Reference curves for a fitness battery developed for children ages 5-12 years in England

Purpose: Reference curves have already been created for a variety of different physical testing batteries across a number of countries. Due to results differing between countries for the same sex and age, it is important that reference curves are created specific for each country. Therefore, the aim of this study was to provide reference curves for five different fitness tests that assess the core components of health related fitness within children in England. Method: Following institutional ethics approval, parental informed consent and child assent was obtained for a total of 39,199 children aged between 5 and 12 years completed tests for explosive power, agility, hand eye coordination, lower body strength and upper body strength. To calculate reference values Generalised Additive Models for Location, Scale and Shape (GAMLSS) were used. Results: Reference curves and centiles show differences in performance levels of the fitness tests between sex and age groups. These reference curves and centiles provide age and sex comparisons to enable progress monitoring of children's physical fitness competence within England and comparisons to other countries. Conclusion: Girls are outperformed from a young age group and both upper and lower body strength decreases are seen at ages nine and ten. In physical activity and health related fitness interventions, both girls and boys in Key stage two should be targeted to maintain progression and lessen the gender divide

Justifying the Special Theory of Relativity with Unconceived Methods

Many realists argue that present scientific theories will not follow the fate of past scientific theories because the former are more successful than the latter. Critics object that realists need to show that present theories have reached the level of success that warrants their truth. I reply that the special theory of relativity has been repeatedly reinforced by unconceived scientific methods, so it will be reinforced by infinitely many unconceived scientific methods. This argument for the special theory of relativity overcomes the critics’ objection, and has advantages over the no-miracle argument and the selective induction for it

Особенности развития малого предпринимательства в Украине

В этой работе рассмотрена эволюция предпринимательства Украины на всех этапах ее общественной жизни, в том числе в период экономического кризиса в годы становления независимости. Отражены основные параметры отнесения предприятий к субъектам малого предпринимательства и их роль в развитии экономики государств.У цій роботі розглянута еволюція підприємництва України на всіх етапах її суспільного життя, зокрема в період економічної кризи в роки становлення незалежності. Відображені основні параметри віднесення підприємств до суб'єктів малого підприємництва і їх роль в розвитку економіки держав

Blur Reduction in Ultrasonic Images Using Pseudo Three-Dimensional Wiener Filtering

The ability to quantitatively image material anomalies with ultrasonic methods is severely restricted by the axial and lateral resolution of the interrogating transducer. Axial resolution is controlled by the pulse duration of the transducer with shorter pulse durations yielding better axial resolution. Lateral resolution is controlled by the width of the interrogating beam with narrower beams providing better lateral resolutio

Association between serum secretory phospholipase A2 and risk of ischaemic stroke

Background and purpose: Previous literature has demonstrated an association between high serum levels of type II secretory phospholipase A2 (sPLA2) concentration and an increased risk of coronary artery disease. However, such association has not been established in terms of ischaemic stroke risk. The aim was to evaluate the association between both sPLA2 concentration and activity as continuous variables with risk of future ischaemic stroke. / Methods: A nested case–control study was conducted using data from the European Prospective Investigation into Cancer—Norfolk study. Cases (n = 145) in the current study were participants who developed ischaemic stroke during follow-up, with controls (n = 290) matched in a 2:1 ratio based on age and sex. Statistical analyses were performed using SPSS (version 25.0) software. Logistic regression was used to determine odds ratios (OR) and corresponding 95% confidence intervals (95% CIs) for ischaemic stroke. / Results: After adjusting for a wide array of cardiovascular confounders, sPLA2 activity was found to be associated with an increased risk of ischaemic stroke using both multiple imputations with chained equations and complete case analysis: OR 1.20 (95% CI 1.01–1.43) and OR 1.23 (95% CI 1.01−1.49), respectively. However, sPLA2 concentration was not found to be associated with increased risk of ischaemic stroke. / Conclusions: The activity of sPLA2, but not sPLA2 concentration, is associated with an increased risk of future ischaemic stroke. This finding may be significant in risk group stratification, allowing targeted prophylactic treatment, or the development of novel therapeutic agents

Development of a new fusion-enhanced oncolytic immunotherapy platform based on herpes simplex virus type 1.

BackgroundOncolytic viruses preferentially replicate in tumors as compared to normal tissue and promote immunogenic cell death and induction of host systemic anti-tumor immunity. HSV-1 was chosen for further development as an oncolytic immunotherapy in this study as it is highly lytic, infects human tumor cells broadly, kills mainly by necrosis and is a potent activator of both innate and adaptive immunity. HSV-1 also has a large capacity for the insertion of additional, potentially therapeutic, exogenous genes. Finally, HSV-1 has a proven safety and efficacy profile in patients with cancer, talimogene laherparepvec (T-VEC), an oncolytic HSV-1 which expresses GM-CSF, being the only oncolytic immunotherapy approach that has received FDA approval. As the clinical efficacy of oncolytic immunotherapy has been shown to be further enhanced by combination with immune checkpoint inhibitors, developing improved oncolytic platforms which can synergize with other existing immunotherapies is a high priority. In this study we sought to further optimize HSV-1 based oncolytic immunotherapy through multiple approaches to maximize: (i) the extent of tumor cell killing, augmenting the release of tumor antigens and danger-associated molecular pattern (DAMP) factors; (ii) the immunogenicity of tumor cell death; and (iii) the resulting systemic anti-tumor immune response.MethodsTo sample the wide diversity amongst clinical strains of HSV-1, twenty nine new clinical strains isolated from cold sores from otherwise healthy volunteers were screened across a panel of human tumor cell lines to identify the strain with the most potent tumor cell killing ability, which was then used for further development. Following deletion of the genes encoding ICP34.5 and ICP47 to provide tumor selectivity, the extent of cell killing and the immunogenicity of cell death was enhanced through insertion of a gene encoding a truncated, constitutively highly fusogenic form of the envelope glycoprotein of gibbon ape leukemia virus (GALV-GP-R-). A number of further armed derivatives of this virus were then constructed intended to further enhance the anti-tumor immune response which was generated following fusion-enhanced, oncolytic virus replication-mediated cell death. These viruses expressed GMCSF, an anti-CTLA-4 antibody-like molecule, CD40L, OX40L and/or 4-1BB, each of which is expected to act predominantly at the site and time of immune response initiation. Expression of these proteins was confirmed by ELISA and/or western blotting. Immunogenic cell death was assessed by measuring the levels of HMGB1 and ATP from cell free supernatants from treated cells, and by measuring the surface expression of calreticulin. GALV-GP-R- mediated cell to cell fusion and killing was tested in a range of tumor cell lines in vitro. Finally, the in vivo therapeutic potential of these viruses was tested using human A549 (lung cancer) and MDA-MB-231(breast cancer) tumor nude mouse xenograft models and systemic anti-tumor effects tested using dual flank syngeneic 4434 (melanoma), A20 (lymphoma) mouse tumor models alone and in combination with a murine anti-PD1 antibody, and 9 L (gliosarcoma) tumors in rats.ResultsThe twenty nine clinical strains of HSV-1 isolated and tested demonstrated a broad range of tumor cell killing abilities allowing the most potent strain to be identified which was then used for further development. Oncolytic ability was demonstrated to be further augmented by the expression of GALV-GP-R- in a range of tumor cell lines in vitro and in mouse xenograft models in nude mice. The expression of GALV-GP-R- was also demonstrated to lead to enhanced immunogenic cell death in vitro as confirmed by the increased release of HMGB1 and ATP and increased levels of calreticulin on the cell surface. Experiments using the rat 9 L syngeneic tumor model demonstrated that GALV-GP-R- expression increased abscopal uninjected (anenestic) tumor responses and data using mouse 4434 tumors demonstrated that virus treatment increased CD8+ T cell levels both in the injected and uninjected tumor, and also led to increased expression of PD-L1. A combination study using varying doses of a virus expressing GALV-GP-R- and mGM-CSF and an anti-murine PD1 antibody showed enhanced anti-tumor effects with the combination which was most evident at low virus doses, and also lead to immunological memory. Finally, treatment of mice with derivatives of this virus which additionally expressed anti-mCTLA-4, mCD40L, m4-1BBL, or mOX40L demonstrated enhanced activity, particularly in uninjected tumors.ConclusionThe new HSV-1 based platform described provides a potent and versatile approach to developing new oncolytic immunotherapies for clinical use. Each of the modifications employed was demonstrated to aid in optimizing the potential of the virus to both directly kill tumors and to lead to systemic therapeutic benefit. For clinical use, these viruses are expected to be most effective in combination with other anti-cancer agents, in particular PD1/L1-targeted immune checkpoint blockade. The first virus from this program (expressing GALV-GP-R- and hGM-CSF) has entered clinical development alone and in combination with anti-PD1 therapy in a number of tumor types (NCT03767348)

Spectroscopic investigation of quantum confinement effects in ion implanted silicon-on-sapphire films

Crystalline Silicon-on-Sapphire (SOS) films were implanted with boron (B$^+$) and phosphorous (P$^+$) ions. Different samples, prepared by varying the ion dose in the range $10^{14}$ to 5 x $10^{15}$ and ion energy in the range 150-350 keV, were investigated by the Raman spectroscopy, photoluminescence (PL) spectroscopy and glancing angle x-ray diffraction (GAXRD). The Raman results from dose dependent B$^+$ implanted samples show red-shifted and asymmetrically broadened Raman line-shape for B$^+$ dose greater than $10^{14}$ ions cm$^{-2}$. The asymmetry and red shift in the Raman line-shape is explained in terms of quantum confinement of phonons in silicon nanostructures formed as a result of ion implantation. PL spectra shows size dependent visible luminescence at $\sim$ 1.9 eV at room temperature, which confirms the presence of silicon nanostructures. Raman studies on P$^+$ implanted samples were also done as a function of ion energy. The Raman results show an amorphous top SOS surface for sample implanted with 150 keV P$^+$ ions of dose 5 x $10^{15}$ ions cm$^{-2}$. The nanostructures are formed when the P$^+$ energy is increased to 350 keV by keeping the ion dose fixed. The GAXRD results show consistency with the Raman results.Comment: 9 Pages, 6 Figures and 1 Table, \LaTex format To appear in SILICON(SPRINGER

Does hyperprolactinemia affect hepatic regeneration independent of sex steroids?

Prolactin, administered exogeneously, has been shown to be trophic to the liver, causing increases in the liver weight-to-body weight ratio, in ornithine decarboxylase activity, and in thymidine kinase activity. To investigate the effect of endogenous hyperprolactinemia on hepatic regeneration, pituitary isografts were placed beneath the renal capsule in rats 2 weeks before the rats underwent a two-thirds partial hepatectomy. Prolactin levels 2 weeks after the transplant were greater in the animals with the pituitary isografts compared with levels in controls. The increase in the liver weight-to-body weight ratio after hepatectomy was similar in the rats with pituitary transplant and the controls. However, chronic hyperprolactinemia was associated with increased basal levels of ornithine decarboxylase activity and thymidine kinase activity. Both ornithine decarboxylase activity and thymidine kinase activity increased after partial hepatectomy, and the magnitude of the changes was similar for both groups of animals. The levels of estrogen receptor activity before the partial hepatectomy and the reduction in receptor activity that follows partial hepatectomy were similar in the two groups of animals. Moreover, the levels of androgen receptor activity within the liver before partial hepatectomy and the increase in receptor activity after hepatectomy were similar in the two groups of animals. Thus, chronic sustained hyperprolactinemia has no beneficial effect on the hepatic regenerative response, despite induction of both basal ornithine decarboxylase and thymidine kinase activities

Bullying girls - Changes after brief strategic family therapy: A randomized, prospective, controlled trial with one-year follow-up

Background: Many girls bully others. They are conspicuous because of their risk-taking behavior, increased anger, problematic interpersonal relationships and poor quality of life. Our aim was to determine the efficacy of brief strategic family therapy (BSFT) for bullying-related behavior, anger reduction, improvement of interpersonal relationships, and improvement of health-related quality of life in girls who bully, and to find out whether their expressive aggression correlates with their distinctive psychological features. Methods: 40 bullying girls were recruited from the general population: 20 were randomly selected for 3 months of BSFT. Follow-up took place 12 months after the therapy had ended. The results of treatment were examined using the Adolescents' Risk-taking Behavior Scale (ARBS), the State-Trait Anger Expression Inventory (STAXI), the Inventory of Interpersonal Problems (IIP-D), and the SF-36 Health Survey (SF-36). Results: In comparison with the control group (CG) (according to the intent-to-treat principle), bullying behavior in the BSFT group was reduced (BSFT-G from n = 20 to n = 6; CG from n = 20 to n = 18, p = 0.05) and statistically significant changes in all risk-taking behaviors (ARBS), on most STAXI, IIP-D, and SF-36 scales were observed after BSFT. The reduction in expressive aggression (Anger-Out scale of the STAXI) correlated with the reduction on several scales of the ARBS, IIP-D, and SF-36. Follow-up a year later showed relatively stable events. Conclusions: Our findings suggest that bullying girls suffer from psychological and social problems which may be reduced by the use of BSFT. Expressive aggression in girls appears to correlate with several types of risk-taking behavior and interpersonal problems, as well as with health-related quality of life. Copyright (c) 2006 S. Karger AG, Basel