Functional Limit Theorems for Multiparameter Fractional Brownian Motion

We prove a general functional limit theorem for multiparameter fractional Brownian motion. The functional law of the iterated logarithm, functional L\'{e}vy's modulus of continuity and many other results are its particular cases. Applications to approximation theory are discussed.Comment: AMS-LaTeX, 23 page

Rhythm in the speech of a person with right hemisphere damage: Applying the pairwise variability index

Although several aspects of prosody have been studied in speakers with right hemisphere damage (RHD), rhythm remains largely uninvestigated. This study compares the rhythm of an Australian English speaker with right hemisphere damage (due to a stroke, but with no concomitant dysarthria) to that of a neurologically unimpaired individual. The speakers' rhythm is compared using the pairwise variability index (PVI) which allows for an acoustic characterization of rhythm by comparing the duration of successive vocalic and intervocalic intervals. A sample of speech from a structured interview between a speech and language therapist and each participant was analysed. Previous research has shown that speakers with RHD may have difficulties with intonation production, and therefore it was hypothesized that there may also be rhythmic disturbance. Results show that the neurologically normal control uses a similar rhythm to that reported for British English (there are no previous studies available for Australian English), whilst the speaker with RHD produces speech with a less strongly stress-timed rhythm. This finding was statistically significant for the intervocalic intervals measured (t(8) = 4.7, p < .01), and suggests that some aspects of prosody may be right lateralized for this speaker. The findings are discussed in relation to previous findings of dysprosody in RHD populations, and in relation to syllable-timed speech of people with other neurological conditions

Performance and parasitosis in heifers grazing mixed with sows

Summary The aim of the study was to investigate the effect of mixed grazing with first season heifers and pregnant sows on animal performance, gastro-intestinal helminths, pasture quality and sward structure during three grazing seasons. This presentation will focus on results from 1999, primarily regarding performance and parasitosis in heifers. There have been no earlier reports on such mixed grazing systems. Three grazing systems were studied in replicate: 1) Heifers grazing alone; 2) sows grazing alone; 3) heifers grazing together with sows. The heifers were inoculated with low doses of infective O.ostertagi larvae at turn-out. Continuous grazing was practised in paddocks regulated in size according to herbage allowance. Individual weight gain, faecal egg output and serum pepsinogen concentrations -as indicator of O.ostertagi infection -were measured fortnightly. The sward structure and quality were greatly influenced by the applied grazing system. The average daily gain of the heifers was significantly higher (P=0.0006) when grazing together with sows (1,121±45 g/day, n=16) than when grazing alone (869±48 g/day, n=14). The mean pepsinogen concentrations were elevated in the heifers grazing alone. It is concluded, that weight gains were significantly better and infection levels with O.ostertagi were significantly reduced in heifers grazing together with sows. Introduction Outdoor pig production is increasing, especially in connection with organic farming. When sows with nose-ring graze alone, experience shows that the sward gets dirty and stemmy, and the sows destroy the sward in spots. It is well known that mixed grazing with sheep and cattle usually improves the utilization of the pasture and reduces parasite infectio

SvSXP:a <em>Strongylus vulgaris</em> antigen with potential for prepatent diagnosis

BACKGROUND: Strongyle parasites are ubiquitous in grazing horses. Strongylus vulgaris, the most pathogenic of the large strongyles, is known for its extensive migration in the mesenteric arterial system. The lifecycle of S. vulgaris is characterised by a long prepatent period where the migrating larvae are virtually undetectable as there currently is no test available for diagnosing prepatent S. vulgaris infection. Presence of S. vulgaris larvae in the arterial system causes endarteritis and thrombosis with a risk of non-strangulating intestinal infarctions. Emergence of anthelmintic resistance among cyathostomins has led to recommendations of reduced treatment intensity by targeting horses that exceed a predetermined strongyle faecal egg count threshold. One study suggests an apparent increase in prevalence of S. vulgaris on farms where reduced anthelmintic treatment intensity has been implemented. These issues highlight the need for an accurate and reliable assay for diagnosing prepatent S. vulgaris infection. METHODS: Immunoscreening of a larval S. vulgaris cDNA library using hyperimmune serum raised against S. vulgaris excretory/secretory antigens was performed to identify potential diagnostic antigens. Immunoreactive clones were sequenced, one potential antigen was characterised, expressed as a recombinant protein, initially evaluated by western blot (WB) analysis, the diagnostic potential of the IgG subclasses was evaluated by ELISA, and the diagnostic accuracy evaluated using serum from 102 horses with known S. vulgaris infection status. RESULTS: The clone expressing the potential antigen encoded a S. vulgaris SXP/RAL2 homologue. The recombinant protein, rSvSXP, was shown to be a potential diagnostic antigen by WB analysis, and a target of serum IgGa, IgG(T) and total IgG in naturally infected horses, with IgG(T) antibodies being the most reliable indicator of S. vulgaris infection in horses. Evaluation of diagnostic accuracy of the ELISA resulted in a sensitivity of 73.3%, a specificity of 81.0%, a diagnostic odds ratio of 11.69; a positive likelihood ratio (LR) of 3.85 and a negative LR was 0.33. The area under the ROC curve was 0.820. CONCLUSION: IgG(T) antibodies to recombinant SvSXP show potential for use as an antigen for prepatent diagnosis of migrating stages of S. vulgaris with moderate to good diagnostic accuracy

SvSXP: a Strongylus vulgaris antigen with potential for prepatent diagnosis

BACKGROUND: Strongyle parasites are ubiquitous in grazing horses. Strongylus vulgaris, the most pathogenic of the large strongyles, is known for its extensive migration in the mesenteric arterial system. The lifecycle of S. vulgaris is characterised by a long prepatent period where the migrating larvae are virtually undetectable as there currently is no test available for diagnosing prepatent S. vulgaris infection. Presence of S. vulgaris larvae in the arterial system causes endarteritis and thrombosis with a risk of non-strangulating intestinal infarctions. Emergence of anthelmintic resistance among cyathostomins has led to recommendations of reduced treatment intensity by targeting horses that exceed a predetermined strongyle faecal egg count threshold. One study suggests an apparent increase in prevalence of S. vulgaris on farms where reduced anthelmintic treatment intensity has been implemented. These issues highlight the need for an accurate and reliable assay for diagnosing prepatent S. vulgaris infection. METHODS: Immunoscreening of a larval S. vulgaris cDNA library using hyperimmune serum raised against S. vulgaris excretory/secretory antigens was performed to identify potential diagnostic antigens. Immunoreactive clones were sequenced, one potential antigen was characterised, expressed as a recombinant protein, initially evaluated by western blot (WB) analysis, the diagnostic potential of the IgG subclasses was evaluated by ELISA, and the diagnostic accuracy evaluated using serum from 102 horses with known S. vulgaris infection status. RESULTS: The clone expressing the potential antigen encoded a S. vulgaris SXP/RAL2 homologue. The recombinant protein, rSvSXP, was shown to be a potential diagnostic antigen by WB analysis, and a target of serum IgGa, IgG(T) and total IgG in naturally infected horses, with IgG(T) antibodies being the most reliable indicator of S. vulgaris infection in horses. Evaluation of diagnostic accuracy of the ELISA resulted in a sensitivity of 73.3%, a specificity of 81.0%, a diagnostic odds ratio of 11.69; a positive likelihood ratio (LR) of 3.85 and a negative LR was 0.33. The area under the ROC curve was 0.820. CONCLUSION: IgG(T) antibodies to recombinant SvSXP show potential for use as an antigen for prepatent diagnosis of migrating stages of S. vulgaris with moderate to good diagnostic accuracy

CD169 (Siglec-1) as a Robust Human Cell Biomarker of Toll-Like Receptor 9 Agonist Immunotherapy

Immunotherapy is a promising therapeutic area in cancer and chronic viral infections. An important component of immunotherapy in these contexts is the activation of innate immunity. Here we investigate the potential for CD169 (Siglec 1) expression on monocytes to serve as a robust biomarker for activation of innate immunity and, particular, as a proxy for IFN-α production. Specifically, we investigated the effects of Toll-like receptor 9 agonism with MGN1703 (lefitolimod) across experimental conditions ex vivo, in humanized mice, and in clinical trial participants. Ex vivo we observed that the percentage of classical monocytes expressing CD169 increased dramatically from 10% pre-stimulation to 97% 24 hrs after MGN1703 stimulation (p\u3c0.0001). In humanized NOG mice, we observed prominent upregulation of the proportions of monocytes expressing CD169 after two doses of MGN1703 where 73% of classical monocytes were CD169 positive in bone marrow following MGN1703 treatment vs 19% in vehicle treated mice (p=0.0159). Finally, in a clinical trial in HIV-infected individuals receiving immunotherapy treatment with MGN1703, we observed a uniform upregulation of CD169 on monocytes after dosing with 97% of classical monocytes positive for CD169 (p=0.002). Hence, in this comprehensive evaluation ex vivo, in an animal model, and in a clinical trial, we find increases in the percentage of CD169 positive monocytes to be a reliable and robust biomarker of immune activation following TLR9 agonist treatment

Extraction of cocoa proanthocyanidins and their fractionation by sequential centrifugal partition chromatography and gel permeation chromatography

Erworben im Rahmen der Schweizer Nationallizenzen (http://www.nationallizenzen.ch)Cocoa beans contain secondary metabolites ranging from simple alkaloids to complex polyphenols with most of them believed to possess significant health benefits. The increasing interest in these health effects has prompted the need to develop techniques for their extraction, fractionation, separation, and analysis. This work provides an update on analytical procedures with a focus on establishing a gentle extraction technique. Cocoa beans were finely ground to an average particle size of <100 μm, defatted at 20°C using n-hexane, and extracted three times with 50 % aqueous acetone at 50°C. Determination of the total phenolic content was done using the Folin-Ciocalteu assay, the concentration of individual polyphenols was analyzed by electrospray ionization high performance liquid chromatography-mass spectrometry (ESI-HPLC/MS). Fractions of bioactive compounds were separated by combining sequential centrifugal partition chromatography (SCPC) and gel permeation column chromatography using Sephadex LH-20. For SCPC, a two-phase solvent system consisting of ethyl acetate/n-butanol/water (4:1:5, v/v/v) was successfully applied for the separation of theobromine, caffeine, and representatives of the two main phenolic compound classes flavan-3-ols and flavonols. Gel permeation chromatography on Sephadex LH-20 using a stepwise elution sequence with aqueous acetone has been shown for effectively separating individual flavan-3-ols. Separation was obtained for (-)-epicatechin, proanthocyanidin dimer B2, trimer C1, and tetramer cinnamtannin A2. The purity of alkaloids and phenolic compounds was determined by HPLC analysis and their chemical identity was confirmed by mass spectrometry

Comparative evaluation of left ventricular mass regression after aortic valve replacement: a prospective randomized analysis

Background: We assessed the hemodynamic performance of various prostheses and the clinical outcomes after aortic valve replacement, in different age groups. Methods: One-hundred-and-twenty patients with isolated aortic valve stenosis were included in this prospective randomized randomised trial and allocated in three age-groups to receive either pulmonary autograft (PA, n = 20) or mechanical prosthesis (MP, Edwards Mira n = 20) in group 1 (age 75). Clinical outcomes and hemodynamic performance were evaluated at discharge, six months and one year. Results: In group 1, patients with PA had significantly lower mean gradients than the MP (2.6 vs. 10.9 mmHg, p = 0.0005) with comparable left ventricular mass regression (LVMR). Morbidity included 1 stroke in the PA population and 1 gastrointestinal bleeding in the MP subgroup. In group 2, mean gradients did not differ significantly between both populations (7.0 vs. 8.9 mmHg, p = 0.81). The rate of LVMR and EF were comparable at 12 months; each group with one mortality. Morbidity included 1 stroke and 1 gastrointestinal bleeding in the stentless and 3 bleeding complications in the MP group. In group 3, mean gradients did not differ significantly (7.8 vs 6.5 mmHg, p = 0.06). Postoperative EF and LVMR were comparable. There were 3 deaths in the stented group and no mortality in the stentless group. Morbidity included 1 endocarditis and 1 stroke in the stentless compared to 1 endocarditis, 1 stroke and one pulmonary embolism in the stented group. Conclusions: Clinical outcomes justify valve replacement with either valve substitute in the respective age groups. The PA hemodynamically outperformed the MPs. Stentless valves however, did not demonstrate significantly superior hemodynamics or outcomes in comparison to stented bioprosthesis or MPs