187 research outputs found

    Evaluation of human acellular dermis versus porcine acellular dermis in an in vivo model for incisional hernia repair

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    Incisional hernias commonly occur following abdominal wall surgery. Human acellular dermal matrices (HADM) are widely used in abdominal wall defect repair. Xenograft acellular dermal matrices, particularly those made from porcine tissues (PADM), have recently experienced increased usage. The purpose of this study was to compare the effectiveness of HADM and PADM in the repair of incisional abdominal wall hernias in a rabbit model. A review from earlier work of differences between human allograft acellular dermal matrices (HADM) and porcine xenograft acellular dermal matrices (PADM) demonstrated significant differences (P < 0.05) in mechanical properties: Tensile strength 15.7 MPa vs. 7.7 MPa for HADM and PADM, respectively. Cellular (fibroblast) infiltration was significantly greater for HADM vs. PADM (Armour). The HADM exhibited a more natural, less degraded collagen by electrophoresis as compared to PADM. The rabbit model surgically established an incisional hernia, which was repaired with one of the two acellular dermal matrices 3 weeks after the creation of the abdominal hernia. The animals were euthanized at 4 and 20 weeks and the wounds evaluated. Tissue ingrowth into the implant was significantly faster for the HADM as compared to PADM, 54 vs. 16% at 4 weeks, and 58 vs. 20% for HADM and PADM, respectively at 20 weeks. The original, induced hernia defect (6 cm2) was healed to a greater extent for HADM vs. PADM: 2.7 cm2 unremodeled area for PADM vs. 1.0 cmÂČ for HADM at 20 weeks. The inherent uniformity of tissue ingrowth and remodeling over time was very different for the HADM relative to the PADM. No differences were observed at the 4-week end point. However, the 20-week data exhibited a statistically different level of variability in the remodeling rate with the mean standard deviation of 0.96 for HADM as contrasted to a mean standard deviation of 2.69 for PADM. This was significant with P < 0.05 using a one tail F test for the inherent variability of the standard deviation. No significant differences between the PADM and HADM for adhesion, inflammation, fibrous tissue or neovascularization were noted

    Solution-Phase Combinatorial Chemistry in Lead Discovery

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    Solution-phase approaches in combinatorial chemistry complement solid-phase approaches and each can be used to advantage in particular circumstances. Solution-phase synthesis of pools of compounds, whilst allowing successful identification of a selection of good lead structures for medicinal chemistry programmes, also reinforced a number of the disadvantages of such an approach. Solution-phase parallel synthesis of discrete compounds has, however, proved to be a very useful and popular approach both for lead generation and in lead optimisation work. The range of chemistry suitable for use in such approaches is expanding rapidly and some of these chemistries are discussed. The current focus is on enhancing the quality of compounds prepared in array formats, and we describe a number of useful approaches which are being developed to that end

    Neural response to monetary loss among youth with disruptive behavior disorders and callous-unemotional traits in the ABCD study

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    Etiological models highlight reduced punishment sensitivity as a core risk factor for disruptive behavior disorders (DBD) and callous-unemotional (CU) traits. The current study examined neural sensitivity to the anticipation and receipt of loss, one key aspect of punishment sensitivity, among youth with DBD, comparing those with and without CU traits. Data were obtained from the Adolescent Brain and Cognitive Development (ABCD)SM Study (N = 11,874; Mage = 9.51; 48% female). Loss-related fMRI activity during the monetary incentive delay task was examined across 16 empirically-derived a priori brain regions (e.g., striatum, amygdala, insula, anterior cingulate cortex, medial prefrontal cortex) and compared across the following groups: (1) typically developing (n = 693); (2) DBD (n = 995), subdivided into those (3) with CU traits (DBD + CU, n = 198), and (4) without CU traits (DBD-only, n = 276). Latent variable modeling was also employed to examine network-level activity. There were no significant between-group differences in brain activity to loss anticipation or receipt. Null findings were confirmed with and without covariates, using alternative grouping approaches, and in dimensional models. Network-level analyses also demonstrated comparable activity across groups during loss anticipation and receipt. Findings suggest that differences in punishment sensitivity among youth with DBD are unrelated to loss anticipation or receipt. More precise characterizations of other aspects punishment sensitivity are needed to understand risk for DBD and CU traits

    Asymptotic Scaling and Infrared Behavior of the Gluon Propagator

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    The Landau gauge gluon propagator for the pure gauge theory is evaluated on a 32^3x64 lattice with a physical volume of (3.35^3x6.7)fm^4. Comparison with two smaller lattices at different lattice spacings allows an assessment of finite volume and finite lattice spacing errors. Cuts on the data are imposed to minimize these errors. Scaling of the gluon propagator is verified between beta=6.0 and beta=6.2. The tensor structure is evaluated and found to be in good agreement with the Landau gauge form, except at very small momentum values, where some small finite volume errors persist. A number of functional forms for the momentum dependence of the propagator are investigated. The form D(q^2)=D_ir+D_uv, where D_ir(q^2) ~ (q^2+M^2)^-\eta and D_uv is an infrared regulated one-loop asymptotic form, is found to provide an adequate description of the data over the entire momentum region studied - thereby bridging the gap between the infrared confinement region and the ultraviolet asymptotic region. The best estimate for the exponent \eta is 3.2(+0.1/-0.2)(+0.2/-0.3), where the first set of errors represents the uncertainty associated with varying the fitting range, while the second set of errors reflects the variation arising from different choices of infrared regulator in D_uv. Fixing the form of D_uv, we find that the mass parameter M is (1020+/-100)MeV.Comment: 37 pages, RevTeX, 16 postscript figures, 7 gif figures. Revised version accepted for publication in Phys. Rev. D. Model functions and discussion of asymptotic behaviour modified; all model fits have been redone. This paper, including postscript version of all figures, can be found at http://www.physics.adelaide.edu.au/~jskuller/papers

    Schwinger functions and light-quark bound states

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    We examine the applicability and viability of methods to obtain knowledge about bound-states from information provided solely in Euclidean space. Rudimentary methods can be adequate if one only requires information about the ground and first excited state and assumptions made about analytic properties are valid. However, to obtain information from Schwinger functions about higher mass states, something more sophisticated is necessary. A method based on the correlator matrix can be dependable when operators are carefully tuned and errors are small. This method is nevertheless not competitive when an unambiguous analytic continuation of even a single Schwinger function to complex momenta is available.Comment: 27 pages, 14 figure

    EUS-derived criteria for distinguishing benign from malignant metastatic solid hepatic masses

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    Background Detection of hepatic metastases during EUS is an important component of tumor staging. Objective To describe our experience with EUS-guided FNA (EUS-FNA) of solid hepatic masses and derive and validate criteria to help distinguish between benign and malignant hepatic masses. Design Retrospective study, survey. Setting Single, tertiary-care referral center. Patients Medical records were reviewed for all patients undergoing EUS-FNA of solid hepatic masses over a 12-year period. Interventions EUS-FNA of solid hepatic masses. Main Outcome Measurements Masses were deemed benign or malignant according to predetermined criteria. EUS images from 200 patients were used to create derivation and validation cohorts of 100 cases each, matched by cytopathologic diagnosis. Ten expert endosonographers blindly rated 15 initial endosonographic features of each of the 100 images in the derivation cohort. These data were used to derive an EUS scoring system that was then validated by using the validation cohort by the expert endosonographer with the highest diagnostic accuracy. Results A total of 332 patients underwent EUS-FNA of a hepatic mass. Interobserver agreement regarding the initial endosonographic features among the expert endosonographers was fair to moderate, with a mean diagnostic accuracy of 73% (standard deviation 5.6). A scoring system incorporating 7 EUS features was developed to distinguish benign from malignant hepatic masses by using the derivation cohort with an area under the receiver operating curve (AUC) of 0.92; when applied to the validation cohort, performance was similar (AUC 0.86). The combined positive predictive value of both cohorts was 88%. Limitations Single center, retrospective, only one expert endosonographer deriving and validating the EUS criteria. Conclusion An EUS scoring system was developed that helps distinguish benign from malignant hepatic masses. Further study is required to determine the impact of these EUS criteria among endosonographers of all experience

    Genomic and serologic characterization of enterovirus A71 brainstem encephalitis

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    OBJECTIVE: In 2016, Catalonia experienced a pediatric brainstem encephalitis outbreak caused by enterovirus A71 (EV-A71). Conventional testing identified EV in the periphery but rarely in CSF. Metagenomic next-generation sequencing (mNGS) and CSF pan-viral serology (VirScan) were deployed to enhance viral detection and characterization. METHODS: RNA was extracted from the CSF (n = 20), plasma (n = 9), stool (n = 15), and nasopharyngeal samples (n = 16) from 10 children with brainstem encephalitis and 10 children with meningitis or encephalitis. Pathogens were identified using mNGS. Available CSF from cases (n = 12) and pediatric other neurologic disease controls (n = 54) were analyzed with VirScan with a subset (n = 9 and n = 50) validated by ELISA. RESULTS: mNGS detected EV in all samples positive by quantitative reverse transcription polymerase chain reaction (qRT-PCR) (n = 25). In qRT-PCR-negative samples (n = 35), mNGS found virus in 23% (n = 8, 3 CSF samples). Overall, mNGS enhanced EV detection from 42% (25/60) to 57% (33/60) (p-value = 0.013). VirScan and ELISA increased detection to 92% (11/12) compared with 46% (4/12) for CSF mNGS and qRT-PCR (p-value = 0.023). Phylogenetic analysis confirmed the EV-A71 strain clustered with a neurovirulent German EV-A71. A single amino acid substitution (S241P) in the EVA71 VP1 protein was exclusive to the CNS in one subject. CONCLUSION: mNGS with VirScan significantly increased the CNS detection of EVs relative to qRT-PCR, and the latter generated an antigenic profile of the acute EV-A71 immune response. Genomic analysis confirmed the close relation of the outbreak EV-A71 and neuroinvasive German EV-A71. A S241P substitution in VP1 was found exclusively in the CSF.Grants supporting this project include the National Multiple Sclerosis Society and the American Academy of Neurology award FAN-1608-25607 (R.D.S.), Clinical Research Training Scholarship P0534134 (P.S.R.), Sandler and William K. Bowes Jr Foundations (M.R.W., J.L.D., L.M.K., H.A.S., K.C.Z.), Rachleff Family Foundation (M.R.W.), and NINDS of the NIH under award K08NS096117 (M.R.W.) and F31NS113432 (K.E.L.). This study was partially supported by a grant from the Spanish National Health Institute [grant number PI15CIII-00020] and the European Regional Development Fund (FEDER funds). UCSF Biomedical Sciences Program (I.A.H., K.E.L.), UCSF Medical Scientist Training Program (K.E.L.), and the Chan Zuckerberg Biohub (J.E.P., W.W., C.K.C., J.L.D., E.D.C.) also supported this project.S

    Role of iron, light, and silicate in controlling algal biomass in subantarctic waters SE of New Zealand

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    Phytoplankton processes in subantarctic (SA) waters southeast of New Zealand were studied during austral autumn and spring 1997. Chlorophyll a (0.2–0.3 ÎŒg L−1) and primary production (350–650 mg C m−2 d−1) were dominated by cells 1 nmol kg−1, there was little evidence of Fe-stressed algal populations, and Fυ/Fm approached 0.60 at the STC. In addition to these trends, waters of SA origin were occasionally observed within the STC and north of the STC, and thus survey data were interpreted with caution. In vitro Fe enrichment incubations in SA waters resulted in a switch from flavodoxin expression to that of ferredoxin, indicating the alleviation of Fe stress. In another 6-day experiment, iron-mediated increases in chlorophyll a (in particular, increases in large diatoms) were of similar magnitude to those observed in a concurrent Si/Fe enrichment; ambient silicate levels were 4 ÎŒM. A concurrent in vitro Fe enrichment, at irradiance levels comparable to the calculated mean levels experienced by cells in situ, resulted in relatively small increases (approximately twofold) in chlorophyll a. Thus, in spring, irradiance and Fe may both control diatom growth. In contrast, during summer, as mean irradiance increases and silicate levels decrease, Fe limitation, Fe/Si colimitation, or silicate limitation may determine diatom growth
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