Salmonella immunization confers cross protection without confounding pre-harvest serologic monitoring

Food borne Salmonella Typhimurium is a valid concern for the global pork industry. An attenuated oral swine Salmonella Choleraesuis vaccine has proven to be an effective tool for the pre-harvest reduction of carrier rates for multiple Salmonella spp. Serum antibody assays are available to monitor exposure to wild-type Salmonella infection. This clinical study assessed protection induced by an attenuated oral Salmonella Choleraesuis vaccine against challenge infection with S. Typhimurium in swine. A serologic antibody assay was concurrently evaluated for its ability to differentiate vaccinated pigs from those challenged with Salmonella Typhimurium. Vaccination significantly improved clinical scores, pyrexia, and enteric lesion prevalence, while numerically improving average daily weight gain, and group body weight variation in comparison to unvaccinated/challenged pigs. Vaccination, while protecting pigs against disease, did not generate detectable serum antibodies prior to challenge. No vaccinated animals became seropositive prior to challenge, indicating that conventional ELISA tests could be used in vaccinated pigs to monitor wild-type exposure. Following challenge, there was no detectable difference between vaccinated/challenged and non-vaccinated/challenged animals. All strict control pigs remained serum antibody negative. These findings support the use of this vaccine to protect swine against S. Typhimurium, without confounding pre-harvest Salmonella serologic monitoring programs

Increased trans-glycosylation activity of hexosaminidases for synthesis of human milk oligosaccharides

It is well known that the composition of human breast milk differs significantly from the one of ordinary bovine milk. Especially the presence of sialylated and fucosylated oligosaccharides contributes to its health and development promoting features for newborn infants. [1] Nevertheless, not all newborns and especially premature infants sometimes cannot be breast fed for different reasons. For those children it is important that they receive a proper balanced formula product containing the above mentioned human milk oligosaccharides (HMOs). With respect to this we are developing new enzymatic routes for synthesis of sialylated and fucosylated oligosaccharides, which can be used as functional ingredient for infant formula. In a previous work two candidate hexoasaminidases (both belonging to the GH20 family) were identified from a metagenomic library, which were able to synthesize the basic HMO backbone structure, Lacto-N-triose II, from chitobiose and lactose by trans-glycosylation. [2] Since the yields using these enzymes were low (2% for hex1 and 8% for hex2 based on the donor substrate chitobiose) we wanted to increase their trans-glycosylation activity to increase their applicability for a feasible process. It was decided to follow a rational design approach first to keep the screening effort low. Therefore peptide pattern recognition (PPR) [3] analysis was performed on the whole GH20 CAZy family (approx. 3000 sequences) to identify other enzymes with potential trans-glycosylation activity based on relatedness. By phylogenetic analysis of the group containing the two known enzymes (approx. 1000 sequences) and subsequent alignment of the closely related sequences a loop insertion close to the active site was identified. Homology modelling revealed that introduction of this loop structure into hex1 and hex2 would lead to a significantly narrower active site and therefore contribute to exclusion of water from the active site, which is a well-known strategy to increase trans-glycosylation activity. The proposed loop mutants were then expressed, purified and characterized towards trans-glycosylation activity. For hex2 it turned out that none of the loop mutants showed an improved trans-glycosylation activity compared to the wild-type. But for hex1 three out of four showed an up to seven-fold improved trans-glycosylation activity compared to the wild-type, which refers even to a higher trans-glycosylation activity than previously observed for the hex2 wild-type. [4] In conclusion we succeeded in engineering an enzyme towards increased trans-glycosylation activity using a custom-made rational approach utilizing available sequence analysis methods. [1] L. Bode, Glycobiology 2012, 22, 1147–1162. [2] C. Nyffenegger, R. T. Nordvang, B. Zeuner, M. Łężyk, E. Difilippo, M. J. Logtenberg, H. A. Schols, A. S. Meyer, J. D. Mikkelsen, Appl. Microbiol. Biotechnol. 2015, 99, 7997–8009. [3] P. K. Busk, L. Lange, Appl. Environ. Microbiol. 2013, 79, 3380–3391. [4] S. B. Jamek, J. Muschiol, J. Holck, P. K. Busk, L. Lange, J. D. Mikkelsen, A. S. Meyer, 2017, manuscript submitted

Localized prostate cancer in Norway, the United States, and Spain: between-country differences of variables before treatment among patients eligible for curative treatment

Between-country differences in medical and sociodemographic variables, and patient-related outcomes (PROs) before treatment might explain published variations of side effects after radical prostatecomy (RP) or radiotherapy (RAD) for prostate cancer (PCa). This hypothesis was tested among 1908 patients from the United States, Spain, and Norway. Significant between-country differences were observed for most factors investigated before treatment. The observations should be considered in comparison of the frequency and severity of internationally published studies. Background: In men with PCa, large variations of PROs after RP or high-dose RAD might be related to betweencountry differences of medical and sociodemographic variables, and differences in PROs before treatment in the sexual and urinary domains. Patients and Methods: In 1908 patients with localized PCa from Norway, the United States, or Spain, the relation between medical (prostate-specific antigen, Gleason score, cT-category) and sociodemographic variables (age, education, marital status) before treatment was investigated. Using the Expanded Prostate Cancer Index Composite questionnaire, PROs before treatment within the sexual and urinary domains were also considered. Results: Compared with the European patients, American patients were younger, fewer had comorbid conditions, and more had a high education level. Fifty-three percent of the US men eligible for RP had low-risk tumors compared with 42% and 31% among the Norwegian and the Spanish patients, respectively. Among the Spanish RAD patients, 54% had had low-risk tumors compared with 34% of the American and 21% of the Norwegian men planned for RAD, respectively. Compared with the European patients, significantly fewer US patients reported moderate or severe sexual dysfunction and related problems. In most subgroups, the number of patients with sexual or urinary dysfunction exceeded that of patients with bother related to the reported dysfunction. Conclusion: Statistically significant between-country differences were observed in medical and sociodemographic variables, and in PROs before treatment within the sexual and urinary domains. Large differences between reported dysfunction and related problems within the sexual and urinary domains indicate that dysfunction and bother should be reported separately in addition to calculation of summary scores. The documented differences, not at least regarding PROs, might in part explain the large variation of side effects after treatment evident in the medical literatur

Use of SC54 for the reduction of salmonella in swine

Infections caused by S. choleraesuis have significant economic impact on pork production in the United States (Wilcock and Schwartz 1992). An avirulent live culture vaccine has been described for the purpose of protecting pigs against infections caused by S. choleraesuis (Kramer, Roof et al. 1992) (Roof and Doitchinoff 1995). Other serotypes of Salmonella have been associated with infections in swine in the United States. These includeS. typhimurium and S. typhisuis (Wilcock and Schwartz 1992), S. heidelberg (Reed, Olander et al. 1985), and S. agona (Fernandez, Duhamel et al. 1993). Two experiments were conducted. Experiment number I was designed to determine the effect of an avirulent live culture vaccine (SC540, NOBL Laboratories, Inc.) in swine on an experimental infection of S. typhimurium. Experiment number 2 was designed to determine the effect of SC540 on Salmonella serogroups within a commercial swine farm

New monotonicity formulas for Ricci curvature and applications. I

Original manuscript November 21, 2011We prove three new monotonicity formulas for manifolds with a lower Ricci curvature bound and show that they are connected to rate of convergence to tangent cones. In fact, we show that the derivative of each of these three monotone quantities is bounded from below in terms of the Gromov–Hausdorff distance to the nearest cone. The monotonicity formulas are related to the classical Bishop–Gromov volume comparison theorem and Perelman’s celebrated monotonicity formula for the Ricci flow. We will explain the connection between all of these. Moreover, we show that these new monotonicity formulas are linked to a new sharp gradient estimate for the Green function that we prove. This is parallel to the fact that Perelman’s monotonicity is closely related to the sharp gradient estimate for the heat kernel of Li–Yau. In [CM4] one of the monotonicity formulas is used to show uniqueness of tangent cones with smooth cross-sections of Einstein manifolds. Finally, there are obvious parallelisms between our monotonicity and the positive mass theorem of Schoen–Yau and Witten.National Science Foundation (U.S.) (Grant DMS-11040934)National Science Foundation (U.S.). Focused Research Group (Grant DMS 0854774)National Science Foundation (U.S.) (Grant 0932078

Стратегічне планування як основний інструмент ефективності підприємства

Наук. кер.: А.Ю. Жулавськи

Effects of motifs in music therapy on the attention of children with externalizing behavior problems

Recent studies highlight the role of attention (i.e., executive attention and joint attention) in the negative association between children’s externalizing behavior problems (EBPs) and self-regulation. In music therapy improvisation, “Motifs” represent a repeated and meaningful use of freely improvised or structured music. They have been reported to be effective in drawing attention toward joint musical engagement. This study aimed to examine the effects of clinically derived motifs on the attention of a child with EBPs. Video microanalysis of four therapy sessions was employed. Interaction segments with/without motifs were then selected for analysis: (a) Executive attention measurement: a two-way analysis of variance (ANOVA) was conducted to examine the effects of Motifs (Factor I) across sessions (Factor II) on the duration of interaction segments. (b) Joint attention measurement: another two-way ANOVA investigated the effects of these two factors on the duration of joint attentive responses in each segment. Results showed that (a) the segments with Motifs tended to decrease in duration throughout the sessions, while (b) these segments showed a significant increase in proportions of joint attentional responses. These findings suggest a positive effect of Motifs on enhancing efficiency of joint attention execution over time, indicating the child’s recognition of the Motifs through learning

Randomised controlled trial of improvisational music therapy's effectiveness for children with autism spectrum disorders (TIME-A): study protocol

<p>Abstract</p> <p>Background</p> <p>Previous research has suggested that music therapy may facilitate skills in areas typically affected by autism spectrum disorders such as social interaction and communication. However, generalisability of previous findings has been restricted, as studies were limited in either methodological accuracy or the clinical relevance of their approach. The aim of this study is to determine effects of improvisational music therapy on social communication skills of children with autism spectrum disorders. An additional aim of the study is to examine if variation in dose of treatment (i.e., number of music therapy sessions per week) affects outcome of therapy, and to determine cost-effectiveness.</p> <p>Methods/Design</p> <p>Children aged between 4;0 and 6;11 years who are diagnosed with autism spectrum disorder will be randomly assigned to one of three conditions. Parents of all participants will receive three sessions of parent counselling (at 0, 2, and 5 months). In addition, children randomised to the two intervention groups will be offered individual, improvisational music therapy over a period of five months, either one session (low-intensity) or three sessions (high-intensity) per week. Generalised effects of music therapy will be measured using standardised scales completed by blinded assessors (Autism Diagnostic Observation Schedule, ADOS) and parents (Social Responsiveness Scale, SRS) before and 2, 5, and 12 months after randomisation. Cost effectiveness will be calculated as man years. A group sequential design with first interim look at N = 235 will ensure both power and efficiency.</p> <p>Discussion</p> <p>Responding to the need for more rigorously designed trials examining the effectiveness of music therapy in autism spectrum disorders, this pragmatic trial sets out to generate findings that will be well generalisable to clinical practice. Addressing the issue of dose variation, this study's results will also provide information on the relevance of session frequency for therapy outcome.</p> <p>Trial Registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN78923965">ISRCTN78923965</a>.</p

Measurement of the Strong Coupling Constant from Inclusive Jet Production at the Tevatron pˉp\bar pp Collider

We report a measurement of the strong coupling constant, $\alpha_s(M_Z)$, extracted from inclusive jet production in $p\bar{p}$ collisions at $\sqrt{s}=$1800 GeV. The QCD prediction for the evolution of $\alpha_s$ with jet transverse energy $E_T$ is tested over the range 40<$E_T$<450 GeV using $E_T$ for the renormalization scale. The data show good agreement with QCD in the region below 250 GeV. In the text we discuss the data-theory comparison in the region from 250 to 450 GeV. The value of $\alpha_s$ at the mass of the $Z^0$ boson averaged over the range 40<$E_T$<250 GeV is found to be $\alpha_s(M_{Z})= 0.1178 \pm 0.0001{(\rm stat)}^{+0.0081}_{-0.0095}{\rm (exp. syst)}$. The associated theoretical uncertainties are mainly due to the choice of renormalization scale (^{+6%}_{-4%}) and input parton distribution functions (5%).Comment: 7 pages, 3 figures, using RevTeX. Submitted to Physical Review Letter