Post-Irradiation Morphea of the Breast in a Patient with Subacute Cutaneous Lupus Erythematosus: Case Report and a Literature Review.

The appearance of morphea after radiotherapy, especially in the context of breast cancer, is a rare but known phenomenon. The incidence of post-irradiation morphea (PIM) of the breast is approximately one in every 500 patients, a higher rate than morphea of any other etiology, which is three per 100,000 per year. PIM usually appears less than 1 year after irradiation (range 1 month to 32 years). The histological pattern of PIM is different from the one in post-irradiation fibrosis, which is a common side effect of radiotherapy and usually appears during the first 3 months after irradiation. Several theories have been proposed to explain the pathogenesis of PIM, probably caused by a disturbance of the cytokine pattern. The development of PIM in patients with autoimmune diseases has been described in the literature. To our knowledge, we report the first case of PIM in a patient with subacute cutaneous lupus erythematosus. We should therefore pay attention when looking at patients with PIM to search for an underlying autoimmune disease

Inter-Observer and Intra-Observer Variations in the Assessment of Epithelial Dysplasia in Oral Lichenoid Diseases.

Oral lichen planus (OLP) and oral lichenoid lesions (OLL) can both present with histological dysplasia. Despite the presence of WHO-defined criteria for the evaluation of epithelial dysplasia, its assessment is frequently subjective (inter-observer variability). The lack of reproducibility in the evaluation of dysplasia is even more complex in the presence of a lichenoid inflammation. We evaluated dysplasia in 112 oral biopsies with lichenoid inflammation in order to study the inter-observer and the intra-observer variability

Simulating permeability reduction by clay mineral nanopores in a tight sandstone by combining computer X-ray microtomography and focussed ion beam scanning electron microscopy imaging

Computer X-ray microtomography (µXCT) represents a powerful tool for investigating the physical properties of porous rocks. While calculated porosities determined by this method typically match experimental measurements, computed permeabilities are often overestimated by more than 1 order of magnitude. This effect increases towards smaller pore sizes, as shown in this study, in which nanostructural features related to clay minerals reduce the permeability of tight reservoir sandstone samples. Focussed ion beam scanning electron microscopy (FIB-SEM) tomography was applied to determine the permeability effects of illites at the nanometre scale, and Navier–Stokes equations were applied to calculate the permeability of these domains. With these data, microporous domains (porous voxels) were defined using microtomography images of a tight reservoir sample. The distribution of these domains could be extrapolated by calibration against size distributions measured in FIB-SEM images. For this, we assumed a mean permeability for the dominant clay mineral (illite) in the rock and assigned it to the microporous domains within the structure. The results prove the applicability of our novel approach by combining FIB-SEM with X-ray tomographic rock core scans to achieve a good correspondence between measured and simulated permeabilities. This methodology results in a more accurate representation of reservoir rock permeability in comparison to that estimated purely based on µXCT images

An algorithm to identify patients with treated type 2 diabetes using medico-administrative data

<p>Abstract</p> <p>Background</p> <p>National authorities have to follow the evolution of diabetes to implement public health policies. An algorithm was developed to identify patients with treated type 2 diabetes and estimate its annual prevalence in Luxembourg using health insurance claims when no diagnosis code is available.</p> <p>Methods</p> <p>The DIABECOLUX algorithm was based on patients' age as well as type and number of hypoglycemic agents reimbursed between 1995 and 2006. Algorithm validation was performed using the results of a national study based on medical data. Sensitivity, specificity and predictive values were estimated.</p> <p>Results</p> <p>The sensitivity of the DIABECOLUX algorithm was found superior to 98.2%. Between 2000 and 2006, 22,178 patients were treated for diabetes in Luxembourg, among whom 21,068 for type 2 diabetes (95%). The prevalence was estimated at 3.79% in 2006 and followed an increasing linear trend during the period. In 2005, the prevalence was low for young age classes and increased rapidly from 40 to 70 for male and 80 for female, reaching a peak of, respectively 17.0% and 14.3% before decreasing.</p> <p>Conclusions</p> <p>The DIABECOLUX algorithm is relevant to identify treated type 2 diabetes patients. It is reproducible and should be transferable to every country using medico-administrative databases not including diagnosis codes. Although undiagnosed patients and others with lifestyle recommendations only were not considered in this study, this algorithm is a cheap and easy-to-use tool to inform health authorities. Further studies will use this tool with the aim of improving the quality of health care dedicated to diabetic patients in Luxembourg.</p

Mode of action of DNA-competitive small molecule inhibitors of tyrosyl DNA phosphodiesterase 2

TDP2 is a 5’-tyrosyl DNA phosphodiesterase important for the repair of DNA adducts generated by non-productive (abortive) activity of topoisomerase II. TDP2 facilitates therapeutic resistance to topoisomerase poisons, which are widely used in the treatment of a range of cancer types. Consequently, TDP2 is an interesting target for the development of small molecule inhibitors that could restore sensitivity to topoisomerase-directed therapies. Previous studies identified a class of deazaflavin-based molecules that showed inhibitory activity against TDP2 at therapeutically useful concentrations, but their mode of action was uncertain. We have confirmed that the deazaflavin series inhibits TDP2 enzyme activity in a fluorescence-based assay, suitable for HTS-screening. We have gone on to determine crystal structures of these compounds bound to a ‘humanised’ form of murine TDP2. The structures reveal their novel mode of action as competitive ligands for the binding site of an incoming DNA substrate, and point the way to generating novel and potent inhibitors of TDP2

GTOSat: Radiation Belt Dynamics from the Inside

GTOSat, a 6U SmallSat integrated and tested at NASA Goddard Space Flight Center (GSFC), has a scheduled launch date of July 31st, 2022, on an Atlas V. From a low inclination geosynchronous transfer orbit (GTO), GTOSat has the primary science goal of advancing our quantitative understanding of acceleration and loss of relativistic electrons in the Earth’s outer radiation belt. It will measure energy spectra and pitch angles of both the seed and the energized electron populations simultaneously using a compact, high-heritage Relativistic Electron Magnetic Spectrometer (REMS) built by The Aerospace Corporation. A boom-mounted Fluxgate Magnetometer (FMAG), developed by NASA GSFC, will provide 3-axis knowledge of the ambient local magnetic field. The spacecraft bus uses a combination of commercial and in-house/custom designed components. Design, integration, and testing of the spacecraft bus was performed by a small, dedicated team at GSFC. Throughout development GTOSat has encountered numerous challenges, expected and unexpected, that we’re ready to share with the community

Kant, race, and natural history

This article presents a new argument concerning the relation between Kant’s theory of race and aspects of the critical philosophy. It argues that Kant’s treatment of the problem of the systematic unity of nature and knowledge in the Critique of Pure Reason and the Critique of the Power of Judgment can be traced back a methodological problem in the natural history of the period – that of the possibility of a natural system of nature. Kant’s transformation of the methodological problem from natural history into a set of philosophical (and specifically epistemological) problems proceeds by way of the working out of his own problem in natural history – the problem of the natural history of the human races – and specifically the problem of the unity in diversity of the human species, in response to which he develops a theory of race. This theory of race is, further, the first developed model of the use of teleological judgment in Kant’s work. The article thus argues that Kant’s philosophical position on the systematic unity of nature and of knowledge in the first and third Critiques, and his account and defense of teleological judgment, are developed out of problems first articulated in his solution to the problem of the unity in diversity of the human species – that is, in his theory of race. The article does not seek to establish that these aspects of the critical philosophy are therefore racialised. But it does demonstrate, against those who deny its salience to his philosophy, how the problem of the unity in diversity of the human species and Kant’s theory of race is significant for the development of aspects of the critical philosophy and thus contributes to their philosophical problematics

The CardioMetabolic Health Alliance Working Toward a New Care Model for the Metabolic Syndrome

AbstractThe Cardiometabolic Think Tank was convened on June 20, 2014, in Washington, DC, as a “call to action” activity focused on defining new patient care models and approaches to address contemporary issues of cardiometabolic risk and disease. Individual experts representing >20 professional organizations participated in this roundtable discussion. The Think Tank consensus was that the metabolic syndrome (MetS) is a complex pathophysiological state comprised of a cluster of clinically measured and typically unmeasured risk factors, is progressive in its course, and is associated with serious and extensive comorbidity, but tends to be clinically under-recognized. The ideal patient care model for MetS must accurately identify those at risk before MetS develops and must recognize subtypes and stages of MetS to more effectively direct prevention and therapies. This new MetS care model introduces both affirmed and emerging concepts that will require consensus development, validation, and optimization in the future