Homeosis in a scorpion supports a telopodal origin of pectines and components of the book lungs

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Economic Evaluations of Occupational Health Interventions from a Company’s Perspective: A Systematic Review of Methods to Estimate the Cost of Health-Related Productivity Loss

Objectives: To investigate the methods used to estimate the indirect costs of health-related productivity in economic evaluations from a company’s perspective. Methods: The primary literature search was conducted in Medline and Embase. Supplemental searches were conducted in the Cochrane NHS Economic Evaluation Database, the National Institute for Occupational Safety and Health database, the Ryerson International Labour, Occupational Safety and Health Index database, scans of reference lists and researcher’s own literature database. Article selection was conducted independently by two researchers based on title, keywords, and abstract, and if needed, full text. Differences were resolved by a consensus procedure. Articles were selected based on seven criteria addressing study population, type of intervention, comparative intervention, outcome, costs, language and perspective, respectively. Characteristics of the measurement and valuation of health-related productivity were extracted and analyzed descriptively. Results: A total of 34 studies were included. Costs of health-related productivity were estimated using (a combination of) data related to sick leave, compensated sick leave, light or modified duty or work presenteeism. Data were collected from different sources (e.g. administrative databases, worker self-report, supervisors) and by different methods (e.g. questionnaires, interviews). Valuation varied in terms of reported time units, composition and source of the corresponding price weights, and whether additional elements, such as replacement costs, were included. Conclusions: Methods for measuring and valuing health-related productivity vary widely, hindering comparability of results and decision-making. We provide suggestions for improvement

The potential of optical proteomic technologies to individualize prognosis and guide rational treatment for cancer patients

Genomics and proteomics will improve outcome prediction in cancer and have great potential to help in the discovery of unknown mechanisms of metastasis, ripe for therapeutic exploitation. Current methods of prognosis estimation rely on clinical data, anatomical staging and histopathological features. It is hoped that translational genomic and proteomic research will discriminate more accurately than is possible at present between patients with a good prognosis and those who carry a high risk of recurrence. Rational treatments, targeted to the specific molecular pathways of an individual’s high-risk tumor, are at the core of tailored therapy. The aim of targeted oncology is to select the right patient for the right drug at precisely the right point in their cancer journey. Optical proteomics uses advanced optical imaging technologies to quantify the activity states of and associations between signaling proteins by measuring energy transfer between fluorophores attached to specific proteins. Förster resonance energy transfer (FRET) and fluorescence lifetime imaging microscopy (FLIM) assays are suitable for use in cell line models of cancer, fresh human tissues and formalin-fixed paraffin-embedded tissue (FFPE). In animal models, dynamic deep tissue FLIM/FRET imaging of cancer cells in vivo is now also feasible. Analysis of protein expression and post-translational modifications such as phosphorylation and ubiquitination can be performed in cell lines and are remarkably efficiently in cancer tissue samples using tissue microarrays (TMAs). FRET assays can be performed to quantify protein-protein interactions within FFPE tissue, far beyond the spatial resolution conventionally associated with light or confocal laser microscopy. Multivariate optical parameters can be correlated with disease relapse for individual patients. FRET-FLIM assays allow rapid screening of target modifiers using high content drug screens. Specific protein-protein interactions conferring a poor prognosis identified by high content tissue screening will be perturbed with targeted therapeutics. Future targeted drugs will be identified using high content/throughput drug screens that are based on multivariate proteomic assays. Response to therapy at a molecular level can be monitored using these assays while the patient receives treatment: utilizing re-biopsy tumor tissue samples in the neoadjuvant setting or by examining surrogate tissues. These technologies will prove to be both prognostic of risk for individuals when applied to tumor tissue at first diagnosis and predictive of response to specifically selected targeted anticancer drugs. Advanced optical assays have great potential to be translated into real-life benefit for cancer patients

Governmental influences on drug development: striking a better balance

The article of record as published may be found at https://doi.org/0.1038/nrd2323There is currently considerable debate in many countries over the effects of public policy — in particular, governmental regulation — on the development of innovative pharmaceuticals. Regulators must balance patients’ access to therapies with ensuring the safety of drugs. The consequences of poor decisions can be dire: if access is promoted at the expense of safety, a dangerous product can cause incalculable harm; conversely, if safety is over-emphasized at the expense of access, patients can suffer from the absence of life-saving and life- enhancing medications. Using the United States as an example, we discuss the influence of governmental bodies such as the US Food and Drug Administration (FDA), as well as recent legislative initiatives, on pharmaceutical innovation. We argue for a balanced approach to governmental interventions

The CD44 standard/ezrin complex regulates Fas-mediated apoptosis in Jurkat cells

The transmembrane receptor CD44 conveys important signals from the extracellular microenvironment to the cytoplasm, a phenomena known as "outside-in" signaling. CD44 exists as several isoforms that result from alternative splicing, which differ only in the extracellular domain but yet exhibit different activities. CD44 is a binding partner for the membrane-cytoskeleton cross-linker protein ezrin. In this study, we demonstrate that only CD44 standard (CD44s) colocalizes and interacts with the actin cross-linkers ezrin and moesin using well-characterized cell lines engineered to express different CD44 isoforms. Importantly, we also show that the association CD44s-ezrin-actin is an important modulator of Fas-mediated apoptosis. The results highlight a mechanism by which signals from the extracellular milieu regulate intracellular signaling activities involved in programmed cell death