Reliability Analysis of Concurrent Systems using LTSA

The analysis for software dependability is considered an important task within the software engineering life cycle. However, it is often impossible to carry out this task due to the complexity of available tools, lack of expert personnel and time-to-market pressures. As a result, released software versions may present unverified dependability properties subjecting customers to blind software reliability assessment. In particular, concurrent systems present certain behaviour that require a more complex system analysis not easily grasped at system design and architecture level

Using patient-reported outcome measures to evaluate care for patients with inflammatory chronic rheumatic disease

Objectives: Few countries integrate Patient-Reported Outcome Measures (PROMs) in routine performance assessment, and those that do focus on elective surgery. This study addresses the challenges of using PROMs to evaluate care in chronic conditions. We set out a modelling strategy to assess the extent to which changes over time in self-reported health status by patients with inflammatory chronic rheumatic disease are related to their biological drug therapy and Rheumatology centre primarily responsible for their care. Methods: Using data from the Portuguese Register of Rheumatic Diseases, we assess the health status using the Health Assessment Questionnaire-Disability Index (HAQ-DI) for rheumatic patients receiving biological drugs between 2000 and 2017. We employ a fixed effects model using the Least Squares Dummy Variables estimator. Results: Patients receiving infliximab or rituximab report lower health status than those on etanercept (the most common therapy) and patients in 4 of the 26 Rheumatology centres report higher health status than those at other centres. Conclusions: PROMs can be used for those with chronic conditions to provide the patient’s perspective about the impact on their health status of the choice of drug therapy and care provider. Care for chronic patients might be improved if healthcare organisations monitor PROMs and engage in performance assessment initiatives on a routine basis

Evidence that regulation of intramembrane proteolysis is mediated by substrate gating during sporulation in Bacillus subtilis

© 2018 Ramírez-Guadiana et al. http://creativecommons.org/licenses/by/4.0/. During the morphological process of sporulation in Bacillus subtilis two adjacent daughter cells (called the mother cell and forespore) follow different programs of gene expression that are linked to each other by signal transduction pathways. At a late stage in development, a signaling pathway emanating from the forespore triggers the proteolytic activation of the mother cell transcription factor σK. Cleavage of pro-σK to its mature and active form is catalyzed by the intramembrane cleaving metalloprotease SpoIVFB (B), a Site-2 Protease (S2P) family member. B is held inactive by two mother-cell membrane proteins SpoIVFA (A) and BofA. Activation of pro-σK processing requires a site-1 signaling protease SpoIVB (IVB) that is secreted from the forespore into the space between the two cells. IVB cleaves the extracellular domain of A but how this cleavage activates intramembrane proteolysis has remained unclear. Structural studies of the Methanocaldococcus jannaschii S2P homolog identified closed (substrate-occluded) and open (substrate-accessible) conformations of the protease, but the biological relevance of these conformations has not been established. Here, using co-immunoprecipitation and fluorescence microscopy, we show that stable association between the membrane-embedded protease and its substrate requires IVB signaling. We further show that the cytoplasmic cystathionine-β-synthase (CBS) domain of the B protease is not critical for this interaction or for pro-σK processing, suggesting the IVB-dependent interaction site is in the membrane protease domain. Finally, we provide evidence that the B protease domain adopts both open and closed conformations in vivo. Collectively, our data support a substrate-gating model in which IVB-dependent cleavage of A on one side of the membrane triggers a conformational change in the membrane-embedded protease from a closed to an open state allowing pro-σK access to the caged interior of the protease

Establishing a link between endothelial cell metabolism and vascular behaviour in a type 1 diabetes mouse model

Background/Aims: Vascular complications contribute significantly to the extensive morbidity and mortality rates observed in people with diabetes. Despite well known that the diabetic kidney and heart exhibit imbalanced angiogenesis, the mechanisms implicated in this angiogenic paradox remain unknown. In this study, we examined the angiogenic and metabolic gene expression profile (GEP) of endothelial cells (ECs) isolated from a mouse model with type1 diabetes mellitus (T1DM). Methods: ECs were isolated from kidneys and hearts of healthy and streptozocin (STZ)-treated mice. RNA was then extracted for molecular studies. GEP of 84 angiogenic and 84 AMP-activated Protein Kinase (AMPK)-dependent genes were examined by microarrays. Real time PCR confirmed the changes observed in significantly altered genes. Microvessel density (MVD) was analysed by immunohistochemistry, fibrosis was assessed by the Sirius red histological staining and connective tissue growth factor (CTGF) was quantified by ELISA. Results: The relative percentage of ECs and MVD were increased in the kidneys of T1DM animals whereas the opposite trend was observed in the hearts of diabetic mice. Accordingly, the majority of AMPK-associated genes were upregulated in kidneys and downregulated in hearts of these animals. Angiogenic GEP revealed significant differences in Tgfß, Notch signaling and Timp2 in both diabetic organs. These findings were in agreement with the angiogenesis histological assays. Fibrosis was augmented in both organs in diabetic as compared to healthy animals. Conclusion: Altogether, our findings indicate, for the first time, that T1DM heart and kidney ECs present opposite metabolic cues, which are accompanied by distinct angiogenic patterns. These findings enable the development of innovative organ-specific therapeutic strategies targeting diabetic-associated vascular disorders.This work was supported by CAPES (Sciences without Borders - Full Doctorate Fellowship – Process 10010-13-0); FEDER funds by COMPETE: [POCI-01-0145-FEDER-007440, POCI-01-0145-FEDER-016385]; NORTE2020 [NORTE-01-0145FEDER-000012]; HealthyAging2020 [CENTRO-01-0145-FEDER-000012-N2323]; FCT - Fundação para a Ciência e a Tecnologia [UID/BIM/04293/2013, EXPL/BIM-MED/0492/2012, SFRH/BPD/88745/2012, SFRH/BD/111799/2015]; Claude Pepper Older Americans Independence Center; grant: P30 AG028718, NIGMS Award P20GM109096; European Structural and Investment Funds (ESIF). AUTHOR CONTRIBUTION: CS and RS participated in the design and conception of the study; CS performed the whole laboratory and statistical analyses and drafted the manuscript; VSP, PPO, DSN carried out the FACS assay design and data acquisition, as well as the interpretation of FACS data; SA advised and performed microarray and RT-PCR assays; IR headed the parafin embedded tissue and histologial staining; SG, EC were responsible for the animal studies and immunohistochemistry analyses; RC advised the methodological laboratorial analysis and animal studies; RS and EC critically revised the manuscript for important intellectual content. All authors were involved in drafting and revising the article. All authors read and approved the final version of the manuscript

Omental whirl associated with bilateral inguinal hernia: a case report

INTRODUCTION: Torsion of the omentum is a rare cause of abdominal pain. It is clinically similar to common causes of acute surgical abdomen and is often diagnosed during surgery. Inguinal hernia is a common condition but not frequently related with torsion of the omentum. CASE PRESENTATION: A 40-year-old Caucasian man came to our emergency department with abdominal pain of the left quadrant and abdominal distension for 2 days. His medical history included an untreated left inguinal hernia in the last year. Computed tomography revealed densification of mesocolon with left omentum "whirl" component and other signs of omental torsion. During an exploratory laparoscopy, a wide twist of his omentum with necrotic alterations that extended to the bilateral inguinal hernial content was observed. Omentectomy and surgical repair of bilateral inguinal hernia were performed. CONCLUSIONS: Torsion of the omentum is a rare entity and usually presents a diagnostic challenge. The use of abdominal computed tomography can help diagnosing torsion of the omentum preoperatively and, thus, prevents a surgical approach. Nonetheless, some cases of torsion of the omentum require surgical repair. Accordingly, a laparoscopic approach is minimally invasive and efficient in performing omentectomy.(undefined

Quantification of key retinal features in early and late age-related macular degeneration using deep learning

PURPOSE: To develop and validate a deep learning model for segmentation of 13 features associated with neovascular and atrophic age-related macular degeneration (AMD). DESIGN: Development and validation of a deep-learning model for feature segmentation METHODS: Data for model development were obtained from 307 optical coherence tomography volumes. Eight experienced graders manually delineated all abnormalities in 2,712 B-scans. A deep neural network was trained with this data to perform voxel-level segmentation of the 13 most common abnormalities (features). For evaluation, 112 B-scans from 112 patients with a diagnosis of neovascular AMD were annotated by four independent observers. Main outcome measures were Dice score, intra-class correlation coefficient (ICC), and free-response receiver operating characteristic (FROC) curve. RESULTS: On 11 of the 13 features, the model obtained a mean Dice score of 0.63 ± 0.15, compared to 0.61 ± 0.17 for the observers. The mean ICC for the model was 0.66 ± 0.22, compared to 0.62 ± 0.21 for the observers. Two features were not evaluated quantitatively due to lack of data. FROC analysis demonstrated that the model scored similar or higher sensitivity per false positives compared to the observers. CONCLUSIONS: The quality of the automatic segmentation matches that of experienced graders for most features, exceeding human performance for some features. The quantified parameters provided by the model can be used in the current clinical routine and open possibilities for further research into treatment response outside clinical trials

Institutionalisation of Social Movements: Co-option And Democratic Policy-making

Over the past 30 years, urban policy in Brazil has undergone a major transformation, both in terms of regulatory frameworks and the involvement of citizens in the process of policy-making. As an intense process of institutional innovation and mobilisation for decent publicservices took place, academics started to consider the impact of institutionalisation on the autonomy of social movements. Using empirical evidence from a city in the northeast of Brazil, this article addresses the wider literature on citizen participation and social movements to examine specifically the problem with co-optation. I examine the risks linked to co-optation, risks that can undermine the credibility of social movements as agents of change, and explore the tensions that go beyond the ‘co-optation versus autonomy’ divide, an issue frequently found in the practices of social movements, in their dealings with those in power. In particular, this article explores the learning processes and contentious relationships between mainly institutionally oriented urban movements and local government. This study found that the learning of deliberative skills not only led to changes in the objectives and repertoires of housing movements, but also to the inclusion of new components in their objectives that provide room for creative agency and which, in some cases, might allow them to maintain their autonomy from the state

Combining remote sensing and household level data for regional scale analysis of land cover change in the Brazilian Amazon

Land cover change in the Brazilian Amazon depends on the spatial variability of political, socioeconomic and biophysical factors, as well as on the land use history and its actors. A regional scale analysis was made in Rondônia State to identify possible differences in land cover change connected to spatial policies of land occupation, size and year of establishment of properties, accessibility measures and soil fertility. The analysis was made based on remote sensing data and household level data gathered with a questionnaire. Both types of analyses indicate that the highest level of total deforestation is found inside agrarian projects, especially in those established more than 20 years ago. Even though deforestation rates are similar inside and outside official settlements, inside agrarian projects forest depletion can exceed 50% at the property level within 10–14 years after establishment. The data indicate that both small-scale and medium to large-scale farmers contribute to deforestation processes in Rondônia State encouraged by spatial policies of land occupation, which provide better accessibility to forest fringes where soil fertility and forest resources are important determinants of location choic

Jet production in charged current deep inelastic e⁺p scatteringat HERA

The production rates and substructure of jets have been studied in charged current deep inelastic e⁺p scattering for Q² > 200 GeV² with the ZEUS detector at HERA using an integrated luminosity of 110.5 pb⁻¹. Inclusive jet cross sections are presented for jets with transverse energies E_{T}^{jet} > 5 GeV. Measurements of the mean subjet multiplicity, 〈n_{sbj}〉, of the inclusive jet sample are presented. Predictions based on parton-shower Monte Carlo models and next-to-leading-order QCD calculations are compared to the measurements. The value of α_{s} (M_{z}), determined from 〈n_{sbj}〉 at y_{cut} = 10⁻² for jets with 25 < E_{T}^{jet} < 119 GeV, is α_{s} (M_{z}) = 0.1202 ± 0.0052 (stat.)_{-0.0019}^{+0.0060} (syst.)_{-0.0053}^{+0.0065} (th.). The mean subjet multiplicity as a function of Q² is found to be consistent with that measured in NC DIS