Predictors of stable return-to-work in non-acute, non-specific spinal pain: low total prior sick-listing, high self prediction and young age. A two-year prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Non-specific spinal pain (NSP), comprising back and/or neck pain, is one of the leading disorders in long-term sick-listing. During 2000-2004, 125 Swedish primary-care patients with non-acute NSP, full-time sick-listed 6 weeks-2 years, were included in a randomized controlled trial to compare a cognitive-behavioural programme with traditional primary care. This prospective cohort study is a re-assessment of the data from the randomized trial with the 2 treatment groups considered as a single cohort. The aim was to investigate which baseline variables predict a stable return-to-work during a 2-year period after baseline: objective variables from function tests, socioeconomic, subjective and/or treatment variables. Stable return-to-work was a return-to-work lasting for at least 1 month from the start of follow-up.</p> <p>Methods</p> <p><it>Stable return-to-work </it>was the outcome variable, the above-mentioned factors were the predictive variables in multiple-logistic regression models, one per follow-up at 6, 12, 18 and 24 months after baseline. The factors from univariate analyzes with a <it>p</it>-value of at most .10 were included. The non-significant variables were excluded stepwise to yield models comprising only significant factors (<it>p </it>< .05). As the comparatively few cases made it risky to associate certain predictors with certain time-points, we finally considered the predictors which were represented in at least 3 follow-ups. They are presented with odds ratios (OR) and 95% confidence intervals.</p> <p>Results</p> <p>Three variables qualified, all of them represented in 3 follow-ups: <it>Low total prior sick-listing </it>(including all diagnoses) was the strongest predictor in 2 follow-ups, 18 and 24 months, OR 4.8 [1.9-12.3] and 3.8 [1.6-8.7] respectively, <it>High self prediction </it>(the patients' own belief in return-to-work) was the strongest at 12 months, OR 5.2 [1.5-17.5] and <it>Young age </it>(max 44 years) the second strongest at 18 months, OR 3.5 [1.3-9.1].</p> <p>Conclusions</p> <p>In primary-care patients with non-acute NSP, the strong predictors of stable return-to-work were 2 socioeconomic variables, <it>Low total prior sick-listing </it>and <it>Young age</it>, and 1 subjective variable, <it>High self-prediction</it>. Objective variables from function tests and treatment variables were non-predictors. Except for <it>Young age</it>, the predictors have previously been insufficiently studied, and so our study should widen knowledge within clinical practice.</p> <p>Trial registration</p> <p>Trial registration number for the original trial NCT00488735.</p

Persistent and polarised global actin flow is essential for directionality during cell migration

Cell migration is hypothesized to involve a cycle of behaviours beginning with leading edge extension. However, recent evidence suggests that the leading edge may be dispensable for migration, raising the question of what actually controls cell directionality. Here, we exploit the embryonic migration of Drosophila macrophages to bridge the different temporal scales of the behaviours controlling motility. This approach reveals that edge fluctuations during random motility are not persistent and are weakly correlated with motion. In contrast, flow of the actin network behind the leading edge is highly persistent. Quantification of actin flow structure during migration reveals a stable organization and asymmetry in the cell-wide flowfield that strongly correlates with cell directionality. This organization is regulated by a gradient of actin network compression and destruction, which is controlled by myosin contraction and cofilin-mediated disassembly. It is this stable actin-flow polarity, which integrates rapid fluctuations of the leading edge, that controls inherent cellular persistence

Microarray analysis and scale-free gene networks identify candidate regulators in drought-stressed roots of loblolly pine (P. taeda L.)

<p>Abstract</p> <p>Background</p> <p>Global transcriptional analysis of loblolly pine (<it>Pinus taeda </it>L.) is challenging due to limited molecular tools. PtGen2, a 26,496 feature cDNA microarray, was fabricated and used to assess drought-induced gene expression in loblolly pine propagule roots. Statistical analysis of differential expression and weighted gene correlation network analysis were used to identify drought-responsive genes and further characterize the molecular basis of drought tolerance in loblolly pine.</p> <p>Results</p> <p>Microarrays were used to interrogate root cDNA populations obtained from 12 genotype × treatment combinations (four genotypes, three watering regimes). Comparison of drought-stressed roots with roots from the control treatment identified 2445 genes displaying at least a 1.5-fold expression difference (false discovery rate = 0.01). Genes commonly associated with drought response in pine and other plant species, as well as a number of abiotic and biotic stress-related genes, were up-regulated in drought-stressed roots. Only 76 genes were identified as differentially expressed in drought-recovered roots, indicating that the transcript population can return to the pre-drought state within 48 hours. Gene correlation analysis predicts a scale-free network topology and identifies eleven co-expression modules that ranged in size from 34 to 938 members. Network topological parameters identified a number of central nodes (hubs) including those with significant homology (E-values ≤ 2 × 10^-30) to 9-cis-epoxycarotenoid dioxygenase, zeatin O-glucosyltransferase, and ABA-responsive protein. Identified hubs also include genes that have been associated previously with osmotic stress, phytohormones, enzymes that detoxify reactive oxygen species, and several genes of unknown function.</p> <p>Conclusion</p> <p>PtGen2 was used to evaluate transcriptome responses in loblolly pine and was leveraged to identify 2445 differentially expressed genes responding to severe drought stress in roots. Many of the genes identified are known to be up-regulated in response to osmotic stress in pine and other plant species and encode proteins involved in both signal transduction and stress tolerance. Gene expression levels returned to control values within a 48-hour recovery period in all but 76 transcripts. Correlation network analysis indicates a scale-free network topology for the pine root transcriptome and identifies central nodes that may serve as drivers of drought-responsive transcriptome dynamics in the roots of loblolly pine.</p

Polygenic Risk Modelling for Prediction of Epithelial Ovarian Cancer Risk

Funder: Funding details are provided in the Supplementary MaterialAbstractPolygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally-efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, “select and shrink for summary statistics” (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestry; 7,669 women of East Asian ancestry; 1,072 women of African ancestry, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestry. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38(95%CI:1.28–1.48,AUC:0.588) per unit standard deviation, in women of European ancestry; 1.14(95%CI:1.08–1.19,AUC:0.538) in women of East Asian ancestry; 1.38(95%CI:1.21-1.58,AUC:0.593) in women of African ancestry; hazard ratios of 1.37(95%CI:1.30–1.44,AUC:0.592) in BRCA1 pathogenic variant carriers and 1.51(95%CI:1.36-1.67,AUC:0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.</jats:p

Influence of inherited topography on gravitational slope failure: three-dimensional numerical modelling of the La Clapière slope, Alpes-Maritimes, France,

International audienceGravitational slope failure involves rock slopes at various scales. Nowadays, it is accepted that different factors influence slope destabilization, including topography. In many cases, slope failure occurs between tributary valleys cutting the slope. In this study, we ask what influence tributary valleys have on slope failure. To tackle this question, we developed a 3-D numerical model of the La Clapière Slope and then examined a series of simplified 3-D models with different geometries of tributary valleys (spacing and depth). Our results show that: (1) whatever considered in situ stresses are, including the third dimension reduces the destabilization threshold compared with 2-D models; and (2) the spacing and the depth of tributary valleys influence slope failure. For shallow incisions, increasing the lateral spacing between tributary valleys does not affect failure localization but does increase slope damage (to a stable value from 2000 m). However, deeper incision does not affect slope damage but does contribute to failure localization. When the spacing is less than 1500 m, the part of the slope between tributary valleys is not involved in the failure process, but for spacings above 1500 m slope failure occurs between tributary valleys

X-band high PAE MMIC HPA for space radar applications

A MMIC 2-Watt 5-stage amplifier (HPA) has been successfully designed in one foundry run. This HPA, developed for a space Radar application at X band, has a 40dB linear gain, an output power of 34dBm with a 32% associated Power Added Efficiency (with a maximum of 39%) and uses the THOMSON TCS HP07 technology (Lg=0.7um) which is on the way to be qualified for Space Application. The tests have been performed both on wafer and in package

Paraglacial gravitational deformations in the SW Alps: a review of field investigations, 10Be cosmogenic dating and physical modeling,

International audienceCatastrophic deep-seated landslides (DSL) are generally considered to be the result of large slope deformations also known as deep-seated gravitational slope deformation (DSGSD). This paper aims to build a synthesis of multiple studies made in the Tinée Valley (southern French Alps) to assess the geometrical, kinematical, mechanical and chronological relationships between these two gravitational processes. At the scale of the valley, data issued from geological, geomorphological and 10Be dating indicate a clear geometrical link between DSGSD and DSL occurring at the base of the slope and suggest that gravitational slope evolution began after the glacial retreat (13 ka BP). This is supported by the example of the well-documented La Clapière slope. A continuous evolution process is characterized geometrically and temporally from geomorphic observations and analogue modelling. Coupling structural, geomorphological, physical and chronological studies allowed us to propose a four-dimensional (4D) deformation model mechanically correlated with progressive failure concept. The validity and variability of this reference site are discussed at the valley scale (taking Isola and Le Pra slope deformation as examples). It allows a rough estimation of the state of slope deformation at the valley scale to be constructed and the slope evolution with time to be considered. This 4D model could then be considered as a reference for other deep-seated gravitational slope deformations in comparable Alpine valleys