Comorbidity in polymyalgia rheumatica

Polymyalgia rheumatica (PMR) is the commonest inflammatory rheumatic disease affecting older people. The current mainstay of treatment is long-term oral glucocorticoid therapy. Management of these patients in clinical practice is often complicated by the presence of comorbidity. Comorbidity might be due to shared risk factors such as age, sex, or genetic background; to the presence of the disease itself; or to adverse effects of glucocorticoid therapy. Cardiovascular disease, osteoporosis/fracture, metabolic and ocular comorbidity are of particular interest to clinicians because of their relationship to glucocorticoid therapy and the relevance to clinical treatment decisions regarding glucocorticoid tapering. Patients at high risk of exacerbation of comorbidity by glucocorticoid therapy may be considered for adjunctive steroid-sparing therapies and thus may need specialist management. From a public health perspective, with the ageing population the prevalence of PMR is predicted to increase; accurate data on comorbidity will be needed for planning and delivery of healthcare services

Interactions of the potent synthetic AT1 antagonist analog BV6 with membrane bilayers and mesoporous silicate matrices

The present work describes the drug:membrane interactions and a drug delivery system of the novel potent AT1 blocker BV6. This designed analog has most of the pharmacological segments of losartan and an additional biphenyltetrazole moiety resulting in increased lipophilicity. We found that BV6:membrane interactions lead to compact bilayers that may in part explain its higher in vitro activity compared to losartan since such environment may facilitate its approach to AT1 receptor. Its high docking score to AT1 receptor stems from more hydrophobic interactions compared to losartan. X-ray powder diffraction (XRPD) and thermogravimetric analysis (TGA) have shown that BV6 has a crystalline form that is not decomposed completely up to 600 °C. These properties are desirable for a drug molecule. BV6 can also be incorporated into a mesoporous silicate drug-delivery matrix SBA-15. The properties of the obtained drug-delivery system have been inspected by XRD, 13C CP/MAS, TGA and nitrogen sorption experiments

Lifetime risk and genetic predisposition to post-traumatic OA of the knee in the UK Biobank

Objective Acute knee injury is associated with post-traumatic OA (PTOA). Very little is known about the genome-wide associations of PTOA when compared with idiopathic OA (iOA). Our objective was to describe the development of knee OA after knee injury and its genetic associations in UK Biobank (UKB). Design Clinically significant structural knee injuries in those <=50 years were identified from electronic health record and self-reported data in 502,409 UKB participants. Time-to-first knee OA code was compared in injured cases and age-/sex-matched non-injured controls using Cox Proportional Hazards models. A time-to-OA genome-wide association study (GWAS) sought evidence for PTOA risk variants 6 months-20 years following injury. Evidence for associations of two iOA polygenic risk scores (PRS) was sought. Results Of 4233 knee injury cases, 1896 (44.8%) were female (mean age at injury 34.1 years [SD10.4]). Over a median of 30.2 (IQR19.5-45.4) years, 1096 (25.9%) of injured cases developed knee OA. The overall hazards ratio (HR) for knee OA after injury was 1.81[1.70,1.93],P=8.9x10-74. Female sex and increasing age at injury were associated with knee OA following injury (HR1.15[1.02,1.30];1.07[1,07,1.07] respectively). OA risk was highest in the first 5 years after injury (HR3.26[2.67,3.98]), persisting for 40 years. In 3074 knee injury cases included in the time-to-OA GWAS, no variants reached genome-wide significance. iOA PRS was not associated with time-to-OA (HR 0.43[0.02,8.41]). Conclusions Increasing age at injury and female sex appear to be associated with future development of PTOA in UKB, the risk of which was greatest in the 5 years after injury. Further international efforts towards a better-powered meta-analysis will definitively elucidate genetic similarities and differences of PTOA and iOA

On energy debt: Managing consumption on evolving software

This paper introduces the concept of energy debt: a new metric, reflecting the implied cost in terms of energy consumption over time, of choosing a flawed implementation of a software system rather than a more robust, yet possibly time consuming, approach. A flawed implementation is considered to contain code smells, known to have a negative influence on the energy consumption. Similar to technical debt, if energy debt is not properly addressed, it can accumulate an energy "interest". This interest will keep increasing as new versions of the software are released, and eventually reach a point where the interest will be higher than the initial energy debt. Addressing the issues/smells at such a point can remove energy debt, at the cost of having already consumed a significant amount of energy which can translate into high costs. We present all underlying concepts of energy debt, bridging the connection with the existing concept of technical debt and show how to compute the energy debt through a motivational example.This work is financed by National Funds through the Portuguese funding agency, FCT - Fundação para a Ciência e a Tecnologia, within project UIDB/50014/2020. The first author is also financed by FCT grant SFRH/BD/132485/2017. The last author is also supported by operation Centro-01-0145-FEDER-000019 - C4 - Centro de Competências em Cloud Computing, cofinanced by the European Regional Development Fund (ERDF) through the Programa Operacional Regional do Centro (Centro 2020), in the scope of the Sistema de Apoio à Investigação Científica e Tecnológica - Programas Integrados de IC&DT

E-Debitum: managing software energy debt

35th IEEE/ACM International Conference on Automated Software Engineering Workshops (ASEW ’20) - International Workshop on Sustainable Software Engineering (SUSTAIN-SE)This paper extends previous work on the concept of a new software energy metric: Energy Debt. This metric is a reflection on the implied cost, in terms of energy consumption over time, of choosing an energy flawed software implementation over a more robust and efficient, yet time consuming, approach. This paper presents the implementation a SonarQube tool called E-Debitum which calculates the energy debt of Android applications throughout their versions. This plugin uses a robust, well defined, and extendable smell catalogue based on current green software literature, with each smell defining the potential energy savings. To conclude, an experimental validation of E-Debitum was executed on 3 popular Android applications with various releases, showing how their energy debt fluctuated throughout releases.This work is financed by National Funds through the Portuguese funding agency, FCT -Fundação para a Ciência e a Tecnologia within project UIDB/50014/2020

A process model for developing learning design patterns with international scope

This paper investigates the process of identifying design patterns in international collaborative learning environments. In this context, design patterns are referred to as structured descriptions of best practice with pre-defined sections such as problem, solution and consequences. We pay special attention to how the scope of a design pattern is identified and articulated. Based on a review of the seminal design patterns literature and current practice in the area of learning design, the lack of a more specific process description for developing patterns with international scope is identified. The paper suggests a process model for developing patterns with international scope. This model is exemplified in a case study that links the analysis of observation in international learning environments to the articulation of design patterns by identifying culturally independent core values that constitute the foundations of a design pattern with international scope. These core values are linked to recurrent learning behaviors and specific artefacts that support learning in the articulation of a design pattern. The findings contribute to gaining a deeper understanding of the pattern scoping and abstraction process in international learning environments

Multicenter evaluation of the vitek MS matrix-assisted laser desorption ionization-time of flight mass spectrometry system for identification of gram-positive aerobic bacteria

Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF) is gaining momentum as a tool for bacterial identification in the clinical microbiology laboratory. Compared with conventional methods, this technology can more readily and conveniently identify a wide range of organisms. Here, we report the findings from a multicenter study to evaluate the Vitek MS v2.0 system (bioMérieux, Inc.) for the identification of aerobic Gram-positive bacteria. A total of 1,146 unique isolates, representing 13 genera and 42 species, were analyzed, and results were compared to those obtained by nucleic acid sequence-based identification as the reference method. For 1,063 of 1,146 isolates (92.8%), the Vitek MS provided a single identification that was accurate to the species level. For an additional 31 isolates (2.7%), multiple possible identifications were provided, all correct at the genus level. Mixed-genus or single-choice incorrect identifications were provided for 18 isolates (1.6%). Although no identification was obtained for 33 isolates (2.9%), there was no specific bacterial species for which the Vitek MS consistently failed to provide identification. In a subset of 463 isolates representing commonly encountered important pathogens, 95% were accurately identified to the species level and there were no misidentifications. Also, in all but one instance, the Vitek MS correctly differentiated Streptococcus pneumoniae from other viridans group streptococci. The findings demonstrate that the Vitek MS system is highly accurate for the identification of Gram-positive aerobic bacteria in the clinical laboratory setting