Testing the structural and cross-cultural validity of the KIDSCREEN-27 quality of life questionnaire

OBJECTIVES: The aim of this study is to assess the structural and cross-cultural validity of the KIDSCREEN-27 questionnaire. METHODS: The 27-item version of the KIDSCREEN instrument was derived from a longer 52-item version and was administered to young people aged 8-18 years in 13 European countries in a cross-sectional survey. Structural and cross-cultural validity were tested using multitrait multi-item analysis, exploratory and confirmatory factor analysis, and Rasch analyses. Zumbo's logistic regression method was applied to assess differential item functioning (DIF) across countries. Reliability was assessed using Cronbach's alpha. RESULTS: Responses were obtained from n = 22,827 respondents (response rate 68.9%). For the combined sample from all countries, exploratory factor analysis with procrustean rotations revealed a five-factor structure which explained 56.9% of the variance. Confirmatory factor analysis indicated an acceptable model fit (RMSEA = 0.068, CFI = 0.960). The unidimensionality of all dimensions was confirmed (INFIT: 0.81-1.15). Differential item functioning (DIF) results across the 13 countries showed that 5 items presented uniform DIF whereas 10 displayed non-uniform DIF. Reliability was acceptable (Cronbach's alpha = 0.78-0.84 for individual dimensions). CONCLUSIONS: There was substantial evidence for the cross-cultural equivalence of the KIDSCREEN-27 across the countries studied and the factor structure was highly replicable in individual countries. Further research is needed to correct scores based on DIF results. The KIDSCREEN-27 is a new short and promising tool for use in clinical and epidemiological studies.

Radiofrequency electromagnetic field exposure and non-specific symptoms of ill health: A systematic review

This article is a systematic review of whether everyday exposure to radiofrequency electromagnetic field (RF-EMF) causes symptoms, and whether some individuals are able to detect low-level RF-EMF (below the ICNIRP [International Commission on Non-Ionizing Radiation Protection] guidelines). Peer-reviewed articles published before August 2007 were identified by means of a systematic literature search. Meta-analytic techniques were used to pool the results from studies investigating the ability to discriminate active from sham RF-EMF exposure. RF-EMF discrimination was investigated in seven studies including a total of 182 self-declared electromagnetic hypersensitive (EHS) individuals and 332 non-EHS individuals. The pooled correct field detection rate was 4.2% better than expected by chance (95% CI: -2.1 to 10.5). There was no evidence that EHS individuals could detect presence or absence of RF-EMF better than other persons. There was little evidence that short-term exposure to a mobile phone or base station causes symptoms based on the results of eight randomized trials investigating 194 EHS and 346 non-EHS individuals in a laboratory. Some of the trials provided evidence for the occurrence of nocebo effects. In population based studies an association between symptoms and exposure to RF-EMF in the everyday environment was repeatedly observed. This review showed that the large majority of individuals who claims to be able to detect low level RF-EMF are not able to do so under double-blind conditions. If such individuals exist, they represent a small minority and have not been identified yet. The available observational studies do not allow differentiating between biophysical from EMF and nocebo effects.

Body fat changes among antiretroviral-naive patients on PI- and NNRTI-based HAART in the Swiss HIV cohort study

BACKGROUND: Body fat changes are common in patients with HIV. For patients on protease inhibitor (PI)-based highly active antiretroviral therapy (HAART), these changes have been associated with increasing exposure to therapy in general and to stavudine in particular. Our objective is to show whether such associations are more or less likely for patients on non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART. METHODS: We included all antiretroviral-naive patients in the Swiss HIV Cohort Study starting HAART after April 2000 who had had body weight, CD4 cell count and plasma HIV RNA measured between 6 months before and 3 months after starting HAART, and at least one assessment of body fat changes after starting HAART. At visits scheduled every 6 months, fat loss or fat gain is reported by agreement between patient and physician. We estimate the association between reported body fat changes and both time on therapy and time on stavudine, using conditional logistical regression. RESULTS: Body fat changes were reported for 85 (9%) out of 925 patients at their first assessment; a further 165 had only one assessment. Of the remaining 675 patients, body fat changes were reported for 156 patients at a rate of 13.2 changes per 100 patient-years. Body fat changes are more likely with increasing age [odds ratio (OR) 1.18 (1.00-1.38) per 10 years], with increasing BMI [OR 1.06 (1.01-1.11)] and in those with a lower baseline CD4 cell count [OR 0.91 (0.83-1.01) per 100 cells/microl]. There is only weak evidence that body fat changes are more likely with increasing time on HAART [OR 1.16 (0.93-1.46)]. After adjusting for time on HAART, fat loss is more likely with increasing stavudine use [OR 1.70 (1.34-2.15)]. There is no evidence of an association between reported fat changes and time on NNRTI therapy relative to PI therapy in those patients who used either one therapy or the other [OR 0.98 (0.56-1.63)]. CONCLUSION: Fat loss is more likely to be reported with increasing exposure to stavudine. We find no evidence of major differences between PI and NNRTI therapy in the risk of reported body fat changes.

Non-Hodgkin lymphoma incidence in the Swiss HIV Cohort Study before and after highly active antiretroviral therapy

OBJECTIVE: To assess the long-term effect of HAART on non-Hodgkin lymphoma (NHL) incidence in people with HIV (PHIV). DESIGN: Follow-up of the Swiss HIV Cohort Study (SHCS). METHODS: Between 1984 and 2006, 12 959 PHIV contributed a total of 75 222 person-years (py), of which 36 787 were spent under HAART. Among these PHIV, 429 NHL cases were identified from the SHCS dataset and/or by record linkage with Swiss Cantonal Cancer Registries. Age- and gender-standardized incidence was calculated and Cox regression was used to estimate hazard ratios (HR). RESULTS: NHL incidence reached 13.6 per 1000 py in 1993-1995 and declined to 1.8 in 2002-2006. HAART use was associated with a decline in NHL incidence [HR = 0.26; 95% confidence interval (CI), 0.20-0.33], and this decline was greater for primary brain lymphomas than other NHL. Among non-HAART users, being a man having sex with men, being 35 years of age or older, or, most notably, having low CD4 cell counts at study enrollment (HR = 12.26 for < 50 versus >or= 350 cells/microl; 95% CI, 8.31-18.07) were significant predictors of NHL onset. Among HAART users, only age was significantly associated with NHL risk. The HR for NHL declined steeply in the first months after HAART initiation (HR = 0.46; 95% CI, 0.27-0.77) and was 0.12 (95% CI, 0.05-0.25) 7 to10 years afterwards. CONCLUSIONS: HAART greatly reduced the incidence of NHL in PHIV, and the influence of CD4 cell count on NHL risk. The beneficial effect remained strong up to 10 years after HAART initiation.

One size does not fit all: Entrepreneurial families’ reliance on family offices

Family offices are organisations dedicated to the management of entrepreneurial families’ private wealth. Based on agency theory, we analyse types of family offices with regard to the families’ goals and the control mechanisms used to ensure goal achievement. Family-dominant management and private client structures involve stronger emphasis on non-financial goals in single and multi-family offices than in non-family-dominant management and open client structures. Variations in family involvement, ranging from family dominance to the complete absence of family ownership and/or management, and diverse client structures justify the differential reliance on formal and informal control mechanisms.

An adjustable focusing system for a 2 MeV H- ion beam line based on permanent magnet quadrupoles

A compact adjustable focusing system for a 2 MeV H- RFQ Linac is designed, constructed and tested based on four permanent magnet quadrupoles (PMQ). A PMQ model is realised using finite element simulations, providing an integrated field gradient of 2.35 T with a maximal field gradient of 57 T/m. A prototype is constructed and the magnetic field is measured, demonstrating good agreement with the simulation. Particle track simulations provide initial values for the quadrupole positions. Accordingly, four PMQs are constructed and assembled on the beam line, their positions are then tuned to obtain a minimal beam spot size of (1.2 x 2.2) mm^2 on target. This paper describes an adjustable PMQ beam line for an external ion beam. The novel compact design based on commercially available NdFeB magnets allows high flexibility for ion beam applications.

Allelopathic effects of three plant invaders on germination of native species: a field study

The ability of some invasive plant species to produce biochemical compounds toxic to native species, called allelopathy, is thought to be one of the reasons for their success when introduced to a novel range, an idea known as the Novel Weapons Hypothesis. However, support for this hypothesis mainly comes from bioassays and experiments conducted under controlled environments, whereas field evidence is rare. In a field experiment, we investigated whether three plant species invasive in Europe, Solidago gigantea, Impatiens glandulifera and Erigeron annuus, inhibit the germination of native species through allelopathy more than an adjacent native plant community. At three sites for each invasive species, we compared the germination of native species that were sown on invaded and non-invaded plots. Half of these plots were amended with activated carbon to reduce the influence of potential allelopathic compounds. The germination of sown seeds and of seeds from the seedbank was monitored over a period of 9 weeks. Activated carbon generally enhanced seed germination. This effect was equally pronounced in invaded and adjacent non-invaded plots, indicating that invasive species do not suppress germination more than a native plant community. In addition, more seeds germinated from the seedbank on invaded than on non-invaded soil, probably due to previous suppression of germination by the invasive species. Our field study does not provide evidence for the Novel Weapons Hypothesis with respect to the germination success of natives. Instead, our results suggest that if invasive species release allelopathic compounds that suppress germination, they do so to a similar degree as the native plant community.

Impact of Team Familiarity in the Operating Room on Surgical Complications

BACKGROUND: The quality of surgical performance depends on the technical skills of the surgical team as well as on non-technical skills, including teamwork. The present study evaluated the impact of familiarity among members of the surgical team on morbidity in patients undergoing elective open abdominal surgery. METHODS: A retrospective analysis was performed to compare the surgical outcomes of patients who underwent major abdominal operations between the first month (period I) and the last month (period II) of a 6-month period of continuous teamwork (stable dyads of one senior and one junior surgeon formed every 6 months). Of 117 patients, 59 and 58 patients underwent operations during period I and period II, respectively, between January 2010 and June 2012. Team performance was assessed via questionnaire by specialized work psychologists; in addition, intraoperative sound levels were measured. RESULTS: The incidence of overall complications was significantly higher in period I than in period II (54.2 vs. 34.5 %; P = 0.041). Postoperative complications grade <3 were significantly more frequently diagnosed in patients who had operations during period I (39.0 vs. 15.5 %; P = 0.007), whereas no between-group differences in grade ≥3 complications were found (15.3 vs. 19.0 %; P = 0.807). Concentration scores from senior surgeons were significantly higher in period II than in period I (P = 0.033). Sound levels during the middle third part of the operations were significantly higher in period I (median above the baseline 8.85 dB [range 4.5-11.3 dB] vs. 7.17 dB [5.24-9.43 dB]; P < 0.001). CONCLUSIONS: Team familiarity improves team performance and reduces morbidity in patients undergoing abdominal surgery.

Non-illness-related factors contributing to traffic safety in older drivers: a litterature review

Background/Study Context: Older drivers are at increased risk of becoming involved in car crashes. Contrary to well-studied illness-related factors contributing to crash risk, the non-illness-related factors that can influence safety of older drivers are underresearched. METHODS: Here, the authors review the literature on non-illness-related factors influencing driving in people over age 60. We identified six safety-relevant factors: road infrastructure, vehicle characteristics, traffic-related knowledge, accuracy of self-awareness, personality traits, and self-restricted driving. RESULTS: The literature suggests that vehicle preference, the quality of traffic-related knowledge, the location and time of traffic exposure, and personality traits should all be taken into account when assessing fitness-to-drive in older drivers. Studies indicate that self-rating of driving skills does not reliably predict fitness-to-drive. CONCLUSIONS: Most factors discussed are adaptable or accessible to training and collectively may have the potential to increase traffic safety for older drivers and other road users.

Depletion of regulatory T cells augments a vaccine-induced T effector cell response against the liver-stage of malaria but fails to increase memory

Regulatory T cells (T(reg)) have been shown to restrict vaccine-induced T cell responses in different experimental models. In these studies CD4(+)CD25(+) T(reg) were depleted using monoclonal antibodies against CD25, which might also interfere with CD25 on non-regulatory T cell populations and would have no effect on Foxp3(+)CD25(-) T(reg). To obtain more insights in the specific function of T(reg) during vaccination we used mice that are transgenic for a bacterial artificial chromosome expressing a diphtheria toxin (DT) receptor-eGFP fusion protein under the control of the foxp3 gene locus (depletion of regulatory T cell mice; DEREG). As an experimental vaccine-carrier recombinant Bordetella adenylate cyclase toxoid fused with a MHC-class I-restricted epitope of the circumsporozoite protein (ACT-CSP) of Plasmodium berghei (Pb) was used. ACT-CSP was shown by us previously to introduce the CD8+ epitope of Pb-CSP into the MHC class I presentation pathway of professional antigen-presenting cells (APC). Using this system we demonstrate here that the number of CSP-specific T cells increases when T(reg) are depleted during prime but also during boost immunization. Importantly, despite this increase of T effector cells no difference in the number of antigen-specific memory cells was observed.

Working memory training in children: Effectiveness depends on temperament

Studies revealing transfer effects of working memory (WM) training on non-trained cognitive performance of children hold promising implications for scholastic learning. However, the results of existing training studies are not consistent and provoke debates about the potential and limitations of cognitive enhancement. To examine the influence of individual differences on training outcomes is a promising approach for finding causes for such inconsistencies. In this study, we implemented WM training in an elementary school setting. The aim was to investigate near and far transfer effects on cognitive abilities and academic achievement and to examine the moderating effects of a dispositional and a regulative temperament factor, neuroticism and effortful control. Ninetynine second-graders were randomly assigned to 20 sessions of computer-based adaptiveWMtraining, computer-based reading training, or a no-contact control group. For the WM training group, our analyses reveal near transfer on a visual WM task, far transfer on a vocabulary task as a proxy for crystallized intelligence, and increased academic achievement in reading and math by trend. Considering individual differences in temperament, we found that effortful control predicts larger training mean and gain scores and that there is a moderation effect of both temperament factors on post-training improvement: WM training condition predicted higher post-training gains compared to both control conditions only in children with high effortful control or low neuroticism. Our results suggest that a short but intensive WM training program can enhance cognitive abilities in children, but that sufficient selfregulative abilities and emotional stability are necessary for WM training to be effective.

CopywriteR: DNA copy number detection from off-target sequence data.

Current methods for detection of copy number variants (CNV) and aberrations (CNA) from targeted sequencing data are based on the depth of coverage of captured exons. Accurate CNA determination is complicated by uneven genomic distribution and non-uniform capture efficiency of targeted exons. Here we present CopywriteR, which eludes these problems by exploiting 'off-target' sequence reads. CopywriteR allows for extracting uniformly distributed copy number information, can be used without reference, and can be applied to sequencing data obtained from various techniques including chromatin immunoprecipitation and target enrichment on small gene panels. CopywriteR outperforms existing methods and constitutes a widely applicable alternative to available tools.

Retinal slit lamp video mosaicking

Purpose To this day, the slit lamp remains the first tool used by an ophthalmologist to examine patient eyes. Imaging of the retina poses, however, a variety of problems, namely a shallow depth of focus, reflections from the optical system, a small field of view and non-uniform illumination. For ophthalmologists, the use of slit lamp images for documentation and analysis purposes, however, remains extremely challenging due to large image artifacts. For this reason, we propose an automatic retinal slit lamp video mosaicking, which enlarges the field of view and reduces amount of noise and reflections, thus enhancing image quality. Methods Our method is composed of three parts: (i) viable content segmentation, (ii) global registration and (iii) image blending. Frame content is segmented using gradient boosting with custom pixel-wise features. Speeded-up robust features are used for finding pair-wise translations between frames with robust random sample consensus estimation and graph-based simultaneous localization and mapping for global bundle adjustment. Foreground-aware blending based on feathering merges video frames into comprehensive mosaics. Results Foreground is segmented successfully with an area under the curve of the receiver operating characteristic curve of 0.9557. Mosaicking results and state-of-the-art methods were compared and rated by ophthalmologists showing a strong preference for a large field of view provided by our method. Conclusions The proposed method for global registration of retinal slit lamp images of the retina into comprehensive mosaics improves over state-of-the-art methods and is preferred qualitatively.

Non-Viral Gene Therapy to Cells of the bovine Intervertebral Disc

Background. Low back pain is an increasing global health problem, which is associated with intervertebral disc (IVD) damage and degeneration. Major changes occur in the nucleus pulposus (NP), with the degradation of the extracellular matrix (ECM).1 Further studies showed that growth factors from transforming growth factor β (TGFβ) and bone morphogenic proteins (BMP) family may induce chondrogenic differentiation of mesenchymal stem cells (MSC).2 Focusing on non-viral gene therapies and their possible translation into the clinics, we investigated if GDF6 (syn. BMP13 or CDMP2) can induce regeneration of degraded NP. We hypothesized that IVD transfected with plasmid over-expressing GDF6 also up-regulates other NP- and chondrogenic cell markers and enhances ECM deposition. Methods. Bovine nucleus pulposus (bNPC) and annulus fibrosus cells (bAFC) were harvested from bovine coccygeal IVD. Primary cells were then electroporized with plasmid GDF6 (Origene, vector RG211366) by optimizing parameters using the Neon Transfection system (Life Technologies, Basel). After transfection, cells were cultured in 2D monolayer or 3D alginate beads for 7, 14 or 21 days. Transfection efficiency of pGDF6 was analyzed by immunohistochemistry and fluorescent microscopy. Cell phenotype was quantified by real-time RT-PCR. To test a non-viral gene therapy applied directly to 3D whole organ culture, coccygeal bovine IVDs were harvested as previously described. Bovine IVDs were transfected by injection of plasmid GDF6 into the center. Electroporation was performed with ECM830 Square Wave Electroporation System (Harvard Apparatus, MA) using 2-needle array electrode or tweezertrodes. 72 h after tranfection discs were fixed and cryosectioned and analyzed by immunofluorescence against GDF6. Results. RT-PCR and immunohistochemistry confirmed up-regulation of GFP and GDF6 in the primary bNPC/bAFC culture. The GFP-tagged GDF6 protein, however, was not visible, possibly due to failure of dimer formation as a result of fusion structure. Organ IVD culture transfection revealed GDF6 positive staining in the center of the disc using 2-needle array electrode. Results from tweezertrodes did not show any GDF6 positive cells. Conclusion. Non-viral transfection is an appealing approach for gene therapy as it fulfills the translational safety aspects of transiency and lacks the toxic effects of viral transduction. We identified novel parameters to successfully transfect primary bovine IVD cells. For transfection of whole IVD explants electroporation parameters need to be further optimized. Acknowledgements. This project was funded by the Lindenhof Foundation (Funds “Research & Teaching”) Project no. 13-02-F. The imaging part of this study was performed with the facility of the Microscopy Imaging Center (MIC), University of Bern. References. Roughly PJ (2004): Spine (Phila), 29:2691-2699 Clarke LE, McConell JC, Sherratt MJ, Derby B, Richardson SM, Hoyland JA (2014), Arthritis Research & Therapy, 16:R67