The KIDSCREEN-27 quality of life measure for children and adolescents: psychometric results from a cross-cultural survey in 13 European countries

OBJECTIVE: To assess the construct and criterion validity of the KIDSCREEN-27 health-related quality of life (HRQoL) questionnaire, a shorter version of the KIDSCREEN-52. METHODS: The five-dimensional KIDSCREEN-27 was tested in a sample of 22,827. For criterion validity the correlation with and the percentage explained variance of the scores of the KIDSCREEN-52 instrument were examined. Construct validity was assessed by testing a priori expected associations with other generic HRQoL measures (YQOL-S, PedsQL, CHIP), indicators of physical and mental health, and socioeconomic status. Age and gender differences were investigated. RESULTS: Correlation with corresponding scales of the KIDSCREEN-52 ranged from r = 0.63 to r = 0.96, and r2 ranged from 0.39 to 0.92. Correlations between other HRQoL questionnaires and KIDSCREEN-27 dimensions were moderate to high for those assessing similar constructs (r = 0.36 to 0.63). Statistically significant and sizeable differences between physically and mentally healthy and ill children were found in all KIDSCREEN-27 dimensions together with strong associations with psychosomatic complaints (r = -0.52). Most of the KIDSCREEN-27 dimensions showed a gradient according to socio-economic status, age and gender. CONCLUSIONS: The KIDSCREEN-27 seems to be a valid measure of HRQoL in children and adolescents. Further research is needed to assess longitudinal validity and sensitivity to change.

On the variability of return periods of European winter precipitation extremes over the last three centuries

We investigate the changes of extreme European winter (December-February) precipitation back to 1700 and show for various European regions that return periods of extremely wet and dry winters are subject to significant changes both before and after the onset of anthropogenic influences. Generally, winter precipitation has become more extreme. We also examine the spatial pattern of the changes of the extremes covering the last 300 years where data quality is sufficient. Over central and Eastern Europe dry winters occurred more frequently during the 18th and the second part of the 19th century relative to 1951–2000. Dry winters were less frequent during both the 18th and 19th century over the British Isles and the Mediterranean. Wet winters have been less abundant during the last three centuries compared to 1951–2000 except during the early 18th century in central Europe. Although winter precipitation extremes are affected by climate change, no obvious connection of these changes was found to solar, volcanic or anthropogenic forcing. However, physically meaningful interpretation with atmospheric circulation changes was possible.

Osteoblast responses to different oxide coatings produced by the sol-gel process on titanium substrates

In order to improve the osseointegration of endosseous implants made from titanium, the structure and composition of the surface were modified. Mirror-polished commercially pure (cp) titanium substrates were coated by the sol-gel process with different oxides: TiO(2), SiO(2), Nb(2)O(5) and SiO(2)-TiO(2). The coatings were physically and biologically characterized. Infrared spectroscopy confirmed the absence of organic residues. Ellipsometry determined the thickness of layers to be approximately 100nm. High resolution scanning electron microscopy (SEM) and atomice force microscopy revealed a nanoporous structure in the TiO(2) and Nb(2)O(5) layers, whereas the SiO(2) and SiO(2)-TiO(2) layers appeared almost smooth. The R(a) values, as determined by white-light interferometry, ranged from 20 to 50nm. The surface energy determined by the sessile-drop contact angle method revealed the highest polar component for SiO(2) (30.7mJm(-2)) and the lowest for cp-Ti and 316L stainless steel (6.7mJm(-2)). Cytocompatibility of the oxide layers was investigated with MC3T3-E1 osteoblasts in vitro (proliferation, vitality, morphology and cytochemical/immunolabelling of actin and vinculin). Higher cell proliferation rates were found in SiO(2)-TiO(2) and TiO(2), and lower in Nb(2)O(5) and SiO(2); whereas the vitality rates increased for cp-Ti and Nb(2)O(5). Cytochemical assays showed that all substrates induced a normal cytoskeleton and well-developed focal adhesion contacts. SEM revealed good cell attachment for all coating layers. In conclusion, the sol-gel-derived oxide layers were thin, pure and nanostructured; consequent different osteoblast responses to those coatings are explained by the mutual action and coadjustment of different interrelated surface parameters.

Posttranslational modification of the AU-rich element binding protein HuR by protein kinase Cdelta elicits angiotensin II-induced stabilization and nuclear export of cyclooxygenase 2 mRNA

The mRNA stabilizing factor HuR is involved in the posttranscriptional regulation of many genes, including that coding for cyclooxygenase 2 (COX-2). Employing RNA interference technology and actinomycin D experiments, we demonstrate that in human mesangial cells (hMC) the amplification of cytokine-induced COX-2 by angiotensin II (AngII) occurs via a HuR-mediated increase of mRNA stability. Using COX-2 promoter constructs with different portions of the 3' untranslated region of COX-2, we found that the increase in COX-2 mRNA stability is attributable to a distal class III type of AU-rich element (ARE). Likewise, the RNA immunoprecipitation assay showed AngII-induced binding of HuR to this ARE. Using the RNA pulldown assay, we demonstrate that the AngII-caused HuR assembly with COX-2 mRNA is found in free and cytoskeleton-bound polysomes indicative of an active RNP complex. Mechanistically, the increased HuR binding to COX-2-ARE by AngII is accompanied by increased nucleocytoplasmic HuR shuttling and depends on protein kinase Cdelta (PKCdelta), which physically interacts with nuclear HuR, thereby promoting its phosphorylation. Mapping of phosphorylation sites identified serines 221 and 318 as critical target sites for PKCdelta-triggered HuR phosphorylation and AngII-induced HuR export to the cytoplasm. Posttranslational modification of HuR by PKCdelta represents an important novel mode of HuR activation implied in renal COX-2 regulation.

Translocation and cellular entering mechanisms of nanoparticles in the respiratory tract

Anthropogenic nano-sized particles (NSP), ie, particles with a diameter of less than 100 nm, are generated with or without purpose as chemically and physically well-defined materials or as a consequence of combustion processes respectively. Inhalation of NSP occurs on a regular basis due to air pollution and is associated with an increase in respiratory and cardiovascular morbidity and mortality. Manufactured NSP may intentionally be inhaled as pharmaceuticals or unintentionally during production at the workplace. Hence the interactions of NSP with the respiratory tract are currently under intensive investigation. Due to special physicochemical features of NSP, its biological behaviour may differ from that of larger sized particles. Here we review two important themes of current research into the effects of NSP on the lungs: 1) The potential of NSP to cross the blood-air barrier of the lungs, thus gaining access to the circulation and extrapulmonary organs. It is currently accepted that a small fraction of inhaled NSP may translocate to the circulation. The significance of this translocation requires further research. 2) The entering mechanisms of NSP into different cell types. There is evidence that NSP are taken up by cells via well-known pathways of endocytosis but also via different mechanisms not well understood so far. Knowledge of the quantitative relationship between the different entering mechanisms and cellular responses is not yet available but is urgently needed in order to understand the effects of intentionally or unintentionally inhaled NSP on the respiratory tract.

Quantifying the ecological benefits of lakeshore restoration in northern Wisconsin

Housing development has increased dramatically in the Midwest with a high concentration around lakes. This development plays an important role in the economy of Northwoods communities. However, poorly planned development has the potential to alter a lake’s ecological processes and integrity. Studies have documented the impacts of housing developments and reported dramatic, negative changes to the flora and fauna in Vilas County, Wisconsin. One component of my research included examining the previously unstudied effects of residential development on the abundance and diversity of medium to large-bodied mammals using lakeshore ecosystems. The results suggest that a higher diversity of mammals were detected on low-development lakes. Coyotes were the most numerous species detected with the majority encountered on low-development lakes. White-tailed deer and red fox were more abundant on high-development lakes as compared to low-development lakes. I concluded that high-development lakes are having a negative affect on the mammal community in this area. Recently, lakeshore restoration has occurred on privately owned property in Vilas County and elsewhere in the Northwoods, but little is known about the benefit, if any, from these restoration efforts. A partnership between government agencies and academia has launched a long-term research project investigating the ecological benefits of lakeshore restoration. I investigated the impacts of using down woody material (DWM) to increase the success of restoration projects. Specifically, I tested the hypothesis that down woody material would reduce the variation in soil temperature, retain soil moisture, and improve plant survival and growth rates. I randomly assigned three DWM coverage treatments (0%, 25%, and 50%) on 3 m × 3 m experimental plots (n = 10 per treatment). The mean maximum soil temperature, temperature variation, and change in soil moisture content were significantly lower in the 25% and 50% DWM plots. I found no difference in survival, but snowberry (Symphoricarpos albus) and Barren strawberry (Waldstenia fragaroides) growth was significant greater in the 25% and 50% DWM plots. DWM addition can be considered a useful technique to physically manipulate soil properties and improve plant growth. Finally, I provided baseline data on vegetation structure, bird and small mammal community diversity and abundance for three lakes targeted for restoration efforts and their paired reference lakes. This study is one of the first of it kind in the area and continuing to document the degree of change in subsequent years will provide insight into the way the local ecosystem functions and how ecological communities are structured.

Hsp90 transcriptionally and post-translationally regulates the expression of NDRG1 and maintains the stability of its modifying kinase GSK3beta

N-myc downstream-regulated gene 1 (NRDG1) is a stress-induced protein whose putative function is suppression of tumor metastasis. A recent proteonomic study showed NDRG1 interacts with the molecular chaperone heat shock protein 90 (Hsp90). From their reported association, we investigated if NDRG1 is dependent on Hsp90 for its stability and is therefore a yet unidentified Hsp90 client protein. Here, we demonstrate that endogenous NDRG1 and Hsp90 physically associate in hepatocellular cancer cell lines. However, geldanamycin (GA)-mediated inhibition of Hsp90 did not disrupt their interaction or result in NDRG1 protein destabilization. On the contrary, inhibition of Hsp90 led to a transcriptional increase of NDRG1 protein which was associated with cell growth arrest. We also observed that GA inhibited the phosphorylation of NDRG1 by targeting its regulating kinases, serum- and glucocorticoid-induced kinase 1 (SGK1) and glycogen synthase kinase 3 beta (GSK3beta). We demonstrate that in the presence of GA, GSK3beta protein and activity were decreased thus indicating that Hsp90 is necessary for GSK3beta stability. Taken together, our data demonstrate that NDRG1 is not a classic client protein but interacts with Hsp90 and is still dually regulated by Hsp90 at a transcriptional and post-translational level. Finally, we suggest for the first time GSK3beta as a new client protein of Hsp90.

Constitutive interaction of the P2Y2 receptor with the hematopoietic cell-specific G protein G(alpha16) and evidence for receptor oligomers

Hematopoietic cells uniquely express G(alpha16), a G protein alpha-subunit of the G(q)-type. G(alpha16) is obligatory for P2Y2 receptor-dependent Ca2+-mobilization in human erythroleukemia cells and induces hematopoietic cell differentiation. We tested whether P2Y2 receptors physically interact with G(alpha16). Receptor and G protein were fused to cyan (CFP) and yellow (YFP) variants of the green fluorescent protein (GFP), respectively. When expressed in K562 leukemia cells, the fusion proteins were capable of triggering a Ca2+-signal upon receptor stimulation, demonstrating their functional integrity. In fluorescence resonance energy transfer (FRET) measurements using confocal microscopy, a strong FRET signal from the plasma membrane region of fixed, resting cells was detected when the receptor was co-expressed with the G protein as the FRET acceptor, as well as when the CFP-tagged receptor was co-expressed with receptor fused to YFP. We conclude that, under resting conditions, G(alpha16) and P2Y2 receptors form constitutive complexes, and that the P2Y2 receptor is present as an oligomer.

Changing Europe and The Relevance of Care and The Caring Professions

The aim of the paper is to introduce the challenges of the international care debate of the last ten years in order to grasp basic social needs, to analyse their treatment in the public and private sphere and to look at the orientation of professional answers by the care-professions. The concept of care enhances the societal dealing with - or ignoring of - different forms of dependency on informal and formal personal and social services throughout the life-cycle (child-care, nursing sick or handicapped persons, supporting the elderly) and in special life situations (from help to lone mothers and their children, via help to drug-addicts to help for homeless people). All societies have different approaches to deal with these life-situations, they do so by employ-ing various mixtures of: familial support, mostly provided by women, social politics, organized by the state, public and/or private social services. This welfare-mix shows different combinations of private and public obligations, paid and und unpaid work, professional and laymen's tasks based on a specific understanding of mo-rality and justice embedded in the gender structure and intergenerational relationships. The importance of social work as a profession in this context differs according to the historical developments and cultural traditions. Characteristic for the profile of social work is the rele-vance of a care ethics and the existence of social rights, the tension of mothering and profes-sional methods, the relationship between help, denial and punishment and the ways of institu-tionalisation. The actuality of this debate is closely intertwined with the restructuring of societal bonds in the face of globalisation, the political reorganisation of states, the changes in the living to-gether of different generations and both sexes and the consequences for the organisation and contents of welfare. Looking at Germany and Eastern Europe two new phenomena of social relevance for the dis-cussion of care work and care needs can be taken as an example: the extent of cheap illegal women laborers travelling between east and west, especially Polish women working intermit-tendly in private care for old people and the highly organized traffiking of women from Russia to Germany to work in the sex business. The care debate entails a reframing of welfare issues in the light of social justice between classes, ethnicities and gender groups.

The art to keep in touch: The ''good use'' of Lagrange multipliers

Physically-based modeling for computer animation allows to produce more realistic motions in less time without requiring the expertise of skilled animators. But, a computer animation is not only a numerical simulation based on classical mechanics since it follows a precise story-line. One common way to define aims in an animation is to add geometric constraints. There are several methods to manage these constraints within a physically-based framework. In this paper, we present an algorithm for constraints handling based on Lagrange multipliers. After few remarks on the equations of motion that we use, we present a first algorithm proposed by Platt. We show with a simple example that this method is not reliable. Our contribution consists in improving this algorithm to provide an efficient and robust method to handle simultaneous active constraints.

A Physically Based Transmission Model of Rough Surfaces

Transparent and translucent objects involve both light reflection and transmission at surfaces. This paper presents a physically based transmission model of rough surface. The surface is assumed to be locally smooth, and statistical techniques is applied to calculate light transmission through a local illumination area. We have obtained an analytical expression for single scattering. The analytical model has been compared to our Monte Carlo simulations as well as to the previous simulations, and good agreements have been achieved. The presented model has potential applications for realistic rendering of transparent and translucent objects.

Historical weather extremes in the “Twentieth Century Reanalysis”

Meteorological or climatological extremes are rare and hence studying them requires long meteorological data sets. Moreover, for addressing the underlying atmospheric processes, detailed three-dimensional data are desired. Until recently the two requirements were incompatible as long meteorological series were only available for a few locations, whereas detailed 3-dimensional data sets such as reanalyses were limited to the past few decades. In 2011, the “Twentieth Century Reanalysis” (20CR) was released, a 6-hourly global atmospheric data set covering the past 140 years, thus combining the two properties. The collection of short papers in this volume contains case studies of individual extreme events in the 20CR data set. In this overview paper we introduce the first six cases and summarise some common findings. All of the events are represented in 20CR in a physically consistent way, allowing further meteorological interpretations and process studies. Also, for most of the events, the magnitudes are underestimated in the ensemble mean. Possible causes are addressed. For interpreting extrema it may be necessary to address individual ensemble members. Also, the density of observations underlying 20CR should be considered. Finally, we point to problems in wind speeds over the Arctic and the northern North Pacific in 20CR prior to the 1950s.

The effect of a single 2 h bout of aerobic exercise on ectopic lipids in skeletal muscle, liver and the myocardium.

AIMS/HYPOTHESIS Ectopic lipids are fuel stores in non-adipose tissues (skeletal muscle [intramyocellular lipids; IMCL], liver [intrahepatocellular lipids; IHCL] and heart [intracardiomyocellular lipids; ICCL]). IMCL can be depleted by physical activity. Preliminary data suggest that aerobic exercise increases IHCL. Data on exercise-induced changes on ICCL is scarce. Increased IMCL and IHCL have been related to insulin resistance in skeletal muscles and liver, whereas this has not been documented in the heart. The aim of this study was to assess the acute effect of aerobic exercise on the flexibility of IMCL, IHCL and ICCL in insulin-sensitive participants in relation to fat availability, insulin sensitivity and exercise capacity. METHODS Healthy physically active men were included. [Formula: see text] was assessed by spiroergometry and insulin sensitivity was calculated using the HOMA index. Visceral and subcutaneous fat were separately quantified by MRI. Following a standardised dietary fat load over 3 days, IMCL, IHCL and ICCL were measured using MR spectroscopy before and after a 2 h exercise session at 50-60% of [Formula: see text]. Metabolites were measured during exercise. RESULTS Ten men (age 28.9 ± 6.4 years, mean ± SD; [Formula: see text] 56.3 ± 6.4 ml kg(-1) min(-1); BMI 22.75 ± 1.4 kg/m(2)) were recruited. A 2 h exercise session resulted in a significant decrease in IMCL (-17 ± 22%, p = 0.008) and ICCL (-17 ± 14%, p = 0.002) and increase in IHCL (42 ± 29%, p = 0.004). No significant correlations were found between the relative changes in ectopic lipids, fat availability, insulin sensitivity, exercise capacity or changes of metabolites during exercise. CONCLUSIONS/INTERPRETATION In this group, physical exercise decreased ICCL and IMCL but increased IHCL. Fat availability, insulin sensitivity, exercise capacity and metabolites during exercise are not the only factors affecting ectopic lipids during exercise.

Rtr1 is the Saccharomyces cerevisiae homolog of a novel family of RNA polymerase II-binding proteins.

Cells must rapidly sense and respond to a wide variety of potentially cytotoxic external stressors to survive in a constantly changing environment. In a search for novel genes required for stress tolerance in Saccharomyces cerevisiae, we identified the uncharacterized open reading frame YER139C as a gene required for growth at 37 degrees C in the presence of the heat shock mimetic formamide. YER139C encodes the closest yeast homolog of the human RPAP2 protein, recently identified as a novel RNA polymerase II (RNAPII)-associated factor. Multiple lines of evidence support a role for this gene family in transcription, prompting us to rename YER139C RTR1 (regulator of transcription). The core RNAPII subunits RPB5, RPB7, and RPB9 were isolated as potent high-copy-number suppressors of the rtr1Delta temperature-sensitive growth phenotype, and deletion of the nonessential subunits RPB4 and RPB9 hypersensitized cells to RTR1 overexpression. Disruption of RTR1 resulted in mycophenolic acid sensitivity and synthetic genetic interactions with a number of genes involved in multiple phases of transcription. Consistently, rtr1Delta cells are defective in inducible transcription from the GAL1 promoter. Rtr1 constitutively shuttles between the cytoplasm and nucleus, where it physically associates with an active RNAPII transcriptional complex. Taken together, our data reveal a role for members of the RTR1/RPAP2 family as regulators of core RNAPII function.

IMMUNE MODULATION OF THE MYCOBACTERIUM TUBERCULOSIS GRANULOMATOUS RESPONSE

Tuberculosis (TB) remains a major public health burden. The immunocompetant host responds to Mycobacterium tuberculosis (MTB) infection by the formation of granulomas, which initially prevent uncontrolled bacterial proliferation and dissemination. However, increasing evidence suggests that granuloma formation promotes persistence of the organism by physically separating infected cells from effector lymphocytes and by inducing a state of non-replicating persistence in the bacilli, making them resistant to the action of antibiotics. Additionally, immune-mediated tissue destruction likely facilitates disease transmission. The granulomatous response is in part due to mycobacterial glycolipid antigens. Therefore, studies were first undertaken to determine the innate mechanisms of mycobacterial cord factor trehalose-6’6-dimycolate (TDM) on granuloma formation. Investigations using knock-out mice suggest that TNF-a is involved in the initiation of the granulomatous response, complement factor C5a generates granuloma cohesiveness, and IL-6 is necessary for maintenance of an established granulomatous responses. Studies were next performed to determine the ability of lactoferrin to modulate the immune response and pathology to mycobacterial cord factor. Lactoferrin is an iron-binding glycoprotein with immunomodulatory properties that decrease tissue damage and promote Th1 responses. Mice challenged with TDM and treated with lactoferrin had decreased size and numbers of granulomas at the peak of the granulomatous response, accompanied by increased IL-10 and TGF-b production. Finally, the ability of lactoferrin to serve as a novel therapeutic for the treatment of TB was performed by aerosol challenging mice with MTB and treating them with lactoferrin added to the drinking water. Mice given tap water had lung log10 CFUs of 7.5 ± 0.3 at week 3 post-infection. Lung CFUs were significantly decreased in mice given lactoferrin starting the day of infection (6.4 ± 0.7) and mice started therapeutically on lactoferrin at day 7 after established infection (6.5 ± 0.4). Total lung inflammation in lactoferrin treated mice was significantly decreased, with fewer areas of macrophages, increased total lymphocytes, and increased numbers of CD4+ and CD8+ cells. The lungs of lactoferrin treated mice had increased CD4+ IFN-g+ cells and IL-17 producing cells on ELISpot analysis. It is hypothesized that lactoferrin decreases bacterial burden during MTB infection by early induction of Th1 responses.