Translation and validation of non-English versions of the Ankylosing Spondylitis Quality of Life (ASQOL) questionnaire

BACKGROUND: The Ankylosing Spondylitis Quality of Life (ASQOL) questionnaire is a unidimensional, disease-specific measure developed in the UK and the Netherlands. This study describes its adaptation into other languages. METHODS: The UK English ASQOL was translated into US English; Canadian French and English; French; German; Italian; Spanish; and Swedish (dual-panel methods). Cognitive debriefing interviews were conducted with AS patients. Psychometric/scaling properties were assessed using data from two Phase III studies of adalimumab. Baseline and Week-2 data were used to assess test-retest reliability. Validity was determined by correlation of ASQOL with SF-36 and BASFI and by discriminative ability of ASQOL based on disease severity. Item response theory (Rasch model) was used to test ASQOL's scaling properties. RESULTS: Cognitive debriefing showed the new ASQOL versions to be clear, relevant and comprehensive. Sample sizes varied, but were sufficient for: psychometric/scaling assessment for US English and Canadian English; psychometric but not scaling analyses for German; and preliminary evidence of these properties for the remaining languages. Test-retest reliability and Cronbach's alpha coefficients were high: US English (0.85, 0.85), Canadian English (0.87, 0.86), and German (0.77, 0.79). Correlations of ASQOL with SF-36 and BASFI for US English, Canadian English, and German measures were moderate, but ASQOL discriminated between patients based on perceived disease severities (p < 0.01). Results were comparable for the other languages. US English and Canadian English exhibited fit to the Rasch model (non-significant p-values: 0.54, 0.68), confirming unidimensionality. CONCLUSION: The ASQOL was successfully translated into all eight languages. Psychometric properties were excellent for US English, Canadian English, and German, and extremely promising for the other languages

Influence of laser polarization on collective electron dynamics in ultraintense laser-foil interactions

The collective response of electrons in an ultrathin foil target irradiated by an ultraintense laser pulse is investigated experimentally and via 3D particle-in-cell simulations. It is shown that if the target is sufficiently thin that the laser induces significant radiation pressure, but not thin enough to become relativistically transparent to the laser light, the resulting relativistic electron beam is elliptical, with the major axis of the ellipse directed along the laser polarization axis. When the target thickness is decreased such that it becomes relativistically transparent early in the interaction with the laser pulse, diffraction of the transmitted laser light occurs through a so called 'relativistic plasma aperture', inducing structure in the spatial-intensity profile of the beam of energetic electrons. It is shown that the electron beam profile can be modified by variation of the target thickness and degree of ellipticity in the laser polarization

Next generation sequencing has lower sequence coverage and poorer SNP-detection capability in the regulatory regions

The rapid development of next generation sequencing (NGS) technology provides a new chance to extend the scale and resolution of genomic research. How to efficiently map millions of short reads to the reference genome and how to make accurate SNP calls are two major challenges in taking full advantage of NGS. In this article, we reviewed the current software tools for mapping and SNP calling, and evaluated their performance on samples from The Cancer Genome Atlas (TCGA) project. We found that BWA and Bowtie are better than the other alignment tools in comprehensive performance for Illumina platform, while NovoalignCS showed the best overall performance for SOLiD. Furthermore, we showed that next-generation sequencing platform has significantly lower coverage and poorer SNP-calling performance in the CpG islands, promoter and 5′-UTR regions of the genome. NGS experiments targeting for these regions should have higher sequencing depth than the normal genomic region

Preparation, structured deliberate practice and decision making in elite level football: The case study of Gary Neville (Manchester United FC and England)

Decision making in elite level sporting competition is often regarded as distinguishing success from failure. As an intricate brain-based process it is unlike other physical processes because it is invisible and is typically only evidenced after the event. This case study shows how an individual achieved great success in elite level professional football through consistent positive decision making on and off the field of play. Through prolonged interviewing, Gary Neville, a player from Manchester United Football Club, explored personal behaviours, the structure and activities of deliberate practice and his professional choices in match preparation. His career-long devotion to purposeful organised practice was focused on cognition, physical preparation, context-relative physical action and refined repetition to optimise his mental comfort while enhancing his match day performances. This approach was underpinned by diligent personal and collective organisation and by concerted action. Results provide an insight into the categorical nature of his deliberate practice, sport-specific information processing and match-based decision making. At the operational level, his process was mediated by a complex mental representation of ongoing and anticipated game situations; these representations were continuously updated during each match. Allowing for the limitations of the design, implications are provided for developmental and educational coaching, match preparation, deliberate practice activity and improved use of the performance analysis software packages in professional football

RNAseq Analyses Identify Tumor Necrosis Factor-Mediated Inflammation as a Major Abnormality in ALS Spinal Cord

ALS is a rapidly progressive, devastating neurodegenerative illness of adults that produces disabling weakness and spasticity arising from death of lower and upper motor neurons. No meaningful therapies exist to slow ALS progression, and molecular insights into pathogenesis and progression are sorely needed. In that context, we used high-depth, next generation RNA sequencing (RNAseq, Illumina) to define gene network abnormalities in RNA samples depleted of rRNA and isolated from cervical spinal cord sections of 7 ALS and 8 CTL samples. We aligned \u3e50 million 2X150 bp paired-end sequences/sample to the hg19 human genome and applied three different algorithms (Cuffdiff2, DEseq2, EdgeR) for identification of differentially expressed genes (DEG’s). Ingenuity Pathways Analysis (IPA) and Weighted Gene Co-expression Network Analysis (WGCNA) identified inflammatory processes as significantly elevated in our ALS samples, with tumor necrosis factor (TNF) found to be a major pathway regulator (IPA) and TNFα-induced protein 2 (TNFAIP2) as a major network “hub” gene (WGCNA). Using the oPOSSUM algorithm, we analyzed transcription factors (TF) controlling expression of the nine DEG/hub genes in the ALS samples and identified TF’s involved in inflammation (NFkB, REL, NFkB1) and macrophage function (NR1H2::RXRA heterodimer). Transient expression in human iPSC-derived motor neurons of TNFAIP2 (also a DEG identified by all three algorithms) reduced cell viability and induced caspase 3/7 activation. Using high-density RNAseq, multiple algorithms for DEG identification, and an unsupervised gene co-expression network approach, we identified significant elevation of inflammatory processes in ALS spinal cord with TNF as a major regulatory molecule. Overexpression of the DEG TNFAIP2 in human motor neurons, the population most vulnerable to die in ALS, increased cell death and caspase 3/7 activation. We propose that therapies targeted to reduce inflammatory TNFα signaling may be helpful in ALS patients

A Study of Time-Dependent CP-Violating Asymmetries and Flavor Oscillations in Neutral B Decays at the Upsilon(4S)

We present a measurement of time-dependent CP-violating asymmetries in neutral B meson decays collected with the BABAR detector at the PEP-II asymmetric-energy B Factory at the Stanford Linear Accelerator Center. The data sample consists of 29.7 ${\rm fb}^{-1}$ recorded at the $\Upsilon(4S)$ resonance and 3.9 ${\rm fb}^{-1}$ off-resonance. One of the neutral B mesons, which are produced in pairs at the $\Upsilon(4S)$, is fully reconstructed in the CP decay modes $J/\psi K^0_S$, $\psi(2S) K^0_S$, $\chi_{c1} K^0_S$, $J/\psi K^{*0}$ ($K^{*0}\to K^0_S\pi^0$) and $J/\psi K^0_L$, or in flavor-eigenstate modes involving $D^{(*)}\pi/\rho/a_1$ and $J/\psi K^{*0}$ ($K^{*0}\to K^+\pi^-$). The flavor of the other neutral B meson is tagged at the time of its decay, mainly with the charge of identified leptons and kaons. The proper time elapsed between the decays is determined by measuring the distance between the decay vertices. A maximum-likelihood fit to this flavor eigenstate sample finds $\Delta m_d = 0.516\pm 0.016 {\rm (stat)} \pm 0.010 {\rm (syst)} {\rm ps}^{-1}$. The value of the asymmetry amplitude $\sin2\beta$ is determined from a simultaneous maximum-likelihood fit to the time-difference distribution of the flavor-eigenstate sample and about 642 tagged $B^0$ decays in the CP-eigenstate modes. We find $\sin2\beta=0.59\pm 0.14 {\rm (stat)} \pm 0.05 {\rm (syst)}$, demonstrating that CP violation exists in the neutral B meson system. (abridged)Comment: 58 pages, 35 figures, submitted to Physical Review

Measurement of the Branching Fraction for B- --> D0 K*-

We present a measurement of the branching fraction for the decay B- --> D0 K*- using a sample of approximately 86 million BBbar pairs collected by the BaBar detector from e+e- collisions near the Y(4S) resonance. The D0 is detected through its decays to K- pi+, K- pi+ pi0 and K- pi+ pi- pi+, and the K*- through its decay to K0S pi-. We measure the branching fraction to be B.F.(B- --> D0 K*-)= (6.3 +/- 0.7(stat.) +/- 0.5(syst.)) x 10^{-4}.Comment: 7 pages, 1 postscript figure, submitted to Phys. Rev. D (Rapid Communications