Cost-effectiveness of a participatory return-to-work intervention for temporary agency workers and unemployed workers sick-listed due to musculoskeletal disorders: design of a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Within the working population there is a vulnerable group: workers without an employment contract and workers with a flexible labour market arrangement, e.g. temporary agency workers. In most cases, when sick-listed, these workers have no workplace/employer to return to. Also, for these workers access to occupational health care is limited or even absent in many countries. For this vulnerable working population there is a need for tailor-made occupational health care, including the presence of an actual return-to-work perspective. Therefore, a participatory return-to-work program has been developed based on a successful return-to-work intervention for workers, sick-listed due to low back pain.</p> <p>The objective of this paper is to describe the design of a randomised controlled trial to study the (cost-)effectiveness of this newly developed participatory return-to-work program adapted for temporary agency workers and unemployed workers, sick-listed due to musculoskeletal disorders, compared to usual care.</p> <p>Methods/Design</p> <p>The design of this study is a randomised controlled trial with one year of follow-up. The study population consists of temporary agency workers and unemployed workers sick-listed between 2 and 8 weeks due to musculoskeletal disorders. The new return-to-work program is a stepwise program aimed at making a consensus-based return-to-work implementation plan with the possibility of a (therapeutic) workplace to return-to-work. Outcomes are measured at baseline, 3, 6, 9 and 12 months. The primary outcome measure is duration of the sickness benefit period after the first day of reporting sick. Secondary outcome measures are: time until first return-to-work, total number of days of sickness benefit during follow-up; functional status; intensity of musculoskeletal pain; pain coping; and attitude, social influence and self-efficacy determinants. Cost-benefit is evaluated from an insurer's perspective. A process evaluation is part of this study.</p> <p>Discussion</p> <p>For sick-listed workers without an employment contract there can be gained a lot by improving occupational health care, including return-to-work guidance, and by minimising the 'labour market handicap' by creating a return-to-work perspective. In addition, reduction of sickness absence and work disability, i.e. a reduction of disability claims, may result in substantial benefits for the Dutch Social Security System.</p> <p>Trial registration</p> <p>Trial registration number: NTR1047.</p

Grid Cells, Place Cells, and Geodesic Generalization for Spatial Reinforcement Learning

Reinforcement learning (RL) provides an influential characterization of the brain's mechanisms for learning to make advantageous choices. An important problem, though, is how complex tasks can be represented in a way that enables efficient learning. We consider this problem through the lens of spatial navigation, examining how two of the brain's location representations—hippocampal place cells and entorhinal grid cells—are adapted to serve as basis functions for approximating value over space for RL. Although much previous work has focused on these systems' roles in combining upstream sensory cues to track location, revisiting these representations with a focus on how they support this downstream decision function offers complementary insights into their characteristics. Rather than localization, the key problem in learning is generalization between past and present situations, which may not match perfectly. Accordingly, although neural populations collectively offer a precise representation of position, our simulations of navigational tasks verify the suggestion that RL gains efficiency from the more diffuse tuning of individual neurons, which allows learning about rewards to generalize over longer distances given fewer training experiences. However, work on generalization in RL suggests the underlying representation should respect the environment's layout. In particular, although it is often assumed that neurons track location in Euclidean coordinates (that a place cell's activity declines “as the crow flies” away from its peak), the relevant metric for value is geodesic: the distance along a path, around any obstacles. We formalize this intuition and present simulations showing how Euclidean, but not geodesic, representations can interfere with RL by generalizing inappropriately across barriers. Our proposal that place and grid responses should be modulated by geodesic distances suggests novel predictions about how obstacles should affect spatial firing fields, which provides a new viewpoint on data concerning both spatial codes

The MPI Facial Expression Database — A Validated Database of Emotional and Conversational Facial Expressions

The ability to communicate is one of the core aspects of human life. For this, we use not only verbal but also nonverbal signals of remarkable complexity. Among the latter, facial expressions belong to the most important information channels. Despite the large variety of facial expressions we use in daily life, research on facial expressions has so far mostly focused on the emotional aspect. Consequently, most databases of facial expressions available to the research community also include only emotional expressions, neglecting the largely unexplored aspect of conversational expressions. To fill this gap, we present the MPI facial expression database, which contains a large variety of natural emotional and conversational expressions. The database contains 55 different facial expressions performed by 19 German participants. Expressions were elicited with the help of a method-acting protocol, which guarantees both well-defined and natural facial expressions. The method-acting protocol was based on every-day scenarios, which are used to define the necessary context information for each expression. All facial expressions are available in three repetitions, in two intensities, as well as from three different camera angles. A detailed frame annotation is provided, from which a dynamic and a static version of the database have been created. In addition to describing the database in detail, we also present the results of an experiment with two conditions that serve to validate the context scenarios as well as the naturalness and recognizability of the video sequences. Our results provide clear evidence that conversational expressions can be recognized surprisingly well from visual information alone. The MPI facial expression database will enable researchers from different research fields (including the perceptual and cognitive sciences, but also affective computing, as well as computer vision) to investigate the processing of a wider range of natural facial expressions

Synthetic biology approaches in drug discovery and pharmaceutical biotechnology

Synthetic biology is the attempt to apply the concepts of engineering to biological systems with the aim to create organisms with new emergent properties. These organisms might have desirable novel biosynthetic capabilities, act as biosensors or help us to understand the intricacies of living systems. This approach has the potential to assist the discovery and production of pharmaceutical compounds at various stages. New sources of bioactive compounds can be created in the form of genetically encoded small molecule libraries. The recombination of individual parts has been employed to design proteins that act as biosensors, which could be used to identify and quantify molecules of interest. New biosynthetic pathways may be designed by stitching together enzymes with desired activities, and genetic code expansion can be used to introduce new functionalities into peptides and proteins to increase their chemical scope and biological stability. This review aims to give an insight into recently developed individual components and modules that might serve as parts in a synthetic biology approach to pharmaceutical biotechnology

Goal-directed and habitual control in the basal ganglia: implications for Parkinson's disease

Progressive loss of the ascending dopaminergic projection in the basal ganglia is a fundamental pathological feature of Parkinson's disease. Studies in animals and humans have identified spatially segregated functional territories in the basal ganglia for the control of goal-directed and habitual actions. In patients with Parkinson's disease the loss of dopamine is predominantly in the posterior putamen, a region of the basal ganglia associated with the control of habitual behaviour. These patients may therefore be forced into a progressive reliance on the goal-directed mode of action control that is mediated by comparatively preserved processing in the rostromedial striatum. Thus, many of their behavioural difficulties may reflect a loss of normal automatic control owing to distorting output signals from habitual control circuits, which impede the expression of goal-directed action. © 2010 Macmillan Publishers Limited. All rights reserved

The dominant Anopheles vectors of human malaria in the Asia-Pacific region: occurrence data, distribution maps and bionomic précis

<p>Abstract</p> <p>Background</p> <p>The final article in a series of three publications examining the global distribution of 41 dominant vector species (DVS) of malaria is presented here. The first publication examined the DVS from the Americas, with the second covering those species present in Africa, Europe and the Middle East. Here we discuss the 19 DVS of the Asian-Pacific region. This region experiences a high diversity of vector species, many occurring sympatrically, which, combined with the occurrence of a high number of species complexes and suspected species complexes, and behavioural plasticity of many of these major vectors, adds a level of entomological complexity not comparable elsewhere globally. To try and untangle the intricacy of the vectors of this region and to increase the effectiveness of vector control interventions, an understanding of the contemporary distribution of each species, combined with a synthesis of the current knowledge of their behaviour and ecology is needed.</p> <p>Results</p> <p>Expert opinion (EO) range maps, created with the most up-to-date expert knowledge of each DVS distribution, were combined with a contemporary database of occurrence data and a suite of open access, environmental and climatic variables. Using the Boosted Regression Tree (BRT) modelling method, distribution maps of each DVS were produced. The occurrence data were abstracted from the formal, published literature, plus other relevant sources, resulting in the collation of DVS occurrence at 10116 locations across 31 countries, of which 8853 were successfully geo-referenced and 7430 were resolved to spatial areas that could be included in the BRT model. A detailed summary of the information on the bionomics of each species and species complex is also presented.</p> <p>Conclusions</p> <p>This article concludes a project aimed to establish the contemporary global distribution of the DVS of malaria. The three articles produced are intended as a detailed reference for scientists continuing research into the aspects of taxonomy, biology and ecology relevant to species-specific vector control. This research is particularly relevant to help unravel the complicated taxonomic status, ecology and epidemiology of the vectors of the Asia-Pacific region. All the occurrence data, predictive maps and EO-shape files generated during the production of these publications will be made available in the public domain. We hope that this will encourage data sharing to improve future iterations of the distribution maps.</p

Measurement and interpretation of same-sign W boson pair production in association with two jets in pp collisions at s = 13 TeV with the ATLAS detector

This paper presents the measurement of fducial and diferential cross sections for both the inclusive and electroweak production of a same-sign W-boson pair in association with two jets (W±W±jj) using 139 fb−1 of proton-proton collision data recorded at a centre-of-mass energy of √s = 13 TeV by the ATLAS detector at the Large Hadron Collider. The analysis is performed by selecting two same-charge leptons, electron or muon, and at least two jets with large invariant mass and a large rapidity diference. The measured fducial cross sections for electroweak and inclusive W±W±jj production are 2.92 ± 0.22 (stat.) ± 0.19 (syst.)fb and 3.38±0.22 (stat.)±0.19 (syst.)fb, respectively, in agreement with Standard Model predictions. The measurements are used to constrain anomalous quartic gauge couplings by extracting 95% confdence level intervals on dimension-8 operators. A search for doubly charged Higgs bosons H±± that are produced in vector-boson fusion processes and decay into a same-sign W boson pair is performed. The largest deviation from the Standard Model occurs for an H±± mass near 450 GeV, with a global signifcance of 2.5 standard deviations

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Combination of searches for heavy spin-1 resonances using 139 fb−1 of proton-proton collision data at s = 13 TeV with the ATLAS detector

A combination of searches for new heavy spin-1 resonances decaying into different pairings of W, Z, or Higgs bosons, as well as directly into leptons or quarks, is presented. The data sample used corresponds to 139 fb−1 of proton-proton collisions at = 13 TeV collected during 2015–2018 with the ATLAS detector at the CERN Large Hadron Collider. Analyses selecting quark pairs (qq, bb, , and tb) or third-generation leptons (τν and ττ) are included in this kind of combination for the first time. A simplified model predicting a spin-1 heavy vector-boson triplet is used. Cross-section limits are set at the 95% confidence level and are compared with predictions for the benchmark model. These limits are also expressed in terms of constraints on couplings of the heavy vector-boson triplet to quarks, leptons, and the Higgs boson. The complementarity of the various analyses increases the sensitivity to new physics, and the resulting constraints are stronger than those from any individual analysis considered. The data exclude a heavy vector-boson triplet with mass below 5.8 TeV in a weakly coupled scenario, below 4.4 TeV in a strongly coupled scenario, and up to 1.5 TeV in the case of production via vector-boson fusion