Evaluation of the therapeutic potential of ant-TLR4-antibody MTS510 in experimental stroke and significa of different routes of application

Toll-like receptors (TLRs) are central sensors for the inflammatory response in ischemia-reperfusion injury. We therefore investigated whether TLR4 inhibition could be used to treat stroke in a standard model of focal cerebral ischemia. Anti-TLR4/MD2-antibody (mAb clone MTS510) blocked TLR4-induced cell activation in vitro, as reported previously. Here, different routes of MTS510 application in vivo were used to study the effects on stroke outcome up to 2d after occlusion of the middle cerebral artery (MCAO) for 45 min in adult male C57Bl/6 wild-type mice. Improved neurological performance, reduced infarct volumes, and reduced brain swelling showed that intravascular application of MTS510 had a protective effect in the model of 45 min MCAO. Evaluation of potential long-term adverse effects of anti-TLR4-mAb-treament revealed no significant deleterious effect on infarct volumes nor neurological deficit after 14d of reperfusion in a mild model of stroke (15 min MCAO). Interestingly, inhibition of TLR4 resulted in an altered adaptive immune response at 48 hours after reperfusion. We conclude that blocking TLR4 by the use of specific mAb is a promising strategy for stroke therapy. However, long-term studies with increased functional sensitivity, larger sampling sizes and use of other species are required before a clinical use could be envisaged

Inequality, material well-being, and subjective well-being: Exploring associations for children across 15 diverse countries

Children's material well-being, and the levels of wealth and inequality in societies within which children live, are important factors in determining outcomes. However, less is known about the extent to which these factors have an impact children's subjective well-being, especially in an internationally comparative context. This study draws on data from the Children's Worlds survey, an international study of child subjective well-being, to explore links between national level indicators of wealth and inequality (GDP and Gini coefficients), individual indicators of material well-being (the material resources children report having access to), and subjective well-being. The survey covers 15 diverse countries covering the continents of Europe, Asia, Africa and South America, with samples of at least 3000 per country, ages 8, 10 and 12. Analysis takes the form of a multilevel, varying intercepts and slopes model, examining the association between financial and material resources and inequality and subjective well-being across and between countries. Findings suggest that material resources that children report are significantly associated with subjective well-being, while indicators of financial resources and inequality at the national level are not. While a significant association between material resources and subjective well-being is found across the whole sample, the magnitude of this association, and the association between school- and country-level material resources, varies markedly. Within different countries, the strongest material resources-related predictor of overall subjective well-being may be either at the individual, school or country level

Reply to the Comment by B. Andresen

All the comments made by Andresen's comments are replied and are shown not to be pertinent. The original discussions [ABE S., Europhys. Lett. 90 (2010) 50004] about the absence of nonextensive statistical mechanics with q-entropies for classical continuous systems are reinforced.Comment: 5 pages. This is Reply to B. Andresen's Comment on the paper entitled "Essential discreteness in generalized thermostatistics with non-logarithmic entropy", Europhys. Lett. 90 (2010) 5000

The association of selected multiple sclerosis symptoms with disability and quality of life:a large Danish self-report survey

Abstract Background People with multiple sclerosis (MS) experience a wide range of unpredictable and variable symptoms. The symptomatology of MS has previously been reported in large sample registry studies; however, some symptoms may be underreported in registries based on clinician-reported outcomes and how the symptoms are associated with quality of life (QoL) are often not addressed. The aim of this study was to comprehensively evaluate the frequency of selected MS related symptoms and their associations with disability and QoL in a large self-report study. Methods We conducted a cross-sectional questionnaire survey among all patients at the Danish Multiple Sclerosis Center, Copenhagen University Hospital, Denmark. The questionnaire included information on clinical and sociodemographic characteristics, descriptors of QoL and disability, as well as prevalence and severity of the following MS symptoms: impaired ambulation, spasticity, chronic pain, fatigue, bowel and bladder dysfunction, and sleep disturbances. Results Questionnaires were returned by 2244/3606 (62%). Participants without MS diagnosis or incomplete questionnaires were excluded, n = 235. A total of 2009 questionnaires were included for analysis (mean age 49.4 years; mean disease duration 11.7 years; and 69% were women). The most frequently reported symptoms were bowel and bladder dysfunction (74%), fatigue (66%), sleep disturbances (59%), spasticity (51%) and impaired ambulation (38%). With exception of fatigue and sleep disturbances, all other symptoms increased in severity with higher disability level. Invisible symptoms (also referred to as hidden symptoms) such as fatigue, pain and sleep disturbances had the strongest associations with the overall QoL. Conclusion We found invisible symptoms highly prevalent, even at mild disability levels. Fatigue, pain and sleep disturbances had the strongest associations with the overall QoL and were more frequently reported in our study compared with previous registry-based studies. These symptoms may be underreported in registries based on clinician reported outcomes, which emphasizes the importance of including standardized patient reported outcomes in nationwide registries to better understand the impact of the symptom burden in MS

A Highly Pathogenic Strain of Staphylococcus sciuri Caused Fatal Exudative Epidermitis in Piglets

Staphylococcus sciuri are important human pathogens responsible for endocarditis, peritonitis, septic shock, urinary tract infection, pelvic inflammatory disease and wound infections. However, little information is known regarding the pathogenicity of S. sciuri to animals. From the pericardial fluid of a diseased piglet with exudative epidermitis (EE), we isolated a strain of Staphylococcus in pure culture. Surprisingly, this isolate was a member of S. sciuri rather than S. hyicus as identified by its biochemical traits and also by analysis of 23S ribosomal DNA using Internal Transcribed Spacer PCR. In addition, inoculation of newborn piglets with 1×10(10) CFU of the isolate by oral feeding or intra-muscular injection successfully reproduced EE in piglets, which suggested that the oral intake of the pathogen by the animals is one of the major routes of exposure. These unexpected findings prioritized S. sciuri as important zoonotic agents, which may have ramifications for human medicine

Staphylococcus sciuri Exfoliative Toxin C (ExhC) is a Necrosis-Inducer for Mammalian Cells

Staphylococcus sciuri (S. sciuri) is a rare pathogen in humans, but it can cause a wide array of human infections. Recently a S. sciuri isolate (HBXX06) was reported to cause fatal exudative epidermitis (EE) in piglets and thus considered as a potential zoonotic agent. To investigate the pathogenicity of this bacterium, we cloned exfoliative toxin C (ExhC), a major toxin of the S. sciuri isolate and performed functional analysis of the recombinant ExhC-his (rExhC) protein using in vitro cell cultures and newborn mice as models. We found that rExhC could induce necrosis in multiple cell lines and peritoneal macrophages as well as skin lesions in newborn mice, and that the rExhC-induced necrosis in cells or skin lesions in newborn mice could be completely abolished if amino acids 79-128 of rExhC were deleted or blocked with a monoclonal antibody (3E4), indicating aa 79-128 portion as an essential necrosis-inducing domain. This information contributes to further understandings of the mechanisms underlying S. sciuri infection

Remedies for Managing Bottlenecks and Time Thieves in Norwegian Construction Projects – Public vs Private Sector

Reducing project execution time is an important aspect in today's construction industry. In practice, most construction projects are delivered behind schedule. This creates an incentive to find methods, processes and techniques to deal with elements which steal time and bottlenecks which cause delays. This paper address the magnitude, frequency and type of time-thieves and bottlenecks in various phases of construction projects from different construction firms and organizations in the public sector in Norway. It also discusses remedies to mitigate time thieves and bottlenecks. The questionnaire used was designed and tested to give a broad and open data collection. The purpose was to collect opinions from senior project managers and project members in order to identify time-thieves, bottlenecks and remedies and analyse the data to assertain if there are common and/or different opinions or perspectives in public and in private sectors. This study will provide an insight into the problem, time-thieves and bottlenecks, itself. The firms in this study are part of a larger national programme called SpeedUp. The programme focuses on every aspect of speeding up projects. The SpeedUp programme is a 10 million USD research programme with 5 researchers and 7-8 PhD students. It is linked to Project Norway which is a research-based collaboration of Norwegian project-based organizations in the public and private sector

Structure and Magnetic Properties of the MnBi Low Temperature Phase

High purity MnBi low temperature phase has been prepared and analyzed using magnetic measurements and neutron diffraction. The low-temperature phase of the MnBi alloy has a coercivity μ0iHc of 2.0 T at 400 K, and exhibits a positive temperature coefficient from 0 to at least 400 K. The neutron data refinement indicated that the Mn atom changes its spin direction from c axis above room temperature to nearly perpendicular to the c axis at 50 K. A canted magnetic structure has been observed below 200 K. The anisotropy field increases with increasing temperature which gives rise to a high coercivity at the higher temperatures. The anisotropic bonded magnets have maximum energy products (BH)max of 7.7 and 4.6 MGOe at room temperature and 400 K, respectively