC) (equivalent to 30.91, 20.70 and 16.86µM of NEC-1, 2 and 3 respectively), as compared to plain curcumin at 50µM after 72h of treatment. Cytotoxicity was also confirmed by microscopy of treated cells stained with acridine orange and propidium iodide. The cells treated with 50µM of curcumin, 30.91µM (NEC-1), 20.70µM (NEC-2) and 16.86µM (NEC-3) showed enhanced activation of p53 and elevated bax/Bcl2 expression (NEC-3), increased cytochrome-c in cytosol (NEC-2) confirming the enhanced cytotoxicity. To confirm the increased bioavailability, the intracellular curcumin was measured using fluorescence intensity. The fluorescent signal for intracellular curcumin was increased by 12, 30, and 21% for NEC-1, NEC-2, and NEC-3 respectively as compared to plain curcumin at 4h. Based on these results, we conclude that nanoencapsulated curcumin with whey protein will have potential to be considered for clinical applications for future studies. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. The initial experience of antithrombin III in the management of neonates with necrotizing enterocolitis.

    PubMed

    St Peter, Shawn D; Little, Danny C; Calkins, Casey M; Holcomb, George W; Snyder, Charles L; Ostlie, Daniel J

    2007-04-01

    Necrotizing enterocolitis (NEC), the devastating enteric process of premature neonates, is marked by severe intravascular abnormalities and disseminated intravascular coagulation. Treatment to date remains historical and continues to be merely supportive without attempts to ameliorate progress within the inflammatory or coagulation cascades. Antithrombin III (ATIII) supplementation has been shown to favorably alter the process of disseminated intravascular coagulation and sepsis in adults. However, no reported use of this treatment exists in neonates. Therefore, we analyze the efficacy of our recent experience with ATIII replacement therapy in neonates with NEC. Age and diseased-matched controls with NEC were identified before the introduction of ATIII in our institution and compared against neonates with NEC undergoing ATIII replacement for diminished ATIII levels. Data collected included demographics, course of treatment parameters, and outcomes. Course of treatment parameters included hemoglobin, platelet count, prothrombin time, and partial thromboplastin time over the first 10 consecutive days of treatment. Outcome variables included packed red blood cell, platelet, fresh frozen plasma, and cryoprecipitate transfusions, as well as transfusion cost, length of stay, and survival. Over a 5-year period, 19 neonates with NEC received ATIII and were compared to 17 historical controls. Treatment hematologic profiles were not worsened in the ATIII-treated patients. The control patients received less overall transfusions and had a shorter length of stay. Antithrombin III appears to be safe in neonates with NEC, and its impact on reversing intravascular pathology in these patients warrants more thorough investigation.

  17. Oral Administration of Nano-Emulsion Curcumin in Mice Suppresses Inflammatory-Induced NFκB Signaling and Macrophage Migration

    PubMed Central

    Young, Nicholas A.; Bruss, Michael S.; Gardner, Mark; Willis, William L.; Mo, Xiaokui; Valiente, Giancarlo R.; Cao, Yu; Liu, Zhongfa; Jarjour, Wael N.; Wu, Lai-Chu

    2014-01-01

    Despite the widespread use of curcumin for centuries in Eastern medicine as an anti-inflammatory agent, its molecular actions and therapeutic viability have only recently been explored. While curcumin does have potential therapeutic efficacy, both solubility and bioavailability must be improved before it can be more successfully translated to clinical care. We have previously reported a novel formulation of nano-emulsion curcumin (NEC) that achieves significantly greater plasma concentrations in mice after oral administration. Here, we confirm the immunosuppressive effects of NEC in vivo and further examine its molecular mechanisms to better understand therapeutic potential. Using transgenic mice harboring an NFκB-luciferase reporter gene, we demonstrate a novel application of this in vivo inflammatory model to test the efficacy of NEC administration by bioluminescent imaging and show that LPS-induced NFκB activity was suppressed with NEC compared to an equivalent amount of curcumin in aqueous suspension. Administration of NEC by oral gavage resulted in a reduction of blood monocytes, decreased levels of both TLR4 and RAGE expression, and inhibited secretion of MCP-1. Mechanistically, curcumin blocked LPS-induced phosphorylation of the p65 subunit of NFκB and IκBα in murine macrophages. In a mouse model of peritonitis, NEC significantly reduced macrophage recruitment, but not T-cell or B-cell levels. In addition, curcumin treatment of monocyte derived cell lines and primary human macrophages in vitro significantly inhibited cell migration. These data demonstrate that curcumin can suppress inflammation by inhibiting macrophage migration via NFκB and MCP-1 inhibition and establish that NEC is an effective therapeutic formulation to increase the bioavailability of curcumin in order to facilitate this response. PMID:25369140

  18. Performance modeling of a wearable brain PET (BET) camera

    NASA Astrophysics Data System (ADS)

    Schmidtlein, C. R.; Turner, J. N.; Thompson, M. O.; Mandal, K. C.; Häggström, I.; Zhang, J.; Humm, J. L.; Feiglin, D. H.; Krol, A.

    2016-03-01

    Purpose: To explore, by means of analytical and Monte Carlo modeling, performance of a novel lightweight and low-cost wearable helmet-shaped Brain PET (BET) camera based on thin-film digital Geiger Avalanche Photo Diode (dGAPD) with LSO and LaBr3 scintillators for imaging in vivo human brain processes for freely moving and acting subjects responding to various stimuli in any environment. Methods: We performed analytical and Monte Carlo modeling PET performance of a spherical cap BET device and cylindrical brain PET (CYL) device, both with 25 cm diameter and the same total mass of LSO scintillator. Total mass of LSO in both the BET and CYL systems is about 32 kg for a 25 mm thick scintillator, and 13 kg for 10 mm thick scintillator (assuming an LSO density of 7.3 g/ml). We also investigated a similar system using an LaBr3 scintillator corresponding to 22 kg and 9 kg for the 25 mm and 10 mm thick systems (assuming an LaBr3 density of 5.08 g/ml). In addition, we considered a clinical whole body (WB) LSO PET/CT scanner with 82 cm ring diameter and 15.8 cm axial length to represent a reference system. BET consisted of distributed Autonomous Detector Arrays (ADAs) integrated into Intelligent Autonomous Detector Blocks (IADBs). The ADA comprised of an array of small LYSO scintillator volumes (voxels with base a×a: 1.0 <= a <= 2.0 mm and length c: 3.0 <= c <= 6.0 mm) with 5-65 μm thick reflective layers on its five sides and sixth side optically coupled to the matching array of dGAPDs and processing electronics with total thickness of 50 μm. Simulated energy resolution was 10.8% and 3.3% for LSO and LaBr3 respectively and the coincidence window was set at 2 ns. The brain was simulated as a sphere of uniform F-18 activity with diameter of 10 cm embedded in a center of water sphere with diameter of 10 cm. Results: Analytical and Monte Carlo models showed similar results for lower energy window values (458 keV versus 445 keV for LSO, and 492 keV versus 485 keV for LaBr3), and for the relative performance of system sensitivity. Monte Carlo results further showed that the BET geometry had >50% better noise equivalent count (NEC) performance relative to the CYL geometry, and >1100% better performance than a WB geometry for 25 mm thick LSO and LaBr3. For 10 mm thick LaBr3 equivalent mass systems LSO (7 mm thick) performed ~40% higher NEC than LaBr3. Analytic and Monte Carlo simulations also showed that 1×1×3 mm scintillator crystals can achieve ~1.2 mm FWHM spatial resolution. Conclusions: This study shows that a spherical cap brain PET system can provide improved NEC while preserving spatial resolution when compared to an equivalent dedicated cylindrical PET brain camera and shows greatly improved PET performance relative to a conventional whole body PET/CT. In addition, our simulations show that LSO will generally outperform LaBr3 for NEC unless the timing resolution for LaBr3 is considerably smaller than presently used for LSO, i.e. well below 300 ps.

  19. A Maximum NEC Criterion for Compton Collimation to Accurately Identify True Coincidences in PET

    PubMed Central

    Chinn, Garry; Levin, Craig S.

    2013-01-01

    In this work, we propose a new method to increase the accuracy of identifying true coincidence events for positron emission tomography (PET). This approach requires 3-D detectors with the ability to position each photon interaction in multi-interaction photon events. When multiple interactions occur in the detector, the incident direction of the photon can be estimated using the Compton scatter kinematics (Compton Collimation). If the difference between the estimated incident direction of the photon relative to a second, coincident photon lies within a certain angular range around colinearity, the line of response between the two photons is identified as a true coincidence and used for image reconstruction. We present an algorithm for choosing the incident photon direction window threshold that maximizes the noise equivalent counts of the PET system. For simulated data, the direction window removed 56%–67% of random coincidences while retaining > 94% of true coincidences from image reconstruction as well as accurately extracted 70% of true coincidences from multiple coincidences. PMID:21317079

  20. Impact of umbilical cord milking and pasteurized donor human milk on necrotizing enterocolitis: a retrospective review.

    PubMed

    Sekhon, Mehtab K; Yoder, Bradley A

    2018-05-08

    Necrotizing enterocolitis (NEC) is a serious complication of prematurity. Our objective was to evaluate the impact of an umbilical cord milking protocol (UCM) and pasteurized donor human milk (PDHM) on NEC rates in infants less than 30 weeks gestational age from January 1, 2010 to September 30, 2016. We hypothesized an incremental decrease in NEC after each intervention. We performed a retrospective review of 638 infants born less than 30 weeks gestational age. Infants were grouped into three epochs: pre-UCM/pre-PDHM (Epoch 1, n = 159), post-UCM/pre-PDHM (Epoch 2, n = 133), and post-UCM/post-PDHM (Epoch 3, n = 252). The incidence of NEC, surgical NEC, and NEC/death were compared. Logistic regression was used to determine independent significance of time epoch, gestational age, birth weight, and patent ductus arteriosus for NEC, surgical NEC, and death/NEC. At birth, infants in Epoch 1 were younger than Epoch 2 and 3 (26.8 weeks versus 27.3 and 27.2, respectively, P = 0.036) and smaller (910 g versus 1012 and 983, respectively, P = 0.012). Across epochs, there was a significant correlation between patent ductus arteriosus treatment and NEC rate (P < 0.001, Cochran-Mantel-Haenszel). There was a significant decrease in rates of NEC, surgical NEC, and NEC/death between groups. Logistic regression showed this as significant for rates of NEC and surgical NEC between Epoch 1 and 3. Patent ductus arteriosus was a significant variable affecting the incidence of NEC, but not surgical NEC or death/NEC. An umbilical cord milking protocol and pasteurized donor human milk availability was associated with decreased rates of NEC and surgical NEC. This suggests an additive effect of these interventions in preventing NEC.

  1. A critical question for NEC researchers: Can we create a consensus definition of NEC that facilitates research progress?

    PubMed

    Gordon, Phillip V; Swanson, Jonathan R; MacQueen, Brianna C; Christensen, Robert D

    2017-02-01

    In the last decades the reported incidence of preterm necrotizing enterocolitis (NEC) has been declining in large part due to implementing comprehensive NEC prevention initiatives, including breast milk feeding, standardized feeding protocols, transfusion guidelines, and antibiotic stewardship and improving the rigor with which non-NEC cases are excluded from NEC data. However, after more than 60 years of NEC research in animal models, the promise of a "magic bullet" to prevent NEC has yet to materialize. There are also serious issues involving clinical NEC research. There is a lack of a common, comprehensive definition of NEC. National datasets have their own unique definition and staging definitions. Even within academia, randomized trials and single center studies have widely disparate definitions. This makes NEC metadata of very limited value. The world of neonatology needs a comprehensive, universal, consensus definition of NEC. It also needs a de-identified, international data warehouse. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Tumor Infiltration in Enhancing and Non-Enhancing Parts of Glioblastoma: A Correlation with Histopathology.

    PubMed

    Eidel, Oliver; Burth, Sina; Neumann, Jan-Oliver; Kieslich, Pascal J; Sahm, Felix; Jungk, Christine; Kickingereder, Philipp; Bickelhaupt, Sebastian; Mundiyanapurath, Sibu; Bäumer, Philipp; Wick, Wolfgang; Schlemmer, Heinz-Peter; Kiening, Karl; Unterberg, Andreas; Bendszus, Martin; Radbruch, Alexander

    2017-01-01

    To correlate histopathologic findings from biopsy specimens with their corresponding location within enhancing areas, non-enhancing areas and necrotic areas on contrast enhanced T1-weighted MRI scans (cT1). In 37 patients with newly diagnosed glioblastoma who underwent stereotactic biopsy, we obtained a correlation of 561 1mm3 biopsy specimens with their corresponding position on the intraoperative cT1 image at 1.5 Tesla. Biopsy points were categorized as enhancing (CE), non-enhancing (NE) or necrotic (NEC) on cT1 and tissue samples were categorized as "viable tumor cells", "blood" or "necrotic tissue (with or without cellular component)". Cell counting was done semi-automatically. NE had the highest content of tissue categorized as viable tumor cells (89% vs. 60% in CE and 30% NEC, respectively). Besides, the average cell density for NE (3764 ± 2893 cells/mm2) was comparable to CE (3506 ± 3116 cells/mm2), while NEC had a lower cell density with 2713 ± 3239 cells/mm2. If necrotic parts and bleeds were excluded, cell density in biopsies categorized as "viable tumor tissue" decreased from the center of the tumor (NEC, 5804 ± 3480 cells/mm2) to CE (4495 ± 3209 cells/mm2) and NE (4130 ± 2817 cells/mm2). The appearance of a glioblastoma on a cT1 image (circular enhancement, central necrosis, peritumoral edema) does not correspond to its diffuse histopathological composition. Cell density is elevated in both CE and NE parts. Hence, our study suggests that NE contains considerable amounts of infiltrative tumor with a high cellularity which might be considered in resection planning.

  3. Recovery and normalization of triple coincidences in PET.

    PubMed

    Lage, Eduardo; Parot, Vicente; Moore, Stephen C; Sitek, Arkadiusz; Udías, Jose M; Dave, Shivang R; Park, Mi-Ae; Vaquero, Juan J; Herraiz, Joaquin L

    2015-03-01

    Triple coincidences in positron emission tomography (PET) are events in which three γ-rays are detected simultaneously. These events, though potentially useful for enhancing the sensitivity of PET scanners, are discarded or processed without special consideration in current systems, because there is not a clear criterion for assigning them to a unique line-of-response (LOR). Methods proposed for recovering such events usually rely on the use of highly specialized detection systems, hampering general adoption, and/or are based on Compton-scatter kinematics and, consequently, are limited in accuracy by the energy resolution of standard PET detectors. In this work, the authors propose a simple and general solution for recovering triple coincidences, which does not require specialized detectors or additional energy resolution requirements. To recover triple coincidences, the authors' method distributes such events among their possible LORs using the relative proportions of double coincidences in these LORs. The authors show analytically that this assignment scheme represents the maximum-likelihood solution for the triple-coincidence distribution problem. The PET component of a preclinical PET/CT scanner was adapted to enable the acquisition and processing of triple coincidences. Since the efficiencies for detecting double and triple events were found to be different throughout the scanner field-of-view, a normalization procedure specific for triple coincidences was also developed. The effect of including triple coincidences using their method was compared against the cases of equally weighting the triples among their possible LORs and discarding all the triple events. The authors used as figures of merit for this comparison sensitivity, noise-equivalent count (NEC) rates and image quality calculated as described in the NEMA NU-4 protocol for the assessment of preclinical PET scanners. The addition of triple-coincidence events with the authors' method increased peak NEC rates of the scanner by 26.6% and 32% for mouse- and rat-sized objects, respectively. This increase in NEC-rate performance was also reflected in the image-quality metrics. Images reconstructed using double and triple coincidences recovered using their method had better signal-to-noise ratio than those obtained using only double coincidences, while preserving spatial resolution and contrast. Distribution of triple coincidences using an equal-weighting scheme increased apparent system sensitivity but degraded image quality. The performance boost provided by the inclusion of triple coincidences using their method allowed to reduce the acquisition time of standard imaging procedures by up to ∼25%. Recovering triple coincidences with the proposed method can effectively increase the sensitivity of current clinical and preclinical PET systems without compromising other parameters like spatial resolution or contrast.

  4. Liver damage, proliferation, and progenitor cell markers in experimental necrotizing enterocolitis.

    PubMed

    Miyake, Hiromu; Li, Bo; Lee, Carol; Koike, Yuhki; Chen, Yong; Seo, Shogo; Pierro, Agostino

    2018-05-01

    Necrotizing enterocolitis (NEC) is a disease known to cause injury to multiple organs including the liver. Liver regeneration is essential for the recovery after NEC-induced liver injury. Our aim was to investigate hepatic proliferation and progenitor cell marker expression in experimental NEC. Following ethical approval (#32238), NEC was induced in mice by hypoxia, gavage feeding of hyperosmolar formula, and lipopolysaccharide. Breastfed pups were used as control. We analyzed serum ALT level, liver inflammatory cytokines, liver proliferation markers, and progenitor cell marker expression. Comparison was made between NEC and controls. Serum ALT level was higher in NEC (p<0.05). The mRNA expression of inflammatory cytokines in the liver was also higher in NEC (IL6: p<0.05, TNF-α: p<0.01). Conversely, mRNA expression of proliferation markers in the liver was lower in NEC (Ki67; p<0.01, PCNA: p<0.01). LGR5 expression was also significantly decreased in NEC as demonstrated by mRNA (p<0.05) and protein (p<0.01) levels. Inflammatory injury was present in the liver during experimental NEC. Proliferation and LGR5 expression were impaired in the NEC liver. Modulation of progenitor cell expressing LGR5 may result in stimulation of liver regeneration in NEC-induced liver injury and improved clinical outcome. Level IV. Copyright © 2018. Published by Elsevier Inc.

  5. Clostridial Strain-Specific Characteristics Associated with Necrotizing Enterocolitis.

    PubMed

    Schönherr-Hellec, Sophia; Klein, Geraldine L; Delannoy, Johanne; Ferraris, Laurent; Rozé, Jean Christophe; Butel, Marie José; Aires, Julio

    2018-04-01

    We aimed at identifying potential bacterial factors linking clostridia with necrotizing enterocolitis (NEC). We compared the phenotypic traits, stress responses, cellular cytotoxicity, and inflammatory capabilities of the largest collection of Clostridium butyricum and Clostridium neonatale strains isolated from fecal samples of NEC preterm neonates (PN) and control PNs. When strain characteristics were used as explanatory variables, a statistical discriminant analysis allowed the separation of NEC and control strains into separate groups. Strains isolated from NEC PN were characterized by a higher viability at 30°C ( P = 0.03) and higher aerotolerance ( P = 0.01), suggesting that NEC strains may have a competitive and/or survival advantage in the environmental gastrointestinal tract conditions of NEC PN. Heat-treated NEC bacteria induced higher production of interleukin-8 in Caco-2 cells ( P = 0.03), suggesting proinflammatory activity. In vitro , bacteria, bacterial components, and fecal filtrates showed variable cytotoxic effects affecting the cellular network and/or cell viability, without specific association with NEC or control samples. Altogether, our data support the existence of a specific clostridial strain signature associated with NEC. IMPORTANCE Clostridia are part of the commensal microbiota in preterm neonates (PN). However, microbiota analyses by culture and metagenomics have linked necrotizing enterocolitis (NEC) and intestinal colonization with clostridial species. Nevertheless, little is known about the specific characteristics that may be shared by clostridia associated with NEC compared to commensal clostridia. Therefore, our goal was to identify specific bacterial factors linking clostridial strains with NEC. We report the existence of a specific bacterial signature associated with NEC and propose that activation of the innate immune response may be a unifying causative mechanism for the development of NEC independent of a specific pathogenic organism. The present study provides new insights into NEC pathophysiology that are needed for better diagnostics and strategies for implementing prevention of the disease. Copyright © 2018 American Society for Microbiology.

  6. Can a national dataset generate a nomogram for necrotizing enterocolitis onset?

    PubMed

    Gordon, P V; Clark, R; Swanson, J R; Spitzer, A

    2014-10-01

    Mother's own milk and donor human milk use is increasing as a means of necrotizing enterocolitis (NEC) prevention. Early onset of enteral feeding has been associated with improvement of many outcomes but has not been shown to reduce the incidence of NEC. Better definition of the window of risk for NEC by gestational strata should improve resource management with respect to donor human milk and enhance our understanding of NEC timing and pathogenesis. Our objective was to establish a NEC dataset of sufficient size and quality, then build a generalizable model of NEC onset from the dataset across gestational strata. We used de-identified data from the Pediatrix national dataset and filtered out all diagnostic confounders that could be identified by either specific diagnoses or logical exclusions (example dual diagnoses), with a specific focus on NEC and spontaneous intestinal perforation (SIP) as the outcomes of interest. The median day of onset was plotted against the gestational age for each of these diagnoses and analyzed for similarities and differences in the day of diagnosis. Onset time of medical NEC was inversely proportional to gestation in a linear relationship across all gestational ages. We found the medical NEC dataset displayed characteristics most consistent with a homogeneous disease entity, whereas there was a skew towards early presentation in the youngest gestation groups of surgical NEC (suggesting probable SIP contamination). Our national dataset demonstrates that NEC onset occurs in an inverse stereotypic, linear relationship with gestational age at birth. Medical NEC is the most reliable sub-cohort for the purpose of determining the temporal window of NEC risk.

  7. Effects of boric acid and 2-aminoethoxydiphenyl borate on necrotizing enterocolitis.

    PubMed

    Yazıcı, Selçuk; Akşit, Hasan; Korkut, Oğuzhan; Sunay, Bahar; Çelik, Tanju

    2014-01-01

    The aim was to study the effects of boric acid (BA) and 2-aminoethoxydiphenyl borate (2-APB) on oxidative stress and inflammation in an experimental necrotizing enterocolitis (NEC) rat model. Experimental NEC was induced in 40 newborn Sprague-Dawley rats by asphyxia and hypothermia applied in 3 consecutive days. Rats were subdivided into 4 subgroups as NEC, NEC+BA, NEC+2-APB, and controls. BA and 2-APB were applied daily before the procedure. Serum total antioxidant status, superoxide dismutase (SOD), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and erythrocyte glutathione (GSH) levels were measured. Pathological changes for NEC in intestinal architecture were evaluated by a grading system. Pretreatment with BA and 2-APB resulted in a decrease in NEC incidence. In all of the NEC groups, decreased serum levels of GSH and SOD were measured. Boron limited GSH consumption but had no effect on SOD levels. Total antioxidant status levels were not statistically different among groups. In our experimental NEC model, BA, but not 2-APB, prevented the increase of TNF-α. Pretreatment with BA and 2-APB downregulated the activity levels of IL-6 in NEC. In the experimental NEC model, BA and 2-APB partly prevent NEC formation, modulate the oxidative stress parameters, bring a significant decrease in GSH consumption, and enhance the antioxidant defense mechanism, but have no effect on total antioxidant status. BA inhibits the hypoxia and hypothermia-induced increase in both IL-6 and TNF-a, but 2-APB only in IL-6. Boron may be beneficial in preventing NEC.

  8. Outcomes of Left Ventricular Function According to Treatment Response for a Patent Ductus Arteriosus in Preterm Infants.

    PubMed

    Kang, Soo Jung; Cho, Young Sun; Hwang, Seo Jung; Kim, Hyo Jin

    2017-12-01

    To evaluate the outcomes of left ventricular (LV) function according to treatment response for a hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants. Echocardiograms of 21 preterm infants born at gestational age < 31 weeks obtained at term-equivalent age were retrospectively studied. Among preterm infants with a hsPDA, 9 underwent ligation after failure of pharmacological closure (ligation group) and 6 experienced successful pharmacological closure (medication group). Six preterm infants without hsPDA (no-hsPDA group) were studied as controls. LV peak longitudinal systolic strain (ε) of each infant was retrospectively obtained from echocardiograms using velocity vector imaging, along with neonatal outcomes. Pharmacological closures were attempted at postnatal day 2-3. In the ligation group, the median postnatal age at ligation was 20 days. In the ligation group, LV peak longitudinal systolic ε was significantly decreased at term-equivalent age compared to the other groups. Between the medication and no-hsPDA groups, LV peak longitudinal systolic ε did not differ significantly. Among the neonatal outcomes, infants who experienced necrotizing enterocolitis (NEC) showed significantly decreased LV peak longitudinal systolic ε compared to the infants who did not experience NEC . We speculate that in preterm infants with an hsPDA, in cases of medical treatment failure, early PDA ligation at less than 20 days of postnatal age would be beneficial for preserving LV systolic function.

  9. Association of necrotizing enterocolitis with anemia and packed red blood cell transfusions in preterm infants

    PubMed Central

    Singh, Rachana; Visintainer, Paul F.; Frantz, Ivan D.; Shah, Bhavesh L.; Meyer, Kathleen M.; Favila, Sarah A.; Thomas, Meredith S.; Kent, David M.

    2011-01-01

    Objective To determine association of anemia and RBC transfusions with NEC in preterm infants. Study Design 111 preterm infants with NEC ≥ Stage 2a were compared with 222 matched controls. 28 clinical variables, including hematocrit and RBC transfusions were recorded. Propensity scores and multivariate logistic regression models were created to examine effects on the risk of NEC. Results Controlling for other factors, lower hematocrit was associated with increased odds of NEC [OR 1.10, p =0.01]. RBC transfusion has a temporal relationship with NEC onset. Transfusion within 24h (OR=7.60, p=0.001) and 48h (OR=5.55, p=0.001) has a higher odds of developing NEC but this association is not significant by 96h (OR= 2.13, p =0.07), post transfusion Conclusions Anemia may increase the risk of developing NEC in preterm infants. RBC transfusions are temporally related to NEC. Prospective studies are needed to better evaluate the potential influence of transfusions on the development of NEC. PMID:21273983

  10. Differential disease resistance response in the barley necrotic mutant nec1.

    PubMed

    Keisa, Anete; Kanberga-Silina, Krista; Nakurte, Ilva; Kunga, Laura; Rostoks, Nils

    2011-04-15

    Although ion fluxes are considered to be an integral part of signal transduction during responses to pathogens, only a few ion channels are known to participate in the plant response to infection. CNGC4 is a disease resistance-related cyclic nucleotide-gated ion channel. Arabidopsis thaliana CNGC4 mutants hlm1 and dnd2 display an impaired hypersensitive response (HR), retarded growth, a constitutively active salicylic acid (SA)-mediated pathogenesis-related response and elevated resistance against bacterial pathogens. Barley CNGC4 shares 67% aa identity with AtCNGC4. The barley mutant nec1 comprising of a frame-shift mutation of CNGC4 displays a necrotic phenotype and constitutively over-expresses PR-1, yet it is not known what effect the nec1 mutation has on barley resistance against different types of pathogens. nec1 mutant accumulated high amount of SA and hydrogen peroxide compared to parental cv. Parkland. Experiments investigating nec1 disease resistance demonstrated positive effect of nec1 mutation on non-host resistance against Pseudomonas syringae pv. tomato (Pst) at high inoculum density, whereas at normal Pst inoculum concentration nec1 resistance did not differ from wt. In contrast to augmented P. syringae resistance, penetration resistance against biotrophic fungus Blumeria graminis f. sp. hordei (Bgh), the causal agent of powdery mildew, was not altered in nec1. The nec1 mutant significantly over-expressed race non-specific Bgh resistance-related genes BI-1 and MLO. Induction of BI-1 and MLO suggested putative involvement of nec1 in race non-specific Bgh resistance, therefore the effect of nec1on mlo-5-mediated Bgh resistance was assessed. The nec1/mlo-5 double mutant was as resistant to Bgh as Nec1/mlo-5 plants, suggesting that nec1 did not impair mlo-5 race non-specific Bgh resistance. Together, the results suggest that nec1 mutation alters activation of systemic acquired resistance-related physiological markers and non-host resistance in barley, while not changing rapid localized response during compatible interaction with host pathogen. Increased resistance of nec1 against non-host pathogen Pst suggests that nec1 mutation may affect certain aspects of barley disease resistance, while it remains to be determined, if the effect on disease resistance is a direct response to changes in SA signaling. © 2011 Keisa et al; licensee BioMed Central Ltd.

  11. Incidence and timing of presentation of necrotizing enterocolitis in preterm infants.

    PubMed

    Yee, Wendy H; Soraisham, Amuchou Singh; Shah, Vibhuti S; Aziz, Khalid; Yoon, Woojin; Lee, Shoo K

    2012-02-01

    To examine the variation in the incidence and to identify the timing of the presentation of necrotizing enterocolitis (NEC) in a cohort of preterm infants within the Canadian Neonatal Network (CNN). This was a population-based cohort of 16 669 infants with gestational age (GA) <33 weeks, admitted to 25 NICUs participating in the CNN between January 1, 2003, and December 31(,) 2008. Variations in NEC incidence among the participating NICUs for the study period were examined. We categorized early-onset NEC as occurring at <14 days of age and late-onset NEC occurring at ≥14 days. Multivariate logistic regression analysis was performed to identify risk factors for early-onset NEC. The overall incidence of NEC was 5.1%, with significant variation in the risk adjusted incidence among the participating NICUs in the CNN. Early-onset NEC occurred at a mean of 7 days compared with 32 days for late-onset NEC. Early-onset NEC infants had lower incidence of respiratory distress syndrome, patent ductus treated with indomethacin, less use of postnatal steroids, and shorter duration of ventilation days. Multivariate logistic regression analysis identified that greater GA and vaginal delivery were associated with increased risk of early-onset NEC. Among infants <33 weeks' gestation, NEC appears to present at mean age of 7 days in more mature infants, whereas onset of NEC is delayed to 32 days of age in smaller, lower GA infants. Further studies are required to understand the etiology of this disease process.

  12. Linking Training Course Support to Fleet Platforms: An Equipment-Based Approach.

    DTIC Science & Technology

    1981-01-01

    6408 ZDB:ZT-2154T CAT:AP NEC 1: NEC 2: REQUIREMENT SPONSOR:OP-120E RESOURCE SPONSOR:OP-Ol COURSE TITLE - BE/E-ET-COMM 4YO ACTIVITY ADDRESS...CAT:AP NEC 1: NEC 2: REQUIREMENT SPONSOR:OP-120E RESOURCE SPONSOR:OP-01 COURSE TITLE - BE/E-ET-RAD 4YO ACTIVITY ADDRESS- SERVSCOLCOM SAN DIEGO FIND...0454S CAT:AP NEC 1: NEC 2: REQUIREMENT SPONSOR:OP-120E RESOURCE SPONSOR:OP-O1 COURSE TITLE - BE/E-ET-COMM 4YO ACTIVITY ADDRESS- SERVSCOLCOM GREAT LAKES

  13. Longitudinal Analysis of the Premature Infant Intestinal Microbiome Prior to Necrotizing Enterocolitis: A Case-Control Study

    PubMed Central

    Zhou, Yanjiao; Shan, Gururaj; Sodergren, Erica; Weinstock, George; Walker, W. Allan; Gregory, Katherine E.

    2015-01-01

    Necrotizing enterocolitis (NEC) is an inflammatory disease of the newborn bowel, primarily affecting premature infants. Early intestinal colonization has been implicated in the pathogenesis of NEC. The objective of this prospective case-control study was to evaluate differences in the intestinal microbiota between infants who developed NEC and unaffected controls prior to disease onset. We conducted longitudinal analysis of the 16S rRNA genes of 312 samples obtained from 12 NEC cases and 26 age-matched controls with a median frequency of 7 samples per subject and median sampling interval of 3 days. We found that the microbiome undergoes dynamic development during the first two months of life with day of life being the major factor contributing to the colonization process. Depending on when the infant was diagnosed with NEC (i.e. early vs. late onset), the pattern of microbial progression was different for cases and controls. The difference in the microbiota was most overt in early onset NEC cases and controls. In proximity to NEC onset, the abundances of Clostridium sensu stricto from Clostridia class were significantly higher in early onset NEC subjects comparing to controls. In late onset NEC, Escherichia/Shigella among Gammaproteobacteria, showed an increasing pattern prior to disease onset, and was significantly higher in cases than controls six days before NEC onset. Cronobacter from Gammaproteobacteria was also significantly higher in late onset NEC cases than controls 1-3 days prior to NEC onset. Thus, the specific infectious agent associated with NEC may vary by the age of infant at disease onset. We found that intravenously administered antibiotics may have an impact on the microbial diversity present in fecal material. Longitudinal analysis at multiple time points was an important strategy utilized in this study, allowing us to appreciate the dynamics of the premature infant intestinal microbiome while approaching NEC at various points. PMID:25741698

  14. A data-driven algorithm integrating clinical and laboratory features for the diagnosis and prognosis of necrotizing enterocolitis.

    PubMed

    Ji, Jun; Ling, Xuefeng B; Zhao, Yingzhen; Hu, Zhongkai; Zheng, Xiaolin; Xu, Zhening; Wen, Qiaojun; Kastenberg, Zachary J; Li, Ping; Abdullah, Fizan; Brandt, Mary L; Ehrenkranz, Richard A; Harris, Mary Catherine; Lee, Timothy C; Simpson, B Joyce; Bowers, Corinna; Moss, R Lawrence; Sylvester, Karl G

    2014-01-01

    Necrotizing enterocolitis (NEC) is a major source of neonatal morbidity and mortality. Since there is no specific diagnostic test or risk of progression model available for NEC, the diagnosis and outcome prediction of NEC is made on clinical grounds. The objective in this study was to develop and validate new NEC scoring systems for automated staging and prognostic forecasting. A six-center consortium of university based pediatric teaching hospitals prospectively collected data on infants under suspicion of having NEC over a 7-year period. A database comprised of 520 infants was utilized to develop the NEC diagnostic and prognostic models by dividing the entire dataset into training and testing cohorts of demographically matched subjects. Developed on the training cohort and validated on the blind testing cohort, our multivariate analyses led to NEC scoring metrics integrating clinical data. Machine learning using clinical and laboratory results at the time of clinical presentation led to two nec models: (1) an automated diagnostic classification scheme; (2) a dynamic prognostic method for risk-stratifying patients into low, intermediate and high NEC scores to determine the risk for disease progression. We submit that dynamic risk stratification of infants with NEC will assist clinicians in determining the need for additional diagnostic testing and guide potential therapies in a dynamic manner. http://translationalmedicine.stanford.edu/cgi-bin/NEC/index.pl and smartphone application upon request.

  15. Maternal Risk Factors for Neonatal Necrotizing Enterocolitis

    PubMed Central

    March, Melissa I.; Gupta, Munish; Modest, Anna M.; Wu, Lily; Hacker, Michele R.; Martin, Camilia R.; Rana, Sarosh

    2015-01-01

    Objective This study aimed to investigate the relationship between maternal hypertensive disease and other risk factors and the neonatal development of necrotizing enterocolitis (NEC). Methods This was a retrospective case control study of infants with NEC from 2008 to 2012. The primary exposure of interest was maternal hypertensive disease, which has been hypothesized to put infants at risk for NEC. Other variables collected included demographics, pregnancy complications, medications, and neonatal hospital course. Data was abstracted from medical records. Results 28 cases of singleton neonates with NEC and 81 matched controls were identified and analyzed. There was no significant difference in the primary outcome. Fetuses with an antenatal diagnosis of growth restriction were more likely to develop NEC (p=0.008). Infants with NEC had lower median birth weight than infants without NEC (p=0.009). Infants with NEC had more late-onset sepsis (p=0.01) and mortality before discharge (p=0.001). Conclusions The factors identified by this case-control study that increased the risk of neonatal NEC included intrauterine growth restriction and lower neonatal birth weight. The primary exposure, hypertensive disease, did not show a significantly increased risk of neonatal NEC, however there was a nearly two-fold difference observed. Our study was underpowered to detect the observed difference. PMID:25162307

  16. A Functional ATG16L1 (T300A) Variant is Associated with Necrotizing Enterocolitis in Premature Infants

    PubMed Central

    Sampath, Venkatesh; Bhandari, Vineet; Berger, Jessica; Merchant, Daniel; Zhang, Liyun; Ladd, Mihoko; Menden, Heather; Garland, Jeffery; Ambalavanan, Namasivayam; Mulrooney, Neil; Quasney, Michael; Dagle, John; Lavoie, Pascal M; Simpson, Pippa; Dahmer, Mary

    2017-01-01

    Background The genetic basis of dysfunctional immune responses in necrotizing enterocolitis (NEC) remains unknown. We hypothesized that variants in Nucleotide binding and Oligomerization Domain (NOD)-Like Receptors (NLRs) and Autophagy (ATG) genes modulate vulnerability to NEC. Methods We genotyped a multi-center cohort of premature infants with and without NEC for NOD1, NOD2, ATG16L1, CARD8 and NLRP3 variants. Chi-square tests and logistic regression were used for statistical analysis. Results In our primary cohort (n=1015), 86 (8.5%) infants developed NEC. The A allele of the ATG16L1 (Thr300Ala) variant was associated with increased NEC (AA vs. AG vs. GG; 11.3% vs. 8.4% vs. 4.8%, p=0.009). In regression models for NEC that adjusted for epidemiological confounders, GA (p=0.033) and the AA genotype (p=0.038) of ATG16L1 variant were associated with NEC. The association between the A allele of the ATG16L1 variant and NEC remained significant among Caucasian infants (p=0.02). In a replication cohort (n=259), NEC rates were highest among infants with the AA genotype but did not reach statistical significance. Conclusion We report a novel association between a hypomorphic variant in an autophagy gene (ATG16L1) and NEC in premature infants. Our data suggest that decreased autophagy arising from genetic variants may confer protection against NEC. PMID:27893720

  17. MR imaging features and staging of neuroendocrine carcinomas of the uterine cervix with pathological correlations.

    PubMed

    Duan, Xiaohui; Ban, Xiaohua; Zhang, Xiang; Hu, Huijun; Li, Guozhao; Wang, Dongye; Wang, Charles Qian; Zhang, Fang; Shen, Jun

    2016-12-01

    To determine MR imaging features and staging accuracy of neuroendocrine carcinomas (NECs) of the uterine cervix with pathological correlations. Twenty-six patients with histologically proven NECs, 60 patients with squamous cell carcinomas (SCCs), and 30 patients with adenocarcinomas of the uterine cervix were included. The clinical data, pathological findings, and MRI findings were reviewed retrospectively. MRI features of cervical NECs, SCCs, and adenocarcinomas were compared, and MRI staging of cervical NECs was compared with the pathological staging. Cervical NECs showed a higher tendency toward a homogeneous signal intensity on T2-weighted imaging and a homogeneous enhancement pattern, as well as a lower ADC value of tumour and a higher incidence of lymphadenopathy, compared with SCCs and adenocarcinomas (P < 0.05). An ADC value cutoff of 0.90 × 10 -3  mm 2 /s was robust for differentiation between cervical NECs and other cervical cancers, with a sensitivity of 63.3 % and a specificity of 95 %. In 21 patients who underwent radical hysterectomy and lymphadenectomy, the overall accuracy of tumour staging by MR imaging was 85.7 % with reference to pathology staging. Homogeneous lesion texture and low ADC value are likely suggestive features of cervical NECs and MR imaging is reliable for the staging of cervical NECs. • Cervical NECs show a tendency of lesion homogeneity and lymphadenopathy • Low ADC values are found in cervical NECs • MRI is an accurate imaging modality for the cervical NEC staging.

  18. Cost savings of human milk as a strategy to reduce the incidence of necrotizing enterocolitis in very low birth weight infants.

    PubMed

    Johnson, Tricia J; Patel, Aloka L; Bigger, Harold R; Engstrom, Janet L; Meier, Paula P

    2015-01-01

    Necrotizing enterocolitis (NEC) is a costly morbidity in very low birth weight (VLBW; <1,500 g birth weight) infants that increases hospital length of stay and requires expensive treatments. To evaluate the cost of NEC as a function of dose and exposure period of human milk (HM) feedings received by VLBW infants during the neonatal intensive care unit (NICU) hospitalization and determine the drivers of differences in NICU hospitalization costs for infants with and without NEC. This study included 291 VLBW infants enrolled in an NIH-funded prospective observational cohort study between February 2008 and July 2012. We examined the incidence of NEC, NICU hospitalization cost, and cost of individual resources used during the NICU hospitalization. Twenty-nine (10.0%) infants developed NEC. The average total NICU hospitalization cost (in 2012 USD) was USD 180,163 for infants with NEC and USD 134,494 for infants without NEC (p = 0.024). NEC was associated with a marginal increase in costs of USD 43,818, after controlling for demographic characteristics, risk of NEC, and average daily dose of HM during days 1-14 (p < 0.001). Each additional ml/kg/day of HM during days 1-14 decreased non-NEC-related NICU costs by USD 534 (p < 0.001). Avoidance of formula and use of exclusive HM feedings during the first 14 days of life is an effective strategy to reduce the risk of NEC and resulting NICU costs in VLBW infants. Hospitals investing in initiatives to feed exclusive HM during the first 14 days of life could substantially reduce NEC-related NICU hospitalization costs. © 2015 S. Karger AG, Basel.

  19. Cost Savings of Human Milk as a Strategy to Reduce the Incidence of Necrotizing Enterocolitis in Very Low Birth Weight Infants

    PubMed Central

    Johnson, Tricia J.; Patel, Aloka L.; Bigger, Harold R.; Engstrom, Janet L.; Meier, Paula P.

    2015-01-01

    Background Necrotizing enterocolitis (NEC) is a costly morbidity in very low birth weight (VLBW; <1500g birth weight) infants that increases hospital length of stay and requires expensive treatments. Objectives To evaluate the cost of NEC as a function of dose and exposure period of human milk (HM) feedings received by VLBW infants during the neonatal intensive care unit (NICU) hospitalization and determine the drivers of differences in NICU hospitalization costs for infants with and without NEC. Methods This study included 291 VLBW infants enrolled in an NIH-funded prospective observational cohort study between February 2008 and July 2012. We examined the incidence of NEC, NICU hospitalization cost, and cost of individual resources used during the NICU hospitalization. Results Twenty-nine (10.0%) infants developed NEC. The average total NICU hospitalization cost (in 2012 dollars) was $180,163 for infants with NEC and $134,494 for infants without NEC (p=0.024). NEC was associated with a marginal increase in costs of $43,818, after controlling for demographic characteristics, risk of NEC and average daily dose of HM during Days 1–14 (p<0.001). Each additional mL/kg/day of HM during Days 1–14 decreased non-NEC-related NICU costs by $534 (p<0.001). Conclusions Avoidance of formula and use of exclusive HM feedings during the first 14 days of life is an effective strategy to reduce the risk of NEC and resulting NICU costs in VLBW infants. Hospitals investing in initiatives to feed exclusive HM during the first 14 days of life could substantially reduce NEC-related NICU hospitalization costs. PMID:25765818

  20. Rapid and sensitive quantification of isotopic mixtures using a rapidly-swept external cavity quantum cascade laser

    DOE PAGES

    Brumfield, Brian E.; Taubman, Matthew S.; Phillips, Mark C.

    2016-05-23

    A rapidly-swept external-cavity quantum cascade laser with an open-path Herriott cell is used to quantify gas-phase chemical mixtures of D 2O and HDO at a rate of 40 Hz (25-ms measurement time). The chemical mixtures were generated by evaporating D 2O liquid near the open-path Herriott cell, allowing the H/D exchange reaction with ambient H 2O to produce HDO. Fluctuations in the ratio of D 2O and HDO on timescales of <1 s due to the combined effects of plume transport and the H/D exchange chemical reaction are observed. Noise-equivalent concentrations (1σ) (NEC) of 147.0 ppbv and 151.6 ppbv inmore » a 25-ms measurement time are determined for D 2O and HDO, respectively, with a 127-m optical path. These NECs are improved to 23.0 and 24.0 ppbv with a 1-s averaging time for D 2O and HDO, respectively. NECs <200 ppbv are also estimated for N2O, 1,1,1,2–tetrafluoroethane (F134A), CH 4, acetone and SO 2 for a 25-ms measurement time. Finally, the isotopic precision for measurement of the [D 2O]/[HDO] concentration ratio of 33‰ and 5‰ is calculated for the current experimental conditions for measurement times of 25 ms and 1 s, respectively.« less

  1. Probiotics for the prevention of necrotizing enterocolitis in neonates: an 8-year retrospective cohort study.

    PubMed

    Li, D; Rosito, G; Slagle, T

    2013-12-01

    Probiotic therapy has been shown to reduce morbidity and mortality of necrotizing enterocolitis (NEC) in premature infants in several international studies using various probiotic agents. The purpose of this study(*) is to describe our experience of using probiotic therapy in preventing NEC in infants with very low birth weight (VLBW) in a neonatal intensive care unit (NICU) and to evaluate whether our records provide evidence of effectiveness for probiotic therapy. In a retrospective cohort study, the efficacy of probiotic therapy in preventing NEC in VLBW infants was investigated via chart review. A probiotic administration protocol using a three-strain (Streptococcus thermophilus, Bifidobacterium infantis and Bifidobacterium bifidum) supplement was implemented in August 2007. Patients admitted to the NICU from August 2003 through July 2011 were screened. Primary outcomes are the morbidity and mortality of NEC. The secondary outcomes were severity of NEC and incidence of where infant feeds were stopped but NEC was not diagnosed (NEC scare). There was a significant increased baseline risk of NEC development in the probiotics group, including younger gestational age, higher incidence of patent ductus arteriosus (PDA) and use of indomethacin. The incidence of NEC is similar between the control group (2·8%) and probiotics group (2·4%) (hazard ratio, 1·15; 95% confidence interval [CI], 0·42, 3·12). Mortality of NEC is also not statistically different. Incidence of NEC scare was decreased from 2·8% in control group to 1·4% in probiotics group, although the difference was not statistically significant (P = 0·38). Our findings suggest that probiotics are safe in NEC prevention in VLBW infants. We had no cases of infection related to the strains of bacteria used in our product. With the low incidence of NEC (2·8%) and NEC scare (2·8%) in our cohort, we do not have enough power to detect any change in outcome, particularly as our study was observational. However, it is hoped that our data give useful information for others on probiotic prophylactic therapy in the routine clinical management of VLBW infants. © 2013 John Wiley & Sons Ltd.

  2. Poly(ADP-Ribose) Polymerase-1: A Novel Therapeutic Target in Necrotizing Enterocolitis

    PubMed Central

    Giannone, Peter J.; Alcamo, Alicia A.; Schanbacher, Brandon L.; Nankervis, Craig A.; Besner, Gail E.; Bauer, John A.

    2011-01-01

    Necrotizing enterocolitis (NEC) is the most common gastrointestinal disease of infancy, afflicting 11% of infants born 22–28 weeks gestational age. Both inflammation and oxidation may be involved in NEC pathogenesis through reactive nitrogen species production, protein oxidation and DNA damage. Poly(ADP-ribose) polymerase-1 (PARP-1) is a critical enzyme activated to facilitate DNA repair using nicotinamide adenine dinucleotide (NAD+) as a substrate. However, in the presence of severe oxidative stress and DNA damage, PARP-1 over-activation may ensue, depleting cells of NAD+ and ATP, killing them by metabolic catastrophe. Here we tested the hypothesis that NO dysregulation in intestinal epithelial cells during NEC leads to marked PARP-1 expression and that administration of a PARP-1 inhibitor (nicotinamide) attenuates intestinal injury in a newborn rat model of NEC. In this model, 56% of control pups developed NEC (any stage), versus 14% of pups receiving nicotinamide. Forty-four percent of control pups developed high-grade NEC (grades 3–4), whereas only 7% of pups receiving nicotinamide developed high-grade NEC. Nicotinamide treatment protects pups against intestinal injury incurred in the newborn rat NEC model. We speculate that PARP-1 over-activation in NEC may drive mucosal cell death in this disease and that PARP-1 may be a novel therapeutic target in NEC. PMID:21399558

  3. Outcomes of Left Ventricular Function According to Treatment Response for a Patent Ductus Arteriosus in Preterm Infants

    PubMed Central

    Cho, Young Sun; Hwang, Seo Jung; Kim, Hyo Jin

    2017-01-01

    Background To evaluate the outcomes of left ventricular (LV) function according to treatment response for a hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants. Methods Echocardiograms of 21 preterm infants born at gestational age < 31 weeks obtained at term-equivalent age were retrospectively studied. Among preterm infants with a hsPDA, 9 underwent ligation after failure of pharmacological closure (ligation group) and 6 experienced successful pharmacological closure (medication group). Six preterm infants without hsPDA (no-hsPDA group) were studied as controls. LV peak longitudinal systolic strain (ε) of each infant was retrospectively obtained from echocardiograms using velocity vector imaging, along with neonatal outcomes. Results Pharmacological closures were attempted at postnatal day 2–3. In the ligation group, the median postnatal age at ligation was 20 days. In the ligation group, LV peak longitudinal systolic ε was significantly decreased at term-equivalent age compared to the other groups. Between the medication and no-hsPDA groups, LV peak longitudinal systolic ε did not differ significantly. Among the neonatal outcomes, infants who experienced necrotizing enterocolitis (NEC) showed significantly decreased LV peak longitudinal systolic ε compared to the infants who did not experience NEC . Conclusion We speculate that in preterm infants with an hsPDA, in cases of medical treatment failure, early PDA ligation at less than 20 days of postnatal age would be beneficial for preserving LV systolic function. PMID:29333220

  4. Enteric serotonin and oxytocin: endogenous regulation of severity in a murine model of necrotizing enterocolitis.

    PubMed

    Gross Margolis, Kara; Vittorio, Jennifer; Talavera, Maria; Gluck, Karen; Li, Zhishan; Iuga, Alina; Stevanovic, Korey; Saurman, Virginia; Israelyan, Narek; Welch, Martha G; Gershon, Michael D

    2017-11-01

    Necrotizing enterocolitis (NEC), a gastrointestinal inflammatory disease of unknown etiology that may also affect the liver, causes a great deal of morbidity and mortality in premature infants. We tested the hypothesis that signaling molecules, which are endogenous to the bowel, regulate the severity of intestinal and hepatic damage in an established murine NEC model. Specifically, we postulated that mucosal serotonin (5-HT), which is proinflammatory, would exacerbate experimental NEC and that oxytocin (OT), which is present in enteric neurons and is anti-inflammatory, would oppose it. Genetic deletion of the 5-HT transporter (SERT), which increases and prolongs effects of 5-HT, was found to increase the severity of systemic manifestations, intestinal inflammation, and associated hepatotoxicity of experimental NEC. In contrast, genetic deletion of tryptophan hydroxylase 1 (TPH1), which is responsible for 5-HT biosynthesis in enterochromaffin (EC) cells of the intestinal mucosa, and TPH inhibition with LP-920540 both decrease the severity of experimental NEC in the small intestine and liver. These observations suggest that 5-HT from EC cells helps to drive the inflammatory damage to the gut and liver that occurs in the murine NEC model. Administration of OT decreased, while the OT receptor antagonist atosiban exacerbated, the intestinal inflammation of experimental NEC. Data from the current investigation are consistent with the tested hypotheses-that the enteric signaling molecules, 5-HT (positively) and OT (negatively) regulate severity of inflammation in a mouse model of NEC. Moreover, we suggest that mucosally restricted inhibition of 5-HT biosynthesis and/or administration of OT may be useful in the treatment of NEC. NEW & NOTEWORTHY Serotonin (5-HT) and oxytocin reciprocally regulate the severity of intestinal inflammation and hepatotoxicity in a murine model of necrotizing enterocolitis (NEC). Selective depletion of mucosal 5-HT through genetic deletion or inhibition of tryptophan hydroxylase-1 ameliorates, while deletion of the 5-HT uptake transporter, which increases 5-HT availability, exacerbates the severity of NEC. In contrast, oxytocin reduces, while the oxytocin receptor antagonist atosiban enhances, NEC severity. Peripheral tryptophan hydroxylase inhibition may be useful in treatment of NEC. Copyright © 2017 the American Physiological Society.

  5. Sonic hedgehog (Shh)/Gli modulates the spatial organization of neuroepithelial cell proliferation in the developing chick optic tectum.

    PubMed

    Rapacioli, Melina; Botelho, Joao; Cerda, Gustavo; Duarte, Santiago; Elliot, Matías; Palma, Verónica; Flores, Vladimir

    2012-10-02

    Sonic hedgehog (Shh)/Gli pathway plays an important regulatory role on the neuroepithelial cells (NEc) proliferation in the dorsal regions of the developing vertebrate Central Nervous System. The aim of this paper was to analyze the effect of the Shh/Gli signaling pathway activation on the proliferation dynamics and/or the spatial organization of the NEc proliferation activity during early stages of the developing chick optic tectum (OT). In ovo pharmacological gain and loss of hedgehog function approaches were complemented with in vivo electroporation experiments in order to create ectopic sources of either Shh or Gli activator (GliA) proteins in the OT. NEc proliferating activity was analyzed at ED 4/4.5 by recording the spatial co-ordinates of the entire population of mitotic NEc (mNEc) located along OT dorsal-ventral sections. Several space signals (numerical sequences) were derived from the mNEc spatial co-ordinate records and analyzed by different standardized non-linear methods of signal analysis. In ovo pharmacologic treatment with cyclopamine resulted in dramatic failure in the OT expansion while the agonist purmorphamine produced the opposite result, a huge expansion of the OT vesicle. Besides, GliA and Shh misexpressions interfere with the formation of the intertectal fissure located along the dorsal midline. This morphogenetic alteration is accompanied by an increase in the mNEc density. There is a gradient in the response of NEcs to Shh and GliA: the increase in mNEc density is maximal near the dorsal regions and decrease towards the OT-tegmental boundary. Biomathematical analyses of the signals derived from the mNEc records show that both Shh and GliA electroporations change the proliferation dynamics and the spatial organization of the mNEc as revealed by the changes in the scaling index estimated by these methods. The present results show that the Shh/Gli signaling pathway plays a critical role in the OT expansion and modelling. This effect is probably mediated by a differential mitogenic effect that increases the NEc proliferation and modulates the spatial organization of the NEc proliferation activity.

  6. Effect of routine probiotic, Lactobacillus reuteri DSM 17938, use on rates of necrotizing enterocolitis in neonates with birthweight < 1000 grams: a sequential analysis.

    PubMed

    Hunter, Chelsea; Dimaguila, Mary Ann V T; Gal, Peter; Wimmer, John E; Ransom, James Laurence; Carlos, Rita Q; Smith, McCrae; Davanzo, Christie C

    2012-09-04

    Necrotizing enterocolitis (NEC) is a disease in neonates, often resulting in death or serious medical or neurodevelopmental complications. The rate of NEC is highest in the smallest babies and many efforts have been tried to reduce the rate of NEC. In neonates born below 1500 grams, the rate of NEC has been significantly reduced with the use of various probiotics. This study examines the impact of routine use of a probiotic, Lactobacillus reuteri DSM 17938 (BioGaia®), on the rate of NEC in neonates at highest risk for developing NEC, those with birth weight ≤1000 grams. This is a retrospective cohort study comparing the rates of NEC in neonates with birth weight ≤ 1000 grams. The groups are separated into those neonates born from January 2004 to June 30, 2009, before introduction of L. reuteri , and neonates born July 2009 through April 2011 who received routine L. reuteri prophylaxis. The chart review study was approved by our institutional review board and exempted from informed consent.Neonates were excluded if they died or were transferred within the first week of life. The remainder were categorized as having no NEC, medical NEC, surgical NEC, or NEC associated death. Since no major changes occurred in our NICU practice in recent years, and the introduction of L. reuteri as routine prophylaxis was abrupt, we attributed the post-probiotic changes to the introduction of this new therapy. Rates of NEC were compared using Chi square analysis with Fisher exact t-test. Medical records for 311 neonates were reviewed, 232 before- and 79 after-introduction of L. reuteri prophylaxis. The incidence of NEC was significantly lower in the neonates who received L. reuteri (2 of 79 neonates [2.5%] versus 35 of 232 untreated neonates [15.1%]). Rates of late-onset gram-negative or fungal infections (22.8 versus 31%) were not statistically different between treated and untreated groups. No adverse events related to use of L reuteri were noted. Prophylactic initiation of L. reuteri as a probiotic for prevention of necrotizing enterocolitis resulted in a statistically significant benefit, with avoidance of 1 NEC case for every 8 patients given prophylaxis.

  7. Long term healthcare costs of infants who survived neonatal necrotizing enterocolitis: a retrospective longitudinal study among infants enrolled in Texas Medicaid

    PubMed Central

    2013-01-01

    Background Infants who survive advanced necrotizing enterocolitis (NEC) at the time of birth are at increased risk of having poor long term physiological and neurodevelopmental growth. The economic implications of the long term morbidity in these children have not been studied to date. This paper compares the long term healthcare costs beyond the initial hospitalization period incurred by medical and surgical NEC survivors with that of matched controls without a diagnosis of NEC during birth hospitalization. Methods The longitudinal healthcare utilization claim files of infants born between January 2002 and December 2003 and enrolled in the Texas Medicaid fee-for-service program were used for this research. Propensity scoring was used to match infants diagnosed with NEC during birth hospitalization to infants without a diagnosis of NEC on the basis of gender, race, prematurity, extremely low birth weight status and presence of any major birth defects. The Medicaid paid all-inclusive healthcare costs for the period from 6 months to 3 years of age among children in the medical NEC, surgical NEC and matched control groups were evaluated descriptively, and in a generalized linear regression framework in order to model the impact of NEC over time and by birth weight. Results Two hundred fifty NEC survivors (73 with surgical NEC) and 2,909 matched controls were available for follow-up. Medical NEC infants incurred significantly higher healthcare costs than matched controls between 6–12 months of age (mean incremental cost = US$ 5,112 per infant). No significant difference in healthcare costs between medical NEC infants and matched controls was seen after 12 months. Surgical NEC survivors incurred healthcare costs that were consistently higher than that of matched controls through 36 months of age. The mean incremental healthcare costs of surgical NEC infants compared to matched controls between 6–12, 12–24 and 24–36 months of age were US$ 18,274, 14,067 (p < 0.01) and 8,501 (p = 0.06) per infant per six month period, respectively. These incremental costs were found to vary between sub-groups of infants born with birth weight < 1,000g versus ≥ 1,000g (p < 0.05). Conclusions The all-inclusive healthcare costs of surgical NEC survivors continued to be substantially higher than that of matched controls through the early childhood development period. These results can have important treatment and policy implications. Further research in this topic is needed. PMID:23962093

  8. Recovery and normalization of triple coincidences in PET

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

    Lage, Eduardo, E-mail: elage@mit.edu; Parot, Vicente; Dave, Shivang R.

    2015-03-15

    Purpose: Triple coincidences in positron emission tomography (PET) are events in which three γ-rays are detected simultaneously. These events, though potentially useful for enhancing the sensitivity of PET scanners, are discarded or processed without special consideration in current systems, because there is not a clear criterion for assigning them to a unique line-of-response (LOR). Methods proposed for recovering such events usually rely on the use of highly specialized detection systems, hampering general adoption, and/or are based on Compton-scatter kinematics and, consequently, are limited in accuracy by the energy resolution of standard PET detectors. In this work, the authors propose amore » simple and general solution for recovering triple coincidences, which does not require specialized detectors or additional energy resolution requirements. Methods: To recover triple coincidences, the authors’ method distributes such events among their possible LORs using the relative proportions of double coincidences in these LORs. The authors show analytically that this assignment scheme represents the maximum-likelihood solution for the triple-coincidence distribution problem. The PET component of a preclinical PET/CT scanner was adapted to enable the acquisition and processing of triple coincidences. Since the efficiencies for detecting double and triple events were found to be different throughout the scanner field-of-view, a normalization procedure specific for triple coincidences was also developed. The effect of including triple coincidences using their method was compared against the cases of equally weighting the triples among their possible LORs and discarding all the triple events. The authors used as figures of merit for this comparison sensitivity, noise-equivalent count (NEC) rates and image quality calculated as described in the NEMA NU-4 protocol for the assessment of preclinical PET scanners. Results: The addition of triple-coincidence events with the authors’ method increased peak NEC rates of the scanner by 26.6% and 32% for mouse- and rat-sized objects, respectively. This increase in NEC-rate performance was also reflected in the image-quality metrics. Images reconstructed using double and triple coincidences recovered using their method had better signal-to-noise ratio than those obtained using only double coincidences, while preserving spatial resolution and contrast. Distribution of triple coincidences using an equal-weighting scheme increased apparent system sensitivity but degraded image quality. The performance boost provided by the inclusion of triple coincidences using their method allowed to reduce the acquisition time of standard imaging procedures by up to ∼25%. Conclusions: Recovering triple coincidences with the proposed method can effectively increase the sensitivity of current clinical and preclinical PET systems without compromising other parameters like spatial resolution or contrast.« less

  9. Patient-specific optimisation of administered activity and acquisition times for 18F-FDG PET imaging.

    PubMed

    Wickham, Fred; McMeekin, Helena; Burniston, Maria; McCool, Daniel; Pencharz, Deborah; Skillen, Annah; Wagner, Thomas

    2017-12-01

    The purpose of this study is to identify a method for optimising the administered activity and acquisition time for 18 F-FDG PET imaging, yielding images of consistent quality for patients with varying body sizes and compositions, while limiting radiation doses to patients and staff. Patients referred for FDG scans had bioimpedance measurements. They were injected with 3 MBq/kg of 18 F up to 370 MBq and scanned on a Siemens Biograph mCT at 3 or 4 min per bed position. Data were rebinned to simulate 2- and 1-min acquisitions. Subjective assessments of image quality made by an experienced physician were compared with objective measurements based on signal-to-noise ratio and noise equivalent counts (NEC). A target objective measure of image quality was identified. The activity and acquisition time required to achieve this were calculated for each subject. Multiple regression analysis was used to identify expressions for the activity and acquisition time required in terms of easily measurable patient characteristics. One hundred and eleven patients were recruited, and subjective and objective assessments of image quality were compared for 321 full and reduced time scans. NEC-per-metre was identified as the objective measure which best correlated with the subjective assessment (Spearman rank correlation coefficient 0.77) and the best discriminator for images with a subjective assessment of "definitely adequate" (area under the ROC curve 0.94). A target of 37 Mcount/m was identified. Expressions were identified in terms of patient sex, height and weight for the activity and acquisition time required to achieve this target. Including measurements of body composition in these expressions was not useful. Using these expressions would reduce the mean activity administered to this patient group by 66 MBq compared to the current protocol. Expressions have been identified for the activity and acquisition times required to achieve consistent image quality in FDG imaging with reduced patient and staff doses. These expressions might need to be adapted for other systems and reconstruction protocols.

  10. Evaluation of Bias and Variance in Low-count OSEM List Mode Reconstruction

    PubMed Central

    Jian, Y; Planeta, B; Carson, R E

    2016-01-01

    Statistical algorithms have been widely used in PET image reconstruction. The maximum likelihood expectation maximization (MLEM) reconstruction has been shown to produce bias in applications where images are reconstructed from a relatively small number of counts. In this study, image bias and variability in low-count OSEM reconstruction are investigated on images reconstructed with MOLAR (motion-compensation OSEM list-mode algorithm for resolution-recovery reconstruction) platform. A human brain ([11C]AFM) and a NEMA phantom are used in the simulation and real experiments respectively, for the HRRT and Biograph mCT. Image reconstructions were repeated with different combination of subsets and iterations. Regions of interest (ROIs) were defined on low-activity and high-activity regions to evaluate the bias and noise at matched effective iteration numbers (iterations x subsets). Minimal negative biases and no positive biases were found at moderate count levels and less than 5% negative bias was found using extremely low levels of counts (0.2 M NEC). At any given count level, other factors, such as subset numbers and frame-based scatter correction may introduce small biases (1–5%) in the reconstructed images. The observed bias was substantially lower than that reported in the literature, perhaps due to the use of point spread function and/or other implementation methods in MOLAR. PMID:25479254

  11. Evaluation of bias and variance in low-count OSEM list mode reconstruction

    NASA Astrophysics Data System (ADS)

    Jian, Y.; Planeta, B.; Carson, R. E.

    2015-01-01

    Statistical algorithms have been widely used in PET image reconstruction. The maximum likelihood expectation maximization reconstruction has been shown to produce bias in applications where images are reconstructed from a relatively small number of counts. In this study, image bias and variability in low-count OSEM reconstruction are investigated on images reconstructed with MOLAR (motion-compensation OSEM list-mode algorithm for resolution-recovery reconstruction) platform. A human brain ([11C]AFM) and a NEMA phantom are used in the simulation and real experiments respectively, for the HRRT and Biograph mCT. Image reconstructions were repeated with different combinations of subsets and iterations. Regions of interest were defined on low-activity and high-activity regions to evaluate the bias and noise at matched effective iteration numbers (iterations × subsets). Minimal negative biases and no positive biases were found at moderate count levels and less than 5% negative bias was found using extremely low levels of counts (0.2 M NEC). At any given count level, other factors, such as subset numbers and frame-based scatter correction may introduce small biases (1-5%) in the reconstructed images. The observed bias was substantially lower than that reported in the literature, perhaps due to the use of point spread function and/or other implementation methods in MOLAR.

  12. Protective effects of dexpanthenol in an experimental model of necrotizing enterocolitis.

    PubMed

    Karadag, Ahmet; Ozdemir, Ramazan; Kurt, Ahmet; Parlakpinar, Hakan; Polat, Alaadin; Vardi, Nigar; Taslidere, Elif; Karaman, Abdurrahman

    2015-07-01

    In pathogenesis of necrotizing enterocolitis (NEC), both oxidative stress and inflammation are considerable risk factors. The study was designed to evaluate whether administration of dexpanthenol (Dxp) is able to attenuate intestinal injury through the antioxidant and antiinflammatory mechanisms in a neonatal rat model of NEC. Forty newborn pups divided into four groups were included in the study: control, control+Dxp, NEC, and NEC+Dxp. NEC was induced by hyperosmolar formula and additionally the pups were exposed to hypoxia/hyperoxia and cold stress. They were sacrificed on postnatal day four, and their intestinal tissues were analyzed biochemically and histopathologically. Dxp caused a significant decrease in intestinal damage as determined by the histological score, villus height and number of goblet cells in NEC groups (p<0.0001). Tissue malondialdehyde, total oxidant status, and oxidative stress indexes levels were higher in the NEC group than in the control and control+Dxp groups (p<0.001). These values were reduced in the pups treated with Dxp (p≤0.004). Superoxide dismutase, glutathione peroxidase, and reduced glutathione activities were significantly reduced in the NEC group compared to the others (p<0.005). Treatment with Dxp significantly reduced elevations in tissue homogenate levels of tumor necrosis factor-α and interleukin-1β in the NEC+Dxp group (p=0.002 and p=0.01, respectively). Dexpanthenol seems to have antiinflammatory and antioxidant properties. Prophylaxis with Dxp has a potential to reduce the severity of intestinal damage in NEC in the animals. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Cost and Cost-Effectiveness of Donor Human Milk to Prevent Necrotizing Enterocolitis: Systematic Review.

    PubMed

    Buckle, Abigail; Taylor, Celia

    2017-11-01

    Necrotizing enterocolitis (NEC) is a costly gastrointestinal disorder that mainly affects preterm and low-birth-weight infants and can lead to considerable morbidity and mortality. Mother's own milk is protective against NEC but is not always available. In such cases, donor human milk has also been shown to be protective (although to a lesser extent) compared with formula milk, but it is more expensive. This systematic review aimed at evaluating the cost of donor milk, the cost of treating NEC, and the cost-effectiveness of exclusive donor milk versus formula milk feeding to reduce the short-term health and treatment costs of NEC. We systematically searched five relevant databases to find studies with verifiable costs or charges of donor milk and/or treatment of NEC and any economic evaluations comparing exclusive donor milk with exclusive formula milk feeding. All search results were double screened. Seven studies with verifiable donor milk costs and 17 with verifiable NEC treatment costs were included. The types of cost or charge included varied considerably across studies, so quantitative synthesis was not attempted. Estimates of the incremental length of stay associated with NEC were ∼18 days for medical NEC and 50 days for surgical NEC. Two studies claimed to report economic evaluations but did not do so in practice. It is likely that donor milk provides short-term cost savings by reducing the incidence of NEC. Future studies should provide more details on cost components included and a full economic evaluation, including long-term outcomes, should be undertaken.

  14. Packed red blood cell transfusion is not associated with increased risk of necrotizing enterocolitis in premature infants

    PubMed Central

    Sharma, R; Kraemer, DF; Torrazza, RM; Mai, V; Neu, J; Shuster, JJ; Hudak, ML

    2015-01-01

    OBJECTIVE Recent reports have posited a temporal association between blood transfusion with packed red blood cells (BT) and necrotizing enterocolitis (NEC). We evaluated the relationship between BT and NEC among infants at three hospitals who were consented at birth into a prospective observational study of NEC. STUDY DESIGN We used a case–control design to match each case of NEC in our study population of infants born at <33 weeks postmenstrual age (PMA) to one control infant using hospital of birth, PMA, birth weight and date of birth. RESULT The number of transfusions per infant did not differ between 42 NEC cases and their controls (4.0 ± 4.6 vs 5.4 ± 4.1, mean ± s.d., P = 0.063). A matched-pair analysis did not identify an association of transfusion with NEC in either the 48-h or 7-day time periods before the onset of NEC. Stratifying on matched-sets, the Cox proportional hazard model did not identify any difference in the total number of BTs between the two groups (hazard ratio 0.78, 95% confidence interval 0.57 to 1.07, P = 0.11). CONCLUSION In contrast to previous studies, our case–control study did not identify a significant temporal association between BT and NEC. Additional large prospective randomized studies are needed to clarify the relationship between BT and NEC. PMID:25144159

  15. Broad-spectrum Antibiotic Plus Metronidazole May Not Prevent the Deterioration of Necrotizing Enterocolitis From Stage II to III in Full-term and Near-term Infants

    PubMed Central

    Luo, Li-Juan; Li, Xin; Yang, Kai-Di; Lu, Jiang-Yi; Li, Lu-Quan

    2015-01-01

    Abstract Necrotizing enterocolitis (NEC) is the most common and frequently dangerous neonatal gastrointestinal disease. Studies have shown broad-spectrum antibiotics plus anaerobic antimicrobial therapy did not prevent the deterioration of NEC among very low birth preterm infants. However, few studies about this therapy which focused on full-term and near-term infant with NEC has been reported. The aim of this study was to evaluate the effect of broad-spectrum antibiotic plus metronidazole in preventing the deterioration of NEC from stage II to III in full-term and near-term infants. A retrospective cohort study based on the propensity score (PS) 1:1 matching was performed among the full-term and near-term infants with NEC (Bell stage ≥II). All infants who received broad-spectrum antibiotics were divided into 2 groups: group with metronidazole treatment (metronidazole was used ≥4 days continuously, 15 mg/kg/day) and group without metronidazole treatment. The depraved rates of stage II NEC between the 2 groups were compared. Meanwhile, the risk factors associated with the deterioration of stage II NEC were analyzed by case-control study in the PS-matched cases. A total of 229 infants met the inclusion criteria. Before PS-matching, we found the deterioration of NEC rate in the group with metronidazole treatment was higher than that in the group without metronidazole treatment (18.1% [28/155] vs 8.1% [6/74]; P = 0.048). After PS-matching, 73 pairs were matched, and the depraved rate of NEC in the group with metronidazole treatment was not lower than that in the group without metronidazole treatment (15.1% vs 8.2%; P = 0.2). Binary logistic regression analysis showed that sepsis after NEC (odds ratio [OR] 3.748, 95% confidence interval [CI] 1.171–11.998, P = 0.03), the need to use transfusion of blood products after diagnosis of NEC (OR 8.003, 95% CI 2.365–27.087, P = 0.00), and the need of longer time for nasogastric suction were risk factors for stage II NEC progressing to stage III (OR 1.102, 95% CI 1.004–1.21, P = 0.04). Broad-spectrum antibiotic plus metronidazole may not prevent the deterioration of NEC in full-term and near-term infants. Those infants who had sepsis required transfusion of blood products, and needed longer time for nasogastric suction after stage II NEC was more likely to progress to stage III. PMID:26496340

  16. Costs of necrotizing enterocolitis and cost-effectiveness of exclusively human milk-based products in feeding extremely premature infants.

    PubMed

    Ganapathy, Vaidyanathan; Hay, Joel W; Kim, Jae H

    2012-02-01

    This study evaluated the cost-effectiveness of a 100% human milk-based diet composed of mother's milk fortified with a donor human milk-based human milk fortifier (HMF) versus mother's milk fortified with bovine milk-based HMF to initiate enteral nutrition among extremely premature infants in the neonatal intensive care unit (NICU). A net expected costs calculator was developed to compare the total NICU costs among extremely premature infants who were fed either a bovine milk-based HMF-fortified diet or a 100% human milk-based diet, based on the previously observed risks of overall necrotizing enterocolitis (NEC) and surgical NEC in a randomized controlled study that compared outcomes of these two feeding strategies among 207 very low birth weight infants. The average NICU costs for an extremely premature infant without NEC and the incremental costs due to medical and surgical NEC were derived from a separate analysis of hospital discharges in the state of California in 2007. The sensitivity of cost-effectiveness results to the risks and costs of NEC and to prices of milk supplements was studied. The adjusted incremental costs of medical NEC and surgical NEC over and above the average costs incurred for extremely premature infants without NEC, in 2011 US$, were $74,004 (95% confidence interval, $47,051-$100,957) and $198,040 (95% confidence interval, $159,261-$236,819) per infant, respectively. Extremely premature infants fed with 100% human-milk based products had lower expected NICU length of stay and total expected costs of hospitalization, resulting in net direct savings of 3.9 NICU days and $8,167.17 (95% confidence interval, $4,405-$11,930) per extremely premature infant (p < 0.0001). Costs savings from the donor HMF strategy were sensitive to price and quantity of donor HMF, percentage reduction in risk of overall NEC and surgical NEC achieved, and incremental costs of surgical NEC. Compared with feeding extremely premature infants with mother's milk fortified with bovine milk-based supplements, a 100% human milk-based diet that includes mother's milk fortified with donor human milk-based HMF may result in potential net savings on medical care resources by preventing NEC.

  17. Small cell and large cell neuroendocrine carcinomas of the pancreas are genetically similar and distinct from well-differentiated pancreatic neuroendocrine tumors.

    PubMed

    Yachida, Shinichi; Vakiani, Efsevia; White, Catherine M; Zhong, Yi; Saunders, Tyler; Morgan, Richard; de Wilde, Roeland F; Maitra, Anirban; Hicks, Jessica; Demarzo, Angelo M; Shi, Chanjuan; Sharma, Rajni; Laheru, Daniel; Edil, Barish H; Wolfgang, Christopher L; Schulick, Richard D; Hruban, Ralph H; Tang, Laura H; Klimstra, David S; Iacobuzio-Donahue, Christine A

    2012-02-01

    Poorly differentiated neuroendocrine carcinomas (NECs) of the pancreas are rare malignant neoplasms with a poor prognosis. The aim of this study was to determine the clinicopathologic and genetic features of poorly differentiated NECs and compare them with other types of pancreatic neoplasms. We investigated alterations of KRAS, CDKN2A/p16, TP53, SMAD4/DPC4, DAXX, ATRX, PTEN, Bcl2, and RB1 by immunohistochemistry and/or targeted exomic sequencing in surgically resected specimens of 9 small cell NECs, 10 large cell NECs, and 11 well-differentiated neuroendocrine tumors (PanNETs) of the pancreas. Abnormal immunolabeling patterns of p53 and Rb were frequent (p53, 18 of 19, 95%; Rb, 14 of 19, 74%) in both small cell and large cell NECs, whereas Smad4/Dpc4, DAXX, and ATRX labeling was intact in virtually all of these same carcinomas. Abnormal immunolabeling of p53 and Rb proteins correlated with intragenic mutations in the TP53 and RB1 genes. In contrast, DAXX and ATRX labeling was lost in 45% of PanNETs, whereas p53 and Rb immunolabeling was intact in these same cases. Overexpression of Bcl-2 protein was observed in all 9 small cell NECs (100%) and in 5 of 10 (50%) large cell NECs compared with only 2 of 11 (18%) PanNETs. Bcl-2 overexpression was significantly correlated with higher mitotic rate and Ki67 labeling index in neoplasms in which it was present. Small cell NECs are genetically similar to large cell NECs, and these genetic changes are distinct from those reported in PanNETs. The finding of Bcl-2 overexpression in poorly differentiated NECs, particularly small cell NEC, suggests that Bcl-2 antagonists/inhibitors may be a viable treatment option for these patients.

  18. Association of neonatal necrotizing enterocolitis with myeloid differentiation-2 and GM2 activator protein genetic polymorphisms.

    PubMed

    Zhou, Wei; Yuan, Weiming; Huang, Longguang; Wang, Ping; Rong, Xiao; Tang, Juan

    2015-07-01

    The aim of the present study was to investigate the association of neonatal necrotizing enterocolitis (NEC) with myeloid differentiation-(MD-2) and GM2 activator protein (GM2A) genetic polymorphisms. Gene resequencing of the MD-2 and GM2A gene exons was performed on 42 neonates, diagnosed with NEC (NEC group), as well as in the rs11465996 locus, located in the MD-2 gene promoter region. The aim was to detect the genetic polymorphisms present in the neonates with NEC and compare the functional polymorphic loci with 83 neonates without NEC (control group), who had been born during the same period. A polymorphic locus with abnormal frequency was detected in the exon region of the MD-2 gene. In the NEC group, the frequency of genotypes carrying the low frequency allele (G) in the rs11465996 locus (MD-2 promoter region) was significantly higher compared with the control group (χ(2)=4.388, P=0.036). Furthermore, the frequencies of genotypes carrying the low frequency A and C alleles in the rs1048719 (GM2A gene exon 1) and rs2075783 loci (GM2A intron), respectively, were significantly higher in the NEC group compared with the control group (χ(2)=4.316, P=0.038; and χ(2)=13.717, P=0.000, respectively). In addition, the rs11465996 polymorphism in the MD-2 gene promoter region was found to be associated with the severity of NEC. Furthermore, the rs2075783 polymorphism in the GM2A gene exon 1 and the rs1048719 polymorphism in the intron region of this gene, were associated with the occurrence of NEC. The present study demonstrated that gene polymorphisms of MD-2 and GM2A were associated with the occurrence or severity of NEC; however, further in-depth exploration is required to clarify the associations between genetic predispositions to polymorphisms, and NEC.

  19. Outcomes at 7 years for babies who developed neonatal necrotising enterocolitis: the ORACLE Children Study.

    PubMed

    Pike, Katie; Brocklehurst, Peter; Jones, David; Kenyon, Sarah; Salt, Alison; Taylor, David; Marlow, Neil

    2012-09-01

    Within the ORACLE Children Study Cohort, the authors have evaluated long-term consequences of the diagnosis of confirmed or suspected neonatal necrotising enterocolitis (NEC) at age of 7 years. Outcomes were assessed using a parental questionnaire, including the Health Utilities Index (HUI-3) to assess functional impairment, and specific medical and behavioural outcomes. Educational outcomes for children in England were explored using national standardised tests. Multiple logistic regression was used to explore independent associates of NEC within the cohort. The authors obtained data for 119 (77%) of 157 children following proven or suspected NEC and compared their outcomes with those of the remaining 6496 children. NEC was associated with an increase in risk of neonatal death (OR 14.6 (95% CI 10.4 to 20.6)). At 7 years, NEC conferred an increased risk of all grades of impairment. Adjusting for confounders, risks persisted for any HUI-3 defined functional impairment (adjusted OR 1.55 (1.05, 2.29)), particularly mild impairment (adjusted OR 1.61 (1.03, 2.53)) both in all NEC children and in those with proven NEC, which appeared to be independent. No behavioural or educational associations were confirmed. Following NEC, children were more likely to suffer bowel problems than non-NEC children (adjusted OR 3.96 (2.06, 7.61)). The ORACLE Children Study provided opportunity for the largest evaluation of school age outcome following neonatal NEC and demonstrates significant long-term consequences of both gut function (presence of stoma, admission for bowel problems and continuing medical care for gut-related problems) and motor, sensory and cognitive outcomes as measured using HUI-3.

  20. Intestinal alkaline phosphatase to treat necrotizing enterocolitis.

    PubMed

    Biesterveld, Ben E; Koehler, Shannon M; Heinzerling, Nathan P; Rentea, Rebecca M; Fredrich, Katherine; Welak, Scott R; Gourlay, David M

    2015-06-15

    Intestinal alkaline phosphatase (IAP) activity is decreased in necrotizing enterocolitis (NEC), and IAP supplementation prevents NEC development. It is not known if IAP given after NEC onset can reverse the course of the disease. We hypothesized that enteral IAP given after NEC induction would not reverse intestinal injury. NEC was induced in Sprague-Dawley pups by delivery preterm followed by formula feedings with lipopolysaccharide (LPS) and hypoxia exposure and continued up to 4 d. IAP was added to feeds on day 2 until being sacrificed on day 4. NEC severity was scored based on hematoxylin and eosin-stained terminal ileum sections, and AP activity was measured using a colorimetric assay. IAP and interleukin-6 expression were measured using real time polymerase chain reaction. NEC pups' alkaline phosphatase (AP) activity was decreased to 0.18 U/mg compared with controls of 0.57 U/mg (P < 0.01). Discontinuation of LPS and hypoxia after 2 d increased AP activity to 0.36 U/mg (P < 0.01). IAP supplementation in matched groups did not impact total AP activity or expression. Discontinuing LPS and hypoxia after NEC onset improved intestinal injury scores to 1.14 compared with continued stressors, score 2.25 (P < 0.01). IAP supplementation decreased interleukin-6 expression two-fold (P < 0.05), though did not reverse NEC intestinal damage (P = 0.5). This is the first work to demonstrate that removing the source of NEC improves intestinal damage and increases AP activity. When used as a rescue treatment, IAP decreased intestinal inflammation though did not impact injury making it likely that IAP is best used preventatively to those neonates at risk. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Protein kinases responsible for the phosphorylation of the nuclear egress core complex of human cytomegalovirus.

    PubMed

    Sonntag, Eric; Milbradt, Jens; Svrlanska, Adriana; Strojan, Hanife; Häge, Sigrun; Kraut, Alexandra; Hesse, Anne-Marie; Amin, Bushra; Sonnewald, Uwe; Couté, Yohann; Marschall, Manfred

    2017-10-01

    Nuclear egress of herpesvirus capsids is mediated by a multi-component nuclear egress complex (NEC) assembled by a heterodimer of two essential viral core egress proteins. In the case of human cytomegalovirus (HCMV), this core NEC is defined by the interaction between the membrane-anchored pUL50 and its nuclear cofactor, pUL53. NEC protein phosphorylation is considered to be an important regulatory step, so this study focused on the respective role of viral and cellular protein kinases. Multiply phosphorylated pUL50 varieties were detected by Western blot and Phos-tag analyses as resulting from both viral and cellular kinase activities. In vitro kinase analyses demonstrated that pUL50 is a substrate of both PKCα and CDK1, while pUL53 can also be moderately phosphorylated by CDK1. The use of kinase inhibitors further illustrated the importance of distinct kinases for core NEC phosphorylation. Importantly, mass spectrometry-based proteomic analyses identified five major and nine minor sites of pUL50 phosphorylation. The functional relevance of core NEC phosphorylation was confirmed by various experimental settings, including kinase knock-down/knock-out and confocal imaging, in which it was found that (i) HCMV core NEC proteins are not phosphorylated solely by viral pUL97, but also by cellular kinases; (ii) both PKC and CDK1 phosphorylation are detectable for pUL50; (iii) no impact of PKC phosphorylation on NEC functionality has been identified so far; (iv) nonetheless, CDK1-specific phosphorylation appears to be required for functional core NEC interaction. In summary, our findings provide the first evidence that the HCMV core NEC is phosphorylated by cellular kinases, and that the complex pattern of NEC phosphorylation has functional relevance.

  2. Interaction of Nectarin 4 with a fungal protein triggers a microbial surveillance and defense mechanism in nectar.

    PubMed

    Harper, April D; Stalnaker, Stephanie H; Wells, Lance; Darvill, Alan; Thornburg, Robert; York, William S

    2010-12-01

    Understanding the biochemical mechanisms by which plants respond to microbial infection is a fundamental goal of plant science. Extracellular dermal glycoproteins (EDGPs) are widely expressed in plant tissues and have been implicated in plant defense responses. Although EDGPs are known to interact with fungal proteins, the downstream effects of these interactions are poorly understood. To gain insight into these phenomena, we used tobacco floral nectar as a model system to identify a mechanism by which the EDGP known as Nectarin IV (NEC4) functions as pathogen surveillance molecule. Our data demonstrates that the interaction of NEC4 with a fungal endoglucanase (XEG) promotes the catalytic activity of Nectarin V (NEC5), which catalyzes the conversion of glucose and molecular oxygen to gluconic acid and H(2)O(2). Significantly enhanced NEC5 activity was observed when XEG was added to nectar or nectarin solutions that contain NEC4. This response was also observed when the purified NEC4:XEG complex was added to NEC4-depleted nectarin solutions, which did not respond to XEG alone. These results indicate that formation of the NEC4:XEG complex is a key step leading to induction of NEC5 activity in floral nectar, resulting in an increase in concentrations of reactive oxygen species (ROS), which are known to inhibit microbial growth directly and activate signal transduction pathways that induce innate immunity responses in the plant. Copyright © 2010. Published by Elsevier Ltd.

  3. Quantifying the Benefits of NEC

    DTIC Science & Technology

    2005-04-01

    R UNCLASSIFIED/UNLIMITED Quantifying the Benefits of NEC Georgia Court and Lynda CM Sharp Dstl/UK MoD A2 Building, Dstl Farnborough Ively...transformation of UK forces is dependent on exploiting the benefits of Network Enabled Capability (NEC). The white paper notes that NEC, through... benefit to defence; • what can be traded off to pay for it; • what changes are required to processes, structures, equipment etc, to deliver the

  4. Contrast-Enhanced Ultrasound and Near-Infrared Spectroscopy of the Neonatal Bowel: Novel, Bedside, Noninvasive, and Radiation-Free Imaging for Early Detection of Necrotizing Enterocolitis.

    PubMed

    Al-Hamad, Suzanne; Hackam, David J; Goldstein, Seth D; Huisman, Thierry A G M; Darge, Kassa; Hwang, Misun

    2018-05-31

    Despite extensive research and improvements in the field of neonatal care, the morbidity and mortality associated with necrotizing enterocolitis (NEC) have remained unchanged over the past three decades. Early detection of ischemia and necrotic bowel is vital in improving morbidity and mortality associated with NEC; however, strategies for predicting and preventing NEC are lacking. Contrast-enhanced ultrasound (CEUS) and near-infrared spectroscopy (NIRS) are novel techniques in pediatrics that have been proven as safe modalities. CEUS has benefits over conventional ultrasound (US) by its improved real-time evaluation of the micro- and macrovascularities of normally and abnormally perfused tissue. US has been implemented as a useful adjunct to X-ray for earlier evaluation of NEC. NIRS is another noninvasive technique that has shown promise in improving early detection of NEC. The purpose of this article is to review the current understanding of changes in bowel perfusion in NEC, discuss the accuracy of abdominal US in detecting NEC, and explain how the use of CEUS and NIRS will enhance the precise and early detection of altered/pathological bowel wall perfusion in the initial development and course of NEC. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  5. Improving NEC Fit

    DTIC Science & Technology

    2015-09-01

    issues The Navy primarily uses Rating Control Number ( RCN ) Fit and NEC Fit to measure and assess enlisted fleet manning levels.1 In general, Fit...measures the quantity and quality of the crew relative to the unit’s authorized requirements. RCN Fit measures how well units are manned at the rating...below RCN Fit, and levels for non-critical NECs have been even lower. The levels in September 2014 indicate that a quarter of the critical NEC

  6. Hysteresis between coral reef calcification and the seawater aragonite saturation state

    NASA Astrophysics Data System (ADS)

    McMahon, Ashly; Santos, Isaac R.; Cyronak, Tyler; Eyre, Bradley D.

    2013-09-01

    predictions of how ocean acidification (OA) will affect coral reefs assume a linear functional relationship between the ambient seawater aragonite saturation state (Ωa) and net ecosystem calcification (NEC). We quantified NEC in a healthy coral reef lagoon in the Great Barrier Reef during different times of the day. Our observations revealed a diel hysteresis pattern in the NEC versus Ωa relationship, with peak NEC rates occurring before the Ωa peak and relatively steady nighttime NEC in spite of variable Ωa. Net ecosystem production had stronger correlations with NEC than light, temperature, nutrients, pH, and Ωa. The observed hysteresis may represent an overlooked challenge for predicting the effects of OA on coral reefs. If widespread, the hysteresis could prevent the use of a linear extrapolation to determine critical Ωa threshold levels required to shift coral reefs from a net calcifying to a net dissolving state.

  7. Joseph's Story: A Case Study of Late-Onset Necrotizing Enterocolitis From Early Birth to Recovery.

    PubMed

    Gephart, Sheila M; Martin, Laura B; Kijewski, Amy; Johnson, Scott R

    2015-01-01

    Although necrotizing enterocolitis (NEC) is often catastrophic among premature infants, most cases occur in the first month after birth. This case study presents Joseph's story about a 24-week surviving twin who developed severe NEC at 5 months of age just days before he was to go home. The purpose of this case study report is to place Joseph and his parents' experience in the context of what is known about NEC risk factors, clinical presentation, and treatment, and then to offer recommendations to healthcare professionals to support families from NEC diagnosis to recovery. Now 5 years old, Joseph continues to manage consequences of NEC including deafness, developmental delay, multiple food allergies, and recurrent gastrointestinal challenges from short gut syndrome. Although NEC struck late and kept Joseph in the neonatal intensive care unit for 228 days, its consequences remain with this resilient child and his family.

  8. Necrotizing Enterocolitis in the Premature Infant

    PubMed Central

    Gregory, Katherine E.; DeForge, Christine E.; Natale, Kristan M.; Phillips, Michele; Van Marter, Linda J.

    2013-01-01

    Necrotizing enterocolitis (NEC) remains one of the most catastrophic comorbidities associated with prematurity. In spite of extensive research, the disease remains unsolved. The aims of this paper are to present the current state of the science on the pathogenesis of NEC, summarize the clinical presentation and severity staging of the disease, and highlight the nursing assessments required for early identification of NEC and ongoing care for infants diagnosed with this gastrointestinal disease. The distributions of systemic and intestinal clinical signs that are most sensitive to nursing assessment and associated with Bell Staging Criteria are presented. This descriptive data is representative of 117 cases of NEC diagnosed in low gestational age infants (<29 weeks gestation). The data highlights the clinical signs most commonly observed in infants with NEC, and thus, provides NICU nurses an evidence-based guide for assessment and care of infants with NEC. PMID:21730907

  9. Necrotizing Enterocolitis Risk

    PubMed Central

    Gephart, Sheila M.; McGrath, Jacqueline M.; Effken, Judith A.; Halpern, Melissa D.

    2012-01-01

    Necrotizing enterocolitis (NEC) is the most common cause of gastrointestinal-related morbidity and mortality in the neonatal intensive care unit (NICU). Its onset is sudden and the smallest, most premature infants are the most vulnerable. Necrotizing enterocolitis is a costly disease, accounting for nearly 20% of NICU costs annually. Necrotizing enterocolitis survivors requiring surgery often stay in the NICU more than 90 days and are among those most likely to stay more than 6 months. Significant variations exist in the incidence across regions and units. Although the only consistent independent predictors for NEC remain prematurity and formula feeding, others exist that could increase risk when combined. Awareness of NEC risk factors and adopting practices to reduce NEC risk, including human milk feeding, the use of feeding guidelines, and probiotics, have been shown to reduce the incidence of NEC. The purpose of this review is to examine the state of the science on NEC risk factors and make recommendations for practice and research. PMID:22469959

  10. The hepatic bile acid transporters Ntcp and Mrp2 are downregulated in experimental necrotizing enterocolitis.

    PubMed

    Cherrington, Nathan J; Estrada, Teresa E; Frisk, Harrison A; Canet, Mark J; Hardwick, Rhiannon N; Dvorak, Bohuslav; Lux, Katie; Halpern, Melissa D

    2013-01-01

    Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency of premature infants and is characterized by an extensive hemorrhagic inflammatory necrosis of the distal ileum and proximal colon. We have previously shown that, during the development of experimental NEC, the liver plays an important role in regulating inflammation in the ileum, and accumulation of ileal bile acids (BA) along with dysregulation of ileal BA transporters contributes to ileal damage. Given these findings, we speculated that hepatic BA transporters would also be altered in experimental NEC. Using both rat and mouse models of NEC, levels of Cyp7a1, Cyp27a1, and the hepatic BA transporters Bsep, Ntcp, Oatp2, Oatp4, Mrp2, and Mrp3 were investigated. In addition, levels of hepatic BA transporters were also determined when the proinflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-18, which are both elevated in NEC, are neutralized during disease development. Ntcp and Mrp2 were decreased in NEC, but elevated ileal BA levels were not responsible for these reductions. However, neutralization of TNF-α normalized Ntcp, whereas removal of IL-18 normalized Mrp2 levels. These data show that the hepatic transporters Ntcp and Mrp2 are downregulated, whereas Cyp27a1 is increased in rodent models of NEC. Furthermore, increased levels of TNF-α and IL-18 in experimental NEC may play a role in the regulation of Ntcp and Mrp2, respectively. These data suggest the gut-liver axis should be considered when therapeutic modalities for NEC are developed.

  11. Current Knowledge of Necrotizing Enterocolitis in Preterm Infants and the Impact of Different Types of Enteral Nutrition Products.

    PubMed

    Shulhan, Jocelyn; Dicken, Bryan; Hartling, Lisa; Larsen, Bodil Mk

    2017-01-01

    Preterm infants are extremely vulnerable to a range of morbidities and mortality. Underdeveloped cardiac, respiratory, gastrointestinal, and immune systems in the preterm period increase the risk of necrotizing enterocolitis (NEC), a serious disease of the gut. NEC affects 5-12% of very-low birth-weight infants, leads to surgery in 20-40% of cases, and is fatal in 25-50% of cases. There are multiple factors that may contribute to NEC, but the exact cause is not yet fully understood. Severe cases can result in intestinal resection or death, and the health care costs average >$300,000/infant when surgical management is required. Different types of nutrition may affect the onset or progression of NEC. Several studies have indicated that bovine milk-based infant formulas lead to a higher incidence of NEC in preterm infants than does human milk (HM). However, it is not clear why HM is linked to a lower incidence of NEC or why some infants fed an exclusively HM diet still develop NEC. An area that has not been thoroughly explored is the use of semielemental or elemental formulas. These specialty formulas are easy to digest and absorb in the gut and may be an effective nutritional intervention for reducing the risk of NEC. This review summarizes what is known about the factors that contribute to the onset and progression of NEC, discusses its health care cost implications, and explores the impact that different formulas and HM have on this disease. © 2017 American Society for Nutrition.

  12. Current Knowledge of Necrotizing Enterocolitis in Preterm Infants and the Impact of Different Types of Enteral Nutrition Products12

    PubMed Central

    Dicken, Bryan; Hartling, Lisa

    2017-01-01

    Preterm infants are extremely vulnerable to a range of morbidities and mortality. Underdeveloped cardiac, respiratory, gastrointestinal, and immune systems in the preterm period increase the risk of necrotizing enterocolitis (NEC), a serious disease of the gut. NEC affects 5–12% of very–low birth-weight infants, leads to surgery in 20–40% of cases, and is fatal in 25–50% of cases. There are multiple factors that may contribute to NEC, but the exact cause is not yet fully understood. Severe cases can result in intestinal resection or death, and the health care costs average >$300,000/infant when surgical management is required. Different types of nutrition may affect the onset or progression of NEC. Several studies have indicated that bovine milk–based infant formulas lead to a higher incidence of NEC in preterm infants than does human milk (HM). However, it is not clear why HM is linked to a lower incidence of NEC or why some infants fed an exclusively HM diet still develop NEC. An area that has not been thoroughly explored is the use of semielemental or elemental formulas. These specialty formulas are easy to digest and absorb in the gut and may be an effective nutritional intervention for reducing the risk of NEC. This review summarizes what is known about the factors that contribute to the onset and progression of NEC, discusses its health care cost implications, and explores the impact that different formulas and HM have on this disease. PMID:28096129

  13. Proteomic Analysis of the Multimeric Nuclear Egress Complex of Human Cytomegalovirus*

    PubMed Central

    Milbradt, Jens; Kraut, Alexandra; Hutterer, Corina; Sonntag, Eric; Schmeiser, Cathrin; Ferro, Myriam; Wagner, Sabrina; Lenac, Tihana; Claus, Claudia; Pinkert, Sandra; Hamilton, Stuart T.; Rawlinson, William D.; Sticht, Heinrich; Couté, Yohann; Marschall, Manfred

    2014-01-01

    Herpesviral capsids are assembled in the host cell nucleus before being translocated into the cytoplasm for further maturation. The crossing of the nuclear envelope represents a major event that requires the formation of the nuclear egress complex (NEC). Previous studies demonstrated that human cytomegalovirus (HCMV) proteins pUL50 and pUL53, as well as their homologs in all members of Herpesviridae, interact with each other at the nuclear envelope and form the heterodimeric core of the NEC. In order to characterize further the viral and cellular protein content of the multimeric NEC, the native complex was isolated from HCMV-infected human primary fibroblasts at various time points and analyzed using quantitative proteomics. Previously postulated components of the HCMV-specific NEC, as well as novel potential NEC-associated proteins such as emerin, were identified. In this regard, interaction and colocalization between emerin and pUL50 were confirmed by coimmunoprecipitation and confocal microscopy analyses, respectively. A functional validation of viral and cellular NEC constituents was achieved through siRNA-mediated knockdown experiments. The important role of emerin in NEC functionality was demonstrated by a reduction of viral replication when emerin expression was down-regulated. Moreover, under such conditions, reduced production of viral proteins and deregulation of viral late cytoplasmic maturation were observed. Combined, these data prove the functional importance of emerin as an NEC component, associated with pUL50, pUL53, pUL97, p32/gC1qR, and further regulatory proteins. Summarized, our findings provide the first proteomics-based characterization and functional validation of the HCMV-specific multimeric NEC. PMID:24969177

  14. RIPK1/RIPK3/MLKL-mediated necroptosis contributes to compression-induced rat nucleus pulposus cells death.

    PubMed

    Chen, Songfeng; Lv, Xiao; Hu, Binwu; Shao, Zengwu; Wang, Baichuan; Ma, Kaige; Lin, Hui; Cui, Min

    2017-05-01

    The aim of this study was to systematically investigate the role of necroptosis in compression-induced rat nucleus pulposus (NP) cells death, as well as explore the underlying mechanisms involved. Rat NP cells underwent various periods of exposure to 1.0 MPa pressure. Cell viability and cell death were quantified by using cell counting kit-8 (CCK-8), and Calcein-AM/propidium iodine (PI) staining respectively. Necroptosis-associated target molecules receptor-interacing protein kinase 1 (RIPK1), phosphorylated RIPK1 (pRIPK1), receptor-interacing protein kinase 3 (RIPK3), phosphorylated RIPK3 (pRIPK3) and mixed lineage kinase domain-like (MLKL) were analyzed by Western-blot and RT-PCR. NP cells were also examined for morphological and ultrastructural changes, which can indicate necroptosis. To indirectly establish the presence of necroptosis, the RIPK1 specific inhibitor necrostatin-1 (Nec-1), RIPK3 inhibitor GSK'872, MLKL inhibitor necrosulfonamide (NSA) and small interfering RNA (siRNA) were utilized. The results established necroptosis was taking place in NP cells. The level of necroptosis increased in a time-dependent manner, and this effect was reduced by Nec-1 in vitro. Additionally, NP cells death were significantly attenuated following treatment with Nec-1, GSK'872 or NSA. SiRNA-induced knockdown of RIPK3 or MLKL increased cell survival rate, while knockdown of RIPK1 resulted in a decreased cell survival rate. In summary, RIPK1/RIPK3/MLKL-mediated necroptosis may play an important role in NP cells death induced by continuous mechanical stress. Treatment strategies which aim to regulate necroptosis may prove beneficial, by both reducing NP cells death and slowing IVD degeneration.

  15. Lipopolysaccharide Binding Protein Enables Intestinal Epithelial Restitution Despite Lipopolysaccharide Exposure

    PubMed Central

    Richter, Juli M.; Schanbacher, Brandon L.; Huang, Hong; Xue, Jianjing; Bauer, John A.; Giannone, Peter J.

    2011-01-01

    Intestinal epithelial restitution is the first part in the process of mucosal repair after injury in the intestine. Integrity of the intestinal mucosal barrier is important as a first line of defense against bacteria and endotoxin. Necrotizing enterocolitis (NEC) is a major cause of morbidity and mortality in extremely low birth weight infants, but its mechanisms are not well defined. Abnormal bacterial colonization, immature barrier function, innate immunity activation and inflammation likely play a role. Lipopolysaccharide (LPS) binding protein (LBP) is secreted by enterocytes in response to inflammatory stimuli and has concentration-dependent effects. At basal concentrations, LBP stimulates the inflammatory response by presenting LPS to its receptor. However, at high concentrations, LBP is able to neutralize LPS and prevent an exaggerated inflammatory response. We sought to determine how LBP would affect wound healing in an in vitro model of intestinal cell restitution and protect against intestinal injury in a rodent model of NEC. Immature intestinal epithelial cells (IEC-6) were seeded in poly-l-lysine coated 8 chamber slides and grown to confluence. A 500μm wound was created using a cell scraper mounted on the microscope to achieve uniform wounding. Media was replaced with media containing LPS +/− LBP. Slide wells were imaged after 0, 8, and 24 hours and then fixed. Cellular restitution was evaluated via digital images captured on an inverted microscope and wound closure was determined by automated analysis. TLR4 was determined by rtPCR after RNA isolation from wounded cells 24 hours after treatment. LPS alone attenuated wound healing in immature intestinal epithelium. This attenuation is reversed by 24 hours with increasing concentrations of LBP so that wound healing is equivalent to control (p< 0.001). TLR4 was increased with LPS alone but levels returned to that of control after addition of LBP in the higher concentrations. LBP had no effect on the development of intestinal injury when given during our rodent model of NEC. Abnormal bacterial colonization and activation of innate immunity by LPS are likely involved in the pathogenesis of NEC. The attentuation of wound healing was reversed when LBP was added to LPS but only in the higher concentrations. At these same concentrations of LBP, TLR4 was decreased to that of control. These results indicate that LBP may be a novel therapeutic strategy to facilitate wound healing after the acute phase of NEC and other forms of intestinal injury. PMID:22002480

  16. Severe neurodevelopmental disability and healthcare needs among survivors of medical and surgical necrotizing enterocolitis: A prospective cohort study.

    PubMed

    Fullerton, Brenna S; Hong, Charles R; Velazco, Cristine S; Mercier, Charles E; Morrow, Kate A; Edwards, Erika M; Ferrelli, Karla R; Soll, Roger F; Modi, Biren P; Horbar, Jeffrey D; Jaksic, Tom

    2017-10-12

    This study characterizes neurodevelopmental outcomes and healthcare needs of extremely low birth weight (ELBW) survivors of necrotizing enterocolitis (NEC) compared to ELBW infants without NEC. Data were collected prospectively on neonates born 22-27weeks' gestation or 401-1000g at 47 Vermont Oxford Network member centers from 1999 to 2012. Detailed neurodevelopmental evaluations were conducted at 18-24months corrected age. Information regarding rehospitalizations, postdischarge surgeries, and feeding was also collected. "Severe neurodevelopmental disability" was defined as: bilateral blindness, hearing impairment requiring amplification, inability to walk 10 steps with support, cerebral palsy, and/or Bayley Mental or Psychomotor Developmental Index <70. Diagnosis of NEC required both clinical and radiographic findings. There were 9063 children without NEC, 417 with medical NEC, and 449 with surgical NEC evaluated. Significantly higher rates of morbidity were observed among infants with a history of NEC. Those with surgical NEC were more frequently affected across all outcome measures at 18-24months corrected age: 38% demonstrated severe neurodevelopmental disability, nearly half underwent postdischarge operations, and a quarter required tube feeding at home. At 18-24months, extremely low birth weight survivors of necrotizing enterocolitis were at markedly increased risk (p<0.001) for severe neurodevelopmental disability, postdischarge surgery, and tube feeding. II (prospective cohort study with <80% follow-up rate). Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Gender differences in satisfaction ratings for nicotine electronic cigarettes by first-time users.

    PubMed

    Grace, Randolph C; Kivell, Bronwyn M; Laugesen, Murray

    2015-11-01

    Nicotine electronic cigarettes (NECs) are becoming increasingly popular as a potentially safer alternative to tobacco but little is known regarding their subjective effects, including possible gender differences. Participants were New Zealand smokers with no intention to quit (N = 357) and whom had never used an NEC. During an interview in November-December 2012, participants sampled an NEC and rated it and their own-brand tobacco for satisfaction on a 10-point visual analogue scale. Participants were contacted again in February-March 2013 after a 10% increase in the tobacco excise tax on 1 January 2013. Overall participants rated NECs 83.3% as satisfying as own-brand tobacco. Females rated NECs more highly than males. Of those who agreed to be re-interviewed (n = 227), 37.8% said they had cut back or made a change in their smoking habit and 7% had quit in February-March 2013. NEC satisfaction ratings predicted changes in smoking habit and reductions in nicotine dependence after controlling for covariates including demographic variables, factory-made vs. roll-your-own tobacco preference, and addiction scores. Smokers' first impressions of NECs were very favourable, and were correlated with readiness to change after a tobacco tax increase. NECs appear to be particularly attractive for female smokers, and their use may help to improve the efficacy of nicotine replacement therapy for women. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Metabolomic signatures distinguish the impact of formula carbohydrates on disease outcome in a preterm piglet model of NEC.

    PubMed

    Call, Lee; Stoll, Barbara; Oosterloo, Berthe; Ajami, Nadim; Sheikh, Fariha; Wittke, Anja; Waworuntu, Rosaline; Berg, Brian; Petrosino, Joseph; Olutoye, Oluyinka; Burrin, Douglas

    2018-06-19

    Major risk factors for necrotizing enterocolitis (NEC) include premature birth and formula feeding in the context of microbial colonization of the gastrointestinal tract. We previously showed that feeding formula composed of lactose vs. corn syrup solids protects against NEC in preterm pigs; however, the microbial and metabolic effects of these different carbohydrates used in infant formula has not been explored. Our objective was to characterize the effects of lactose- and corn syrup solid-based formulas on the metabolic and microbial profiles of preterm piglets and to determine whether unique metabolomic or microbiome signatures correlate with severity or incidence of NEC. Preterm piglets (103 days gestation) were given total parenteral nutrition (2 days) followed by gradual (5 days) advancement of enteral feeding of formulas matched in nutrient content but containing either lactose (LAC), corn syrup solids (CSS), or 1:1 mix (MIX). Gut contents and mucosal samples were collected and analyzed for microbial profiles by sequencing the V4 region of the 16S rRNA gene. Metabolomic profiles of cecal contents and plasma were analyzed by LC/GC mass spectrometry. NEC incidence was 14, 50, and 44% in the LAC, MIX, and CSS groups, respectively. The dominant classes of bacteria were Bacilli, Clostridia, and Gammaproteobacteria. The number of observed OTUs was lowest in colon contents of CSS-fed pigs. CSS-based formula was associated with higher Bacilli and lower Clostridium from clusters XIVa and XI in the colon. NEC was associated with decreased Gammaproteobacteria in the stomach and increased Clostridium sensu stricto in the ileum. Plasma from NEC piglets was enriched with metabolites of purine metabolism, aromatic amino acid metabolism, and bile acids. Markers of glycolysis, e.g., lactate, were increased in the cecal contents of CSS-fed pigs and in plasma of pigs which developed NEC. Feeding formula containing lactose is not completely protective against NEC, yet selects for greater microbial richness associated with changes in Bacilli and Clostridium and lower NEC incidence. We conclude that feeding preterm piglets a corn syrup solid vs. lactose-based formula increases the incidence of NEC and produces distinct metabolomic signatures despite modest changes in microbiome profiles.

  19. Carbohydrate maldigestion induces necrotizing enterocolitis in preterm pigs

    USDA-ARS?s Scientific Manuscript database

    Necrotizing enterocolitis (NEC) is a major gastrointestinal disorder in preterm infants. Key risk factors for NEC are enteral feeding and microbial colonization. Maldigestion of carbohydrate secondary to immature digestive function has been suspected to cause bacterial overgrowth and NEC. We investi...

  20. An animal model of necrotizing enterocolitis (NEC) in preterm rabbits.

    PubMed

    Bozeman, Andrew P; Dassinger, Melvin S; Birusingh, Rhea J; Burford, Jeffrey M; Smith, Samuel D

    2013-04-01

    Creation of an animal model of necrotizing enterocolitis (NEC) allowing adjustment of severity and potential recoverability is needed to study effectiveness of prevention and treatment strategies. This study describes a novel model in preterm rabbits capable of adjusting severity of NEC-like histologic changes. Rabbit pups (n = 151) were delivered by cesarean section 2 days preterm. In the treatment groups, tissue adhesive was applied to anal openings to simulate the poor intestinal function and dysmotility of preterm neonates. Pups were placed into five groups: 3INT (3 day intermittent block), 4INT (4 day intermittent block), 3COM (3 day complete block), 4COM (4 day complete block), based on differences in type of anal blockage and day of life sacrificed. The fifth group, 4CON, was comprised of a control arm (n = 28) without anal block, with sacrifice of subjects on day 4. All pups were gavage fed with formula contaminated with Enterobacter cloacae, ranitidine, and indomethacin. Following sacrifice, the intestines were harvested for pathologic evidence of NEC. A blinded pathologist graded histologic changes consistent with NEC using a grading scale 0-4 with 4 being most severe. Fifty-seven pups (57/123) (46%) in the research arm survived to sacrifice, compared to 26/28 (93%) in the control arm of the investigation, p < 0.0001. The incidence and severity of NEC-like damage increased with the duration and completeness of the anal blockage. 44/57 (77%) of survivors revealed various degrees of NEC-like damage to large and small bowel, and 3/26 (12%) exhibited early NEC-like mucosal injury in the research and control arms, respectively. This animal model produces NEC-like pathologic changes in both small and large intestine in preterm rabbits. Because incidence and severity of damage increases with duration and completeness of intestinal dysmotility, this allows future effectiveness studies for nonsurgical treatment and prevention of NEC.

  1. Transient effects of transfusion and feeding advances (volumetric and caloric) on necrotizing enterocolitis development: A case-crossover study.

    PubMed

    Le, Vi T; Klebanoff, Mark A; Talavera, Maria M; Slaughter, Jonathan L

    2017-01-01

    To evaluate the short-term effects of feed fortification, feed volume increase, and PRBC transfusion on the odds of developing NEC. Case-crossover study of neonatal intensive care infants born at ≤ 32 weeks' gestation who were admitted to 5 central Ohio intensive care units from January 2012-July 2016 and developed NEC Bell Stage ≥2. Each patient served as their own control, with exposure during the 48-hour period just prior to NEC onset (hazard period) being compared to a preceding 48-hour control period, thus eliminating confounding by patient factors fixed between both intervals. NEC onset was determined by chart review as the earliest occurrence of one of the following within 24 hours of confirmatory x-ray: (1) antibiotic initiation, (2) enteral feeding cessation, (3) physician first notified of abdominal concerns, or (4) abdominal x-ray ordered. Conditional logistic regression compared exposures to feed volume increase, fortification, and PRBC transfusion during the 48-hour period prior to NEC onset to those during a preceding 48-hour control period. Analyses were stratified by gestational age and anemia (defined: hemoglobin ≤ 9.3 g/dL within 7 days of NEC onset). We included 63 infants with confirmed NEC. Acute exposure to fortification (odds ratio [OR]: 1.67, 95% confidence interval [CI]: 0.61, 4.59), feed volume increase (OR: 0.63, 95% CI: 0.28, 1.38), and PRBC transfusion (OR: 1.80, 95% CI: 0.60, 5.37) was not associated with the onset of NEC. Gestational age and anemia did not significantly modify the associations. Sensitivity testing substituting 24- and 72-hour hazard and control periods produced similar results. Using a case-crossover design, we did not detect an association between NEC development and feed fortification, feed volume increase, or PRBC transfusion within 48-hours prior to NEC-onset. Replication in a larger set of cases is needed.

  2. Bifidobacterium breve prevents necrotising enterocolitis by suppressing inflammatory responses in a preterm rat model.

    PubMed

    Satoh, T; Izumi, H; Iwabuchi, N; Odamaki, T; Namba, K; Abe, F; Xiao, J Z

    2016-02-01

    Necrotising enterocolitis (NEC) is associated with inflammatory responses and barrier dysfunction in the gut. In this study, we investigated the effect of Bifidobacterium breve M-16V on factors related to NEC development using an experimental rat model. Caesarean-sectioned rats were given formula milk with or without B. breve M-16V by oral gavage thrice daily, and experimental NEC was induced by exposing the rats to hypoxic conditions. Naturally delivered rats that were reared by their mother were used as healthy controls. The pathological score of NEC and the expression of molecules related to inflammatory responses and the barrier function were assessed in the ileum. B. breve M-16V reduced the pathological scores of NEC and resulted in some improvement in survivability. B. breve M-16V suppressed the increased expression of molecules related to inflammation and barrier function that resulted from NEC induction. B. breve M-16V normalised Toll-like receptor (TRL)4 expression and enhanced TLR2 expression. Our data suggest that B. breve M-16V prevents NEC development by modulating TLR expressions and suppressing inflammatory responses in a rat model.

  3. Modeling and Measurement of Electromagnetic Fields Near LORAN-C and OMEGA Stations

    DTIC Science & Technology

    1987-06-15

    radial guy anchor point Figure 11. Nantucket LORAN NEC wire model 24 (625’ monopole ) Figure 12. Nantucket LORAN NEC model (top view, 25 numbered...LORAN measured vs. predicted H fields 28 Figure 16. Dana LORAN measured vs. predicted E fields 29 Figure 17. Seneca LORAN NEC wire model (700’ monopole ...antenna 4. Power outputs and rms-to-peak ratios for 625 23 foot monopoles 5. NEC predicted electric field strengths for 31 625 foot LORAN-C monopoles 6

  4. SATCOM antenna siting study on P-3C aircraft, volume 1

    NASA Technical Reports Server (NTRS)

    Bensman, D. A.; Marhefka, R. J.

    1991-01-01

    The NEC-BSC (Basic Scattering Code) was used to study the performance of a SATCOM antenna on a P-3C aircraft. After plate cylinder fields are added to version 3.1 of the NEC-BSC, it is shown that the NEC-BSC can be used to accurately predict the performance of a SATCOM antenna system on a P-3C aircraft. The study illustrates that the NEC-BSC gives good results when compared with scale model measurements provided by Boeing and Lockheed.

  5. Pathogenesis of NEC: Role of the Innate and Adaptive Immune Response

    PubMed Central

    Denning, Timothy L.; Bhatia, Amina M.; Kane, Andrea F.; Patel, Ravi M.; Denning, Patricia L.

    2017-01-01

    Necrotizing enterocolitis (NEC) is a devastating disease in premature infants with high case fatality and significant morbidity among survivors. Immaturity of intestinal host defenses predisposes the premature infant gut to injury. An abnormal bacterial colonization pattern with a deficiency of commensal bacteria may lead to a further breakdown of these host defense mechanisms, predisposing the infant to NEC. Here, we review the role of the innate and adaptive immune system in the pathophysiology of NEC. PMID:27940091

  6. Bacterial invasion of HT29-MTX-E12 monolayers: effects of human breast milk.

    PubMed

    Hall, Tim; Dymock, David; Corfield, Anthony P; Weaver, Gillian; Woodward, Mark; Berry, Monica

    2013-02-01

    The supramucosal gel, crucial for gut barrier function, might be compromised in necrotizing enterocolitis (NEC). Breast milk is associated with a reduced incidence of NEC. We compared the effects of human breast milk (BM) versus a neonatal formula, Nutriprem 1 (FF), on adherence, internalisation, and penetration of NEC-associated Escherichia coli through monolayers of mucus producing intestinal cells, HT29-MTX-E12 (E12). E12 cells were grown to confluence on membranes permeable to bacteria. E. coli, reference strain and isolated from a NEC-affected intestine, were cultured in LB broth, labelled with fluorescein and biotinylated. Bacteria were suspended in tissue culture medium (TC) or mixtures of TC with BM or FF and applied to the E12 cultures. Bacterial numbers were assessed by fluorescence. DyLight 650-labelled neutravidin, which cannot cross cell membrane, evaluated extracellular bacteria. Fluorescence of basolateral medium was measured to quantify translocation. Bacterial concentrations were compared using the Mann Whitney U test. After 1h exposure, E12 cultures adhered or internalised more NEC-derived bacteria than standard strain E. coli and more suspended in FF than BM (P<0.001). A greater proportion of NEC-derived bacteria internalised when suspended in TC or BM. In FF, the NEC-derived strain internalised least. More translocation occurred in BM incubations compared to FF in the first 1-4h: NEC-E. coli less than the reference strain. After 24h translocated bacterial populations were equal. In this pilot study, breast milk was associated with relatively less adhesion and internalisation of NEC-associated E. coli to mucus covered E12s compared to formula milk. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Contaminated milk is a common cause of necrotising enterocolitis: A hypothesis.

    PubMed

    Boo, N Y

    2016-12-01

    Necrotising enterocolitis (NEC) is the most commonly acquired gastrointestinal disease of neonates, particularly the very preterm (gestation <32 weeks) and/or very low birth weight (<1500g). It is associated with high morbidity and mortality. Despite improvement in neonatal care and increased use of expressed breast milk (EBM), the incidence remains high in many neonatal intensive care units (NICU), and even shows increasing trend in some countries. Numerous studies have pointed to the infective nature of NEC. Some investigators have reported an increase in the incidence of NEC in their NICU when the percentage of infants with pathogens isolated from their gut increased, and decreased when gut colonisation rate was low. Both bacteria and viruses have been reported to be associated with outbreaks of NEC. The majority (>90%) of the NEC cases occurred in neonates on enteral feeding. Studies have shown that milk (whether EBM or formula) fed to neonates was not sterile and were further contaminated during collection, transport, storage and/or feeding. Other investigators have reported a reduction in the incidence of NEC when they improved infection control measures and hygienic procedures in handling milk. It is, therefore, hypothesised that the most common cause of NEC is due to the feeding of neonates, particularly the vulnerable very preterm small neonates, with milk heavily contaminated during collection at source, transport, storage and/or feeding. Because of the immaturity of the immune system of the neonates, excessive inflammatory response to the pathogen load in the gut leads to the pathogenesis of NEC.

  8. Serum Heat Shock Protein 70 Level as a Biomarker of Exceptional Longevity

    PubMed Central

    Terry, Dellara F.; Wyszynski, Diego F.; Nolan, Vikki G.; Atzmon, Gil; Schoenhofen, Emily A.; Pennington, JaeMi Y.; Andersen, Stacy L.; Wilcox, Marsha A.; Farrer, Lindsay A.; Barzilai, Nir; Baldwin, Clinton T.; Asea, Alexzander

    2006-01-01

    Heat shock proteins are highly conserved proteins that, when produced intracellularly, protect stress exposed cells. In contrast, extracellular Hsp70 has been shown to have both protective and deleterious effects. In this study, we assessed heat shock protein 70 (Hsp70) for its potential role in human longevity. Because of the importance of HSP to disease processes, cellular protection, and inflammation, we hypothesized that: (1) Hsp70 levels in centenarians and centenarian offspring are different from controls and (2) alleles in genes associated with Hsp70 explain these differences. In this cross-sectional study, we assessed serum Hsp70 levels from participants enrolled in either the New England Centenarian Study (NECS) or the Longevity Genes Project (LGP): 87 centenarians (from LGP), 93 centenarian offspring (from NECS), and 126 controls (43 from NECS, 83 from LGP). We also examined genotypic and allelic frequencies of polymorphisms in HSP70-A1A and HSP70-A1B in 347 centenarians (266 from the NECS, 81 from the LGP), 260 NECS centenarian offspring, and 238 controls (NECS: 53 spousal controls and 106 septuagenarian offspring controls; LGP: 79 spousal controls). The adjusted mean serum Hsp70 levels (ng/mL) for the NECS centenarian offspring, LGP centenarians, LGP spousal controls, and NECS controls were 1.05, 1.13, 3.05, 6.93, respectively, suggesting that a low serum Hsp70 level is associated with longevity; however, no genetic associations were found with two SNPs within two hsp70 genes. PMID:17027907

  9. Serum heat shock protein 70 level as a biomarker of exceptional longevity.

    PubMed

    Terry, Dellara F; Wyszynski, Diego F; Nolan, Vikki G; Atzmon, Gil; Schoenhofen, Emily A; Pennington, JaeMi Y; Andersen, Stacy L; Wilcox, Marsha A; Farrer, Lindsay A; Barzilai, Nir; Baldwin, Clinton T; Asea, Alexzander

    2006-11-01

    Heat shock proteins are highly conserved proteins that, when produced intracellularly, protect stress exposed cells. In contrast, extracellular heat shock protein 70 (Hsp70) has been shown to have both protective and deleterious effects. In this study, we assessed heat shock protein 70 for its potential role in human longevity. Because of the importance of HSP to disease processes, cellular protection, and inflammation, we hypothesized that: (1) Hsp70 levels in centenarians and centenarian offspring are different from controls and (2) alleles in genes associated with Hsp70 explain these differences. In this cross-sectional study, we assessed serum Hsp70 levels from participants enrolled in either the New England Centenarian Study (NECS) or the Longevity Genes Project (LGP): 87 centenarians (from LGP), 93 centenarian offspring (from NECS), and 126 controls (43 from NECS, 83 from LGP). We also examined genotypic and allelic frequencies of polymorphisms in HSP70-A1A and HSP70-A1B in 347 centenarians (266 from the NECS, 81 from the LGP), 260 NECS centenarian offspring, and 238 controls (NECS: 53 spousal controls and 106 septuagenarian offspring controls; LGP: 79 spousal controls). The adjusted mean serum Hsp70 levels (ng/mL) for the NECS centenarian offspring, LGP centenarians, LGP spousal controls, and NECS controls were 1.05, 1.13, 3.07, 6.93, respectively, suggesting that a low serum Hsp70 level is associated with longevity; however, no genetic associations were found with two SNPs within two hsp70 genes.

  10. SATCOM antenna siting study on a P-3C using the NEC-BSC V3.1

    NASA Technical Reports Server (NTRS)

    Bensman, D.; Marhefka, R. J.

    1990-01-01

    The location of a UHF SATCOM antenna on a P-3C aircraft is studied using the NEC-Basic Scattering Code V3.1 (NEC-BSC3). The NEC-BSC3 is a computer code based on the uniform theory of diffraction. The code is first validated for this application using scale model measurements. In general, the comparisons are good except in 10 degree regions near the nose and tail of the aircraft. Patterns for various antenna locations are analyzed to achieve a prescripted performance.

  11. Infectious causes of necrotizing enterocolitis

    PubMed Central

    Coggins, Sarah A.; Wynn, James L.; Weitkamp, Jörn-Hendrik

    2014-01-01

    Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency among premature infants. Although a large body of research has focused on understanding its pathogenesis, the exact mechanism has not been elucidated. Of particular interest is the potential causative role of infectious culprits in the development of NEC. A variety of reports describe bacterial, viral, and fungal infections occurring in association with NEC; however, no organism has emerged as being definitively involved in NEC pathogenesis. In this review, we summarize the body of research on infectious causes of necrotizing enterocolitis. PMID:25678001

  12. Anemia, red blood cell transfusions, and necrotizing enterocolitis.

    PubMed

    Maheshwari, Akhil; Patel, Ravi M; Christensen, Robert D

    2018-02-01

    In the past 15 years, multiple clinical studies have identified a temporal association between red blood cell (RBC) transfusions and necrotizing enterocolitis (NEC). With some variability, most of these studies indicate that up to one-third of all cases of NEC involving very low-birth weight infants may occur within 24-48h after receiving a RBC transfusion. There is also evidence that the risk of such transfusion-associated NEC may be higher in infants transfused with the greatest severity of anemia. In this article, we summarize the clinical evidence pertaining to these issues; specifically, the contribution of RBC transfusions, and the contribution of severity of underlying anemia, to the pathogenesis of a type of NEC potentially termed, "transfusion/anemia-associated NEC." Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Intestinal microbiota and blue baby syndrome

    PubMed Central

    Ellis, Collin L; Rutledge, John C

    2010-01-01

    Necrotizing enterocolitis (NEC) is the most common intestinal emergency among premature infants. Risk factors in premature infants include immature intestinal immunity and an intestinal microbiota dominated by hospital-acquired bacteria. Some probiotics have been shown to decrease the incidence of NEC in premature infants. Among term infants, NEC is rare. However, among term infants with cyanotic congenital heart disease (CCHD), the incidence of NEC is similar to that of premature infants but with even greater mortality rates. Mechanisms by which NEC occurs in term infants with CCHD are unknown. Of central interest is the potential role of changes in the intestinal microbiota and whether these can be modified with probiotic bacteria; accordingly, we review the literature, propose hypotheses and present the rationale for future studies involving preliminary probiotic clinical trials. PMID:21468216

  14. Dual Roles of Endogenous Platelet-activating Factor Acetylhydrolase in a Murine Model of Necrotizing Enterocolitis

    PubMed Central

    Lu, Jing; Pierce, Marissa; Franklin, Andrew; Jilling, Tamas; Stafforini, Diana M.; Caplan, Michael

    2010-01-01

    Human preterm infants with necrotizing enterocolitis (NEC) have increased circulating and luminal levels of platelet-activating factor (PAF) and decreased serum PAF-acetylhydrolase (PAF-AH), the enzyme that inactivates PAF. Formula supplemented with recombinant PAF-AH decreases NEC in a neonatal rat model. We hypothesized that endogenous PAF-AH contributes to neonatal intestinal homeostasis, and therefore developed PAF-AH−/− mice using standard approaches to study the role of this enzyme in the neonatal NEC model. Following exposure to a well-established NEC model, intestinal tissues were evaluated for histology, pro-inflammatory cytokine mRNA synthesis, and death using standard techniques. We found that mortality rates were significantly lower in PAF-AH−/− pups compared to wild-type controls before 24 hours of life but surviving PAF-AH−/− animals were more susceptible to NEC development compared to wild-type controls. Increased NEC incidence was associated with prominent inflammation characterized by elevated intestinal mRNA expression of sPLA2, iNOS and CXCL1. In conclusion, the data support a protective role for endogenous PAF-AH in the development of NEC, and since preterm neonates have endogenous PAF-AH deficiency, this may place them at increased risk for disease. PMID:20531249

  15. Variability of cold season surface air temperature over northeastern China and its linkage with large-scale atmospheric circulations

    NASA Astrophysics Data System (ADS)

    Zhuang, Yuanhuang; Zhang, Jingyong; Wang, Lin

    2018-05-01

    Cold temperature anomalies and extremes have profound effects on the society, the economy, and the environment of northeastern China (NEC). In this study, we define the cold season as the months from October to April, and investigate the variability of cold season surface air temperature (CSAT) over NEC and its relationships with large-scale atmospheric circulation patterns for the period 1981-2014. The empirical orthogonal function (EOF) analysis shows that the first EOF mode of the CSAT over NEC is characterized by a homogeneous structure that describes 92.2% of the total variance. The regionally averaged CSAT over NEC is closely linked with the Arctic Oscillation ( r = 0.62, 99% confidence level) and also has a statistically significant relation with the Polar/Eurasian pattern in the cold season. The positive phases of the Arctic Oscillation and the Polar/Eurasian pattern tend to result in a positive geopotential height anomaly over NEC and a weakened East Asian winter monsoon, which subsequently increase the CSAT over NEC by enhancing the downward solar radiation, strengthening the subsidence warming and warm air advection. Conversely, the negative phases of these two climate indices result in opposite regional atmospheric circulation anomalies and decrease the CSAT over NEC.

  16. The science and necessity of using animal models in the study of necrotizing enterocolitis.

    PubMed

    Ares, Guillermo J; McElroy, Steven J; Hunter, Catherine J

    2018-02-01

    Necrotizing enterocolitis (NEC) remains one of the highest causes of mortality and of acute and long-term morbidity in premature infants. Multiple factors are involved in the pathophysiology of NEC including the immaturity of the immune system and the complex changing composition of the intestinal microbiome. This is compounded by the fact that the premature infant should ideally still be a developing fetus and has an immature intestinal tract. Because these complexities are beyond the scope of studies in single-cell cultures, animal models are absolutely essential to understand the mechanisms involved in the pathophysiology of NEC and the effects of inflammation on the immature intestinal tract. To this end, investigators have utilized many different species (e.g., rats, mice, rabbits, quails, piglets, and non-human primates) and conditions to develop models of NEC. Each animal has distinct advantages and drawbacks related to its preterm viability, body size, genetic variability, and cost. The choice of animal model is strongly influenced by the scientific question being addressed. While no model perfectly mimics human NEC, each has greatly improved our understanding of disease. Examples of recent discoveries in NEC pathogenesis and prevention underscore the importance of continued animal research in NEC. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Design study of a high-resolution breast-dedicated PET system built from cadmium zinc telluride detectors

    PubMed Central

    Peng, Hao; Levin, Craig S

    2013-01-01

    We studied the performance of a dual-panel positron emission tomography (PET) camera dedicated to breast cancer imaging using Monte Carlo simulation. The proposed system consists of two 4 cm thick 12 × 15 cm2 area cadmium zinc telluride (CZT) panels with adjustable separation, which can be put in close proximity to the breast and/or axillary nodes. Unique characteristics distinguishing the proposed system from previous efforts in breast-dedicated PET instrumentation are the deployment of CZT detectors with superior spatial and energy resolution, using a cross-strip electrode readout scheme to enable 3D positioning of individual photon interaction coordinates in the CZT, which includes directly measured photon depth-of-interaction (DOI), and arranging the detector slabs edge-on with respect to incoming 511 keV photons for high photon sensitivity. The simulation results show that the proposed CZT dual-panel PET system is able to achieve superior performance in terms of photon sensitivity, noise equivalent count rate, spatial resolution and lesion visualization. The proposed system is expected to achieve ~32% photon sensitivity for a point source at the center and a 4 cm panel separation. For a simplified breast phantom adjacent to heart and torso compartments, the peak noise equivalent count (NEC) rate is predicted to be ~94.2 kcts s−1 (breast volume: 720 cm3 and activity concentration: 3.7 kBq cm−3) for a ~10% energy window around 511 keV and ~8 ns coincidence time window. The system achieves 1 mm intrinsic spatial resolution anywhere between the two panels with a 4 cm panel separation if the detectors have DOI resolution less than 2 mm. For a 3 mm DOI resolution, the system exhibits excellent sphere resolution uniformity (σrms/mean) ≤ 10%) across a 4 cm width FOV. Simulation results indicate that the system exhibits superior hot sphere visualization and is expected to visualize 2 mm diameter spheres with a 5:1 activity concentration ratio within roughly 7 min imaging time. Furthermore, we observe that the degree of spatial resolution degradation along the direction orthogonal to the two panels that is typical of a limited angle tomography configuration is mitigated by having high-resolution DOI capabilities that enable more accurate positioning of oblique response lines. PMID:20400807

  18. Sexual dimorphism in BDNF signaling after neonatal hypoxia-ischemia and treatment with necrostatin-1

    PubMed Central

    Chavez-Valdez, Raul; Martin, Lee J.; Razdan, Sheila; Gauda, Estelle B.; Northington, Frances J.

    2014-01-01

    Brain injury due to neonatal hypoxia-ischemia (HI) is more homogenously severe in male than in female mice. Because, necrostatin-1 (nec-1) prevents injury progression only in male mice, we hypothesized that changes in BDNF signaling after HI and nec-1 are also sex-specific providing differential conditions to promote recovery of those more severely injured. The increased aromatization of testosterone in male mice during early development and the link between 17-β-estradiol (E2) levels and BDNF transcription substantiate this hypothesis. Hence, we aimed to investigate if sexual differences in BDNF signaling existed in forebrain and diencephalon after HI and HI/ nec-1 and their correlation with estrogen receptors (ER). C57B6 mice (p7) received nec-1(0.1 μL[8μM]) or vehicle (veh) intracerebroventricularly after HI. At 24h after HI, BDNF levels increased in both sexes in forebrain without evidence of TrkB activation. At 96h after HI, BDNF levels in forebrain decreased below those seen in control mice of both sexes. Additionally, only in female mice, truncated TrkB (Tc.TrkB) and p75ntr levels increased in forebrain and diencephalon. In both, forebrain and diencephalon, nec-1 treatment increased BDNF levels and TrkB activation in male mice while, prevented Tc.TrkB and p75ntr increases in female mice. While E2 levels were unchanged by HI or HI/ nec-1 in either sex or treatment, ERα: ERβ ratios were increased in diencephalon of nec-1 treated male mice and directly correlated with BDNF levels. Neonatal HI produces sex-specific signaling changes in the BDNF system, that are differentially modulated by nec-1. The regional differences in BDNF levels may be a consequence of injury severity after HI, but sexual differences in response to nec-1 after HI may represent a differential thalamo-cortical preservation or alternatively off-target regional effect of nec-1. The biological significance of ERα predominance and its correlation with BDNF levels is still unclear. PMID:24361177

  19. Ultrasonography-driven combination antibiotic therapy with tigecycline significantly increases survival among patients with neutropenic enterocolitis following cytarabine-containing chemotherapy for the remission induction of acute myeloid leukemia.

    PubMed

    Pugliese, Novella; Salvatore, Paola; Iula, Dora Vita; Catania, Maria Rosaria; Chiurazzi, Federico; Della Pepa, Roberta; Cerchione, Claudio; Raimondo, Marta; Giordano, Claudia; Simeone, Luigia; Caruso, Simona; Pane, Fabrizio; Picardi, Marco

    2017-07-01

    Neutropenic enterocolitis (NEC) is an abdominal infection reported primarily in patients with acute myeloid leukemia (AML) following chemotherapy, especially cytarabine, a notable efficacious cytotoxic agent for AML remission. Specific data regarding the impact of different cytarabine schedules and/or antibacterial regimens for NEC are sparse. The aim of the study was to identify the predictors of outcome within 30 days of NEC onset. NEC episodes were retrospectively pinpointed among 440 patients with newly diagnosed AML hospitalized in our Institution, over a 10-year period, for receiving chemotherapy protocols with 100-6000 mg/m 2 daily of cytarabine. Two subgroups, survivors versus nonsurvivors, were compared by using logistic regression analysis. NEC was documented in 100 of 420 (23.8%) analyzed patients: 42.5% had received high-dose cytarabine, whereas 19% and 15% intermediate-dose and standard-dose cytarabine, respectively (P < 0.001). The 30-day NEC attributable mortality rate was 23%. In univariate analysis, antileukemic protocols containing robust dosages of cytarabine were significantly associated with high mortality (P < 0.001); whereas, standard-dose cytarabine and prompt initiation (at the ultrasonographic appearance of intestinal mural thickening) of NEC therapy with antibiotic combinations including tigecycline were significantly associated with low mortality. In multivariate analysis, high-dose cytarabine-containing chemotherapy was the independent predictor of poor outcome (odds ratio [OR]: 0.109; 95% confidence interval [CI]: 0.032-0.364; P < 0.001), whereas ultrasonography-driven NEC therapy with antibiotic regimens including tigecycline was associated with a favorable outcome (OR: 13.161; 95% CI: 1.587-109.17; P = 0.017). Chemotherapy schedules with robust dosages of cytarabine for AML remission are associated with a high rate of NEC incidence and attributable. Vigorous antibacterial therapy, triggered off pathologic ultrasonographic findings, with drug combinations which have broad antimicrobial coverage and good gut penetration, specifically those also including tigecycline, may be effective in improving 30-day survival rate after NEC onset. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  20. Net Ecosystem Calcification by a Coral Reef Community under Natural Acidification

    NASA Astrophysics Data System (ADS)

    Shamberger, K.; Lentz, S. J.; Cohen, A. L.

    2016-02-01

    Net Ecosystem Calcification (NEC) is a measure of the balance between calcium carbonate production (calcification) and loss (dissolution) within a coral reef system. Establishing baseline NEC estimates for a broad range of coral reef systems today provides much needed information to constrain spatial and temporal variability within and amongst different systems, investigate the sensitivity of ecosystem scale calcification to environmental forcing, and improve projections of coral reef futures under ocean acidification throughout this century. Previous NEC studies have been limited to coral reefs with unidirectional (Lagrangian and flow respirometry studies) or negligible (slack water Eulerian studies) water flow across the reef for at least part of the day, usually on the order of hours. Here, we present NEC rates in a naturally low pH, semi-enclosed coral reef lagoon with high coral cover and diversity and tidally driven flow within the Palau Rock Islands. NEC was determined from data collected over the full diel cycle for four consecutive days, during two successive years and different seasons, using total alkalinity (TA), salinity, and volume budgets. Two different methods used to calculate NEC are in good agreement and show that the coral community is net calcifying despite high rates of bioerosion and pH (mean pH = 7.88 ± 0.02) and aragonite saturation state (Ωar = 2.66 ± 0.11) levels close to those projected for the end of this century. Critically, NEC rates in year 1 (17.0 - 23.7 mmol m-2 d-1) were half those of year 2 (42.0 - 48.1 mmol m-2 d-1), though the carbonate chemistry of the source water did not change between years. This suggests that single occupations and short term measurements do not adequately capture the full range of NEC variability within a system and that factors other than ocean acidification play an important role in modulating NEC rates.

  1. Brain Barrier Disruption and Region-Specific Neuronal Degeneration during Necrotizing Enterocolitis in Preterm Pigs.

    PubMed

    Brunse, Anders; Abbaspour, Afrouz; Sangild, Per Torp

    2018-06-06

    Necrotizing enterocolitis (NEC) increases the risk of brain injury and impaired neurodevelopment. Rapid brain maturation prior to birth may explain why preterm brains are particularly vulnerable to serious infections. Using pigs as models, we hypothesized that preterm birth was associated with altered blood-cerebrospinal fluid (CSF) barrier (BCSFB) function and cerebral structural deficits, and that NEC was associated with systemic inflammation, BCSFB disruption, and neuroinflammation. First, cesarean-delivered preterm and term pigs (n = 43-44) were euthanized at birth to investigate BCSFB function and markers of brain structural maturation, or on day 5 to measure markers of blood-brain barrier maturation in the hippocampus and striatum (experiment 1). Next, preterm pigs (n = 162) were fed increasing volumes of infant formula to assess NEC lesions, systemic inflammation, BCSFB permeability, cerebral histopathology, hippocampal micro-glial density, and cytokine levels on day 5 (experiments 2 and 3). In experiment 1, preterm newborns had increased CSF-plasma ratios of albumin and raffinose, reduced CSF glucose levels, as well as increased cerebral hydration and reduced white matter myelination compared with term animals. We observed lower hippocampal (but not striatal) perivascular astrocyte coverage for the first 5 days after preterm birth, accompanied by altered cell junction protein levels. In experiments 2 and- 3, piglets with severe NEC lesions showed reduced blood thrombocytes and increased plasma C-reactive protein and interleukin-6 levels. NEC was associated with increased CSF-plasma albumin and raffinose ratios, reduced CSF leukocyte numbers, and increased cerebral hydration. In the hippocampus, NEC was associated with pyramidal neuron loss and increased interleukin-6 levels. In the short term, NEC did not affect cerebral myelination or microglia density. In conclusion, altered BCSFB properties and brain structural deficits were observed in pigs after preterm birth. Acute gastrointestinal NEC lesions were associated with systemic inflammation, increased BCSFB permeability and region-specific neuronal damage. The results demonstrate the importance of early interventions against NEC to prevent brain injury in preterm infants. © 2018 S. Karger AG, Basel.

  2. [Risk factors of necrotizing enterocolitis].

    PubMed

    Tapia-Rombo, C A; Velasco-Lavín, M R; Nieto-Caldelas, A

    1993-09-01

    The purpose of the present study is to compare risk factors of necrotizing enterocolitis (NEC) between two group: group A, newborns with the disease and group B, newborns with other diseases different from NEC, in order to know if these risk factors are more frequent or not in the first group. We assessed the clinical records of all the patients hospitalized in the Neonatal Intensive Care Unit and Neonatology Service of the La Raza General Hospital between 1987 and 1991 with the diagnosis of NEC. They were compared with 65 clinical records chosen at random of patients hospitalized in the same Unit with other diagnosis at the same time, and who were discharged by improvement or deceased. In all of them were look for known risk factors for NEC generally accepted such as: prematurity, neonatal asphyxia, poliglobulia, cyanotic congenital heart disease, patent ductus arteriosus, respiratory distress syndrome, catheterization of umbilical vessels, early feeding of elevated formula increases, exchange exchange transfusion, hypoxic ischemic encephalopathy, infection, etc. Just 25 records of the possible 50 with the diagnosis of NEC full filled inclusion criteria. There were no statistically significant difference in weight, sex, mortality and known risk factors of NEC between both groups. Were concluded that NEC is a disease of unknown etiology that should be studied more thoroughly. The known risk factors must be avoided because the patient susceptibility probably play an important role.

  3. Human Cytomegalovirus Nuclear Capsids Associate with the Core Nuclear Egress Complex and the Viral Protein Kinase pUL97

    PubMed Central

    Sonntag, Eric; Wagner, Sabrina; Strojan, Hanife; Wangen, Christina; Lenac Rovis, Tihana; Lisnic, Berislav; Jonjic, Stipan; Schlötzer-Schrehardt, Ursula; Marschall, Manfred

    2018-01-01

    The nuclear phase of herpesvirus replication is regulated through the formation of regulatory multi-component protein complexes. Viral genomic replication is followed by nuclear capsid assembly, DNA encapsidation and nuclear egress. The latter has been studied intensely pointing to the formation of a viral core nuclear egress complex (NEC) that recruits a multimeric assembly of viral and cellular factors for the reorganization of the nuclear envelope. To date, the mechanism of the association of human cytomegalovirus (HCMV) capsids with the NEC, which in turn initiates the specific steps of nuclear capsid budding, remains undefined. Here, we provide electron microscopy-based data demonstrating the association of both nuclear capsids and NEC proteins at nuclear lamina budding sites. Specifically, immunogold labelling of the core NEC constituent pUL53 and NEC-associated viral kinase pUL97 suggested an intranuclear NEC-capsid interaction. Staining patterns with phospho-specific lamin A/C antibodies are compatible with earlier postulates of targeted capsid egress at lamina-depleted areas. Important data were provided by co-immunoprecipitation and in vitro kinase analyses using lysates from HCMV-infected cells, nuclear fractions, or infectious virions. Data strongly suggest that nuclear capsids interact with pUL53 and pUL97. Combined, the findings support a refined concept of HCMV nuclear trafficking and NEC-capsid interaction. PMID:29342872

  4. The Numerical Electromagnetics Code (NEC) - A Brief History

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

    Burke, G J; Miller, E K; Poggio, A J

    The Numerical Electromagnetics Code, NEC as it is commonly known, continues to be one of the more widely used antenna modeling codes in existence. With several versions in use that reflect different levels of capability and availability, there are now 450 copies of NEC4 and 250 copies of NEC3 that have been distributed by Lawrence Livermore National Laboratory to a limited class of qualified recipients, and several hundred copies of NEC2 that had a recorded distribution by LLNL. These numbers do not account for numerous copies (perhaps 1000s) that were acquired through other means capitalizing on the open source code,more » the absence of distribution controls prior to NEC3 and the availability of versions on the Internet. In this paper we briefly review the history of the code that is concisely displayed in Figure 1. We will show how it capitalized on the research of prominent contributors in the early days of computational electromagnetics, how a combination of events led to the tri-service-supported code development program that ultimately led to NEC and how it evolved to the present day product. The authors apologize that space limitations do not allow us to provide a list of references or to acknowledge the numerous contributors to the code both of which can be found in the code documents.« less

  5. Heparin-binding EGF-like growth factor and enteric neural stem cell transplantation in the prevention of experimental necrotizing enterocolitis in mice.

    PubMed

    Wei, Jia; Zhou, Yu; Besner, Gail E

    2015-07-01

    Necrotizing enterocolitis (NEC) is associated with loss of neurons and glial cells in the enteric nervous system (ENS). Our goal was to determine whether enteric neural stem cell (NSC) transplantation, in conjunction with heparin-binding epidermal growth factor-like growth factor (HB-EGF), could protect against experimental NEC. In vitro, HB-EGF on NSC proliferation and migration, and the effects of receptors utilized by HB-EGF to exert these effects, were determined. In vivo, mouse pups were exposed to experimental NEC and treated with NSC alone, HB-EGF alone, NSC+HB-EGF, or HB-EGF overexpressing NSC. NSC engraftment and differentiation into neurons in the ENS, intestinal injury, intestinal permeability, and intestinal motility were determined. HB-EGF promoted NSC proliferation via ErbB-1 receptors and enhanced NSC migration via ErbB-1, ErbB-4, and Nardilysin receptors. HB-EGF significantly enhanced the engraftment of transplanted NSC into the ENS during NEC. NSC transplantation significantly reduced NEC incidence and improved gut barrier function and intestinal motility, and these effects were augmented by simultaneous administration of HB-EGF or by transplantation of HB-EGF overexpressing NSC. HB-EGF promotes NSC proliferation and migration. HB-EGF and NSC reduce intestinal injury and improve gut barrier function and intestinal motility in experimental NEC. Combined HB-EGF and NSC transplantation may represent a potential future therapy to prevent NEC.

  6. Human Cytomegalovirus Nuclear Capsids Associate with the Core Nuclear Egress Complex and the Viral Protein Kinase pUL97.

    PubMed

    Milbradt, Jens; Sonntag, Eric; Wagner, Sabrina; Strojan, Hanife; Wangen, Christina; Lenac Rovis, Tihana; Lisnic, Berislav; Jonjic, Stipan; Sticht, Heinrich; Britt, William J; Schlötzer-Schrehardt, Ursula; Marschall, Manfred

    2018-01-13

    The nuclear phase of herpesvirus replication is regulated through the formation of regulatory multi-component protein complexes. Viral genomic replication is followed by nuclear capsid assembly, DNA encapsidation and nuclear egress. The latter has been studied intensely pointing to the formation of a viral core nuclear egress complex (NEC) that recruits a multimeric assembly of viral and cellular factors for the reorganization of the nuclear envelope. To date, the mechanism of the association of human cytomegalovirus (HCMV) capsids with the NEC, which in turn initiates the specific steps of nuclear capsid budding, remains undefined. Here, we provide electron microscopy-based data demonstrating the association of both nuclear capsids and NEC proteins at nuclear lamina budding sites. Specifically, immunogold labelling of the core NEC constituent pUL53 and NEC-associated viral kinase pUL97 suggested an intranuclear NEC-capsid interaction. Staining patterns with phospho-specific lamin A/C antibodies are compatible with earlier postulates of targeted capsid egress at lamina-depleted areas. Important data were provided by co-immunoprecipitation and in vitro kinase analyses using lysates from HCMV-infected cells, nuclear fractions, or infectious virions. Data strongly suggest that nuclear capsids interact with pUL53 and pUL97. Combined, the findings support a refined concept of HCMV nuclear trafficking and NEC-capsid interaction.

  7. Lactobacillus rhamnosus HN001 decreases the severity of necrotizing enterocolitis in neonatal mice and preterm piglets: evidence in mice for a role of TLR9

    PubMed Central

    Good, Misty; Sodhi, Chhinder P.; Ozolek, John A.; Buck, Rachael H.; Goehring, Karen C.; Thomas, Debra L.; Vikram, Amit; Bibby, Kyle; Morowitz, Michael J.; Firek, Brian; Lu, Peng

    2014-01-01

    Necrotizing enterocolitis (NEC) is the leading cause of death from gastrointestinal disease in premature infants and develops partly from an exaggerated intestinal epithelial immune response to indigenous microbes. There has been interest in administering probiotic bacteria to reduce NEC severity, yet concerns exist regarding infection risk. Mechanisms of probiotic activity in NEC are unknown although activation of the microbial DNA receptor Toll-like receptor-9 (TLR9) has been postulated. We now hypothesize that the Gram-positive bacterium Lactobacillus rhamnosus HN001 can attenuate NEC in small and large animal models, that its microbial DNA is sufficient for its protective effects, and that protection requires activation of the Toll-like receptor 9 (TLR9). We now show that oral administration of live or UV-inactivated Lactobacillus rhamnosus HN001 attenuates NEC severity in newborn mice and premature piglets, as manifest by reduced histology score, attenuation of mucosal cytokine response, and improved gross morphology. TLR9 was required for Lactobacillus rhamnosus-mediated protection against NEC in mice, as the selective decrease of TLR9 from the intestinal epithelium reversed its protective effects. Strikingly, DNA of Lactobacillus rhamnosus HN001 reduced the extent of proinflammatory signaling in cultured enterocytes and in samples of resected human ileum ex vivo, suggesting the therapeutic potential of this probiotic in clinical NEC. Taken together, these findings illustrate that Lactobacillus rhamnosus HN001 is an effective probiotic for NEC via activation of the innate immune receptor TLR9 and that Lactobacillus rhamnosus DNA is sufficient for its protective effects, potentially reducing concerns regarding the infectious risk of this novel therapeutic approach. PMID:24742987

  8. Abdominal and hepatic uptake of /sup 99m/Tc-pyrophosphate in neonatal necrotizing enterocolitis

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

    Caride, V.J.; Touloukian, R.J.; Ablow, R.C.

    1981-04-01

    Abdominal /sup 99m/Tc-pyrophosphate (/sup 99m/Tc-PYP) scans were obtained in 15 neonates: 12 with neonatal necrotizing enterocolitis (NEC), two with osteomyelitis, and one with myocarditis. Ten of the babies with NEC had at least one positive scan; of these 10 studies, seven (Group A) showed both diffuse abdominal uptake and localized hepatic activity, two (Group B) showed abdominal uptake and questionable hepatic uptake, and one (Group C) demonstrated diffuse abdominal uptake only. The other two babies with NEC had normal scans (Group D). All NEC patients had normal scans. A patient with myocarditis had hepatic uptake of /sup 99m/Tc-PYP while themore » abdominal scan in the two infants with osteomyelitis was normal. These preliminary observations suggest that further study of a relationship between abdominal scan findings and the course of NEC is warranted.« less

  9. An Exploratory Case Study of Young Children's Interactive Play Behaviours with a Non-English Speaking Child

    ERIC Educational Resources Information Center

    Lee, Joohi; Md-Yunus, Sham'ah; Son, Won In; Meadows, Michelle

    2009-01-01

    This study is an examination of preschool-age English speaking children's interactive play behaviours with a non-English speaking child (NEC). The play types of a NEC were reported using the Parten's categories of solitary, parallel and interactive play. In addition, English-speaking children's interactive play with a NEC were reported in this…

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

    Fitzpatrick, F.C.; Gray, D.D.; Hyndman, J.R.

    The thermal, ecological, and social impacts of a 40-reactor NEC are compared to impacts from four 10-reactor NECs and ten 4-reactor power plants. The comparison was made for surrogate sites in western Tennessee. The surrogate site for the 40-reactor NEC is located on Kentucky Lake. A layout is postulated for ten clusters of four reactors each with 2.5-mile spacing between clusters. The plants use natural-draft cooling towers. A transmission system is proposed for delivering the power (48,000 MW) to five load centers. Comparable transmission systems are proposed for the 10-reactor NECs and the 4-reactor dispersed sites delivering power to themore » same load centers. (auth)« less

  11. Necrotizing Enterocolitis and Human Milk Feeding: A Systematic Review.

    PubMed

    Cacho, Nicole Theresa; Parker, Leslie A; Neu, Josef

    2017-03-01

    This article summarizes evidence regarding whether a donor human milk (DHM) and/or an exclusively human milk (EHM) diet decreases the incidence of necrotizing enterocolitis (NEC) and the dose of human milk (HM) necessary to reduce the risk of NEC in premature infants. Additional research regarding protection afforded by DHM and EHM is necessary as well as research elucidating the exact dose of HM necessary for NEC risk reduction. Research is also needed to determine whether there is a dose-dependent effect of DHM, a combination of mother's own milk and DHM, and an EHM diet on NEC incidence. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Update in Pathogenesis and Prospective in Treatment of Necrotizing Enterocolitis

    PubMed Central

    Terrin, Gianluca; Scipione, Antonella; De Curtis, Mario

    2014-01-01

    Necrotizing enterocolitis (NEC) is among the most common and devastating diseases in neonates and, despite the significant advances in neonatal clinical and basic science investigations, its etiology is largely understood, specific treatment strategies are lacking, and morbidity and mortality remain high. Improvements in the understanding of pathogenesis of NEC may have therapeutic consequences. Pharmacologic inhibition of toll-like receptor signaling, the use of novel nutritional strategies, and microflora modulation may represent novel promising approaches to the prevention and treatment of NEC. This review, starting from the recent acquisitions in the pathogenic mechanisms of NEC, focuses on current and possible therapeutic perspectives. PMID:25147804

  13. Neuroendocrine Carcinomas of the Gastroenteropancreatic System: A Comprehensive Review

    PubMed Central

    Ilett, Emma Elizabeth; Langer, Seppo W.; Olsen, Ingrid Holst; Federspiel, Birgitte; Kjær, Andreas; Knigge, Ulrich

    2015-01-01

    To date, empirical literature has generally been considered lacking in relation to neuroendocrine carcinomas (NECs), the highly malignant subgroup of neuroendocrine neoplasms. NECs are often found in the lungs or the gastroenteropancreatic (GEP) system and can be of small or large cell type. Concentrating on GEP-NECs, we can conclude that survival times are poor, with a median of only 4–16 months depending on disease stage and primary site. Further, this aggressive disease appears to be on the rise, with incidence numbers increasing while survival times are stagnant. Treatment strategies concerning surgery are often undecided and second-line chemotherapy is not yet established. After an analysis of over 2600 articles, we can conclude that there is indeed more empirical literature concerning GEP-NECs available than previously assumed. This unique review is based on 333 selected articles and contains detailed information concerning all aspects of GEP-NECs. Namely, the classification, histology, genetic abnormalities, epidemiology, origin, biochemistry, imaging, treatment and survival of GEP-NECs are described. Also, organ-specific summaries with more detail in relation to disease presentation, diagnosis, treatment and survival are presented. Finally, key points are discussed with directions for future research priorities. PMID:26854147

  14. Necrotizing Enterocolitis is associated with Ureaplasma Colonization in Preterm Infants

    PubMed Central

    Okogbule-Wonodi, Adora C.; Gross, George W.; Sun, Chen-Chih J.; Agthe, Alexander G.; Xiao, Li; Waites, Ken B.; Viscardi, Rose Marie

    2014-01-01

    The study objective was to determine whether Ureaplasma respiratory tract colonization of preterm infants <33 weeks gestation is associated with an increased risk for necrotizing enterocolitis (NEC). One or more tracheal or nasopharyngeal aspirates for Ureaplasma culture and PCR were obtained during the first week of life from 368 infants <33 weeks gestation enrolled from 1999-2003 or from 2007-2009. NEC Bell stage ≥2 was confirmed by radiological criteria, and pathology, if available. Cord serum samples were analyzed for IL-6 and IL-1β concentrations and placentas were reviewed for histological chorioamnionitis in the first cohort. NEC was confirmed in 29/368 (7.9%) of the combined cohorts. The incidence of NEC was 2.2-fold higher in Ureaplasma-positive (12.3%) than Ureaplasma-negative infants (5.5%) <33 wk (OR 2.43, 95%CI 1.13-5.22, P=0.023) and 3.3-fold higher in Ureaplasma-positive (14.6%) than Ureaplasma-negative (4.4%) infants ≤28 wks (OR 3.67, 95%CI 1.36-9.93, P=0.01). Age of onset, hematologic parameters at onset, and NEC severity were similar between Ureaplasma-positive and negative infants. Cord serum IL-6 and IL-1β concentrations were significantly higher in Ureaplasma-positive than in Ureaplasma-negative NEC-affected infants. Ureaplasma may be a factor in NEC pathogenesis in preterm infants by contributing to intestinal mucosal injury and/or altering systemic or local immune responses. PMID:21258263

  15. Necrotizing enterocolitis is associated with earlier achievement of enteral autonomy in children with short bowel syndrome.

    PubMed

    Sparks, Eric A; Khan, Faraz A; Fisher, Jeremy G; Fullerton, Brenna S; Hall, Amber; Raphael, Bram P; Duggan, Christopher; Modi, Biren P; Jaksic, Tom

    2016-01-01

    Necrotizing enterocolitis (NEC) remains one of the most common underlying diagnoses of short bowel syndrome (SBS) in children. The relationship between the etiology of SBS and ultimate enteral autonomy has not been well studied. This investigation sought to evaluate the rate of achievement of enteral autonomy in SBS patients with and without NEC. Following IRB approval, 109 patients (2002-2014) at a multidisciplinary intestinal rehabilitation program were reviewed. The primary outcome evaluated was achievement of enteral autonomy (i.e. fully weaning from parenteral nutrition). Patient demographics, primary diagnosis, residual small bowel length, percent expected small bowel length, median serum citrulline level, number of abdominal operations, status of the ileocecal valve (ICV), presence of ileostomy, liver function tests, and treatment for bacterial overgrowth were recorded for each patient. Median age at PN onset was 0 weeks [IQR 0-0]. Median residual small bowel length was 33.5 cm [IQR 20-70]. NEC was present in 37 of 109 (33.9%) of patients. 45 patients (41%) achieved enteral autonomy after a median PN duration of 15.3 [IQR 7.2-38.4]months. Overall, 64.9% of patients with NEC achieved enteral autonomy compared to 29.2% of patients with a different primary diagnosis (p=0.001, Fig. 1). Patients with NEC remained more likely than those without NEC to achieve enteral autonomy after two (45.5% vs. 12.0%) and four (35.7% vs. 6.3%) years on PN (Fig. 1). Logistic regression analysis demonstrated the following parameters as independent predictors of enteral autonomy: diagnosis of NEC (p<0.002), median serum citrulline level (p<0.02), absence of a jejunostomy or ileostomy (p=0.013), and percent expected small bowel length (p=0.005). Children with SBS because of NEC have a significantly higher likelihood of fully weaning from parenteral nutrition compared to children with other causes of SBS. Additionally, patients with NEC may attain enteral autonomy even after long durations of parenteral support. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Ischemia Reperfusion Injury Triggers TNFα Induced-Necroptosis in Rat Retina.

    PubMed

    Kim, Cho Rong; Kim, Jie Hyun; Park, Hae-Young Lopilly; Park, Chan Kee

    2017-05-01

    A recent study revealed a novel form of cell death, termed necroptosis, or programmed necrosis. Previous research indicated that after ischemia-reperfusion (IR) injury to the retina, Tumor Necrosis Factor α (TNFα) is increased, which may activate necroptosis. This study observed macroglial cell activation, and in particular, astrocyte activation, after the release of TNFα and other necroptosis factors in the rat retina due to IR. IR was induced in the retinas of adult male Sprague-Dawley rats by increasing the intraocular pressure to 160 mmHg and then allowing reperfusion. In addition, to inhibit necroptosis, Nec-1 (necrostatin-1) was injected intravitreally after IR. Rats were sacrificed after reperfusion at 12 hours, 1, 3, and 5 days, and 1 and 2 weeks. Retinas from each time point were analyzed by immunohistochemistry (IHC) and Western blotting (WB) to identify the initiator of necroptosis, TNFα, the expression of necroptosis factors, such as receptor interacting protein (RIP) 1, 3, and inactive caspase 8, and Brn3a. Cell death in the IR-injured retinas was identified by cell counting. We found decreased retinal cell numbers in the inner and outer nuclear layers (INL and ONL), as well as in the ganglion cell layer (GCL). Increased glial cell activation was detected by using glial fibrillary acidic protein (GFAP) IHC. TNFα, RIP1, RIP3, and inactive caspase 8 were mainly expressed in the GCL after IR, as determined by IHC and WB. Nec-1 inhibited RIP1, a necroptosis factor, indicating protection against retinal cell loss after IR injury. We showed that IR injury triggered increases in both activation of astrocytes and the expression of TNFα. In addition, TNFα, which was activated by IR, triggered the release of necroptosis factors, particularly, in GCL. Inhibition of necroptosis using Nec-1 decreased the level of RIP1 and retinal cell loss in IR-injured retinas.

  17. A quality improvement initiative to reduce necrotizing enterocolitis across hospital systems.

    PubMed

    Nathan, Amy T; Ward, Laura; Schibler, Kurt; Moyer, Laurel; South, Andrew; Kaplan, Heather C

    2018-04-20

    Necrotizing enterocolitis (NEC) is a devastating intestinal disease in premature infants. Local rates of NEC were unacceptably high. We hypothesized that utilizing quality improvement methodology to standardize care and apply evidence-based practices would reduce our rate of NEC. A multidisciplinary team used the model for improvement to prioritize interventions. Three neonatal intensive care units (NICUs) developed a standardized feeding protocol for very low birth weight (VLBW) infants, and employed strategies to increase the use of human milk, maximize intestinal perfusion, and promote a healthy microbiome. The primary outcome measure, NEC in VLBW infants, decreased from 0.17 cases/100 VLBW patient days to 0.029, an 83% reduction, while the compliance with a standardized feeding protocol improved. Through reliable implementation of evidence-based practices, this project reduced the regional rate of NEC by 83%. A key outcome and primary driver of success was standardization across multiple NICUs, resulting in consistent application of best practices and reduction in variation.

  18. Case of gastric neuroendocrine carcinoma showing an interesting tumorigenic pathway.

    PubMed

    Uesugi, Noriyuki; Sugimoto, Ryo; Eizuka, Makoto; Fujita, Yasuko; Osakabe, Mitsumasa; Koeda, Keisuke; Kosaka, Takashi; Yanai, Shunichi; Ishida, Kazuyuki; Sasaki, Akira; Matsumoto, Takayuki; Sugai, Tamotsu

    2017-11-16

    Here, we report a case of gastric neuroendocrine carcinoma showing an interesting tumorigenic pathway. A 57-year-old Japanese woman presented with epigastric tenderness, and distal gastrectomy was performed. In the surgical specimen, histologically, the tumor tissue was composed of three subtypes of tumor components showing different histological architecture and cellular atypia, diagnosed as neuroendocrine tumor (NET) G2, NET G3, and neuroendocrine carcinoma (NEC) components. Immunohistochemically, the Ki-67-positive rates of NET G2, NET G3, and NEC components were 6.5%, 99.5% and 88.1%, respectively. Although allelic imbalance (AI) on chromosomes 1p, 3p, 8q, TP53, 18q and 22q was commonly found in all components, AI of 4p was found in NET G3 and NEC components (but not in the NET G2 component). In contrast, AIs of 5q and 9p were found in only the NEC component. Thus, we showed the progression from NET G2 to NEC, via NET G3, within the same tumor.

  19. Preterm infants with necrotising enterocolitis demonstrate an unbalanced gut microbiota.

    PubMed

    Itani, Tarek; Ayoub Moubareck, Carole; Melki, Imad; Rousseau, Clotilde; Mangin, Irène; Butel, Marie-José; Karam-Sarkis, Dolla

    2018-01-01

    This Lebanese study tested the hypothesis that differences would exist in the gut microbiota of preterm infants with and without necrotising enterocolitis (NEC), as reported in Western countries. This study compared 11 infants with NEC and 11 controls, all born at 27-35 weeks, in three neonatal intensive care units between January 2013 and March 2015. Faecal samples were collected at key time points, and microbiota was analysed by culture, quantitative PCR (qPCR) and temperature temporal gel electrophoresis (TTGE). The cultures revealed that all preterm infants were poorly colonised and harboured no more than seven species. Prior to NEC diagnosis, significant differences were observed by qPCR with a higher colonisation by staphylococci (p = 0.034) and lower colonisations by enterococci (p = 0.039) and lactobacilli (p = 0.048) in the NEC group compared to the healthy controls. Throughout the study, virtually all of the infants were colonised by Enterobacteriaceae at high levels. TTGE analysis revealed no particular clusterisation, showing high interindividual variability. The NEC infants were poorly colonised with no more than seven species, and the controls had a more diversified and balanced gut microbiota. Understanding NEC aetiology better could lead to more effective prophylactic interventions and a reduced incidence. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  20. Attenuation of cadmium-induced necrotic cell death by necrostatin-1: Potential necrostatin-1 acting sites

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

    Hsu, T.-S.; Yang, P.-M.; Tsai, J.-S.

    2009-03-01

    Cadmium (Cd) induces necrotic death in Chinese hamster ovary (CHO) K1 cells and we have established the responsible signaling pathway. Reportedly, necrostatin-1 (Nec-1) rescues cells from necrotic death by mediating through the death domain receptor (DR) signaling pathway. We show here that Nec-1 also effectively attenuates necrotic death triggered by Cd. Two other treatments that cause necrotic cell death, one can (z-VAD-fmk/TNF-{alpha} on U937 cells) and the other cannot (etherynic acid (EA) on DLD-1 cells) be rescued by Nec-1, were also studied in parallel for comparison. Results show that Nec-1 is ineffectual in modulating intracellular calcium contents, calpain activity (amore » downstream protease), or reactive oxygen species production. It can counteract the reduction in mitochondrial membrane potential (MMP) caused by treating CHO K1 or U937 cells with necrosis-inducing agent. However, this effect was not found in EA-treated DLD-1 cells. Notably, Nec-1 elevates NF-{kappa}B activity in the presence or absence of necrosis-inducing agents. Our study shows that, in addition to DR-mediated necrosis, Nec-1 is effective in attenuating Cd-induced necrosis. It rescues cells with reduced MMP implying that mitochondrion is its major acting site.« less

  1. Differential effects of lesion mimic mutants in barley on disease development by facultative pathogens

    PubMed Central

    McGrann, Graham R. D.; Steed, , Andrew; Burt, Christopher; Nicholson, Paul; Brown, James K. M.

    2015-01-01

    Lesion mimic mutants display spontaneous necrotic spots and chlorotic leaves as a result of mis-regulated cell death programmes. Typically these mutants have increased resistance to biotrophic pathogens but their response to facultative fungi that cause necrotrophic diseases is less well studied. The effect of altered cell death regulation on the development of disease caused by Ramularia collo-cygni, Fusarium culmorum and Oculimacula yallundae was explored using a collection of barley necrotic (nec) lesion mimic mutants. nec8 mutants displayed lower levels of all three diseases compared to nec9 mutants, which had increased R. collo-cygni but decreased F. culmorum disease symptoms. nec1 mutants reduced disease development caused by both R. collo-cygni and F. culmorum. The severity of the nec1-induced lesion mimic phenotype and F. culmorum symptom development was reduced by mutation of the negative cell death regulator MLO. The significant reduction in R. collo-cygni symptoms caused by nec1 was completely abolished in the presence of the mlo-5 allele and both symptoms and fungal biomass were greater than in the wild-type. These results indicate that physiological pathways involved in regulation of cell death interact with one another in their effects on different fungal pathogens. PMID:25873675

  2. Bifidobacterium bifidum in a Rat Model of Necrotizing Enterocolitis: Antimicrobial Peptide and Protein Responses

    PubMed Central

    Underwood, Mark A.; Kananurak, Anchasa; Coursodon, Christine F.; Adkins-Reick, Camille K.; Chu, Hiutung; Bennett, Stephen H.; Wehkamp, Jan; Castillo, Patricia A.; Leonard, Brian C.; Tancredi, Daniel J.; Sherman, Michael P.; Dvorak, Bohuslav; Bevins, Charles L.

    2013-01-01

    Necrotizing enterocolitis (NEC) is a devastating disease of premature infants. Probiotics decrease the risk of NEC in clinical and experimental studies. Antimicrobial peptides protect the gut against noxious microbes and shape the commensal microbiota, but their role in NEC remains unclear. We report that like in human ontogeny, the rat pup has low expression of Paneth cell antimicrobials, which increases rapidly during normal development. To investigate the expression of antimicrobial peptides in experimental NEC and the impact of probiotics on their expression, premature rats were divided into three groups: dam fed (DF), hand fed with formula (FF), or hand fed with formula containing Bifidobacterium bifidum (FF+BIF). All groups were exposed to asphyxia and cold stress. The expression of lysozyme, secretory phospholipase A2, pancreatic-associated proteins 1 and 3 mRNA was elevated in the FF (NEC) group, compared to the DF and FF+BIF groups where disease was attenuated. We conclude that induction of antimicrobial peptides occurs in experimental NEC similar to that reported in human disease and is attenuated when disease is averted by probiotic B. bifidum. The induction of antimicrobial peptides is likely an adaptive mucosal response that is often not sufficient to prevent disease in the premature gut. PMID:22322385

  3. Interferon-gamma inhibits intestinal restitution by preventing gap junction communication between enterocytes.

    PubMed

    Leaphart, Cynthia L; Qureshi, Faisal; Cetin, Selma; Li, Jun; Dubowski, Theresa; Baty, Catherine; Batey, Catherine; Beer-Stolz, Donna; Guo, Fengli; Murray, Sandra A; Hackam, David J

    2007-06-01

    Necrotizing enterocolitis (NEC) is characterized by interferon-gamma (IFN-gamma) release and inadequate intestinal restitution. Because enterocytes migrate together, mucosal healing may require interenterocyte communication via connexin 43-mediated gap junctions. We hypothesize that enterocyte migration requires interenterocyte communication, that IFN impairs migration by impairing connexin 43, and that impaired healing during NEC is associated with reduced gap junctions. NEC was induced in Swiss-Webster or IFN(-/-) mice, and restitution was determined in the presence of the gap junction inhibitor oleamide, or via time-lapse microscopy of IEC-6 cells. Connexin 43 expression, trafficking, and localization were detected in cultured or primary enterocytes or mouse or human intestine by confocal microscopy and (35)S-labeling, and gap junction communication was assessed using live microscopy with oleamide or connexin 43 siRNA. Enterocytes expressed connexin 43 in vitro and in vivo, and exchanged fluorescent dye via gap junctions. Gap junction inhibition significantly reduced enterocyte migration in vitro and in vivo. NEC was associated with IFN release and loss of enterocyte connexin 43 expression. IFN inhibited enterocyte migration by reducing gap junction communication through the dephosphorylation and internalization of connexin 43. Gap junction inhibition significantly increased NEC severity, whereas reversal of the inhibitory effects of IFN on gap junction communication restored enterocyte migration after IFN exposure. Strikingly, IFN(-/-) mice were protected from the development of NEC, and showed restored connexin 43 expression and intestinal restitution. IFN inhibits enterocyte migration by preventing interenterocyte gap junction communication. Connexin 43 loss may provide insights into the development of NEC, in which restitution is impaired.

  4. The human milk oligosaccharide 2'-fucosyllactose attenuates the severity of experimental necrotising enterocolitis by enhancing mesenteric perfusion in the neonatal intestine.

    PubMed

    Good, Misty; Sodhi, Chhinder P; Yamaguchi, Yukihiro; Jia, Hongpeng; Lu, Peng; Fulton, William B; Martin, Laura Y; Prindle, Thomas; Nino, Diego F; Zhou, Qinjie; Ma, Congrong; Ozolek, John A; Buck, Rachael H; Goehring, Karen C; Hackam, David J

    2016-10-01

    Necrotising enterocolitis (NEC) is a common disease in premature infants characterised by intestinal ischaemia and necrosis. The only effective preventative strategy against NEC is the administration of breast milk, although the protective mechanisms remain unknown. We hypothesise that an abundant human milk oligosaccharide (HMO) in breast milk, 2'-fucosyllactose (2'FL), protects against NEC by enhancing intestinal mucosal blood flow, and we sought to determine the mechanisms underlying this protection. Administration of HMO-2'FL protected against NEC in neonatal wild-type mice, resulted in a decrease in pro-inflammatory markers and preserved the small intestinal mucosal architecture. These protective effects occurred via restoration of intestinal perfusion through up-regulation of the vasodilatory molecule endothelial nitric oxide synthase (eNOS), as administration of HMO-2'FL to eNOS-deficient mice or to mice that received eNOS inhibitors did not protect against NEC, and by 16S analysis HMO-2'FL affected the microbiota of the neonatal mouse gut, although these changes do not seem to be the primary mechanism of protection. Induction of eNOS by HMO-2'FL was also observed in cultured endothelial cells, providing a link between eNOS and HMO in the endothelium. These data demonstrate that HMO-2'FL protects against NEC in part through maintaining mesenteric perfusion via increased eNOS expression, and suggest that the 2'FL found in human milk may be mediating some of the protective benefits of breast milk in the clinical setting against NEC.

  5. Antibiotics modulate intestinal immunity and prevent necrotizing enterocolitis in preterm neonatal piglets

    PubMed Central

    Jensen, Michael L.; Thymann, Thomas; Cilieborg, Malene S.; Lykke, Mikkel; Mølbak, Lars; Jensen, Bent B.; Schmidt, Mette; Kelly, Denise; Mulder, Imke; Burrin, Douglas G.

    2013-01-01

    Preterm birth, bacterial colonization, and formula feeding predispose to necrotizing enterocolitis (NEC). Antibiotics are commonly administered to prevent sepsis in preterm infants, but it is not known whether this affects intestinal immunity and NEC resistance. We hypothesized that broad-spectrum antibiotic treatment improves NEC resistance and intestinal structure, function, and immunity in neonates. Caesarean-delivered preterm pigs were fed 3 days of parenteral nutrition followed by 2 days of enteral formula. Immediately after birth, they were assigned to receive either antibiotics (oral and parenteral doses of gentamycin, ampicillin, and metronidazole, ANTI, n = 11) or saline in the control group (CON, n = 13), given twice daily. NEC lesions and intestinal structure, function, microbiology, and immunity markers were recorded. None of the ANTI but 85% of the CON pigs developed NEC lesions by day 5 (0/11 vs. 11/13, P < 0.05). ANTI pigs had higher intestinal villi (+60%), digestive enzyme activities (+53–73%), and goblet cell densities (+110%) and lower myeloperoxidase (−51%) and colonic microbial density (105 vs. 1010 colony-forming units, all P < 0.05). Microarray transcriptomics showed strong downregulation of genes related to inflammation and innate immune response to microbiota and marked upregulation of genes related to amino acid metabolism, in particular threonine, glucose transport systems, and cell cycle in 5-day-old ANTI pigs. In a follow-up experiment, 5 days of antibiotics prevented NEC at least until day 10. Neonatal prophylactic antibiotics effectively reduced gut bacterial load, prevented NEC, intestinal atrophy, dysfunction, and inflammation and enhanced expression of genes related to gut metabolism and immunity in preterm pigs. PMID:24157972

  6. The human milk oligosaccharide 2′-fucosyllactose attenuates the severity of experimental necrotising enterocolitis by enhancing mesenteric perfusion in the neonatal intestine

    PubMed Central

    Good, Misty; Sodhi, Chhinder P.; Yamaguchi, Yukihiro; Jia, Hongpeng; Lu, Peng; Fulton, William B.; Martin, Laura Y.; Prindle, Thomas; Nino, Diego F.; Zhou, Qinjie; Ma, Congrong; Ozolek, John A.; Buck, Rachael H.; Goehring, Karen C.; Hackam, David J.

    2016-01-01

    Necrotising enterocolitis (NEC) is a common disease in premature infants characterised by intestinal ischaemia and necrosis. The only effective preventative strategy against NEC is the administration of breast milk, although the protective mechanisms remain unknown. We hypothesise that an abundant human milk oligosaccharide (HMO) in breast milk, 2′-fucosyllactose (2′FL), protects against NEC by enhancing intestinal mucosal blood flow, and we sought to determine the mechanisms underlying this protection. Administration of HMO-2′FL protected against NEC in neonatal wild-type mice, resulted in a decrease in pro-inflammatory markers and preserved the small intestinal mucosal architecture. These protective effects occurred via restoration of intestinal perfusion through up-regulation of the vasodilatory molecule endothelial nitric oxide synthase (eNOS), as administration of HMO-2′FL to eNOS-deficient mice or to mice that received eNOS inhibitors did not protect against NEC, and by 16S analysis HMO-2′FL affected the microbiota of the neonatal mouse gut, although these changes do not seem to be the primary mechanism of protection. Induction of eNOS by HMO-2′FL was also observed in cultured endothelial cells, providing a link between eNOS and HMO in the endothelium. These data demonstrate that HMO-2′FL protects against NEC in part through maintaining mesenteric perfusion via increased eNOS expression, and suggest that the 2′FL found in human milk may be mediating some of the protective benefits of breast milk in the clinical setting against NEC. PMID:27609061

  7. Necrotizing enterocolitis - classification and two initial steps towards prevention.

    PubMed

    Juhl, Sandra Meinich

    2017-06-01

    The premature infant suffers from immaturity of all organ systems, one of them being the gastrointestinal tract. When the infant is born, the immature gastrointestinal tract is exposed to milk and simultaneously colonized by high densities of bacteria. The combination of milk, microbiota and an immature gut, leaves the infant vulnerable to developing the dreaded intestinal emergency necrotizing enterocolitis (NEC). NEC is often very aggressive and no cure exists, which means that prevention is an utmost important topic to researchers, physicians, parents - and infants.   Despite immense research during the last decades, no specific test to determine if an infant suffers from NEC exists. Most neonatal units use Bell's staging criteria, which are based on clinical and radiographic findings, as a diagnostic tool; however the diagnosis given according to Bell's stages has not been validated. In study I, we aimed to determine the validity of the NEC diagnosis given at discharge. An expert panel consisting of a neonatologist, a paediatric surgeon and a paediatric radiologist served as the golden standard. We found that the diagnosis given at discharge had a poor validity which significantly affected the reported incidence of NEC in the neonatal department at Rigshospitalet, Denmark. The validity of the NEC diagnosis was worse than the validity of most other paediatric diagnoses that had been investigated.   In studies II and III, we aimed to explore possible means of NEC prevention. The role of nutrition in NEC development is well established with mother's milk as the best option to avoid NEC in the preterm infant. Maternal milk is, however, most often not available in sufficient amounts during the first days of life, and preterm infant formula or human donor milk is used in its absence. Studies in preterm piglets showed that bovine colostrum equally to human donor milk protected against NEC compared to infant formula. Furthermore, bovine colostrum was superior to human donor milk in stimulating gut immunity and digestive functions.   Hence, in study II we aimed to design a pilot study of bovine colostrum used as a supplement to maternal milk in the first days of life and to determine if the study was feasible. In the paper, we present the protocol and the results of the first two phases of the Precolos study in which 12 infants were included and received pasteurized, spray-dried and reconstituted bovine colostrum during the first days of life as the first infants in the world. We found that the infants tolerated bovine colostrum without clinical adverse effects, but we also observed a transient hypertyrosinemia on day seven of life in five infants. The results were evaluated by a safety management board which encouraged us to continue the pilot study with the last phase, which was a randomized controlled trial of 20+20 infants comparing supplementation with bovine colostrum to supplementation with standard nutrition. The randomized trial has just finished recruitment.   At last, we wanted to shed light on a possible microbiological angle of NEC prevention. Dysbiosis and bacterial translocation are believed to play a crucial role in the development of NEC as intestinal pneumatosis, which occurs when bacteria produce gas inside the intestinal wall, is a pathognomonic radiographic finding. In a quality improvement study from the US published in 2014, NEC incidence was significantly reduced after the implementation of several quality improvement interventions. Standardized weekly exchange of nasogastric feeding tubes was suggested as one of the potential NEC-reducing interventions.   In the neonatal unit at Rigshospitalet, Denmark, preterm infants are fed 8-12 times daily through a resident nasogastric feeding tube which is exposed to body temperature, contains milk residuals from the last meal and is handled by both parents and personnel. Since bacterial pollution of milk given through the nasogastric feeding tube might be NEC-inducing, we aimed in study III to determine the bacterial load given to the infants when feeding them through a tube. We collected 92 used nasogastric feeding tubes and flushed them with one ml saline each to imitate a meal given through them. Eighty-nine percent of the tubes contaminated the meals with more than 1000 colony-forming units of bacteria and fifty-five percent contaminated the meals with the possible pathogens Enterobacteriaceae or Staphylococcus aureus. The concentration of bacteria in the saline flushed through the tubes was as high as 109 colony-forming units per ml; however, neither the risk of contamination nor the concentration of bacteria in the flush was associated with the duration of use. Implementation of standardized weekly exchange of feeding tubes would therefore not prevent the contamination of meals.   In conclusion, the studies included in this thesis serve as a base for future studies investigating the prevention of NEC. We found a poor validity of the NEC diagnosis given at discharge. This should be kept in mind when conducting epidemiological studies of NEC and especially when conducting interventional trials with NEC as an outcome. If the findings of the randomized part of the Precolos study indicate a positive effect of bovine colostrum and do not give rise to concerns regarding feasibility, safety or tolerability, a large-scale randomized controlled study with NEC as the primary outcome will be planned. Based on the high concentrations of bacteria found in the nasogastric feeding tubes, a randomized controlled trial investigating whether the frequency of feeding tube exchange affects the early colonization has been commenced in the neonatal department at Rigshospitalet. Hopefully, the results of these studies will bring us closer to preventing NEC in the future. Articles published in the Danish Medical Journal are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

  8. Bacterial community structure and functional contributions to emergence of health or necrotizing enterocolitis in preterm infants

    PubMed Central

    2013-01-01

    Background Preterm infants represent a unique patient population that is born functionally immature and must accomplish development under the influence of a hospital environment. Neonatal necrotizing enterocolitis (NEC) is an inflammatory intestinal disorder affecting preterm infants. The purpose of this study was to evaluate the progression of intestinal microbiota community development between preterm infants who remained healthy compared to preterm infants who developed NEC. Results Weekly fecal samples from ten preterm infants, five with NEC and five matched healthy controls were obtained. Bacterial DNA from individual fecal samples was subjected to sequencing of 16S rRNA-based inventories using the 454 GS-FLX platform. Fecal samples from control infants demonstrated a temporal pattern in their microbiota, which converged toward that of a healthy full term breast-fed infant. Microbiota development in NEC patients diverged from controls beginning three weeks prior to diagnosis. Shotgun metagenomic sequencing was performed to identify functional differences in the respective microbiota of fecal samples from a set of twins in which one twin developed NEC and one did not. The majority of the differentially abundant genes in the NEC patient were associated with carbohydrate metabolism and mapped to members of the family Enterobacteriaceae. This may indicate an adaptation of the community to an altered profile of substrate availability for specific members as a first step towards the development of NEC. We propose that the microbial communities as a whole may metabolize milk differently, resulting in differential substrate availability for specific microbial groups. Additional differentially represented gene sets of interest were related to antibiotic resistance and vitamin biosynthesis. Conclusions Our results suggest that there is a temporal component to microbiome development in healthy preterm infants. Thus, bacteriotherapy for the treatment or prevention of NEC must consider this temporal component of the microbial community in addition to its taxonomic composition and functional content. PMID:24450928

  9. [MAPK signaling pathways involved in aluminum-induced apoptosis and necroptosis in SH-SY5Y cells].

    PubMed

    Jia, Xiaofang; Zhang, Qinli; Niu, Qiao

    2014-11-01

    To explore the role of MAPK signaling pathway in apoptosis and necroptosis induced by aluminum in SH-SY5Y cells. To imitate neural cell death induced by aluminium, AlCl3 x 6H2O (4 mmol/L) was used to treat SH-SY5Y cells. Necrostatin-1 (Nec-1,60 μmol/L), the specific inhibitor for necroptosis, and zVAD-fmk (20 μmol/L), the specific inhibitor for apoptosis, were added into cultures for inhibiting the occurrence of necroptosis and apoptosis. CCK-8 was performed to measure cell viability, flow cytometry was used to test the difference of apoptosis rate and necrosis rate between groups, and western-blot was used to detect the change of MAPK protein. Compared with blank control group, solvent control group, Nec-1 control group and zVAD-fmk control group, cell viabiligy of Al(3+) exposed group, Al(3+) plus Nec-1 group and Al(3+) plus zVAD-fmk group decreaced (P < 0.05). Compared with Al(3+) exposed group, cell viability of Al(3+) plus Nec-1 group and Al(3+) plus zVAD-fmk group increased (P < 0.05). Necrotic rate and apoptotic rate in Al(3+) exposed group, Al(3+) plus Nec-1 group and Al(3+) plus zVAD-fmk group obviously increased compared with blank control group, solvent control group, Nec-1 control group and zVAD-fmk control group (P < 0.05). Compared with Al(3+) exposed group, necrotic and apaptotic rate of Al(3+) plus zVAD-fmk group and Al(3+) plus Nec-1 group were statistically significant decreased (P < 0.05). Compared with blank control group, solvent control group, Nec-1 control group and zVAD-fmk control group, expression of p-p38 in Al(3+) exposed group, Al(3+) plus Nec-1 group and Al(3+) plus zVAD-fmk group increased obviously (P < 0.05), and expression of p-ERK decreased significantly (P < 0.05). Compared with Al(3+) exposed group, expression of p-p38 decreased (P < 0.05), but p-ERK increased in Al(3+) plus Nec-1 group (P < 0.05). The ERK and p38 MAPK signaling pathways are involved in aluminum-induced necroptosis in SH-SY5Y cells, but only ERK signaling pathway is involved in aluminum-induced apoptosis, and JNK signaling pathway is not involved in aluminum-induced cell death.

  10. Digital SPC Switching Technology--Foreign Technology Assessment

    DTIC Science & Technology

    1990-12-01

    India C DOT MAX C DOT DSS 0 TDX 1 Samsung , Goldstar Korea TDX 10 Daewoo, Otelco (ROK) System X Plessey/GEC U.K. (Siemens) Fetex 150 Fujitsu Japan HDX...x South Korea Alcatel ATT Malaysia Ericsson NEC New Zealand NEC Philippines DAEWOO Siemens Singapore Fujitsu (AU-, NEC Gateway Switches) Taiwan...Yes Israel Northern Telecom DMS 10 Telrad Yes OMS 100 * Malaysia Ericsson AXE Pewira Ericsson Future SDN BHD Mexico Alcatel System 12 Indetel No

  11. The importance of pro-inflammatory signaling in neonatal NEC

    PubMed Central

    Frost, Brandy L.; Jilling, Tamas; Caplan, Michael S.

    2008-01-01

    Despite modern medical advances, necrotizing enterocolitis (NEC) remains a significant cause of morbidity and mortality in neonatal intensive care units, affecting 10 percent of premature neonates born weighing less than 1500 grams. Although many advances have been made in the understanding of this disease, the etiology and pathophysiology remain incompletely understood, and treatment is limited to supportive care. In recent years, studies have focused on the role of the inflammatory cascade and its’ impact on the disease process, and investigators are evaluating strategies to attenuate inflammatory signaling that might prevent and/or ameliorate neonatal NEC. In this review, we examine the key points in the signaling pathways involved in NEC, and potential strategies for prevention and treatment of this dreaded disease. PMID:18346533

  12. Postoperative Outcomes of Extremely Low Birth-Weight Infants With Necrotizing Enterocolitis or Isolated Intestinal Perforation

    PubMed Central

    Blakely, Martin L.; Lally, Kevin P.; McDonald, Scott; Brown, Rebeccah L.; Barnhart, Douglas C.; Ricketts, Richard R.; Thompson, W Raleigh; Scherer, L R.; Klein, Michael D.; Letton, Robert W.; Chwals, Walter J.; Touloukian, Robert J.; Kurkchubasche, Arlett G.; Skinner, Michael A.; Moss, R Lawrence; Hilfiker, Mary L.

    2005-01-01

    Objective: Purposes of this study were: 1) to compare mortality and postoperative morbidities (intra-abdominal abscess, wound dehiscence, and intestinal stricture) in extremely low birth weight (ELBW) infants who underwent initial laparotomy or drainage for necrotizing enterocolitis (NEC) or isolated intestinal perforation (IP); 2) to determine the ability to distinguish NEC from IP preoperatively and the importance of this distinction on outcome measures; and 3) to evaluate the association between extent of intestinal disease determined at operation and outcome measures. Background: ELBW infants who undergo operation for NEC or IP have a postoperative, in-hospital mortality rate of approximately 50%. Whether to perform laparotomy or drainage initially is controversial. Also unknown is the importance of distinguishing NEC from IP and the current ability to make this distinction based on objective data available prior to operation. Methods: A prospective, multicenter cohort study of 156 ELBW infants at 16 neonatal intensive care units (NICU) within the NICHD Neonatal Research Network. Results: Among the 156 enrolled infants, 80 underwent initial peritoneal drainage and 76 initial laparotomy. Mortality rate was 49% (76 of 156). Ninety-six patients had a preoperative diagnosis of NEC and 60 had presumed IP. There was a high level of agreement between the presumed preoperative diagnosis and intraoperative diagnosis in patients undergoing initial laparotomy (kappa = 0.85). The relative risk for death with a preoperative diagnosis of NEC (versus IP) was 1.4 (95% confidence interval, 0.99–2.1, P = 0.052). The overall incidence of postoperative intestinal stricture was 10.3%, wound dehiscence 4.4%, and intra-abdominal abscess 5.8%, and did not significantly differ between groups undergoing initial laparotomy versus initial drainage. Conclusions: Survival to hospital discharge after operation for NEC or IP in ELBW neonates remains poor (51%). Patients with a preoperative diagnosis of NEC have a relative risk for death of 1.4 compared with those with a preoperative diagnosis of IP. A distinction can be made preoperatively between NEC and IP based on abdominal radiographic findings and the patient's age at operation. Future randomized trials that compare laparotomy versus drainage would likely benefit from stratification of treatment assignment based on preoperative diagnosis. PMID:15912048

  13. [Role of necroptosis in aluminum induced SH-SY5Y cell death].

    PubMed

    Niu, Qiao; Zhang, Qin-li; Zheng, Jin-ping; Liu, Cheng-yun; Wang, Liang

    2009-02-01

    To study whether necroptosis exists or not in neural cell death induced by aluminum. SH-SY5Y cells were treated with 4 mmol/L AlCl(3) x 6H(2)O The cell viability was determined with CCK-8 kit after treated with Nec-1 at different dosages (0, 30, 60, 90 micromol/L). Mitochondria membrane potential (MMP), content of reactive oxygen species (ROS), and apoptotic rate/necrotic rates were measured with cytometry. Nec-1 ameliorated the necrotic-like cell morphology, the cell viability were 0.28 +/- 0.05, 0.58 +/- 0.03, 0.68 +/- 0.04, and 1.03 +/- 0.17, there were significant differences between the Nec-1 treated groups and that of controls (t values were 3.25, 3.36, 4.56; P < 0.05). After Nec-1 treatment, the necrotic rates were 16.46% +/- 0.54%, 10.40% +/- 0.64%, 5.43% +/- 0.68%, and 6.28% +/- 0.35%, there were significant differences between the Nec-1 treated cells and that of controls (t values were 3.62, 7.32, 6.96; P < 0.05); while the apoptotic rates were 8.68 +/- 0.36, 7.66 +/- 0.53, 5.68 +/- 0.41, and 4.13 +/- 0.41, there was no significant difference among the groups (F = 6.33, P = 0.11). Cytometry had shown the increased cell MMPs after Nec-1 treatment, which were 67.54 +/- 6.36, 49.42 +/- 5.96, 84.79 +/- 6.86, and 95.51 +/- 7.01, there were significant differences as comparing MMPs of the middle and high dosage of Nec-1 treated cells with those of controls (t values were 3.21, 4.01; P < 0.05); while ROS contents in the Nec-1 treated SH-SY5Y cells were 54.07 +/- 3.32, 52.79 +/- 2.36, 54.68 +/- 1.91, and 59.23 +/- 2.96, there was no significant difference among the groups (F = 5.26, P = 0.19). Nec-1, as a specific inhibitor of necroptosis, might effectively block the cell death pathway induced by aluminum, it indicates that necroptosis should be one of the major causes of the SH-SY5Y cell toxicity induced by aluminum, and necroptosis also plays an important role in aluminum induced SH-SY5Y cell death.

  14. The Roles of Bacteria and TLR4 in Rat and Murine Models of Necrotizing Enterocolitis1

    PubMed Central

    Jilling, Tamas; Simon, Dyan; Lu, Jing; Meng, Fan Jing; Li, Dan; Schy, Robert; Thomson, Richard B.; Soliman, Antoine; Arditi, Moshe; Caplan, Michael S.

    2009-01-01

    Bacteria are thought to contribute to the pathogenesis of necrotizing enterocolitis (NEC), but it is unknown whether their interaction with the epithelium can participate in the initiation of mucosal injury or they can act only following translocation across a damaged intestinal barrier. Our aims were to determine whether bacteria and intestinal epithelial TLR4 play roles in a well-established neonatal rat model and a novel neonatal murine model of NEC. Neonatal rats, C57BL/6J, C3HeB/FeJ (TLR4 wild type), and C3H/HeJ (TLR4 mutant) mice were delivered by Cesarean section and were subjected to formula feeding and cold asphyxia stress or were delivered naturally and were mother-fed. NEC incidence was evaluated by histological scoring, and gene expression was quantified using quantitative real-time PCR from cDNA generated from intestinal total RNA or from RNA obtained by laser capture microdissection. Spontaneous feeding catheter colonization or supplementation of cultured bacterial isolates to formula increased the incidence of experimental NEC. During the first 72 h of life, i.e., the time frame of NEC development in this model, intestinal TLR4 mRNA gradually decreases in mother-fed but increases in formula feeding and cold asphyxia stress, correlating with induced inducible NO synthase. TLR4, inducible NO synthase, and inflammatory cytokine induction occurred in the intestinal epithelium but not in the submucosa. NEC incidence was diminished in C3H/HeJ mice, compared with C3HeB/FeJ mice. In summary, bacteria and TLR4 play significant roles in experimental NEC, likely via an interaction of intraluminal bacteria and aberrantly overexpressed TLR4 in enterocytes. PMID:16920968

  15. Using a Mathematical Model to Analyze the Role of Probiotics and Inflammation in Necrotizing Enterocolitis

    PubMed Central

    Arciero, Julia C.; Ermentrout, G. Bard; Upperman, Jeffrey S.; Vodovotz, Yoram; Rubin, Jonathan E.

    2010-01-01

    Background Necrotizing enterocolitis (NEC) is a severe disease of the gastrointestinal tract of pre-term babies and is thought to be related to the physiological immaturity of the intestine and altered levels of normal flora in the gut. Understanding the factors that contribute to the pathology of NEC may lead to the development of treatment strategies aimed at re-establishing the integrity of the epithelial wall and preventing the propagation of inflammation in NEC. Several studies have shown a reduced incidence and severity of NEC in neonates treated with probiotics (beneficial bacteria species). Methodology/Principal Findings The objective of this study is to use a mathematical model to predict the conditions under which probiotics may be successful in promoting the health of infants suffering from NEC. An ordinary differential equation model is developed that tracks the populations of pathogenic and probiotic bacteria in the intestinal lumen and in the blood/tissue region. The permeability of the intestinal epithelial layer is treated as a variable, and the role of the inflammatory response is included. The model predicts that in the presence of probiotics health is restored in many cases that would have been otherwise pathogenic. The timing of probiotic administration is also shown to determine whether or not health is restored. Finally, the model predicts that probiotics may be harmful to the NEC patient under very specific conditions, perhaps explaining the detrimental effects of probiotics observed in some clinical studies. Conclusions/Significance The reduced, experimentally motivated mathematical model that we have developed suggests how a certain general set of characteristics of probiotics can lead to beneficial or detrimental outcomes for infants suffering from NEC, depending on the influences of probiotics on defined features of the inflammatory response. PMID:20419099

  16. Enteral but not parenteral antibiotics enhance gut function and prevent necrotizing enterocolitis in formula-fed newborn preterm pigs.

    PubMed

    Birck, Malene M; Nguyen, Duc Ninh; Cilieborg, Malene S; Kamal, Shamrulazhar S; Nielsen, Dennis S; Damborg, Peter; Olsen, John E; Lauridsen, Charlotte; Sangild, Per T; Thymann, Thomas

    2016-03-01

    Preterm infants are susceptible to infection and necrotizing enterocolitis (NEC) and are often treated with antibiotics. Simultaneous administration of enteral and parenteral antibiotics during the first days after preterm birth prevents formula-induced NEC lesions in pigs, but it is unknown which administration route is most effective. We hypothesized that only enteral antibiotics suppress gut bacterial colonization and NEC progression in formula-fed preterm pigs. Caesarean-delivered preterm pigs (90-92% of gestation) were fed increasing amounts of infant formula from birth to day 5 and given saline (CON) or antibiotics (ampicillin, gentamicin, and metronidazole) via the enteral (ENT) or parenteral (PAR) route (n = 16-17). NEC lesions, intestinal morphology, function, microbiology, and inflammatory mediators were evaluated. NEC lesions were completely prevented in ENT pigs, whereas there were high incidences of mild NEC lesions (59-63%) in CON and PAR pigs (P < 0.001). ENT pigs had elevated intestinal weight, villus height/crypt depth ratio, and goblet cell density and reduced gut permeability, mucosal adherence of bacteria, IL-8 levels, colonic lactic acid levels, and density of Gram-positive bacteria, relative to CON pigs (P < 0.05). Values in PAR pigs were intermediate with few affected parameters (reduced lactic acid levels and density and adherence of Gram-positive bacteria, relative to CON pigs, P < 0.05). There was no evidence of increased antimicrobial resistance following the treatments. We conclude that enteral, but not parenteral, administration of antibiotics reduces gut bacterial colonization, inflammation, and NEC lesions in newborn, formula-fed preterm pigs. Delayed colonization may support intestinal structure, function, and immunity in the immediate postnatal period of formula-fed preterm neonates. Copyright © 2016 the American Physiological Society.

  17. Risk factors associated with necrotising enterocolitis in very low birth weight infants in Malaysian neonatal intensive care units.

    PubMed

    Boo, Nem-Yun; Cheah, Irene Guat Sim

    2012-12-01

    This study aimed to identify the risk factors associated with necrotising enterocolitis (NEC) in very low birth weight (VLBW; weight < 1,501 g) infants in Malaysian neonatal intensive care units (NICUs). This was a retrospective study based on data collected in a standardised format for all VLBW infants born in 2007 (n = 3,601) and admitted to 31 NICUs in Malaysian public hospitals. A diagnosis of NEC was made based on clinical, radiological and/or histopathological evidence of stage II or III, according to Bell's criteria. Logistic regression analysis was performed to determine the significant risk factors associated with NEC. 222 (6.2%) infants developed NEC (stage II, n = 197; stage III, n = 25). 69 (31.3%) infants died (stage II, n = 58; stage III, n = 11). The significant risk factors associated with NEC were: maternal age (adjusted odds ratio [OR] 1.024, 95% confidence interval [CI] 1.003-1.046; p = 0.027), intrapartum antibiotics (OR 0.639, 95% CI 0.421-0.971; p = 0.036), birth weight (OR 0.999, 95% CI 0.998-0.999; p < 0.001), surfactant therapy (OR 1.590, 95% CI 1.170-2.161; p = 0.003), congenital pneumonia (OR 2.00, 95% CI 1.405-2.848; p < 0.001) and indomethacin therapy for the closure of patent ductus arteriosus (PDA) (OR 1.821, 95% CI 1.349-2.431; p = 0.001). Increasing maternal age, decreasing birth weight, surfactant therapy, congenital pneumonia and indomethacin therapy for the closure of PDA were associated with an increased risk of NEC in Malaysian VLBW infants. Infants that received intrapartum antibiotics were associated with a reduced risk of developing NEC.

  18. Benefits of Bifidobacterium breve M-16V Supplementation in Preterm Neonates - A Retrospective Cohort Study.

    PubMed

    Patole, Sanjay K; Rao, Shripada C; Keil, Anthony D; Nathan, Elizabeth A; Doherty, Dorota A; Simmer, Karen N

    2016-01-01

    Systematic reviews of randomised controlled trials report that probiotics reduce the risk of necrotising enterocolitis (NEC) in preterm neonates. To determine whether routine probiotic supplementation (RPS) to preterm neonates would reduce the incidence of NEC. The incidence of NEC ≥ Stage II and all-cause mortality was compared for an equal period of 24 months 'before' (Epoch 1) and 'after' (Epoch 2) RPS with Bifidobacterium breve M-16V in neonates <34 weeks. Multivariate logistic regression analysis was conducted to adjust for relevant confounders. A total of 1755 neonates (Epoch I vs. II: 835 vs. 920) with comparable gestation and birth weights were admitted. There was a significant reduction in NEC ≥ Stage II: 3% vs. 1%, adjusted odds ratio (aOR) = 0.43 (95%CI: 0.21-0.87); 'NEC ≥ Stage II or all-cause mortality': 9% vs. 5%, aOR = 0.53 (95%CI: 0.32-0.88); but not all-cause mortality alone: 7% vs. 4%, aOR = 0.58 (95% CI: 0.31-1.06) in Epoch II. The benefits in neonates <28 weeks did not reach statistical significance: NEC ≥ Stage II: 6% vs. 3%, aOR 0.51 (95%CI: 0.20-1.27), 'NEC ≥ Stage II or all-cause mortality', 21% vs. 14%, aOR = 0.59 (95%CI: 0.29-1.18); all-cause mortality: 17% vs. 11%, aOR = 0.63 (95%CI: 0.28-1.41). There was no probiotic sepsis. RPS with Bifidobacterium breve M-16V was associated with decreased NEC≥ Stage II and 'NEC≥ Stage II or all-cause mortality' in neonates <34 weeks. Large sample size is required to assess the potential benefits of RPS in neonates <28 weeks.

  19. Inhibition of Necroptosis Attenuates Kidney Inflammation and Interstitial Fibrosis Induced By Unilateral Ureteral Obstruction.

    PubMed

    Xiao, Xia; Du, Chunyang; Yan, Zhe; Shi, Yonghong; Duan, Huijun; Ren, Yunzhuo

    2017-01-01

    Inflammation plays a crucial role in renal interstitial fibrosis, the pathway of chronic kidney diseases. Necroptosis is a novel form of regulated cell death, which plays a potential role in inflammation and renal diseases. The small molecule necrostatin-1 (Nec-1) is a specific inhibitor of necroptosis. This study was aimed at determining the role of necroptosis, RIP1/RIP3/mixed lineage kinase domain-like (MLKL) signaling pathway, in renal inflammation and interstitial fibrosis related to primitive tubulointerstitial injury. It was also aimed at evaluating the effect of Nec-1 in renal fibrosis induced by unilateral ureteral obstruction (UUO). Renal histology, immunohistochemistry, western blot, and real-time polymerase chain reaction were performed using UUO C57BL/6J mice model. Moreover, we tested whether Nec-1 was renal-protective in the interstitial fibrosis kidney. Mice were exposed to UUO and injected intraperitoneal with Nec-1 or vehicle. The levels of RIP1/RIP3/MLKL protein and mRNA were increased in the obstructed kidneys 7 days after UUO; this was accompanied by changes in renal pathological lesions. Renal histological examination showed lesser renal damage in Nec-1-treated UUO mice. Renal inflammation, assessed by tumor necrosis factor-α, interleukin-1β, and monocyte chemotactic protein-1 was markedly attenuated by Nec-1. Furthermore, Nec-1 treatment also significantly reduced TGF-β and α-smooth muscle actin, indicating lesser renal interstitial fibrosis. These findings suggest that the participation of necroptosis in UUO is partly demonstrated. And necroptosis inhibition may have a potential role in the treatment of diseases with increased inflammatory response and interstitial fibrosis in renal. © 2017 S. Karger AG, Basel.

  20. Protective Effect of Dual-Strain Probiotics in Preterm Infants: A Multi-Center Time Series Analysis

    PubMed Central

    Schwab, Frank; Garten, Lars; Geffers, Christine; Gastmeier, Petra; Piening, Brar

    2016-01-01

    Objective To determine the effect of dual-strain probiotics on the development of necrotizing enterocolitis (NEC), mortality and nosocomial bloodstream infections (BSI) in preterm infants in German neonatal intensive care units (NICUs). Design A multi-center interrupted time series analysis. Setting 44 German NICUs with routine use of dual-strain probiotics on neonatal ward level. Patients Preterm infants documented by NEO-KISS, the German surveillance system for nosocomial infections in preterm infants with birth weights below 1,500 g, between 2004 and 2014. Intervention Routine use of dual-strain probiotics containing Lactobacillus acidophilus and Bifidobacterium spp. (Infloran) on the neonatal ward level. Main outcome measures Incidences of NEC, overall mortality, mortality following NEC and nosocomial BSI. Results Data from 10,890 preterm infants in 44 neonatal wards was included in this study. Incidences of NEC and BSI were 2.5% (n = 274) and 15.0%, (n = 1631), respectively. Mortality rate was 6.1% (n = 665). The use of dual-strain probiotics significantly reduced the risk of NEC (HR = 0.48; 95% CI = 0.38–0.62), overall mortality (HR = 0.60, 95% CI = 0.44–0.83), mortality after NEC (HR = 0.51, 95% CI = 0.26–0.999) and nosocomial BSI (HR = 0.89, 95% CI = 0.81–0.98). These effects were even more pronounced in the subgroup analysis of preterm infants with birth weights below 1,000 g. Conclusion In order to reduce NEC and mortality in preterm infants, it is advisable to add routine prophylaxis with dual-strain probiotics to clinical practice in neonatal wards. PMID:27332554

  1. Toll-like Receptor 4-mediated Endoplasmic Reticulum Stress in Intestinal Crypts Induces Necrotizing Enterocolitis*

    PubMed Central

    Afrazi, Amin; Branca, Maria F.; Sodhi, Chhinder P.; Good, Misty; Yamaguchi, Yukihiro; Egan, Charlotte E.; Lu, Peng; Jia, Hongpeng; Shaffiey, Shahab; Lin, Joyce; Ma, Congrong; Vincent, Garrett; Prindle, Thomas; Weyandt, Samantha; Neal, Matthew D.; Ozolek, John A.; Wiersch, John; Tschurtschenthaler, Markus; Shiota, Chiyo; Gittes, George K.; Billiar, Timothy R.; Mollen, Kevin; Kaser, Arthur; Blumberg, Richard; Hackam, David J.

    2014-01-01

    The cellular cues that regulate the apoptosis of intestinal stem cells (ISCs) remain incompletely understood, yet may play a role in diseases characterized by ISC loss including necrotizing enterocolitis (NEC). Toll-like receptor-4 (TLR4) was recently found to be expressed on ISCs, where its activation leads to ISC apoptosis through mechanisms that remain incompletely explained. We now hypothesize that TLR4 induces endoplasmic reticulum (ER) stress within ISCs, leading to their apoptosis in NEC pathogenesis, and that high ER stress within the premature intestine predisposes to NEC development. Using transgenic mice and cultured enteroids, we now demonstrate that TLR4 induces ER stress within Lgr5 (leucine-rich repeat-containing G-protein-coupled receptor 5)-positive ISCs, resulting in crypt apoptosis. TLR4 signaling within crypts was required, because crypt ER stress and apoptosis occurred in TLR4ΔIEC-OVER mice expressing TLR4 only within intestinal crypts and epithelium, but not TLR4ΔIEC mice lacking intestinal TLR4. TLR4-mediated ER stress and apoptosis of ISCs required PERK (protein kinase-related PKR-like ER kinase), CHOP (C/EBP homologous protein), and MyD88 (myeloid differentiation primary response gene 88), but not ATF6 (activating transcription factor 6) or XBP1 (X-box-binding protein 1). Human and mouse NEC showed high crypt ER stress and apoptosis, whereas genetic inhibition of PERK or CHOP attenuated ER stress, crypt apoptosis, and NEC severity. Strikingly, using intragastric delivery into fetal mouse intestine, prevention of ER stress reduced TLR4-mediated ISC apoptosis and mucosal disruption. These findings identify a novel link between TLR4-induced ER stress and ISC apoptosis in NEC pathogenesis and suggest that increased ER stress within the premature bowel predisposes to NEC development. PMID:24519940

  2. Toll-like receptor 4-mediated endoplasmic reticulum stress in intestinal crypts induces necrotizing enterocolitis.

    PubMed

    Afrazi, Amin; Branca, Maria F; Sodhi, Chhinder P; Good, Misty; Yamaguchi, Yukihiro; Egan, Charlotte E; Lu, Peng; Jia, Hongpeng; Shaffiey, Shahab; Lin, Joyce; Ma, Congrong; Vincent, Garrett; Prindle, Thomas; Weyandt, Samantha; Neal, Matthew D; Ozolek, John A; Wiersch, John; Tschurtschenthaler, Markus; Shiota, Chiyo; Gittes, George K; Billiar, Timothy R; Mollen, Kevin; Kaser, Arthur; Blumberg, Richard; Hackam, David J

    2014-04-04

    The cellular cues that regulate the apoptosis of intestinal stem cells (ISCs) remain incompletely understood, yet may play a role in diseases characterized by ISC loss including necrotizing enterocolitis (NEC). Toll-like receptor-4 (TLR4) was recently found to be expressed on ISCs, where its activation leads to ISC apoptosis through mechanisms that remain incompletely explained. We now hypothesize that TLR4 induces endoplasmic reticulum (ER) stress within ISCs, leading to their apoptosis in NEC pathogenesis, and that high ER stress within the premature intestine predisposes to NEC development. Using transgenic mice and cultured enteroids, we now demonstrate that TLR4 induces ER stress within Lgr5 (leucine-rich repeat-containing G-protein-coupled receptor 5)-positive ISCs, resulting in crypt apoptosis. TLR4 signaling within crypts was required, because crypt ER stress and apoptosis occurred in TLR4(ΔIEC-OVER) mice expressing TLR4 only within intestinal crypts and epithelium, but not TLR4(ΔIEC) mice lacking intestinal TLR4. TLR4-mediated ER stress and apoptosis of ISCs required PERK (protein kinase-related PKR-like ER kinase), CHOP (C/EBP homologous protein), and MyD88 (myeloid differentiation primary response gene 88), but not ATF6 (activating transcription factor 6) or XBP1 (X-box-binding protein 1). Human and mouse NEC showed high crypt ER stress and apoptosis, whereas genetic inhibition of PERK or CHOP attenuated ER stress, crypt apoptosis, and NEC severity. Strikingly, using intragastric delivery into fetal mouse intestine, prevention of ER stress reduced TLR4-mediated ISC apoptosis and mucosal disruption. These findings identify a novel link between TLR4-induced ER stress and ISC apoptosis in NEC pathogenesis and suggest that increased ER stress within the premature bowel predisposes to NEC development.

  3. Fracture Strength of Endodontically Treated Teeth with Different Access Cavity Designs.

    PubMed

    Plotino, Gianluca; Grande, Nicola Maria; Isufi, Almira; Ioppolo, Pietro; Pedullà, Eugenio; Bedini, Rossella; Gambarini, Gianluca; Testarelli, Luca

    2017-06-01

    The purpose of this study was to compare in vitro the fracture strength of root-filled and restored teeth with traditional endodontic cavity (TEC), conservative endodontic cavity (CEC), or ultraconservative "ninja" endodontic cavity (NEC) access. Extracted human intact maxillary and mandibular premolars and molars were selected and assigned to control (intact teeth), TEC, CEC, or NEC groups (n = 10/group/type). Teeth in the TEC group were prepared following the principles of traditional endodontic cavities. Minimal CECs and NECs were plotted on cone-beam computed tomographic images. Then, teeth were endodontically treated and restored. The 160 specimens were then loaded to fracture in a mechanical material testing machine (LR30 K; Lloyd Instruments Ltd, Fareham, UK). The maximum load at fracture and fracture pattern (restorable or unrestorable) were recorded. Fracture loads were compared statistically, and the data were examined with analysis of variance and the Student-Newman-Keuls test for multiple comparisons. The mean load at fracture for TEC was significantly lower than the one for the CEC, NEC, and control groups for all types of teeth (P < .05), whereas no difference was observed among CEC, NEC, and intact teeth (P > .05). Unrestorable fractures were significantly more frequent in the TEC, CEC, and NEC groups than in the control group in each tooth type (P < .05). Teeth with TEC access showed lower fracture strength than the ones prepared with CEC or NEC. Ultraconservative "ninja" endodontic cavity access did not increase the fracture strength of teeth compared with the ones prepared with CEC. Intact teeth showed more restorable fractures than all the prepared ones. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  4. Human milk and necrotizing enterocolitis.

    PubMed

    Patel, Aloka L; Kim, Jae H

    2018-02-01

    NEC is a multifactorial disease that occurs when multiple risk factors and/or stressors overlap, leading to profound inflammation and intestinal injury. Human milk feedings, both from the infant's mother and donor human milk, have been associated with reductions in NEC in preterm infants. This article will review the protective factors in human milk, clinical studies of human milk and NEC, and practices to enhance human milk use in neonatal intensive care units. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Probiotics Reduce Necrotizing Enterocolitis Severity in HIV-exposed Premature Infants.

    PubMed

    Van Niekerk, Evette; Nel, Daniel G; Blaauw, Reneé; Kirsten, Gert F

    2015-06-01

    To assess the effect of probiotics on the incidence of necrotizing enterocolitis (NEC) in premature infants born to human immunodeficiency virus (HIV)-positive and HIV-negative women. HIV-exposed and HIV-unexposed premature infants were randomized to either the probiotic or the placebo group. The probiotic consisted of 1 × 10(9) colony-forming units, Lactobacillus rhamnosus GG and Bifidobacterium infantis per day. In total, 74 HIV-exposed and 110 HIV-unexposed infants were enrolled and randomized. The incidence of death [4 (5.4%) vs. 7 (6%); p = 0.79] and NEC [4 (5%) vs. 5 (5%); p = 0.76] did not differ significantly between the HIV-exposed and HIV-unexposed groups. A significant difference was found for total NEC incidence between the study and control groups [3 (3%) vs. 6 (6%); p = 0.029]. The incidence of NEC in the HIV-exposed group differed significantly [Bells I 2 (5%) vs. Bells III 2 (5%); p = 0.045). Probiotic supplementation reduced the incidence of NEC in the premature very low birth weight infants; however, results failed to show a lower incidence of NEC in HIV-exposed premature infants. A reduction in the severity of disease was found in the HIV-exposed study group. © The Author [2015]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Improving Growth for Infants ≤1250 Grams Receiving an Exclusive Human Milk Diet.

    PubMed

    Huston, Robert K; Markell, Andrea M; McCulley, Elizabeth A; Gardiner, Stuart K; Sweeney, Sean L

    2018-02-16

    An exclusive human milk diet (EHM) fortified with human milk-based fortifier decreases necrotizing enterocolitis (NEC) compared to maternal milk supplemented with preterm formula and bovine fortifier (PTF). Growth has been less with EHM and also maternal milk supplemented with donor human milk and bovine fortifier (HMBF). The objective was to evaluate the effect of a standardized feeding protocol on the growth of infants ≤1250 g birth weight supported with EHM and HMBF. The effect on the incidence of NEC was also evaluated. A retrospective study of growth before and after implementation of a feeding protocol for infants who received either EHM or HMBF. Primary outcomes were weight, length, and head circumference gain velocities from birth to discharge. The incidence of NEC was also recorded. Analysis of covariance for 379 total infants showed that earlier day of life for fortification to 24 Kcal/oz was associated with increased weight gain (p = 0.0166) and length gain (p = 0.0064). Implementation of the feeding protocol was associated with increased head circumference gain (p = 0.006). EHM was associated with decreased incidence of NEC (p = 0.0302). Implementation of a standardized feeding protocol including earlier fortification of maternal milk was associated with improved growth for infants receiving human milk feedings. EHM significantly decreased NEC. Earlier fortification had no effect on NEC. © 2018 American Society for Parenteral and Enteral Nutrition.

  7. Development of a Gestational Age-Specific Case Definition for Neonatal Necrotizing Enterocolitis.

    PubMed

    Battersby, Cheryl; Longford, Nick; Costeloe, Kate; Modi, Neena

    2017-03-01

    Necrotizing enterocolitis (NEC) is a major cause of neonatal morbidity and mortality. Preventive and therapeutic research, surveillance, and quality improvement initiatives are hindered by variations in case definitions. To develop a gestational age (GA)-specific case definition for NEC. We conducted a prospective 34-month population study using clinician-recorded findings from the UK National Neonatal Research Database between December 2011 and September 2014 across all 163 neonatal units in England. We split study data into model development and validation data sets and categorized GA into groups (group 1, less than 26 weeks' GA; group 2, 26 to less than 30 weeks' GA; group 3, 30 to less than 37 weeks' GA; group 4, 37 or more weeks' GA). We entered GA, birth weight z score, and clinical and abdominal radiography findings as candidate variables in a logistic regression model, performed model fitting 1000 times, averaged the predictions, and used estimates from the fitted model to develop an ordinal NEC score and cut points to develop a dichotomous case definition based on the highest area under the receiver operating characteristic curves [AUCs] and positive predictive values [PPVs]. Abdominal radiography performed to investigate clinical concerns. Ordinal NEC likelihood score, dichotomous case definition, and GA-specific probability plots. Of the 3866 infants, the mean (SD) birth weight was 2049.1 (1941.7) g and mean (SD) GA was 32 (5) weeks; 2032 of 3663 (55.5%) were male. The total included 2978 infants (77.0%) without NEC and 888 (23.0%) with NEC. Infants with NEC in group 1 were less likely to present with pneumatosis (31.1% vs 47.2%; P = .01), blood in stool (11.8% vs 29.6%; P < .001), or mucus in stool (2.1% vs 5.6%; P = .048) but more likely to present with gasless abdominal radiography findings (6.3% vs 0.9%; P = .009) compared with infants with NEC in group 3. In the ordinal NEC score analysis, we allocated 3 points to pneumatosis, 2 points to blood in stool, and 1 point each to abdominal tenderness and abdominal discoloration; 1 point was assigned if 1 or more of pneumoperitoneum, fixed loop, and portal venous gas were present, and 1 point was assigned if both increased and/or bilious aspirates and abdominal distension were present. The cutoff scores for the dichotomous GA-specific case definition were 2 or greater for infants in groups 1 and 2, 3 or greater for infants in group 3, and 4 or greater for infants in group 4. The ordinal NEC score and dichotomous case definition discriminated well between infants with (AUC, 87%) and without (AUC, 80%) NEC. The case definition has a sensitivity of 66.2% (95% CI, 63.0-69.4), a specificity of 94.4% (95% CI, 93.2-95.4), an AUC of 80.0% (95% CI, 79-82), and a PPV of 85.5% (95% CI, 82.6-88.1). Applying the cut points to the 431 infants who underwent a laparotomy yielded a sensitivity of 76.5% (95% CI, 70.0-82.1), a specificity of 74.4% (95% CI, 68.3-80.0), an AUC of 75.0% (95% CI, 71.0- 80.0), and a PPV of 72.9% (95% CI, 66.4-78.7). The risk of NEC and clinical presentation are associated with GA. Adoption of a consistent GA-specific case definition would strengthen global efforts to reduce the population burden of this devastating neonatal disease.

  8. Modern Antenna Design Using Computers and Measurement: Application to Antenna Problems of Military Interest

    DTIC Science & Technology

    1989-01-01

    admittance of a dipole antenna co’puted Fig. 2. Input admittance of a A/2 dipole antenna corn - by NEC-3S, NEC-3D and NEC3VLF. The dipole was puted by...The upper half space is air, the corn - results are incorrect as a result of using the reflection plex relative permittivity of the medium surrounding...UNCLASSIFIED UNLIMITED (U) ANAFTIM AIUI 87-03964 UNCLASSIFIED UNLIMITED STC Defence Systems, Paigonton (England) (U) AIRIAFT IJ= ANITEIAS AGAR -LS-151

  9. Prevention of Necrotizing Enterocolitis Through Manipulation of the Intestinal Microbiota of the Premature Infant

    PubMed Central

    Vongbhavit, Kannikar; Underwood, Mark A.

    2016-01-01

    In spite of four decades of research, necrotizing enterocolitis (NEC) remains the most common gastrointestinal complication in premature infants with high mortality and long-term morbidity. The composition of the intestinal microbiota of the premature infant differs dramatically from that of the healthy term infant and appears to be an important risk factor for NEC. Promising NEC prevention strategies that alter the intestinal microbiota include probiotics, prebiotics, synbiotics, lacteroferrin, and human milk feeding. PMID:26872618

  10. Traction studies of northeast corridor rail passenger service: Executive summary

    NASA Technical Reports Server (NTRS)

    Macie, T. W.; Stallkamp, J. A.

    1980-01-01

    The enabling legislation of 1976 for improvement of service in the Northeast corridor (NEC) requires a schedule of 2 h 40 min between Washington and New York City by 1981 and 3 h 40 min between NYC and Boston, when the electrification is completed. Various options of the NEC operation that may satisfy the legislation were investigated, particularly in terms of travel time and energy consumption. NEC operations were compared with overseas systems and practices. The emerging new technology of AC traction was also evaluated.

  11. Immunoregulatory Protein Profiles of Necrotizing Enterocolitis versus Spontaneous Intestinal Perforation in Preterm Infants

    PubMed Central

    Leung, Fiona Wan Lun; Lam, Hugh Simon; Tam, Yuk Him; To, Ka Fai; Cheung, Hon Ming; Leung, Kam Tong; Poon, Terence Chuen Wai; Lee, Kim Hung; Li, Karen; Fok, Tai Fai

    2012-01-01

    Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are the most common acute surgical emergencies associated with high morbidity and mortality in preterm infants. We aimed to compare the profiles of immunoregulatory proteins and identify novel mediators in plasma of NEC and SIP infants. We also investigated the expression of target genes in resected intestinal tissues and an enterocyte cell line. Using Cytokine Antibody Array assay, we reported the first comparative profiles of immunoregulatory proteins in plasma of NEC and SIP infants, and showed that dysregulated proteins belonged to functionally diversified categories, including pro- and anti-inflammation, angiogenesis, cell growth, wound healing, anti-apoptosis, cell adhesion and extracellular matrix reorganization. Validation by ELISA confirmed significantly higher concentrations of interleukin (IL)-6, angiopoietin (Ang)-2, soluble type II interleukin-1 receptor (sIL-1RII), and soluble urokinase-type plasminogen activator receptor (suPAR) in NEC infants compared with gestational age-matched control, and a lower level of an epidermal growth factor receptor, secreted form of receptor tyrosine-protein kinase ErbB3 (sErbB3), compared with SIP infants. mRNA expressions of IL1-RII and uPAR were up-regulated in resected bowel tissues from NEC infants, indicating that immunoregulation also occurred at the cellular level. In FHs-74 Int cells, Ang-2, IL1-RII and uPAR mRNA expressions were significantly induced by the combined treatment with lipopolysaccharide (LPS) and platelet activating factor (PAF). Our study provided plasmatic signatures of immunoregulatory proteins in NEC and SIP infants, and demonstrated involvement of multiple functional pathways. The magnitude of changes in these proteins was significantly more extensive in NEC infants, reflecting the different nature of injury and/or severity of inflammation. We speculate that dysregulation of IL-6, Ang-2, IL-1RII and uPAR occurred at both systemic and cellular levels, and probably mediated via LPS and endogeneous PAF signals. Such exaggerated immunologic responses may account for the high morbidity and mortality in NEC compared with SIP patients. PMID:22606320

  12. miR-200a/miR-141 and miR-205 upregulation might be associated with hormone receptor status and prognosis in endometrial carcinomas.

    PubMed

    Dong, Ying; Si, Jing-Wen; Li, Wen-Ting; Liang, Li; Zhao, Jian; Zhou, Mei; Li, Dong; Li, Ting

    2015-01-01

    The aim of this study was to compare the clinicopathological significance of miR-200a/miR-141 and miR-205 expression in endometrioid carcinomas (ECs) versus nonendometrioid carcinomas (NECs) and to assess their correlation with hormone receptor status. miR-200a/miR-141 and miR-205 expression in 154 endometrial cancers was determined by qRT-PCR. The status of estrogen and progesterone receptor (ER/PR) was assessed using immunohistochemistry. miR-200a/miR-141 and miR-205 increased significantly in ECs and in NECs. The expression level of miR-200a was significantly higher in NECs than in ECs (P=0.025). Furthermore, there was a trend that NECs with worse clinicopathological variables had a higher miR-200a expression, while an inverse trend existed in ECs. miR-205 upregulation occurred frequently in NECs without lymph node metastases (P=0.030), whereas such association was not present in ECs. Interestingly, In ECs, miR-200a/miR-141 upregulation occurred frequently in the hormone receptor positive subgroups than the negative subgroups (P<0.05). Similarly, the expression level of miR-205 was higher in the hormone receptor positive subgroups and the association between miR-205 and PR reached statistical significance (P=0.024). In contrast, in NECs, a negative correlation was found between miR-200a/miR-141 and ER or PR status. Meanwhile, in ECs, miR-200a upregulation correlated with prolonged survival in the ER positive subgroup (P=0.046), whereas an inverse trend existed in the ER negative subgroup. Our findings suggest that miR-200a/miR-141 and miR-205 increased significantly in ECs and in NECs. However, they might behave differently in ECs versus NECs. miR-200a/miR-141 and miR-205 might be associated with hormone receptor status in endometrial cancer and may possess prognostic impacts.

  13. 7 CFR 51.1216 - Size requirements.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...) The numerical count or a count-size based on equivalent tray pack size designations or the minimum... numerical count is not shown the minimum diameter shall be plainly stamped, stenciled, or otherwise marked...

  14. 7 CFR 51.1216 - Size requirements.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...) The numerical count or a count-size based on equivalent tray pack size designations or the minimum... numerical count is not shown the minimum diameter shall be plainly stamped, stenciled, or otherwise marked...

  15. Therapeutic Use of Prebiotics, Probiotics, and Postbiotics to Prevent Necrotizing Enterocolitis: What is the Current Evidence?

    PubMed Central

    Patel, Ravi Mangal; Denning, Patricia Wei

    2013-01-01

    Synopsis Necrotizing enterocolitis (NEC) is a leading cause of neonatal morbidity and mortality and preventative therapies that are both effective and safe are urgently needed. Current evidence from therapeutic trials suggests that probiotics are effective in decreasing NEC in preterm infants and probiotics are currently the most promising therapy on the horizon for this devastating disease. However, concerns regarding safety and optimal dosing have limited the widespread adoption of routine clinical use of probiotics in preterm infants. In addition, prebiotics and postbiotics may be potential alternatives or adjunctive therapies to the administration of live microorganisms, although studies demonstrating their clinical efficacy in preventing NEC are lacking. This review summarizes the current evidence regarding the use of probiotics, prebiotics and postbiotics in the preterm infant, including its therapeutic role in preventing NEC. PMID:23415261

  16. Intestinal Microbiota and Its Relationship with Necrotizing Enterocolitis

    PubMed Central

    Patel, Ravi Mangal; Denning, Patricia W.

    2015-01-01

    Necrotizing enterocolitis is a leading cause of morbidity and mortality in infants born prematurely. After birth, the neonatal gut must acquire a healthy complement of commensal bacteria. Disruption or delay of this critical process, leading to deficient or abnormal microbial colonization of the gut, has been implicated as key risk factor in the pathogenesis of NEC. Conversely, a beneficial complement of commensal intestinal microbiota may protect the immature gut from inflammation and injury. Interventions aimed at providing or restoring a healthy complement of commensal bacteria, such as probiotic therapy, are currently the most promising treatment to prevent NEC. Shifting the balance of intestinal microbiota from a pathogenic to protective complement of bacteria can protect the gut from inflammation and subsequent injury that leads to NEC. Herein, we review the relationship of intestinal microbiota and NEC in preterm infants. PMID:25992911

  17. Isolated tumor endothelial cells maintain specific character during long-term culture

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

    Matsuda, Kohei; Oral Pathology and Biology, Hokkaido University Graduate School of Dental Medicine, N13 W7, Kita-ku, Sapporo 060-8586; Oral and Maxillofacial Surgery, Hokkaido University Graduate School of Dental Medicine, N13 W7, Kita-ku, Sapporo 060-8586

    Tumor angiogenesis is necessary for solid tumor progression and metastasis. Increasing evidence indicates that tumor endothelial cells (TECs) are more relevant to the study of tumor angiogenesis than normal endothelial cells (NECs) because their morphologies and gene expression are different from NECs. However, it is challenging to isolate and culture large numbers of pure ECs from tumor tissue since the percentage of ECs is only about 1-2% and tumor cells and fibroblasts easily overgrow them. In addition, there has been concern that isolated TECs may lose their special phenotype once they are dissociated from tumor cells. In this study, wemore » have successfully purified murine TECs from four different human tumor xenografts and NECs from murine dermal tissue. Isolated ECs expressed endothelial markers, such as CD31, VE-cadherin (CD144), and endoglin (CD105), for more than 3 months after isolation. TECs maintained tumor endothelial-specific markers, such as tumor endothelial marker 8 (TEM8) and aminopeptidase N (APN), as in tumor blood vessels in vivo. In addition, TECs were more proliferative and motile than NECs. TECs showed a higher response to VEGF and higher expression of VEGF receptors-1 and -2 than NECs did. Stem cell antigen-1 was up-regulated in all four TECs, suggesting that they have a kind of stemness. Cultured TECs maintain distinct biological differences from NECs as in vivo. In conclusion, it was suggested that TECs are relevant material for tumor angiogenesis research.« less

  18. Pathologic Progression, Possible Origin, and Management of Multiple Primary Intracranial Neuroendocrine Carcinomas.

    PubMed

    Cao, Jingwei; Xu, Wenzhe; Du, Zhenhui; Sun, Bin; Li, Feng; Liu, Yuguang

    2017-10-01

    Primary intracranial neuroendocrine carcinomas (NECs) are extremely rare malignant tumors with no previous reports of multiple ones in the literatures. The clinical presentation, preoperative and reexamined magnetic resonance imaging findings, as well as histopathologic studies of a 56-year-old female subject with multiple intracranial NECs mimicking multiple intracranial meningiomas, who underwent 3 operations with left parietal craniotomy, right occipital parietal craniotomy, and left frontal craniotomy, separately and chronologically, are presented in this article. Noteworthy, the first and second tumors were confirmed as NECs exhibiting histologic characteristics of typical anaplastic meningiomas with features of whorl formation, while the third tumor was a typical NEC with features of organoid cancer nests. In other words, the first 2 lesions were diagnosed as meningioma as opposed to NEC. It was only after the third surgery that the pathology for the first 2 cases was reviewed and had a revised diagnosis. After the third surgical resection, the patient further received whole brain radiotherapy and systemic chemotherapy (temozolomide combined with YH-16). At her 10-month follow-up, the patient achieved a good outcome. Multiple primary intracranial NECs are extremely rare. The tumor might be of arachnoidal or leptomeningeal origin, with histologic patterns that might lead to transformation and/or progression. Maximal surgical resection is warranted for symptomatic mass effect. Postoperative adjuvant treatments including radiotherapy and chemotherapy should be a recommended therapeutic modality. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Influence of the Northeast Cold Vortex on Flooding in Northeast China in Summer 2013

    NASA Astrophysics Data System (ADS)

    Gao, Jing; Gao, Hui

    2018-04-01

    Severe flooding occurred in Northeast China (NEC) in summer 2013. Compared with the rainfall climatology of the region, the rainy season began earlier in 2013 and two main rainy periods occurred from late June to early July and from mid July to early August, respectively. During the summer season of 2013, the western Pacific subtropical high (WPSH) was located farther westward, which strengthened the southerly winds on its west side in the lower troposphere. Under this circulation pattern, more water vapor was transported to North China and NEC. Another moisture transport pathway to NEC was traced to the cross-equatorial flow over the Bay of Bengal. In mid-high latitudes in summer 2013, the Northeast Cold Vortex (NECV) was much stronger and remained stable over NEC. Thus, the cold air flow from its northwest side frequently met with the warm and wet air from the south to form stronger moisture convergence at lower levels in the troposphere, resulting in increased precipitation over the region. Correlation analysis indicated that the NECV played a more direct role than the WPSH. Synoptic analyses of the two heaviest flood cases on 2 and 16 July confirmed this conclusion. The four wettest summers in NEC before 2000 were also analyzed and the results were consistent with the conclusion that both the WPSH and the NECV led to the intense rainfall in NEC, but the NECV had a more direct role.

  20. Roles and Experiences of Parents in Necrotizing Enterocolitis: An International Survey of Parental Perspectives of Communication in the NICU.

    PubMed

    Gadepalli, Samir K; Canvasser, Jennifer; Eskenazi, Yael; Quinn, Megan; Kim, Jae H; Gephart, Sheila M

    2017-12-01

    Although partnering with parents is important to improving neonatal outcomes, no studies have investigated what parents are taught, remember, or experience when their child is afflicted with necrotizing enterocolitis (NEC). To characterize parental perceptions of communication and support they were given about NEC. An online survey was developed, reviewed for face validity, and then administered to parents whose child had experienced NEC. Quantitative data were analyzed using descriptive statistics, and qualitative data were analyzed using a qualitative descriptive approach. Parents (N = 110) wanted to know the risk factors and warning signs for NEC and wanted to be told as soon as their child was admitted to the neonatal intensive care unit (NICU). Information provided before diagnosis was felt to be poor by the majority of families, with only 32% feeling satisfied or very satisfied. No parent wrote that they were "scared" by information provided to them about NEC; in fact, parents were dissatisfied when they received "sugar-coated" information. Engaged parents were significantly more satisfied than those who were not informed, had their concerns and suggestions dismissed, or who had to advocate for their baby against clinician opposition (eg, activating the chain of command). Areas for quality improvement include better communication and collaboration with parents through early engagement in NEC prevention using modalities beyond verbal instruction. More research is needed on how best to engage parents, especially to engage in prevention, and how doing so affects satisfaction and outcomes.

  1. 24. Elevated SEPTA subway Bridge crossing NEC. Philadelphia, Philadelphia Co., ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    24. Elevated SEPTA subway Bridge crossing NEC. Philadelphia, Philadelphia Co., PA. Sec. 1101, MP 81.69. - Northeast Railroad Corridor, Amtrak route between Delaware-Pennsylvania & Pennsylvania-New Jersey state lines, Philadelphia, Philadelphia County, PA

  2. 26. Elevated SEPTA subway Bridge crossing NEC. Philadelphia, Philadelphia Co., ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    26. Elevated SEPTA subway Bridge crossing NEC. Philadelphia, Philadelphia Co., PA. Sec. 1101, MP 81.69. - Northeast Railroad Corridor, Amtrak route between Delaware-Pennsylvania & Pennsylvania-New Jersey state lines, Philadelphia, Philadelphia County, PA

  3. 25. Elevated SEPTA subway Bridge crossing NEC. Philadelphia, Philadelphia Co., ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    25. Elevated SEPTA subway Bridge crossing NEC. Philadelphia, Philadelphia Co., PA. Sec. 1101, MP 81.69. - Northeast Railroad Corridor, Amtrak route between Delaware-Pennsylvania & Pennsylvania-New Jersey state lines, Philadelphia, Philadelphia County, PA

  4. Test Basic Page | FNLCR Staging

    Cancer.gov

    Lorem ipsum dolor sit amet, consectetur adipiscing elit. Quisque elementum risus erat, nec porttitor velit pulvinar id. Fusce euismod facilisis mi ut semper. Vestibulum non libero sed sem tempor dignissim vitae nec ex. Donec fermentum gravida facilis

  5. Multiple strains probiotics appear to be the most effective probiotics in the prevention of necrotizing enterocolitis and mortality: An updated meta-analysis.

    PubMed

    Chang, Hung-Yang; Chen, Jin-Hua; Chang, Jui-Hsing; Lin, Hung-Chih; Lin, Chien-Yu; Peng, Chun-Chih

    2017-01-01

    Some oral probiotics have been shown to prevent necrotizing enterocolitis (NEC) and decrease mortality effectively in preterm very low birth weight (PVLBW) infants. However, it is unclear whether a single probiotic or a mixture of probiotics is most effective for the prevention of NEC. A meta-analysis was conducted by reviewing the most up to date literature to investigate whether multiple strains probiotics are more effective than a single strain in reducing NEC and death in PVLBW infants. Relevant studies were identified by searches of the MEDLINE, EMBASE, and Cochrane CENTRAL databases, from 2001 to 2016. The inclusion criteria were randomized controlled trials of any enteral probiotic supplementation that was initiated within the first 7 days and continued for at least 14 days in preterm infants (≤ 34 weeks' gestation) and/or those of a birth weight ≤1500 g. A total of 25 trials (n = 7345 infants) were eligible for inclusion in the meta-analysis using a fixed-effects model. Multiple strains probiotics were associated with a marked reduction in the incidence of NEC, with a pooled OR of 0.36 (95% CI, 0.24-0.53; P < .00001). Single strain probiotic using Lactobacillus species had a borderline effect in reducing NEC (OR of 0.60; 95% CI 0.36-1.0; P = .05), but not mortality. Multiple strains probiotics had a greater effectiveness in reducing mortality and were associated with a pooled OR of 0.58 (95% CI, 0.43-0.79; P = .0006). Trials using single strain of Bifidobacterium species and Saccharomyces boulardii did not reveal any beneficial effects in terms of reducing NEC or mortality. This updated report found that multiple strains probiotics appear to be the most feasible and effective strategy for the prevention of NEC and reduction of mortality in PVLBW neonates. Further clinical trials should focus on which probiotic combinations are most effective.

  6. Reduced Hospital Mortality With Surgical Ligation of Patent Ductus Arteriosus in Premature, Extremely Low Birth Weight Infants: A Propensity Score-matched Outcome Study.

    PubMed

    Tashiro, Jun; Perez, Eduardo A; Sola, Juan E

    2016-03-01

    To evaluate outcomes after surgical ligation (SL) of patent ductus arteriosus (PDA) in premature, extremely low birth weight (ELBW) infants. Optimal management of PDA in this specialized population remains undefined. Currently, surgical therapy is largely reserved for infants failing medical management. To date, a large-scale, risk-matched population-based study has not been performed to evaluate differences in mortality and resource utilization. Data on identified premature (<37 weeks) and ELBW (<1000  g) infants with PDA (International Classification of Diseases, 9th revision, Clinical Modification, 747.0) and respiratory distress (769) were obtained from Kids' Inpatient Database (2003-2009). Overall, 12,470 cases were identified, with 3008 undergoing SL. Propensity score-matched analysis of 1620 SL versus 1584 non-SL found reduced mortality (15% vs 26%) and more routine disposition (48% vs 41%) for SL (P < 0.001). SL had longer length of stay and higher total cost (P < 0.001). On multivariate analysis, SL mortality predictors were necrotizing enterocolitis (NEC; surgical odds ratio, 5.95; medical odds ratio, 4.42) and sepsis (3.43) (P < 0.006). Length of stay increased with bronchopulmonary dysplasia (BPD; 1.77), whereas total cost increased with surgical NEC (1.82) and sepsis (1.26) (P < 0.04). Non-SL mortality predictors were NEC (surgical, 76.3; medical, 6.17), sepsis (2.66), and intraventricular hemorrhage (1.97) (P < 0.005). Length of stay increased with BPD (2.92) and NEC (surgical, 2.04; medical, 1.28) (P < 0.03). Total cost increased with surgical NEC (2.06), medical NEC (1.57), sepsis (1.43), and BPD (1.30) (P < 0.001). Propensity score-matched analysis demonstrates reduced mortality in premature/ELBW infants with SL for PDA. NEC and sepsis are predictors of mortality and resource utilization.

  7. Necrotizing enterocolitis as a prognostic factor for the neurodevelopmental outcome of preterm infants - match control study after 2years.

    PubMed

    Allendorf, Antje; Dewitz, Ruth; Weber, Joy; Bakthiar, Shahrzad; Schloesser, Rolf; Rolle, Udo

    2018-01-31

    Necrotizing enterocolitis (NEC) in very low birth weight infants is a risk factor for developmental delay. To our knowledge, there are no studies published investigating the neurodevelopmental outcome of patients with NEC comparing surgically treated and conservatively treated patients versus match paired controls. The aim of this retrospective case control study was to measure the neurodevelopmental outcome of patients with NEC who were treated surgically or conservatively METHODS: All patients were identified, who have been diagnosed with NEC (ICD-10 code, P77) born between 2006 and 2013. Patients with NEC received antibiotic therapy, nasogastric decompression and fasting. Surgical treatment was indicated for patients with Bell stages IIIb. We excluded patients suffering from other relevant diseases with a possible impact on their neurodevelopmental outcome (e.g., intraventricular hemorrhage, associated malformations, asphyxia, focal intestinal perforation, short bowel syndrome). Patients were tested at the corrected gestational age of 24months according to the Bayley Scales of Infant Development II. Each participant was compared to a child of the same sex, gestational age at birth (+/-two days), birth weight (+/-10%), and age at neurodevelopmental testing (IRB approval, No. 14/2014). The outcome measures were the psychomotor index (PDI) and the mental developmental index (MDI). We included 13 conservatively and 24 surgically treated patients. The patients in group A (without surgery) achieved a mean PDI of 106, and those in group B (with surgery) a mean PDI of 90. These values were significantly higher in the conservative group A. The mean MDIs were 99 in the patient group A and 85 in patient group B. This difference was also significant. We found significantly lower MDIs and PDIs in children with surgical treatment of NEC. Further systematic prospective research on the prevention of NEC and systematic follow-ups at later stages in the patients' development are necessary in order to implement early intervention. case control study. III. Copyright © 2018. Published by Elsevier Inc.

  8. Probiotics, Prebiotics, and Synbiotics for the Prevention of Necrotizing Enterocolitis.

    PubMed

    Johnson-Henry, Kathene C; Abrahamsson, Thomas R; Wu, Richard You; Sherman, Philip M

    2016-09-01

    Necrotizing enterocolitis (NEC) is a devastating intestinal disease in preterm infants characterized by barrier disruption, intestinal microbial dysbiosis, and persistent inflammation of the colon, which results in high mortality rates. Current strategies used to manage this disease are not sufficient, although the use of human breast milk reduces the risk of NEC. Mother's milk is regarded as a fundamental nutritional source for neonates, but pasteurization of donor breast milk affects the composition of bioactive compounds. Current research is evaluating the benefits and potential pitfalls of adding probiotics and prebiotics to pasteurized milk so as to improve the functionality of the milk and thereby reduce the burden of illness caused by NEC. Probiotics (live micro-organisms that confer health to the host) and prebiotics (nondigestible oligosaccharides that stimulate the growth of healthy bacteria) are functional foods known to mediate immune responses and modulate microbial populations in the gut. Clinical research shows strain- and compound-specific responses when probiotics or prebiotics are administered in conjunction with donor breast milk for the prevention of NEC. Despite ongoing controversy surrounding optimal treatment strategies, randomized controlled studies are now investigating the use of synbiotics to reduce the incidence and severity of NEC. Synbiotics, a combination of probiotics and prebiotics, have been proposed to enhance beneficial health effects in the intestinal tract more than either agent administered alone. This review considers the implications of using probiotic-, prebiotic-, and synbiotic-supplemented breast milk as a strategy to prevent NEC and issues that could be encountered with the preparations. © 2016 American Society for Nutrition.

  9. Probiotics, Prebiotics, and Synbiotics for the Prevention of Necrotizing Enterocolitis12

    PubMed Central

    Wu, Richard You

    2016-01-01

    Necrotizing enterocolitis (NEC) is a devastating intestinal disease in preterm infants characterized by barrier disruption, intestinal microbial dysbiosis, and persistent inflammation of the colon, which results in high mortality rates. Current strategies used to manage this disease are not sufficient, although the use of human breast milk reduces the risk of NEC. Mother’s milk is regarded as a fundamental nutritional source for neonates, but pasteurization of donor breast milk affects the composition of bioactive compounds. Current research is evaluating the benefits and potential pitfalls of adding probiotics and prebiotics to pasteurized milk so as to improve the functionality of the milk and thereby reduce the burden of illness caused by NEC. Probiotics (live micro-organisms that confer health to the host) and prebiotics (nondigestible oligosaccharides that stimulate the growth of healthy bacteria) are functional foods known to mediate immune responses and modulate microbial populations in the gut. Clinical research shows strain- and compound-specific responses when probiotics or prebiotics are administered in conjunction with donor breast milk for the prevention of NEC. Despite ongoing controversy surrounding optimal treatment strategies, randomized controlled studies are now investigating the use of synbiotics to reduce the incidence and severity of NEC. Synbiotics, a combination of probiotics and prebiotics, have been proposed to enhance beneficial health effects in the intestinal tract more than either agent administered alone. This review considers the implications of using probiotic-, prebiotic-, and synbiotic-supplemented breast milk as a strategy to prevent NEC and issues that could be encountered with the preparations. PMID:27633108

  10. Efficacy of Saccharomyces boulardii on necrotizing enterocolitis or sepsis in very low birth weight infants: a randomised controlled trial.

    PubMed

    Serce, Ozge; Benzer, Derya; Gursoy, Tugba; Karatekin, Guner; Ovali, Fahri

    2013-12-01

    Probiotics have strain specific effects and the effects of fungi in preventing diseases in preterm infants have been investigated poorly. Saccharomyces boulardii is a yeast which acts both as a probiotic and a polyamine producer. The objective of this study was to investigate the efficacy of S. boulardii in preventing necrotizing enterocolitis (NEC) or sepsis in very low birth weight infants. A prospective, double blind, placebo controlled trial was conducted in preterm infants (≤ 32 GWs, ≤ 1500 g birth weight). They were randomized either to receive feeding supplementation with S. boulardii 50 mg/kg every 12 h or placebo, starting with the first feed until discharged. Necrotizing enterocolitis (NEC) or sepsis and NEC or death. Birth weight and gestational age of the study (n = 104) and the control (n = 104) groups were 1126 ± 232 vs 1162 ± 216 g and 28.8 ± 2.2 vs 28.7 ± 2.1 weeks, respectively. Neither the incidence of stage ≥ 2 NEC or death nor stage ≥ 2 NEC or late onset culture proven sepsis was significantly lower in the study group when compared with the control group (9.6% vs 7.7%, p = 0.62; 28.8% vs 23%, p = 0.34). Time to reach 100 mL/kg/day of enteral feeding (11.9 ± 7 vs 12.6 ± 7 days, p = 0.37) was not different between the groups. Saccharomyces boulardii did not decrease the incidence of NEC or sepsis. © 2013 Elsevier Ireland Ltd. All rights reserved.

  11. Glutamate-glutamine and GABA in brain of normal aged and patients with cognitive impairment.

    PubMed

    Huang, Dandan; Liu, Dan; Yin, Jianzhong; Qian, Tianyi; Shrestha, Susan; Ni, Hongyan

    2017-07-01

    To explore the changes of glutamate-glutamine (Glx) and gamma-aminobutyric acid (GABA) in the brain in normal old age and cognitive impairment using magnetic resonance spectroscopy (MRS). Seventeen normal young controls (NYC), 15 normal elderly controls (NEC), 21 patients with mild cognitive impairment (MCI) and 17 with Alzheimer disease (AD) patients were included in this study. Glx and GABA+ levels in the anterior cingulate cortex (ACC) and right hippocampus (rHP) were measured by using a MEGA-PRESS sequence. Glx/Cr and GABA+/Cr ratios were compared between NYC and NEC and between the three elderly groups using analysis of covariance (ANCOVA); the tissue fractions of voxels were used as covariates. The relationships between metabolite ratios and cognitive performance were analysed using Spearman correlation coefficients. For NEC and NYC groups, Glx/Cr and GABA+/Cr ratios were lower in NEC in ACC and rHP. For the three elderly groups, Glx/Cr ratio was lower in AD in ACC compared to NEC and MCI; Glx/Cr ratio was lower in AD in rHP compared to NEC. There was no significant decrease for GABA+/Cr ratio. Glx and GABA levels may decrease simultaneously in normal aged, and Glx level decreased predominantly in AD, and it is helpful in the early diagnosis of AD. • Glx and GABA levels may decrease simultaneously in normal aged. • Glx level may decrease predominantly in Alzheimer disease. • The balance in excitatory-inhibitory systems may be broken in AD. • Decreased Glx level may be helpful in early diagnosis of AD.

  12. Characteristics and incidence of transfusion-associated necrotizing enterocolitis in the UKCharacteristics and incidence of transfusion-associated necrotizing enterocolitis in the UK.

    PubMed

    Faraday, Christopher; Hamad, Sheima; Jones, Kelsey; Sim, Kathleen; Cherian, Shobha; James, Anitha; Godambe, Sunit; New, Helen; Kroll; Clarke, Paul

    2018-06-26

    The etiology of necrotizing enterocolitis (NEC) is unclear and postulated as being multifactorial. It has been suggested that one causative factor is the transfusion of packed red bloods cells (PRBCs) leading to the disease entity commonly referred to as transfusion-associated NEC (TANEC). TANEC has been reported in North America but its incidence has not been formally investigated in the United Kingdom (UK). Our aims were to identify the incidence of NEC and TANEC in tertiary-level UK neonatal units and to describe characteristics of TANEC cases. Using strict case definitions for NEC and TANEC, we undertook a retrospective review to estimate the incidence of TANEC cases occurring in four UK tertiary-level centers during a 38-month period. Of 8007 consecutive neonatal admissions of all gestations to the four centers, 68 babies went on to develop NEC and all affected infants were of very low birth weight (VLBW); 34 of these had previously received a transfusion of PRBCs but did not fit the diagnostic criteria for TANEC, while 15 (22%) of the 68 babies with NEC qualified as TANEC cases. UK cases occurred at an earlier postnatal age than cases reported in multiple large North American series and were of a lower birth weight. We have confirmed the presence of TANEC in the UK VLBW neonatal population. Its incidence lies within the wide range described in previous reports of this phenomenon globally, though with some local variation in characteristics. Further work is needed to clarify causation, pathophysiology, and possible mechanisms of prevention of TANEC.

  13. 24. Looking E toward Boston harbor along NEC; Berkley Avenue ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    24. Looking E toward Boston harbor along NEC; Berkley Avenue Bridge in foreground. Boston, Suffolk Co., MA. Sec. 4116, MP 227.99. - Northeast Railroad Corridor, Amtrak Route between RI/MA State Line & South Station, Boston, Suffolk County, MA

  14. Born again universe

    NASA Astrophysics Data System (ADS)

    Graham, Peter W.; Kaplan, David E.; Rajendran, Surjeet

    2018-02-01

    We present a class of nonsingular, bouncing cosmologies that evade singularity theorems through the use of vorticity in compact extra dimensions. The vorticity combats the focusing of geodesics during the contracting phase. The construction requires fluids that violate the null energy condition (NEC) in the compact dimensions, where they can be provided by known stable NEC violating sources such as Casimir energy. The four dimensional effective theory contains an NEC violating fluid of Kaluza-Klein excitations of the higher dimensional metric. These spacetime metrics could potentially allow dynamical relaxation to solve the cosmological constant problem. These ideas can also be used to support traversable Lorentzian wormholes.

  15. Cultivate Primary Nasal Epithelial Cells from Children and Reprogram into Induced Pluripotent Stem Cells

    PubMed Central

    Ulm, Ashley; Mayhew, Christopher N.; Debley, Jason; Khurana Hershey, Gurjit K.; Ji, Hong

    2016-01-01

    Nasal epithelial cells (NECs) are the part of the airways that respond to air pollutants and are the first cells infected with respiratory viruses. They are also involved in many airway diseases through their innate immune response and interaction with immune and airway stromal cells. NECs are of particular interest for studies in children due to their accessibility during clinical visits. Human induced pluripotent stem cells (iPSCs) have been generated from multiple cell types and are a powerful tool for modeling human development and disease, as well as for their potential applications in regenerative medicine. This is the first protocol to lay out methods for successful generation of iPSCs from NECs derived from pediatric participants for research purposes. It describes how to obtain nasal epithelial cells from children, how to generate primary NEC cultures from these samples, and how to reprogram primary NECs into well-characterized iPSCs. Nasal mucosa samples are useful in epidemiological studies related to the effects of air pollution in children, and provide an important tool for studying airway disease. Primary nasal cells and iPSCs derived from them can be a tool for providing unlimited material for patient-specific research in diverse areas of airway epithelial biology, including asthma and COPD research. PMID:27022951

  16. The interannual variation in monthly temperature over Northeast China during summer

    NASA Astrophysics Data System (ADS)

    Chen, Wei; Lu, Riyu

    2014-05-01

    The interannual variations of summer surface air temperature over Northeast China (NEC) were investigated through a month-to-month analysis from May to August. The results suggested that the warmer temperature over NEC is related to a local positive 500-hPa geopotential height anomaly for all four months. However, the teleconnection patterns of atmospheric circulation anomalies associated with the monthly surface air temperature over NEC behave as a distinguished subseasonal variation, although the local positive height anomaly is common from month to month. In May and June, the teleconnection pattern is characterized by a wave train in the upper and middle troposphere from the Indian Peninsula to NEC. This wave train is stronger in June than in May, possibly due to the positive feedback between the wave train and the South Asian rainfall anomaly in June, when the South Asian summer monsoon has been established. In July and August, however, the teleconnection pattern associated with the NEC temperature anomalies is characterized by an East Asia/Pacific (EAP) or Pacific/Japan (PJ) pattern, with the existence of precipitation anomalies over the Philippine Sea and the South China Sea. This pattern is much clearer in July corresponding to the stronger convection over the Philippine Sea compared to that in August.

  17. Association of the gut microbiota mobilome with hospital location and birth weight in preterm infants.

    PubMed

    Ravi, Anuradha; Estensmo, Eva Lena F; Abée-Lund, Trine M L'; Foley, Steven L; Allgaier, Bernhard; Martin, Camilia R; Claud, Erika C; Rudi, Knut

    2017-11-01

    BackgroundThe preterm infant gut microbiota is vulnerable to different biotic and abiotic factors. Although the development of this microbiota has been extensively studied, the mobilome-i.e. the mobile genetic elements (MGEs) in the gut microbiota-has not been considered. Therefore, the aim of this study was to investigate the association of the mobilome with birth weight and hospital location in the preterm infant gut microbiota.MethodsThe data set consists of fecal samples from 62 preterm infants with and without necrotizing enterocolitis (NEC) from three different hospitals. We analyzed the gut microbiome by using 16S rRNA amplicon sequencing, shot-gun metagenome sequencing, and quantitative PCR. Predictive models and other data analyses were performed using MATLAB and QIIME.ResultSThe microbiota composition was significantly different between NEC-positive and NEC-negative infants and significantly different between hospitals. An operational taxanomic unit (OTU) showed strong positive and negative correlation with NEC and birth weight, respectively, whereas none showed significance for mode of delivery. Metagenome analyses revealed high levels of conjugative plasmids with MGEs and virulence genes. Results from quantitative PCR showed that the plasmid signature genes were significantly different between hospitals and in NEC-positive infants.ConclusionOur results point toward an association of the mobilome with hospital location in preterm infants.

  18. The sensing of respiratory gases in fish: Mechanisms and signalling pathways.

    PubMed

    Perry, S F; Tzaneva, V

    2016-04-01

    Chemoreception in fish is critical for sensing changes in the chemical composition of the external and internal environments and is often the first step in a cascade of events leading to cardiorespiratory and metabolic adjustments. Of paramount importance is the ability to sense changes in the levels of the three respiratory gases, oxygen (O2), carbon dioxide (CO2) and ammonia (NH3). In this review, we discuss the role of piscine neuroepithelial cells (NEC), putative peripheral chemoreceptors, as tri-modal sensors of O2, CO2 and NH3. Where possible, we elaborate on the signalling pathways linking NEC stimulation to afferent responses, the potential role of neurotransmitters in activating downstream neuronal pathways and the impact of altered levels of the respiratory gases on NEC structure and function. Although serotonin, the major neurotransmitter contained within NECs, is presumed to be the principal agent eliciting the reflex responses to altered levels of the respiratory gases, there is accumulating evidence for the involvement of "gasomitters", a class of gaseous neurotransmitters which includes nitric oxide (NO), carbon monoxide (CO) and hydrogen sulphide (H2S). Recent data suggest that CO inhibits and H2S stimulates NEC activity whereas NO can either be inhibitory or stimulatory depending on developmental age. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Cultivate Primary Nasal Epithelial Cells from Children and Reprogram into Induced Pluripotent Stem Cells.

    PubMed

    Ulm, Ashley; Mayhew, Christopher N; Debley, Jason; Khurana Hershey, Gurjit K; Ji, Hong

    2016-03-10

    Nasal epithelial cells (NECs) are the part of the airways that respond to air pollutants and are the first cells infected with respiratory viruses. They are also involved in many airway diseases through their innate immune response and interaction with immune and airway stromal cells. NECs are of particular interest for studies in children due to their accessibility during clinical visits. Human induced pluripotent stem cells (iPSCs) have been generated from multiple cell types and are a powerful tool for modeling human development and disease, as well as for their potential applications in regenerative medicine. This is the first protocol to lay out methods for successful generation of iPSCs from NECs derived from pediatric participants for research purposes. It describes how to obtain nasal epithelial cells from children, how to generate primary NEC cultures from these samples, and how to reprogram primary NECs into well-characterized iPSCs. Nasal mucosa samples are useful in epidemiological studies related to the effects of air pollution in children, and provide an important tool for studying airway disease. Primary nasal cells and iPSCs derived from them can be a tool for providing unlimited material for patient-specific research in diverse areas of airway epithelial biology, including asthma and COPD research.

  20. Characterization of a swept external cavity quantum cascade laser for rapid broadband spectroscopy and sensing

    DOE PAGES

    Brumfield, Brian E.; Taubman, Matthew S.; Suter, Jonathan D.; ...

    2015-09-21

    The performance of a rapidly swept external cavity quantum cascade laser (ECQCL) system combined with an open-path Herriott cell was evaluated for time-resolved measurements of chemical species with broad and narrow absorption spectra. A spectral window spanning 1278 – 1390 cm -1 was acquired at a 200 Hz acquisition rate, corresponding to a tuning rate of 2x10 4 cm -1/s, with a spectral resolution of 0.2 cm -1. The capability of the ECQCL to measure < 100 ppbv changes in N 2O and F134A concentrations on millisecond timescales was demonstrated in simulated plume studies with releases near the open-path Herriottmore » cell. Absorbance spectra measured using the ECQCL system exhibited noise-equivalent absorption coefficients of 5x10 -9 cm -1Hz -1/2. For a spectrum acquisition time of 5 ms, noise-equivalent concentrations (NEC) for N 2O and F134A were measured to be 70 and 16 ppbv respectively, which improved to sub-ppbv levels with averaging to 100 s. Noise equivalent column densities of 0.64 and 0.25 ppmv x m in 1 sec are estimated for N 2O and F134A.« less

  1. Probiotics for prevention of necrotizing enterocolitis in preterm infants.

    PubMed

    AlFaleh, Khalid; Anabrees, Jasim

    2014-09-01

    Necrotizing enterocolitis (NEC) and nosocomial sepsis are associated with increased morbidity and mortality in preterm infants. Through prevention of bacterial migration across the mucosa, competitive exclusion of pathogenic bacteria, and enhancing the immune responses of the host, prophylactic enteral probiotics (live microbial supplements) may play a role in reducing NEC and the associated morbidity. To compare the efficacy and safety of prophylactic enteral probiotics administration versus placebo or no treatment in the prevention of severe NEC or sepsis, or both, in preterm infants. For this update, searches were made of MEDLINE (1966 to October 2013), EMBASE (1980 to October 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2013, Issue 10), and abstracts of annual meetings of the Society for Pediatric Research (1995 to 2013). Only randomized or quasi-randomized controlled trials that enrolled preterm infants < 37 weeks gestational age or < 2500 g birth weight, or both, were considered. Trials were included if they involved enteral administration of any live microbial supplement (probiotics) and measured at least one prespecified clinical outcome. Standard methods of The Cochrane Collaboration and its Neonatal Group were used to assess the methodologic quality of the trials and for data collection and analysis. Twenty-four eligible trials were included. Included trials were highly variable with regard to enrolment criteria (that is birth weight and gestational age), baseline risk of NEC in the control groups, timing, dose, formulation of the probiotics, and feeding regimens. In a meta-analysis of trial data, enteral probiotics supplementation significantly reduced the incidence of severe NEC (stage II or more) (typical relative risk (RR) 0.43, 95% confidence interval (CI) 0.33 to 0.56; 20 studies, 5529 infants) and mortality (typical RR 0.65, 95% CI 0.52 to 0.81; 17 studies, 5112 infants). There was no evidence of significant reduction of nosocomial sepsis (typical RR 0.91, 95% CI 0.80 to 1.03; 19 studies, 5338 infants). The included trials reported no systemic infection with the supplemental probiotics organism. Probiotics preparations containing either lactobacillus alone or in combination with bifidobacterium were found to be effective. Enteral supplementation of probiotics prevents severe NEC and all cause mortality in preterm infants. Our updated review of available evidence strongly supports a change in practice. Head to head comparative studies are required to assess the most effective preparations, timing, and length of therapy to be utilized. Probiotics for prevention of necrotizing enterocolitis in preterm infants Necrotizing enterocolitis (NEC) is a serious disease that affects the bowel of premature infants in the first few weeks of life. Although the cause of NEC is not entirely known, milk feeding and bacterial growth play a role. Probiotics (dietary supplements containing potentially beneficial bacteria or yeast) have been used to prevent NEC. Our review of studies found that the use of probiotics reduces the occurrence of NEC and death in premature infants born weighing less than 1500 grams. There is insufficient data with regard to the benefits and potential adverse effects in the most at risk infants weighing less than 1000 grams at birth. Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

  2. Transnational Alliances: "La Clase Mágica--Nepohualtzitzin" Ethnomathematics Club

    ERIC Educational Resources Information Center

    Prieto, Linda; Claeys, Lorena; González, Everardo Lara

    2015-01-01

    This article exposes the ancient "Nepohualtzitzin" as an important contemporary mathematical tool. The design and development of "Nepohualtzitzin" Ethnomathematics Clubs (NECs) in predominantly Latina/o and low-income schools is also presented. NECs provide informal learning opportunities to develop and strengthen cultural…

  3. 7 CFR 2900.3 - Essential agricultural uses.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...). 4971Irrigation Systems. Fertilizer and Agricultural Chemicals (Process and Feedstock Use Only) 1474Potash, Soda, and Borate Materials. 1475Phosphate Rock. 1477Sulfur. 2819Industrial Inorganic Chemicals, n.e.c... related only). 2869Industrial Organic Chemicals, n.e.c. (Agricutural related only). 287Agricultural...

  4. 7 CFR 2900.3 - Essential agricultural uses.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...). 4971Irrigation Systems. Fertilizer and Agricultural Chemicals (Process and Feedstock Use Only) 1474Potash, Soda, and Borate Materials. 1475Phosphate Rock. 1477Sulfur. 2819Industrial Inorganic Chemicals, n.e.c... related only). 2869Industrial Organic Chemicals, n.e.c. (Agricutural related only). 287Agricultural...

  5. 7 CFR 2900.3 - Essential agricultural uses.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...). 4971Irrigation Systems. Fertilizer and Agricultural Chemicals (Process and Feedstock Use Only) 1474Potash, Soda, and Borate Materials. 1475Phosphate Rock. 1477Sulfur. 2819Industrial Inorganic Chemicals, n.e.c... related only). 2869Industrial Organic Chemicals, n.e.c. (Agricutural related only). 287Agricultural...

  6. 7 CFR 2900.3 - Essential agricultural uses.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...). 4971Irrigation Systems. Fertilizer and Agricultural Chemicals (Process and Feedstock Use Only) 1474Potash, Soda, and Borate Materials. 1475Phosphate Rock. 1477Sulfur. 2819Industrial Inorganic Chemicals, n.e.c... related only). 2869Industrial Organic Chemicals, n.e.c. (Agricutural related only). 287Agricultural...

  7. A decrease in the number of cases of necrotizing enterocolitis associated with the enhancement of infection prevention and control measures during a Staphylococcus aureus outbreak in a neonatal intensive care unit.

    PubMed

    Lemyre, Brigitte; Xiu, Wenlong; Bouali, Nicole Rouvinez; Brintnell, Janet; Janigan, Jo-Anne; Suh, Kathryn N; Barrowman, Nicholas

    2012-01-01

    Most cases of necrotizing enterocolitis (NEC) are sporadic, but outbreaks in hospital settings suggest an infectious cause. Our neonatal intensive care unit (NICU) experienced an outbreak of methicillin-sensitive Staphylococcus aureus (MSSA). We aimed to assess whether the enhancement of infection prevention and control measures would be associated with a reduction in the number of cases of NEC. Retrospective chart review. A 24-bed, university-affiliated, inborn level 3 NICU. Infants of less than 30 weeks gestation or birth weight ≤ 1,500 g admitted to the NICU between January 2007 and December 2008 were considered at risk of NEC. All cases of NEC were reviewed. Infection prevention and control measures, including hand hygiene education, were enhanced during the outbreak. Avoidance of overcapacity in the NICU was reinforced, environmental services (ES) measures were enhanced, and ES hours were increased. Two hundred eighty-two at-risk infants were admitted during the study. Their gestational age and birth weight (mean ± SD) were 28.2 ± 2.7 weeks and 1,031 ± 290 g, respectively. The proportion of NEC was 18/110 (16.4%) before the outbreak, 1/54 (1.8%) during the outbreak, and 4/118 (3.4%) after the outbreak. After adjustment for gestational age, birth weight, gender, and singleton versus multiple births, the proportion was lower in the postoutbreak period than in the preoutbreak period (P < .002). Although this observational study cannot establish a causal relationship, there was a significant decrease in the incidence of NEC following implementation of enhanced infection prevention and control measures to manage an MSSA outbreak.

  8. Neuroepithelial cells and the hypoxia emersion response in the amphibious fish Kryptolebias marmoratus.

    PubMed

    Regan, Kelly S; Jonz, Michael G; Wright, Patricia A

    2011-08-01

    Teleost fish have oxygen-sensitive neuroepithelial cells (NECs) in the gills that appear to mediate physiological responses to hypoxia, but little is known about oxygen sensing in amphibious fish. The mangrove rivulus, Kryptolebias marmoratus, is an amphibious fish that respires via the gills and/or the skin. First, we hypothesized that both the skin and gills are sites of oxygen sensing in K. marmoratus. Serotonin-positive NECs were abundant in both gills and skin, as determined by immunohistochemical labelling and fluorescence microscopy. NECs retained synaptic vesicles and were found near nerve fibres labelled with the neuronal marker zn-12. Skin NECs were 42% larger than those of the gill, as estimated by measurement of projection area, and 45% greater in number. Moreover, for both skin and gill NECs, NEC area increased significantly (30-60%) following 7 days of exposure to hypoxia (1.5 mg l(-1) dissolved oxygen). Another population of cells containing vesicular acetylcholine transporter (VAChT) proteins were also observed in the skin and gills. The second hypothesis we tested was that K. marmoratus emerse in order to breathe air cutaneously when challenged with severe aquatic hypoxia, and this response will be modulated by neurochemicals associated chemoreceptor activity. Acute exposure to hypoxia induced fish to emerse at 0.2 mg l(-1). When K. marmoratus were pre-exposed to serotonin or acetylcholine, they emersed at a significantly higher concentration of oxygen than untreated fish. Pre-exposure to receptor antagonists (ketanserin and hexamethonium) predictably resulted in fish emersing at a lower concentration of oxygen. Taken together, these results suggest that oxygen sensing occurs at the branchial and/or cutaneous surfaces in K. marmoratus and that serotonin and acetylcholine mediate, in part, the emersion response.

  9. New Medical and Surgical Insights Into Neonatal Necrotizing Enterocolitis: A Review.

    PubMed

    Frost, Brandy L; Modi, Biren P; Jaksic, Tom; Caplan, Michael S

    2017-01-01

    Necrotizing enterocolitis (NEC) has long remained a significant cause of morbidity and mortality in neonatal intensive care units. While the mainstay of treatment for this devastating condition remains largely supportive, research efforts continue to be directed toward understanding pathophysiology as well as how best to approach surgical management when indicated. In this review, we first examine recent medical observations, including overviews on the microbiome and a brief review of the use of probiotics. Next, we discuss the use of biomarkers and how clinicians may be able to use them in the future to predict the course of disease and, perhaps, the need for surgical intervention. We then provide an overview on the use of exclusive human milk feeding and the utility of this approach in preventing NEC. Finally, we discuss recent developments in the surgical management of NEC, beginning with indications for surgery and following with a section on technical surgical considerations, including peritoneal drain vs laparotomy. The review concludes with outcomes from infants with surgically treated NEC. Although medical treatment options for NEC are largely unchanged, understanding of the disease continues to evolve. As new research methods are developed, NEC pathophysiology can be more completely understood. In time, it is hoped that data from ongoing and planned clinical trials will allow us to routinely add targeted preventive measures in addition to human milk, such as prebiotics and probiotics, to the management of high-risk infants. In addition, the discovery of novel biomarkers may not only prove useful in predicting severity of illness but also will hopefully allow for identification of the disease prior to onset of clinical signs. Finally, continued investigation into optimizing surgical outcomes is essential in this population of infants, many of whom require long-term parenteral therapy and intestinal rehabilitation.

  10. Impact of Optimized Breastfeeding on the Costs of Necrotizing Enterocolitis in Extremely Low Birthweight Infants.

    PubMed

    Colaizy, Tarah T; Bartick, Melissa C; Jegier, Briana J; Green, Brittany D; Reinhold, Arnold G; Schaefer, Andrew J; Bogen, Debra L; Schwarz, Eleanor Bimla; Stuebe, Alison M

    2016-08-01

    To estimate risk of necrotizing enterocolitis (NEC) for extremely low birth weight (ELBW) infants as a function of preterm formula (PF) and maternal milk intake and calculate the impact of suboptimal feeding on the incidence and costs of NEC. We used aORs derived from the Glutamine Trial to perform Monte Carlo simulation of a cohort of ELBW infants under current suboptimal feeding practices, compared with a theoretical cohort in which 90% of infants received at least 98% human milk. NEC incidence among infants receiving ≥98% human milk was 1.3%; 11.1% among infants fed only PF; and 8.2% among infants fed a mixed diet (P = .002). In adjusted models, compared with infants fed predominantly human milk, we found an increased risk of NEC associated with exclusive PF (aOR = 12.1, 95% CI 1.5, 94.2), or a mixed diet (aOR 8.7, 95% CI 1.2-65.2). In Monte Carlo simulation, current feeding of ELBW infants was associated with 928 excess NEC cases and 121 excess deaths annually, compared with a model in which 90% of infants received ≥98% human milk. These models estimated an annual cost of suboptimal feeding of ELBW infants of $27.1 million (CI $24 million, $30.4 million) in direct medical costs, $563 655 (CI $476 191, $599 069) in indirect nonmedical costs, and $1.5 billion (CI $1.3 billion, $1.6 billion) in cost attributable to premature death. Among ELBW infants, not being fed predominantly human milk is associated with an increased risk of NEC. Efforts to support milk production by mothers of ELBW infants may prevent infant deaths and reduce costs. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Microbial and metabolic signatures of necrotizing enterocolitis in formula-fed piglets

    USDA-ARS?s Scientific Manuscript database

    Major risk factors for necrotizing enterocolitis (NEC) include premature birth, formula feeding, and microbial colonization of the gastrointestinal tract. We previously showed that feeding formula composed of lactose vs corn syrup solids protects against NEC in preterm pigs, however the microbial an...

  12. Antibiotics modulate intestinal immunity and prevent necrotizing enterocolitis in preterm neonatal piglets

    USDA-ARS?s Scientific Manuscript database

    Preterm birth, bacterial colonization, and formula feeding predispose to necrotizing enterocolitis (NEC). Antibiotics are commonly administered to prevent sepsis in preterm infants, but it is not known whether this affects intestinal immunity and NEC resistance. We hypothesized that broad-spectrum a...

  13. Function Point Analysis Depot

    NASA Technical Reports Server (NTRS)

    Muniz, R.; Martinez, El; Szafran, J.; Dalton, A.

    2011-01-01

    The Function Point Analysis (FPA) Depot is a web application originally designed by one of the NE-C3 branch's engineers, Jamie Szafran, and created specifically for the Software Development team of the Launch Control Systems (LCS) project. The application consists of evaluating the work of each developer to be able to get a real estimate of the hours that is going to be assigned to a specific task of development. The Architect Team had made design change requests for the depot to change the schema of the application's information; that information, changed in the database, needed to be changed in the graphical user interface (GUI) (written in Ruby on Rails (RoR and the web service/server side in Java to match the database changes. These changes were made by two interns from NE-C, Ricardo Muniz from NE-C3, who made all the schema changes for the GUI in RoR and Edwin Martinez, from NE-C2, who made all the changes in the Java side.

  14. Rb Loss and KRAS Mutation Are Predictors of the Response to Platinum-Based Chemotherapy in Pancreatic Neuroendocrine Neoplasm with Grade 3: A Japanese Multicenter Pancreatic NEN-G3 Study.

    PubMed

    Hijioka, Susumu; Hosoda, Waki; Matsuo, Keitaro; Ueno, Makoto; Furukawa, Masayuki; Yoshitomi, Hideyuki; Kobayashi, Noritoshi; Ikeda, Masafumi; Ito, Tetsuhide; Nakamori, Shoji; Ishii, Hiroshi; Kodama, Yuzo; Morizane, Chigusa; Okusaka, Takuji; Yanagimoto, Hiroaki; Notohara, Kenji; Taguchi, Hiroki; Kitano, Masayuki; Yane, Kei; Maguchi, Hiroyuki; Tsuchiya, Yoshiaki; Komoto, Izumi; Tanaka, Hiroki; Tsuji, Akihito; Hashigo, Syunpei; Kawaguchi, Yoshiaki; Mine, Tetsuya; Kanno, Atsushi; Murohisa, Go; Miyabe, Katsuyuki; Takagi, Tadayuki; Matayoshi, Nobutaka; Yoshida, Tsukasa; Hara, Kazuo; Imamura, Masayuki; Furuse, Junji; Yatabe, Yasushi; Mizuno, Nobumasa

    2017-08-15

    Purpose: Patients with pancreatic neuroendocrine neoplasm grade-3 (PanNEN-G3) show variable responses to platinum-based chemotherapy. Recent studies indicated that PanNEN-G3 includes well-differentiated neuroendocrine tumor with G3 (NET-G3). Here, we examined the clinicopathologic and molecular features of PanNEN-G3 and assessed the responsiveness to chemotherapy and survival. Experimental Design: A total of 100 patients with PanNEN-G3 were collected from 31 institutions, and after central review characteristics of each histologic subtype [NET-G3 vs. pancreatic neuroendocrine carcinoma (NEC-G3)] were analyzed, including clinical, radiological, and molecular features. Factors that correlate with response to chemotherapy and survival were assessed. Results: Seventy patients analyzed included 21 NETs-G3 (30%) and 49 NECs-G3 (70%). NET-G3 showed lower Ki67-labeling index (LI; median 28.5%), no abnormal Rb expression (0%), and no mutated KRAS (0%), whereas NEC-G3 showed higher Ki67-LI (median 80.0%), Rb loss (54.5%), and KRAS mutations (48.7%). Chemotherapy response rate (RR), platinum-based chemotherapy RR, and prognosis differed significantly between NET-G3 and NEC-G3. Chemotherapeutic outcomes were worse in NET-G3 ( P < 0.001). When we stratified PanNEN-G3 with Rb and KRAS , PanNENs-G3 with Rb loss and those with mutated KRAS showed significantly higher RRs to platinum-based chemotherapy than those without (Rb loss, 80% vs. normal Rb, 24%, P = 0.006; mutated KRAS , 77% versus wild type, 23%, P = 0.023). Rb was a predictive marker of response to platinum-based chemotherapy even in NEC-G3 ( P = 0.035). Conclusions: NET-G3 and NEC-G3 showed distinct clinicopathologic characteristics. Notably, NET-G3 does not respond to platinum-based chemotherapy. Rb and KRAS are promising predictors of response to platinum-based chemotherapy for PanNEN-G3, and Rb for NEC-G3. Clin Cancer Res; 23(16); 4625-32. ©2017 AACR . ©2017 American Association for Cancer Research.

  15. Multiple strains probiotics appear to be the most effective probiotics in the prevention of necrotizing enterocolitis and mortality: An updated meta-analysis

    PubMed Central

    Chang, Hung-Yang; Chen, Jin-Hua; Chang, Jui-Hsing; Lin, Hung-Chih; Lin, Chien-Yu; Peng, Chun-Chih

    2017-01-01

    Background Some oral probiotics have been shown to prevent necrotizing enterocolitis (NEC) and decrease mortality effectively in preterm very low birth weight (PVLBW) infants. However, it is unclear whether a single probiotic or a mixture of probiotics is most effective for the prevention of NEC. Objective A meta-analysis was conducted by reviewing the most up to date literature to investigate whether multiple strains probiotics are more effective than a single strain in reducing NEC and death in PVLBW infants. Data sources Relevant studies were identified by searches of the MEDLINE, EMBASE, and Cochrane CENTRAL databases, from 2001 to 2016. Data extraction and synthesis The inclusion criteria were randomized controlled trials of any enteral probiotic supplementation that was initiated within the first 7 days and continued for at least 14 days in preterm infants (≤ 34 weeks’ gestation) and/or those of a birth weight ≤1500 g. Results A total of 25 trials (n = 7345 infants) were eligible for inclusion in the meta-analysis using a fixed-effects model. Multiple strains probiotics were associated with a marked reduction in the incidence of NEC, with a pooled OR of 0.36 (95% CI, 0.24–0.53; P < .00001). Single strain probiotic using Lactobacillus species had a borderline effect in reducing NEC (OR of 0.60; 95% CI 0.36–1.0; P = .05), but not mortality. Multiple strains probiotics had a greater effectiveness in reducing mortality and were associated with a pooled OR of 0.58 (95% CI, 0.43–0.79; P = .0006). Trials using single strain of Bifidobacterium species and Saccharomyces boulardii did not reveal any beneficial effects in terms of reducing NEC or mortality. Conclusion This updated report found that multiple strains probiotics appear to be the most feasible and effective strategy for the prevention of NEC and reduction of mortality in PVLBW neonates. Further clinical trials should focus on which probiotic combinations are most effective. PMID:28182644

  16. Oral lactoferrin for the treatment of sepsis and necrotizing enterocolitis in neonates

    USDA-ARS?s Scientific Manuscript database

    Neonatal sepsis and necrotizing enterocolitis (NEC) cause significant neonatal mortality and morbidity in spite of appropriate antibiotic therapy. Enhancing host defense and modulating inflammation by using lactoferrin as an adjunct to antibiotics in the treatment of sepsis and/or NEC may improve cl...

  17. Oral lactoferrin for the treatment of sepsis and necrotizing enterocolitis in neonates

    USDA-ARS?s Scientific Manuscript database

    Neonatal sepsis and necrotizing enterocolitis (NEC) cause significant neonatal mortality and morbidity in spite of appropriate antibiotic therapy. Enhancing host defence and modulating inflammation by using lactoferrin as an adjunct to antibiotics in the treatment of sepsis and/or NEC may improve cl...

  18. Association of Red Blood Cell Transfusion, Anemia, and Necrotizing Enterocolitis in Very Low-Birth-Weight Infants.

    PubMed

    Patel, Ravi M; Knezevic, Andrea; Shenvi, Neeta; Hinkes, Michael; Keene, Sarah; Roback, John D; Easley, Kirk A; Josephson, Cassandra D

    2016-03-01

    Data regarding the contribution of red blood cell (RBC) transfusion and anemia to necrotizing enterocolitis (NEC) are conflicting. These associations have not been prospectively evaluated, accounting for repeated, time-varying exposures. To determine the relationship between RBC transfusion, severe anemia, and NEC. In a secondary, prospective, multicenter observational cohort study from January 2010 to February 2014, very low-birth-weight (VLBW, ≤1500 g) infants, within 5 days of birth, were enrolled at 3 level III neonatal intensive care units in Atlanta, Georgia. Two hospitals were academically affiliated and 1 was a community hospital. Infants received follow-up until 90 days, hospital discharge, transfer to a non-study-affiliated hospital, or death (whichever came first). Multivariable competing-risks Cox regression was used, including adjustment for birth weight, center, breastfeeding, illness severity, and duration of initial antibiotic treatment, to evaluate the association between RBC transfusion, severe anemia, and NEC. The primary exposure was RBC transfusion. The secondary exposure was severe anemia, defined a priori as a hemoglobin level of 8 g/dL or less. Both exposures were evaluated as time-varying covariates at weekly intervals. Necrotizing enterocolitis, defined as Bell stage 2 or greater by preplanned adjudication. Mortality was evaluated as a competing risk. Of 600 VLBW infants enrolled, 598 were evaluated. Forty-four (7.4%) infants developed NEC. Thirty-two (5.4%) infants died (all cause). Fifty-three percent of infants (319) received a total of 1430 RBC transfusion exposures. The unadjusted cumulative incidence of NEC at week 8 among RBC transfusion-exposed infants was 9.9% (95% CI, 6.9%-14.2%) vs 4.6% (95% CI, 2.6%-8.0%) among those who were unexposed. In multivariable analysis, RBC transfusion in a given week was not significantly related to the rate of NEC (adjusted cause-specific hazard ratio, 0.44 [95% CI, 0.17-1.12]; P = .09). Based on evaluation of 4565 longitudinal measurements of hemoglobin (median, 7 per infant), the rate of NEC was significantly increased among VLBW infants with severe anemia in a given week compared with those who did not have severe anemia (adjusted cause-specific hazard ratio, 5.99 [95% CI, 2.00-18.0]; P = .001). Among VLBW infants, severe anemia, but not RBC transfusion, was associated with an increased risk of NEC. Further studies are needed to evaluate whether preventing severe anemia is more important than minimizing RBC transfusion.

  19. Enhancement of curcumin oral absorption and pharmacokinetics of curcuminoids and curcumin metabolites in mice

    PubMed Central

    Zhongfa, Liu; Chiu, Ming; Wang, Jiang; Chen, Wei; Yen, Winston; Fan-Havard, Patty; Yee, Lisa D.; Chan, Kenneth K.

    2012-01-01

    Purpose Curcumin has shown a variety of biological activity for various human diseases including cancer in preclinical setting. Its poor oral bioavailability poses significant pharmacological barriers to its clinical application. Here, we established a practical nano-emulsion curcumin (NEC) containing up to 20% curcumin (w/w) and conducted the pharmacokinetics of curcuminoids and curcumin metabolites in mice. Methods This high loading NEC was formulated based on the high solubility of curcumin in polyethylene glycols (PEGs) and the synergistic enhancement of curcumin absorption by PEGs and Cremophor EL. The pharmacokinetics of curcuminoids and curcumin metabolites was characterized in mice using a LC–MS/MS method, and the pharmacokinetic parameters were determined using WinNonlin computer software. Results A tenfold increase in the AUC0→24h and more than 40-fold increase in the Cmax in mice were observed after an oral dose of NEC compared with suspension curcumin in 1% methylcellulose. The plasma pharmacokinetics of its two natural congeners, demethoxycurcumin and bisdemethoxycurcumin, and three metabolites, tetrahydrocurcumin (THC), curcumin-O-glucuronide, and curcumin-O-sulfate, was characterized for the first time in mice after an oral dose of NEC. Conclusion This oral absorption enhanced NEC may provide a practical formulation to conduct the correlative study of the PK of curcuminoids and their pharmacodynamics, e.g., hypomethylation activity in vivo. PMID:21968952

  20. Does abdominal sonography provide additional information over abdominal plain radiography for diagnosis of necrotizing enterocolitis in neonates?

    PubMed

    Dilli, Dilek; Suna Oğuz, S; Erol, Reyhan; Ozkan-Ulu, Hülya; Dumanlı, Hüseyin; Dilmen, Uğur

    2011-03-01

    To explore whether addition of abdominal sonography (AUS) to plain radiography is helpful in the management of premature newborns with necrotizing enterocolitis (NEC). This study is a prospective analysis of 93 premature neonates with NEC who were followed-up in our neonatal intensive care unit between October 2007 and April 2009. Patients were classified into two groups; group I with suspected NEC (stage I) (n = 54) and group II with definite NEC (stage ≥II) (n = 39). Pneumatosis intestinalis (PI) (n = 29), free air (n = 9), and portal venous gas (PVG) (n = 1) were observed in group II on plain radiography. In the same group, echoic free fluid (EFF) (n = 9), PVG (n = 6), PI (n = 5), and focal fluid collection (n = 3) were the most prominent sonographic findings. In patients with intestinal perforation, whereas EFF and bowel wall thinning were observed on AUS, free air was not detected on plain radiography as a sign of intestinal perforation. Our results suggest AUS to be superior to plain radiography on early detection of intestinal perforation by demonstrating PVG and EFF collection. Therefore, it may be life-saving by directing the surgeon to perform surgical intervention in the case of clinical deterioration in the course of NEC.

  1. Comparability of children's sedentary time estimates derived from wrist worn GENEActiv and hip worn ActiGraph accelerometer thresholds.

    PubMed

    Boddy, Lynne M; Noonan, Robert J; Kim, Youngwon; Rowlands, Alex V; Welk, Greg J; Knowles, Zoe R; Fairclough, Stuart J

    2018-03-28

    To examine the comparability of children's free-living sedentary time (ST) derived from raw acceleration thresholds for wrist mounted GENEActiv accelerometer data, with ST estimated using the waist mounted ActiGraph 100count·min -1 threshold. Secondary data analysis. 108 10-11-year-old children (n=43 boys) from Liverpool, UK wore one ActiGraph GT3X+ and one GENEActiv accelerometer on their right hip and left wrist, respectively for seven days. Signal vector magnitude (SVM; mg) was calculated using the ENMO approach for GENEActiv data. ST was estimated from hip-worn ActiGraph data, applying the widely used 100count·min -1 threshold. ROC analysis using 10-fold hold-out cross-validation was conducted to establish a wrist-worn GENEActiv threshold comparable to the hip ActiGraph 100count·min -1 threshold. GENEActiv data were also classified using three empirical wrist thresholds and equivalence testing was completed. Analysis indicated that a GENEActiv SVM value of 51mg demonstrated fair to moderate agreement (Kappa: 0.32-0.41) with the 100count·min -1 threshold. However, the generated and empirical thresholds for GENEActiv devices were not significantly equivalent to ActiGraph 100count·min -1 . GENEActiv data classified using the 35.6mg threshold intended for ActiGraph devices generated significantly equivalent ST estimates as the ActiGraph 100count·min -1 . The newly generated and empirical GENEActiv wrist thresholds do not provide equivalent estimates of ST to the ActiGraph 100count·min -1 approach. More investigation is required to assess the validity of applying ActiGraph cutpoints to GENEActiv data. Future studies are needed to examine the backward compatibility of ST data and to produce a robust method of classifying SVM-derived ST. Copyright © 2018 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  2. Digital scale converter

    DOEpatents

    Upton, Richard G.

    1978-01-01

    A digital scale converter is provided for binary coded decimal (BCD) conversion. The converter may be programmed to convert a BCD value of a first scale to the equivalent value of a second scale according to a known ratio. The value to be converted is loaded into a first BCD counter and counted down to zero while a second BCD counter registers counts from zero or an offset value depending upon the conversion. Programmable rate multipliers are used to generate pulses at selected rates to the counters for the proper conversion ratio. The value present in the second counter at the time the first counter is counted to the zero count is the equivalent value of the second scale. This value may be read out and displayed on a conventional seven-segment digital display.

  3. Hadrons registration in emulsion chamber with carbon block

    NASA Technical Reports Server (NTRS)

    Tomaszewski, A.; Wlodarczyk, Z.

    1985-01-01

    Nuclear-electro-magnetic cascade (NEC) in X-ray emulsion chambers with carbon block, which are usually used in the Pamir experiment, was Monte-Carlo simulated. Going over from optical density to Summary E sub gamma is discussed. The hole of NEC in the interpretation of energy spectra is analyzed.

  4. 40 CFR 372.23 - SIC and NAICS codes to which this Part applies.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...); 211112Natural Gas Liquid Extraction Limited to facilities that recover sulfur from natural gas (previously classified under SIC 2819, Industrial Inorganic chemicals, NEC (recovering sulfur from natural gas... engaged in providing combinations of electric, gas, and other services, not elsewhere classified (N.E.C...

  5. 40 CFR 372.23 - SIC and NAICS codes to which this Part applies.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...); 211112Natural Gas Liquid Extraction Limited to facilities that recover sulfur from natural gas (previously classified under SIC 2819, Industrial Inorganic chemicals, NEC (recovering sulfur from natural gas... engaged in providing combinations of electric, gas, and other services, not elsewhere classified (N.E.C...

  6. 40 CFR 372.23 - SIC and NAICS codes to which this Part applies.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...); 211112Natural Gas Liquid Extraction Limited to facilities that recover sulfur from natural gas (previously classified under SIC 2819, Industrial Inorganic chemicals, NEC (recovering sulfur from natural gas... engaged in providing combinations of electric, gas, and other services, not elsewhere classified (N.E.C...

  7. Diminished citrulline-arginine-nitric oxide production rates are associated with necrotizing enterocolitis incidence in premature pigs

    USDA-ARS?s Scientific Manuscript database

    Necrotizing enterocolitis (NEC) is a major gastrointestinal disease in premature infants that is associated with formula feeding and intestinal hypoxia. Low arginine availability in these infants has been linked to NEC since arginine is the sole precursor of nitric oxide (NO), a critical mediator of...

  8. Oral lactoferrin for the prevention of sepsis and necrotizing enterocolotis in preterm infants

    USDA-ARS?s Scientific Manuscript database

    Lactoferrin, a normal component of human colostrum, milk, tears and saliva can enhance host defence and may be effective in the prevention of sepsis and necrotizing enterocolitis (NEC) in preterm neonates. To assess the safety and effectiveness of oral lactoferrin in the prevention of sepsis and NEC...

  9. Low abdominal NIRS values and elevated plasma intestinal fatty acid-binding protein in a premature piglet model of necrotizing enterocolitis

    USDA-ARS?s Scientific Manuscript database

    To identify early markers of necrotizing enterocolitis (NEC), we hypothesized that continuous abdominal near-infrared spectroscopy (A-NIRS) measurement of splanchnic tissue oxygen saturation and intermittent plasma intestinal fatty-acid binding protein (pI-FABP) measured every 6 hours can detect NEC...

  10. Evolution of the hypoxia-sensitive cells involved in amniote respiratory reflexes

    PubMed Central

    Hockman, Dorit; Burns, Alan J; Schlosser, Gerhard; Gates, Keith P; Jevans, Benjamin; Mongera, Alessandro; Fisher, Shannon; Unlu, Gokhan; Knapik, Ela W; Kaufman, Charles K; Mosimann, Christian; Zon, Leonard I; Lancman, Joseph J; Dong, P Duc S; Lickert, Heiko; Tucker, Abigail S; Baker, Clare V H

    2017-01-01

    The evolutionary origins of the hypoxia-sensitive cells that trigger amniote respiratory reflexes – carotid body glomus cells, and ‘pulmonary neuroendocrine cells’ (PNECs) - are obscure. Homology has been proposed between glomus cells, which are neural crest-derived, and the hypoxia-sensitive ‘neuroepithelial cells’ (NECs) of fish gills, whose embryonic origin is unknown. NECs have also been likened to PNECs, which differentiate in situ within lung airway epithelia. Using genetic lineage-tracing and neural crest-deficient mutants in zebrafish, and physical fate-mapping in frog and lamprey, we find that NECs are not neural crest-derived, but endoderm-derived, like PNECs, whose endodermal origin we confirm. We discover neural crest-derived catecholaminergic cells associated with zebrafish pharyngeal arch blood vessels, and propose a new model for amniote hypoxia-sensitive cell evolution: endoderm-derived NECs were retained as PNECs, while the carotid body evolved via the aggregation of neural crest-derived catecholaminergic (chromaffin) cells already associated with blood vessels in anamniote pharyngeal arches. DOI: http://dx.doi.org/10.7554/eLife.21231.001 PMID:28387645

  11. Necrotizing Enterocolitis and Growth in Preterm Infants Fed Predominantly Maternal Milk, Pasteurized Donor Milk, or Preterm Formula: A Retrospective Study.

    PubMed

    Sisk, Paula M; Lambeth, Tinisha M; Rojas, Mario A; Lightbourne, Teisha; Barahona, Maria; Anthony, Evelyn; Auringer, Sam T

    2017-06-01

    Objective  To evaluate the association between necrotizing enterocolitis (NEC), growth, and feeding. Methods  This is a retrospective study of 551 infants (birth weight ≤ 1,500 g, ≤32 weeks' gestation). NEC, Bell's stage ≥ 2, was confirmed by independent review of sentinel radiographs. Feeding type was defined as ≥ 50% maternal milk (MM), pasteurized donor human milk (PDHM), or preterm formula (PF). Demographic and clinical characteristics including growth were compared between the three groups. Multivariable regression analysis was performed to control variables that differed in bivariate analysis. Results  PDHM and PF mothers were more likely to be African-American, be enrolled in Medicaid, and have chorioamnionitis. PF mothers received antenatal steroids less frequently. NEC rates were different by feeding group (MM: 5.3%; PHDM: 4.3%; PF: 11.4%; p  = 0.04). Adjusting for group differences, lower gestational age (adjusted odds ratio [aOR]: 0.85; 95% confidence interval [CI]: 0.74-0.97; p  = 0.02], and PF (aOR: 2.53; 95% CI: 1.15-5.53; p  = 0.02] were associated with NEC. There were no differences in other health outcomes or growth at hospital discharge. Conclusion  MM and PDHM feedings, given until 34 weeks postmenstrual age, were associated with lower rates of NEC in very low birth weight infants without interfering with growth. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  12. Low-Cost Ultrasonic Distance Sensor Arrays with Networked Error Correction

    PubMed Central

    Dai, Hongjun; Zhao, Shulin; Jia, Zhiping; Chen, Tianzhou

    2013-01-01

    Distance has been one of the basic factors in manufacturing and control fields, and ultrasonic distance sensors have been widely used as a low-cost measuring tool. However, the propagation of ultrasonic waves is greatly affected by environmental factors such as temperature, humidity and atmospheric pressure. In order to solve the problem of inaccurate measurement, which is significant within industry, this paper presents a novel ultrasonic distance sensor model using networked error correction (NEC) trained on experimental data. This is more accurate than other existing approaches because it uses information from indirect association with neighboring sensors, which has not been considered before. The NEC technique, focusing on optimization of the relationship of the topological structure of sensor arrays, is implemented for the compensation of erroneous measurements caused by the environment. We apply the maximum likelihood method to determine the optimal fusion data set and use a neighbor discovery algorithm to identify neighbor nodes at the top speed. Furthermore, we adopt the NEC optimization algorithm, which takes full advantage of the correlation coefficients for neighbor sensors. The experimental results demonstrate that the ranging errors of the NEC system are within 2.20%; furthermore, the mean absolute percentage error is reduced to 0.01% after three iterations of this method, which means that the proposed method performs extremely well. The optimized method of distance measurement we propose, with the capability of NEC, would bring a significant advantage for intelligent industrial automation. PMID:24013491

  13. Hospitalized Premature Infants Are Colonized by Related Bacterial Strains with Distinct Proteomic Profiles

    PubMed Central

    Xiong, Weili; Olm, Matthew R.; Thomas, Brian C.; Baker, Robyn; Firek, Brian; Morowitz, Michael J.; Hettich, Robert L.

    2018-01-01

    ABSTRACT During the first weeks of life, microbial colonization of the gut impacts human immune system maturation and other developmental processes. In premature infants, aberrant colonization has been implicated in the onset of necrotizing enterocolitis (NEC), a life-threatening intestinal disease. To study the premature infant gut colonization process, genome-resolved metagenomics was conducted on 343 fecal samples collected during the first 3 months of life from 35 premature infants housed in a neonatal intensive care unit, 14 of whom developed NEC, and metaproteomic measurements were made on 87 samples. Microbial community composition and proteomic profiles remained relatively stable on the time scale of a week, but the proteome was more variable. Although genetically similar organisms colonized many infants, most infants were colonized by distinct strains with metabolic profiles that could be distinguished using metaproteomics. Microbiome composition correlated with infant, antibiotics administration, and NEC diagnosis. Communities were found to cluster into seven primary types, and community type switched within infants, sometimes multiple times. Interestingly, some communities sampled from the same infant at subsequent time points clustered with those of other infants. In some cases, switches preceded onset of NEC; however, no species or community type could account for NEC across the majority of infants. In addition to a correlation of protein abundances with organism replication rates, we found that organism proteomes correlated with overall community composition. Thus, this genome-resolved proteomics study demonstrated that the contributions of individual organisms to microbiome development depend on microbial community context. PMID:29636439

  14. [Spatial-temporal variations of spring maize potential yields in a changing climate in Northeast China.

    PubMed

    Liu, Zhi Juan; Yang, Xiao Guang; Lyu, Shuo; Wang, Jing; Lin, Xiao Mao

    2018-01-01

    Based on meteorological data, agro-meteorological observations, and agricultural statistical data in Northeast China (NEC), by using the validated Agricultural Production System sIMulator (APSIM-maize), the potential, attainable, potential farmers' and actual farmers' yields of spring maize during the period 1961 to 2015 were analyzed, and the effects of climate variation on maize potential yield in NEC were quantified. Results indicated that the potential yield of spring maize was 12.2 t·hm -2 during the period 1961 to 2015, with those in northeast being lower than southwest within the study region. The attainable yield of spring maize was 11.3 t·hm -2 , and showed a similar spatial distribution with potential yield. Under the current farmers' management practices, mean simulated potential and actual farmers' yields were 6.5 and 4.5 t·hm -2 , respectively. Assuming there were no changes in cultivars and management practices in NEC, the mean potential, attainable, and potential farmers' yields of spring maize would decrease by 0.34, 0.25 and 0.10 t·hm -2 per decade in NEC. However, the actual farmers' yields increased with the value of 1.27 t·hm -2 per decade averaged over NEC. Due to climate variation, year-to-year variations of spring maize potential, attainable, and potential farmers' yields were significant, ranging from 10.0 to 14.4, 9.8 to 13.3, 4.4 to 8.5 t·hm -2 , respectively.

  15. An exclusively human milk diet reduces necrotizing enterocolitis.

    PubMed

    Herrmann, Kenneth; Carroll, Katherine

    2014-05-01

    This study tested the hypothesis that feeding an exclusively human milk (EHM) diet to premature infants reduces the incidence of necrotizing enterocolitis (NEC) associated with enteral feeding. An observational study for infants born at less than 33 weeks of gestational age was performed in a single neonatal intensive care unit. An EHM diet prospectively eliminated bovine-based artificial milk, including bovine-based fortifier, through 33 weeks postmenstrual age (PMA). The clinical data from a 2.5-year interval of the EHM diet were compared with data from the previous 6.5 years for similar infants who received bovine-based milk products before 33 weeks PMA. In the EHM diet cohort, 148 of 162 infants (91%) received EHM through 33 weeks PMA. In order to achieve an EHM diet, 140 of 162 infants (86%) received their own mother's milk, and 98 of 162 infants (60%) received donor human milk. The EHM cohort was also fed a human milk-based fortifier to truly eliminate bovine products. The distribution of NEC onset in the EHM cohort was significantly different from that in the control cohort for the day of onset (p=0.042) and the PMA at onset (p=0.011). In the control cohort, NEC onset after Day 7 of life occurred in 15 of 443 infants (3.4%), significantly more than in the EHM cohort where NEC occurred in two of 199 infants (1%) (p=0.009). Changing to an EHM milk diet through 33 weeks PMA reduced the incidence of NEC associated with enteral feeding.

  16. Toxicities, safeties and clinical response of dacarbazine-based chemotherapy on neuroendocrine tumors in Taiwan population.

    PubMed

    Chiu, Hwa-Yen; Lin, Liang-Yu; Chou, Wen-Chi; Fang, Wen-Liang; Shyr, Yi-Ming; Yeh, Yi-Chen; Mu-Hsin Chang, Peter; Chen, Ming-Han; Hung, Yi-Ping; Chao, Yee; Chien, Sheng-Hsuan; Chen, Ming-Huang

    2018-05-01

    Currently, the role of dacarbazine (DTIC) based chemotherapy in neuroendocrine tumors (NETs) in Asia is unclear. Here, we report the outcomes of dacarbazine (DTIC)-based chemotherapy in Taiwan population. DTIC alone (250 mg/m 2 /day), or 5-fluorouracil (5-FU, 500 mg/m 2 /day) and DTIC (200 mg/m 2 /day) with or without epirubicin (200 mg/m 2 /day), for 3 days, every 3-4 weeks. Subgroups were analyzed by grading, and by Ki-67 index. 48 patients were reviewed in this study, including 3 had grade 1 tumors, 23 had grade 2, while 22 were grade 3. In grade 3 NEC patients, the tumor Ki-67 index of 21-55% were noted in 8 patients, and >55% in 14 patients. Progression-free survival (PFS) was 5.1 months, and overall survival (OS) was 31.6 months. The PFS (in months) were 12.5 and 1.8 for patients with NETs and neuroendocrine carcinomas (NECs), respectively (p < 0.001). The OS were not reached and 5.9 months for patients with NETs and NECs, respectively (p = 0.001). Patients with NECs were divided into two groups, according to their Ki-67 index. In patients with a tumor Ki-67 index of 21-55%, PFS was 4.1 months, and OS was not reached; in those with a tumor Ki-67 index of >55%, they were 1.5 and 1.8 months, respectively (p < 0.001 and p = 0.013). NETs, and grade 3 NECs, with Ki-67 indices of 20-55% had good responses to DTIC-based chemotherapy, with acceptable side effects. Ki-67 index could predict prognosis for grade 3 NEC patients, and guide further chemotherapy choices. Copyright © 2017 the Chinese Medical Association. Published by Elsevier Taiwan LLC. All rights reserved.

  17. Multicenter retrospective analysis of systemic chemotherapy for advanced neuroendocrine carcinoma of the digestive system.

    PubMed

    Yamaguchi, Tomohiro; Machida, Nozomu; Morizane, Chigusa; Kasuga, Akiyoshi; Takahashi, Hideaki; Sudo, Kentaro; Nishina, Tomohiro; Tobimatsu, Kazutoshi; Ishido, Kenji; Furuse, Junji; Boku, Narikazu; Okusaka, Takuji

    2014-09-01

    This study analyzed outcomes of systemic chemotherapy for advanced neuroendocrine carcinoma (NEC) of the digestive system. Clinical data from 258 patients with unresectable or recurrent NEC of the gastrointestinal tract (GI) or hepato-biliary-pancreatic system (HBP), who received chemotherapy, were collected from 23 Japanese institutions and analyzed retrospectively. Patients had primary sites in the esophagus (n = 85), stomach (n = 70), small bowel (n = 6), colorectum (n = 31), hepato-biliary system (n = 31) and pancreas (n = 31). Median overall survival (OS) was 13.4 months the esophagus, 13.3 months for the stomach, 29.7 months for the small bowel, 7.6 months for the colorectum, 7.9 months for the hepato-biliary system and 8.5 months for the pancreas. Irinotecan plus cisplatin (IP) and etoposide plus cisplatin (EP) were most commonly selected for GI-NEC and HBP-NEC. For patients treated with IP/EP (n = 160/46), the response rate was 50/28% and median OS was 13.0/7.3 months. Multivariate analysis among patients treated with IP or EP showed that the primary site (GI vs HBP; hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.35-0.97) and baseline serum lactate dehydrogenase levels (not elevated vs elevated; HR 0.65, 95% CI 0.46-0.94) were independent prognostic factors for OS, while the efficacy of IP was slightly better than for EP (HR 0.80, 95% CI 0.48-1.33; P = 0.389). IP and EP are the most common treatment regimens for NEC of the digestive system. HBP primary sites and elevated lactate dehydrogenase levels are unfavorable prognostic factors for survival. A randomized controlled trial is required to establish the appropriate chemotherapy regimen for advanced NEC of the digestive system. This study was registered at UMIN as trial number 000005176. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  18. Considering Bone Marrow Blasts From Nonerythroid Cellularity Improves the Prognostic Evaluation of Myelodysplastic Syndromes.

    PubMed

    Arenillas, Leonor; Calvo, Xavier; Luño, Elisa; Senent, Leonor; Alonso, Esther; Ramos, Fernando; Ardanaz, María Teresa; Pedro, Carme; Tormo, Mar; Marco, Víctor; Montoro, Julia; Díez-Campelo, María; Brunet, Salut; Arrizabalaga, Beatriz; Xicoy, Blanca; Andreu, Rafael; Bonanad, Santiago; Jerez, Andrés; Nomdedeu, Benet; Ferrer, Ana; Sanz, Guillermo F; Florensa, Lourdes

    2016-09-20

    WHO classification of myeloid malignancies is based mainly on the percentage of bone marrow (BM) blasts. This is considered from total nucleated cells (TNCs), unless there is erythroid-hyperplasia (erythroblasts ≥ 50%), calculated from nonerythroid cells (NECs). In these instances, when BM blasts are ≥ 20%, the disorder is classified as erythroleukemia, and when BM blasts are < 20%, as myelodysplastic syndrome (MDS). In the latter, the percentage of blasts is considered from TNCs. We assessed the percentage of BM blasts from TNCs and NECs in 3,692 patients with MDS from the Grupo Español de Síndromes Mielodisplásicos, 465 patients with erythroid hyperplasia (MDS-E) and 3,227 patients without erythroid hyperplasia. We evaluated the relevance of both quantifications on classification and prognostication. By enumerating blasts systematically from NECs, 22% of patients with MDS-E and 12% with MDS from the whole series diagnosed within WHO categories with < 5% BM blasts, were reclassified into higher-risk categories and showed a poorer overall survival than did those who remained in initial categories (P = .006 and P = .001, respectively). Following WHO recommendations, refractory anemia with excess blasts (RAEB)-2 diagnosis is not possible in MDS-E, as patients with 10% to < 20% BM blasts from TNCs fulfill erythroleukemia criteria; however, by considering blasts from NECs, 72 patients were recoded as RAEB-2 and showed an inferior overall survival than did patients with RAEB-1 without erythroid hyperplasia. Recalculating the International Prognostic Scoring System by enumerating blasts from NECs in MDS-E and in the overall MDS population reclassified approximately 9% of lower-risk patients into higher-risk categories, which indicated the survival expected for higher-risk patients. Regardless of the presence of erythroid hyperplasia, calculating the percentage of BM blasts from NECs improves prognostic assessment of MDS. This fact should be considered in future WHO classification reviews. © 2016 by American Society of Clinical Oncology.

  19. Delayed initiation but not gradual advancement of enteral formula feeding reduces the incidence of necrotizing enterocolitis (NEC) in preterm pigs

    USDA-ARS?s Scientific Manuscript database

    Enteral formula feeding is a risk factor for necrotizing enterocolitis (NEC) in premature infants, yet studies are conflicting regarding the safest timing for introduction and advancement of feeds. Our aim was to test the effects of early vs. late initiation and abrupt vs. gradual advancement of ent...

  20. Near-infrared spectroscopy measurement of abdominal tissue oxygenation is a useful indicator of intestinal blood flow and necrotizing enterocolitis in premature piglets

    USDA-ARS?s Scientific Manuscript database

    A major objective of necrotizing enterocolitis (NEC)research is to devise a noninvasive method of early detection. We hypothesized that abdominal near-infrared spectroscopy (A-NIRS) readings will identify impending NEC in a large animal model. Piglets were prematurely delivered and received parenter...

  1. [FACTORS RELATED TO MORTALITY IN NECROTIZINGENTEROCOLITIS(NEC) IN NEONATES AND OLDER INFANTS

    PubMed

    Ríos D , Hugo; Rivera M , Juan

    1997-01-01

    In order to determine the factors related to mortality in Necrotizing enterocolitis (NEC), medical records of neonates and older infants diagnosed of NEC in the Instituto de Salud del Niño between 1984 and 1993 were retrospectively reviewed. Only the cases with a reliable roentgenologic, surgical or pathologic diagnosis were included. Sixty cases (46 infants and 14 neonates) were found, with a higher incidence in males (37 males vs 23 females). Twenty six cases required surgical treatment. Overall mortality was 77%, with no significant differences between neonates and infants, nor between those who were operated or not. Moderate or severe malnutrition, diarrhea as an early clinical manifestations, bronchopneumonia, shock and poor nutricional management were found as factors related to mortality.

  2. In vitro glucose measurement using tunable mid-infrared laser spectroscopy combined with fiber-optic sensor

    PubMed Central

    Yu, Songlin; Li, Dachao; Chong, Hao; Sun, Changyue; Yu, Haixia; Xu, Kexin

    2013-01-01

    Because mid-infrared (mid-IR) spectroscopy is not a promising method to noninvasively measure glucose in vivo, a method for minimally invasive high-precision glucose determination in vivo by mid-IR laser spectroscopy combined with a tunable laser source and small fiber-optic attenuated total reflection (ATR) sensor is introduced. The potential of this method was evaluated in vitro. This research presents a mid-infrared tunable laser with a broad emission spectrum band of 9.19 to 9.77μm(1024~1088 cm−1) and proposes a method to control and stabilize the laser emission wavelength and power. Moreover, several fiber-optic ATR sensors were fabricated and investigated to determine glucose in combination with the tunable laser source, and the effective sensing optical length of these sensors was determined for the first time. In addition, the sensitivity of this system was four times that of a Fourier transform infrared (FT-IR) spectrometer. The noise-equivalent concentration (NEC) of this laser measurement system was as low as 3.8 mg/dL, which is among the most precise glucose measurements using mid-infrared spectroscopy. Furthermore, a partial least-squares regression and Clarke error grid were used to quantify the predictability and evaluate the prediction accuracy of glucose concentration in the range of 5 to 500 mg/dL (physiologically relevant range: 30~400 mg/dL). The experimental results were clinically acceptable. The high sensitivity, tunable laser source, low NEC and small fiber-optic ATR sensor demonstrate an encouraging step in the work towards precisely monitoring glucose levels in vivo. PMID:24466493

  3. Severe hemolysis after plasma transfusion in a neonate with necrotizing enterocolitis, Clostridium perfringens infection, and red blood cell T-polyagglutination.

    PubMed

    Moh-Klaren, Julia; Bodivit, Gwellaouen; Jugie, Myriam; Chadebech, Philippe; Chevret, Laurent; Mokhtari, Mostafa; Chamillard, Xavier; Gallon, Philippe; Tissières, Pierre; Bierling, Philippe; Djoudi, Rachid; Pirenne, France; Burin-des-Roziers, Nicolas

    2017-11-01

    Red blood cell (RBC) Thomsen-Friedenreich antigen exposure (T activation) in infants with necrotizing enterocolitis (NEC) has occasionally been associated with posttransfusional intravascular hemolysis thought to be due to anti-T antibodies in the donor plasma. We describe an infant with NEC and Clostridium perfringens infection complicated by severe hemolysis after plasma transfusion. After this case, infants with confirmed NEC were prospectively evaluated for T activation. We checked for hemolysis in patients with T activation receiving plasma-containing blood products. The infant had received 80 mL of fresh-frozen plasma (FFP). His RBCs displayed strong T activation, and agglutination was observed with four of six ABO-compatible FFP units. A direct antiglobulin test was negative. IgM-class anti-T antibodies were present in small amounts (titer of 8) in the transfused FFP. Anti-T antibodies from the blood donor were not hemolytic in vitro. In the prospective study, T activation was observed in three of 28 infants with NEC (11%). One infant presented moderate T activation and two infants presented very strong T activation but only moderate decreases in sialic acid expression on the RBC membrane. These three infants presented no signs of hemolysis after transfusion with unwashed blood products or FFP. Anti-T antibodies are unlikely to be the etiologic factor for the hemolytic reactions observed in infants with NEC and T activation. Massive RBC desialylation and the direct action of bacterial toxins are more probable causes. Strict avoidance of plasma-containing blood products does not seem justified in these infants. © 2017 AABB.

  4. 25 CFR 12.36 - Does other law enforcement training count?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Does other law enforcement training count? 12.36 Section 12.36 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAW AND ORDER INDIAN COUNTRY LAW ENFORCEMENT Qualifications and Training Requirements § 12.36 Does other law enforcement training count? All requests for evaluation of equivalent...

  5. Projected Defense Purchases: Detail by Industry and State Calendar Years 2000 Through 2005

    DTIC Science & Technology

    2000-07-01

    2087 14 Other Food Products 44 Vegetable Oil Mills 2074, 2075, 2076 45 Animal and Marine Fats and Oils 2077 46 Shortening, Table Oils, and Edible Fats...Stampings 3465 155 Crowns and Closures 3466 156 Metal Stampings, n.e.c. 3469 157 Cutlery and Hand Tools 3421 3423 3425 158 Hardware, n.e.c. 3429 159 Metal

  6. NEC violation in mimetic cosmology revisited

    DOE PAGES

    Ijjas, Anna; Ripley, Justin; Steinhardt, Paul J.

    2016-06-28

    In the context of Einstein gravity, if the null energy condition (NEC) is satisfied, the energy density in expanding space–times always decreases while in contracting space–times the energy density grows and the universe eventually collapses into a singularity. In particular, no non-singular bounce is possible. It is, though, an open question if this energy condition can be violated in a controlled way, i.e., without introducing pathologies, such as unstable negative-energy states or an imaginary speed of sound. In this letter, we will re-examine the claim that the recently proposed mimetic scenario can violate the NEC without pathologies. We show thatmore » mimetic cosmology is prone to gradient instabilities even in cases when the NEC is satisfied (except for trivial examples). Most interestingly, the source of the instability is always the Einstein–Hilbert term in the action. The matter stress-energy component does not contribute spatial gradient terms but instead makes the problematic curvature modes dynamical. Finally, we also show that mimetic cosmology can be understood as a singular limit of known, well-behaved theories involving higher-derivative kinetic terms and discuss ways of removing the instability.« less

  7. NEC violation in mimetic cosmology revisited

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

    Ijjas, Anna; Ripley, Justin; Steinhardt, Paul J.

    In the context of Einstein gravity, if the null energy condition (NEC) is satisfied, the energy density in expanding space–times always decreases while in contracting space–times the energy density grows and the universe eventually collapses into a singularity. In particular, no non-singular bounce is possible. It is, though, an open question if this energy condition can be violated in a controlled way, i.e., without introducing pathologies, such as unstable negative-energy states or an imaginary speed of sound. In this letter, we will re-examine the claim that the recently proposed mimetic scenario can violate the NEC without pathologies. We show thatmore » mimetic cosmology is prone to gradient instabilities even in cases when the NEC is satisfied (except for trivial examples). Most interestingly, the source of the instability is always the Einstein–Hilbert term in the action. The matter stress-energy component does not contribute spatial gradient terms but instead makes the problematic curvature modes dynamical. Finally, we also show that mimetic cosmology can be understood as a singular limit of known, well-behaved theories involving higher-derivative kinetic terms and discuss ways of removing the instability.« less

  8. An immunohistochemical study of the gut neuroendocrine system in juvenile pejerrey Odontesthes bonariensis (Valenciennes).

    PubMed

    Vigliano, F A; Muñoz, L; Hernández, D; Cerutti, P; Bermúdez, R; Quiroga, M I

    2011-03-01

    In this study, several neuropeptides were identified by immunohistochemistry in neuroendocrine cells (NEC) located in the gut epithelium and nerve cell bodies of the enteric nervous system of pejerrey Odontesthes bonariensis, a species that is a promising candidate for intensive aquaculture. The neuropeptides involved in orexigenic or anorexigenic action, i.e. gastrin, cholecystokinin-8, neuropeptide Y and calcitonin gene-related peptide (CGRP), displayed a significantly higher number of immunoreactive NECs in the anterior intestine, suggesting that this region of the gut plays an important role in the peripheral control of food intake. On the other hand, leu-enkephalin and vasoactive intestinal peptide (VIP), both associated with the modulation of the enteric immune system, showed no significant variations in the mean value of immunopositive NECs between the anterior and posterior intestine. This may indicate that their activity is required at a similar level along the entire gut. In addition, CGRP and VIP-immunoreactive neurons and nerve fibres were observed in the myenteric plexus, which might exert synergistic effects with the neuropeptides immunolocalized in NECs. © 2011 The Authors. Journal of Fish Biology © 2011 The Fisheries Society of the British Isles.

  9. Detection of CFTR function and modulation in primary human nasal cell spheroids.

    PubMed

    Brewington, John J; Filbrandt, Erin T; LaRosa, F J; Ostmann, Alicia J; Strecker, Lauren M; Szczesniak, Rhonda D; Clancy, John P

    2018-01-01

    Expansion of CFTR modulators to patients with rare/undescribed mutations will be facilitated by patient-derived models quantifying CFTR function and restoration. We aimed to generate a personalized model system of CFTR function and modulation using non-surgically obtained nasal epithelial cells (NECs). NECs obtained by curettage from healthy volunteers and CF patients were expanded and grown in 3-dimensional culture as spheroids, characterized, and stimulated with cAMP-inducing agents to activate CFTR. Spheroid swelling was quantified as a proxy for CFTR function. NEC spheroids recapitulated characteristics of pseudostratified respiratory epithelia. When stimulated with forskolin/IBMX, spheroids swelled in the presence of functional CFTR, and shrank in its absence. Spheroid swelling quantified mutant CFTR restoration in F508del homozygous cells using clinically available CFTR modulators. NEC spheroids hold promise for understanding rare CFTR mutations and personalized modulator testing to drive evaluation for CF patients with common, rare or undescribed mutations. Portions of this data have previously been presented in abstract form at the 2016 meetings of the American Thoracic Society and the 2016 North American Cystic Fibrosis Conference. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  10. An improved pi/4-QPSK with nonredundant error correction for satellite mobile broadcasting

    NASA Technical Reports Server (NTRS)

    Feher, Kamilo; Yang, Jiashi

    1991-01-01

    An improved pi/4-quadrature phase-shift keying (QPSK) receiver that incorporates a simple nonredundant error correction (NEC) structure is proposed for satellite and land-mobile digital broadcasting. The bit-error-rate (BER) performance of the pi/4-QPSK with NEC is analyzed and evaluated in a fast Rician fading and additive white Gaussian noise (AWGN) environment using computer simulation. It is demonstrated that with simple electronics the performance of a noncoherently detected pi/4-QPSK signal in both AWGN and fast Rician fading can be improved. When the K-factor (a ratio of average power of multipath signal to direct path power) of the Rician channel decreases, the improvement increases. An improvement of 1.2 dB could be obtained at a BER of 0.0001 in the AWGN channel. This performance gain is achieved without requiring any signal redundancy and additional bandwidth. Three types of noncoherent detection schemes of pi/4-QPSK with NEC structure, such as IF band differential detection, baseband differential detection, and FM discriminator, are discussed. It is concluded that the pi/4-QPSK with NEC is an attractive scheme for power-limited satellite land-mobile broadcasting systems.

  11. Nanoclay/Polymer Composite Powders for Use in Laser Sintering Applications: Effects of Nanoclay Plasma Treatment

    NASA Astrophysics Data System (ADS)

    Almansoori, Alaa; Majewski, Candice; Rodenburg, Cornelia

    2017-11-01

    Plasma-etched nanoclay-reinforced Polyamide 12 (PA12) powder is prepared with its intended use in selective laser sintering (LS) applications. To replicate the LS process we present a downward heat sintering (DHS) process, carried out in a hot press, to fabricate tensile test specimens from the composite powders. The DHS parameters are optimized through hot stage microscopy, which reveal that the etched clay (EC)-based PA12 (EC/PA12) nanocomposite powder melts at a temperature 2°C higher than that of neat PA12, and 1-3°C lower than that of the nonetched clay-based nanocompsite (NEC/PA12 composite). We show that these temperature differences are critical to successful LS. The distribution of EC and NEC onto PA12 is investigated by scanning electron microscopy (SEM). SEM images show clearly that the plasma treatment prevents the micron-scale aggregation of the nanoclay, resulting in an improved elastic modulus of EC/PA12 when compared with neat PA12 and NEC/PA12. Moreover, the reduction in elongation at break for EC/PA12 is less pronounced than for NEC/PA12.

  12. Fully stable cosmological solutions with a non-singular classical bounce

    DOE PAGES

    Ijjas, Anna; Steinhardt, Paul J.

    2016-11-28

    Recently, we showed how it is possible to use a cubic Galileon action to construct classical cosmological solutions that enter a contracting null energy condition (NEC) violating phase, bounce at finite values of the scale factor and exit into an expanding NEC-satisfying phase without encountering any singularities or pathologies. One drawback of these examples is that singular behavior is encountered at some time either just before or just after the NEC-violating phase. In this Letter, we show that it is possible to circumvent this problem by extending our method to actions that include the next order L 4 Galileon interaction.more » In using this approach, we construct non-singular classical bouncing cosmological solutions that are non-pathological for all times.« less

  13. Heavy truck data in Virginia : collection, uses, and needs.

    DOT National Transportation Integrated Search

    1988-01-01

    This report describes the collection and uses of heavy truck data by Virginia agencies. Data categories include: (I) classification counts, (2) accidents; (3) off-tracking; (4) passenger car equivalents (PCE), (5) equivalent axle load (EAL), (6) spee...

  14. Imaging the secretory compartments involved in the intracellular traffic of CHS-4, a class IV chitin synthase, in Neurospora crassa.

    PubMed

    Rico-Ramírez, Adriana M; Roberson, Robert W; Riquelme, Meritxell

    2018-03-27

    In Neurospora crassa hyphae the localization of all seven chitin synthases (CHSs) at the Spitzenkörper (Spk) and at developing septa has been well analyzed. Hitherto, the mechanisms of CHSs traffic and sorting from synthesis to delivery sites remain largely unexplored. In Saccharomyces cerevisiae exit of Chs3p from the endoplasmic reticulum (ER) requires chaperone Chs7p. Here, we analyzed the role of CSE-7, N. crassa Chs7p orthologue in the biogenesis of CHS-4 (orthologue of Chs3p). In a N. crassa Δcse-7 mutant, CHS-4-GFP no longer accumulated at the Spk and septa. Instead, fluorescence was retained in hyphal subapical regions in an extensive network of elongated cisternae (NEC) referred to previously as tubular vacuoles. In a complemented strain expressing a copy of cse-7 the localization of CHS-4-GFP at the Spk and septa was restored, providing evidence that CSE-7 is necessary for the localization of CHS-4 at hyphal tips and septa. CSE-7 was revealed at delimited regions of the ER at the immediacies of nuclei, at the NEC, and remarkably also at septa and the Spk. The organization of the NEC was dependent on the cytoskeleton. SEC-63, an extensively used ER marker, and NCA-1, a SERCA-type ATPase previously localized at the nuclear envelope, were used as markers to discern the nature of the membranes containing CSE-7. Both SEC-63 and NCA-1 were found at the nuclear envelope, but also at regions of the NEC. However, at the NEC only NCA-1 co-localized extensively with CSE-7. Observations by transmission electron microscopy revealed abundant rough ER sheets and distinct electron translucent smooth flattened cisternae, which could correspond collectively to the NEC, thorough the subapical cytoplasm. This study identifies CSE-7 as the putative ER receptor for its cognate cargo, the polytopic membrane protein CHS-4, and elucidates the complexity of the ER system in filamentous fungi. Copyright © 2018. Published by Elsevier Inc.

  15. Variability in Antibiotic Regimens for Surgical Necrotizing Enterocolitis Highlights the Need for New Guidelines.

    PubMed

    Blackwood, Brian P; Hunter, Catherine J; Grabowski, Julia

    Necrotizing enterocolitis or NEC is the most common gastrointestinal emergency in the newborn. The etiology of NEC remains unknown, and treatment consists of antibiotic therapy and supportive care with the addition of surgical intervention as necessary. Unlike most surgical diseases, clear guidelines for the type and duration of peri-operative antibiotic therapy have not been established. Our aim was to review the antibiotic regimen(s) applied to surgical patients with NEC within a single neonatal intensive care unit (NICU) and to evaluate outcomes and help develop guidelines for antibiotic administration in this patient population. A single-center retrospective review was performed of all patients who underwent surgical intervention for NEC from August 1, 2005 through August 1, 2015. Relevant data were extracted including gestational age, age at diagnosis, gender, pre-operative antibiotic treatment, post-operative antibiotic treatment, development of stricture, and mortality. Patients were excluded if there was incomplete data documentation. A total of 90 patients were identified who met inclusion criteria. There were 56 male patients and 34 female patients. The average gestational age was 30 5/7 wks and average age of diagnosis 16.7 d. A total of 22 different pre-operative antibiotic regimens were identified with an average duration of 10.6 d. The most common pre-operative regimen was ampicillin, gentamicin, and metronidazole for 14 d. A total of 15 different post-operative antibiotic regimens were identified with an average duration of 6.6 d. The most common post-operative regimen was ampicillin, gentamicin, and metronidazole for two days. There were 26 strictures and 15 deaths. No regimen or duration proved superior. We found that there is a high degree of variability in the antibiotic regimen for the treatment of NEC, even within a single NICU, with no regimen appearing superior over another. As data emerge that demonstrate the adverse effects of antibiotic overuse, our findings highlight the need for guidelines in the antibiotic treatment of NEC and suggest that an abbreviated course of post-operative antibiotics may be safe.

  16. Role of amino acid supplementation in the prevention of necrotizing enterocolitis in preterm neonates - a review of current evidences.

    PubMed

    Garg, Bhawan Deep; Kabra, Nandkishor S

    2018-09-01

    Necrotizing enterocolitis (NEC) is one of the most common acute and fatal gastrointestinal emergency in very low birth weight (VLBW) preterm neonates with mortality range from 15 to 30%. NEC is likely due to multifactorial process such as oxidative injury, ischemic necrosis, and over-reactive inflammatory response to intestinal microbes. To evaluate the role of amino acid supplementation for reduction of neonatal NEC in preterm neonates. The literature search was done for various randomized control trial (RCT) by searching the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Web of Science, Scopus, Index Copernicus, African Index Medicus (AIM), Thomson Reuters (ESCI), Chemical Abstracts Service (CAS) and other database. This review included 15 RCTs that fulfilled inclusion criteria. The total neonates enrolled in these different RCT are 3424 (amino acid group 1711 and control 1713). Almost all participating neonates were of VLBW or extremely low birth weight (ELBW). In two trials, birth weight was between 1500-2000 grams. The intervention was started within first few days after birth and continued up to 30th day of postnatal age in most of the trials. In two trials, intervention was continued up to 120th day of postnatal age. Arginine, glutamine and N-acetyl cysteine (NAC) were used at the dose of 1.5 mol/kg/day (261 mg/kg/day), 0.3 grams/kg/day and 16-32 mg/kg/day, respectively. Role of amino acid in the prevention of neonatal NEC is not exclusively supported by the current evidence. Only three studies were able to show reduction in the incidence of NEC with amino acid supplementation (arginine, glutamine), and the remaining studies did not report any positive effect. Amino acid supplementation was not associated with significant reduction in mortality due to any causes. However, arginine supplementation was associated with significant reduction in mortality due to NEC. Two studies on glutamine were reported significant reduction in the incidence of invasive infection. Only one study reported significant positive effects on growth parameters and less time to reach full enteral feeds. None of the studies showed any effect on the duration of hospital stay.

  17. The Impact of Maternal Antibiotics on Neonatal Disease.

    PubMed

    Reed, Benjamin D; Schibler, Kurt R; Deshmukh, Hitesh; Ambalavanan, Namasivayam; Morrow, Ardythe L

    2018-06-01

    We examined the impact of prenatal exposure to maternal antibiotics on risk of necrotizing enterocolitis (NEC), late onset sepsis (LOS), and death in infants born preterm. Secondary data analysis was conducted via an extant cohort of 580 infants born <32 weeks of gestation and enrolled in 3 level III neonatal intensive care units. Prenatal antibiotic exposure was defined as antibiotics received by the mother within 72 hours before delivery. Postnatal empiric antibiotic exposure was defined as antibiotic initiated within the first day of life without documented infection, categorized as low (<5 days) or high (>5 days) duration. Two-thirds of mothers received antibiotics within 72 hours before delivery, of whom 59.8% received >1 antibiotic. Ampicillin (37.6%) and azithromycin (26.4%) were the most common antibiotics given. NEC occurred in 7.5%, LOS in 11.1%, death in 9.6%, and the combined outcome of NEC, LOS, or death in 21.3% of study infants. In multiple logistic regression models adjusted for gestational age, postnatal empiric antibiotic exposure, and other factors, prenatal antibiotic exposure was associated with reduced risk of NEC (OR 0.28; 95% CI 0.14-0.56; P < .001), death (OR 0.29; 95% CI 0.14-0.60; P = .001), but not LOS (OR 1.59; 95% CI 0.84-2.99; P = .15), although protection was significant for the combined outcome (OR 0.52, P < .001). High postnatal empiric antibiotic exposure was associated with greater risk of death but not other outcomes in multiple regression models (OR 3.18, P = .002). Prenatal antibiotic exposure was associated with lower rates of NEC or death of infants born preterm, and its impact on infant outcomes warrants further study. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Hemodynamic and permeability characteristics of acute experimental necrotizing enterocolitis

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

    Miller, M.J.; Adams, J.; Gu, X.A.

    1990-10-01

    We examined the local hemodynamic response of intestinal loops during acute necrotizing enterocolitis (NEC) in anesthetized rabbits. NEC was induced in ileal loops by transmural injection of a solution containing casein (10 mg/ml) and calcium gluconate (50 mg/ml) acidified to pH 4.0 with propionic or acetic acid. Control loops received casein only (pH 5.0). Mucosal damage was quantified by the blood-to-lumen movement of (51Cr)EDTA, fluid shifts into the lumen, and histology. Mean arterial pressure and loop blood flow were steady over the 3-hr period, loop fluid volume decreased, and there was no evidence of necrosis or epithelial damage. In loopsmore » receiving acidified casein and calcium gluconate, there was an immediate dramatic increase in loop blood flow that returned to baseline by 50 min. In addition, loop fluid volume was dramatically increased, necrosis was noted in the form of blunting and loss of villi, and sevenfold increase in (51Cr)EDTA permeability was evident. Administration of CV 1808 (30 mg/kg/hr), a selective adenosine2 agonist, which maintained and elevated loop blood flow throughout the 3 hr protocol, failed to alter the changes in loop fluid volume or prevent necrosis. Histamine levels in loop fluid levels were significantly elevated 20-30 min after NEC induction when compared to saline controls, indicating an early activation of mucosal defenses with this luminal insult. Thus, this model of NEC is characterized by a transient, acute hyperemia, increased intestinal permeability, and histamine release. As mucosal damage was independent of ischemia and could not be prevented by vasodilatory therapy, this model supports the clinical findings that NEC is correlated with luminal factors related to feeding and independent of cardiovascular stress.« less

  19. Incidence of neonatal necrotising enterocolitis in high-income countries: a systematic review.

    PubMed

    Battersby, Cheryl; Santhalingam, Tharsika; Costeloe, Kate; Modi, Neena

    2018-03-01

    To conduct a systematic review of neonatal necrotising enterocolitis (NEC) rates in high-income countries published in peer-reviewed journals. We searched MEDLINE, Embase and PubMed databases for observational studies published in peer-reviewed journals. We selected studies reporting national, regional or multicentre rates of NEC in 34 Organisation for Economic Co-operation and Development countries. Two investigators independently screened studies against predetermined criteria. For included studies, we extracted country, year of publication in peer-reviewed journal, study time period, study population inclusion and exclusion criteria, case definition, gestation or birth weight-specific NEC and mortality rates. Of the 1888 references identified, 120 full manuscripts were reviewed, 33 studies met inclusion criteria, 14 studies with the most recent data from 12 countries were included in the final analysis. We identified an almost fourfold difference, from 2% to 7%, in the rate of NEC among babies born <32 weeks' gestation and an almost fivefold difference, from 5% to 22%, among those with a birth weight <1000 g but few studies covered the entire at-risk population. The most commonly applied definition was Bell's stage ≥2, which was used in seven studies. Other definitions included Bell's stage 1-3, definitions from the Centers for Disease Control and Prevention, International Classification for Diseases and combinations of clinical and radiological signs as specified by study authors. The reasons for international variation in NEC incidence are an important area for future research. Reliable inferences require clarity in defining population coverage and consistency in the case definition applied. PROSPERO INTERNATIONAL PROSPECTIVE REGISTER OF SYSTEMATIC REVIEWS REGISTRATION NUMBER: CRD42015030046. © 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.

  20. Land surface phenology of Northeast China during 2000-2015: temporal changes and relationships with climate changes.

    PubMed

    Zhang, Yue; Li, Lin; Wang, Hongbin; Zhang, Yao; Wang, Naijia; Chen, Junpeng

    2017-10-01

    As an important crop growing area, Northeast China (NEC) plays a vital role in China's food security, which has been severely affected by climate change in recent years. Vegetation phenology in this region is sensitive to climate change, and currently, the relationship between the phenology of NEC and climate change remains unclear. In this study, we used a satellite-derived normalized difference vegetation index (NDVI) to obtain the temporal patterns of the land surface phenology in NEC from 2000 to 2015 and validated the results using ground phenology observations. We then explored the relationships among land surface phenology, temperature, precipitation, and sunshine hours for relevant periods. Our results showed that the NEC experienced great phenological changes in terms of spatial heterogeneity during 2000-2015. The spatial patterns of land surface phenology mainly changed with altitude and land cover type. In most regions of NEC, the start date of land surface phenology had advanced by approximately 1.0 days year -1 , and the length of land surface phenology had been prolonged by approximately 1.0 days year -1 except for the needle-leaf and cropland areas, due to the warm conditions. We found that a distinct inter-annual variation in land surface phenology related to climate variables, even if some areas presented non-significant trends. Land surface phenology was coupled with climate variables and distinct responses at different combinations of temperature, precipitation, sunshine hours, altitude, and anthropogenic influence. These findings suggest that remote sensing and our phenology extracting methods hold great potential for helping to understand how land surface phenology is sensitive to global climate change.

  1. Serotonergic and cholinergic elements of the hypoxic ventilatory response in developing zebrafish.

    PubMed

    Shakarchi, Kamila; Zachar, Peter C; Jonz, Michael G

    2013-03-01

    The chemosensory roles of gill neuroepithelial cells (NECs) in mediating the hyperventilatory response to hypoxia are not clearly defined in fish. While serotonin (5-HT) is the predominant neurotransmitter in O(2)-sensitive gill NECs, acetylcholine (ACh) plays a more prominent role in O(2) sensing in terrestrial vertebrates. The present study characterized the developmental chronology of potential serotonergic and cholinergic chemosensory pathways of the gill in the model vertebrate, the zebrafish (Danio rerio). In immunolabelled whole gills from larvae, serotonergic NECs were observed in epithelia of the gill filaments and gill arches, while non-serotonergic NECs were found primarily in the gill arches. Acclimation of developing zebrafish to hypoxia (P(O2)=75 mmHg) reduced the number of serotonergic NECs observed at 7 days post-fertilization (d.p.f.), and this effect was absent at 10 d.p.f. In vivo administration of 5-HT mimicked hypoxia by increasing ventilation frequency (f(V)) in early stage (7-10 d.p.f.) and late stage larvae (14-21 d.p.f.), while ACh increased f(V) only in late stage larvae. In time course experiments, application of ketanserin inhibited the hyperventilatory response to acute hypoxia (P(O2)=25 mmHg) at 10 d.p.f., while hexamethonium did not have this effect until 12 d.p.f. Cells immunoreactive for the vesicular acetylcholine transporter (VAChT) began to appear in the gill filaments by 14 d.p.f. Characterization in adult gills revealed that VAChT-positive cells were a separate population of neurosecretory cells of the gill filaments. These studies suggest that serotonergic and cholinergic pathways in the zebrafish gill develop at different times and contribute to the hyperventilatory response to hypoxia.

  2. Variation of the North Equatorial Current, Mindanao Current, and Kuroshio Current in a high-resolution data assimilation during 2008-2012

    NASA Astrophysics Data System (ADS)

    Zhai, Fangguo; Wang, Qingye; Wang, Fujun; Hu, Dunxin

    2014-11-01

    Outputs from a high-resolution data assimilation system, the global Hybrid Coordinate Ocean Model and Navy Coupled Ocean Data Assimilation (HYCOM+NCODA) 1/12° analysis, were analyzed for the period September 2008 to February 2012. The objectives were to evaluate the performance of the system in simulating ocean circulation in the tropical northwestern Pacific and to examine the seasonal to interannual variations of the western boundary currents. The HYCOM assimilation compares well with altimetry observations and mooring current measurements. The mean structures and standard deviations of velocities of the North Equatorial Current (NEC), Mindanao Current (MC) and Kuroshio Current (KC) also compare well with previous observations. Seasonal to interannual variations of the NEC transport volume are closely correlated with the MC transport volume, instead of that of the KC. The NEC and MC transport volumes mainly show well-defined annual cycles, with their maxima in spring and minima in fall, and are closely related to the circulation changes in the Mindanao Dome (MD) region. In seasons of transport maxima, the MD region experiences negative SSH anomalies and a cyclonic gyre anomaly, and in seasons of transport minima the situation is reversed. The sea surface NEC bifurcation latitude (NBL) in the HYCOM assimilation also agrees well with altimetry observations. In 2009, the NBL shows an annual cycle similar to previous studies, reaching its southernmost position in summer and its northernmost position in winter. In 2010 and 2011, the NBL variations are dominantly influenced by La Niña events. The dynamics responsible for the seasonal to interannual variations of the NEC-MC-KC current system are also discussed.

  3. Use of ranitidine is associated with infections in newborns hospitalized in a neonatal intensive care unit: a cohort study.

    PubMed

    Santana, Ruth N S; Santos, Victor S; Ribeiro-Júnior, Ruy F; Freire, Marina S; Menezes, Maria A S; Cipolotti, Rosana; Gurgel, Ricardo Q

    2017-05-30

    The inhibition of gastric acid secretion with ranitidine is frequently prescribed off-label to newborns admitted to neonatal intensive care units (NICU). Some studies show that the use of inhibitors of gastric acid secretion (IGAS) may predispose to infections and necrotising enterocolitis (NEC), but there are few data to confirm this association. This study aimed to compare the rates of neonatal infections and NEC among preterm infants (<37 weeks gestation) hospitalised in a NICU exposed or not to treatment with ranitidine. A retrospective cohort study was conducted with all consecutive preterm newborns admitted to a NICU between August-2014 and October-2015. The rates of infection, NEC, and death of newborns exposed or not to ranitidine were recorded. A total of 300 newborns were enrolled, of which 115 had received ranitidine and 185 had not. The two groups were similar with regard to the main demographic and clinical characteristics. Forty-eight (41.7%) of the 115 infants exposed to ranitidine and 49 (26.5%) of the 185 infants not exposed were infected (RR = 1.6, 95%CI 1.1-2.2, p = 0.006). The late onset (>48 h) blood culture positive infection rate was higher in the group exposed to ranitidine than in the untreated group (13.0% vs. 3.8%, p = 0.001). There was no significant association between the use of ranitidine and NEC (Bell stage >II) (p = 0.36). The mortality rate risk was 4-fold higher in infants receiving ranitidine (16.5% vs. 8.6%, p < 0.001). Ranitidine use in neonates was associated with an increased risk of infections and mortality, but not with NEC.

  4. Enhanced influence of early-spring tropical Indian Ocean SST on the following early-summer precipitation over Northeast China

    NASA Astrophysics Data System (ADS)

    Han, Tingting; He, Shengping; Wang, Huijun; Hao, Xin

    2017-04-01

    The relationship between the tropical Indian Ocean (TIO) and East Asian summer monsoon/precipitation has been documented in many studies. However, the precursor signals of summer precipitation in the TIO sea surface temperature (SST), which is important for climate prediction, have drawn little attention. This study identified a strong relationship between early-spring TIO SST and subsequent early-summer precipitation in Northeast China (NEC) since the late 1980s. For 1961-1986, the correlations between early-spring TIO SST and early-summer NEC precipitation were statistically insignificant; for 1989-2014, they were positively significant. Since the late 1980s, the early-spring positive TIO SST anomaly was generally followed by a significant anomalous anticyclone over Japan; that facilitated anomalous southerly winds over NEC, conveying more moisture from the North Pacific. Further analysis indicated that an early TIO SST anomaly showed robust persistence into early summer. However, the early-summer TIO SST anomaly displayed a more significant influence on simultaneous atmospheric circulation and further affected NEC precipitation since the late 1980s. In 1989-2014, the early-summer Hadley and Ferrell cell anomalies associated with simultaneous TIO SST anomaly were much more significant and extended further north to mid-latitudes, which provided a dynamic foundation for the TIO-mid-latitude connection. Correspondingly, the TIO SST anomaly could lead to significant divergence anomalies over the Mediterranean. The advections of vorticity by the divergent component of the flow effectively acted as a Rossby wave source. Thus, an apparent Rossby wave originated from the Mediterranean and propagated east to East Asia; that further influenced the NEC precipitation through modulation to the atmospheric circulation (e.g., surface wind, moisture, vertical motion).

  5. Preventing necrotizing enterocolitis by food additives in neonates: A network meta-analysis revealing the efficacy and safety.

    PubMed

    Yu, Wentao; Sui, Wu; Mu, Linsong; Yi, Wenying; Li, Haijuan; Wei, Liqin; Yin, Weihong

    2017-05-01

    Necrotizing enterocolitis (NEC) is a serious multifactorial gastrointestinal disease which is often discovered in premature infants. Various additives have been used to prevent NEC; yet, their relative efficacy and safety remain disputed. This study aims to compare the efficacy and safety of 5 food additives, namely, probiotics, probiotics + fructo-oligosaccharides, pentoxifylline, arginine, and lactoferrin in preventing NEC in neonates. Embase, PubMed, and Cochrane Library had been searched for all eligible randomized control trials. Odds ratios (ORs) were estimated for dichotomous data and mean differences with 95% credible intervals (CrIs) were estimated for continuous data. Surface under the cumulative ranking curve was used to rank efficacy and safety of the prevention methods on each endpoint. A total of 27 eligible studies with 4649 preterm infants were included in this network meta-analysis (NMA), and the efficacy and safety of 5 food additives were evaluated. Probiotic and arginine exhibited better preventive efficacy compared with placebo (OR = 0.50, 95% CrIs: 0.32-0.73; OR = 0.30, 95% CrIs: 0.12-0.73, respectively). Only probiotic achieved a considerable decrease in the risk of mortality compared to placebo (OR = 0.68, 95% CrIs: 0.46-0.98). NEC patients with lactoferrin appeared to have lower incidence of sepsis than those of placebo (OR = 0.13, 95% CrIs: 0.03-0.61) or probiotic (OR = 0.18, 95% CrIs: 0.03-0.83). Based on this NMA, probiotics had the potential to be the most preferable additive, since it exhibited a significant superiority for NEC and mortality as well as a relatively balanced performance in safety.

  6. Pain threshold, tolerance and intensity in adolescents born very preterm or with low birth weight.

    PubMed

    van Ganzewinkel, Christ-Jan J L M; Been, Jasper V; Verbeek, Inge; van der Loo, Tera Boelen; van der Pal, Sylvia M; Kramer, Boris W; Andriessen, Peter

    2017-07-01

    Data on long-term consequences of neonatal pain is limited. To assess whether perinatal factors, later pain experience and pain coping strategies are associated with altered pain threshold, pain tolerance and pain intensity in adolescents born preterm. Observational, longitudinal study (Project on Preterm and SGA-infants, POPS-19). We analyzed data of 412 adolescents at the age of 19years, who were born at a gestational age<32weeks or with a birth weight<1500g. Participants performed a standardized cold pressor test to assess pain threshold, tolerance and intensity. Furthermore, they completed a pain coping questionnaire (PCQ). In univariate analysis, female gender and necrotizing enterocolitis (NEC) were associated with lower pain tolerance, indicated by reaching the ceiling time of 180s in ice water (females 19% vs males 29%, NEC 7% vs no NEC 25%). Female gender was associated with higher pain intensity (mean difference 0.58; 95%CI 0.21; 0.95) and lower pain threshold (log rank test p 0.007). In a multivariate Cox regression analyses, emotion focused avoidance pain coping style was significantly associated with lower pain threshold (hazard ratio HR 1.38; 95%CI 1.02; 1.87) and pain tolerance (HR 1.72; 95%CI 1.21; 2.42). NEC was significantly associated with lower pain threshold (HR 1.47; 95%CI 1.01; 2.14) and pain tolerance (HR 1.63; 95%CI 1.09; 2.41). In adolescence, maladaptive pain coping strategy was associated with lower pain threshold, pain tolerance and higher pain intensity. NEC was associated with altered pain response in adolescents born preterm. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. 45 CFR 261.31 - How many hours must a work-eligible individual participate for the family to count in the...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... three activities may also count as participation: job skills training directly related to employment... study leading to a certificate of general equivalence. (d)(1) We will deem a work-eligible individual...

  8. Acquisition of an Underway CTD System for the Flow Encountering Abrupt Topography DRI

    DTIC Science & Technology

    2015-09-30

    Acquisition of an Underway CTD System for the Flow Encountering Abrupt Topography DRI T. M. Shaun Johnston Scripps Institution of Oceanography...westward flow in the North Equatorial Current (NEC) encounters tall, steep, submarine topography and islands. During the Flow Encountering Abrupt... Topography (FLEAT) DRI, investigators will determine: • Whether appreciable energy/momentum is lost from the large-scale NEC flow to smaller scales and

  9. LO-CO-GRAF (Low Cost Graphics): Generating Maps to Support Command and Control/Crisis Management Using Small Computers.

    DTIC Science & Technology

    1988-03-01

    Kernel System (GKS). This combination of hardware and software allows real-time generation of maps using DMA digitized data.[Ref. 4: p. 44, 46] Though...releases are in MST*.BOO. MSV55X.BOO Sanyo MBC-550 with IBM compatible video board MSVAP3.BOO NEC APC3 MSVAPC.BOO NEC APC MSVAPR.BOO ACT Apricot MSVDM2

  10. The potential of gut microbiota and fecal volatile organic compounds analysis as early diagnostic biomarker for necrotizing enterocolitis and sepsis in preterm infants.

    PubMed

    Berkhout, Daniel Johannes Cornelis; Niemarkt, Hendrik Johannes; de Boer, Nanne Klaas Hendrik; Benninga, Marc Alexander; de Meij, Timotheüs Gualtherus Jacob

    2018-05-01

    Although the exact pathophysiological mechanisms of both necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) in preterm infants are yet to be elucidated, evidence is emerging that the gut microbiota plays a key role in their pathophysiology. Areas covered: In this review, initial microbial colonization and factors influencing microbiota composition are discussed. For both NEC and LOS, an overview of studies investigating preclinical alterations in gut microbiota composition and fecal volatile organic compounds (VOCs) is provided. Fecal VOCs are considered to reflect not only gut microbiota composition, but also their metabolic activity and concurrent interaction with the host. Expert review: Heterogeneity in study protocols and applied analytical techniques hampers reliable comparison between outcomes of different microbiota studies, limiting the ability to draw firm conclusions. This dilemma is illustrated by the finding that study results often cannot be reproduced, or even contradict each other. A NEC- and sepsis specific microbial or metabolic signature has not yet been discovered. Identification of 'disease-specific' VOCs and microbiota composition may increase understanding on pathophysiological mechanisms and may allow for development of an accurate screening tool, opening avenues towards timely identification and initiation of targeted treatment for preterm infants at increased risk for NEC and sepsis.

  11. Characterisation of putative oxygen chemoreceptors in bowfin (Amia calva).

    PubMed

    Porteus, Cosima S; Wright, Patricia A; Milsom, William K

    2014-04-15

    Serotonin containing neuroepithelial cells (NECs) are putative oxygen sensing cells found in different locations within the gills of fish. In this study we wished to determine the effect of sustained internal (blood) hypoxaemia versus external (aquatic) hypoxia on the size and density of NECs in the first gill arch of bowfin (Amia calva), a facultative air breather. We identified five different populations of serotonergic NECs in this species (Types I-V) based on location, presence of synaptic vesicles (SV) that stain for the antibody SV2, innervation and labelling with the neural crest marker HNK-1. Cell Types I-III were innervated, and these cells, which participate in central O2 chemoreflexes, were studied further. Although there was no change in the density of any cell type in bowfin after exposure to sustained hypoxia (6.0 kPa for 7 days) without access to air, all three of these cell types increased in size. In contrast, only Type II and III cells increased in size in bowfin exposed to sustained hypoxia with access to air. These data support the suggestion that NECs are putative oxygen-sensing cells, that they occur in several locations, and that Type I cells monitor only hypoxaemia, whereas both other cell types monitor hypoxia and hypoxaemia.

  12. Nucleosome eviction along with H3K9ac deposition enhances Sox2 binding during human neuroectodermal commitment

    PubMed Central

    Du, Yanhua; Liu, Zhenping; Cao, Xinkai; Chen, Xiaolong; Chen, Zhenyu; Zhang, Xiaobai; Zhang, Xiaoqing; Jiang, Cizhong

    2017-01-01

    Neuroectoderm is an important neural precursor. However, chromatin remodeling and its epigenetic regulatory roles during the differentiation of human neuroectodermal cells (hNECs) from human embryonic stem cells (hESCs) remain largely unexplored. Here, we obtained hNECs through directed differentiation from hESCs, and determined chromatin states in the two cell types. Upon differentiation, H2A.Z-mediated nucleosome depletion leads to an open chromatin structure in promoters and upregulates expression of neuroectodermal genes. Increase in H3K9ac signals and decrease in H3K27me3 signals in promoters result in an active chromatin state and activate neuroectodermal genes. Conversely, decrease in H3K9ac signals and increase in H3K27me3 signals in promoters repress pluripotency genes. Moreover, H3K9ac signals facilitate the pluripotency factor Sox2 binding to target sites unique to hNECs. Knockdown of the acetyltransferase Kat2b erases H3K9ac signals, disrupts Sox2 binding, and fails the differentiation. Our results demonstrate a hierarchy of epigenetic regulation of gene expression during the differentiation of hNECs from hESCs through chromatin remodeling. PMID:28475175

  13. Role of cyclooxygenase-2 in intestinal injury in neonatal rats.

    PubMed

    Lu, Hui; Zhu, Bing

    2014-11-01

    Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in premature neonates. The pathogenesis of NEC remains poorly understood. The present study aimed to investigate the dynamic change and role of cyclooxygenase-2 (COX-2) in neonatal rats with intestinal injury. Wistar rats, <24 h in age, received an intraperitoneal injection with 5 mg/kg lipopolysaccharide (LPS). Ileal tissues were collected at 1, 3, 6, 12 and 24 h following the LPS challenge for histological evaluation of NEC and for measurements of COX-2 mRNA. The correlation between the degree of intestinal injury and expression of COX-2 mRNA was determined. The LPS-injected pups showed a significant increase in injury scores compared to the control, and the most deteriorating change was at 12 h. COX-2 mRNA expression was upregulated following LPS injection. There was a significantly positive correlation between COX-2 mRNA and the grade of intestinal injury within 12 h, whereas COX-2 mRNA expression had a significantly negative correlation with the severity of intestinal injury at 24 h. COX-2 plays an important role in LPS-induced intestinal injury and the repair processes. Caution should be exerted concerning the potential therapeutic uses of COX-2 inhibitors or promoters in NEC.

  14. NMR-based metabolomics study of the biochemical relationship between sugarcane callus tissues and their respective nutrient culture media

    PubMed Central

    Mahmud, Iqbal; Thapaliya, Monica; Boroujerdi, Arezue; Chowdhury, Kamal

    2014-01-01

    The culture of sugarcane leaf explant onto culture induction medium triggers the stimulation of cell metabolism into both embryogenic and non-embryogenic callus tissues. Previous analyses demonstrated that embryogenic and nonembryogenic callus tissues have distinct metabolic profiles. This study is the follow-up to understand the biochemical relationship between the nutrient media and callus tissues using one-dimensional (1D 1H) and two-dimensional (2D 1H–13C) NMR spectroscopy followed by principal component analysis (PCA). 1D 1H spectral comparisons of fresh unspent media (FM), embryogenic callus media (ECM), non-embryogenic callus media (NECM), embryogenic callus (EC), and non-embryogenic callus (NEC), showed different metabolic relationships between callus tissues and media. Based on metabolite fold change analysis, significantly changing sugar compounds such as glucose, fructose, sucrose, and maltose were maintained in large quantities by EC only. Significantly different amino acid compounds such as valine, leucine, alanine, threonine, asparagine, and glutamine and different organic acid derivatives such as lactate, 2-hydroxyisobutyrate, 4-aminobutyrate, malonate, and choline were present in EC, NEC, and NECM, which indicates that EC maintained these nutrients, while NEC either maintained or secreted the metabolites. These media and callus-specific results suggest that EC and NEC utilize and/or secrete media nutrients differently. PMID:25012359

  15. Self-duality and a Hall-insulator phase near the superconductor-to-insulator transition in indium-oxide films

    PubMed Central

    Breznay, Nicholas P.; Steiner, Myles A.; Kivelson, Steven Allan; Kapitulnik, Aharon

    2016-01-01

    We combine measurements of the longitudinal (ρxx) and Hall (ρxy) resistivities of disordered 2D amorphous indium-oxide films to study the magnetic-field tuned superconductor-to-insulator transition (H-SIT) in the T→0 limit. At the critical field, Hc, the full resistivity tensor is T independent with ρxx(Hc)=h/4e2 and ρxy(Hc)=0 within experimental uncertainty in all films (i.e., these appear to be “universal” values); this is strongly suggestive that there is a particle–vortex self-duality at H=Hc. The transition separates the (presumably) superconducting state at HHc, at which the Hall resistance is T independent and roughly equal to its classical value, ρxy≈H/nec, marks an additional crossover to a high-field regime (probably to a Fermi insulator) in which ρxy>H/nec and possibly diverges as T→0. We also highlight a profound analogy between the H-SIT and quantum-Hall liquid-to-insulator transitions (QHIT). PMID:26712029

  16. Self-duality and a Hall-insulator phase near the superconductor-to-insulator transition in indium-oxide films.

    PubMed

    Breznay, Nicholas P; Steiner, Myles A; Kivelson, Steven Allan; Kapitulnik, Aharon

    2016-01-12

    We combine measurements of the longitudinal (ρxx) and Hall (ρxy) resistivities of disordered 2D amorphous indium-oxide films to study the magnetic-field tuned superconductor-to-insulator transition (H-SIT) in the T --> 0 limit. At the critical field, Hc, the full resistivity tensor is T independent with ρxx(Hc) = h/4e(2) and ρxy(Hc) = 0 within experimental uncertainty in all films (i.e., these appear to be "universal" values); this is strongly suggestive that there is a particle-vortex self-duality at H = Hc. The transition separates the (presumably) superconducting state at H < Hc from a "Hall-insulator" phase in which ρxx --> ∞ as T --> 0 whereas ρxy approaches a nonzero value smaller than its "classical value" H/nec; i.e., 0 < ρxy < H/nec. A still higher characteristic magnetic field, Hc* > Hc, at which the Hall resistance is T independent and roughly equal to its classical value, ρxy ≈ H/nec, marks an additional crossover to a high-field regime (probably to a Fermi insulator) in which ρxy > H/nec and possibly diverges as T --> 0. We also highlight a profound analogy between the H-SIT and quantum-Hall liquid-to-insulator transitions (QHIT).

  17. Primary anastomosis or ostomy in necrotizing enterocolitis?

    PubMed

    Haricharan, Ramanathapura N; Gallimore, Jade Palazzola; Nasr, Ahmed

    2017-11-01

    In neonates requiring operation for necrotizing enterocolitis (NEC), the complications due to enterostomy (ES) and the need for another operation to restore continuity have prompted several surgeons to employ primary anastomosis (PA) after resection as the operative strategy of choice. Our objective was to compare primary anastomosis to stoma formation in this population using systematic review and meta-analysis. Publications describing both interventions were identified by searching multiple databases. Appropriate studies that reported outcomes after PA and ES for NEC were included for analysis that was performed using the MedCalc3000 software. Results are reported as odds ratios (OR, 95% CI). No randomized trials were identified. Twelve studies were included for the final analysis. Neonates who underwent PA were associated with significantly less risk of mortality when compared to those who underwent ES (OR 0.34, 95% CI 0.17-0.68, p 0.002), possibly due to differences in severity of NEC. Although the types of complications in these groups were different, there was no significant difference in risk of complication (OR 0.86, 0.55-1.33, p 0.50). In neonates undergoing an operation for severe NEC, there is no significant difference in the risk of complications between primary anastomosis and enterostomy. A definitive suggestion cannot be made regarding the choice of one operative strategy over another.

  18. Comparative analyses of viable bacterial counts in foods and seawater under microplate based liquid- and conventional agar plate cultivation: increased culturability of marine bacteria under liquid cultivation.

    PubMed

    Shigematsu, Toru; Ueno, Shigeaki; Tsuchida, Yasuharu; Hayashi, Mayumi; Okonogi, Hiroko; Masaki, Haruhiko; Fujii, Tomoyuki

    2007-12-01

    Bacterial counts under liquid cultivation using 96-well microplates were performed. The counts under liquid and under solid cultivation were equivalent in foods, although the counts under liquid cultivation exceeded those under solid cultivation in seawater, suggesting that some bacteria in seawater were viable but did not form detectable colonies. Phylogenetic analysis of bacteria obtained under liquid cultivation was also performed.

  19. The use of noise equivalent count rate and the NEMA phantom for PET image quality evaluation.

    PubMed

    Yang, Xin; Peng, Hao

    2015-03-01

    PET image quality is directly associated with two important parameters among others: count-rate performance and image signal-to-noise ratio (SNR). The framework of noise equivalent count rate (NECR) was developed back in the 1990s and has been widely used since then to evaluate count-rate performance for PET systems. The concept of NECR is not entirely straightforward, however, and among the issues requiring clarification are its original definition, its relationship to image quality, and its consistency among different derivation methods. In particular, we try to answer whether a higher NECR measurement using a standard NEMA phantom actually corresponds to better imaging performance. The paper includes the following topics: 1) revisiting the original analytical model for NECR derivation; 2) validating three methods for NECR calculation based on the NEMA phantom/standard; and 3) studying the spatial dependence of NECR and quantitative relationship between NECR and image SNR. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  20. Relaxing the cosmological constant: a proof of concept

    NASA Astrophysics Data System (ADS)

    Alberte, Lasma; Creminelli, Paolo; Khmelnitsky, Andrei; Pirtskhalava, David; Trincherini, Enrico

    2016-12-01

    We propose a technically natural scenario whereby an initially large cosmological constant (c.c.) is relaxed down to the observed value due to the dynamics of a scalar evolving on a very shallow potential. The model crucially relies on a sector that violates the null energy condition (NEC) and gets activated only when the Hubble rate becomes sufficiently small — of the order of the present one. As a result of NEC violation, this low-energy universe evolves into inflation, followed by reheating and the standard Big Bang cosmology. The symmetries of the theory force the c.c. to be the same before and after the NEC-violating phase, so that a late-time observer sees an effective c.c. of the correct magnitude. Importantly, our model allows neither for eternal inflation nor for a set of possible values of dark energy, the latter fixed by the parameters of the theory.

  1. The Missions of National Commissions: Mapping the Forms and Functions of Bioethics Advisory Bodies.

    PubMed

    Schmidt, Harald; Schwartz, Jason L

    The findings, conclusions, and recommendations of national ethics commissions (NECs) have received considerable attention throughout the 40-year history of these groups in the United States and worldwide. However, the procedures or types of argument by which these bodies arrive at their decisions have received far less scrutiny. This paper explores how the diversity of ethical principles, concepts, or theories is featured in publications or decisions of these bodies, with particular emphasis on the need for NECs to be inclusive of pluralist positions that typically exist in contemporary democracies. The discussion is centered on the extent to which NECs may focus on providing focal frameworks, primarily framing the ethical issues at stake, or normative frameworks, additionally providing transparent justifications for any conclusions and recommendations that are made. The structure allows for assessments of the relative merits and drawbacks of different approaches in both theory and practice.

  2. Performance Equivalence and Validation of the Soleris Automated System for Quantitative Microbial Content Testing Using Pure Suspension Cultures.

    PubMed

    Limberg, Brian J; Johnstone, Kevin; Filloon, Thomas; Catrenich, Carl

    2016-09-01

    Using United States Pharmacopeia-National Formulary (USP-NF) general method <1223> guidance, the Soleris(®) automated system and reagents (Nonfermenting Total Viable Count for bacteria and Direct Yeast and Mold for yeast and mold) were validated, using a performance equivalence approach, as an alternative to plate counting for total microbial content analysis using five representative microbes: Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Candida albicans, and Aspergillus brasiliensis. Detection times (DTs) in the alternative automated system were linearly correlated to CFU/sample (R(2) = 0.94-0.97) with ≥70% accuracy per USP General Chapter <1223> guidance. The LOD and LOQ of the automated system were statistically similar to the traditional plate count method. This system was significantly more precise than plate counting (RSD 1.2-2.9% for DT, 7.8-40.6% for plate counts), was statistically comparable to plate counting with respect to variations in analyst, vial lots, and instruments, and was robust when variations in the operating detection thresholds (dTs; ±2 units) were used. The automated system produced accurate results, was more precise and less labor-intensive, and met or exceeded criteria for a valid alternative quantitative method, consistent with USP-NF general method <1223> guidance.

  3. The equivalence of three techniques for estimating ground reflectance from LANDSAT digital count data

    NASA Technical Reports Server (NTRS)

    Richardson, A. J. (Principal Investigator)

    1983-01-01

    The equivalence of three separate investigations that related LANDSAT digital count (DC) to ground measured reflectance (R) was demonstrated. One investigator related DC data to the cosZ, where Z is the solar zenith angle, for surfaces of constant R. The second investigator corrected the DC data to the solar zenith angle of 39 degrees before relating to surface R. Both of these investigators used LANDSAT 1 and 2 data from overpass dates 1972 through 1977. A third investigator calculated the relation between DC and R based on atmospheric radiative transfer theory. The equation coefficients obtained from these three investigators for all four LANDSAT MSS bands were shown to be equivalent although differences in ground reflectance measurement procedures have created coefficient variations among the three investigations. These relations should be useful for testing atmospheric radiative transfer theory.

  4. Equivalent Colorings with "Maple"

    ERIC Educational Resources Information Center

    Cecil, David R.; Wang, Rongdong

    2005-01-01

    Many counting problems can be modeled as "colorings" and solved by considering symmetries and Polya's cycle index polynomial. This paper presents a "Maple 7" program link http://users.tamuk.edu/kfdrc00/ that, given Polya's cycle index polynomial, determines all possible associated colorings and their partitioning into equivalence classes. These…

  5. 75 FR 29508 - The 2010 Census Count Question Resolution Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-26

    .... Relevant 2010 Census Data Releases The Redistricting Data (Pub. L. 94-171) are scheduled for release from... redistricting functions within each State and State equivalents who are acting on the behalf of a local or... 2010 Census base files, 2010 Census apportionment counts, redistricting data, or 2010 Census data...

  6. Transport and Thermohaline Structure in the Western Tropical North Pacific

    NASA Astrophysics Data System (ADS)

    Schonau, Martha Coakley

    Transport and thermohaline structure of water masses and their respective variability are observed and modeled in the western tropical North Pacific using autonomous underwater gliders, Argo climatology and a numerical ocean state estimate. The North Equatorial Current (NEC) advects subtropical and subpolar water masses into the region that are transported equatorward by the Mindanao Current (MC). Continuous glider observations of these two currents from June 2009 to December 2013 provide absolute geostrophic velocity, water mass structure, and transport. The observations are compared to Argo climatology (Roemmich and Gilson, 2009), wind and precipitation to assess forcing, and annual and interannual variability. Observations are assimilated into a regional ocean state estimate (1/6°) to examine regional transport variability and its relationship to the El Nino-Southern Oscillation phenomena (ENSO). The NEC, described in Chapter 1, is observed along 134.3°E, from 8.5°N to 16.5°N. NEC thermocline transport is relatively constant, with a variable subthermocline transport that is distinguished by countercurrents centered at 9.6°N and 13.1°N. Correlation between thermocline and subthermocline transport is strong. Isopycnals with subducted water masses, the North Pacific Tropical Water and North Pacific Intermediate Water, have the greatest fine-scale thermohaline variance. The NEC advects water masses into the MC, described in Chapter 2, that flows equatorward along the coast of Mindanao. Gliders observed the MC at a mean latitude of 8.5°N. The Mindanao Undercurrent (MUC) persists in the subthermocline offshore of the MC, with a net poleward transport of intermediate water typical of South Pacific origin. The variable subthermocline transport in the MC/MUC has an inverse linear relationship with the Nino 3.4 index and strongly impacts total transport variability. For each the MC and NEC, surface salinity and thermocline depth have a strong relationship with ENSO, and there is relationship between the fine-scale and large-scale isopycnal thermohaline structure. In Chapter 3, a numerical ocean state estimates shows strong interannual variability of regional transport with ENSO. Prior to mature ENSO events, transport in each the NEC, MC and North Equatorial Counter Current (NECC) increase. The increase is from meridional gradients in isopycnal depth related to interannual wind anomalies.

  7. Secure Service Oriented Architectures (SOA) Supporting NEC (Architecture orientee service (soa) gerant la NEC)

    DTIC Science & Technology

    2009-01-01

    reproduced directly from material supplied by RTO or the authors. Published January 2009 Copyright © RTO/NATO 2009 All Rights Reserved ISBN 978...in Kosovo, • SIR: “Système d’Information Régimentaire”, the French regiment level system, and • FURET: French production chain of tactical...for these COIs are described below. Four relationships between assets and COIs are supplied : 1. The topicSpaces an asset has the right to

  8. Immune Checkpoint Inhibitors in the Treatment of Patients with Neuroendocrine Neoplasia.

    PubMed

    Weber, Matthias M; Fottner, Christian

    2018-01-01

    Well-differentiated neuroendocrine neoplasms (NENs) are usually controlled by antiproliferative, local ablative and/or radionuclide therapies, whereas poorly differentiated NENs generally require cytotoxic chemotherapy. However, treatment options for patients with advanced/metastatic high-grade NENs remain limited. Review of the literature and international congress abstracts on the efficacy and safety of immunotherapy by checkpoint inhibition in advanced/metastatic NENs. Evidence points to an important role of immune phenomena in the pathogenesis and treatment of neuroendocrine tumors (NETs). Programmed cell death 1 (PD-1) protein and its ligand are mainly expressed in poorly differentiated NENs. Microsatellite instability and high mutational load are more pronounced in high-grade NENs and may predict response to immunotherapy. Clinical experience of immune checkpoint blockade mainly exists for Merkel cell carcinoma, a high-grade cutaneous neuroendocrine carcinoma (NEC), which has led to approval of the anti-PD-1 antibody avelumab. In addition, there is anecdotal evidence for the efficacy of checkpoint inhibitors in large-cell lung NECs, ovarian NECs and others, including gastroenteropancreatic NENs. Currently, phase II studies investigate PDR001, pembrolizumab, combined durvalumab and tremelimumab, and avelumab treatment in patients with advanced/metastatic NENs. Immune checkpoint inhibitors are a promising therapeutic option, especially in progressive NECs or high-grade NETs with high tumor burden, microsatellite instability, and/or mutational load. © 2018 S. Karger GmbH, Freiburg.

  9. Saccharomyces boulardii for prevention of necrotizing enterocolitis in preterm infants: a randomized, controlled study.

    PubMed

    Demirel, Gamze; Erdeve, Omer; Celik, Istemi Han; Dilmen, Ugur

    2013-12-01

    To evaluate the efficacy of orally administered Saccharomyces boulardii (S. boulardii) for reducing the incidence and severity of necrotizing enterocolitis (NEC) in very low-birth-weight (VLBW) infants. A prospective, randomised controlled trial was conducted in infants with gestational age ≤32 weeks and birth weight ≤1500 g. The study group received S. boulardii supplementation, and the control group did not. The primary outcomes were death or NEC (Bell's stage ≥2), and secondary outcomes were feeding intolerance and clinical or culture-proven sepsis. A total of 271 infants were enrolled in the study, 135 in the study group and 136 in the control group. There was no significant difference in the incidence of death (3.7% vs. 3.6%, 95% CI of the difference, -5.20-5.25; p = 1.0) or NEC (4.4% vs. 5.1%, 95% CI, -0.65-5.12; p = 1.0) between the groups. However, feeding intolerance and clinical sepsis were significantly lower in the probiotic group compared with control. Although Saccharomyces boulardii supplementation at a dose of 250 mg/day was not effective at reducing the incidence of death or NEC in VLBW infants, it improved feeding tolerance and reduced the risk of clinical sepsis. ©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  10. Spectrum of Gastroenteropancreatic NENs in Routine Histological Examinations of Bioptic and Surgical Specimen: A Study of 161 Cases Collected from 17 Departments of Pathology in the Czech Republic

    PubMed Central

    Mandys, Václav

    2014-01-01

    Objective. To characterize GEP-NENs in routine biopsies and surgical specimen in the Czech Republic and to evaluate how WHO Classification (2010) is acceptable in diagnostic practice. Methods. Paraffin-embedded blocks and bioptic reports were collected from 17 departments of pathology. Histologic slides were stained with H&E and immunohistologically for CgA, synaptophysin, and Ki-67. Results. Out of 28 gastric NENs, there were 22 NETs, G1, 5 NETs, G2, and 1 NEC. Ten duodenal NENs were NETs, G1. Among 27 NENs of jejunum and ileum, 23 were NETs, G1, 2 NETs, G2, and 1 NEC and 1 mixed adenoneuroendocrine carcinoma (MANEC). Among 42 appendiceal “incidentalomas”, 39 were NETs G1, 2 goblet cell carcinoids, and 1 MANEC. Out of 34 large intestinal NENs, 30 were NETs, G1, 3 NETs, G2, and 1 NEC. One small intestinal and 6 large bowel neoplasms were reclassified as poorly differentiated adenocarcinomas. In 12 pancreatic NENs, there were 7 NETs, G1, 3 NETs, G2, and 2 NECs. Conclusions. Our study demonstrates differences in GEP-NENs frequency in sites of origin in our region, comparing to other countries. Regarding routine bioptic diagnostics, we gave evidence that the WHO 2010 classification of NENs is fully acceptable for exact categorisation of tumours. PMID:24695372

  11. Ranitidine is associated with infections, necrotizing enterocolitis, and fatal outcome in newborns.

    PubMed

    Terrin, Gianluca; Passariello, Annalisa; De Curtis, Mario; Manguso, Francesco; Salvia, Gennaro; Lega, Laura; Messina, Francesco; Paludetto, Roberto; Canani, Roberto Berni

    2012-01-01

    Gastric acidity is a major nonimmune defense mechanism against infections. The objective of this study was to investigate whether ranitidine treatment in very low birth weight (VLBW) infants is associated with an increased risk of infections, necrotizing enterocolitis (NEC), and fatal outcome. Newborns with birth weight between 401 and 1500 g or gestational age between 24 and 32 weeks, consecutively observed in neonatal intensive care units, were enrolled in a multicenter prospective observational study. The rates of infectious diseases, NEC, and death in enrolled subjects exposed or not to ranitidine were recorded. We evaluated 274 VLBW infants: 91 had taken ranitidine and 183 had not. The main clinical and demographic characteristics did not differ between the 2 groups. Thirty-four (37.4%) of the 91 children exposed to ranitidine and 18 (9.8%) of the 183 not exposed to ranitidine had contracted infections (odds ratio 5.5, 95% confidence interval 2.9-10.4, P < .001). The risk of NEC was 6.6-fold higher in ranitidine-treated VLBW infants (95% confidence interval 1.7-25.0, P = .003) than in control subjects. Mortality rate was significantly higher in newborns receiving ranitidine (9.9% vs 1.6%, P = .003). Ranitidine therapy is associated with an increased risk of infections, NEC, and fatal outcome in VLBW infants. Caution is advocated in the use of this drug in neonatal age.

  12. Development of a 3D Brain PET Scanner Using CdTe Semiconductor Detectors and Its First Clinical Application

    NASA Astrophysics Data System (ADS)

    Morimoto, Y.; Ueno, Y.; Takeuchi, W.; Kojima, S.; Matsuzaki, K.; Ishitsu, T.; Umegaki, K.; Kiyanagi, Y.; Kubo, N.; Katoh, C.; Shiga, T.; Shirato, H.; Tamaki, N.

    2011-10-01

    Targeting improved spatial resolution, a three-dimensional positron-emission-tomography (PET) scanner employing CdTe semiconductor detectors and using depth-of-interaction (DOI) information was developed, and its physical performance was evaluated. This PET scanner is the first to use semiconductor detectors dedicated to the human brain and head-and-neck region. Imaging performance of the scanner used for 18F -fluorodeoxy glucose (FDG) scans of phantoms and human brains was evaluated. The gantry of the scanner has a 35.0-cm-diameter patient port, the trans-axial field of view (FOV) is 31.0 cm, and the axial FOV is 24.6 cm. The energy resolution averaged over all detector channels and timing resolution were 4.1% and 6.8 ns (each in FWHM), respectively. Spatial resolution measured at the center of FOV was 2.3-mm FWHM-which is one of the best resolutions achieved by human PET scanners. Noise-equivalent count ratio (NEC2R) has a maximum in the energy window of 390 to 540 keV and is 36 kcps/Bq/cm3 at 3.7 kBq/cm3 . The sensitivity of the system according to NEMA 1994 was 25.9 cps/Bq/cm3. Scatter fraction of the scanner is 37% for the energy window of 390 to 540 keV and 23% for 450 to 540 keV. Images of a hot-rod phantom and images of brain glucose metabolism show that the structural accuracy of the images obtained with the semiconductor PET scanner is higher than that possible with a conventional Bismuth Germanium Oxide (BGO) PET scanner. In addition, the developed scanner permits better delineation of the head-and-neck cancer. These results show that the semiconductor PET scanner will play a major role in the upcoming era of personalized medicine.

  13. Observations Regarding Scatter Fraction and NEC Measurements for Small Animal PET

    NASA Astrophysics Data System (ADS)

    Yang, Yongfeng; Cherry, S. R.

    2006-02-01

    The goal of this study was to evaluate the magnitude and origin of scattered radiation in a small-animal PET scanner and to assess the impact of these findings on noise equivalent count rate (NECR) measurements, a metric often used to optimize scanner acquisition parameters and to compare one scanner with another. The scatter fraction (SF) was measured for line sources in air and line sources placed within a mouse-sized phantom (25 mm /spl phi//spl times/70 mm) and a rat-sized phantom (60 mm /spl phi//spl times/150 mm) on the microPET II small-animal PET scanner. Measurements were performed for lower energy thresholds ranging from 150-450 keV and a fixed upper energy threshold of 750 keV. Four different methods were compared for estimating the SF. Significant scatter fractions were measured with just the line source in the field of view, with the spatial distribution of these events consistent with scatter from the gantry and room environment. For mouse imaging, this component dominates over object scatter, and the measured SF is strongly method dependent. The environmental SF rapidly increases as the lower energy threshold decreases and can be more than 30% for an open energy window of 150-750 keV. The object SF originating from the mouse phantom is about 3-4% and does not change significantly as the lower energy threshold increases. The object SF for the rat phantom ranges from 10 to 35% for different energy windows and increases as the lower energy threshold decreases. Because the measured SF is highly dependent on the method, and there is as yet no agreed upon standard for animal PET, care must be exercised when comparing NECR for small objects between different scanners. Differences may be methodological rather than reflecting any relevant difference in the performance of the scanner. Furthermore, these results have implications for scatter correction methods when the majority of the detected scatter does not arise from the object itself.

  14. Role of necroptosis in autophagy signaling during hepatic ischemia and reperfusion

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

    Hong, Jeong-Min; Kim, Seok-Joo; Lee, Sun-Mee, E-ma

    Ischemia and reperfusion (I/R) is a complex phenomenon involving massive inflammation and cell death. Necroptosis refers to a newly described cell death as “programmed necrosis” that is controlled by receptor-interacting protein kinase (RIP) 1 and RIP3, which is involved in the pathogenesis of several inflammatory diseases. Autophagy is an essential cytoprotective system that is rapidly activated in response to various stimuli and involves crosstalk between different modes of cell death and inflammation. In this study, we investigated pattern changes in necroptosis and its role in autophagy signaling during hepatic I/R. Male C57BL/6 mice were subjected to 60 min of ischemiamore » followed by 3 h reperfusion. Necrostatin-1 (Nec-1, a necroptosis inhibitor; 1.65 mg/kg) was administered intraperitoneally 5 min before reperfusion. Hepatic I/R significantly increased the level of RIP3, phosphorylated RIP1 and RIP3 protein expression, and RIP1/RIP3 necrosome formation, which were attenuated by Nec-1. I/R also significantly increased serum levels of alanine aminotransferase, tumor necrosis factor-α, and interleukin-6, which were attenuated by Nec-1. Meanwhile, hepatic I/R activated autophagy and mitophagy, as evidenced by increased LC3-II, PINK1, and Parkin, and decreased sequestosome 1/p62 protein expression. Nec-1 attenuated these changes and attenuated the increased levels of autophagy-related protein (ATG) 3, ATG7, Rab7, and cathepsin B protein expression during hepatic I/R. Moreover, hepatic I/R activated the extracellular signal-regulated kinase (ERK) pathway, and Nec-1 attenuated this increase. Taken together, our findings suggest that necroptosis contributes to hepatic damage during I/R, which induces autophagy via ERK activation. - Highlights: • Hepatic I/R induces RIP1/RIP3-dependent necroptosis. • Necroptosis contributes to hepatic I/R injury. • Necroptosis activates autophagic flux via ERK activation during hepatic I/R.« less

  15. Differences in sensory reweighting due to loss of visual and proprioceptive cues in postural stability support among sleep-deprived cadet pilots.

    PubMed

    Cheng, Shan; Ma, Jin; Sun, Jicheng; Wang, Jian; Xiao, Xiao; Wang, Yihan; Hu, Wendong

    2018-04-26

    Sleep deprivation is known to diminish postural control. We investigated whether sleep deprivation affects sensory reweighting for postural control due to loss of visual and proprioceptive cues. Two cohorts of cadet pilots were deprived of sleep for 40 h. Variabilty in force-platform center of pressure was analyzed based on the whole path length (WPL); circumference area (CA); mean of displacement along x and y axes and corresponding standard deviations (SDx, SDy); and frequency of body-sway intensity, all of which were recorded while the cadets stood with eyes open (NEO), eyes closed (NEC), and eyes closed on a foam platform base (FEC) A sleepiness index (SUBI) based on principal component analysis of selected Cohort 1 data (n = 37) was used to compare Cohort 2 data (n = 29) with scores for the Stanford Sleepiness Scale (SSS) and Pittsburg Sleep Quality Index (PSQI). Balance began to deteriorate at 16 h for NEO and at 28 h for NEC and FEC (p < 0.05). At 40 h, WPL, CA, and SDy of COP for NEO indicated balance deteriorated further while WPL and SDy for NEC and WPL, CA, SDx, and SDy for FEC indicated balance incrementally improved. Frequency bias of body-sway differed between NEO, NEC, and FEC. In Cohort 2, the SUBI correlated significantly with SSS (p < 0.05), but not with PSQI. Effects of sleep deprivation were mitigated over time, suggesting that compensatory mechanisms influenced sensory reweighting for NEC and FEC between 28 and 40 h of sleep deprivation, but not for NEO. Frequency bias of body-sway suggested that sensory reweighting in the absence of visual cues differed from that in the absence of both visual and proprioceptive cues. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Negative effects of climate warming on maize yield are reversed by the changing of sowing date and cultivar selection in Northeast China.

    PubMed

    Liu, Zhijuan; Hubbard, Kenneth G; Lin, Xiaomao; Yang, Xiaoguang

    2013-11-01

    Northeast China (NEC) accounts for about 30% of the nation's maize production in China. In the past three decades, maize yields in NEC have increased under changes in climate, cultivar selection and crop management. It is important to investigate the contribution of these changing factors to the historical yield increases to improve our understanding of how we can ensure increased yields in the future. In this study, we use phenology observations at six sites from 1981 to 2007 to detect trends in sowing dates and length of maize growing period, and then combine these observations with in situ temperature data to determine the trends of thermal time in the maize growing period, as a measure of changes in maize cultivars. The area in the vicinity of these six sites accounts for 30% of NEC's total maize production. The agricultural production systems simulator, APSIM-Maize model, was used to separate the impacts of changes in climate, sowing dates and thermal time requirements on maize phenology and yields. In NEC, sowing dates trended earlier in four of six sites and maturity dates trended later by 4-21 days. Therefore, the period from sowing to maturity ranged from 2 to 38 days longer in 2007 than it was in 1981. Our results indicate that climate trends alone would have led to a negative impact on maize. However, results from the adaptation assessments indicate that earlier sowing dates increased yields by up to 4%, and adoption of longer season cultivars caused a substantial increase in yield ranging from 13% to 38% over the past 27 years. Therefore, earlier sowing dates and introduction of cultivars with higher thermal time requirements in NEC have overcome the negative effects of climate change and turned what would have otherwise been a loss into a significant increase in maize yield. © 2013 John Wiley & Sons Ltd.

  17. Carbohydrate maldigestion induces necrotizing enterocolitis in preterm pigs

    PubMed Central

    Thymann, Thomas; Møller, Hanne K.; Stoll, Barbara; Støy, Ann Cathrine F.; Buddington, Randal K.; Bering, Stine B.; Jensen, Bent B.; Olutoye, Oluyinka O.; Siggers, Richard H.; Mølbak, Lars; Sangild, Per T.

    2009-01-01

    Necrotizing enterocolitis (NEC) remains the most severe gastrointestinal disorder in preterm infants. It is associated with the initiation of enteral nutrition and may be related to immature carbohydrate digestive capacity. We tested the hypothesis that a formula containing maltodextrin vs. a formula containing lactose as the principal source of carbohydrate would predispose preterm pigs to a higher NEC incidence. Cesarean-derived preterm pigs were given total parenteral nutrition for 48 h followed by total enteral nutrition with a lactose-based (n = 11) or maltodextrin-based (n = 11) formula for 36 h. A higher incidence (91% vs. 27%) and severity (score of 3.3 vs. 1.8) of NEC were observed in the maltodextrin than in the lactose group. This higher incidence of NEC in the maltodextrin group was associated with significantly lower activities of lactase, maltase, and aminopeptidase; reduced villus height; transiently reduced in vivo aldohexose uptake; and reduced ex vivo aldohexose uptake capacity in the middle region of the small intestine. Bacterial diversity was low for both diets, but alterations in bacterial composition and luminal concentrations of short-chain fatty acids were observed in the maltodextrin group. In a second study, we quantified net portal absorption of aldohexoses (glucose and galactose) during acute jejunal infusion of a maltodextrin- or a lactose-based formula (n = 8) into preterm pigs. We found lower net portal aldohexose absorption (4% vs. 42%) and greater intestinal recovery of undigested carbohydrate (68% vs. 27%) in pigs acutely perfused with the maltodextrin-based formula than those perfused with the lactose-based formula. The higher digestibility of the lactose than the maltodextrin in the formulas can be attributed to a 5- to 20-fold higher hydrolytic activity of tissue-specific lactase than maltases. We conclude that carbohydrate maldigestion is sufficient to increase the incidence and severity of NEC in preterm pigs. PMID:19808655

  18. Dry-wet variations and cause analysis in Northeast China at multi-time scales

    NASA Astrophysics Data System (ADS)

    Hu, Qi; Pan, Feifei; Pan, Xuebiao; Hu, Liting; Wang, Xiaoxiao; Yang, Pengyu; Wei, Pei; Pan, Zhihua

    2017-07-01

    Global warming has caused unevenly distributed changes in precipitation and evapotranspiration, which has and will certainly impact on the wet-dry variations. Based on daily meteorological data collected at 91 weather stations in Northeast China (NEC), the spatiotemporal characteristics of dry and wet climatic variables (precipitation, crop reference evapotranspiration (ET0), and humid index (HI)) are analyzed, and the probable reasons causing the changes in these variables are discussed during the period of 1961-2014. Precipitation showed non-significant trend over the period of 1961-2014, while ET0 showed a significant decreasing trend, which led to climate wetting in NEC. The period of 2001-2012 exhibited smaller semiarid area and larger humid area compared to the period of 1961-1980, indicating NEC has experienced wetting process at decadal scale. ET0 was most sensitive to relative humidity, and wind speed was the second most sensitive variable. Sunshine hours and temperature were found to be less influential to ET0 in the study area. The changes in wind speed in the recent 54 years have caused the greatest influence on ET0, followed by temperature. For each month, wind speed was the most significant variable causing ET0 reduction in all months except July. Temperature, as a dominant factor, made a positive contribution to ET0 in February and March, as well as sunshine hours in June and July, and relative humidity in August and September. In summary, NEC has experienced noticeable climate wetting due to the significantly decreasing ET0, and the decrease in wind speed was the biggest contributor for the ET0 reduction. Although agricultural drought crisis is expected to be partly alleviated, regional water resources management and planning in Northeast China should consider the potential water shortage and water conflict in the future because of spatiotemporal dry-wet variations in NEC.

  19. Medical Surveillance Monthly Report (MSMR). Volume 18, Number 07, July 2011

    DTIC Science & Technology

    2011-07-01

    acquired hypothyroidism ; disorders of lipoid metabolism (includes hypercholesterolemia and hyperlipidemia); overweight, obesity, and other...infertility 276 24.6 6.9 77 715 Osteoarthrosis 542 11.3 2.4 114 726 Peripheral enthesopathies 654 58.3 6.5 73 244 Acquired hypothyroidism 597 12.5 2.3 110...integument 115 46.1 7.1 18 307 Special symptoms syndromes nec 19 26.3 6.5 5 739 Nonallopathic lesions nec 89 35.7 6.9 17 244 Acquired hypothyroidism

  20. 47 CFR 36.156 - Interexchange Cable and Wire Facilities (C&WF)-Category 3-apportionment procedures.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... cost per equivalent interexchange telephone circuit kilometer for all circuits in Category 3 is determined and applied to the equivalent interexchange telephone circuit kilometer counts of each of the... Interexchange Cable and Wire Facilities C&WF where feasible. All study areas shall apportion the non-directly...

  1. 47 CFR 36.156 - Interexchange Cable and Wire Facilities (C&WF)-Category 3-apportionment procedures.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... cost per equivalent interexchange telephone circuit kilometer for all circuits in Category 3 is determined and applied to the equivalent interexchange telephone circuit kilometer counts of each of the... Interexchange Cable and Wire Facilities C&WF where feasible. All study areas shall apportion the non-directly...

  2. 47 CFR 36.156 - Interexchange Cable and Wire Facilities (C&WF)-Category 3-apportionment procedures.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... cost per equivalent interexchange telephone circuit kilometer for all circuits in Category 3 is determined and applied to the equivalent interexchange telephone circuit kilometer counts of each of the... Interexchange Cable and Wire Facilities C&WF where feasible. All study areas shall apportion the non-directly...

  3. 47 CFR 36.156 - Interexchange Cable and Wire Facilities (C&WF)-Category 3-apportionment procedures.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... cost per equivalent interexchange telephone circuit kilometer for all circuits in Category 3 is determined and applied to the equivalent interexchange telephone circuit kilometer counts of each of the... Interexchange Cable and Wire Facilities C&WF where feasible. All study areas shall apportion the non-directly...

  4. 45 CFR 286.100 - What activities count towards the work participation rate?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... not received a high school diploma or a certificate of high school equivalency; (11) Satisfactory attendance at secondary school or in a course of study leading to a certificate of general equivalence, if a recipient has not completed secondary school or received such a certificate; (12) Providing child care...

  5. 45 CFR 286.100 - What activities count towards the work participation rate?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... not received a high school diploma or a certificate of high school equivalency; (11) Satisfactory attendance at secondary school or in a course of study leading to a certificate of general equivalence, if a recipient has not completed secondary school or received such a certificate; (12) Providing child care...

  6. 45 CFR 286.100 - What activities count towards the work participation rate?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... not received a high school diploma or a certificate of high school equivalency; (11) Satisfactory attendance at secondary school or in a course of study leading to a certificate of general equivalence, if a recipient has not completed secondary school or received such a certificate; (12) Providing child care...

  7. 45 CFR 286.100 - What activities count towards the work participation rate?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... not received a high school diploma or a certificate of high school equivalency; (11) Satisfactory attendance at secondary school or in a course of study leading to a certificate of general equivalence, if a recipient has not completed secondary school or received such a certificate; (12) Providing child care...

  8. Radiation dosimetry measurements with real time radiation monitoring device (RRMD)-II in Space Shuttle STS-79

    NASA Technical Reports Server (NTRS)

    Sakaguchi, T.; Doke, T.; Hayashi, T.; Kikuchi, J.; Hasebe, N.; Kashiwagi, T.; Takashima, T.; Takahashi, K.; Nakano, T.; Nagaoka, S.; hide

    1997-01-01

    The real-time measurement of radiation environment was made with an improved real-time radiation monitoring device (RRMD)-II onboard Space Shuttle STS-79 (S/MM#4: 4th Shuttle MIR Mission, at an inclination angle of 51.6 degrees and an altitude of 250-400km) for 199 h during 17-25 September, 1996. The observation of the detector covered the linear energy transfer (LET) range of 3.5-6000 keV/micrometer. The Shuttle orbital profile in this mission was equivalent to that of the currently planned Space Station, and provided an opportunity to investigate variations in count rate and dose equivalent rate depending on altitude, longitude, and latitude in detail. Particle count rate and dose equivalent rate were mapped geographically during the mission. Based on the map of count rate, an analysis was made by dividing whole region into three regions: South Atlantic Anomaly (SAA) region, high latitude region and other regions. The averaged absorbed dose rate during the mission was 39.3 microGy/day for a LET range of 3.5-6000 keV/micrometer. The corresponding average dose equivalent rates during the mission are estimated to be 293 microSv/day with quality factors from International Commission on Radiological Protection (ICRP)-Pub. 60 and 270 microSv/day with quality factors from ICRP-Pub. 26. The effective quality factors for ICRP-Pub. 60 and 26 are 7.45 and 6.88, respectively. From the present data for particles of LET > 3.5keV/micrometer, we conclude that the average dose equivalent rate is dominated by the contribution of galactic cosmic ray (GCR) particles. The dose-detector depth dependence was also investigated.

  9. Recent Trends of Summer Convective and Stratiform Precipitation in Mid-Eastern China

    PubMed Central

    Fu, Yunfei; Chen, Fengjiao; Liu, Guosheng; Yang, Yuanjian; Yuan, Renmin; Li, Rui; Liu, Qi; Wang, Yu; Zhong, Lei; Sun, Liang

    2016-01-01

    Many studies have reported on the trends of precipitation in Mid-Eastern China (EC). However, the trends of convective and stratiform precipitation are still unknown. Here, we examine the trends of summer convective and stratiform precipitation in EC from 2002 to 2012 on the basis of the TRMM observations. Results revealed that the rain frequency (RF) for both convective and stratiform precipitation increased in majority regions of Southern EC (SEC), but decreased in Northwest part of Northern EC (NEC). The decreasing rate of RF for stratiform precipitation in NEC is twice as much as that for convective precipitation, while the increase of convective precipitation in SEC is more evident than stratiform precipitation. The rain rate (RR) exhibited a decreasing trend in most portions of EC for both convective and stratiform precipitation. In SEC, neither PW nor WVT has good ability in explaining the precipitation variability. However, in NEC, PW is closely correlated to convective RF and WVT is more closely related to stratiform RF. PMID:27604846

  10. Human performance under two different command and control paradigms.

    PubMed

    Walker, Guy H; Stanton, Neville A; Salmon, Paul M; Jenkins, Daniel P

    2014-05-01

    The paradoxical behaviour of a new command and control concept called Network Enabled Capability (NEC) provides the motivation for this paper. In it, a traditional hierarchical command and control organisation was pitted against a network centric alternative on a common task, played thirty times, by two teams. Multiple regression was used to undertake a simple form of time series analysis. It revealed that whilst the NEC condition ended up being slightly slower than its hierarchical counterpart, it was able to balance and optimise all three of the performance variables measured (task time, enemies neutralised and attrition). From this it is argued that a useful conceptual response is not to consider NEC as an end product comprised of networked computers and standard operating procedures, nor to regard the human system interaction as inherently stable, but rather to view it as a set of initial conditions from which the most adaptable component of all can be harnessed: the human. Copyright © 2013 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  11. Dynamics of the seasonal variation of the North Equatorial Current bifurcation

    NASA Astrophysics Data System (ADS)

    Chen, Zhaohui; Wu, Lixin

    2011-02-01

    The dynamics of the seasonal variation of the North Equatorial Current (NEC) bifurcation is studied using a 1.5-layer nonlinear reduced-gravity Pacific basin model and a linear, first-mode baroclinic Rossby wave model. The model-simulated bifurcation latitude exhibits a distinct seasonal cycle with the southernmost latitude in June and the northernmost latitude in November, consistent with observational analysis. It is found that the seasonal migration of the NEC bifurcation latitude (NBL) not only is determined by wind locally in the tropics, as suggested in previous studies, but is also significantly intensified by the extratropical wind through coastal Kelvin waves. The model further demonstrates that the amplitude of the NEC bifurcation is also associated with stratification. A strong (weak) stratification leads to a fast (slow) phase speed of first-mode baroclinic Rossby waves, and thus large (small) annual range of the bifurcation latitude. Therefore, it is expected that in a warm climate the NBL should have a large range of annual migration.

  12. Survival and morbidity outcomes for very low birth weight infants with Down syndrome.

    PubMed

    Boghossian, Nansi S; Hansen, Nellie I; Bell, Edward F; Stoll, Barbara J; Murray, Jeffrey C; Laptook, Abbot R; Shankaran, Seetha; Walsh, Michele C; Das, Abhik; Higgins, Rosemary D

    2010-12-01

    Our objective was to compare survival and neonatal morbidity rates between very low birth weight (VLBW) infants with Down syndrome (DS) and VLBW infants with non-DS chromosomal anomalies, nonchromosomal birth defects (BDs), and no chromosomal anomaly or major BD. Data were collected prospectively for infants weighing 401 to 1500 g who were born and/or cared for at one of the study centers participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network in 1994-2008. Risk of death and morbidities, including patent ductus arteriosus (PDA), necrotizing enterocolitis (NEC), late-onset sepsis (LOS), retinopathy of prematurity, and bronchopulmonary dysplasia (BPD), were compared between VLBW infants with DS and infants in the other groups. Infants with DS were at increased risk of death (adjusted relative risk: 2.47 [95% confidence interval: 2.00-3.07]), PDA, NEC, LOS, and BPD, relative to infants with no BDs. Decreased risk of death (relative risk: 0.40 [95% confidence interval: 0.31-0.52]) and increased risks of NEC and LOS were observed when infants with DS were compared with infants with other non-DS chromosomal anomalies. Relative to infants with nonchromosomal BDs, infants with DS were at increased risk of PDA and NEC. The increased risk of morbidities among VLBW infants with DS provides useful information for counseling parents and for anticipating the need for enhanced surveillance for prevention of these morbidities.

  13. Modeling the interactions of bacteria and Toll-like receptor-mediated inflammation in necrotizing enterocolitis

    PubMed Central

    Arciero, Julia; Ermentrout, G. Bard; Siggers, Richard; Afrazi, Amin; Hackam, David; Vodovotz, Yoram; Rubin, Jonathan

    2016-01-01

    Necrotizing enterocolitis (NEC) is a severe disease of the gastrointestinal tract in premature infants, characterized by a disrupted intestinal epithelium and an exaggerated pro-inflammatory response. Since the activation of Toll-like receptor-4 (TLR4) blocks cell migration and proliferation and contributes to an uncontrolled inflammatory response within the intestine, this receptor has been identified as a key contributor to the development of NEC. Toll-like receptor-9 (TLR9) has been shown to sense bacterial genome components (CpG DNA) and to play an anti-inflammatory role in NEC. We present in vitro results demonstrating direct inhibition of TLR4 activation by CpG DNA, and we develop a mathematical model of bacteria–immune interactions within the intestine to investigate how such inhibition of TLR4 signaling might alter inflammation, associated bacterial invasion of tissue, and resulting outcomes. The model predicts that TLR9 can inhibit both the beneficial and detrimental effects of TLR4, and thus a proper balance of action by these two receptors is needed to promote intestinal health. The model results are also used to explore three interventions that could potentially prevent the development of NEC: reducing bacteria in the mucus layer, administering probiotic treatment, and blocking TLR4 activation. While the model shows that these interventions would be successful in most cases, the model is also used to identify situations in which the proposed treatments might be harmful. PMID:23238281

  14. Impact of Donor Milk Availability on Breast Milk Use and Necrotizing Enterocolitis Rates.

    PubMed

    Kantorowska, Agata; Wei, Julia C; Cohen, Ronald S; Lawrence, Ruth A; Gould, Jeffrey B; Lee, Henry C

    2016-03-01

    To examine the availability of donor human milk (DHM) in a population-based cohort and assess whether the availability of DHM was associated with rates of breast milk feeding at NICU discharge and rates of necrotizing enterocolitis (NEC). Individual patient clinical data for very low birth weight infants from the California Perinatal Quality Care Collaborative were linked to hospital-level data on DHM availability from the Mothers' Milk Bank of San José for 2007 to 2013. Trends of DHM availability were examined by level of NICU care. Hospitals that transitioned from not having DHM to having DHM availability during the study period were examined to assess changes in rates of breast milk feeding at NICU discharge and NEC. The availability of DHM increased from 27 to 55 hospitals during the study period. The availability increased for all levels of care including regional, community, and intermediate NICUs, with the highest increase occurring in regional NICUs. By 2013, 81.3% of premature infants cared for in regional NICUs had access to DHM. Of the 22 hospitals that had a clear transition to having availability of DHM, there was a 10% increase in breast milk feeding at NICU discharge and a concomitant 2.6% decrease in NEC rates. The availability of DHM has increased over time and has been associated with positive changes including increased breast milk feeding at NICU discharge and decrease in NEC rates. Copyright © 2016 by the American Academy of Pediatrics.

  15. Probiotic Supplementation in Preterm Infants Does Not Affect the Risk of Bronchopulmonary Dysplasia: A Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Mosca, Fabio; Kramer, Boris

    2017-01-01

    Probiotic supplementation reduces the risk of necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) in preterm infants, but it remains to be determined whether this reduction translates into a reduction of other complications. We conducted a systematic review and meta-analysis to evaluate the possible role of probiotics in altering the risk of bronchopulmonary dysplasia (BPD). Fifteen randomized controlled trials (4782 infants; probiotics: 2406) were included. None of the included studies assessed BPD as the primary outcome. Meta-analysis confirmed a significant reduction of NEC (risk ratio (RR) 0.52, 95% confidence interval (CI) 0.33 to 0.81, p = 0.004; random effects model), and an almost significant reduction of LOS (RR 0.82, 95% CI 0.65 to 1.03, p = 0.084). In contrast, meta-analysis could not demonstrate a significant effect of probiotics on BPD, defined either as oxygen dependency at 28 days of life (RR 1.01, 95% CI 0.91 to 1.11, p = 0.900, 6 studies) or at 36 weeks of postmenstrual age (RR 1.07, 95% CI 0.96 to 1.20, p = 0.203, 12 studies). Meta-regression did not show any significant association between the RR for NEC or LOS and the RR for BPD. In conclusion, our results suggest that NEC and LOS prevention by probiotics does not affect the risk of developing BPD in preterm infants. PMID:29088103

  16. Morbidity and Mortality in Preterm Infants following Antacid Use: A Retrospective Audit

    PubMed Central

    Dhayade, Aparna

    2016-01-01

    Background and Objectives. Antacids are often prescribed to preterm infants due to misdiagnosis of gastro-oesophageal reflux. This suppresses gastric acidity, a major defence mechanism against infection. This study aims to determine if ranitidine and omeprazole use in very low birth weight (VLBW) neonates, <1500 grams, is associated with increased risk of late onset sepsis, necrotising enterocolitis (NEC), and mortality. Methods. Retrospective analysis was conducted on neonates, <1500 grams, born and admitted into the Neonatal Intensive Care Unit at The Canberra Hospital during the period from January 2008 to December 2012. Information regarding late onset sepsis, NEC, mortality, ranitidine/omeprazole use, and other neonatal/hospital factors was collected for each neonate. Results. 360 neonates were evaluated, 64 received ranitidine and/or omeprazole, and 296 had not. There were no statistically significant differences in incidence of late onset sepsis (OR = 0.52, CI = 0.24–1.1, and p = 0.117), NEC Stage 2 and above (OR = 0.4, CI = 0.05–3.2, and p = 0.7), or mortality (OR = 0.35, CI = 0.08–1.5, and p = 0.19) between the two groups. After adjusting significant differences in neonatal and hospital factors, risk of late onset sepsis was significantly lower in those that received ranitidine/omeprazole (OR = 0.28, CI = 0.13–0.65, and p = 0.003). Conclusions. Ranitidine and omeprazole use in VLBW preterm infants may not be associated with an increased risk of infection, NEC, and mortality. PMID:27990166

  17. Vital signs and their cross-correlation in sepsis and NEC: a study of 1,065 very-low-birth-weight infants in two NICUs.

    PubMed

    Fairchild, Karen D; Lake, Douglas E; Kattwinkel, John; Moorman, J Randall; Bateman, David A; Grieve, Philip G; Isler, Joseph R; Sahni, Rakesh

    2017-02-01

    Subtle changes in vital signs and their interactions occur in preterm infants prior to overt deterioration from late-onset septicemia (LOS) or necrotizing enterocolitis (NEC). Optimizing predictive algorithms may lead to earlier treatment. For 1,065 very-low-birth-weight (VLBW) infants in two neonatal intensive care units (NICUs), mean, SD, and cross-correlation of respiratory rate, heart rate (HR), and oxygen saturation (SpO 2 ) were analyzed hourly (131 infant-years' data). Cross-correlation (cotrending) between two vital signs was measured allowing a lag of ± 30 s. Cases of LOS and NEC were identified retrospectively (n = 186) and vital sign models were evaluated for ability to predict illness diagnosed in the ensuing 24 h. The best single illness predictor within and between institutions was cross-correlation of HR-SpO 2 . The best combined model (mean SpO 2 , SDHR, and cross-correlation of HR-SpO 2 ,) trained at one site with ROC area 0.695 had external ROC area of 0.754 at the other site, and provided additive value to an established HR characteristics index for illness prediction (Net Reclassification Improvement: 0.205; 95% confidence interval (CI): 0.113, 0.328). Despite minor inter-institutional differences in vital sign patterns of VLBW infants, cross-correlation of HR-SpO 2 and a 3-variable vital sign model performed well at both centers for preclinical detection of sepsis or NEC.

  18. Vital signs and their cross-correlation in sepsis and NEC: A study of 1065 very low birth weight infants in two NICUs

    PubMed Central

    Fairchild, Karen D.; Lake, Douglas E.; Kattwinkel, John; Moorman, J. Randall; Bateman, David A; Grieve, Philip G; Isler, Joseph R; Sahni, Rakesh

    2016-01-01

    Background Subtle changes in vital signs and their interactions occur in preterm infants prior to overt deterioration from late-onset septicemia (LOS) or necrotizing enterocolitis (NEC). Optimizing predictive algorithms may lead to earlier treatment. Methods For 1065 very low birth weight (VLBW) infants in two NICUs, mean, SD, and cross-correlation of respiratory rate, heart rate (HR), and oxygen saturation (SpO2) were analyzed hourly (131 infant-years’ data). Cross-correlation (co-trending) between two vital signs was measured allowing a lag of +/− 30 seconds. Cases of LOS and NEC were identified retrospectively (n=186) and vital sign models were evaluated for ability to predict illness diagnosed in the ensuing 24h. Results The best single illness predictor within and between institutions was cross-correlation of HR-SpO2. The best combined model (mean SpO2, SD HR, and cross correlation of HR-SpO2,) trained at one site with ROC area 0.695 had external ROC area of 0.754 at the other site, and provided additive value to an established HR characteristics index for illness prediction (Net Reclassification Improvement 0.25, 95% CI 0.113, 0.328). Conclusion Despite minor inter-institutional differences in vital sign patterns of VLBW infants, cross-correlation of HR-SpO2 and a 3-variable vital sign model performed well at both centers for preclinical detection of sepsis or NEC. PMID:28001143

  19. Randomized trial of exclusive human milk versus preterm formula diets in extremely premature infants.

    PubMed

    Cristofalo, Elizabeth A; Schanler, Richard J; Blanco, Cynthia L; Sullivan, Sandra; Trawoeger, Rudolf; Kiechl-Kohlendorfer, Ursula; Dudell, Golde; Rechtman, David J; Lee, Martin L; Lucas, Alan; Abrams, Steven

    2013-12-01

    To compare the duration of parenteral nutrition, growth, and morbidity in extremely premature infants fed exclusive diets of either bovine milk-based preterm formula (BOV) or donor human milk and human milk-based human milk fortifier (HUM), in a randomized trial of formula vs human milk. Multicenter randomized controlled trial. The authors studied extremely preterm infants whose mothers did not provide their milk. Infants were fed either BOV or an exclusive human milk diet of pasteurized donor human milk and HUM. The major outcome was duration of parenteral nutrition. Secondary outcomes were growth, respiratory support, and necrotizing enterocolitis (NEC). Birth weight (983 vs 996 g) and gestational age (27.5 vs 27.7 wk), in BOV and HUM, respectively, were similar. There was a significant difference in median parenteral nutrition days: 36 vs 27, in BOV vs HUM, respectively (P = .04). The incidence of NEC in BOV was 21% (5 cases) vs 3% in HUM (1 case), P = .08; surgical NEC was significantly higher in BOV (4 cases) than HUM (0 cases), P = .04. In extremely preterm infants given exclusive diets of preterm formula vs human milk, there was a significantly greater duration of parenteral nutrition and higher rate of surgical NEC in infants receiving preterm formula. This trial supports the use of an exclusive human milk diet to nourish extremely preterm infants in the neonatal intensive care unit. Copyright © 2013 Mosby, Inc. All rights reserved.

  20. A meta-analysis of probiotics for preventing necrotizing enterocolitis in preterm neonates

    PubMed Central

    Yang, Y.; Guo, Y.; Kan, Q.; Zhou, X.G.; Zhou, X.Y.; Li, Y.

    2014-01-01

    Necrotizing enterocolitis (NEC) is one of the most common acquired diseases of the gastrointestinal tract in preterm infants. Some randomized, controlled trials (RCTs) have indicated that probiotics may potentially lower the incidence of NEC and mortality. However, debate still remains about the safety of probiotics and their influence on normal infant growth. We performed this meta-analysis to assess the safety and benefits of probiotic supplementation in preterm infants. We searched in PubMed, Embase, and Cochrane databases for English references, and in Wanfang, VIP, and CNKI databases for Chinese references. Ultimately, 27 RCTs (including 9 Chinese articles) were incorporated into this meta-analysis. Relative risk (RR) and weighted mean difference (WMD) were calculated using a random-effects or fixed-effects model, depending on the data type and heterogeneity. A total of 6655 preterm infants, including the probiotic group (n=3298) and the placebo group (n=3357), were eligible for inclusion in this meta-analysis. For Bell stage ≥I and gestational age <37 weeks, risk of NEC incidence was significantly lower in the probiotic group [RR=0.35, 95% confidence interval (CI)=0.27-0.44, P<0.00001]. For Bell stage ≥II or gestational age <34 weeks, there were likewise significant differences between the probiotic and placebo groups concerning NEC incidence (RR=0.34, 95%CI=0.25-0.48, P<0.00001; and RR=0.39, 95%CI=0.27-0.56, P<0.00001). Risk of death was significantly reduced in the probiotic group (RR=0.58, 95%CI=0.46-0.75, P<0.0001). In contrast, there was no significant difference concerning the risk of sepsis (RR=0.94, 95%CI=0.83-1.06, P=0.31). With respect to weight gain and the age at which infants reached full feeds, no significant differences were found between the probiotic and placebo groups (WMD=1.07, 95%CI=−0.21-2.34, P=0.10; and WMD=−1.66, 95%CI=−3.6-0.27, P=0.09). This meta-analysis has shown that, regardless of gestational age and NEC stage, probiotic supplementation could significantly reduce the risk of NEC in preterm infants. Analysis also indicated that such supplementation did not increase the incidence risk of sepsis or of mortality. Finally, the study showed that probiotic supplementation may have no adverse effect on normal feeding and growth. PMID:25098619

  1. Avian leucocyte counting using the hemocytometer

    USGS Publications Warehouse

    Dein, F.J.; Wilson, A.; Fischer, D.; Langenberg, P.

    1994-01-01

    Automated methods for counting leucocytes in avian blood are not available because of the presence of nucleated erythrocytes and thrombocytes. Therefore, total white blood cell counts are performed by hand using a hemocytometer. The Natt and Herrick and the Unopette methods are the most common stain and diluent preparations for this procedure. Replicate hemocytometer counts using these two methods were performed on blood from four birds of different species. Cells present in each square of the hemocytometer were counted. Counting cells in the corner, side, or center hemocytometer squares produced statistically equivalent results; counting four squares per chamber provided a result similar to that obtained by counting nine squares; and the Unopette method was more precise for hemocytometer counting than was the Natt and Herrick method. The Unopette method is easier to learn and perform but is an indirect process, utilizing the differential count from a stained smear. The Natt and Herrick method is a direct total count, but cell identification is more difficult.

  2. Minásbate Equivalents of Mathematical Concepts: Their Socio-Cultural Undertones

    ERIC Educational Resources Information Center

    Balbuena, Sherwin E.; Cantoria, Uranus E.; Cantoria, Amancio L., Jr.; Ferriol, Eny B.

    2015-01-01

    This paper presents the collection and analysis of Minásbate equivalents of some concepts used in the study of arithmetic, counting, and geometry as provided by the elderly residents of the province of Masbate. The glossary of mathematical terms derived from interviews would serve as an authoritative reference for mother tongue teachers in the…

  3. Risk Factors for Discharge from the Army with a Permanent Disability

    DTIC Science & Technology

    2007-07-01

    Sarcoidosis 182 8.86% 496.0 Chronic Airway Obstruction, NEC 61 2.97% 518.8 Other Diseases of Lung 40 1.95% 519.1 Other Diseases of the Trachea and...135 Sarcoidosis 50 8.24% 112.0 Candidiasis of Mouth 20 3.29% 785.6 Enlargement of Lymph Nodes 19 3.13% V67.5 Treatment Follow-up NEC 19 3.13...Unspecified 27 (1.90%) 414.0 Coronary Atherosclerosis 381 (2.41%) 719.47 Pain in Joint, Ankle and Foot 600 (2.04%) 135 Sarcoidosis

  4. Change of name for the Oriental robber fly Nyssomyia Hull, 1962 (Diptera: Asilidae, Asilinae), nec Nyssomyia Barretto, 1962 (Diptera: Psychodidae, Phlebotominae).

    PubMed

    Ibáñez-Bernal, Sergio; Fisher, Eric

    2015-08-14

    A new name for the Oriental genus Nyssomyia Hull, 1962 (Diptera: Asilidae) is proposed. Homonymy exists between this Oriental robber fly genus and the more senior Neotropical phlebotomine sand fly genus Nyssomyia Barretto, 1962 (sensu Galati 2003) (Diptera: Psychodidae), and the following replacement name is proposed: Ekkentronomyia nom. nov. for Nyssomyia Hull (nec Barretto 1962). Accordingly, a new combination is herein proposed for the only species currently included in this genus: Ekkentronomyia ochracea (Hull, 1962) comb. nov.

  5. Enterocytozoon bieneusi Genotypes in Children in Northeast China and Assessment of Risk of Zoonotic Transmission

    PubMed Central

    Yang, Jinping; Song, Mingxin; Wan, Qiang; Li, Yijing; Lu, Yixin; Jiang, Yanxue; Tao, Wei

    2014-01-01

    The prevalence (7.5%, 19/255) and genotypes of Enterocytozoon bieneusi in children of various age categories and clinical presentations were determined herein. The co-occurrence of the known genotypes (CS-4, EbpC, and Henan-IV) in children and pigs in the same study area, the phylogenetic characterization of novel genotypes (NEC1 to NEC5), and the assessment of potential risk factors associated with zoonotic transmission robustly suggested that pigs could be a significant source of human E. bieneusi infections in northeast China. PMID:25274994

  6. Review of Reports on Lake Erie - Lake Ontario Waterway, New York. Appendix D. Economics.

    DTIC Science & Technology

    1973-10-01

    Venezuela (29 percent). Canada produced 48.3 million tons of iron ore in 1970 ,of which 23.9 million tons were exported to the United States (14.4 million...grain traffic, 1971 D-14 D-6 U.S. - Great Lakes grain exports 1960 - 1971 and projected D-15 D-7 U.S. doal traffic, Lake Erie - Lake Ontario, 1958-1970...Soybeans Wheat Barley Oats Rice Sorghum Grains Flaxseed Oilseeds, n.e.c. Tobacco, leaf Hay and Fodder Field crops, n.e.c. Fresh fruits Co ffee Cocoa beans

  7. Comparison of bacterial counts obtained from naturally contaminated foods by means of Stomacher and blender.

    PubMed

    Purvis, U; Sharpe, A N; Bergener, D M; Lachapelle, G; Milling, M; Spiring, F

    1987-01-01

    Four Regional Health Protection Branch laboratories each compared aerobic colony counts obtained after "stomaching" and blending, for a minimum of 10 samples in each of the seven food groups: dry pastas; chocolate and cocoa powders; frozen entrees (macaroni and cheese, chow mein, chop suey, fried rice, seafood casseroles, and Salisbury steak); nonfat dry milk; shrimp and crabmeats; spices; and breakfast sausages. Overall, counts obtained after using the Stomacher were equivalent to or higher than counts obtained after using the blender in 73% of the comparisons (alpha = 0.05). Where differences existed, counts obtained after using the Stomacher tended to be higher than counts obtained after using the blender from milk powder and lower from sausage. Aerobic colony counts from these foods are not unacceptably biased when obtained by Stomacher.

  8. Assessment of the application of an automated electronic milk analyzer for the enumeration of total bacteria in raw goat milk.

    PubMed

    Ramsahoi, L; Gao, A; Fabri, M; Odumeru, J A

    2011-07-01

    Automated electronic milk analyzers for rapid enumeration of total bacteria counts (TBC) are widely used for raw milk testing by many analytical laboratories worldwide. In Ontario, Canada, Bactoscan flow cytometry (BsnFC; Foss Electric, Hillerød, Denmark) is the official anchor method for TBC in raw cow milk. Penalties are levied at the BsnFC equivalent level of 50,000 cfu/mL, the standard plate count (SPC) regulatory limit. This study was conducted to assess the BsnFC for TBC in raw goat milk, to determine the mathematical relationship between the SPC and BsnFC methods, and to identify probable reasons for the difference in the SPC:BsnFC equivalents for goat and cow milks. Test procedures were conducted according to International Dairy Federation Bulletin guidelines. Approximately 115 farm bulk tank milk samples per month were tested for inhibitor residues, SPC, BsnFC, psychrotrophic bacteria count, composition (fat, protein, lactose, lactose and other solids, and freezing point), and somatic cell count from March 2009 to February 2010. Data analysis of the results for the samples tested indicated that the BsnFC method would be a good alternative to the SPC method, providing accurate and more precise results with a faster turnaround time. Although a linear regression model showed good correlation and prediction, tests for linearity indicated that the relationship was linear only beyond log 4.1 SPC. The logistic growth curve best modeled the relationship between the SPC and BsnFC for the entire sample population. The BsnFC equivalent to the SPC 50,000 cfu/mL regulatory limit was estimated to be 321,000 individual bacteria count (ibc)/mL. This estimate differs considerably from the BsnFC equivalent for cow milk (121,000 ibc/mL). Because of the low frequency of bulk tank milk pickups at goat farms, 78.5% of the samples had their oldest milking in the tank to be 6.5 to 9.0 d old when tested, compared with the cow milk samples, which had their oldest milking at 4 d old when tested. This may be one of the major factors contributing to the larger goat milk BsnFC equivalence. Correlations and interactions between various test results were also discussed to further understand differences between the 2 methods for goat and cow milks. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  9. Performance evaluation of the Ingenuity TF PET/CT scanner with a focus on high count-rate conditions

    NASA Astrophysics Data System (ADS)

    Kolthammer, Jeffrey A.; Su, Kuan-Hao; Grover, Anu; Narayanan, Manoj; Jordan, David W.; Muzic, Raymond F.

    2014-07-01

    This study evaluated the positron emission tomography (PET) imaging performance of the Ingenuity TF 128 PET/computed tomography (CT) scanner which has a PET component that was designed to support a wider radioactivity range than is possible with those of Gemini TF PET/CT and Ingenuity TF PET/MR. Spatial resolution, sensitivity, count rate characteristics and image quality were evaluated according to the NEMA NU 2-2007 standard and ACR phantom accreditation procedures; these were supplemented by additional measurements intended to characterize the system under conditions that would be encountered during quantitative cardiac imaging with 82Rb. Image quality was evaluated using a hot spheres phantom, and various contrast recovery and noise measurements were made from replicated images. Timing and energy resolution, dead time, and the linearity of the image activity concentration, were all measured over a wide range of count rates. Spatial resolution (4.8-5.1 mm FWHM), sensitivity (7.3 cps kBq-1), peak noise-equivalent count rate (124 kcps), and peak trues rate (365 kcps) were similar to those of the Gemini TF PET/CT. Contrast recovery was higher with a 2 mm, body-detail reconstruction than with a 4 mm, body reconstruction, although the precision was reduced. The noise equivalent count rate peak was broad (within 10% of peak from 241-609 MBq). The activity measured in phantom images was within 10% of the true activity for count rates up to those observed in 82Rb cardiac PET studies.

  10. A large surface photomultiplier based on SiPMs

    NASA Astrophysics Data System (ADS)

    Barbarino, Giancarlo; de Asmundis, Riccardo; De Rosa, Gianfranca; Vivolo, Daniele; Mollo, Carlos Maximiliano

    2013-10-01

    Light detection through photosensitive devices represents one of the key issues for a large variety of experiments. In the recent years, Silicon PhotoMultipliers (SiPMs) based on limited Geiger-mode avalanche have been extensively studied in view of their future applications. However, their use is strongly limited by their small sensitive surfaces and by the fact that any increment in the surface turns out into an increase of the dark count rate. In the present work we describe the dark count rate reduction obtained by using a FPGA-based logical circuit for fast pre-processing of pulses from a 3×3 matrix of SiPMs. The prototype we developed supports two SiPMs: we show that a rate reduction from 6.6 Mcps (Mega counts per second) down to 0.436 Mcps at the lowest threshold (0.5 photon-equivalent) and from 1.2 kcps down to 0.02 cps for the highest threshold (3.5 photon-equivalent) is obtainable.

  11. Immature oxidative stress management as a unifying principle in the pathogenesis of necrotizing enterocolitis: insights from an agent-based model.

    PubMed

    Kim, Moses; Christley, Scott; Alverdy, John C; Liu, Donald; An, Gary

    2012-02-01

    Necrotizing enterocolitis (NEC) is a complex disease involving prematurity, enteral feeding, and bacterial effects. We propose that the underlying initial condition in its pathogenesis is reduced ability of the neonatal gut epithelial cells (NGECs) to clear oxidative stress (OS), and that when such a NGEC population is exposed to enteral feeding, the increased metabolic OS tips the population toward apoptosis, inflammation, bacterial activation, and eventual necrosis. The multi-factorial complexity of NEC requires characterization with computational modeling, and herein, we used an agent-based model (ABM) to instantiate and examine our unifying hypothesis of the pathogenesis of NEC. An ABM of the neonatal gut was created with NGEC computational agents incorporating rules for pathways for OS, p53, tight junctions, Toll-like receptor (TLR)-4, nitric oxide, and nuclear factor-kappa beta (NF-κB). The modeled bacteria activated TLR-4 on contact with NGECs. Simulations included parameter sweeps of OS response, response to feeding, addition of bacteria, and alterations in gut mucus production. The ABM reproduced baseline cellular respiration and clearance of OS. Reduction in OS clearance consistent with clinical NEC led to senescence, apoptosis, or inflammation, with disruption of tight junctions, but rarely to NGEC necrosis. An additional "hit" of bacteria activating TLR-4 potentiated a shift to NGEC necrosis across the entire population. The mucus layer was modeled to limit bacterial-NGEC interactions and reduce this effect, but concomitant apoptosis in the goblet cell population reduced the efficacy of the mucus layer and limited its protective effect in simulated experiments. This finding suggests a means by which increased apoptosis at the cellular population level can lead to a transition to the necrosis outcome. Our ABM incorporates known components of NEC and demonstrates that impaired OS management can lead to apoptosis and inflammation of NGECs, rendering the system susceptible to an additional insult involving regionalized mucus barrier failure and TLR-4 activation, which potentiates the necrosis outcome. This type of integrative dynamic knowledge representation can be a useful adjunct to help guide and contextualize research.

  12. Mercury biomagnification in food webs of the northeastern Chukchi Sea, Alaskan Arctic

    NASA Astrophysics Data System (ADS)

    Fox, Austin L.; Trefry, John H.; Trocine, Robert P.; Dunton, Kenneth H.; Lasorsa, Brenda K.; Konar, Brenda; Ashjian, Carin J.; Cooper, Lee W.

    2017-10-01

    Predictive tools and a large new dataset for the northeastern Chukchi Sea (NECS) are used here to help identify regional differences and potential future shifts in the magnitude of Hg biomagnification in the Arctic. At the base of the food web in the NECS, concentrations of total mercury (THg) in phytoplankton (20-μm mesh) ranged from 4-42 ng g-1 dry weight, partly in response to variations in algal biomass and water temperature. A >3-fold increase in monomethylmercury (MMHg) was observed in zooplankton (4.3±0.7 ng g-1) relative to phytoplankton (<1.5 ng g-1), even though concentrations of THg in zooplankton (150-μm mesh) were not significantly different than in phytoplankton. Concentrations and % MMHg increased with trophic level (TL) by >150-fold and from <10 to >85%, respectively, from phytoplankton to muscle in the whelk Plicifusus kroeyeri (279 ng g-1, TL 4.5). For muscle tissue in 10 species plus whole phytoplankton and zooplankton, the trophic magnification slope (TMS) for MMHg (log10[MMHg]=m(δ15N)+b; where m=TMS) was 0.23±0.02 (SE). No significant differences in TMS were found for the NECS plus three other studies from the eastern Canadian Arctic (average TMS=0.24±0.02). Nevertheless, all data for MMHg in biota from the NECS plotted below the combined best fit line for all four studies. Results from an ANCOVA showed that statistically different (p=0.001) intercept values (b), not TMS, best explained the >2-fold lower concentrations of MMHg in biota from the NECS (b=-1.85) relative to the same species from the eastern Canadian Arctic (b=-1.29). Future changes that affect bioaccumulation of MMHg in the Arctic may impact the biomagnification equation by shifting the TMS, intercept or both. The intercept is more likely to respond to changes in productivity and concentrations of dissolved Hg whereas the TMS may respond to changing growth rates due to fluctuations in productivity and food availability. In either case, small changes in the intercept or TMS coincide with predictably large increases or decreases in MMHg concentrations in apex predators.

  13. Combined use of alcohol hand rub and gloves reduces the incidence of late onset infection in very low birthweight infants.

    PubMed

    Ng, P C; Wong, H L; Lyon, D J; So, K W; Liu, F; Lam, R K Y; Wong, E; Cheng, A F B; Fok, T F

    2004-07-01

    To assess the incidence of late onset (> 72 hours) infection and necrotising enterocolitis (NEC) in very low birthweight (VLBW) infants in two 36 month periods using two hand hygiene protocols: conventional handwashing (HW; first 36 month period); an alcohol hand rub and gloves technique (HR; second 36 month period). VLBW infants admitted to the neonatal intensive care unit during the period December 1993-November 1999 were eligible. A new hand hygiene protocol using alcohol handrub and gloves was introduced in December 1996. Each patient's case record was reviewed retrospectively by two independent investigators using a standard data collection form. The incidence of NEC and systemic infections, including bacterial or fungal septicaemia, meningitis, and peritonitis, in the two periods were compared. The HW and HR groups contained 161 and 176 VLBW infants respectively. The incidence of late onset systemic infection decreased from 13.5 to 4.8 episodes (including NEC)/1000 patient days after introduction of the HR regimen, representing a 2.8-fold reduction. Similarly, the incidence of Gram positive, Gram negative, and fungal infections decreased 2.5-fold, 2.6-fold, and 7-fold respectively. There was also a significant reduction in the incidence of NEC in the HR group (p < 0.0001). Subgroup analysis revealed that the incidence of methicillin resistant Staphylococcus aureus (MRSA) septicaemia was significantly decreased in the second 36 month period (p = 0.048). The clinical data suggest that infants in the HW group had significantly earlier onset of sepsis (p < 0.05) and required oxygen supplementation for longer (p < 0.05) than those in the HR group. Significantly more VLBW infants were discharged from the neonatal intensive care unit without ever being infected (p < 0.0001), and also significantly fewer infants had more than one episode of infection in the HR group (p < 0.0001). The introduction of the HR protocol was associated with a 2.8-fold reduction in the incidence of late onset systemic infection, and also a significant decrease in the incidence of MRSA septicaemia and NEC in VLBW infants. This decrease in infection rate was maintained throughout the second 36 month period.

  14. Effect of electro-acupuncture intervention on cognition attention bias in heroin addiction abstinence-a dot-probe-based event-related potential study.

    PubMed

    Jiang, Ying-Ping; Liu, Hao; Xu, Ping; Wang, Yan; Lu, Guang-Hua

    2011-04-01

    To study the changes of cognitive attention-related brain function in the heroin addicts before and after electro-acupuncture (EA) intervention for exploring the concerned neuro-mechanism of addictive relapse and the central action role of EA intervention. Adopting event-related potential (ERP) technique, the ERP at 64 electrode spots in 10 heroin addicts (test group) were recorded before and after EA intervention with dot-probe experimental form during implementing cognitive task on positive emotional clue (PEC), negative emotional clues (NEC), and heroin-related clue (HRC). The P200 amplitude components on the selected observation points (Fz, Cz, and Pz) were analyzed and compared with those obtained from 10 healthy subjects as the control. Before EA, the ERP of attention on HRC in the test group was higher than that on PEC and NEC (P<0.05) and significantly higher than that in the control group (P<0.05); after EA, the P200 amplitude of attention on HRC at Cz and Pz was significantly lowered (P<0.05) and that on PEC at Fz was significantly elevated (P<0.05). After EA, the P200 amplitude at Pz was ranked as NEC > PEC > HRC, but in the control group, it showed PEC > HRC at all three observation points and PEC > NEC at Pz. Heroin addicts show attention bias to HRC, which could be significantly reduced by EA intervention, illustrating that EA could effectively inhibit the attention bias to heroin and so might have potential for lowering the relapse rate.

  15. Conditioned medium from Bifidobacteria infantis protects against Cronobacter sakazakii-induced intestinal inflammation in newborn mice

    PubMed Central

    Weng, Meiqian; Ganguli, Kriston; Zhu, Weishu; Shi, Hai Ning

    2014-01-01

    Necrotizing enterocolitis (NEC) is associated with a high morbidity and mortality in very low birth weight infants. Several hypotheses regarding the pathogenesis of NEC have been proposed but to date no effective treatment is available. Previous studies suggest that probiotic supplementation is protective. We recently reported that probiotic (Bifidobacterium infantis) conditioned medium (PCM) has an anti-inflammatory effect in cultured fetal human intestinal cells (H4) and fetal intestine explants. In this study, we tested in vivo whether PCM protects neonatal mice from developing intestinal inflammation induced by exposure to Cronobacter sakazakii (C. sakazakii), an opportunistic pathogen associated with NEC. We found that infected neonatal mice had a significantly lower body weight than control groups. Infection led to ileal tissue damage including villous rupture, disruption of epithelial cell alignment, intestinal inflammation, apoptotic cell loss, and decreased mucus production. Pretreatment with PCM prevented infection caused decrease in body weight, attenuated enterocyte apoptotic cell death, mitigated reduced mucin production, and maintained ileal structure. Infected ileum expressed reduced levels of IκBα, which could be restored upon pretreatment with PCM. We also observed a nuclear translocation of NF-κB p65 in H4 cells exposed to C. sakazakii, which was prevented in PCM-pretreated cells. Finally, treatment of neonatal mice with PCM prior to infection sustained the capacity of ileal epithelial proliferation. This study suggests that an active component(s) released into the culture medium by B. infantis may prevent ileal damage by a pathogen linked to NEC. PMID:24627567

  16. The role of RIP3 mediated necroptosis in ouabain-induced spiral ganglion neurons injuries.

    PubMed

    Wang, Xi; Wang, Ye; Ding, Zhong-jia; Yue, Bo; Zhang, Peng-zhi; Chen, Xiao-dong; Chen, Xin; Chen, Jun; Chen, Fu-quan; Chen, Yang; Wang, Ren-feng; Mi, Wen-juan; Lin, Ying; Wang, Jie; Qiu, Jian-hua

    2014-08-22

    Spiral ganglion neuron (SGN) injury is a generally accepted precursor of auditory neuropathy. Receptor-interacting protein 3 (RIP3) has been reported as an important necroptosis pathway mediator that can be blocked by necrostatin-1 (Nec-1). In our study, we sought to identify whether necroptosis participated in SGN injury. Ouabain was applied to establish an SGN injury model. We measured the auditory brain-stem response (ABR) threshold shift as an indicator of the auditory conditions. Positive β3-tubulin immunofluorescence staining indicated the surviving SGNs. RIP3 expression was evaluated using immunofluorescence, quantitative real-time polymerase chain reaction and western blot. SGN injury promoted an increase in RIP3 expression that could be suppressed by application of the necroptosis inhibitor Nec-1. A decreased ABR threshold shift and increased SGN density were observed when Nec-1 was administered with apoptosis inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD). These results demonstrated that necroptosis is an indispensable pathway separately from apoptosis leading to SGN death pathway, in which RIP3 plays an important role. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Radiocarbon variability recorded in coral skeletons from the northwest of Luzon Island, Philippines

    NASA Astrophysics Data System (ADS)

    Hirabayashi, Shoko; Yokoyama, Yusuke; Suzuki, Atsushi; Miyairi, Yosuke; Aze, Takahiro; Siringan, Fernando; Maeda, Yasuo

    2017-12-01

    The North Equatorial Current (NEC) bifurcates at the eastern coast of the Philippines and moves northward as the Kuroshio, a North Pacific western boundary current. The NEC bifurcation point and Kuroshio variability are known to be affected by changes in climate such as the El Niño-Southern Oscillation and the pacific decadal oscillation. However, observational data are not sufficient to examine the mechanisms of decadal fluctuation. Here, we report seasonal radiocarbon data recorded from 1968 to 1995 in coral skeletons northwest of Luzon Island. The data suggest that the East Asian winter monsoon is a dominant factor in the seasonal fluctuations in water mass northwest of Luzon Island. Compared with other coral records reported for Guam, Ishigaki, Con Dao, and Hon Tre Island, the data suggest that the area of the Kuroshio loop current through the Luzon Strait decreased from the 1970s to 1980s as a result of the change in Kuroshio transport and the migration of the NEC bifurcation latitude after a regime shift in 1976.

  18. PPAR-{gamma} agonist protects against intestinal injury during necrotizing enterocolitis

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

    Baregamian, Naira; Mourot, Joshua M.; Ballard, Amie R.

    2009-02-06

    Necrotizing enterocolitis (NEC) remains a lethal condition for many premature infants. Peroxisome proliferator-activated receptor-{gamma} (PPAR-{gamma}), a member of the nuclear hormone receptor family, has been shown to play a protective role in cellular inflammatory responses; however, its role in NEC is not clearly defined. We sought to examine the expression of PPAR-{gamma} in the intestine using an ischemia-reperfusion (I/R) model of NEC, and to assess whether PPAR-{gamma} agonist treatment would ameliorate I/R-induced gut injury. Swiss-Webster mice were randomized to receive sham (control) or I/R injury to the gut induced by transient occlusion of superior mesenteric artery for 45 min withmore » variable periods of reperfusion. I/R injury resulted in early induction of PPAR-{gamma} expression and activation of NF-{kappa}B in small intestine. Pretreatment with PPAR-{gamma} agonist, 15d-PGJ{sub 2}, attenuated intestinal NF-{kappa}B response and I/R-induced gut injury. Activation of PPAR-{gamma} demonstrated a protective effect on small bowel during I/R-induced gut injury.« less

  19. Impact of oral probiotics on neurodevelopmental outcomes in preterm infants.

    PubMed

    Akar, Melek; Eras, Zeynep; Oncel, Mehmet Yekta; Arayici, Sema; Guzoglu, Nilufer; Canpolat, Fuat Emre; Uras, Nurdan; Oguz, Serife Suna

    2017-02-01

    The aim of the study was to evaluate the neurodevelopment outcomes of very low birth weight (VLBW) preterm infants supplemented with oral probiotics for the prevention of necrotizing enterocolitis (NEC). A prospective follow-up study was performed in a cohort of VLBW preterm infants enrolled in a single center randomized controlled clinical trial to evaluate the efficacy of oral probiotics for the prevention of NEC. Cognitive and neuromotor developments were assessed by using the Bayley scales of infant development II. Sensory and neurological performance was evaluated by standard techniques. The primary outcome was neurodevelopmental impairment at 18-24 months' corrected age. A total of 400 infants completed the trial protocol. Of the 370 infants eligible for follow-up, 249 infants (124 in the probiotics group and 125 in the control group) were evaluated. There was no significant difference in any of the neurodevelopmental and sensory outcomes between the two groups. Oral probiotic given to VLBW infants to reduce the incidense and severity of NEC started with the first feed did not affect neuromotor, neurosensory and cognitive outcomes at 18-24 months' corrected age.

  20. Spectroscopic evidence for negative electronic compressibility in a quasi-three-dimensional spin–orbit correlated metal

    DOE PAGES

    He, Junfeng; Hogan, T.; Mion, Thomas R.; ...

    2015-04-27

    Negative compressibility is a sign of thermodynamic instability of open1,2,3 or non-equilibrium4,5 systems. In quantum materials consisting of multiple mutually coupled subsystems, the compressibility of one subsystem can be negative if it is countered by positive compressibility of the others. Manifestations of this effect have so far been limited to low-dimensional dilute electron systems6,7,8,9,10,11. Here, we present evidence from angle-resolved photoemission spectroscopy (ARPES) for negative electronic compressibility (NEC) in the quasi-three-dimensional (3D) spin–orbit correlated metal (Sr1-xLax)3Ir2O7. Increased electron filling accompanies an anomalous decrease of the chemical potential, as indicated by the overall movement of the deep valence bands. Such anomaly,more » suggestive of NEC, is shown to be primarily driven by the lowering in energy of the conduction band as the correlated bandgap reduces. Our finding points to a distinct pathway towards an uncharted territory of NEC featuring bulk correlated metals with unique potential for applications in low-power nanoelectronics and novel metamaterials.« less

  1. Human milk is the feeding strategy to prevent necrotizing enterocolitis!

    PubMed

    Maffei, Diana; Schanler, Richard J

    2017-02-01

    Human milk is the preferred diet for preterm infants as it protects against a multitude of NICU challenges, specifically necrotizing enterocolitis. Infants who receive greater than 50% of mother's own milk (MOM) in the 2 weeks after birth have a significantly decreased risk of NEC. An additional factor in the recent declining rates of NEC is the increased utilization of donor human milk (DHM). This creates a bridge until MOM is readily available, thus decreasing the exposure to cow milk protein. Preterm infants are susceptible to NEC due to the immaturity of their gastrointestinal and immune systems. An exclusive human milk diet compensates for these immature systems in many ways such as lowering gastric pH, enhancing intestinal motility, decreasing epithelial permeability, and altering the composition of bacterial flora. Ideally, preterm infants should be fed human milk and avoid bovine protein. A diet consisting of human milk-based human milk fortifier is one way to provide the additional nutritional supplements necessary for adequate growth while receiving the protective benefits of a human milk diet. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Primary Neuroendocrine Breast Carcinoma in a 13-Year-Old Girl: Ultrasonography and Pathology Findings

    PubMed Central

    Folligan, Koué; Sabi, Akomola; Sonhaye, Lantam; Boumé, Azanledji; Bassowa, Akila; Adani-Ifé, Solange; Napo-Koura, Gado

    2017-01-01

    Neuroendocrine carcinoma (NEC) of the breast is a rare disease and has been scarcely reported by African authors. The authors report a case of breast NEC in a 13-year-old African girl initially diagnosed as an atypical adenofibroma by ultrasonography. Ultrasound-guided biopsy and conventional histological examination indicated two potential diagnoses: primary malignant non-Hodgkin's lymphoma and undifferentiated carcinoma. According to immunohistochemistry performed on paraffin blocks in France, infiltrating ductal carcinoma with a strong neuroendocrine component was confirmed by CD56, CD57, and chromogranin A markers. PMID:29082059

  3. Performance Evaluation of Supercomputers using HPCC and IMB Benchmarks

    NASA Technical Reports Server (NTRS)

    Saini, Subhash; Ciotti, Robert; Gunney, Brian T. N.; Spelce, Thomas E.; Koniges, Alice; Dossa, Don; Adamidis, Panagiotis; Rabenseifner, Rolf; Tiyyagura, Sunil R.; Mueller, Matthias; hide

    2006-01-01

    The HPC Challenge (HPCC) benchmark suite and the Intel MPI Benchmark (IMB) are used to compare and evaluate the combined performance of processor, memory subsystem and interconnect fabric of five leading supercomputers - SGI Altix BX2, Cray XI, Cray Opteron Cluster, Dell Xeon cluster, and NEC SX-8. These five systems use five different networks (SGI NUMALINK4, Cray network, Myrinet, InfiniBand, and NEC IXS). The complete set of HPCC benchmarks are run on each of these systems. Additionally, we present Intel MPI Benchmarks (IMB) results to study the performance of 11 MPI communication functions on these systems.

  4. Necrotizing enterocolitis: Pathophysiology from a historical context.

    PubMed

    Hackam, David; Caplan, Michael

    2018-02-01

    Necrotizing enterocolitis (NEC) continues to afflict approximately 7% of preterm infants born weighing less than 1500g, though recent investigations have provided novel insights into the pathogenesis of this complex disease. The disease has been a major cause of morbidity and mortality in neonatal intensive care units worldwide for many years, and our current understanding reflects exceptional observations made decades ago. In this review, we will describe NEC from a historical context and summarize seminal findings that underscore the importance of enteral feeding, the gut microbiota, and intestinal inflammation in this complex pathophysiology. Copyright © 2018. Published by Elsevier Inc.

  5. Equivalence of truncated count mixture distributions and mixtures of truncated count distributions.

    PubMed

    Böhning, Dankmar; Kuhnert, Ronny

    2006-12-01

    This article is about modeling count data with zero truncation. A parametric count density family is considered. The truncated mixture of densities from this family is different from the mixture of truncated densities from the same family. Whereas the former model is more natural to formulate and to interpret, the latter model is theoretically easier to treat. It is shown that for any mixing distribution leading to a truncated mixture, a (usually different) mixing distribution can be found so that the associated mixture of truncated densities equals the truncated mixture, and vice versa. This implies that the likelihood surfaces for both situations agree, and in this sense both models are equivalent. Zero-truncated count data models are used frequently in the capture-recapture setting to estimate population size, and it can be shown that the two Horvitz-Thompson estimators, associated with the two models, agree. In particular, it is possible to achieve strong results for mixtures of truncated Poisson densities, including reliable, global construction of the unique NPMLE (nonparametric maximum likelihood estimator) of the mixing distribution, implying a unique estimator for the population size. The benefit of these results lies in the fact that it is valid to work with the mixture of truncated count densities, which is less appealing for the practitioner but theoretically easier. Mixtures of truncated count densities form a convex linear model, for which a developed theory exists, including global maximum likelihood theory as well as algorithmic approaches. Once the problem has been solved in this class, it might readily be transformed back to the original problem by means of an explicitly given mapping. Applications of these ideas are given, particularly in the case of the truncated Poisson family.

  6. Antibiotic Therapy for Very Low Birth Weigh Newborns in NICU

    PubMed Central

    Afjeh, Seyyed-Abolfazl; Sabzehei, Mohammad-Kazem; Fahimzad, Seyyed-Ali-Reza; Shiva, Farideh; Shamshiri, Ahmad-Reza; Esmaili, Fatemeh

    2016-01-01

    Background Prolonged empiric antibiotics therapy in neonates results in several adverse consequences including widespread antibiotic resistance, late onset sepsis (LOS), necrotizing enterocolitis (NEC), prolonged hospital course (HC) and increase in mortality rates. Objectives To assess the risk factors and the outcome of prolonged empiric antibiotic therapy in very low birth weight (VLBW) newborns. Materials and Methods Prospective study in VLBW neonates admitted to NICU and survived > 2 W, from July 2011 - June 2012. All relevant perinatal and postnatal data including duration of antibiotics therapy (Group I < 2W vs Group II > 2W) and outcome up to the time of discharge or death were documented and compared. Results Out of 145 newborns included in the study, 62 were in group I, and 83 in Group II. Average duration of antibiotic therapy was 14 days (range 3 - 62 days); duration in Group I and Group II was 10 ± 2.3 vs 25.5 ± 10.5 days. Hospital stay was 22.3 ± 11.5 vs 44.3 ± 14.7 days, respectively. Multiple regression analysis revealed following risk factors as significant for prolonged empiric antibiotic therapy: VLBW especially < 1000 g, (P < 0.001), maternal Illness (P = 0.003), chorioamnionitis (P = 0.048), multiple pregnancy (P = 0.03), non-invasive ventilation (P < 0.001) and mechanical ventilation (P < 0.001). Seventy (48.3%) infants developed LOS; 5 with NEC > stage II, 12 (8.3%) newborns died. Infant mortality alone and with LOS/NEC was higher in group II as compared to group I (P < 0.002 and < 0.001 respectively). Conclusions Prolonged empiric antibiotic therapy caused increasing rates of LOS, NEC, HC and infant mortality. PMID:27307961

  7. Thalamocortical neurons display suppressed burst-firing due to an enhanced Ih current in a genetic model of absence epilepsy.

    PubMed

    Cain, Stuart M; Tyson, John R; Jones, Karen L; Snutch, Terrance P

    2015-06-01

    Burst-firing in distinct subsets of thalamic relay (TR) neurons is thought to be a key requirement for the propagation of absence seizures. However, in the well-regarded Genetic Absence Epilepsy Rats from Strasbourg (GAERS) model as yet there has been no link described between burst-firing in TR neurons and spike-and-wave discharges (SWDs). GAERS ventrobasal (VB) neurons are a specific subset of TR neurons that do not normally display burst-firing during absence seizures in the GAERS model, and here, we assessed the underlying relationship of VB burst-firing with Ih and T-type calcium currents between GAERS and non-epileptic control (NEC) animals. In response to 200-ms hyperpolarizing current injections, adult epileptic but not pre-epileptic GAERS VB neurons displayed suppressed burst-firing compared to NEC. In response to longer duration 1,000-ms hyperpolarizing current injections, both pre-epileptic and epileptic GAERS VB neurons required significantly more hyperpolarizing current injection to burst-fire than those of NEC animals. The current density of the Hyperpolarization and Cyclic Nucleotide-activated (HCN) current (Ih) was found to be increased in GAERS VB neurons, and the blockade of Ih relieved the suppressed burst-firing in both pre-epileptic P15-P20 and adult animals. In support, levels of HCN-1 and HCN-3 isoform channel proteins were increased in GAERS VB thalamic tissue. T-type calcium channel whole-cell currents were found to be decreased in P7-P9 GAERS VB neurons, and also noted was a decrease in CaV3.1 mRNA and protein levels in adults. Z944, a potent T-type calcium channel blocker with anti-epileptic properties, completely abolished hyperpolarization-induced VB burst-firing in both NEC and GAERS VB neurons.

  8. Survival and Morbidity Outcomes of Very Low Birth Weight Infants with Down Syndrome

    PubMed Central

    Boghossian, Nansi S.; Hansen, Nellie I.; Bell, Edward F.; Stoll, Barbara J.; Murray, Jeffrey C.; Laptook, Abbot R.; Shankaran, Seetha; Walsh, Michele C.; Das, Abhik; Higgins, Rosemary D.

    2010-01-01

    OBJECTIVE Individuals with Down syndrome (DS) are at increased risk of several morbidities with lifelong health consequences. Little is known about mortality or morbidity risks in early infancy among very-low-birth-weight (VLBW) infants with DS. Our objective was to compare survival and neonatal morbidities between VLBW infants with DS and VLBW infants with other non-DS chromosomal anomalies, other non-chromosomal birth defects, and VLBW infants without major birth defects. METHODS Data were collected prospectively for infants weighing 401-1500 grams born and/or cared for at one of the study centers participating in the NICHD Neonatal Research Network from 1994 through 2008. Risk of death and morbidities including patent ductus arteriosus (PDA), necrotizing enterocolitis (NEC), late onset sepsis (LOS), retinopathy of prematurity (ROP), and bronchopulmonary dysplasia (BPD), were compared between VLBW infants with DS and infants in the other groups. RESULTS Infants with DS were at increased risk of death (adjusted relative risk [RR] 2.47, 95% confidence interval [CI] 2.00-3.07), PDA, NEC, LOS, and BPD relative to infants with no birth defects. Decreased risk of death (RR 0.40, 95% CI 0.31-0.52) and increased risks of NEC and LOS were observed when comparing infants with DS to infants with other non-DS chromosomal anomalies. Relative to infants with non-chromosomal birth defects, infants with DS were at increased risk of PDA and NEC. CONCLUSION The increased risk of morbidities among VLBW infants with DS provides useful information for counseling parents and for caretakers in anticipating the need for enhanced surveillance for prevention of these morbidities. PMID:21098157

  9. Antibiotic exposure in neonates and early adverse outcomes: a systematic review and meta-analysis.

    PubMed

    Esaiassen, Eirin; Fjalstad, Jon Widding; Juvet, Lene Kristine; van den Anker, John N; Klingenberg, Claus

    2017-07-01

    To systematically review and meta-analyse the relationship between antibiotic exposure in neonates and the following early adverse outcomes: necrotizing enterocolitis (NEC), invasive fungal infections (IFIs) and/or death. Data sources were PubMed, Embase, Medline and the Cochrane Database (to December 2016), supplemented by manual searches of reference lists. Randomized controlled trials (RCTs) and observational studies were included if they provided data on different categories of antibiotic exposures (yes versus no, long versus short duration, and/or broad- versus narrow-spectrum regimens) and the risk of developing NEC, IFI and/or death in the neonatal period. Two reviewers extracted data and evaluated the risk of bias using the Cochrane Handbook, adapted to include observational studies. When appropriate, meta-analyses were conducted using the random-effect model. We identified 9 RCTs and 38 observational studies. The quality of the majority of studies was poor to moderate. There was a significant association between prolonged antibiotic exposure and an increased risk of NEC in five observational studies (5003 participants) and/or risk of death in five observational studies (13 534 participants). Eleven of 15 studies with data on broad- versus narrow-spectrum regimens reported an increased risk of IFI after broad-spectrum antibiotic exposure, in particular with third-generation cephalosporins and carbapenems. Meta-analysis was limited by few and old RCTs, insufficient sample sizes and diversity of antibiotic exposure and outcomes reported. Prolonged antibiotic exposure in uninfected preterm infants is associated with an increased risk of NEC and/or death, and broad-spectrum antibiotic exposure is associated with an increased risk of IFI. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Necrotizing enterocolitis, a rare but severe condition with insidious postoperative complications.

    PubMed

    Bălălău, C; Motofei, I; Voiculescu, S; Popa, F; Scăunaşu, R V

    2013-01-01

    Necrotizing enterocolitis (NEC) is one of the most frequent causes of gastrointestinal perforation in premature neonates, only few case series and reports being described in adult patients. Early in the course of the disease, superficial mucosal ulceration, sub mucosal edema and hemorrhage occur. Further progression leads to transmural necrosis leading sometimes to bowel perforation. Six cases encountered in our clinic in recent years led us to resume discussions on necrotizing enteritis, not because it is a rare disease, but due to the severe postoperative complications. Our lot consisted of four stage 1 patients and two with Bell stage III NEC and severe intestinal injury, necrosis, and perforation. All of the patients were diagnosed preoperatory with other surgical conditions, like appendicitis with peritonitis, perforated duodenal ulcer or acute cholecystitis. We present to review two cases. For patients undergoing laparotomy, resection of the involved intestine mandates either enterostomy formation or primary anastomosis. An intermediate option is laparotomy with intestinal resection and delayed anastomosis 48 to 72 hours later. Because of the small number of patients in our lot, we cannot advise a certain surgical treatment, but a strategy involving bienterostomyper primam should be further analyzed. The choice of operative intervention reflects multiple variables, including age, physiologic status, institutional resources and surgeon preference based on experience. Primary peritoneal drainage for perforated NEC may help to resuscitate and treat a critically ill patient initially, and in some instances, may be definitive operative intervention. Relatively rare disease, of unknown etiology and elusive pathogenesis, NEC has initial non-specific symptoms and clinical features that mimic more common surgical diseases. There is considerable controversy regarding which procedure is preferable. Currently, in the absence of rigorous evidence supporting the superiority of one approach over the other, surgical intervention depends mostly on the treating institution or the individual surgeon.

  11. Right service, right place: optimising utilisation of a community nursing service to reduce planned re-presentations to the emergency department.

    PubMed

    Lawton, Jessica Kirsten; Kinsman, Leigh; Dalton, Lisa; Walsh, Fay; Bryan, Helen; Williams, Sharon

    2017-01-01

    Congruent with international rising emergency department (ED) demand, a focus on strategies and services to reduce burden on EDs and improve patient outcomes is necessary. Planned re-presentations of non-urgent patients at a regional Australian hospital exceeded 1200 visits during the 2013-2014 financial year. Planned re-presentations perpetuate demand and signify a lack of alternative services for non-urgent patients. The Community Nursing Enhanced Connections Service (CoNECS) collaboratively evolved between acute care and community services in 2014 to reduce planned ED re-presentations. This study aimed to investigate the evolution and impact of a community nursing service to reduce planned re-presentations to a regional Australian ED and identify enablers and barriers to interventionist effectiveness. A mixed-methods approach evaluated the impact of CoNECS. Data from hospital databases including measured numbers of planned ED re-presentations by month, time of day, age, gender and reason were used to calculate referral rates to CoNECS. These results informed two semistructured focus groups with ED and community nurses. The researchers used a theoretical lens, 'diffusion of innovation', to understand how this service could inform future interventions. Analyses showed that annual ED planned re-presentations decreased by 43% (527 presentations) after implementation. Three themes emerged from the focus groups. These were right service at the right time, nursing uncertainty and system disconnect and medical disengagement. CoNECS reduced overall ED planned re-presentations and was sustained longer than many complex service-level interventions. Factors supporting the service were endorsement from senior administration and strong leadership to drive responsive quality improvement strategies. This study identified a promising alternative service outside the ED, highlighting possibilities for other hospital emergency services aiming to reduce planned re-presentations.

  12. Eleostearic acid induces RIP1-mediated atypical apoptosis in a kinase-independent manner via ERK phosphorylation, ROS generation and mitochondrial dysfunction

    PubMed Central

    Obitsu, S; Sakata, K; Teshima, R; Kondo, K

    2013-01-01

    RIP1 is a serine/threonine kinase, which is involved in apoptosis and necroptosis. In apoptosis, caspase-8 and FADD have an important role. On the other hand, RIP3 is a key molecule in necroptosis. Recently, we reported that eleostearic acid (ESA) elicits caspase-3- and PARP-1-independent cell death, although ESA-treated cells mediate typical apoptotic morphology such as chromatin condensation, plasma membrane blebbing and apoptotic body formation. The activation of caspases, Bax and PARP-1, the cleavage of AIF and the phosphorylation of histone H2AX, all of which are characteristics of typical apoptosis, do not occur in ESA-treated cells. However, the underlying mechanism remains unclear. To clarify the signaling pathways in ESA-mediated apoptosis, we investigated the functions of RIP1, MEK, ERK, as well as AIF. Using an extensive study based on molecular biology, we identified the alternative role of RIP1 in ESA-mediated apoptosis. ESA mediates RIP1-dependent apoptosis in a kinase independent manner. ESA activates serine/threonine phosphatases such as calcineurin, which induces RIP1 dephosphorylation, thereby ERK pathway is activated. Consequently, localization of AIF and ERK in the nucleus, ROS generation and ATP reduction in mitochondria are induced to disrupt mitochondrial cristae, which leads to cell death. Necrostatin (Nec)-1 blocked MEK/ERK phosphorylation and ESA-mediated apoptosis. Nec-1 inactive form (Nec1i) also impaired ESA-mediated apoptosis. Nec1 blocked the interaction of MEK with ERK upon ESA stimulation. Together, these findings provide a new finding that ERK and kinase-independent RIP1 proteins are implicated in atypical ESA-mediated apoptosis. PMID:23788031

  13. Critical contribution of RIPK1 mediated mitochondrial dysfunction and oxidative stress to compression-induced rat nucleus pulposus cells necroptosis and apoptosis.

    PubMed

    Chen, Songfeng; Lv, Xiao; Hu, Binwu; Zhao, Lei; Li, Shuai; Li, Zhiliang; Qing, Xiangcheng; Liu, Hongjian; Xu, Jianzhong; Shao, Zengwu

    2018-04-28

    The aim of this study was to investigate whether RIPK1 mediated mitochondrial dysfunction and oxidative stress contributed to compression-induced nucleus pulposus (NP) cells necroptosis and apoptosis, together with the interplay relationship between necroptosis and apoptosis in vitro. Rat NP cells underwent various periods of 1.0 MPa compression. To determine whether compression affected mitochondrial function, we evaluated the mitochondrial membrane potential, mitochondrial permeability transition pore (mPTP), mitochondrial ultrastructure and ATP content. Oxidative stress-related indicators reactive oxygen species, superoxide dismutase and malondialdehyde were also assessed. To verify the relevance between oxidative stress and necroptosis together with apoptosis, RIPK1 inhibitor necrostatin-1(Nec-1), mPTP inhibitor cyclosporine A (CsA), antioxidants and small interfering RNA technology were utilized. The results established that compression elicited a time-dependent mitochondrial dysfunction and elevated oxidative stress. Nec-1 and CsA restored mitochondrial function and reduced oxidative stress, which corresponded to decreased necroptosis and apoptosis. CsA down-regulated mitochondrial cyclophilin D expression, but had little effects on RIPK1 expression and pRIPK1 activation. Additionally, we found that Nec-1 largely blocked apoptosis; whereas, the apoptosis inhibitor Z-VAD-FMK increased RIPK1 expression and pRIPK1 activation, and coordinated regulation of necroptosis and apoptosis enabled NP cells survival more efficiently. In contrast to Nec-1, SiRIPK1 exacerbated mitochondrial dysfunction and oxidative stress. In summary, RIPK1-mediated mitochondrial dysfunction and oxidative stress play a crucial role in NP cells necroptosis and apoptosis during compression injury. The synergistic regulation of necroptosis and apoptosis may exert more beneficial effects on NP cells survival, and ultimately delaying or even retarding intervertebral disc degeneration.

  14. The "Golden Age" of Probiotics: A Systematic Review and Meta-Analysis of Randomized and Observational Studies in Preterm Infants.

    PubMed

    Dermyshi, Elda; Wang, Yizhong; Yan, Chongbin; Hong, Wenchao; Qiu, Gang; Gong, Xiaohui; Zhang, Ting

    2017-01-01

    Over the last few years, probiotics have been one of the most studied interventions in neonatal medicine. The aim of this work was to analyse all studies (randomized controlled trials, RCTs, and observational studies) assessing the use of probiotics in very low birth weight (VLBW) preterm infants. A systematic literature search was conducted using PubMed, Embase, Cochrane Library, and Web of Science. The data from RCTs and observational studies were pooled and analysed separately. RCTs and observational studies that enrolled VLBW infants with enteral administration of probiotics were considered. Extracted study data included probiotic characteristics and at least 1 clinical outcome (necrotizing enterocolitis [NEC], late-onset sepsis or all-cause mortality). Forty-four studies were eligible for our review: 30 RCTs and 14 observational studies. Severe NEC rates (stage II or more) and all-cause mortality were reduced among the probiotic groups in both the RCTs (RR 0.57, 95% CI 0.47-0.70, and RR 0.77, 95% CI 0.65-0.92, respectively) and the observational studies (RR 0.51, 95% CI 0.37-0.70, and RR 0.71, 95% CI 0.62-0.81, respectively). Furthermore, there was a 12% reduction in the risk of sepsis in RCTs and a 19% reduction in observational studies. The meta-analysis of observational studies showed a reduction in the risk of NEC in extremely low birth weight infants. However, this was not statistically significant. This meta-analysis of RCT and observational studies found that the use of probiotics was beneficial for the prevention of severe NEC, late-onset sepsis, and all-cause mortality in VLBW infants. © 2017 S. Karger AG, Basel.

  15. Prognostic Evaluations Tailored to Specific Gastric Neuroendocrine Neoplasms: Analysis Of 200 Cases with Extended Follow-Up.

    PubMed

    Vanoli, Alessandro; La Rosa, Stefano; Miceli, Emanuela; Klersy, Catherine; Maragliano, Roberta; Capuano, Francesca; Persichella, Andrea; Martino, Michele; Inzani, Frediano; Luinetti, Ombretta; Di Sabatino, Antonio; Sessa, Fausto; Paulli, Marco; Corazza, Gino Roberto; Rindi, Guido; Bordi, Cesare; Capella, Carlo; Solcia, Enrico

    2018-06-12

    Gastric neuroendocrine neoplasms (NENs) are very heterogeneous, ranging from mostly indolent, atrophic gastritis-associated, type I neuroendocrine tumors (NETs), through highly malignant, poorly differentiated neuroendocrine carcinomas (pdNECs), to sporadic type III NETs with intermediate prognosis, and various rare tumor types. Histologic differentiation, proliferative grade, size, level of gastric wall invasion, and local or distant metastases are used as prognostic markers. However, their value remains to be tailored to specific gastric NENs. Series of type I NETs (n = 123 cases), type III NETs (n = 34 cases), and pdNECs (n = 43 cases) were retrospectively collected from four pathology centers specializing in endocrine pathology. All cases were characterized clinically and histopathologically. During follow-up (median 93 months) data were recorded to assess disease-specific patient survival. Type I NETs, type III NETs, and pdNECs differed markedly in terms of tumor size, grade, invasive and metastatic power, as well as patient outcome. Size was used to stratify type I NETs into subgroups with significantly different invasive and metastatic behavior. All 70 type I NETs < 0.5 cm (micro-NETs) were uneventful. Ki67-based grading proved efficient for the prognostic stratification of type III NETs; however, grade 2 (G2) was not associated with tumor behavior in type I NETs. Although G3 NETs (2 type I and 9 type III) had a very poor prognosis, it was found that patient survival was longer with type III G3 NETs compared to pdNECs. Given the marked, tumor type-related behavior differences, evaluation of gastric NEN prognostic parameters should be tailored to the type of neoplastic disease. © 2018 S. Karger AG, Basel.

  16. MLN4924 sensitizes monocytes and maturing dendritic cells for TNF-dependent and -independent necroptosis.

    PubMed

    El-Mesery, Mohamed; Seher, Axel; Stühmer, Thorsten; Siegmund, Daniela; Wajant, Harald

    2015-03-01

    MLN4924 prevents the formation of active cullin-RING ubiquitin ligase complexes and thus inhibits NF-κB signalling. Here, we evaluated the effects of this compound on monocytes and dendritic cells (DCs). Monocytes and DCs were challenged with TNF or LPS in the presence and absence of MLN4924. The effects of MLN4924 on cellular viability, pro-inflammatory gene induction and DC maturation were investigated using the MTT assay, elisa and FACS analysis. Mechanisms of cell death induction were evaluated by using inhibitors of caspases, RIPK1 and MLKL. MLN4924 inhibited NF-κB activation and sensitized monocytes and immature DCs (iDCs) for TNFR1-induced cell death. Neither the caspase inhibitor zVAD-fmk, the RIPK1 inhibitor necrostatin-1 (nec-1) nor the MLKL inhibitor necrosulfonamide (NSA) alone prevented TNF-induced cell death. A combination of zVAD-fmk and nec-1 or NSA, however, rescued monocytes and iDCs from MLN4924/TNF-induced cell death indicating that MLN4924 affects anti-apoptotic and anti-necrotic activities in TNFR1 signalling. MLN4924 also converted the response of iDCs to LPS from maturation to cell death. LPS-induced cell death in MLN4924-treated iDCs was again only effectively blocked by cotreatment with zVAD-fmk and nec-1 or NSA. Noteworthy, MLN4924/LPS-induced cell death was almost completely independent of endogenous TNF. MLN4924 also strongly inhibited maturation and activation of iDCs that were rescued from cell death by zVAD-fmk and nec-1. Our data reveal a strong dual suppressive effect of MLN4924 on DC activity. The targeting of NAE by MLN4924 could be a new way to treat inflammatory diseases. © 2014 The British Pharmacological Society.

  17. Enumerating bone marrow blasts from nonerythroid cellularity improves outcome prediction in myelodysplastic syndromes and permits a better definition of the intermediate risk category of the Revised International Prognostic Scoring System (IPSS-R).

    PubMed

    Calvo, Xavier; Arenillas, Leonor; Luño, Elisa; Senent, Leonor; Arnan, Montserrat; Ramos, Fernando; Pedro, Carme; Tormo, Mar; Montoro, Julia; Díez-Campelo, María; Blanco, María Laura; Arrizabalaga, Beatriz; Xicoy, Blanca; Bonanad, Santiago; Jerez, Andrés; Nomdedeu, Meritxell; Ferrer, Ana; Sanz, Guillermo F; Florensa, Lourdes

    2017-07-01

    The Revised International Prognostic Scoring System (IPSS-R) has been recognized as the score with the best outcome prediction capability in MDS, but this brought new concerns about the accurate prognostication of patients classified into the intermediate risk category. The correct enumeration of blasts is essential in prognostication of MDS. Recent data evidenced that considering blasts from nonerythroid cellularity (NECs) improves outcome prediction in the context of IPSS and WHO classification. We assessed the percentage of blasts from total nucleated cells (TNCs) and NECs in 3924 MDS patients from the GESMD, 498 of whom were MDS with erythroid predominance (MDS-E). We assessed if calculating IPSS-R by enumerating blasts from NECs improves prognostication of MDS. Twenty-four percent of patients classified into the intermediate category were reclassified into higher-risk categories and showed shorter overall survival (OS) and time to AML evolution than those who remained into the intermediate one. Likewise, a better distribution of patients was observed, since lower-risk patients showed longer survivals than previously whereas higher-risk ones maintained the outcome expected in this poor prognostic group (median OS < 20 months). Furthermore, our approach was particularly useful for detecting patients at risk of dying with AML. Regarding MDS-E, 51% patients classified into the intermediate category were reclassified into higher-risk ones and showed shorter OS and time to AML. In this subgroup of MDS, IPSS-R was capable of splitting our series in five groups with significant differences in OS only when blasts were assessed from NECs. In conclusion, our easy-applicable approach improves prognostic assessment of MDS patients. © 2017 Wiley Periodicals, Inc.

  18. Nuclear emulsion measurements of the astronauts' radiation exposure on the Apollo-Soyuz mission

    NASA Technical Reports Server (NTRS)

    Schaefer, H. J.; Sullivan, J. J.

    1976-01-01

    On the Apollo-Soyuz mission each astronaut carried one passive dosimeter containing nuclear photographic emulsions, plastic foils, TLD chips, and neutron-activation foils for recording radiation exposure. This report is limited to the presentation of data retrieved from nuclear emulsions. Protons, most of them trapped particles encountered in numerous passes through the South Atlantic Anomaly, contributed by far the largest share to the mission dose. Their linear energy transfer (LET) spectrum was established from track and grain counts in a G.5 emulsion which is used for medium and high energies, and from ender counts in a K.2 emulsion which is used for low energies. The total mission fluence of protons was found to be equivalent to a unidirectional beam of 448,500 square centimeters. The broad spectrum was broken down into small LET intervals, which allowed for the computation of absorbed doses and dose equivalents. The totals are 51 millirad and 74 millirem. Counts of disintegration stars in K.2 emulsion are incomplete at present. While a total of 467 stars were identified, counting their prong numbers is still in progress. It was concluded that the Apollo-Soyuz astronauts' radiation exposure as such did not contain anything out of the ordinary that would seem to require special attention.

  19. Influence of electrolytes in the QCM response: discrimination and quantification of the interference to correct microgravimetric data.

    PubMed

    Encarnação, João M; Stallinga, Peter; Ferreira, Guilherme N M

    2007-02-15

    In this work we demonstrate that the presence of electrolytes in solution generates desorption-like transients when the resonance frequency is measured. Using impedance spectroscopy analysis and Butterworth-Van Dyke (BVD) equivalent electrical circuit modeling we demonstrate that non-Kanazawa responses are obtained in the presence of electrolytes mainly due to the formation of a diffuse electric double layer (DDL) at the sensor surface, which also causes a capacitor like signal. We extend the BVD equivalent circuit by including additional parallel capacitances in order to account for such capacitor like signal. Interfering signals from electrolytes and DDL perturbations were this way discriminated. We further quantified as 8.0+/-0.5 Hz pF-1 the influence of electrolytes to the sensor resonance frequency and we used this factor to correct the data obtained by frequency counting measurements. The applicability of this approach is demonstrated by the detection of oligonucleotide sequences. After applying the corrective factor to the frequency counting data, the mass contribution to the sensor signal yields identical values when estimated by impedance analysis and frequency counting.

  20. Adaptation of the TH Epsilon Mu formalism for the analysis of the equivalence principle in the presence of the weak and electroweak interaction

    NASA Technical Reports Server (NTRS)

    Fennelly, A. J.

    1981-01-01

    The TH epsilon mu formalism, used in analyzing equivalence principle experiments of metric and nonmetric gravity theories, is adapted to the description of the electroweak interaction using the Weinberg-Salam unified SU(2) x U(1) model. The use of the TH epsilon mu formalism is thereby extended to the weak interactions, showing how the gravitational field affects W sub mu (+ or -1) and Z sub mu (0) boson propagation and the rates of interactions mediated by them. The possibility of a similar extension to the strong interactions via SU(5) grand unified theories is briefly discussed. Also, using the effects of the potentials on the baryon and lepton wave functions, the effects of gravity on transition mediated in high-A atoms which are electromagnetically forbidden. Three possible experiments to test the equivalence principle in the presence of the weak interactions, which are technologically feasible, are then briefly outline: (1) K-capture by the FE nucleus (counting the emitted X-ray); (2) forbidden absorption transitions in high-A atoms' vapor; and (3) counting the relative Beta-decay rates in a suitable alpha-beta decay chain, assuming the strong interactions obey the equivalence principle.

  1. SIRIUS - A new 6 MV accelerator system for IBA and AMS at ANSTO

    NASA Astrophysics Data System (ADS)

    Pastuovic, Zeljko; Button, David; Cohen, David; Fink, David; Garton, David; Hotchkis, Michael; Ionescu, Mihail; Long, Shane; Levchenko, Vladimir; Mann, Michael; Siegele, Rainer; Smith, Andrew; Wilcken, Klaus

    2016-03-01

    The Centre for Accelerator Science (CAS) facility at ANSTO has been expanded with a new 6 MV tandem accelerator system supplied by the National Electrostatic Corporation (NEC). The beamlines, end-stations and data acquisition software for the accelerator mass spectrometry (AMS) were custom built by NEC for rare isotope mass spectrometry, while the beamlines with end-stations for the ion beam analysis (IBA) are largely custom designed at ANSTO. An overview of the 6 MV system and its performance during testing and commissioning phase is given with emphasis on the IBA end-stations and their applications for materials modification and characterisation.

  2. Probiotics and Necrotizing Enterocolitis: Finding the Missing Pieces of the Probiotic Puzzle

    PubMed Central

    Luedtke, Sherry A.; Yang, Jacob T.; Wild, Heather E.

    2012-01-01

    Necrotizing enterocolitis (NEC) is one of the leading causes of death in the neonatal intensive care unit. Morbidity and mortality rates significantly increase with decreases in gestational age and birth weight. Strong evidence suggests probiotic prophylaxis may significantly decrease the incidence of NEC and should therefore be incorporated into the standard of care for preterm infants. However, debate still remains because of limitations of completed studies. The purpose of this review was to provide an overview of the controversies regarding probiotic use in preterm infants and to shed light on the practical considerations for implementation of probiotic supplementation. PMID:23412969

  3. Strategies for prevention of feed intolerance in preterm neonates: a systematic review.

    PubMed

    Patole, Sanjay

    2005-07-01

    Postnatal growth restriction and failure to thrive have been recently identified as a major issue in preterm, especially extremely-low-birth-weight neonates. An increased length of time to reach full enteral feedings is also significantly associated with a poorer mental outcome in preterm neonates at 24 months corrected age. Optimization of enteral nutrition without increasing the risk of necrotizing enterocolitis (NEC) has thus become a priority in preterm neonates. A range of feeding strategies currently exists for preventing/minimizing feed intolerance in preterm neonates reflecting the dilemma surrounding the definition and significance of signs of feed intolerance due to ileus of prematurity and the fear of NEC. The results of a systematic review of current strategies for preventing/minimizing feed intolerance in preterm neonates are discussed. The need for clinical research in the area of signs of feed intolerance is emphasized to develop a scientific basis to feeding strategies. Only large pragmatic trials based on such strategies will reveal whether the benefits (improved growth and long term neurodevelopmental outcomes) of aggressive enteral nutrition can outweigh the risks of a potentially devastating illness like NEC, and of prolonged parenteral nutrition in preterm neonates.

  4. Permanent molar pulpotomy with a new endodontic cement: A case series

    PubMed Central

    Asgary, Saeed; Ehsani, Sara

    2009-01-01

    The aim of this case series was to determine the clinical and radiographic success rate of pulpotomy, with new endodontic cement (NEC), in human mature permanent molar teeth. Twelve molars with established irreversible pulpitis were selected from patients 14 – 62 years old. The selection criteria included carious pulp exposure with a positive history of lingering pain. After isolation, caries removal, and pulp exposure, pulpotomy with NEC was performed and a permanent restoration was immediately placed. At the first recall (+1 day) no patients reported postoperative pain. One wisdom tooth had been extracted after two months because of failure in coronal restoration. Eleven patients were available for the second recall, with a mean time of 15.8 months. Clinical and radiographic examination revealed that all teeth were functional and free of signs and symptoms. Histological examination of the extracted teeth revealed complete dentin bridge formation and a normal pulp. Although the results favored the use of NEC, more studies with larger samples and a longer recall period were suggested, to justify the use of this novel material for treatment of irreversible pulpitis in human permanent molar teeth. PMID:20379438

  5. Intestinal flora in very low-birth weight infants.

    PubMed

    Björkström, Markus V; Hall, Lina; Söderlund, Stina; Håkansson, Eva Grahn; Håkansson, Stellan; Domellöf, Magnus

    2009-11-01

    To study the early faecal microbiota in very low-birth weight infants (VLBW, <1500 g), possible associations between faecal microbiota and faecal calprotectin (f-calprotectin) and to describe the faecal microbiota in cases with necrotizing enterocolitis (NEC) before diagnosis. Stool samples from the first weeks of life were analysed in 48 VLBW infants. Bacterial cultures were performed and f-calprotectin concentrations were measured. In three NEC cases, cultures were performed on stool samples obtained before diagnosis. Bifidobacteria and lactobacilli were often identified in the first stool sample, 55% and 71% of cases, respectively within the first week of life. A positive correlation between lactic acid bacteria (LAB) and volume of enteral feed was found. Other bacteria often identified were Escherichia coli, Enterococcus and Staphyloccus sp. F-calprotectin was not associated with any bacterial species. All NEC cases had an early colonization of LAB. Prior to onset of disease, all cases had a high colonization of non-E. coli Gram-negative species. In contrast to the previous studies in VLBW infants, we found an early colonization with LAB. We speculate that this may be due to early feeding of non-pasteurized breast milk.

  6. Changes in plasma and urinary nitrite after birth in premature infants at risk for necrotizing enterocolitis

    PubMed Central

    Pun, Priti; Jones, Jesica; Wolfe, Craig; Deming, Douglas D.; Power, Gordon G.; Blood, Arlin B.

    2016-01-01

    Background Plasma nitrite serves as a reservoir of nitric oxide (NO) bioactivity. Because nitrite ingestion is markedly lower in newborns than adults, we hypothesized plasma nitrite levels would be lower in newborns than in adults, and that infants diagnosed with necrotizing enterocolitis (NEC), a disease characterized by ischemia and bacterial invasion of intestinal walls, would have lower levels of circulating nitrite in the days prior to diagnosis. Methods Single blood and urine samples were collected from 9 term infants and 12 adults, 72 preterm infants every 5 d for 3 wk, and from 13 lambs before and after cord occlusion. Results Nitrite fell 50% relative to cord levels in the first day after birth; and within 15 min after cord occlusion in lambs. Urinary nitrite was higher in infants than adults. Plasma and urinary nitrite levels in infants who developed NEC were similar to those of preterm control infants on days 1 and 5, but significantly elevated at 15 and 20 d after birth. Conclusion Plasma nitrite falls dramatically at birth while newborn urinary nitrite levels are significantly greater than adults. Acute NEC is associated with elevated plasma and urinary nitrite levels. PMID:26539663

  7. Readiness of ethics review systems for a changing public health landscape in the WHO African Region.

    PubMed

    Motari, Marion; Ota, Martin Okechukwu; Kirigia, Joses Muthuri

    2015-12-02

    The increasing emphasis on research, development and innovation for health in providing solutions to the high burden of diseases in the African Region has warranted a proliferation of studies including clinical trials. This changing public health landscape requires that countries develop adequate ethics review capacities to protect and minimize risks to study participants. Therefore, this study assessed the readiness of national ethics committees to respond to challenges posed by a globalized biomedical research system which is constantly challenged by new public health threats, rapid scientific and technological advancements affecting biomedical research and development, delivery and manufacture of vaccines and therapies, and health technology transfer. This is a descriptive study, which used a questionnaire structured to elicit information on the existence of relevant national legal frameworks, mechanisms for ethical review; as well as capacity requirements for national ethics committees. The questionnaire was available in English and French and was sent to 41 of the then 46 Member States of the WHO African Region, excluding the five Lusophone Member States. Information was gathered from senior officials in ministries of health, who by virtue of their offices were considered to have expert knowledge of research ethics review systems in their respective countries. Thirty three of the 41 countries (80.5 %) responded. Thirty (90.9 %) of respondent countries had a national ethics review committee (NEC); 79 % of which were established by law. Twenty-five (83.3 %) NECs had secretarial and administrative support. Over 50 % of countries with NECs indicated a need for capacity strengthening through periodic training on international guidelines for health research (including clinical trials) ethics; and allocation of funds for administrative and secretariat support. Despite the existing training initiatives, the Region still experiences a shortage of professionals trained in health research ethics/ethicists. Committees continue to face various capacity needs especially for evaluating clinical trials, for monitoring ongoing research, database management and for accrediting institutional ethics committees. Given the growing number of clinical trials involving human participants in the African Region, there is urgent need for supporting countries without NECs to establish them; capacity strengthening where they exist; and creation of a regional network and joint ethical review mechanisms, whose membership would be open to all NECs of the Region.

  8. Detection of Necroptosis in Ligand-Mediated and Hypoxia-Induced Injury of Hepatocytes Using a Novel Optic Probe Detecting Receptor-Interacting Protein (RIP)1/RIP3 Binding.

    PubMed

    Haga, Sanae; Kanno, Akira; Ozawa, Takeaki; Morita, Naoki; Asano, Mami; Ozaki, Michitaka

    2017-07-21

    Liver injury is often observed in various pathological conditions including posthepatectomy state and cancer chemotherapy. It occurs mainly as a consequence of the combined necrotic and apoptotic types of cell death. In order to study liver/hepatocyte injury by necrotic type of cell death, we studied signal-regulated necrosis (necroptosis) by newly developing an optic probe detecting receptor-interacting protein (RIP)1/RIP3 binding, an essential process for necroptosis induction. In the mouse hepatocyte cell line, TIB-73 cells, TNF-a/cycloheximide (T/C) induced RIP1/3 binding only when caspase activity was suppressed by z-VAD-fmk (zVAD), a caspase-specific inhibitor. T/C/zVADinduced RIP1/3-binding was inhibited by necrostatin-1 (Nec-1), an allosteric inhibitor of RIP1. The reduced cell survival by T/C/zVAD was improved by Nec-1. These facts indicate that T/C induces necroptosis of hepatocytes when apoptotic pathway is inhibited/unavailable. FasL also induced cell death which was only partially inhibited by zVAD, indicating the possible involvement of necroptosis other than apoptosis. FasL activated caspase-3 and, similarly, induced RIP1/3-binding when caspases were inactivated. Interestingly, FasL-induced RIP1/3 binding was significantly suppressed by the antioxidants, Trolox and N-acetyl cysteine (NAC), suggesting the involvement of reactive oxygen species (ROS) in FasL-induced necroptotic cellular processes. H₂O₂, by itself, induced RIP1/3 binding that was suppressed by Nec-1, but not by zVAD. Hypoxia induced RIP1/3 binding after reoxygenation, which was suppressed by Nec-1 or by the antioxidants. Cell death induced by hypoxia/reoxygenation (H/R) was also improved by Nec-1. Similar to H₂O₂, H/R did not require caspase inhibition for RIP1/3 binding, suggesting the involvement of a caspase-independent mechanism for non-ligand induced and/or redox-mediated necroptosis. These data indicate that ROS induce necroptosis, and mediate the FasL- and hypoxia-induced necroptosis via a molecular mechanism that differs from a conventional caspase-dependent pathway. In conclusion, necroptosis is potentially involved in liver/hepatocyte injury induced by oxidative stress and FasL, other than apoptosis.

  9. Starting points and pathways in Aboriginal students' learning of number: recognising different world views

    NASA Astrophysics Data System (ADS)

    Treacy, Kaye; Frid, Sandra; Jacob, Lorraine

    2015-09-01

    This research was designed to investigate the conceptualisations and thinking strategies Indigenous Australian students use in counting tasks. Eighteen Aboriginal students, in years 1 to 11 at a remote community school, were interviewed using standard counting tasks and a `counting' task that involved fetching `maku' (witchetty grubs) to have enough to give a maku to each person in a picture. The tasks were developed with, and the interviews conducted by, an Aboriginal research assistant, to ensure appropriate cultural and language contexts. A main finding was that most of the students did not see the need to use counting to make equivalent sets, even though they were able to demonstrate standard counting skills. The findings highlight a need to further examine the world views, orientations and related mathematical concepts and processes that Indigenous students bring to school.

  10. Radiation tolerance of readout electronics for Belle II

    NASA Astrophysics Data System (ADS)

    Higuchi, T.; Nakao, M.; Nakano, E.

    2012-02-01

    We plan to start the Belle II experiment in 2015 and to continue data taking for more than ten years. Because some of the front-end electronics cards of Belle II are located inside the detector, radiation effects onto their components will be a severe problem. Using experimental exposure facilities of neutrons and γ rays, we study the radiation effects from these particles to the Virtex-5 FPGA, optical transceivers, and voltage regulators. The Virtex-5 FPGA is found to keep its operation after irradiation of more than 20-year-equivalent neutron flux of Belle II and 88-year-equivalent γ-ray dose. We observe single event upsets (SEUs) and multiple bit upsets (MBUs) in the Virtex-5 FPGA in the neutron irradiation. We also find almost doubled SEU counts in the Virtex-5 FPGA bombarded from its tail side than its head side. We extrapolate the observed SEU and MBU counts in the Virtex-5 FPGA to the entire readout system of the Belle II central drift chamber, and expect the SEU and MBU rates as one SEU per four minutes and one MBU per 11.5 hours, respectively. The optical transceivers are found to keep its operation after integration of 12-year-equivalent neutron flux, while they are killed by about 3-year-equivalent γ-ray dose, which should be solved in the future research. The voltage regulators are found to keep its operation for more than 10-year-equivalent γ-ray dose.

  11. 24 CFR 572.220 - Implementation grants-matching requirements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... be counted toward the match. (6) Donated labor. All donated labor, including sweat equity provided by..., electricians, carpenters, and architects that is equivalent to work they do in their occupations. Sweat equity...

  12. 24 CFR 572.220 - Implementation grants-matching requirements.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... be counted toward the match. (6) Donated labor. All donated labor, including sweat equity provided by..., electricians, carpenters, and architects that is equivalent to work they do in their occupations. Sweat equity...

  13. 24 CFR 572.220 - Implementation grants-matching requirements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... be counted toward the match. (6) Donated labor. All donated labor, including sweat equity provided by..., electricians, carpenters, and architects that is equivalent to work they do in their occupations. Sweat equity...

  14. 24 CFR 572.220 - Implementation grants-matching requirements.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... be counted toward the match. (6) Donated labor. All donated labor, including sweat equity provided by..., electricians, carpenters, and architects that is equivalent to work they do in their occupations. Sweat equity...

  15. 24 CFR 572.220 - Implementation grants-matching requirements.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... be counted toward the match. (6) Donated labor. All donated labor, including sweat equity provided by..., electricians, carpenters, and architects that is equivalent to work they do in their occupations. Sweat equity...

  16. MO-G-17A-07: Improved Image Quality in Brain F-18 FDG PET Using Penalized-Likelihood Image Reconstruction Via a Generalized Preconditioned Alternating Projection Algorithm: The First Patient Results

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

    Schmidtlein, CR; Beattie, B; Humm, J

    2014-06-15

    Purpose: To investigate the performance of a new penalized-likelihood PET image reconstruction algorithm using the 1{sub 1}-norm total-variation (TV) sum of the 1st through 4th-order gradients as the penalty. Simulated and brain patient data sets were analyzed. Methods: This work represents an extension of the preconditioned alternating projection algorithm (PAPA) for emission-computed tomography. In this new generalized algorithm (GPAPA), the penalty term is expanded to allow multiple components, in this case the sum of the 1st to 4th order gradients, to reduce artificial piece-wise constant regions (“staircase” artifacts typical for TV) seen in PAPA images penalized with only the 1stmore » order gradient. Simulated data were used to test for “staircase” artifacts and to optimize the penalty hyper-parameter in the root-mean-squared error (RMSE) sense. Patient FDG brain scans were acquired on a GE D690 PET/CT (370 MBq at 1-hour post-injection for 10 minutes) in time-of-flight mode and in all cases were reconstructed using resolution recovery projectors. GPAPA images were compared PAPA and RMSE-optimally filtered OSEM (fully converged) in simulations and to clinical OSEM reconstructions (3 iterations, 32 subsets) with 2.6 mm XYGaussian and standard 3-point axial smoothing post-filters. Results: The results from the simulated data show a significant reduction in the 'staircase' artifact for GPAPA compared to PAPA and lower RMSE (up to 35%) compared to optimally filtered OSEM. A simple power-law relationship between the RMSE-optimal hyper-parameters and the noise equivalent counts (NEC) per voxel is revealed. Qualitatively, the patient images appear much sharper and with less noise than standard clinical images. The convergence rate is similar to OSEM. Conclusions: GPAPA reconstructions using the 1{sub 1}-norm total-variation sum of the 1st through 4th-order gradients as the penalty show great promise for the improvement of image quality over that currently achieved with clinical OSEM reconstructions.« less

  17. Quantitative isotopic measurements of gas-phase alcohol mixtures using a broadly tunable swept external cavity quantum cascade laser

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

    Brumfield, B. E.; Phillips, M. C.

    A swept-ECQCL is used for broadband IR spectroscopy of isotopic mixtures of CH3OH, CH3OD, CH3CH2OH, and CH3CH2OD in a static gas cell over a wavelength range of 9.5 to 10.4 µm. A weighted least squares fitting approach with quantitative library spectra illustrates that significant spectral congestion does not negatively impact the ability for in situ quantification of large isotopic species in a mixture. The noise equivalent concentrations for CH3OH, CH3OD, CH3CH2OH, and CH3CH2OD are 19 ppbv x m, 28 ppbv x m, 450 ppbv x m, and 330 ppbv x m respectively for a 50 second integration time. Based onmore » the observed NECs, isotopic precisions of 0.07‰ and 0.79‰ for a 50 s integration time are calculated for measurements of the [MeOD]/[MeOH] and [EtOD]/[EtOH] isotope ratios , respectively, for the species concentrations in the gas cell.« less

  18. Open issues on G3 neuroendocrine neoplasms: back to the future.

    PubMed

    Zatelli, Maria Chiara; Guadagno, Elia; Messina, Erika; Lo Calzo, Fabio; Faggiano, Antongiulio; Colao, Annamaria

    2018-06-01

    The recent recognition that grade 3 (G3) neuroendocrine neoplasms (NENs) can be divided into two different categories according to the histopathological differentiation, that is G3 neuroendocrine tumors (NETs) and G3 neuroendocrine carcinomas (NECs) has generated a lot of interest concerning not only the diagnosis, but also the differential management of such new group of NENs. However, several issues need to be fully clarified in order to put G3 NETs and G3 NECs in the right place. The aim of this review is to focus on those issues that are still undetermined starting from the current knowledge, evaluating the available evidence and the possible clinical implications. © 2018 Society for Endocrinology.

  19. Diffusion on an Ising chain with kinks

    NASA Astrophysics Data System (ADS)

    Hamma, Alioscia; Mansour, Toufik; Severini, Simone

    2009-07-01

    We count the number of histories between the two degenerate minimum energy configurations of the Ising model on a chain, as a function of the length n and the number d of kinks that appear above the critical temperature. This is equivalent to count permutations of length n avoiding certain subsequences depending on d. We give explicit generating functions and compute the asymptotics. The setting considered has a role when describing dynamics induced by quantum Hamiltonians with deconfined quasi-particles.

  20. Estimation of low-level neutron dose-equivalent rate by using extrapolation method for a curie level Am-Be neutron source.

    PubMed

    Li, Gang; Xu, Jiayun; Zhang, Jie

    2015-01-01

    Neutron radiation protection is an important research area because of the strong radiation biological effect of neutron field. The radiation dose of neutron is closely related to the neutron energy, and the connected relationship is a complex function of energy. For the low-level neutron radiation field (e.g. the Am-Be source), the commonly used commercial neutron dosimeter cannot always reflect the low-level dose rate, which is restricted by its own sensitivity limit and measuring range. In this paper, the intensity distribution of neutron field caused by a curie level Am-Be neutron source was investigated by measuring the count rates obtained through a 3 He proportional counter at different locations around the source. The results indicate that the count rates outside of the source room are negligible compared with the count rates measured in the source room. In the source room, 3 He proportional counter and neutron dosimeter were used to measure the count rates and dose rates respectively at different distances to the source. The results indicate that both the count rates and dose rates decrease exponentially with the increasing distance, and the dose rates measured by a commercial dosimeter are in good agreement with the results calculated by the Geant4 simulation within the inherent errors recommended by ICRP and IEC. Further studies presented in this paper indicate that the low-level neutron dose equivalent rates in the source room increase exponentially with the increasing low-energy neutron count rates when the source is lifted from the shield with different radiation intensities. Based on this relationship as well as the count rates measured at larger distance to the source, the dose rates can be calculated approximately by the extrapolation method. This principle can be used to estimate the low level neutron dose values in the source room which cannot be measured directly by a commercial dosimeter. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Evaluation of three portable samplers for monitoring airborne fungi

    NASA Technical Reports Server (NTRS)

    Mehta, S. K.; Mishra, S. K.; Pierson, D. L.

    1996-01-01

    Airborne fungi were monitored at five sample sites with the Burkard portable, the RCS Plus, and the SAS Super 90 air samplers; the Andersen 2-stage impactor was used for comparison. All samplers were calibrated before being used simultaneously to collect 100-liter samples at each site. The Andersen and Burkard samplers retrieved equivalent volumes of airborne fungi; the SAS Super 90 and RCS Plus measurements did not differ from each other but were significantly lower than those obtained with the Andersen or Burkard samplers. Total fungal counts correlated linearly with Cladosporium and Penicillium counts. Alternaria species, although present at all sites, did not correlate with total count or with amounts of any other fungal genera. Sampler and location significantly influenced fungal counts, but no interactions between samplers and locations were found.

  2. Effect of two storage solutions on surface topography of two root-end fillings.

    PubMed

    Asgary, Saeed; Eghbal, Mohammad Jafar; Parirokh, Masoud; Ghoddusi, Jamileh

    2009-12-01

    The effect of different storage solutions on surface topography of mineral trioxide aggregate (MTA) and new experimental cement (NEC) as root-end fillings was investigated. Twenty-four single-rooted teeth were cleaned, shaped and obturated in a same manner. After root-end resection, 3-mm deep root-end cavities were ultrasonically prepared. Samples were randomly divided into four test groups (A1-A2-B1-B2, n = 6). Root-end cavities in groups A and B were filled with MTA and NEC, respectively, and were then stored in 100% humidity for 24 h. The samples of groups 1 and 2 were, respectively, immersed in normal saline (NS) and phosphate buffer saline solutions for 1 week. The samples were imaged under stereomicroscope before and after immersion and were then investigated and analysed by scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDXA). Results showed significant difference among studied groups. Surface topography of all samples was altered by crystal formation and precipitation on root-end fillings except for group A1 (MTA-NS). SEM and EDXA results showed that the composition and structure of precipitated crystals were comparable with that of standard hydroxyapatite. It was concluded that biocompatibility, sealing ability, and cementogenic activity of MTA and probably NEC may be attributed to this fundamental bioactive reaction.

  3. Hot Chips and Hot Interconnects for High End Computing Systems

    NASA Technical Reports Server (NTRS)

    Saini, Subhash

    2005-01-01

    I will discuss several processors: 1. The Cray proprietary processor used in the Cray X1; 2. The IBM Power 3 and Power 4 used in an IBM SP 3 and IBM SP 4 systems; 3. The Intel Itanium and Xeon, used in the SGI Altix systems and clusters respectively; 4. IBM System-on-a-Chip used in IBM BlueGene/L; 5. HP Alpha EV68 processor used in DOE ASCI Q cluster; 6. SPARC64 V processor, which is used in the Fujitsu PRIMEPOWER HPC2500; 7. An NEC proprietary processor, which is used in NEC SX-6/7; 8. Power 4+ processor, which is used in Hitachi SR11000; 9. NEC proprietary processor, which is used in Earth Simulator. The IBM POWER5 and Red Storm Computing Systems will also be discussed. The architectures of these processors will first be presented, followed by interconnection networks and a description of high-end computer systems based on these processors and networks. The performance of various hardware/programming model combinations will then be compared, based on latest NAS Parallel Benchmark results (MPI, OpenMP/HPF and hybrid (MPI + OpenMP). The tutorial will conclude with a discussion of general trends in the field of high performance computing, (quantum computing, DNA computing, cellular engineering, and neural networks).

  4. Community metabolism in shallow coral reef and seagrass ecosystems, lower Florida Keys

    USGS Publications Warehouse

    Turk, Daniela; Yates, Kimberly K.; Vega-Rodriguez, Maria; Toro-Farmer, Gerardo; L'Esperance, Chris; Melo, Nelson; Ramsewak, Deanesch; Estrada, S. Cerdeira; Muller-Karger, Frank E.; Herwitz, Stan R.; McGillis, Wade

    2016-01-01

    Diurnal variation of net community production (NEP) and net community calcification (NEC) were measured in coral reef and seagrass biomes during October 2012 in the lower Florida Keys using a mesocosm enclosure and the oxygen gradient flux technique. Seagrass and coral reef sites showed diurnal variations of NEP and NEC, with positive values at near-seafloor light levels >100–300 µEinstein m-2 s-1. During daylight hours, we detected an average NEP of 12.3 and 8.6 mmol O2 m-2 h-1 at the seagrass and coral reef site, respectively. At night, NEP at the seagrass site was relatively constant, while on the coral reef, net respiration was highest immediately after dusk and decreased during the rest of the night. At the seagrass site, NEC values ranged from 0.20 g CaCO3 m-2 h-1 during daylight to -0.15 g CaCO3 m-2 h-1 at night, and from 0.17 to -0.10 g CaCO3 m-2 h-1 at the coral reef site. There were no significant differences in pH and aragonite saturation states (Ωar) between the seagrass and coral reef sites. Decrease in light levels during thunderstorms significantly decreased NEP, transforming the system from net autotrophic to net heterotrophic.

  5. Intestinal alkaline phosphatase is protective to the preterm rat pup intestine.

    PubMed

    Heinzerling, Nathan P; Liedel, Jennifer L; Welak, Scott R; Fredrich, Katherine; Biesterveld, Ben E; Pritchard, Kirkwood A; Gourlay, David M

    2014-06-01

    Necrotizing enterocolitis (NEC) is the most common surgical emergency in neonates, with a mortality rate between 10 and 50%. The onset of necrotizing enterocolitis is highly variable and associated with numerous risk factors. Prior research has shown that enteral supplementation with intestinal alkaline phosphatase (IAP) decreases the severity of NEC. The aim of this study is to investigate whether IAP is protective to the preterm intestine in the presence of formula feeding and in the absence of NEC. Preterm rat pups were fed formula with or without supplementation with IAP, and intestine was obtained on day of life 3 for analysis of IAP activity, mRNA expression of TNFα, IL-6 and iNOS and permeability and cytokine expression after LPS exposure. There was no difference in the absolute and intestine specific alkaline phosphatase activity in both groups. Rat pups fed IAP had decreased mRNA expression of the inflammatory cytokines TNFα, IL-6 and iNOS. Pups supplemented with IAP had decreased permeability and inflammatory cytokine expression after exposure to LPS ex vivo when compared to formula fed controls. Our results support that IAP is beneficial to preterm intestine and decreases intestinal injury and inflammation caused by LPS. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Intestinal Alkaline Phosphatase Is Protective to the Preterm Rat Pup Intestine

    PubMed Central

    Heinzerling, Nathan P.; Liedel, Jennifer L.; Welak, Scott R.; Fredrich, Katherine; Biesterveld, Ben E.; Pritchard, Kirkwood A.; Gourlay, David M.

    2014-01-01

    Background Necrotizing enterocolitis (NEC) is the most common surgical emergency in neonates, with a mortality rate between 10 and 50%. The onset of necrotizing enterocolitis is highly variable and associated with numerous risk factors. Prior research has shown enteral supplementation with intestinal alkaline phosphatase (IAP) decreases the severity of NEC. The aim of this study is to investigate whether IAP is protective to the preterm intestine in the presence of formula feeding and in the absence of NEC. Methods Preterm rat pups were fed formula with or without supplementation with IAP, and intestine was obtained on day of life 3 for analysis of IAP activity, mRNA expression of TNF-a, IL-6 and iNOS and permeability and cytokine expression after LPS. exposure. Results There was no difference in the absolute and intestine specific alkaline phosphatase activity in both groups. Rat pups fed IAP had decreased mRNA expression of the inflammatory cytokines TNFα, IL-6 and iNOS. Pups supplemented with IAP had decreased permeability and inflammatory cytokine expression after exposure to LPS ex vivo when compared to formula fed controls. Conclusions Our results support that IAP is beneficial to preterm intestine and decreases intestinal injury and inflammation caused by LPS. PMID:24888842

  7. The Genetics of Extreme Longevity: Lessons from the New England Centenarian Study

    PubMed Central

    Sebastiani, Paola; Perls, Thomas T.

    2012-01-01

    The New England Centenarian Study (NECS) was founded in 1994 as a longitudinal study of centenarians to determine if centenarians could be a model of healthy human aging. Over time, the NECS along with other centenarian studies have demonstrated that the majority of centenarians markedly delay high mortality risk-associated diseases toward the ends of their lives, but many centenarians have a history of enduring more chronic age-related diseases for many years, women more so than men. However, the majority of centenarians seem to deal with these chronic diseases more effectively, not experiencing disability until well into their nineties. Unlike most centenarians who are less than 101 years old, people who live to the most extreme ages, e.g., 107+ years, are generally living proof of the compression of morbidity hypothesis. That is, they compress morbidity and disability to the very ends of their lives. Various studies have also demonstrated a strong familial component to extreme longevity and now evidence particularly from the NECS is revealing an increasingly important genetic component to survival to older and older ages beyond 100 years. It appears to us that this genetic component consists of many genetic modifiers each with modest effects, but as a group they can have a strong influence. PMID:23226160

  8. Quantitative proteomic profiling of paired cancerous and normal colon epithelial cells isolated freshly from colorectal cancer patients.

    PubMed

    Tu, Chengjian; Mojica, Wilfrido; Straubinger, Robert M; Li, Jun; Shen, Shichen; Qu, Miao; Nie, Lei; Roberts, Rick; An, Bo; Qu, Jun

    2017-05-01

    The heterogeneous structure in tumor tissues from colorectal cancer (CRC) patients excludes an informative comparison between tumors and adjacent normal tissues. Here, we develop and apply a strategy to compare paired cancerous (CEC) versus normal (NEC) epithelial cells enriched from patients and discover potential biomarkers and therapeutic targets for CRC. CEC and NEC cells are respectively isolated from five different tumor and normal locations in the resected colon tissue from each patient (N = 12 patients) using an optimized epithelial cell adhesion molecule (EpCAM)-based enrichment approach. An ion current-based quantitative method is employed to perform comparative proteomic analysis for each patient. A total of 458 altered proteins that are common among >75% of patients are observed and selected for further investigation. Besides known findings such as deregulation of mitochondrial function, tricarboxylic acid cycle, and RNA post-transcriptional modification, functional analysis further revealed RAN signaling pathway, small nucleolar ribonucleoproteins (snoRNPs), and infection by RNA viruses are altered in CEC cells. A selection of the altered proteins of interest is validated by immunohistochemistry analyses. The informative comparison between matched CEC and NEC enhances our understanding of molecular mechanisms of CRC development and provides biomarker candidates and new pathways for therapeutic intervention. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Establishment of prostate cancer spheres from a prostate cancer cell line after phenethyl isothiocyanate treatment and discovery of androgen-dependent reversible differentiation between sphere and neuroendocrine cells.

    PubMed

    Chen, Yamei; Cang, Shundong; Han, Liying; Liu, Christina; Yang, Patrick; Solangi, Zeeshan; Lu, Quanyi; Liu, Delong; Chiao, J W

    2016-05-03

    Prostate cancer can transform from androgen-responsive to an androgen-independent phenotype. The mechanism responsible for the transformation remains unclear. We studied the effects of an epigenetic modulator, phenethyl isothiocyanate (PEITC), on the androgen-responsive LNCaP cells. After treatment with PEITC, floating spheres were formed with characteristics of prostate cancer stem cells (PCSC). These spheres were capable of self-renewal in media with and without androgen. They have been maintained in both types of media as long term cultures. Upon androgen deprivation, the adherent spheres differentiated to neuroendocrine cells (NEC) with decreased proliferation, expression of androgen receptor, and PSA. NEC reverse differentiated to spheres when androgen was replenished. The sphere cells expressed surface marker CD44 and had enhanced histone H3K4 acetylation, DNMT1 down-regulation and GSTP1 activation. We hypothesize that PEITC-mediated alteration in epigenomics of LNCaP cells may give rise to sphere cells, whereas reversible androgenomic alterations govern the shuttling between sphere PCSC and progeny NEC. Our findings identify unrecognized properties of prostate cancer sphere cells with multi-potential plasticity. This system will facilitate development of novel therapeutic agents and allow further exploration into epigenomics and androgenomics governing the transformation to hormone refractory prostate cancer.

  10. Growth curves of carcass traits obtained by ultrasonography in three lines of Nellore cattle selected for body weight.

    PubMed

    Coutinho, C C; Mercadante, M E Z; Jorge, A M; Paz, C C P; El Faro, L; Monteiro, F M

    2015-10-30

    The effect of selection for postweaning weight was evaluated within the growth curve parameters for both growth and carcass traits. Records of 2404 Nellore animals from three selection lines were analyzed: two selection lines for high postweaning weight, selection (NeS) and traditional (NeT); and a control line (NeC) in which animals were selected for postweaning weight close to the average. Body weight (BW), hip height (HH), rib eye area (REA), back fat thickness (BFT), and rump fat thickness (RFT) were measured and records collected from animals 8 to 20 (males) and 11 to 26 (females) months of age. The parameters A (asymptotic value) and k (growth rate) were estimated using the nonlinear model procedure of the Statistical Analysis System program, which included fixed effect of line (NeS, NeT, and NeC) in the model, with the objective to evaluate differences in the estimated parameters between lines. Selected animals (NeS and NeT) showed higher growth rates than control line animals (NeC) for all traits. Line effect on curves parameters was significant (P < 0.001) for BW, HH, and REA in males, and for BFT and RFT in females. Selection for postweaning weight was effective in altering growth curves, resulting in animals with higher growth potential.

  11. Effects of folic acid deficiency and MTHFRC677T polymorphisms on cytotoxicity in human peripheral blood lymphocytes

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

    Wu Xiayu; Liang Ziqing; Zou Tianning

    2009-02-13

    Apoptosis (APO) and necrosis (NEC) are two different types of cell death occurring in response to cellular stress factors. Cells with DNA damage may undergo APO or NEC. Folate is an essential micronutrient associated with DNA synthesis, repair and methylation. Methylenetetrahydrofolate reductase (MTHFR) regulates intracellular folate metabolism. Folate deficiency and MTHFR C677T polymorphisms have been shown to be related to DNA damage. To verify the cytotoxic effects of folate deficiency on cells with different MTHFR C677T genotypes, 15 human peripheral lymphocyte cases with different MTHFR C677T genotypes were cultured in folic acid (FA)-deficient and -sufficient media for 9 days. Cytotoxicitymore » was quantified using the frequencies of APO and NEC as endpoints, the nuclear division index (NDI), and the number of viable cells (NVC). These results showed that FA is an important factor in reducing cytotoxicity and increasing cell proliferation. Lymphocytes with the TT genotype proliferated easily under stress and exhibited different responses to FA deficiency than lymphocytes with the CC and CT genotypes. A TT individual may accumulate more cytotoxicity under cytotoxic stress, suggesting that the effects of FA deficiency on cytotoxicity are greater than the effects in individuals with the other MTHFR C677T variants.« less

  12. 20 CFR 416.926a - Functional equivalence for children.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... learning to read. Counting, sorting shapes, and building with blocks are skills needed to learn math... and middle school, you should be able to learn to read, write, and do math, and discuss history and...

  13. Higgs potential from derivative interactions

    NASA Astrophysics Data System (ADS)

    Quadri, A.

    2017-06-01

    A formulation of the linear σ model with derivative interactions is studied. The classical theory is on-shell equivalent to the σ model with the standard quartic Higgs potential. The mass of the scalar mode only appears in the quadratic part and not in the interaction vertices, unlike in the ordinary formulation of the theory. Renormalization of the model is discussed. A nonpower-counting renormalizable extension, obeying the defining functional identities of the theory, is presented. This extension is physically equivalent to the tree-level inclusion of a dimension-six effective operator ∂μ(Φ†Φ)∂μ(Φ†Φ). The resulting UV divergences are arranged in a perturbation series around the power-counting renormalizable theory. The application of the formalism to the Standard Model in the presence of the dimension-six operator ∂μ(Φ†Φ)∂μ(Φ†Φ) is discussed.

  14. High channel count and high precision channel spacing multi-wavelength laser array for future PICs.

    PubMed

    Shi, Yuechun; Li, Simin; Chen, Xiangfei; Li, Lianyan; Li, Jingsi; Zhang, Tingting; Zheng, Jilin; Zhang, Yunshan; Tang, Song; Hou, Lianping; Marsh, John H; Qiu, Bocang

    2014-12-09

    Multi-wavelength semiconductor laser arrays (MLAs) have wide applications in wavelength multiplexing division (WDM) networks. In spite of their tremendous potential, adoption of the MLA has been hampered by a number of issues, particularly wavelength precision and fabrication cost. In this paper, we report high channel count MLAs in which the wavelengths of each channel can be determined precisely through low-cost standard μm-level photolithography/holographic lithography and the reconstruction-equivalent-chirp (REC) technique. 60-wavelength MLAs with good wavelength spacing uniformity have been demonstrated experimentally, in which nearly 83% lasers are within a wavelength deviation of ±0.20 nm, corresponding to a tolerance of ±0.032 nm in the period pitch. As a result of employing the equivalent phase shift technique, the single longitudinal mode (SLM) yield is nearly 100%, while the theoretical yield of standard DFB lasers is only around 33.3%.

  15. Clinical outcome and long-term survival of 150 consecutive patients with pancreatic neuroendocrine tumors: A comprehensive analysis by the World Health Organization 2010 grading classification.

    PubMed

    Deng, Ben-Yuan; Liu, Fei; Yin, Si-Neng; Chen, An-Ping; Xu, Lin; Li, Bo

    2018-06-01

    The World Health Organization (WHO) has revised its grading system for pancreatic neuroendocrine tumors (PNETs) in 2010 into three main group, which has not been widely and comprehensively evaluated. We aimed to validate the clinical valve of this system associated with the clinical outcome and long-term survival when applied to PNETs, which were rare and heterogeneous. We retrospectively collected and analyzed the data of 150 consecutive patients with PNETs who underwent a resection. Sixty-four males and 86 females with PNETs were enrolled in our study. The clinical stage from I to IV by European Neuroendocrine Tumor Society were respectively defined in 53, 60, 19 and 18 patients. Seventy-two patients were pathologically diagnosed as neuroendocrine tumor G1 (NET G1), 48 as neuroendocrine tumor G2 (NET G2) and 30 as neuroendocrine carcinoma G3 (NEC G3). Patients with a radical resection obtained a notably higher overall survival (OS) than that of patients who underwent a palliative surgery (P=0.001). The 5-year OS of patients with NET G1 was significantly higher than that of patients with NET G2 (P=0.015) and NEC G3 (P<0.001); the comparison of OS for patients with NET G2 and NEC G3 was also statistically significant (P=0.005). In both univariate and multivariate analysis, clinical staging by ENETS (stage I and II vs. stage III and IV), resection (radical vs. palliative) and WHO 2010 grading classification (NET G1 and G2 vs. NEC G3) were validated to be independent predictors for the survivals of PNETs. The newly-updated WHO 2010 grading classification was prognostic for the OS of PNETs and could be widely adopted in clinical practice. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  16. Evaluating whole genome sequence data from the Genetic Absence Epilepsy Rat from Strasbourg and its related non-epileptic strain

    PubMed Central

    Powell, Kim L.; Zhu, Mingfu; Campbell, C. Ryan; Maia, Jessica M.; Ren, Zhong; Jones, Nigel C.; O’Brien, Terence J.; Petrovski, Slavé

    2017-01-01

    Objective The Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are an inbreed Wistar rat strain widely used as a model of genetic generalised epilepsy with absence seizures. As in humans, the genetic architecture that results in genetic generalized epilepsy in GAERS is poorly understood. Here we present the strain-specific variants found among the epileptic GAERS and their related Non-Epileptic Control (NEC) strain. The GAERS and NEC represent a powerful opportunity to identify neurobiological factors that are associated with the genetic generalised epilepsy phenotype. Methods We performed whole genome sequencing on adult epileptic GAERS and adult NEC rats, a strain derived from the same original Wistar colony. We also generated whole genome sequencing on four double-crossed (GAERS with NEC) F2 selected for high-seizing (n = 2) and non-seizing (n = 2) phenotypes. Results Specific to the GAERS genome, we identified 1.12 million single nucleotide variants, 296.5K short insertion-deletions, and 354 putative copy number variants that result in complete or partial loss/duplication of 41 genes. Of the GAERS-specific variants that met high quality criteria, 25 are annotated as stop codon gain/loss, 56 as putative essential splice sites, and 56 indels are predicted to result in a frameshift. Subsequent screening against the two F2 progeny sequenced for having the highest and two F2 progeny for having the lowest seizure burden identified only the selected Cacna1h GAERS-private protein-coding variant as exclusively co-segregating with the two high-seizing F2 rats. Significance This study highlights an approach for using whole genome sequencing to narrow down to a manageable candidate list of genetic variants in a complex genetic epilepsy animal model, and suggests utility of this sequencing design to investigate other spontaneously occurring animal models of human disease. PMID:28708842

  17. Sialylated galacto-oligosaccharides and 2'-fucosyllactose reduce necrotising enterocolitis in neonatal rats.

    PubMed

    Autran, Chloe A; Schoterman, Margriet H C; Jantscher-Krenn, Evelyn; Kamerling, Johannis P; Bode, Lars

    2016-07-01

    Necrotising enterocolitis (NEC) is one of the most frequent and fatal intestinal disorders in preterm infants and has very limited treatment options. Breast-fed infants are at a 6-10-fold lower NEC risk than formula-fed infants, and we have previously shown that human milk oligosaccharides (HMO) improved survival and reduced pathology in a rat NEC model. The HMO disialyllacto-N-tetraose (DSLNT) was most effective, and sialylation was shown to be essential for its protective effect. Galacto-oligosaccharides (GOS), currently added to some infant formula, but not containing sialic acid, had no effect. In addition to DSLNT, our previous work also showed that the neutral HMO fraction, which contains high concentrations of 2'-fucosyllactose (2'FL), slightly improved pathology scores. Here, we assessed the in vivo efficacy of 2'FL, as well as of GOS that we enzymatically sialylated (Sia-GOS). Neonatal rats were randomised into the following study groups - dam-fed (DF), formula-fed (FF), FF containing pooled HMO (10 mg/ml), GOS (8 mg/ml), Sia-GOS (500 µm) or 2'FL (2 mg/ml) - and subjected to the established NEC protocol. The DF and HMO groups had the lowest pathology scores with mean values of 0·67 (sd 0·34) and 0·90 (sd 0·47), respectively. The FF group had significantly elevated pathology scores of 2·02 (sd 0·63). Although the addition of GOS to the formula had no protective effect and generated scores of 2·00 (sd 0·63), the addition of Sia-GOS or 2'FL significantly lowered pathology scores to 1·32 (sd 0·56) (P<0·0034) and 1·43 (sd 0·51) (P<0·0040), respectively. The results warrant further studies to investigate the underlying mechanisms and to assess safety and efficacy in human neonates.

  18. Right service, right place: optimising utilisation of a community nursing service to reduce planned re-presentations to the emergency department

    PubMed Central

    Lawton, Jessica Kirsten; Kinsman, Leigh; Dalton, Lisa; Walsh, Fay; Bryan, Helen; Williams, Sharon

    2017-01-01

    Background Congruent with international rising emergency department (ED) demand, a focus on strategies and services to reduce burden on EDs and improve patient outcomes is necessary. Planned re-presentations of non-urgent patients at a regional Australian hospital exceeded 1200 visits during the 2013–2014 financial year. Planned re-presentations perpetuate demand and signify a lack of alternative services for non-urgent patients. The Community Nursing Enhanced Connections Service (CoNECS) collaboratively evolved between acute care and community services in 2014 to reduce planned ED re-presentations. Objective This study aimed to investigate the evolution and impact of a community nursing service to reduce planned re-presentations to a regional Australian ED and identify enablers and barriers to interventionist effectiveness. Methods A mixed-methods approach evaluated the impact of CoNECS. Data from hospital databases including measured numbers of planned ED re-presentations by month, time of day, age, gender and reason were used to calculate referral rates to CoNECS. These results informed two semistructured focus groups with ED and community nurses. The researchers used a theoretical lens, ‘diffusion of innovation’, to understand how this service could inform future interventions. Results Analyses showed that annual ED planned re-presentations decreased by 43% (527 presentations) after implementation. Three themes emerged from the focus groups. These were right service at the right time, nursing uncertainty and system disconnect and medical disengagement. Conclusions CoNECS reduced overall ED planned re-presentations and was sustained longer than many complex service-level interventions. Factors supporting the service were endorsement from senior administration and strong leadership to drive responsive quality improvement strategies. This study identified a promising alternative service outside the ED, highlighting possibilities for other hospital emergency services aiming to reduce planned re-presentations. PMID:29450293

  19. Establishment of Airborne Nanoparticle Exposure Chamber System to Assess Nano TiO2 Induced Mice Lung Effects

    NASA Astrophysics Data System (ADS)

    Chen, Chia-Hua; Li, Jui-Ping; Huang, Nai-Chun; Yang, Chung-Shi; Chen, Jen-Kun

    2011-12-01

    A great many governments have schemed their top priority to support the research and development of emerging nanotechnology, which lead to increasing products containing nanomaterials. However, platforms and protocols to evaluate the safety of nanomaterials are not yet established. We therefore design and fabricate a nanoparticle exposure chamber system (NECS) and try to standardize protocols to assess potential health risk of inhalable nanoparticles. This platform comprises: (1) nano-aerosol generators to produce homogeneous airborne nanoparticles, (2) double isolated container to prevent from unexpected exposure to humans, (3) gas supply system for housing animals or incubating cultured cells, and (4) system for automatic control and airborne nanoparticle analysis. The NECS providing multiple functions includes: (1) a secure environment to handle nanomaterials, (2) real-time measurement for the size and distribution of airborne nanoparticles, (3) SOP of safety evaluation for nanomaterials, and (4) key technology for the development of inhalable pharmaceuticals. We used NECS to mimic occupational environment for exploring potential adverse effects of TiO2 nanoparticles. The adult male ICR mice were exposed to 25nm, well-characterized TiO2 particles for 1 and 4 weeks. More than 90% of the inhaled TiO2 nanoparticles deposit in lung tissue, which tends to be captured by alveolar macrophages. Pulmonary function test does not show significant physiological changes between one and 4 weeks exposure. For plasma biochemistry analysis, there are no obvious inflammation responses after exposure for one and 4 weeks; however, disruption of alveolar septa and increased thickness of alveolar epithelial cells were observed. According to our results, the NECS together with our protocols show comprehensive integration and ideally fit the standard of OECD guildelines-TG403, TG412, TG413; it can be further customized to fulfill diverse demands of industry, government, and third party contract research organization (CRO).

  20. Decreased cost and improved feeding tolerance in VLBW infants fed an exclusive human milk diet.

    PubMed

    Assad, M; Elliott, M J; Abraham, J H

    2016-03-01

    Human milk is the best form of nutrition for preterm infants and has been associated with a lower incidence of necrotizing enterocolitis (NEC). Infants that develop NEC have a higher incidence of feeding intolerance and longer hospitalizations. The combination of a donor milk bank and donor milk-derived fortifier has changed feeding practices in neonatal intensive care units (NICU). The purpose of this study is to assess the benefits and cost of an exclusive human milk (EHM) diet in very low birth weight (VLBW) infants in a community level III NICU. This is a retrospective study including preterm infants ⩽28 weeks and/or VLBW (⩽1500 g) who were enrolled from March 2009 until March 2014. Infants were grouped as follows: group H (entirely human milk based, born March 2012 to 2014), group B (bovine-based fortifier and maternal milk, born March 2009 to 2012), group M (mixed combination of maternal milk, bovine-based fortifier and formula, born March 2009 to 2012) and group F (formula fed infants, born March 2009 to 2012). Baseline characteristics among the four groups were similar. The study included 293 infants between gestational ages 23 to 34 weeks and birth weights between 490 and 1700 g. Feeding intolerance occurred less often (P<0.0001), number of days to full feeds was lower (P<0.001), incidence of NEC was lower (P<0.011), and total hospitalization costs were lower by up to $106,968 per infant (P<0.004) in those fed an EHM diet compared with the other groups. Average weight gain per day was similar among the four groups (18.5 to 20.6 g per day). Implementing an EHM diet in our VLBW infants has led to a significant decrease in the incidence of NEC. Other benefits of this diet include: decreased feeding intolerance, shorter time to full feeds, shorter length of stay, and lower hospital and physician charges for extremely premature and VLBW infants.

  1. Genipin protects d-galactosamine and lipopolysaccharide-induced hepatic injury through suppression of the necroptosis-mediated inflammasome signaling.

    PubMed

    Seo, Min-Jong; Hong, Jeong-Min; Kim, Seok-Joo; Lee, Sun-Mee

    2017-10-05

    Acute liver failure (ALF) is a life-threatening syndrome resulting from massive inflammation and hepatocyte death. Necroptosis, a programmed cell death controlled by receptor-interacting protein kinase (RIP) 1 and RIP3, has been shown to play an important role in regulating inflammation via crosstalk between other intracellular signaling. The inflammasome is a major intracellular multiprotein that induces inflammatory responses by mediating immune cell infiltration, thus potentiating injury. Genipin, a major active compound of the gardenia fruit, exhibits anti-inflammatory, antioxidant, and anti-apoptotic properties. This study investigated the hepatoprotective mechanisms of genipin on d-galactosamine (GalN) and lipopolysaccharide (LPS)-induced ALF, particularly focusing on interaction between necroptosis and inflammasome. Mice were given an intraperitoneal injection of genipin (25, 50, and 100mg/kg) or necrostatin-1 (Nec-1, a necroptosis inhibitor; 1.8mg/kg) 1h prior to GalN (800mg/kg)/LPS (40μg/kg) injection and were killed 3h after GalN/LPS injection. Genipin improved the survival rate and attenuated increases in serum aminotransferase activities and inflammatory cytokines after GalN/LPS injection. Genipin reduced GalN/LPS-induced increases in RIP3, phosphorylated RIP1 and RIP3 protein expression, and RIP1/RIP3 necrosome complex, similar to the effects of Nec-1. GalN/LPS significantly increased serum levels of high-mobility group box 1 and interleukin (IL)-33, which were attenuated by genipin and Nec-1. Moreover, similar to Nec-1, genipin attenuated GalN/LPS-induced increases in the protein expression levels of NLRP3, ASC, and caspase-1, inflammasome components, and levels of liver and serum IL-1β. Taken together, our findings suggest that genipin ameliorates GalN/LPS-induced hepatocellular damage by suppressing necroptosis-mediated inflammasome signaling. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. The changing epidemiology of human African trypanosomiasis among patients from nonendemic countries--1902-2012.

    PubMed

    Neuberger, Ami; Meltzer, Eyal; Leshem, Eyal; Dickstein, Yaakov; Stienlauf, Shmuel; Schwartz, Eli

    2014-01-01

    Although human African trypanosomiasis (HAT) is uncommon among patients from non-endemic countries (NEC), there has been an increase in the number of cases reported in recent years. A systematic review of the literature was performed. The number of incoming tourists to HAT endemic countries was obtained from the United Nations World Tourism Organization. All HAT cases diagnosed in patients from NEC were included. Immigrants and refugees were excluded. We compared patients during and after the colonial period, and analyzed the relationship between the number of incoming travellers and the number of HAT cases. Between 1902 and 2012, HAT was reported in 244 patients. Most HAT cases were reported before 1920, and after the year 2000. In the colonial era the average age of patients was lower (32.5±7.8 vs. 43.0±16.1 years, P<0.001), the proportion of females was lower (10.0% vs. 23.9%, P<0.01], most cases were diagnosed in expatriates, missionaries and soldiers (74.3%), and Gambian trypanosomiasis accounted for 86/110, (78%) of cases. In the post-colonial era most patients 91/125 (72.8%) were short-term tourists to game parks in Eastern and South-Eastern Africa (mainly in Tanzania); Rhodesian trypanosomiasis accounted for 94/123 (76.4%) of cases. Between 1995 and 2010 there has been a constant linear increase in the number of incoming tourists to Tanzania, and HAT cases occurred in small outbreaks rather than following a similar linear pattern. In recent decades HAT patients from NEC are older, and more likely to be tourists who acquired the disease while visiting game-parks in Eastern and South-Eastern Africa. While Rhodesian trypanosomiasis is relatively uncommon among Africans, it now accounts for most cases reported among patients from NEC. Returning febrile travellers without an alternative diagnosis should be evaluated for HAT. Cases among travellers may serve as sentinels for Rhodesian trypanosomiasis "hot spots" in Africa.

  3. Delayed introduction of progressive enteral feeds to prevent necrotising enterocolitis in very low birth weight infants.

    PubMed

    Morgan, Jessie; Young, Lauren; McGuire, William

    2014-01-01

    The introduction of enteral feeds for very preterm (less than 32 weeks' gestation) or very low birth weight (VLBW; less than 1500 g) infants is often delayed for several days or longer after birth due to concern that early introduction may not be tolerated and may increase the risk of necrotising enterocolitis (NEC). However, delaying enteral feeding could diminish the functional adaptation of the gastrointestinal tract and prolong the need for parenteral nutrition with its attendant infectious and metabolic risks. To determine the effect of delayed introduction of progressive enteral feeds on the incidence of NEC, mortality and other morbidities in very preterm or VLBW infants. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2014, Issue 8), MEDLINE (1966 to September 2014), EMBASE (1980 to September 2014), CINAHL (1982 to September 2014), conference proceedings and previous reviews. We included randomised or quasi-randomised controlled trials that assessed the effect of delayed (more than four days after birth) versus earlier introduction of progressive enteral feeds on the incidence of NEC, mortality and other morbidities in very preterm or VLBW infants. Two review authors independently assessed trial eligibility and risk of bias and undertook data extraction. We analysed the treatment effects in the individual trials and reported the risk ratio (RR) and risk difference for dichotomous data and mean difference for continuous data, with respective 95% confidence intervals (CI). We used a fixed-effect model in meta-analyses and explored the potential causes of heterogeneity in sensitivity analyses. We identified nine randomised controlled trials in which 1106 infants participated. Few participants were extremely preterm (less 28 weeks' gestation) or extremely low birth weight (less than 1000 g). The trials defined delayed introduction of progressive enteral feeds as later than four to seven days after birth and early introduction as four days or less after birth. Meta-analyses did not detect statistically significant effects on the risk of NEC (typical RR 0.93, 95% CI 0.64 to 1.34; 8 trials; 1092 infants) or all-cause mortality (typical RR 1.18, 95% CI 0.75 to 1.88; 7 trials; 967 infants). Four of the trials restricted participation to growth-restricted infants with Doppler ultrasound evidence of abnormal fetal circulatory distribution or flow. Planned subgroup analyses of these trials found no statistically significant effects on the risk of NEC or all-cause mortality. Infants who had delayed introduction of enteral feeds took longer to establish full enteral feeding (reported median differences two to four days). The evidence available from randomised controlled trials suggested that delaying the introduction of progressive enteral feeds beyond four days after birth did not reduce the risk of developing NEC in very preterm or VLBW infants, including growth-restricted infants. Delaying the introduction of progressive enteral feeds resulted in a few days' delay in establishing full enteral feeds but the clinical importance of this effect was unclear. The applicability of these findings to extremely preterm or extremely low birth weight was uncertain. Further randomised controlled trials in this population may be warranted.

  4. Dose Calibration of the ISS-RAD Fast Neutron Detector

    NASA Technical Reports Server (NTRS)

    Zeitlin, C.

    2015-01-01

    The ISS-RAD instrument has been fabricated by Southwest Research Institute and delivered to NASA for flight to the ISS in late 2015 or early 2016. ISS-RAD is essentially two instruments that share a common interface to ISS. The two instruments are the Charged Particle Detector (CPD), which is very similar to the MSL-RAD detector on Mars, and the Fast Neutron Detector (FND), which is a boron-loaded plastic scintillator with readout optimized for the 0.5 to 10 MeV energy range. As the FND is completely new, it has been necessary to develop methodology to allow it to be used to measure the neutron dose and dose equivalent. This talk will focus on the methods developed and their implementation using calibration data obtained in quasi-monoenergetic (QMN) neutron fields at the PTB facility in Braunschweig, Germany. The QMN data allow us to determine an approximate response function, from which we estimate dose and dose equivalent contributions per detected neutron as a function of the pulse height. We refer to these as the "pSv per count" curves for dose equivalent and the "pGy per count" curves for dose. The FND is required to provide a dose equivalent measurement with an accuracy of ?10% of the known value in a calibrated AmBe field. Four variants of the analysis method were developed, corresponding to two different approximations of the pSv per count curve, and two different implementations, one for real-time analysis onboard ISS and one for ground analysis. We will show that the preferred method, when applied in either real-time or ground analysis, yields good accuracy for the AmBe field. We find that the real-time algorithm is more susceptible to chance-coincidence background than is the algorithm used in ground analysis, so that the best estimates will come from the latter.

  5. Induction of Micronuclei in Human Fibroblasts from the Los Alamos High Energy Neutron Beam

    NASA Technical Reports Server (NTRS)

    Cox, Bradley

    2009-01-01

    The space radiation field includes a broad spectrum of high energy neutrons. Interactions between these neutrons and a spacecraft, or other material, significantly contribute to the dose equivalent for astronauts. The 15 degree beam line in the Weapons Neutron Research beam at Los Alamos Nuclear Science Center generates a neutron spectrum relatively similar to that seen in space. Human foreskin fibroblast (AG1522) samples were irradiated behind 0 to 20 cm of water equivalent shielding. The cells were exposed to either a 0.05 or 0.2 Gy entrance dose. Following irradiation, micronuclei were counted to see how the water shield affects the beam and its damage to cell nuclei. Micronuclei induction was then compared with dose equivalent data provided from a tissue equivalent proportional counter.

  6. 45 CFR 286.100 - What activities count towards the work participation rate?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... service programs; (8) Vocational educational training; (see § 286.105) (9) Job skills training directly... attendance at secondary school or in a course of study leading to a certificate of general equivalence, if a...

  7. Development of a direct experimental test for any violation of the equivalence principle by the weak interaction

    NASA Technical Reports Server (NTRS)

    Parker, P. D. M.

    1981-01-01

    Violation of the equivalence principle by the weak interaction is tested. Any variation of the weak interaction coupling constant with gravitational potential, i.e., a spatial variation of the fundamental constants is investigated. The level of sensitivity required for such a measurement is estimated on the basis of the size of a change in the gravitational potential which is accessible. The alpha particle spectrum is analyzed, and the counting rate was improved by a factor of approximately 100.

  8. Probiotics and Innate and Adaptive Immune Responses in Premature Infants

    PubMed Central

    Underwood, Mark A.

    2017-01-01

    Premature infants are at increased risk for morbidity and mortality due to necrotizing enterocolitis (NEC) and sepsis. Probiotics decrease the risk of NEC and death in premature infants; however, mechanisms of action are unclear. A wide variety of probiotic species have been evaluated for potential beneficial properties in vitro, in animal models, and in clinical trials of premature infants. Although there is variation by species and even strain, common mechanisms of protection include attenuation of intestinal inflammation, apoptosis, dysmotility, permeability, supplanting other gut microbes through production of bacteriocins, and more effective use of available nutrients. Here, we review the most promising probiotics and what is known about their impact on the innate and adaptive immune response. PMID:28966796

  9. Ion Beam Materials Analysis and Modifications at keV to MeV Energies at the University of North Texas

    NASA Astrophysics Data System (ADS)

    Rout, Bibhudutta; Dhoubhadel, Mangal S.; Poudel, Prakash R.; Kummari, Venkata C.; Lakshantha, Wickramaarachchige J.; Manuel, Jack E.; Bohara, Gyanendra; Szilasi, Szabolcs Z.; Glass, Gary A.; McDaniel, Floyd D.

    2014-02-01

    The University of North Texas (UNT) Ion Beam Modification and Analysis Laboratory (IBMAL) has four particle accelerators including a National Electrostatics Corporation (NEC) 9SDH-2 3 MV tandem Pelletron, a NEC 9SH 3 MV single-ended Pelletron, and a 200 kV Cockcroft-Walton. A fourth HVEC AK 2.5 MV Van de Graaff accelerator is presently being refurbished as an educational training facility. These accelerators can produce and accelerate almost any ion in the periodic table at energies from a few keV to tens of MeV. They are used to modify materials by ion implantation and to analyze materials by numerous atomic and nuclear physics techniques. The NEC 9SH accelerator was recently installed in the IBMAL and subsequently upgraded with the addition of a capacitive-liner and terminal potential stabilization system to reduce ion energy spread and therefore improve spatial resolution of the probing ion beam to hundreds of nanometers. Research involves materials modification and synthesis by ion implantation for photonic, electronic, and magnetic applications, micro-fabrication by high energy (MeV) ion beam lithography, microanalysis of biomedical and semiconductor materials, development of highenergy ion nanoprobe focusing systems, and educational and outreach activities. An overview of the IBMAL facilities and some of the current research projects are discussed.

  10. Effect of Digestion and Storage of Human Milk on Free Fatty Acid Concentration and Cytotoxicity

    PubMed Central

    Penn, Alexander H.; Altshuler, Angelina E.; Small, James W.; Taylor, Sharon F.; Dobkins, Karen R.; Schmid-Schönbein, Geert W.

    2014-01-01

    Objectives Fat is digested in the intestine into free fatty acids (FFAs), which are detergents and therefore toxic to cells at micromolar concentration. The mucosal barrier protects cells in the adult intestine, but this barrier may not be fully developed in premature infants. Lipase-digested infant formula, but not fresh human milk, has elevated FFAs and is cytotoxic to intestinal cells, and therefore could contribute to intestinal injury in necrotizing enterocolitis (NEC). But even infants exclusively fed breast milk may develop NEC. Our objective was to determine if stored milk and milk from donor milk banks (DM) could also become cytotoxic, especially after digestion. Methods We exposed cultured rat intestinal epithelial cells or human neutrophils to DM and milk collected fresh and stored at 4 or −20 °C for up to 12 weeks and then treated for 2 hours (37°C) with 0.1 or 1 mg/ml pancreatic lipase and/or trypsin and chymotrypsin. Results DM and milk stored 3 days (at 4 or −20 °C) and then digested were cytotoxic. Storage at −20 °C for 8 and 12 weeks resulted in an additional increase in cytotoxicity. Protease digestion decreased, but did not eliminate cell death. Conclusions Current storage practices may allow milk to become cytotoxic and contribute to intestinal damage in NEC. PMID:24840512

  11. Is necroptosis a death pathway in aluminum-induced neuroblastoma cell demise?

    PubMed

    Zhang, Q L; Niu, Q; Ji, X L; Conti, P; Boscolo, P

    2008-01-01

    Besides being an aggravating factor secondary to major physiological alterations in degenerative diseases, aluminum has also been considered as a risk factor in the etiology. Although many in vivo and in vitro data are in favor of apoptosis and necrosis being involved in Al induced neurodegenerative processes, there is considerable evidence that very complex events may contribute to neural cell death. Necroptosis, a novel cell death pathway, was recently reported to contribute to ischemia brain injury. It is different from, but associated with, apoptosis and necrosis, the two common major pathways of cell demise. In the present study, SH-SY5Y cells were put under stress by Al, a potential degenerative cell death inducer. Nec-1, a specific inhibitor, was used to identify necroptosis. The characteristics observed in Nec-1 and Al treated SH-SY5Y cells showed that necrotic morphological changes were reduced, and a sharp decrease of necrotic rate was detected. Besides, there were Al-induced mitochondria membrane potential decreasing, reactive oxygen species remaining, and autophagosomes declining. The mechanism of Nec-1s effect on cell death may be related to caspases pathways. To our best knowledge, this is the pioneer report on necroptosis in mixed human neural cell death pathways, which might offer a novel therapeutic target for neurodegenerative diseases, and an extended window for neuroprotection.

  12. Comprehensive Gas-Phase Peptide Ion Structure Studies Using Ion Mobility Techniques: Part 2. Gas-Phase Hydrogen/Deuterium Exchange for Ion Population Estimation.

    PubMed

    Khakinejad, Mahdiar; Ghassabi Kondalaji, Samaneh; Tafreshian, Amirmahdi; Valentine, Stephen J

    2017-05-01

    Gas-phase hydrogen/deuterium exchange (HDX) using D 2 O reagent and collision cross-section (CCS) measurements are utilized to monitor the ion conformers of the model peptide acetyl-PAAAAKAAAAKAAAAKAAAAK. The measurements are carried out on a home-built ion mobility instrument coupled to a linear ion trap mass spectrometer containing electron transfer dissociation (ETD) capabilities. ETD is utilized to obtain per-residue deuterium uptake data for select ion conformers, and a new algorithm is presented for interpreting the HDX data. Using molecular dynamics (MD) production data and a hydrogen accessibility scoring (HAS)-number of effective collisions (NEC) model, hypothetical HDX behavior is attributed to various in-silico candidate (CCS match) structures. The HAS-NEC model is applied to all candidate structures, and non-negative linear regression is employed to determine structure contributions resulting in the best match to deuterium uptake. The accuracy of the HAS-NEC model is tested with the comparison of predicted and experimental isotopic envelopes for several of the observed c-ions. It is proposed that gas-phase HDX can be utilized effectively as a second criterion (after CCS matching) for filtering suitable MD candidate structures. In this study, the second step of structure elucidation, 13 nominal structures were selected (from a pool of 300 candidate structures) and each with a population contribution proposed for these ions. Graphical Abstract ᅟ.

  13. Time and resource limits on working memory: cross-age consistency in counting span performance.

    PubMed

    Ransdell, Sarah; Hecht, Steven

    2003-12-01

    This longitudinal study separated resource demand effects from those of retention interval in a counting span task among 100 children tested in grade 2 and again in grades 3 and 4. A last card large counting span condition had an equivalent memory load to a last card small, but the last card large required holding the count over a longer retention interval. In all three waves of assessment, the last card large condition was found to be less accurate than the last card small. A model predicting reading comprehension showed that age was a significant predictor when entered first accounting for 26% of the variance, but counting span accounted for a further 22% of the variance. Span at Wave 1 accounted for significant unique variance at Wave 2 and at Wave 3. Results were similar for math calculation with age accounting for 31% of the variance and counting span accounting for a further 34% of the variance. Span at Wave 1 explained unique variance in math at Wave 2 and at Wave 3.

  14. Wetlands.

    ERIC Educational Resources Information Center

    Nelson, Patricia L.

    1986-01-01

    Suggests studying New York's wetlands, both in the classroom and in the field, to illustrate ecological concepts of diversity, succession, and adaptation and to learn about their importance in controlling flooding, erosion, and pollution. (NEC)

  15. Neuroendocrine carcinoma of the extrahepatic bile duct: A case report

    PubMed Central

    Oshiro, Yukio; Gen, Ryozo; Hashimoto, Shinji; Oda, Tatsuya; Sato, Taiki; Ohkohchi, Nobuhiro

    2016-01-01

    Neuroendocrine carcinoma (NEC) originating from the gastrointestinal hepatobiliary-pancreas is a rare, invasive, and progressive disease, for which the prognosis is extremely poor. The patient was a 72-year-old man referred with complaints of jaundice. He was diagnosed with middle extrahepatic cholangiocarcinoma (cT4N1M0, cStage IV). He underwent a right hepatectomy combined with extrahepatic bile duct and portal vein resection after percutaneous transhepatic portal vein embolization. Microscopic examination showed a large-cell neuroendocrine carcinoma according to the WHO criteria for the clinicopathologic classification of gastroenteropancreatic neuroendocrine tumors. Currently, the patient is receiving combination chemotherapy with cisplatin and etoposide for postoperative multiple liver metastases. Although NEC is difficult to diagnose preoperatively, it should be considered an uncommon alternative diagnosis. PMID:27570432

  16. An experiment to verify that the weak interactions satisfy the strong equivalence principle. [electron capture and gravitational potential

    NASA Technical Reports Server (NTRS)

    Eby, P. B.

    1978-01-01

    The construction of a clock based on the beta decay process is proposed to test for any violations by the weak interaction of the strong equivalence principle bu determining whether the weak interaction coupling constant beta is spatially constant or whether it is a function of gravitational potential (U). The clock can be constructed by simply counting the beta disintegrations of some suitable source. The total number of counts are to be taken a measure of elapsed time. The accuracy of the clock is limited by the statistical fluctuations in the number of counts, N, which is equal to the square root of N. Increasing N gives a corresponding increase in accuracy. A source based on the electron capture process can be used so as to avoid low energy electron discrimination problems. Solid state and gaseous detectors are being considered. While the accuracy of this type of beta decay clock is much less than clocks based on the electromagnetic interaction, there is a corresponding lack of knowledge of the behavior of beta as a function of gravitational potential. No predictions from nonmetric theories as to variations in beta are available as yet, but they may occur at the U/sg C level.

  17. Waveguide integrated low noise NbTiN nanowire single-photon detectors with milli-Hz dark count rate

    PubMed Central

    Schuck, Carsten; Pernice, Wolfram H. P.; Tang, Hong X.

    2013-01-01

    Superconducting nanowire single-photon detectors are an ideal match for integrated quantum photonic circuits due to their high detection efficiency for telecom wavelength photons. Quantum optical technology also requires single-photon detection with low dark count rate and high timing accuracy. Here we present very low noise superconducting nanowire single-photon detectors based on NbTiN thin films patterned directly on top of Si3N4 waveguides. We systematically investigate a large variety of detector designs and characterize their detection noise performance. Milli-Hz dark count rates are demonstrated over the entire operating range of the nanowire detectors which also feature low timing jitter. The ultra-low dark count rate, in combination with the high detection efficiency inherent to our travelling wave detector geometry, gives rise to a measured noise equivalent power at the 10−20 W/Hz1/2 level. PMID:23714696

  18. Counting of fermions and spins in strongly correlated systems in and out of thermal equilibrium

    NASA Astrophysics Data System (ADS)

    Braungardt, Sibylle; Rodríguez, Mirta; Sen(de), Aditi; Sen, Ujjwal; Glauber, Roy J.; Lewenstein, Maciej

    2011-01-01

    Atom counting theory can be used to study the role of thermal noise in quantum phase transitions and to monitor the dynamics of a quantum system. We illustrate this for a strongly correlated fermionic system, which is equivalent to an anisotropic quantum XY chain in a transverse field and can be realized with cold fermionic atoms in an optical lattice. We analyze the counting statistics across the phase diagram in the presence of thermal fluctuations and during its thermalization when the system is coupled to a heat bath. At zero temperature, the quantum phase transition is reflected in the cumulants of the counting distribution. We find that the signatures of the crossover remain visible at low temperature and are obscured with increasing thermal fluctuations. We find that the same quantities may be used to scan the dynamics during the thermalization of the system.

  19. New method for estimating bacterial cell abundances in natural samples by use of sublimation

    NASA Technical Reports Server (NTRS)

    Glavin, Daniel P.; Cleaves, H. James; Schubert, Michael; Aubrey, Andrew; Bada, Jeffrey L.

    2004-01-01

    We have developed a new method based on the sublimation of adenine from Escherichia coli to estimate bacterial cell counts in natural samples. To demonstrate this technique, several types of natural samples, including beach sand, seawater, deep-sea sediment, and two soil samples from the Atacama Desert, were heated to a temperature of 500 degrees C for several seconds under reduced pressure. The sublimate was collected on a cold finger, and the amount of adenine released from the samples was then determined by high-performance liquid chromatography with UV absorbance detection. Based on the total amount of adenine recovered from DNA and RNA in these samples, we estimated bacterial cell counts ranging from approximately 10(5) to 10(9) E. coli cell equivalents per gram. For most of these samples, the sublimation-based cell counts were in agreement with total bacterial counts obtained by traditional DAPI (4,6-diamidino-2-phenylindole) staining.

  20. Genetic association between body energy measured throughout lactation and fertility in dairy cattle.

    PubMed

    Banos, G; Coffey, M P

    2010-02-01

    The objective of this study was to quantify the genetic association of body energy assessed throughout lactation with a cow's fertility. Nine direct and indirect body energy traits were defined at different stages of lactation. Four were daily records of energy balance, energy content, cumulative effective energy (CEE) and body condition score (BCS) calculated between lactation days 4 and 311. The other five traits included duration of negative energy balance (DNEB), rate of recovery during DNEB (RNEB), sum of negative energy balance (SNEB), nadir of energy content (NEC) and number of days from calving to NEC. Of these traits, energy balance, DNEB, RNEB and SNEB were primarily based on individual cow feed intake and milk yield, and considered direct measures of body energy. The other traits were calculated from body lipid and protein changes, predicted from BCS and live weight profiles, and were considered indirect measures of body energy. Fertility was defined by number of days between calving and commencement of luteal activity (DLA), first observed oestrus (DH) and conception (DC), and number of services per conception. A total of 957 cows in their first four lactations were considered in the study. Genetic models fitted cubic splines to define longitudinal traits (energy balance, energy content, CEE and BCS) and calculate heritability and genetic correlation with fertility. Daily heritability estimate ranges were 0.10 to 0.34, 0.35 to 0.61, 0.32 to 0.53 and 0.24 to 0.56 for energy balance, energy content, CEE and BCS, respectively, and, in most cases, tended to increase towards the middle of lactation and remain relatively stable thereafter. Of the other body energy traits, heritability of NEC (0.44) was the most notable. Statistically significant (P < 0.05) genetic correlations of DH with daily energy balance, energy content, CEE and BCS ranged from -0.16 to -0.28, -0.35 to -0.48, -0.16 to -0.26 and -0.37 to -0.44, respectively. For DC, respective estimates were -0.28 to -0.64, -0.37 to -0.60, -0.30 to -0.48 and -0.29 to -0.53. For DLA, they ranged from -0.47 to -0.56 with energy content and from -0.50 to -0.74 with BCS. Of special interest was the genetic correlation of NEC with DH (-0.54) and DC (-0.48). Results suggest that indirect measures of body energy have the strongest genetic association with cow fertility. NEC and early lactation (circa day 50) BCS and energy content are the most useful traits for selection in terms of the correlated improvement in a cow's capacity to resume her reproductive activity post partum.

  1. Learning on Skiis.

    ERIC Educational Resources Information Center

    Neidich, Carole Louise

    1980-01-01

    Describes and illustrates wonders of the winter world encountered during a nature walk on cross-country skis through snow crystal examination, springtail observation, tree study, bird and plant identification, and animal track sighting. (NEC)

  2. 12 CFR 1282.16 - Special counting requirements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... activity of the Enterprise is substantially equivalent to a mortgage purchase and either creates a new market or adds liquidity to an existing market, provided however that such mortgage purchase actually... housing goals: (1) Equity investments in housing development projects; (2) Purchases of State and local...

  3. On the Shapley Value of Unrooted Phylogenetic Trees.

    PubMed

    Wicke, Kristina; Fischer, Mareike

    2018-01-17

    The Shapley value, a solution concept from cooperative game theory, has recently been considered for both unrooted and rooted phylogenetic trees. Here, we focus on the Shapley value of unrooted trees and first revisit the so-called split counts of a phylogenetic tree and the Shapley transformation matrix that allows for the calculation of the Shapley value from the edge lengths of a tree. We show that non-isomorphic trees may have permutation-equivalent Shapley transformation matrices and permutation-equivalent null spaces. This implies that estimating the split counts associated with a tree or the Shapley values of its leaves does not suffice to reconstruct the correct tree topology. We then turn to the use of the Shapley value as a prioritization criterion in biodiversity conservation and compare it to a greedy solution concept. Here, we show that for certain phylogenetic trees, the Shapley value may fail as a prioritization criterion, meaning that the diversity spanned by the top k species (ranked by their Shapley values) cannot approximate the total diversity of all n species.

  4. Dynamics of seawater carbonate chemistry, production, and calcification of a coral reef flat, Central Great Barrier Reef

    NASA Astrophysics Data System (ADS)

    Albright, R.; Langdon, C.; Anthony, K. R. N.

    2013-05-01

    Ocean acidification is projected to shift coral reefs from a state of net accretion to one of net dissolution this century. Presently, our ability to predict global-scale changes to coral reef calcification is limited by insufficient data relating seawater carbonate chemistry parameters to in situ rates of reef calcification. Here, we investigate natural trends in carbonate chemistry of the Davies Reef flat in the central Great Barrier Reef on diel and seasonal timescales and relate these trends to benthic carbon fluxes by quantifying net ecosystem calcification (nec) and net community production (ncp). Results show that seawater carbonate chemistry of the Davies Reef flat is highly variable over both diel and seasonal timescales. pH (total scale) ranged from 7.92 to 8.17, pCO2 ranged from 272 to 542 μatm, and aragonite saturation state (Ωarag) ranged from 2.9 to 4.1. Diel cycles in carbonate chemistry were primarily driven by ncp, and warming explained 35% and 47% of the seasonal shifts in pCO2 and pH, respectively. Daytime ncp averaged 36 ± 19 mmol C m-2 h-1 in summer and 33 ± 13 mmol C m-2 h-1 in winter; nighttime ncp averaged -22 ± 20 and -7 ± 6 mmol C m-2 h-1 in summer and winter, respectively. Daytime nec averaged 11 ± 4 mmol CaCO3 m-2 h-1 in summer and 8 ± 3 mmol CaCO3 m-2 h-1 in winter, whereas nighttime nec averaged 2 ± 4 mmol and -1 ± 3 mmol CaCO3 m-2 h-1 in summer and winter, respectively. Net ecosystem calcification was positively correlated with Ωarag for both seasons. Linear correlations of nec and Ωarag indicate that the Davies Reef flat may transition from a state of net calcification to net dissolution at Ωarag values of 3.4 in summer and 3.2 in winter. Diel trends in Ωarag indicate that the reef flat is currently below this calcification threshold 29.6% of the time in summer and 14.1% of the time in winter.

  5. The Palouse in Eekish Pah.

    ERIC Educational Resources Information Center

    Trafzer, Clifford E.

    1985-01-01

    Relates the removal of the Palouse Indians to northeastern Oklahoma in 1878. Describes the conditions of their exile and the efforts that led to their eventual return to the Pacific Northwest in 1885. (NEC)

  6. Common Diagnoses in the NICU

    MedlinePlus

    ... to the development of NEC, which is the necrosis, or death, of parts of the intestine. Although ... is it? The ductus arteriosus (DA) is a blood vessel in the heart that connects the aorta (which ...

  7. 16. New York, New Haven & Hartford Railroad: Readville Shops. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    16. New York, New Haven & Hartford Railroad: Readville Shops. Readville, Suffolk Co., MA. (Not on NEC). - Northeast Railroad Corridor, Amtrak Route between RI/MA State Line & South Station, Boston, Suffolk County, MA

  8. 18. New York, New Haven & Hartford Railroad: Readville Shops. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    18. New York, New Haven & Hartford Railroad: Readville Shops. Readville, Suffolk Co., MA. (Not on NEC). - Northeast Railroad Corridor, Amtrak Route between RI/MA State Line & South Station, Boston, Suffolk County, MA

  9. The Farm Credit Situation: Implications for Agricultural Policy.

    ERIC Educational Resources Information Center

    Bullock, J. Bruce

    1986-01-01

    Examines issues regarding current farm finance situation from a public policy perspective: origins and causes of current situation, available policy options for dealing with the problems, and impacts of policy options. (NEC)

  10. The Warm-Blooded Plant of the Swamps.

    ERIC Educational Resources Information Center

    Camazine, Scott

    1986-01-01

    Describes remarkable characteristics of the skunk cabbage (Symplocarpus foetidus) which make it an interesting swamp plant to study in February and March: its warm-blooded nature, unpleasant skunky odor, and peculiar root system. (NEC)

  11. Learning from Ethical Dilemmas.

    ERIC Educational Resources Information Center

    Havens, Mark D.

    1987-01-01

    Reports analysis of 60 case studies of ethical dilemmas faced by experiential educators. Identifies issues which enhance likelihood of moral dilemmas: funding, residential programming, and risk-taking. Exposes need for a professional "code of ethics." (NEC)

  12. Energy Crisis Spurs Congress Into Action

    ERIC Educational Resources Information Center

    Chemical and Engineering News, 1973

    1973-01-01

    Discusses legislation recently passed by Congress in response to the energy crisis, and the Nixon Administration's proposal for creating a new Energy Research and Development Administration (ERDA) and a Nuclear Energy Commission (NEC). (JR)

  13. Missouri transportation bulletin : vol. 16, no. 1.

    DOT National Transportation Integrated Search

    2000-01-01

    The Missouri Transportation Bulletin is published by the Technology Transfer Assistance Program of the Missouri Department of Transportation, : Jefferson City, Missouri. The opinions, findings or recommendations expressed in this Bulletin are not nec...

  14. Classically Stable Nonsingular Cosmological Bounces

    NASA Astrophysics Data System (ADS)

    Ijjas, Anna; Steinhardt, Paul J.

    2016-09-01

    One of the fundamental questions of theoretical cosmology is whether the Universe can undergo a nonsingular bounce, i.e., smoothly transit from a period of contraction to a period of expansion through violation of the null energy condition (NEC) at energies well below the Planck scale and at finite values of the scale factor such that the entire evolution remains classical. A common claim has been that a nonsingular bounce either leads to ghost or gradient instabilities or a cosmological singularity. In this Letter, we consider a well-motivated class of theories based on the cubic Galileon action and present a procedure for explicitly constructing examples of a nonsingular cosmological bounce without encountering any pathologies and maintaining a subluminal sound speed for comoving curvature modes throughout the NEC violating phase. We also discuss the relation between our procedure and earlier work.

  15. Onyalai--therapeutic effects of vincristine sulphate. A prospective randomized trial.

    PubMed

    Hesseling, P B; Girdle-Brown, B; Smit, J

    1986-08-16

    Twenty out of 40 patients with onyalai admitted to Rundu State Hospital, Kavango, SWA/Namibia, were randomized to receive a vincristine sulphate bolus of 1.5 mg/m2 or an equivalent volume of normal saline intravenously on days 8 and 15 when haemorrhage or a platelet count of less than 50 X 10(9)/l persisted for more than 1 week after admission. All patients were observed in hospital for at least 21 days. Five out of 10 patients who received vincristine achieved a platelet count in excess of 100 X 10(9)/l on day 21 and only 2 out of 10 patients who received placebo achieved a similar rise in the platelet count. Two patients, neither of whom was treated with vincristine, died of cerebral haemorrhage.

  16. An Automated Statistical Technique for Counting Distinct Multiple Sclerosis Lesions.

    PubMed

    Dworkin, J D; Linn, K A; Oguz, I; Fleishman, G M; Bakshi, R; Nair, G; Calabresi, P A; Henry, R G; Oh, J; Papinutto, N; Pelletier, D; Rooney, W; Stern, W; Sicotte, N L; Reich, D S; Shinohara, R T

    2018-04-01

    Lesion load is a common biomarker in multiple sclerosis, yet it has historically shown modest association with clinical outcome. Lesion count, which encapsulates the natural history of lesion formation and is thought to provide complementary information, is difficult to assess in patients with confluent (ie, spatially overlapping) lesions. We introduce a statistical technique for cross-sectionally counting pathologically distinct lesions. MR imaging was used to assess the probability of a lesion at each location. The texture of this map was quantified using a novel technique, and clusters resembling the center of a lesion were counted. Validity compared with a criterion standard count was demonstrated in 60 subjects observed longitudinally, and reliability was determined using 14 scans of a clinically stable subject acquired at 7 sites. The proposed count and the criterion standard count were highly correlated ( r = 0.97, P < .001) and not significantly different (t 59 = -.83, P = .41), and the variability of the proposed count across repeat scans was equivalent to that of lesion load. After accounting for lesion load and age, lesion count was negatively associated ( t 58 = -2.73, P < .01) with the Expanded Disability Status Scale. Average lesion size had a higher association with the Expanded Disability Status Scale ( r = 0.35, P < .01) than lesion load ( r = 0.10, P = .44) or lesion count ( r = -.12, P = .36) alone. This study introduces a novel technique for counting pathologically distinct lesions using cross-sectional data and demonstrates its ability to recover obscured longitudinal information. The proposed count allows more accurate estimation of lesion size, which correlated more closely with disability scores than either lesion load or lesion count alone. © 2018 by American Journal of Neuroradiology.

  17. Exploring Discrete Mathematics with American Football

    ERIC Educational Resources Information Center

    Muldoon Brown, Tricia; Kahn, Eric B.

    2015-01-01

    This paper presents an extended project that offers, through American football, an application of concepts from enumerative combinatorics and an introduction to proofs course. The questions in this paper and subsequent details concerning equivalence relations and counting techniques can be used to reinforce these new topics to students in such a…

  18. Cycle Counting Methods of the Aircraft Engine

    ERIC Educational Resources Information Center

    Fedorchenko, Dmitrii G.; Novikov, Dmitrii K.

    2016-01-01

    The concept of condition-based gas turbine-powered aircraft operation is realized all over the world, which implementation requires knowledge of the end-of-life information related to components of aircraft engines in service. This research proposes an algorithm for estimating the equivalent cyclical running hours. This article provides analysis…

  19. 42 CFR 415.208 - Services of moonlighting residents.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... IN TEACHING SETTINGS, AND RESIDENTS IN CERTAIN SETTINGS Services of Residents § 415.208 Services of... payment is made for services of a “teaching physician” associated with moonlighting services, and the time spent furnishing these services is not included in the teaching hospital's full-time equivalency count...

  20. On the implementation of a class of upwind schemes for system of hyperbolic conservation laws

    NASA Technical Reports Server (NTRS)

    Yee, H. C.

    1985-01-01

    The relative computational effort among the spatially five point numerical flux functions of Harten, van Leer, and Osher and Chakravarthy is explored. These three methods typify the design principles most often used in constructing higher than first order upwind total variation diminishing (TVD) schemes. For the scalar case the difference in operation count between any two algorithms may be very small and yet the operation count for their system counterparts might be vastly different. The situation occurs even though one starts with two different yet equivalent representations for the scalar case.

  1. Positive train control desense mitigation test : research phase 1.

    DOT National Transportation Integrated Search

    2016-05-01

    Final report for Positive Train Control (PTC) Desense Mitigation Test Research project includes description of Northeast Corridor (NEC) PTC deployments, PTC radio desense scenarios, PTC radio desense mitigation approaches, PTC radio desense mitigatio...

  2. Wilderness as Healing Place.

    ERIC Educational Resources Information Center

    Miles, John

    1987-01-01

    Examines research in a variety of fields to assess the ways in which experiences in the wilderness contribute to physical, emotional, and spiritual health. Considers psychological benefits, enhancement of self-worth, ability to learn, and physical fitness. (NEC)

  3. Treatments for Preterm Labor

    MedlinePlus

    ... brain. NEC is a condition that affects a baby's intestines. Antibiotics . These kill infections caused by bacteria. You may need antibiotics to help prevent infections in you and your baby if you have Group B strep infection or ...

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

    Behnke, M. R.; Bellei, T.A.; Bloethe, W.G.

    This paper presents a summary of the most impor- tant considerations for wind power plant collection system un- derground and overhead cable designs. Various considerations, including conductor selection, soil thermal properties, installa- tion methods, splicing, concentric grounding, and NESC/NEC requirements are discussed.

  5. Teaching Basic Science Environmentally. Concept: Plants Reproduce Their Own Kind.

    ERIC Educational Resources Information Center

    Busch, Phyllis

    1987-01-01

    Offers suggestions for spring activities focusing on plant reproduction both indoors and outdoors. Suggests planting seeds to observe, measure, and record effects of temperature, moisture, fertilizer. Recommends outdoor study of the horsetail plant. (NEC)

  6. Building a Future for Technological Innovation

    DTIC Science & Technology

    2010-08-17

    breakthroughs in health IT • Address scientific “grand challenges” Promote Competitive Markets that Spur Productive Entrepreneurship • Promote... entrepreneurship • Improve public sector innovation and support community innovation Source: http://www.whitehouse.gov/administration/eop/nec/reports

  7. THE INTESTINAL MICROBIOME OF INFANTS AND THE USE OF PROBIOTICS

    PubMed Central

    Indrio, Flavia; Neu, Josef

    2011-01-01

    Purpose of the review The increasing use of probiotics in neonates deserves scrutiny of the therapeutic as well as potentially harmful effects of these bacteria. In this review we describe the possible application of probiotics in the more common disease in the neonatal period. Recent finding Recent advances our capability to identify microbes and their function in the gastrointestinal tract offer exciting opportunities to discover the pathophysiology of enigmatic diseases such as necrotizing enterocolitis (NEC) and late onset sepsis (LOS) in the neonate. The relationship of the resident intestinal microbes to neural and muscular processes such as intestinal motility and neurodevelopment are also being evaluated. Summary We focus the possibility of the application of probiotics for disorders of motility in the infant, NEC and LOS Here we will summarize some of the recent advances in these areas as they relate to clinical practice and discuss areas where additional research is needed. PMID:21415831

  8. Microbial contamination of meat during the skinning of beef carcass hindquarters at three slaughtering plants.

    PubMed

    Gill, C O; McGinnis, J C; Bryant, J

    1998-07-21

    The microbiological effects on the product of the series of operations for skinning the hindquarters of beef carcasses at three packing plants were assessed. Samples were obtained at each plant from randomly selected carcasses, by swabbing specified sites related to opening cuts, rump skinning or flank skinning operations, randomly selected sites along the lines of the opening cuts, or randomly selected sites on the skinned hindquarters of carcasses. A set of 25 samples of each type was collected at each plant, with the collection of a single sample from each selected carcass. Aerobic counts, coliforms and Escherichia coli were enumerated in each sample, and a log mean value was estimated for each set of 25 counts on the assumption of a log normal distribution of the counts. The data indicated that the hindquarters skinning operations at plant A were hygienically inferior to those at the other two plants, with mean numbers of coliforms and E. coli being about two orders of magnitude greater, and aerobic counts being an order of magnitude greater on the skinned hindquarters of carcasses from plant A than on those from plants B or C. The data further indicated that the operation for cutting open the skin at plant C was hygienically superior to the equivalent operation at plant B, but that the operations for skinning the rump and flank at plant B were hygienically superior to the equivalent operations at plant C. The findings suggest that objective assessment of the microbiological effects on carcasses of beef carcass dressing processes will be required to ensure that Hazard Analysis: Critical Control Point and Quality Management Systems are operated to control the microbiological condition of carcasses.

  9. Hydrogen Distribution in the Lunar Polar Regions

    NASA Technical Reports Server (NTRS)

    Sanin, A. B.; Mitrofanov, I. G.; Litvak, M. L.; Bakhtin, B. N.; Bodnarik, J. G.; Boynton, W. V.; Chin, G.; Evans, L. G.; Harshmann, K.; Fedosov, F.; hide

    2016-01-01

    We present a method of conversion of the lunar neutron counting rate measured by the Lunar Reconnaissance Orbiter (LRO) Lunar Exploration Neutron Detector (LEND) instrument collimated neutron detectors, to water equivalent hydrogen (WEH) in the top approximately 1 m layer of lunar regolith. Polar maps of the Moon’s inferred hydrogen abundance are presented and discussed.

  10. Prediction of Energy Expenditure from Wrist Accelerometry in People with and without Down Syndrome

    ERIC Educational Resources Information Center

    Agiovlasitis, Stamatis; Motl, Robert W.; Foley, John T.; Fernhall, Bo

    2012-01-01

    This study examined the relationship between energy expenditure and wrist accelerometer output during walking in persons with and without Down syndrome (DS). Energy expenditure in metabolic equivalent units (METs) and activity-count rate were respectively measured with portable spirometry and a uniaxial wrist accelerometer in 17 persons with DS…

  11. Creative Coin Combinations. Unit Plans.

    ERIC Educational Resources Information Center

    United States Mint (Dept. of Treasury), Washington, DC.

    This unit of study for grades K-2 focuses on counting coins and coin equivalencies up to 50 cents, making use of a literature connection. The unit provides key words; recommends subject areas and approximate length of time; poses an essential question or problem; provides a unit introduction; notes four individual lessons ((1) For Sale!; (2)…

  12. 42 CFR 415.206 - Services of residents in nonprovider settings.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... PHYSICIANS IN TEACHING SETTINGS, AND RESIDENTS IN CERTAIN SETTINGS Services of Residents § 415.206 Services... equivalency residents in the calculation of a teaching hospital's resident count. The teaching physician rules on carrier payments in §§ 415.170 through 415.184 apply in these teaching settings. (b) Physician fee...

  13. Comparison of culture media, simplate, and petrifilm for enumeration of yeasts and molds in food.

    PubMed

    Taniwaki, M H; Silva, N; Banhe, A A; Iamanaka, B T

    2001-10-01

    The efficacy of three culture media, dichloran rose bengal chloramphenicol (DRBC), dichloran 18% glycerol agar (DG18), and potato dextrose agar (PDA) supplemented with two antibiotics, were compared with the Simplate and Petrifilm techniques for mold and yeast enumeration. The following foods were analyzed: corn meal, wheat flour, cassava flour, bread crumbs, whole meal, sliced bread, ground peanuts, mozzarella cheese, grated parmesan cheese, cheese rolls, orange juice, pineapple pulp, pineapple cake, and mushroom in conserve. Correlation coefficients of DRBC versus PDA and DG18 for recovering total mold and yeast counts from the composite of 14 foods indicated that the three media were generally equivalent. Correlation coefficients for Petrifilm versus culture media were acceptable, although not as good as between culture media. Correlation coefficients of Simplate versus DRBC, DG18, PDA, and Petrifilm for recovering total yeasts and molds from a composite of 11 foods demonstrated that there was no equivalence between the counts obtained by Simplate and other culture media and Petrifilm, with significant differences observed for the most foods analyzed.

  14. Aberrant cytokine pattern of the nasal mucosa in granulomatosis with polyangiitis

    PubMed Central

    2012-01-01

    Introduction In granulomatosis with polyangiitis (GPA), a complex autoimmune small-vessel vasculitis frequently associated with chronic necrotizing inflammation of the nasal mucosa, elevated nasal Staphylococcus (S.) aureus carrier rates are a risk factor for relapse. As cytokines are primarily involved in the regulation of defense against potentially pathogenic microorganisms, the aim of this study was to compare healthy individuals and GPA patients with respect to their baseline cytokine expression of nasal epithelial cells (NEC), which form the first barrier against such triggers. The ability of S. aureus to influence the nasal microenvironment's cytokine secretion was assessed by exemplary stimulation experiments. Methods Baseline expression of 19 cytokines of primary NEC of GPA patients and normal controls (NC) was quantified by a multiplex cytokine assay. Stimulation experiments were performed with supernatants of S. aureus and expression of interleukin-8 was determined by ELISA. Results In GPA, an altered pattern of baseline cytokine expression with significantly up-regulated G-CSF and reduced interleukin (IL)-8 concentrations was observed. Both NEC of GPA patients and NC responded to stimulation with S. aureus, but GPA patients displayed a significantly lower IL-8 secretion and a diminished dynamic range of response towards the stimulus. Conclusions The data presented underline the hypothesis of a disturbed epithelial nasal barrier function in GPA. The dysregulated baseline expression of G-CSF and IL-8 and the reduced response to microbial stimulation may facilitate changes in the composition of the nasal flora and favour an imbalanced inflammatory response, which might be relevant for the disease course. PMID:23031229

  15. Expression of the oncoprotein gankyrin and phosphorylated retinoblastoma protein in human testis and testicular germ cell tumor.

    PubMed

    Ando, Satoshi; Matsuoka, Taeko; Kawai, Koji; Sugita, Shintaro; Joraku, Akira; Kojima, Takahiro; Suetomi, Takahiro; Miyazaki, Jun; Fujita, Jun; Nishiyama, Hiroyuki

    2014-10-01

    The oncoprotein, gankyrin, is known to facilitate cell proliferation through phosphorylation and degradation of retinoblastoma protein. In the present study, we evaluated the expression of gankyrin and phosphorylated retinoblastoma protein in human testis and testicular germ cell tumors. The effects of suppression of gankyrin by locked nucleic acid on phosphorylation status of retinoblastoma and cell proliferation were analyzed using western blot analysis and testicular tumor cell line NEC8. The expressions of gankyrin, retinoblastoma and retinoblastoma protein were analyzed in 93 testicular germ cell tumor samples and five normal human testis by immunohistochemistry. The retinoblastoma protein expression was determined using an antibody to retinoblastoma protein, Ser795. Gankyrin was expressed in NEC8 cells as well as a normal human testis and testicular tumors. Suppression of gankyrin by locked nucleic acid led to suppression of retinoblastoma protein and cell proliferation in NEC8 cells. Immunohistochemistry of normal testis showed that gankyrin is expressed dominantly in spermatocytes. In testicular germ cell tumors, high expressions of gankyrin and phosphorylated-retinoblastoma protein were observed in seminoma and embryonal carcinoma, whereas the expressions of both proteins were weak in histological subtypes of non-seminoma. Growing teratoma and testicular malignant transformation tissues expressed phosphorylated-retinoblastoma protein strongly, but gankyrin faintly. Gankyrin is dominantly expressed in normal spermatocytes and seminoma/embryonal carcinoma, and its expression correlates well with retinoblastoma protein expression except in the growing teratoma and testicular malignant transformation cases. These data provide new insights into the molecular mechanisms of normal spermatogenesis and pathogenesis of testicular germ cell tumors. © 2014 The Japanese Urological Association.

  16. Family Meal Frequency among Children and Adolescents with Eating Disorders

    PubMed Central

    Elran-Barak, Roni; Sztainer, Maya; Goldschmidt, Andrea B.; Le Grange, Daniel

    2014-01-01

    Purpose: Previous studies on family meals and disordered eating have mainly drawn their samples from the general population. The goal of the current study is to determine family meal frequency among children and adolescents with Anorexia Nervosa (AN), Bulimia Nervosa (BN), and Feeding or Eating Disorder Not Elsewhere Classified (FED-NEC), and to examine if family meal frequency is associated with eating disorder psychopathology. Methods: Participants included 154 children and adolescents (M=14.92±2.62), who met criteria for AN (n=60), BN (n=32), or FED-NEC (n=62). All participants completed the Eating Disorder Examination (EDE) and the Family Meal Questionnaire (FMQ) prior to treatment at the University of Chicago Eating Disorders Program. Results: AN and BN participants significantly differed in terms of family meal frequency. A majority of participants with AN (71.7%), compared to less than half (43.7%) of participants with BN, reported eating dinner with their family frequently (five or more times per week). Family meal frequency during dinner was significantly and negatively correlated with dietary restraints and eating concerns among participants with BN (r=-.381, r=-.366, p<.05) and FED-NEC (r=-.340, r=-.276, p<.05). Conclusions: AN patients' higher family meal frequency may beexplained bytheir parents' relatively greater vigilance over eating, whereas families of BN patients may be less aware of eating disorder behaviors and hence less insistent upon family meals. Additionally, children and adolescents with AN may be more inhibited and withdrawn, and therefore are perhaps more likely to stay at home and eat together with their families. PMID:24529833

  17. Oxidative stress induced necroptosis activation is involved in the pathogenesis of hyperoxic acute lung injury.

    PubMed

    Han, C H; Guan, Z B; Zhang, P X; Fang, H L; Li, L; Zhang, H M; Zhou, F J; Mao, Y F; Liu, W W

    2018-01-15

    Necroptosis has been found to be involved in the pathogenesis of some lung diseases, but its role in hyperoxic acute lung injury (HALI) is still unclear. This study aimed to investigate contribution of necroptosis to the pathogenesis of HALI induced by hyperbaric hyperoxia exposure in a rat model. Rats were divided into control group, HALI group, Nec-1 (necroptosis inhibitor) group and edaravone group. Rats were exposed to pure oxygen at 250 kPa for 6 h to induce HALI. At 30 min before hyperoxia exposure, rats were intraperitoneally injected with Nec-1 or edaravone, and sacrificed at 24 h after hyperoxia exposure. Lung injury was evaluated by histology, lung water to dry ratio (W/D) and bronchoalveolar lavage fluid (BALF) biochemistry; the serum and plasma oxidative stress, expression of RIP1, RIP3 and MLKL, and interaction between RIP1 and RIP3 were determined. Results showed hyperoxia exposure significantly caused damage to lung and increased necroptotic cells and the expression of RIP1, RIP3 and MLKL. Edaravone pre-treatment not only inhibited the oxidative stress in HALI, but also reduced necroptotic cells, decreased the expression of RIP1, RIP3 and MLKL and improved lung pathology. Nec-1 pretreatment inhibited necroptosis and improved lung pathology, but had little influence on oxidative stress. This study suggests hyperoxia exposure induces oxidative stress may activate necroptosis, involving in the pathology of HALI, and strategies targeting necroptosis may become promising treatments for HALI. Copyright © 2017. Published by Elsevier Inc.

  18. Change in Rural Schools.

    ERIC Educational Resources Information Center

    Edington, Everett D.

    1981-01-01

    Discusses nine major characteristics of rural schools which affected their willingness to accept change, as revealed in a study of the five-year Rural Experimental Schools Program. Available from: Rural Sociological Society, 325 Morgan Hall, University of Tennessee, Knoxville, TN 37916. (NEC)

  19. 17. New York, New Haven & Hartford Railroad: Readville Shops ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    17. New York, New Haven & Hartford Railroad: Readville Shops with Sprague Street Bridge in background. Readville, Suffolk Co., MA. (Not on NEC). - Northeast Railroad Corridor, Amtrak Route between RI/MA State Line & South Station, Boston, Suffolk County, MA

  20. How to Create a Day Camp Using the Resources of Your Community.

    ERIC Educational Resources Information Center

    Hazelwood, James; Hazelwood, Lisa

    1986-01-01

    Outlines process of putting together a local week-long day camp: assessing community resources, developing a curriculum, choosing the staff (coordinator; teachers/counselors; assistants; directors of art, recreation, and music) and marketing the program. (NEC)

  1. Owl Research that's Good for the Birds.

    ERIC Educational Resources Information Center

    Cristol, Daniel A.

    1986-01-01

    Describes and illustrates how to build nest boxes to provide city homes for screech owls to reestablish a healthy ecological balance. Outlines how to conduct a pellet analysis of an owl's diet and how to study screech owl territoriality. (NEC)

  2. Computer Based Expert Systems.

    ERIC Educational Resources Information Center

    Parry, James D.; Ferrara, Joseph M.

    1985-01-01

    Claims knowledge-based expert computer systems can meet needs of rural schools for affordable expert advice and support and will play an important role in the future of rural education. Describes potential applications in prediction, interpretation, diagnosis, remediation, planning, monitoring, and instruction. (NEC)

  3. Ventricular enlargement as a possible measure of Alzheimer's disease progression validated using the Alzheimer's disease neuroimaging initiative database

    PubMed Central

    Nestor, Sean M.; Rupsingh, Raul; Borrie, Michael; Smith, Matthew; Accomazzi, Vittorio; Wells, Jennie L.; Fogarty, Jennifer

    2008-01-01

    Ventricular enlargement may be an objective and sensitive measure of neuropathological change associated with mild cognitive impairment (MCI) and Alzheimer's disease (AD), suitable to assess disease progression for multi-centre studies. This study compared (i) ventricular enlargement after six months in subjects with MCI, AD and normal elderly controls (NEC) in a multi-centre study, (ii) volumetric and cognitive changes between Apolipoprotein E genotypes, (iii) ventricular enlargement in subjects who progressed from MCI to AD, and (iv) sample sizes for multi-centre MCI and AD studies based on measures of ventricular enlargement. Three dimensional T1-weighted MRI and cognitive measures were acquired from 504 subjects (NEC n = 152, MCI n = 247 and AD n = 105) participating in the multi-centre Alzheimer's Disease Neuroimaging Initiative. Cerebral ventricular volume was quantified at baseline and after six months using semi-automated software. For the primary analysis of ventricle and neurocognitive measures, between group differences were evaluated using an analysis of covariance, and repeated measures t-tests were used for within group comparisons. For secondary analyses, all groups were dichotomized for Apolipoprotein E genotype based on the presence of an ε4 polymorphism. In addition, the MCI group was dichotomized into those individuals who progressed to a clinical diagnosis of AD, and those subjects that remained stable with MCI after six months. Group differences on neurocognitive and ventricle measures were evaluated by independent t-tests. General sample size calculations were computed for all groups derived from ventricle measurements and neurocognitive scores. The AD group had greater ventricular enlargement compared to both subjects with MCI (P = 0.0004) and NEC (P < 0.0001), and subjects with MCI had a greater rate of ventricular enlargement compared to NEC (P = 0.0001). MCI subjects that progressed to clinical AD after six months had greater ventricular enlargement than stable MCI subjects (P = 0.0270). Ventricular enlargement was different between Apolipoprotein E genotypes within the AD group (P = 0.010). The number of subjects required to demonstrate a 20% change in ventricular enlargement was substantially lower than that required to demonstrate a 20% change in cognitive scores. Ventricular enlargement represents a feasible short-term marker of disease progression in subjects with MCI and subjects with AD for multi-centre studies. PMID:18669512

  4. The TSO Logic and G2 Software Product

    NASA Technical Reports Server (NTRS)

    Davis, Derrick D.

    2014-01-01

    This internship assignment for spring 2014 was at John F. Kennedy Space Center (KSC), in NASAs Engineering and Technology (NE) group in support of the Control and Data Systems Division (NE-C) within the Systems Hardware Engineering Branch. (NEC-4) The primary focus was in system integration and benchmarking utilizing two separate computer software products. The first half of this 2014 internship is spent in assisting NE-C4s Electronics and Embedded Systems Engineer, Kelvin Ruiz and fellow intern Scott Ditto with the evaluation of a newly piece of software, called G2. Its developed by the Gensym Corporation and introduced to the group as a tool used in monitoring launch environments. All fellow interns and employees of the G2 group have been working together in order to better understand the significance of the G2 application and how KSC can benefit from its capabilities. The second stage of this Spring project is to assist with an ongoing integration of a benchmarking tool, developed by a group of engineers from a Canadian based organization known as TSO Logic. Guided by NE-C4s Computer Engineer, Allen Villorin, NASA 2014 interns put forth great effort in helping to integrate TSOs software into the Spaceport Processing Systems Development Laboratory (SPSDL) for further testing and evaluating. The TSO Logic group claims that their software is designed for, monitoring and reducing energy consumption at in-house server farms and large data centers, allows data centers to control the power state of servers, without impacting availability or performance and without changes to infrastructure and the focus of the assignment is to test this theory. TSOs Aaron Rallo Founder and CEO, and Chris Tivel CTO, both came to KSC to assist with the installation of their software in the SPSDL laboratory. TSOs software is installed onto 24 individual workstations running three different operating systems. The workstations were divided into three groups of 8 with each group having its own operating system. The first group is comprised of Ubuntus Debian -based Linux the second group is windows 7 Professional and the third group ran Red Hat Linux. The highlight of this portion of the assignment is to compose documentation expressing the overall impression of the software and its capabilities.

  5. Short-term depression of gap junctional coupling in reticular thalamic neurons of absence epileptic rats.

    PubMed

    Kohmann, Denise; Lüttjohann, Annika; Seidenbecher, Thomas; Coulon, Philippe; Pape, Hans-Christian

    2016-10-01

    Gap junctional electrical coupling between neurons of the reticular thalamic nucleus (RTN) is critical for hypersynchrony in the thalamo-cortical network. This study investigates the role of electrical coupling in pathological rhythmogenesis in RTN neurons in a rat model of absence epilepsy. Rhythmic activation resulted in a Ca(2+) -dependent short-term depression (STD) of electrical coupling between pairs of RTN neurons in epileptic rats, but not in RTN of a non-epileptic control strain. Pharmacological blockade of gap junctions in RTN in vivo induced a depression of seizure activity. The STD of electrical coupling represents a mechanism of Ca(2+) homeostasis in RTN aimed to counteract excessive synchronization. Neurons in the reticular thalamic nucleus (RTN) are coupled by electrical synapses, which play a major role in regulating synchronous activity. This study investigates electrical coupling in RTN neurons from a rat model of childhood absence epilepsy, genetic absence epilepsy rats from Strasbourg (GAERS), compared with a non-epileptic control (NEC) strain, to assess the impact on pathophysiological rhythmogenesis. Whole-cell recordings were obtained from pairs of RTN neurons of GAERS and NEC in vitro. Coupling was determined by injection of hyperpolarizing current steps in one cell and monitoring evoked voltage responses in both activated and coupled cell. The coupling coefficient (cc) was compared under resting condition, during pharmacological interventions and repeated activation using a series of current injections. The effect of gap junctional coupling on seizure expression was investigated by application of gap junctional blockers into RTN of GAERS in vivo. At resting conditions, cc did not differ between GAERS and NEC. During repeated activation, cc declined in GAERS but not in NEC. This depression in cc was restored within 25 s and was prevented by intracellular presence of BAPTA in the activated but not in the coupled cell. Local application of gap junctional blockers into RTN of GAERS in vivo resulted in a decrease of spike wave discharge (SWD) activity. Repeated activation results in a short-term depression (STD) of gap junctional coupling in RTN neurons of GAERS, depending on intracellular Ca(2+) mechanisms in the activated cell. As blockage of gap junctions in vivo results in a decrease of SWD activity, the STD observed in GAERS is considered a compensatory mechanism, aimed to dampen SWD activity. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

  6. Incidence, clinical features, and implications on outcomes of neonatal late-onset sepsis with concurrent infectious focus.

    PubMed

    Wu, I-Hsyuan; Tsai, Ming-Horng; Lai, Mei-Yin; Hsu, Lee-Fen; Chiang, Ming-Chou; Lien, Reyin; Fu, Ren-Huei; Huang, Hsuan-Rong; Chu, Shih-Ming; Hsu, Jen-Fu

    2017-07-03

    Neonatal bloodstream infection (BSI) is the most important cause of morbidity and mortality in the neonatal intensive care unit (NICU). Although most neonatal BSIs are primary bacteremia, some are associated with a focus of infection. This distinction is not well characterized. All patients with neonatal late-onset sepsis (LOS) between January 2006 and December 2013 were enrolled. LOS was categorized as a BSI with a concurrent focus of infection if LOS occurred before or within 24 h after the diagnosis of a specific infectious entity, and as "primary bacteremia" if no concurrent focus of infection was identified. Data concerning demographics, hospital course, microbiology, and outcomes were compared via univariate and multivariate analyses. Of 948 episodes of neonatal LOS, 781 (82.4%) were primary bacteremia, whereas 167 (17.6%) were associated with a known focus of infection, including meningitis (n = 51, 5.4%), ventilator-associated pneumonia (VAP) (n = 36, 3.8%), catheter-related bloodstream infections (n = 57, 6.0%), and necrotizing enterocolitis (NEC) (n = 21, 2.2%). The majority of NEC-associated BSIs were caused by gram-negative bacilli (85.7%). Group B streptococcus accounted for nearly one-third of all meningitis cases (29.4%). Although sepsis-attributable mortality was comparable between primary bacteremia and neonatal BSIs with a focus of infection, neonatal BSIs with meningitis, VAP, and NEC had significantly higher rates of infectious complications. The independent risk factors of sepsis-attributable mortality were infectious complications (Odds ratio [OR] 6.98; 95% confidence interval [CI] 3.64-13.39, P < 0.001); history of one or more than one previous episode(s) of BSI (OR 2.40 and 7.40; 95% CI 1.21-4.74 and 3.70-14.78, P = 0.012 and <0.001, respectively); and underlying secondary pulmonary hypertension in neonates (OR 4.77; 95% CI 1.91-11.96, P = 0.001). A considerable proportion of neonatal LOS can be associated with known infectious foci in the NICU. The microbiologic etiology of neonatal LOS with a concurrent focus of infection is significantly different from that of primary bacteremia. Neonatal BSIs with concurrent meningitis, VAP, or NEC are significantly more likely to have infectious complications. This association independently leads to sepsis-attributable mortality.

  7. Bowel sonography in sepsis with pathological correlation: an experimental study.

    PubMed

    Kim, Hwa-Young; Kim, In-One; Kim, Woo Sun; Kang, Gyeong Hoon

    2011-02-01

    Sepsis predisposes full-term infants to necrotizing enterocolitis (NEC). As such, experimental induction of NEC was applied to a sepsis model to evaluate the potential role of US in the early diagnosis of NEC in full-term infants. To evaluate the resistive index (RI) of the superior mesenteric artery (SMA) on Doppler sonography in experimentally induced sepsis and correlate it with the pathological findings. Fifteen 1-week-old New Zealand white rabbits (control group n = 3, sepsis group n = 12) were used in this study. We injected 1 mg/kg of E. coli O55-B5 lipopolysaccharide (LPS) into 12 rabbits to induce sepsis. Then we conducted grayscale evaluation of the caliber of the abdominal aorta as well as bowel wall thickness and echogenicity. In addition, we measured peak systolic and end-diastolic velocities and SMA RI on Doppler sonography. Pathological findings were analyzed and correlated with RI readings. Peak systolic and end-diastolic velocities and SMA RI values were analyzed statistically at each hour using the Wilcoxon rank sum test; the control and sepsis groups were compared using the Mann-Whitney test. The bowel wall thickness in the sepsis group was significantly increased after LPS injection. The caliber of the abdominal aorta in the sepsis group was significantly decreased after LPS injection. There were echogenic foci (<10 in axial plane) in the bowel wall after LPS injection. Peak systolic velocity in the sepsis group was not significantly changed, but end-diastolic velocity was decreased. SMA RIs in the sepsis group were significantly increased post-LPS injection from baseline. In the control group there were no significant changes in bowel wall thickness, abdominal aorta caliber, bowel wall echogenicity or peak systolic and end-diastolic velocities and RIs. Pathologically, eight of the 12 rabbits in the sepsis group showed grade 1 intestinal injury, three showed grade 2 injury and one showed grade 3 injury. SMA RIs were higher in grades 2 and 3 than in grade 1 when measured at 2 h and 4 h. Sepsis caused necrotic injury in the animal models, and these findings were accompanied by significant changes on Doppler US. These findings could facilitate early detection of intestinal injury in septic infants with NEC.

  8. Assessment of Blood Collection from the Lateral Saphenous Vein for Microfilaria Counts in Mongolian Gerbils (Meriones unguiculatus) Infected with Brugia pahangi

    PubMed Central

    Alworth, Leanne C; Berghaus, Roy D; Kelly, Lisa M; Supakorndej, Prasit; Burkman, Erica J; Savadelis, Molly D; Cooper, Tanya L; Salyards, Gregory W; Harvey, Stephen B; Moorhead, Andrew R

    2015-01-01

    The NIH guidelines for survival bleeding of mice and rats note that using the retroorbital plexus has a greater potential for complications than do other methods of blood collection and that this procedure should be performed on anesthetized animals. Lateral saphenous vein puncture has a low potential for complications and can be performed without anesthesia. Mongolian gerbils (Meriones unguiculatus) are the preferred rodent model for filarial parasite research. To monitor microfilaria counts in the blood, blood sampling from the orbital plexus has been the standard. Our goal was to refine the blood collection technique. To determine whether blood collection from the lateral saphenous vein was a feasible alternative to retroorbital sampling, we compared microfilaria counts in blood samples collected by both methods from 21 gerbils infected with the filarial parasitic worm Brugia pahangi. Lateral saphenous vein counts were equivalent to retroorbital counts at relatively high counts (greater than 50 microfilariae per 20 µL) but were significantly lower than retroorbital counts when microfilarial concentrations were lower. Our results indicate that although retroorbital collection may be preferable when low concentrations of microfilariae need to be enumerated, the lateral saphenous vein is a suitable alternative site for blood sampling to determine microfilaremia and is a feasible refinement that can benefit the wellbeing of gerbils. PMID:26678366

  9. High-speed photon-counting x-ray computed tomography system utilizing a multipixel photon counter

    NASA Astrophysics Data System (ADS)

    Sato, Eiichi; Enomoto, Toshiyuki; Watanabe, Manabu; Hitomi, Keitaro; Takahashi, Kiyomi; Sato, Shigehiro; Ogawa, Akiro; Onagawa, Jun

    2009-07-01

    High-speed photon counting is useful for discriminating photon energy and for decreasing absorbed dose for patients in medical radiography, and the counting is usable for constructing an x-ray computed tomography (CT) system. A photon-counting x-ray CT system is of the first generation type and consists of an x-ray generator, a turn table, a translation stage, a two-stage controller, a multipixel photon counter (MPPC) module, a 1.0-mm-thick LSO crystal (scintillator), a counter card (CC), and a personal computer (PC). Tomography is accomplished by repeating the linear scanning and the rotation of an object, and projection curves of the object are obtained by the linear scanning using the detector consisting of a MPPC module and the LSO. The pulses of the event signal from the module are counted by the CC in conjunction with the PC. The lower level of the photon energy is roughly determined by a comparator circuit in the module, and the unit of the level is the photon equivalent (pe). Thus, the average photon energy of the x-ray spectra increases with increasing the lower-level voltage of the comparator. The maximum count rate was approximately 20 Mcps, and energy-discriminated CT was roughly carried out.

  10. Comparison of fluorescence microscopy and solid-phase cytometry methods for counting bacteria in water

    USGS Publications Warehouse

    Lisle, John T.; Hamilton, Martin A.; Willse, Alan R.; McFeters, Gordon A.

    2004-01-01

    Total direct counts of bacterial abundance are central in assessing the biomass and bacteriological quality of water in ecological and industrial applications. Several factors have been identified that contribute to the variability in bacterial abundance counts when using fluorescent microscopy, the most significant of which is retaining an adequate number of cells per filter to ensure an acceptable level of statistical confidence in the resulting data. Previous studies that have assessed the components of total-direct-count methods that contribute to this variance have attempted to maintain a bacterial cell abundance value per filter of approximately 106 cells filter-1. In this study we have established the lower limit for the number of bacterial cells per filter at which the statistical reliability of the abundance estimate is no longer acceptable. Our results indicate that when the numbers of bacterial cells per filter were progressively reduced below 105, the microscopic methods increasingly overestimated the true bacterial abundance (range, 15.0 to 99.3%). The solid-phase cytometer only slightly overestimated the true bacterial abundances and was more consistent over the same range of bacterial abundances per filter (range, 8.9 to 12.5%). The solid-phase cytometer method for conducting total direct counts of bacteria was less biased and performed significantly better than any of the microscope methods. It was also found that microscopic count data from counting 5 fields on three separate filters were statistically equivalent to data from counting 20 fields on a single filter.

  11. Personnel electronic neutron dosimeter

    DOEpatents

    Falk, R.B.; Tyree, W.H.

    1982-03-03

    A personnel electronic dosimeter includes a neutron-proton and neutron-alpha converter for providing an electrical signal having a magnitude proportional to the energy of a detected proton or alpha particle produced from the converter, a pulse generator circuit for generating a pulse having a duration controlled by the weighed effect of the amplitude of the electrical signal, an oscillator enabled by the pulse for generating a train of clock pulses for a time dependent upon the pulse length, a counter for counting the clock pulses, and an indicator for providing a direct reading and aural alarm when the count indicates that the wearer has been exposed to a selected level of neutron dose equivalent.

  12. Personnel electronic neutron dosimeter

    DOEpatents

    Falk, Roger B.; Tyree, William H.

    1984-12-18

    A personnel electronic dosimeter includes a neutron-proton and neutron-alpha converter for providing an electrical signal having a magnitude proportional to the energy of a detected proton or alpha particle produced from the converter, a pulse generator circuit for generating a pulse having a duration controlled by the weighed effect of the amplitude of the electrical signal, an oscillator enabled by the pulse for generating a train of clock pulses for a time dependent upon the pulse length, a counter for counting the clock pulses, and an indicator for providing a direct reading and aural alarm when the count indicates that the wearer has been exposed to a selected level of neutron dose equivalent.

  13. 8. BOSTON & PROVIDENCE RAILROAD: CANTON VIADUCT. CANTON, NORFOLK CO., ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    8. BOSTON & PROVIDENCE RAILROAD: CANTON VIADUCT. CANTON, NORFOLK CO., MA. (Not on NEC). (See HAER No. MA-27 for further documentation on this site.) - Northeast Railroad Corridor, Amtrak Route between RI/MA State Line & South Station, Boston, Suffolk County, MA

  14. 9. Boston & Providence Railroad: Canton Viaduct. Canton, Norfolk Co., ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    9. Boston & Providence Railroad: Canton Viaduct. Canton, Norfolk Co., MA. (Not on NEC). (See HAER No. MA-27 for further documentation on this site). - Northeast Railroad Corridor, Amtrak Route between RI/MA State Line & South Station, Boston, Suffolk County, MA

  15. 7. BOSTON & PROVIDENCE RAILROAD: CANTON VIADUCT. CANTON, NORFOLK CO., ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. BOSTON & PROVIDENCE RAILROAD: CANTON VIADUCT. CANTON, NORFOLK CO., MA. (Not on NEC). (See HAER No. MA-27 for further documentation on this site.) - Northeast Railroad Corridor, Amtrak Route between RI/MA State Line & South Station, Boston, Suffolk County, MA

  16. Permeable pavement demonstration at the Edison Environmental Center

    EPA Science Inventory

    There are few studies of full-scale, outdoor, replicated, functioning pervious pavement systems. More studies of pervious pavement operating in its intended use (parking lot, roadway, etc.) during a range of climatic events, daily usage conditions, and maintenance regimes are nec...

  17. Transportation policy and governance in the northeast corridor : an overview of major public agencies.

    DOT National Transportation Integrated Search

    2009-08-01

    One of the most consistent topics of discussion about the Northeast Corridor (hereafter : NEC or the Corridor), particularly the central portion between Boston and Washington, : D.C., is the viability and efficiency of its transportation ...

  18. Risky Business II: Finding Big Bucks. Panel IV.

    ERIC Educational Resources Information Center

    Appalachia, 1986

    1986-01-01

    Five panelists discuss alternatives to venture capital sources for Appalachian business expansion, new institutions created or supported by state and local governments to provide capital, and how businesses can best position themselves to take advantage of all capital sources. (NEC)

  19. Carbohydrate maldigestion induces necrotizing enterocolitis in preterm pigs

    USDA-ARS?s Scientific Manuscript database

    Necrotizing enterocolitis (NEC) remains the most severe gastrointestinal disorder in preterm infants. It is associated with the initiation of enteral nutrition and may be related to immature carbohydrate digestive capacity. We tested the hypothesis that a formula containing maltodextrin vs. lactose ...

  20. High speed rail as a complex sociotechnical system.

    DOT National Transportation Integrated Search

    2015-10-01

    The primary goal of this research is to study the impact of Amtraks performance in the Northeast Corridor (NEC). This report focuses on Amtraks Acela and Regional passengers, as well as the travel time performance of these services in the last ...

  1. Making Every Seat Count: Space Management at Peak Times in a University Library

    ERIC Educational Resources Information Center

    Breen, Michelle; Dundon, Mary; McCaffrey, Ciara

    2018-01-01

    This study explores the library equivalent of the "towels on deck chairs" phenomenon of students reserving library seats: the practice of leaving personal belongings unattended at a library study space for long periods of time, rendering the desk unavailable for use by others. It presents highly inefficient use of high value academic…

  2. 29 CFR 825.603 - Special rules for school employees, duration of FMLA leave.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., DEPARTMENT OF LABOR OTHER LAWS THE FAMILY AND MEDICAL LEAVE ACT OF 1993 Special Rules Applicable to Employees... counted as FMLA leave; however, the employer shall be required to maintain the employee's group health insurance and restore the employee to the same or equivalent job including other benefits at the conclusion...

  3. The Einstein Slew Survey

    NASA Technical Reports Server (NTRS)

    Elvis, Martin; Plummer, David; Schachter, Jonathan; Fabbiano, G.

    1992-01-01

    A catalog of 819 sources detected in the Einstein IPC Slew Survey of the X-ray sky is presented; 313 of the sources were not previously known as X-ray sources. Typical count rates are 0.1 IPC count/s, roughly equivalent to a flux of 3 x 10 exp -12 ergs/sq cm s. The sources have positional uncertainties of 1.2 arcmin (90 percent confidence) radius, based on a subset of 452 sources identified with previously known pointlike X-ray sources (i.e., extent less than 3 arcmin). Identifications based on a number of existing catalogs of X-ray and optical objects are proposed for 637 of the sources, 78 percent of the survey (within a 3-arcmin error radius) including 133 identifications of new X-ray sources. A public identification data base for the Slew Survey sources will be maintained at CfA, and contributions to this data base are invited.

  4. Waveguide integrated superconducting single-photon detectors with high internal quantum efficiency at telecom wavelengths

    PubMed Central

    Kahl, Oliver; Ferrari, Simone; Kovalyuk, Vadim; Goltsman, Gregory N.; Korneev, Alexander; Pernice, Wolfram H. P.

    2015-01-01

    Superconducting nanowire single-photon detectors (SNSPDs) provide high efficiency for detecting individual photons while keeping dark counts and timing jitter minimal. Besides superior detection performance over a broad optical bandwidth, compatibility with an integrated optical platform is a crucial requirement for applications in emerging quantum photonic technologies. Here we present SNSPDs embedded in nanophotonic integrated circuits which achieve internal quantum efficiencies close to unity at 1550 nm wavelength. This allows for the SNSPDs to be operated at bias currents far below the critical current where unwanted dark count events reach milli-Hz levels while on-chip detection efficiencies above 70% are maintained. The measured dark count rates correspond to noise-equivalent powers in the 10−19 W/Hz−1/2 range and the timing jitter is as low as 35 ps. Our detectors are fully scalable and interface directly with waveguide-based optical platforms. PMID:26061283

  5. Waveguide integrated superconducting single-photon detectors with high internal quantum efficiency at telecom wavelengths.

    PubMed

    Kahl, Oliver; Ferrari, Simone; Kovalyuk, Vadim; Goltsman, Gregory N; Korneev, Alexander; Pernice, Wolfram H P

    2015-06-10

    Superconducting nanowire single-photon detectors (SNSPDs) provide high efficiency for detecting individual photons while keeping dark counts and timing jitter minimal. Besides superior detection performance over a broad optical bandwidth, compatibility with an integrated optical platform is a crucial requirement for applications in emerging quantum photonic technologies. Here we present SNSPDs embedded in nanophotonic integrated circuits which achieve internal quantum efficiencies close to unity at 1550 nm wavelength. This allows for the SNSPDs to be operated at bias currents far below the critical current where unwanted dark count events reach milli-Hz levels while on-chip detection efficiencies above 70% are maintained. The measured dark count rates correspond to noise-equivalent powers in the 10(-19) W/Hz(-1/2) range and the timing jitter is as low as 35 ps. Our detectors are fully scalable and interface directly with waveguide-based optical platforms.

  6. Monte Carlo simulation of Ray-Scan 64 PET system and performance evaluation using GATE toolkit

    NASA Astrophysics Data System (ADS)

    Li, Suying; Zhang, Qiushi; Vuletic, Ivan; Xie, Zhaoheng; Yang, Kun; Ren, Qiushi

    2017-02-01

    In this study, we aimed to develop a GATE model for the simulation of Ray-Scan 64 PET scanner and model its performance characteristics. A detailed implementation of system geometry and physical process were included in the simulation model. Then we modeled the performance characteristics of Ray-Scan 64 PET system for the first time, based on National Electrical Manufacturers Association (NEMA) NU-2 2007 protocols and validated the model against experimental measurement, including spatial resolution, sensitivity, counting rates and noise equivalent count rate (NECR). Moreover, an accurate dead time module was investigated to simulate the counting rate performance. Overall results showed reasonable agreement between simulation and experimental data. The validation results showed the reliability and feasibility of the GATE model to evaluate major performance of Ray-Scan 64 PET system. It provided a useful tool for a wide range of research applications.

  7. Demonstration of the feasibility of large-port-count optical switching using a hybrid Mach-Zehnder interferometer-semiconductor optical amplifier switch module in a recirculating loop.

    PubMed

    Cheng, Q; Wonfor, A; Wei, J L; Penty, R V; White, I H

    2014-09-15

    For what we believe is the first time, the feasibility of large-port-count nanosecond-reconfiguration-time optical switches is demonstrated using a hybrid approach, where Mach-Zehnder interferometric (MZI) switches provide low-loss, high-speed routing with short semiconductor optical amplifiers (SOAs) being integrated to enhance extinction. By repeatedly passing signals through a monolithic hybrid dilated 2×2 switch module in a recirculating loop, the potential performance of high-port-count switches using the hybrid approach is demonstrated. Experimentally, a single pass switch penalty of only 0.1 dB is demonstrated for the 2×2 module, while even after seven passes through the switch, equivalent to a 128×128 router, a penalty of only 2.4 dB is recorded at a data rate of 10 Gb/s.

  8. 46 CFR 129.370 - Equipment grounding.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... and to a common ground by a conductor not normally carrying current. (b) Each metallic case of... grounding conductor must be sized to comply with section 250-95 of NEC (NFPA 70). (d) Each nonmetallic mast and topmast must have a lightning-ground conductor. ...

  9. 46 CFR 129.370 - Equipment grounding.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... and to a common ground by a conductor not normally carrying current. (b) Each metallic case of... grounding conductor must be sized to comply with section 250-95 of NEC (NFPA 70). (d) Each nonmetallic mast and topmast must have a lightning-ground conductor. ...

  10. 7 CFR 2900.3 - Essential agricultural uses.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...). 4971Irrigation Systems. Fertilizer and Agricultural Chemicals (Process and Feedstock Use Only) 1474Potash, Soda.... (Agricultural related only). 2865Cyclic Crudes and Cyclic Intermediates, Dyes and Organic Pigments (Agricutural related only). 2869Industrial Organic Chemicals, n.e.c. (Agricutural related only). 287Agricultural...

  11. Computer Model Helps Communities Gauge Effects of New Industry.

    ERIC Educational Resources Information Center

    Long, Celeste; And Others

    1987-01-01

    Describes computer Industrial Impact Model used by Texas Agricultural Extension Service rural planners to assess potential benefits and costs of new firms on community private and public sectors. Presents selected data/results for two communities assessing impact of the same plant. (NEC)

  12. The Challenge of Research on Farm Women.

    ERIC Educational Resources Information Center

    Elbert, Sarah

    1981-01-01

    Researchers studying farm women must ask if successful integration of family and farm systems in the late 20th century involves feminism and, if so, what form of feminism. Available from: Rural Sociological Society, 325 Morgan Hall, University of Tennessee, Knoxville, TN 37916. (NEC)

  13. A Nineteenth-Century French Proposal to Use School Vouchers.

    ERIC Educational Resources Information Center

    Van Vliet, W.; Smyth, J. A.

    1982-01-01

    In light of the current American interest in school vouchers as proposed by economist Milton Friedman, recapitulates the origins, content, and fate of an 1872 law drafted by a French parliamentary commission to establish a countrywide voucher scheme for primary schools. (NEC)

  14. Northeast Corridor Improvement Project Electrification - New Haven, CT to Boston, MA : Draft Environmental Impact Statement. Volume 1.

    DOT National Transportation Integrated Search

    1993-09-01

    The impacts of extending electrification on the National Railroad Passenger Corporation's (Amtrak) Northeast Corridor (NEC) from New Haven, Connecticut to Boston, Massachusetts are of direct concern to the Federal Railroad Administration (FRA). To im...

  15. Safety model assessment and two-lane urban crash model

    DOT National Transportation Integrated Search

    2008-10-01

    There are many reasons to be concerned with estimating the frequency and social costs of highway accidents, but most reasons are motivated by a desire to minimize these costs to the extent feasible. Competition for scarce resources is a practical nec...

  16. EVALUATION OF EXPOSURE MEASUREMENT METHODS AND APPROACHES FOR THE NATIONAL CHILDREN'S STUDY

    EPA Science Inventory

    Several hypotheses have been proposed for the National Children's Study to examine the role of environmental exposures to chemical pollutants in health outcomes including asthma and impaired neurobehaviorial or neurocognitive function. To address these hypotheses, it will be nec...

  17. 2016 National Earthquake Conference

    Science.gov Websites

    Thank you to our Presenting Sponsor, California Earthquake Authority. What's New? What's Next ? What's Your Role in Building a National Strategy? The National Earthquake Conference (NEC) is a , state government leaders, social science practitioners, U.S. State and Territorial Earthquake Managers

  18. EPA’s Lead-based Paint Enforcement Helps Protect Children and Vulnerable Communities

    EPA Pesticide Factsheets

    The Toxic Substances Control Act (TSCA) New and Existing Chemicals (NEC) Program is exclusively a federal program that provides for review of the risk of chemicals prior to their manufacture and importation to prevent unreasonable risk to human health

  19. Capitalizing upon Rural Resources.

    ERIC Educational Resources Information Center

    Worth, Charles E.

    1987-01-01

    Offers three examples of how low cost and innovative methods can be planned to bring expertise and resources to rural school districts: hosting a state/regional educational conference, arranging local evening classes from nearby small colleges/universities, and building/maintaining working contacts with computer software representatives. (NEC)

  20. Fracture resistance of simulated immature teeth after different intra-radicular treatments.

    PubMed

    Sivieri-Araujo, Gustavo; Tanomaru-Filho, Mario; Guerreiro-Tanomaru, Juliane Maria; Bortoluzzi, Eduardo Antunes; Jorge, Érica Gouveia; Reis, José Maurício Dos Santos Nunes

    2015-01-01

    The aim of this study was to evaluate the fracture resistance of simulated immature teeth after different intra-radicular treatments. Crowns and roots of bovine incisors were cut transversally and removed to simulate immature teeth. Root canal preparation and flaring were performed using a bur in crown-apex and apex-crown direction. The samples were distributed into 5 groups (n=10): Positive control (PoC) - no root canal flaring or filling; Negative control (NeC) - teeth were sectioned and their root canals were flared; Direct anatomical glass fiber post (RaP) - #2 Reforpost main glass fiber post relined with composite resin; Double tapered conical glass fiber posts (ExP) - #3 Exacto glass fiber post; and #2 Reforpost main glass fiber + Reforpin accessory glass fiber posts (RrP). In RaP, ExP and RrP, 4.0-mm apical plugs were done with MTA Angelus. The specimens were embedded in polystyrene resin inside cylinders and the periodontal ligament was simulated with a polyether-based impression material. The specimens were submitted to compressive fracture strength test (0.5 mm/min at 135° relative to the long axis of the tooth) in a servo-hydraulic mechanical testing machine MTS 810. Data were subjected to one-way ANOVA and Dunnett's C or Tukey's tests (α=0.05). The control groups (PoC and NeC) showed lower fracture strength than the experimental groups. NeC presented the lowest resistance and ExP presented the highest resistance among the experimental groups. The flaring procedures produced a detrimental effect on the fracture resistance of the bovine teeth. Glass fiber intra-radicular posts increased significantly the fracture resistance of simulated immature teeth.

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

    Dale K. Kotter; Steven D. Novack

    DRAFT For Submittal to Journal of Solar Energy - Rev 10.1 ---SOL-08-1091 SOLAR Nantenna Electromagnetic Collectors Dale K. Kotter Idaho National Laboratory Steven D. Novack Idaho National Laboratory W. Dennis Slafer MicroContinuum, Inc. Patrick Pinhero University of Missouri ABSTRACT The research described in this paper explores a new and efficient approach for producing electricity from the abundant energy of the sun, using nanoantenna (nantenna) electromagnetic collectors (NECs). NEC devices target mid-infrared wavelengths, where conventional photovoltaic (PV) solar cells are inefficient and where there is an abundance of solar energy. The initial concept of designing NECs was based on scaling ofmore » radio frequency antenna theory to the infrared and visible regions. This approach initially proved unsuccessful because the optical behavior of materials in the terahertz (THz) region was overlooked and, in addition, economical nanofabrication methods were not previously available to produce the optical antenna elements. This paper demonstrates progress in addressing significant technological barriers, including: 1) development of frequency-dependent modeling of double-feedpoint square spiral nantenna elements; 2) selection of materials with proper THz properties; and 3) development of novel manufacturing methods that could potentially enable economical large-scale manufacturing. We have shown that nantennas can collect infrared energy and induce THz currents, and we have also developed cost-effective proof-of-concept fabrication techniques for the large-scale manufacture of simple square loop nantenna arrays. Future work is planned to embed rectifiers into the double-feedpoint antenna structures. This work represents an important first step toward the ultimate realization of a low-cost device that will collect as well as convert this radiation into electricity. This could lead to a broadband, high conversion efficiency low-cost solution to complement conventional PV devices.« less

  2. Probiotics feeding in prevention of urinary tract infection, bacterial sepsis and necrotizing enterocolitis in preterm infants. A prospective double-blind study.

    PubMed

    Dani, Carlo; Biadaioli, Roberto; Bertini, Giovanna; Martelli, Elena; Rubaltelli, Firmino F

    2002-08-01

    It has been suggested that probiotics can reduce the overgrowth of pathogens in the bowels of preterm infants and contribute to the reduction of the incidence of nosocomial infections in neonatal intensive care units (NICUs). The purpose of this study was to evaluate the effectiveness of Lactobacillus GG supplementation in reducing the incidence of urinary tract infections (UTIs), bacterial sepsis and necrotizing enterocolitis (NEC) in preterm infants. A double-blind study was conducted in 12 Italian NICUs. Newborn infants with a gestational age <33 weeks or birthweight <1,500 g were randomized to receive standard milk feed supplemented with Lactobacillus GG (Dicoflor), Dicofarm, Rome, Italy) in a dose of 6 x 10(9) colony-forming units (cfu) once a day until discharge, starting with the first feed or placebo. Five hundred eighty-five patients were studied. The probiotics group (n = 295) and the placebo group (n = 290) exhibited similar clinical characteristics. The duration of Lactobacillus GG and placebo supplementation was 47.3 +/- 26.0 and 48.2 +/- 24.3 days, respectively. Although UTIs (3.4 vs. 5.8%) and NEC (1.4 vs. 2.7%) were found less frequently in the probiotic group compared to the control group, these differences were not significant. Bacterial sepsis was more frequent in the probiotics group (4.4%, n = 11) than in the placebo group (3.8%, n = 9), but the difference was not significant. Seven days of Lactobacillus GG supplementation starting with the first feed is not effective in reducing the incidence of UTIs, NEC and sepsis in preterm infants. Further studies are required to confirm our results in lower birthweight populations. Copyright 2002 S. Karger AG, Basel

  3. Genome-wide analysis of transcription factors during somatic embryogenesis in banana (Musa spp.) cv. Grand Naine.

    PubMed

    Shivani; Awasthi, Praveen; Sharma, Vikrant; Kaur, Navjot; Kaur, Navneet; Pandey, Pankaj; Tiwari, Siddharth

    2017-01-01

    Transcription factors BABY BOOM (BBM), WUSCHEL (WUS), BSD, LEAFY COTYLEDON (LEC), LEAFY COTYLEDON LIKE (LIL), VIVIPAROUS1 (VP1), CUP SHAPED COTYLEDONS (CUC), BOLITA (BOL), and AGAMOUS LIKE (AGL) play a crucial role in somatic embryogenesis. In this study, we identified eighteen genes of these nine transcription factors families from the banana genome database. All genes were analyzed for their structural features, subcellular, and chromosomal localization. Protein sequence analysis indicated the presence of characteristic conserved domains in these transcription factors. Phylogenetic analysis revealed close evolutionary relationship among most transcription factors of various monocots. The expression patterns of eighteen genes in embryogenic callus containing somatic embryos (precisely isolated by Laser Capture Microdissection), non-embryogenic callus, and cell suspension cultures of banana cultivar Grand Naine were analyzed. The application of 2, 4-dichlorophenoxyacetic acid (2, 4-D) in the callus induction medium enhanced the expression of MaBBM1, MaBBM2, MaWUS2, and MaVP1 in the embryogenic callus. It suggested 2, 4-D acts as an inducer for the expression of these genes. The higher expression of MaBBM2 and MaWUS2 in embryogenic cell suspension (ECS) as compared to non-embryogenic cells suspension (NECS), suggested that these genes may play a crucial role in banana somatic embryogenesis. MaVP1 showed higher expression in both ECS and NECS, whereas MaLEC2 expression was significantly higher in NECS. It suggests that MaLEC2 has a role in the development of non-embryogenic cells. We postulate that MaBBM2 and MaWUS2 can be served as promising molecular markers for the embryogencity in banana.

  4. Rayleigh Wave and Shear Wave Tomography of Northeastern China: Results Coconstrained by Multiple Datasets

    NASA Astrophysics Data System (ADS)

    Zhou, T.; Chen, J.; Han, J.; Tian, Y.; Wu, M.; Yang, Y.; Ning, J.

    2014-12-01

    We investigate crustal and upper mantle phase velocity structures beneath NorthEastern China (NEC, 40°-54°N, 112°-135°E), a tectonically active region with continental volcanicity divided by active faults. Rayleigh wave phase velocity is obtained respectively by Ambient Noise Method (ANM, Lin et al., GJI, 2009), Two Station Method (TSM, Meier et al., GJI, 2004) and Two Plane Wave Method (TPWM, Yang and Forsyth, JGR, 2005), assuring good frequency coverage. Two-year' events with magnitude Ms>5.5 and epicentral distance Δ>30°recorded by NECESSArray and some permanent stations of CEA are together used in TPWM and TSM, while 1 s continuous seismic observations in the same period are employed in ANM. The period of Rayleigh wave phase velocity spans from 6 s to 150 s, i.e., from 6 s to 30 s (ANM); 30 s to 100 s (TPWM) and 30 s to 150 s (TSM). Shear wave velocity structure of the research region is obtained by Weighted Least Squares Inversion, in which the weight is adopted as function of data quality. Our results not only display close relation with tectonics of this region, such as mountains, sedimentary basins, faults, but also reveal variation feature of crustal thickness. Moreover, our results clearly show that all volcanos in this region have their roots — low velocity zones, among them the roots of Changbai, Jingbohu, Wudalianchi are obviously connected, while the biggest one of Daxinganling is separated. This feature might be result of an early intense eruption in western NEC and a late weak one in eastern NEC.

  5. Beyond Necrotizing Enterocolitis Prevention: Improving Outcomes with an Exclusive Human Milk-Based Diet.

    PubMed

    Hair, Amy B; Peluso, Allison M; Hawthorne, Keli M; Perez, Jose; Smith, Denise P; Khan, Janine Y; O'Donnell, Andrea; Powers, Richard J; Lee, Martin L; Abrams, Steven A

    2016-03-01

    The aim of this study was to compare outcomes of infants pre and post initiation of a feeding protocol providing an exclusive human milk-based diet (HUM). In a multicenter retrospective cohort study, infants with a birth weight <1,250 g who received a bovine-based diet (BOV) of mother's own milk fortified with bovine fortifier and/or preterm formula were compared to infants who received a newly introduced HUM feeding protocol. Infants were excluded if they had major congenital anomalies or died in the first 12 hours of life. Data were collected 2-3 years prior to and after introduction of an exclusive HUM diet. Primary outcomes were necrotizing enterocolitis (NEC) and mortality. Secondary outcomes included late-onset sepsis, retinopathy of prematurity (ROP), and bronchopulmonary dysplasia (BPD). A total of 1,587 infants were included from four centers in Texas, Illinois, Florida, and California. There were no differences in baseline demographics or growth of infants. The HUM group had significantly lower incidence of proven NEC (16.7% versus 6.9%, p < 0.00001), mortality (17.2% versus 13.6%, p = 0.04), late-onset sepsis (30.3% versus 19.0%, p < 0.00001), ROP (9% versus 5.2%, p = 0.003), and BPD (56.3% versus 47.7%, p = 0.0015) compared with the BOV group. Extremely premature infants who received an exclusive HUM diet had a significantly lower incidence of NEC and mortality. The HUM group also had a reduction in late-onset sepsis, BPD, and ROP. This multicenter study further emphasizes the many benefits of an exclusive HUM diet, and demonstrates multiple improved outcomes after implementation of such a feeding protocol.

  6. Genome-wide analysis of transcription factors during somatic embryogenesis in banana (Musa spp.) cv. Grand Naine

    PubMed Central

    Shivani; Awasthi, Praveen; Sharma, Vikrant; Kaur, Navjot; Kaur, Navneet; Pandey, Pankaj

    2017-01-01

    Transcription factors BABY BOOM (BBM), WUSCHEL (WUS), BSD, LEAFY COTYLEDON (LEC), LEAFY COTYLEDON LIKE (LIL), VIVIPAROUS1 (VP1), CUP SHAPED COTYLEDONS (CUC), BOLITA (BOL), and AGAMOUS LIKE (AGL) play a crucial role in somatic embryogenesis. In this study, we identified eighteen genes of these nine transcription factors families from the banana genome database. All genes were analyzed for their structural features, subcellular, and chromosomal localization. Protein sequence analysis indicated the presence of characteristic conserved domains in these transcription factors. Phylogenetic analysis revealed close evolutionary relationship among most transcription factors of various monocots. The expression patterns of eighteen genes in embryogenic callus containing somatic embryos (precisely isolated by Laser Capture Microdissection), non-embryogenic callus, and cell suspension cultures of banana cultivar Grand Naine were analyzed. The application of 2, 4-dichlorophenoxyacetic acid (2, 4-D) in the callus induction medium enhanced the expression of MaBBM1, MaBBM2, MaWUS2, and MaVP1 in the embryogenic callus. It suggested 2, 4-D acts as an inducer for the expression of these genes. The higher expression of MaBBM2 and MaWUS2 in embryogenic cell suspension (ECS) as compared to non-embryogenic cells suspension (NECS), suggested that these genes may play a crucial role in banana somatic embryogenesis. MaVP1 showed higher expression in both ECS and NECS, whereas MaLEC2 expression was significantly higher in NECS. It suggests that MaLEC2 has a role in the development of non-embryogenic cells. We postulate that MaBBM2 and MaWUS2 can be served as promising molecular markers for the embryogencity in banana. PMID:28797040

  7. The effect of group-based exercise on cognitive performance and mood in seniors residing in intermediate care and self-care retirement facilities: a randomised controlled trial.

    PubMed

    Brown, A K; Liu-Ambrose, T; Tate, R; Lord, S R

    2009-08-01

    To determine the effect of a general group-based exercise programme on cognitive performance and mood among seniors without dementia living in retirement villages. Randomised controlled trial. Four intermediate care and four self-care retirement village sites in Sydney, Australia. 154 seniors (19 men, 135 women; age range 62 to 95 years), who were residents of intermediate care and self-care retirement facilities. Participants were randomised to one of three experimental groups: (1) a general group-based exercise (GE) programme composed of resistance training and balance training exercises; (2) a flexibility exercise and relaxation technique (FR) programme; or (3) no-exercise control (NEC). The intervention groups (GE and FR) participated in 1-hour exercise classes twice a week for a total period of 6 months. Using standard neuropsychological tests, we assessed cognitive performance at baseline and at 6-month re-test in three domains: (1) fluid intelligence; (2) visual, verbal and working memory; and (3) executive functioning. We also assessed mood using the Geriatric Depression Scale (GDS) and the Positive and Negative Affect Schedule (PANAS). The GE programme significantly improved cognitive performance of fluid intelligence compared with FR or NEC. There were also significant improvements in the positive PANAS scale within both the GE and FR groups and an indication that the two exercise programmes reduced depression in those with initially high GDS scores. Our GE programme significantly improved cognitive performance of fluid intelligence in seniors residing in retirement villages compared with our FR programme and the NEC group. Furthermore, both group-based exercise programmes were beneficial for certain aspects of mood within the 6-month intervention period.

  8. Impact of maternal diabetes mellitus on mortality and morbidity of very low birth weight infants: a multicenter Latin America study.

    PubMed

    Grandi, Carlos; Tapia, Jose L; Cardoso, Viviane C

    2015-01-01

    To compare mortality and morbidity in very low birth weight infants (VLBWI) born to women with and without diabetes mellitus (DM). This was a cohort study with retrospective data collection (2001-2010, n=11.991) from the NEOCOSUR network. Adjusted odds ratios and 95% confidence intervals were calculated for the outcome of neonatal mortality and morbidity as a function of maternal DM. Women with no DM served as the reference group. The rate of maternal DM was 2.8% (95% CI: 2.5-3.1), but a significant (p=0.019) increase was observed between 2001-2005 (2.4%, 2.1-2.8) and 2006-2010 (3.2%, 2.8-3.6). Mothers with DM were more likely to have received a complete course of prenatal steroids than those without DM. Infants of diabetic mothers had a slightly higher gestational age and birth weight than infants of born to non-DM mothers. Distribution of mean birth weight Z-scores, small for gestational age status, and Apgar scores were similar. There were no significant differences between the two groups regarding respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, and patent ductus arteriosus. Delivery room mortality, total mortality, need for mechanical ventilation, and early-onset sepsis rates were significantly lower in the diabetic group, whereas necrotizing enterocolitis (NEC) was significantly higher in infants born to DM mothers. In the logistic regression analysis, NEC grades 2-3 was the only condition independently associated with DM (adjusted OR: 1.65 [95% CI: 1.2 -2.27]). VLBWI born to DM mothers do not appear to be at an excess risk of mortality or early morbidity, except for NEC. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  9. Community production modulates coral reef pH and the sensitivity of ecosystem calcification to ocean acidification

    NASA Astrophysics Data System (ADS)

    DeCarlo, Thomas M.; Cohen, Anne L.; Wong, George T. F.; Shiah, Fuh-Kwo; Lentz, Steven J.; Davis, Kristen A.; Shamberger, Kathryn E. F.; Lohmann, Pat

    2017-01-01

    Coral reefs are built of calcium carbonate (CaCO3) produced biogenically by a diversity of calcifying plants, animals, and microbes. As the ocean warms and acidifies, there is mounting concern that declining calcification rates could shift coral reef CaCO3 budgets from net accretion to net dissolution. We quantified net ecosystem calcification (NEC) and production (NEP) on Dongsha Atoll, northern South China Sea, over a 2 week period that included a transient bleaching event. Peak daytime pH on the wide, shallow reef flat during the nonbleaching period was ˜8.5, significantly elevated above that of the surrounding open ocean (˜8.0-8.1) as a consequence of daytime NEP (up to 112 mmol C m-2 h-1). Diurnal-averaged NEC was 390 ± 90 mmol CaCO3 m-2 d-1, higher than any other coral reef studied to date despite comparable calcifier cover (25%) and relatively high fleshy algal cover (19%). Coral bleaching linked to elevated temperatures significantly reduced daytime NEP by 29 mmol C m-2 h-1. pH on the reef flat declined by 0.2 units, causing a 40% reduction in NEC in the absence of pH changes in the surrounding open ocean. Our findings highlight the interactive relationship between carbonate chemistry of coral reef ecosystems and ecosystem production and calcification rates, which are in turn impacted by ocean warming. As open-ocean waters bathing coral reefs warm and acidify over the 21st century, the health and composition of reef benthic communities will play a major role in determining on-reef conditions that will in turn dictate the ecosystem response to climate change.

  10. Predictors of Enteral Autonomy in Children with Intestinal Failure: A Multicenter Cohort Study.

    PubMed

    Khan, Faraz A; Squires, Robert H; Litman, Heather J; Balint, Jane; Carter, Beth A; Fisher, Jeremy G; Horslen, Simon P; Jaksic, Tom; Kocoshis, Samuel; Martinez, J Andres; Mercer, David; Rhee, Susan; Rudolph, Jeffrey A; Soden, Jason; Sudan, Debra; Superina, Riccardo A; Teitelbaum, Daniel H; Venick, Robert; Wales, Paul W; Duggan, Christopher

    2015-07-01

    In a large cohort of children with intestinal failure (IF), we sought to determine the cumulative incidence of achieving enteral autonomy and identify patient and institutional characteristics associated with enteral autonomy. A multicenter, retrospective cohort analysis from the Pediatric Intestinal Failure Consortium was performed. IF was defined as severe congenital or acquired gastrointestinal diseases during infancy with dependence on parenteral nutrition (PN) >60 days. Enteral autonomy was defined as PN discontinuation >3 months. A total of 272 infants were followed for a median (IQR) of 33.5 (16.2-51.5) months. Enteral autonomy was achieved in 118 (43%); 36 (13%) remained PN dependent and 118 (43%) patients died or underwent transplantation. Multivariable analysis identified necrotizing enterocolitis (NEC; OR 2.42, 95% CI 1.33-4.47), care at an IF site without an associated intestinal transplantation program (OR 2.73, 95% CI 1.56-4.78), and an intact ileocecal valve (OR 2.80, 95% CI 1.63-4.83) as independent risk factors for enteral autonomy. A second model (n = 144) that included only patients with intraoperatively measured residual small bowel length found NEC (OR 3.44, 95% CI 1.36-8.71), care at a nonintestinal transplantation center (OR 6.56, 95% CI 2.53-16.98), and residual small bowel length (OR 1.04 cm, 95% CI 1.02-1.06 cm) to be independently associated with enteral autonomy. A substantial proportion of infants with IF can achieve enteral autonomy. Underlying NEC, preserved ileocecal valve, and longer bowel length are associated with achieving enteral autonomy. It is likely that variations in institutional practices and referral patterns also affect outcomes in children with IF. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Podocyte Number in Children and Adults: Associations with Glomerular Size and Numbers of Other Glomerular Resident Cells

    PubMed Central

    Puelles, Victor G.; Douglas-Denton, Rebecca N.; Cullen-McEwen, Luise A.; Li, Jinhua; Hughson, Michael D.; Hoy, Wendy E.; Kerr, Peter G.

    2015-01-01

    Increases in glomerular size occur with normal body growth and in many pathologic conditions. In this study, we determined associations between glomerular size and numbers of glomerular resident cells, with a particular focus on podocytes. Kidneys from 16 male Caucasian-Americans without overt renal disease, including 4 children (≤3 years old) to define baseline values of early life and 12 adults (≥18 years old), were collected at autopsy in Jackson, Mississippi. We used a combination of immunohistochemistry, confocal microscopy, and design-based stereology to estimate individual glomerular volume (IGV) and numbers of podocytes, nonepithelial cells (NECs; tuft cells other than podocytes), and parietal epithelial cells (PECs). Podocyte density was calculated. Data are reported as medians and interquartile ranges (IQRs). Glomeruli from children were small and contained 452 podocytes (IQR=335–502), 389 NECs (IQR=265–498), and 146 PECs (IQR=111–206). Adult glomeruli contained significantly more cells than glomeruli from children, including 558 podocytes (IQR=431–746; P<0.01), 1383 NECs (IQR=998–2042; P<0.001), and 367 PECs (IQR=309–673; P<0.001). However, large adult glomeruli showed markedly lower podocyte density (183 podocytes per 106 µm3) than small glomeruli from adults and children (932 podocytes per 106 µm3; P<0.001). In conclusion, large adult glomeruli contained more podocytes than small glomeruli from children and adults, raising questions about the origin of these podocytes. The increased number of podocytes in large glomeruli does not match the increase in glomerular size observed in adults, resulting in relative podocyte depletion. This may render hypertrophic glomeruli susceptible to pathology. PMID:25568174

  12. Family meal frequency among children and adolescents with eating disorders.

    PubMed

    Elran-Barak, Roni; Sztainer, Maya; Goldschmidt, Andrea B; Le Grange, Daniel

    2014-07-01

    Previous studies on family meals and disordered eating have mainly drawn their samples from the general population. The goal of the current study is to determine family meal frequency among children and adolescents with anorexia nervosa (AN), bulimia nervosa (BN), and feeding or eating disorder not elsewhere classified (FED-NEC) and to examine whether family meal frequency is associated with eating disorder psychopathology. Participants included 154 children and adolescents (M = 14.92 ± 2.62), who met criteria for AN (n = 60), BN (n = 32), or FED-NEC (n = 62). All participants completed the Eating Disorder Examination and the Family Meal Questionnaire prior to treatment at the University of Chicago Eating Disorders Program. AN and BN participants significantly differed in terms of family meal frequency. A majority of participants with AN (71.7%), compared with less than half (43.7%) of participants with BN, reported eating dinner with their family frequently (five or more times per week). Family meal frequency during dinner was significantly and negatively correlated with dietary restraints and eating concerns among participants with BN (r = -.381, r = -.366, p < .05) and FED-NEC (r = -.340, r = -.276, p < .05). AN patients' higher family meal frequency may be explained by their parents' relatively greater vigilance over eating, whereas families of BN patients may be less aware of eating disorder behaviors and hence less insistent upon family meals. Additionally, children and adolescents with AN may be more inhibited and withdrawn and therefore are perhaps more likely to stay at home and eat together with their families. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  13. Safety profile comparison between extemporaneous and a licensed preparation of caffeine citrate in preterm infants with apnea of prematurity.

    PubMed

    Vatlach, Scarlet; Arand, Joerg; Engel, Corinna; Poets, Christian F

    2014-01-01

    Given the lack of a licensed product (LP), extemporaneous caffeine citrate (ECC) has been used by many hospital pharmacies. Since July 2011, an LP has been available in Germany. We prospectively compared the safety profile of ECC and LP in preterm infants with apnea of prematurity. Between April 2010 and April 2013, selected side effects occurring with ECC or LP were documented in 6 German NICUs for infants ≤34 weeks' gestation using a longitudinal study design. The software developed for daily prescriptions in NICU residents requires entries if any of the following symptoms occurred during the last 24 h: tachycardia (resting heart rate >200/min), clinical or encephalographic seizures, gastric residuals, vomiting, or necrotizing enterocolitis (NEC). ECC and LP were administered at identical doses (20 mg/kg/day loading, 5-10 mg/kg/day maintenance) and in similar formulations either orally or intravenously. 562 infants with 14,590 treatment days on ECC and 538 infants with 12,813 treatment days on LP were evaluated. The mean gestational age was similar (29.20 weeks for ECC vs. 29.14 weeks for LP). No relevant differences were seen concerning tachycardia, gastric residuals, or vomiting, but ECC was associated with a higher risk of NEC (risk ratio: 2.68, 95% CI: 1.01-7.23, p = 0.047) and, albeit not significantly so, seizures (risk ratio: 1.91, 95% CI: 0.53-6.96, p = 0.35). This survey demonstrates a similar safety profile for both forms of caffeine citrate. The lower NEC and seizure rate seen with the LP is intriguing, but requires confirmation in a controlled study design. © 2013 S. Karger AG, Basel.

  14. The absence of p53 during Human Cytomegalovirus infection leads to decreased UL53 expression, disrupting UL50 localization to the inner nuclear membrane, and thereby inhibiting capsid nuclear egress

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

    Kuan, Man I; O’Dowd, John M.; Fortunato, Elizabeth

    Our electron microscopy study (Kuan et al., 2016) found HCMV nuclear capsid egress was significantly reduced in p53 knockout cells (p53KOs), correlating with inhibited formation of infoldings of the inner nuclear membrane (IINMs). Molecular examination of these phenomena has found p53KOs expressed UL97 and phosphorylated lamins, however the lamina failed to remodel. The nuclear egress complex (NEC) protein UL50 was expressed in almost all cells. UL50 re-localized to the inner nuclear membrane (INM) in ~90% of wt cells, but only ~35% of p53KOs. UL53 expression was significantly reduced in p53KOs, and cells lacking UL50 nuclear staining, expressed no UL53. Re-introductionmore » of p53 into p53KOs largely recovered UL53 positivity and UL50 nuclear re-localization. Nuclear rim located UL50/53 puncta, which co-localized with the major capsid protein, were largely absent in p53KOs. We believe these puncta were IINMs. In the absence of p53, UL53 expression was inhibited, disrupting formation of the NEC/IINMs, and reducing functional virion secretion. -- Highlights: •Phosphorylated nuclear lamins were inefficiently remodeled in p53KO cells. •p53KO cells expressed UL50, but it was not efficiently targeted to the nuclear rim. •UL53 was not expressed in the large majority of p53KO cells. •Cells failing to express UL53 did not localize UL50 to the nucleus. •NEC puncta/infoldings of the inner nuclear membrane were scarce in p53KO cells.« less

  15. Sensitivity of thalamic GABAergic currents to clonazepam does not differ between control and genetic absence epilepsy rats.

    PubMed

    Badiu, Carmen-Ionela

    2004-11-12

    Mutations in GABA-A receptor subunits have been reported in a number of idiopathic generalized epilepsies including childhood absence epilepsy. One of these mutations is located within a high-affinity benzodiazepine-binding domain, and clonazepam is clinically used as an anti-absence drug. The intrathalamic loop consisting of the GABAergic neurons of the nucleus reticularis thalami (NRT) and the thalamocortical (TC) neurons of sensory thalamic nuclei plays an essential role in spike and wave discharges. In a well-established genetic model of absence epilepsy (Genetic Absence Epilepsy rat from Strasbourg, GAERS), systemic injections of benzodiazepines have been shown to suppress spike-and-waves discharges. The aim of this study, therefore, was to determine whether the sensitivity of GABAergic synaptic currents to clonazepam in NRT and TC neurons was different in GAERS and non-epileptic control (NEC) rats. In both pre-seizure GAERS and NEC clonazepam (100 nM) had no effect on the mIPSCs recorded from TC neurons while it increased the decay time constant of the mIPSCs recorded in NRT neurons by a similar amount in GAERS (54.5+/-5%) and NEC (50.7+/-5%). Similar results have been obtained in the presence of 100 microM Cd2+, showing that the effect of clonazepam did not occur via modulation of voltage-activated Ca2+ currents. These results are relevant to understand that in GAERS, the clonazepam anti-absence actions cannot be fully explained by the enhancement of the intra-NRT inhibition and the modulation of the GABAergic synaptic currents in other brain areas, in particular the cortex, must be taken into consideration.

  16. Early gradual feeding with bovine colostrum improves gut function and NEC resistance relative to infant formula in preterm pigs.

    PubMed

    Shen, René L; Thymann, Thomas; Østergaard, Mette V; Støy, Ann Cathrine F; Krych, Łukasz; Nielsen, Dennis S; Lauridsen, Charlotte; Hartmann, Bolette; Holst, Jens J; Burrin, Douglas G; Sangild, Per T

    2015-09-01

    It is unclear when and how to start enteral feeding for preterm infants when mother's milk is not available. We hypothesized that early and slow advancement with either formula or bovine colostrum stimulates gut maturation and prevents necrotizing enterocolitis (NEC) in preterm pigs, used as models for preterm infants. Pigs were given either total parenteral nutrition (TPN, n = 14) or slowly advancing volumes (16-64 ml·kg(-1)·day(-1)) of preterm infant formula (IF, n = 15) or bovine colostrum (BC, n = 13), both given as adjunct to parenteral nutrition. On day 5, both enteral diets increased intestinal mass (27 ± 1 vs. 22 ± 1 g/kg) and glucagon-like peptide 2 release, relative to TPN (P < 0.05). The incidence of mild NEC lesions was higher in IF than BC and TPN pigs (60 vs. 0 and 15%, respectively, P < 0.05). Only the IF pigs showed reduced gastric emptying and gastric inhibitory polypeptide release, and increased tissue proinflammatory cytokine levels (IL-1β and IL-8, P < 0.05) and expression of immune-related genes (AOAH, LBP, CXCL10, TLR2), relative to TPN. The IF pigs also showed reduced intestinal villus-to-crypt ratio, lactose digestion, and some plasma amino acids (Arg, Cit, Gln, Tyr, Val), and higher intestinal permeability, compared with BC pigs (all P < 0.05). Colonic microbiota analyses showed limited differences among groups. Early feeding with formula induces intestinal dysfunction whereas bovine colostrum supports gut maturation when mother's milk is absent during the first week after preterm birth. A diet-dependent feeding guideline may be required for newborn preterm infants. Copyright © 2015 the American Physiological Society.

  17. Cardioprotection of ischaemic preconditioning is associated with inhibition of translocation of MLKL within the plasma membrane.

    PubMed

    Szobi, Adrián; Farkašová-Ledvényiová, Veronika; Lichý, Martin; Muráriková, Martina; Čarnická, Slávka; Ravingerová, Tatiana; Adameová, Adriana

    2018-06-19

    Necroptosis, a form of cell loss involving the RIP1-RIP3-MLKL axis, has been identified in cardiac pathologies while its inhibition is cardioprotective. We investigated whether the improvement of heart function because of ischaemic preconditioning is associated with mitigation of necroptotic signaling, and these effects were compared with a pharmacological antinecroptotic approach targeting RIP1. Langendorff-perfused rat hearts were subjected to ischaemic preconditioning with or without a RIP1 inhibitor (Nec-1s). Necroptotic signaling and the assessment of oxidative damage and a putative involvement of CaMKII in this process were analysed in whole tissue and subcellular fractions. Ischaemic preconditioning, Nec-1s and their combination improved postischaemic heart function recovery and reduced infarct size to a similar degree what was in line with the prevention of MLKL oligomerization and translocation to the membrane. On the other hand, membrane peroxidation and apoptosis were unchanged by either approach. Ischaemic preconditioning failed to ameliorate ischaemia-reperfusion-induced increase in RIP1 and RIP3 while pSer229-RIP3 levels were reduced only by Nec-1s. In spite of the additive phosphorylation of CaMKII and PLN because of ditherapy, the postischaemic contractile force and relaxation was comparably improved in all the intervention groups while antiarrhythmic effects were observed in the ischaemic preconditioning group only. Necroptosis inhibition seems to be involved in cardioprotection of ischaemic preconditioning and is comparable but not intensified by an anti-RIP1 agent. Changes in oxidative stress nor CaMKII signaling are unlikely to explain the beneficial effects. © 2018 Comenius University in Bratislava, Faculty of Pharmacy. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  18. [The pediatric patient at the end-of-life. A challenge for its identification and treatment. A survey in pediatricians and medical residents].

    PubMed

    Rendón-Macías, Mario Enrique; Olvera-González, Héctor; Villasís-Keever, Miguel Angel

    2011-01-01

    Identification of pediatric patients at the end-of-life is not easy because criteria used are based on adults' criteria. In this survey we explore the children end-of-life definition pediatricians have, as well as to determine which interventions they use when caring a patient at end-of-life. Tertiary referral pediatric hospital. Staff pediatricians (SP) and medical residents (MR). A self-administrated questionnaire was built and validated. It contains five vignettes of pediatric patients: Two with WHO criteria for an end-of-life condition (EC) and three without an end-of-life condition (NEC). PARTICIPANTS identified each patient with or without an end-of-life condition, and which palliative actions they would perform accordingly Their responses were recorded in a 4-option Likert scale. Ordinal regression was used to assess if some of the participants' characteristics were related to the identification of an end-of-life condition. Response rate was 84.2% (128/152); of whom 63 were SP and 65 MR. EC cases were well identified in 90 and 93%, while NEC in 30 and 40%, respectively Palliative actions were more according in EC patients, but around 20% would not provide them. Among NEC patients, there were more disparities of palliative actions to be delivered, and it was statistically significantly. Ordinal regression showed that some participants' characteristics are associated to the appropriate identification of end-of-life patients; however, these factors were not consistent across the five scenarios. Among pediatricians, criteria of end-of-life conditions are not well established, neither the palliative actions. Educational interventions are needed to improve the quality of life of these children.

  19. Evaluation of a disposable plastic Neubauer counting chamber for semen analysis.

    PubMed

    Kirkman-Brown, Jackson; Björndahl, Lars

    2009-02-01

    To evaluate whether disposable plastic counting chambers effectively could replace nondisposable, time-consuming, and potentially dangerous glass hemocytometers. Evaluation of equipment in modern laboratory andrology. Comparison of results obtained with plastic chambers with results obtained with "gold-standard" glass hemocytometer counts. Diagnostic laboratory for andrology. Twenty-one patients undergoing investigation for infertility problems. No interventions with patients; sperm in diluted semen samples were used when patients had allowed the use for research and training. Sperm concentration, difference from results obtained with standard equipment. In the first three experimental series, with use of standard routine phase-contrast microscopy, significantly lower count results were obtained consistently from the plastic chambers than from standard chambers. In the fourth series, with use of specialized equipment, equivalent results were obtained but with a considerably greater time commitment because of difficulties in distinguishing sperm adjacent to the gridlines in the plastic chambers. The plastic disposable chamber type was not suitable for routine semen analysis because results are variable depending on the microscope used, and increased time is necessary to do the assessment accurately.

  20. Validation of a Monte Carlo simulation of the Philips Allegro/GEMINI PET systems using GATE

    NASA Astrophysics Data System (ADS)

    Lamare, F.; Turzo, A.; Bizais, Y.; Cheze LeRest, C.; Visvikis, D.

    2006-02-01

    A newly developed simulation toolkit, GATE (Geant4 Application for Tomographic Emission), was used to develop a Monte Carlo simulation of a fully three-dimensional (3D) clinical PET scanner. The Philips Allegro/GEMINI PET systems were simulated in order to (a) allow a detailed study of the parameters affecting the system's performance under various imaging conditions, (b) study the optimization and quantitative accuracy of emission acquisition protocols for dynamic and static imaging, and (c) further validate the potential of GATE for the simulation of clinical PET systems. A model of the detection system and its geometry was developed. The accuracy of the developed detection model was tested through the comparison of simulated and measured results obtained with the Allegro/GEMINI systems for a number of NEMA NU2-2001 performance protocols including spatial resolution, sensitivity and scatter fraction. In addition, an approximate model of the system's dead time at the level of detected single events and coincidences was developed in an attempt to simulate the count rate related performance characteristics of the scanner. The developed dead-time model was assessed under different imaging conditions using the count rate loss and noise equivalent count rates performance protocols of standard and modified NEMA NU2-2001 (whole body imaging conditions) and NEMA NU2-1994 (brain imaging conditions) comparing simulated with experimental measurements obtained with the Allegro/GEMINI PET systems. Finally, a reconstructed image quality protocol was used to assess the overall performance of the developed model. An agreement of <3% was obtained in scatter fraction, with a difference between 4% and 10% in the true and random coincidence count rates respectively, throughout a range of activity concentrations and under various imaging conditions, resulting in <8% differences between simulated and measured noise equivalent count rates performance. Finally, the image quality validation study revealed a good agreement in signal-to-noise ratio and contrast recovery coefficients for a number of different volume spheres and two different (clinical level based) tumour-to-background ratios. In conclusion, these results support the accurate modelling of the Philips Allegro/GEMINI PET systems using GATE in combination with a dead-time model for the signal flow description, which leads to an agreement of <10% in coincidence count rates under different imaging conditions and clinically relevant activity concentration levels.

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