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Primary Systemic Sclerosis heart involvement: a systematic literature review and preliminary data-driven, consensus-based WSF/HFA definition
No full textIntroduction: primary heart involvement in systemic sclerosis (SSc-pHI) may cause morpho-functional and electrical cardiac abnormalities and is a common cause of death. The absence of a clear definition of SSc-pHI limits our understanding and ability to focus clinical research. We aimed to create an expert consensus definition for SSc-pHI.Methods: A systematic literature review of cardiac involvement and manifestations in SSc was conducted to inform an international and multi-disciplinary task-force. In addition, the nominal group technique (NGT) was used to derive a definition that was then subject to voting. Sixteen clinical cases were evaluated to test face validity, feasibility, reliability and criterion validity of the newly created definition.Results: 171 publications met eligibility criteria. Using the NGT, experts added their opinion, provided statements to consider and ranked them to create the consensus definition, which received 100% agreement on face validity. A median 60(5-300) seconds was taken for the feasibility on a single case. Inter-rater agreement was moderate [mKappa(95%CI) 0.56(0.46-1.00) for first and 0.55(0.44-1.00) for second round] and intra-rater agreement was good [mKappa(95%CI) 0.77(0.47-1,00)]. Criterion validity showed a 78(73-84) % correctness versus gold standard.Conclusion: A preliminary SSc-pHI consensus-based definition was created and partially validated, for use in future clinical research
Uncertainty analysis on FDTD computation with artificial neural network
No full textThe artificial neural network (ANN) has appeared as a potential alternative for uncertainty quantification (UQ) in the finite difference time domain (FDTD) computation. It is applied to build a surrogate model for the compute-intensive FDTD simulation and to bypass the numerous simulations required for UQ. However, when the surrogate model utilizes the ANN, a considerable number of data is generally required for high accuracy and generating such large quantities of data becomes computationally prohibitive. To address this drawback, a number of adaptations for ANN are proposed which additionally improves the accuracy of the ANN in UQ for the FDTD computation while maintaining a low computational cost. The proposed algorithm is tested for application in bioelectromagnetics and considerable speed-up, as well as improved accuracy of UQ, is observed compared to traditional methods such as the non-intrusive polynomial chaos method
Xar-Trek: Run-time Execution Migration among FPGAs and Heterogeneous-ISA CPUs
No full textDatacenter servers are increasingly heterogeneous: from x86 host CPUs, to ARM or RISC-V CPUs in NICs/SSDs, to FPGAs. Previous works have demonstrated that migrating application execution at run-time across heterogeneous-ISA CPUs can yield significant performance and energy gains, with relatively little programmer effort. However, FPGAs have often been overlooked in that context: hardware acceleration using FPGAs involves statically implementing select application functions, which prohibits dynamic and transparent migration. We present Xar-Trek, a new compiler and run-time software framework that overcomes this limitation. Xar-Trek compiles an application for several CPU ISAs and select application functions for acceleration on an FPGA, allowing execution migration between heterogeneous-ISA CPUs and FPGAs at run-time. Xar-Trek’s run-time monitors server workloads and migrates application functions to an FPGA or to heterogeneous-ISA CPUs based on a scheduling policy. We develop a heuristic policy that uses application workload profiles to make scheduling decisions. Our evaluations conducted on a system with x86-64 server CPUs, ARM64 server CPUs, and an Alveo accelerator card reveal 88%-1% performance gains over no-migration baselines
Exploiting the SAT Revolution for Automated Software Verification: Report from an Industrial Case Study
No full textIn the last three decades, Boolean Satisfiability (SAT) solvers experienced a dramatic performance revolution; they are now used as the backend of various industrial verification engines. SAT solvers can now check logical formulas that contain millions of propositional variables. In Satisfiability Modulo Theories (SMT) solvers, predicates from various theories are not encoded using propositional variables as in SAT but remain in the problem formulation. Thus, SMT solvers can be used as backends for solving the generated verification conditions to cope with increasing software complexity from industrial applications. This talk will overview automated software verification techniques that rely on sophisticated SMT solvers built over efficient SAT solvers. I will discuss challenges, problems, and recent advances to ensure safety and security in opensource and embedded software applications. I will describe novel algorithms that exploit fuzzing, explicit-state, and SMT-based symbolic model checking for verifying single- and multi-threaded software. These algorithms were the first to verify multi-threaded C/Posix software based on shared-memory synchronization and communication symbolically. They are implemented in industrial strength software verification tools, now considered state-of-the art in the software testing and verification community, receiving 28 medals at SV-COMP and Test-COMP. This achievement enabled industrial research collaborations with Intel and Nokia. Software engineers applied these tools to find real security vulnerabilities in large-scale software systems (e.g., memory safety in firmware for Intel and arithmetic overflow in telecommunication software for Nokia, neither of which had been found before)
Interfered-Naming Therapy for Aphasia (INTA): A neuroscience-based approach to improve linguistic-executive processing
No full textBackground and Aims. Research just started to combine behavioural, computational and neural accounts to investigate the nature of post-stroke aphasia, but the dynamic aspect of aphasia recovery has rarely been integrated. Moreover, executive functions in aphasia recently gained attention as important contributor to language performance. Lexical picture/word interference embraces both executive control and language processing through distracted confrontation naming, as revealed by functional Magnetic Resonance Imaging. Thus, we for the first time applied this complex paradigm in diagnostic and therapeutic settings for persons with aphasia (PWA) on the group level. In consideration of behavioural and computational data, we aimed at investigating the neural responses of persons with aphasia (a) to a novel treatment method targeting both word processing and language control by means of interferednaming, and (b) to the interfering stimuli to determine preserved and impaired processing and changes thereof. Method. 19 PWA at a mean age of 51 years (range 21-74) and 26 months post-onset (4-63) as well as 22 matched healthy controls were included in a diagnostic fMRI studycomprising a pure naming test and the lexical fMRI interference paradigm with five distractor conditions (phonological, associative-semantic, categorical-semantic, unrelated word, unrelated noise) in a 3T Philips scanner. 12 participants completed the 4-weeks therapy, 11 the fMRI therapy study. During therapy, both comprehension of the interfering words and distracted but cued picture naming were trained. Results. The distribution of lexical-semantic and -phonological impairments of PWA in the computational model was well-balanced. The novel linguistic executive treatment significantly improved pure and interfered naming for the PWA group, fostering generalisation to untrained items, reducing repetition of distractors, and ameliorating lexical-semantic processing. The predicted behavioural effects of distractor types were only found for the two semantic conditions. Neuroimaging revealed right-hemisphere compensation before treatment, activation decrease related to enhanced efficiency due to treatment, and both differential and overlapping responses to distractor types. Key brain regions encompassed inferior frontal gyrus and right posterior middle temporal gyrus as well as the basal temporal language area, cerebellum and anterior cingulate cortex. Discussion. The novel inferfered-naming in aphasia therapy revealed to be effective, but differential effects of distractor types were less prominent than expected. Behavioural, computational and neural findings converge on identifying semanticexecutive processing as the core source of improvements. This account of linguisticexecutive processing in aphasia offers a step towards a comprehensive theory of neurorehabilitation
Correlations of Shocks and Stresses with Distribution Network Outages
No full textDistribution network outages have significant socioeconomic impacts, and potentially pose a threat to life when critical infrastructures are affected. Shocks and stresses, such as climate change, extreme weather or intentional attacks, in combination with an expected rise in electricity demand, pose an increasing risk to power network reliability. Detailed data on distribution network outages can be used for further research in prevention and mitigation of such outages. This paper presents and describes a unique and comprehensive dataset of UK distribution network outages. The dataset for 2020 is analyzed to identify correlations with shocks and stresses, such as demand, extreme weather, and COVID-19 lockdown. The results justifyfurther research in prevention and mitigation of distribution network outages, support the industry in future planning of distribution networks, and can feed into models for operational planning in face of upcoming shocks and stresses
Casting a wider net on ocean NETs
No full textSocietal issues involving policies and publics are generally understudied in research on ocean-based Negative Emission Technologies (NETs), yet will be crucial if novel techniques are ever to function at scale. Publics influence political mandates and market uptake, and are key to robust decision-making and responsible incentivisation. Discourses surrounding ocean NETs will also have fundamental effects on governance for the techniques, shaping how they are defined, who is assigned the authority to govern, and what instruments are deemed appropriate. This Perspective brings together key insights on the societal dimensions of ocean NETs, including public acceptability, policy assessment, governance and discourse. Ocean iron fertilisation is the only ocean NET on which there exists considerable social science research, and we show that much evidence points against its social desirability. This, together with considerable natural science uncertainties, leads us to question whether further research is actually necessary to rule out ocean iron fertilisation as an option. For other ocean NETs, there are considerable knowledge gaps, yet the available evidence suggests that the majority of ocean NETs may face a greater public acceptability challenge than terrestrial NETs. Ocean NETs also raise complex governance questions which go well beyond the remit of natural sciences and engineering. Using a conceptual exploration of the ways in which different types of discourse may shape emerging ocean NETs governance, we show that the very idea of ocean NETs is likely to set the stage for a whole new range of contested futures
Maintenance of barrier tissue integrity by unconventional lymphocytes
No full textMucosal surfaces, as a first barrier with the environment are especially susceptible to damage from both pathogens and physical trauma. Thus, these sites require tightly regulated repair programs to maintain barrier function in the face of such insults. Barrier sites are also enriched for unconventional lymphocytes, which lack rearranged antigen receptors or express only a limited range of such receptors, such as ILCs (Innate Lymphoid Cells), γδ T Cells and MAIT (Mucosal Associated Invariant T Cells). Recent studies have uncovered critical roles for unconventional lymphocytes in regulating mucosal barrier function, and, in particular, have highlighted their important involvement in barrier repair. The production of growth factors such as amphiregulin by ILC2, and fibroblast growth factors by γδ T cells have been shown to promote tissue repair at multiple barrier sites. Additionally, MAIT cells have been shown to exhibit pro-repair phenotypes and demonstrate microbiota-dependent promotion of murine skin healing. In this review we will discuss how immune responses at mucosal sites are controlled by unconventional lymphocytes and the ways in which these cells promote tissue repair to maintain barrier integrity in the skin, gut and lungs
High penetrance of myeloid neoplasia with diverse clinical and cytogenetic features in three siblings with a familial GATA2 deficiency
No full textPathogenic germ-line variants in GATA2 (GATA2 deficiency) can cause childhood myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML), and can be associated with distinct clinical syndromic features. However, penetrance and genotype-phenotype correlations are incompletely understood. Here we report on the clinically diverse features of three siblings affected by GATA2c.1021_1031del over an 18-year period, all initially presenting in childhood and adolescence with MDS and AML with monosomy 7 (-7), and one also with monosomy trisomy 8 (+8).The siblings inherited a GATA2c.1021_1031del from their father who remains asymptomatic in his sixth decade. The two younger sisters are well after unrelated haematopoietic stem cell transplantation (HSCT), while the first boy died of severe chronic lung disease after sibling HSCT from his youngest sister, who subsequently also developed GATA2-deficiency associated MDS. This family illustrates high penetrance with variable genotype/phenotype correlation within one generation with GATA2-deficiency. We surmise that the lung disease post sibling HSCT was alsocaused by the GATA2-deficiency. The experience with this family underlines the necessity for GATA2 analysis in all apparently sporadic childhood and teenage MDS and AML with -7 or +8 also in the absence of a family history or other clinical features, and rigorous genetic testing in siblings. Moreover, our findings support the arguments for pre-emptive HSCT in variant-carrying siblings
TEMPERATURE RESPONSE TO COLD CHALLENGE AND MOBILE PHONE THERMOGRAPHY AS OUTCOME MEASURES FOR SYSTEMIC SCLEROSIS-RELATED RAYNAUD'S PHENOMENON
No full textObjectives Objective outcome measures of systemic sclerosis (SSc)-related Raynaud's phenomenon(RP) are badly needed. Our objectives were to (a) further validate thermographic response to a standard hand cold challenge as an outcome measure by assessing sensitivity to change and (b) explore mobile phone thermography as a feasible, ambulatory tool. Methods Twelve patients with a SSc-spectrum disorder admitted for intravenous iloprost infusions underwent a standard cold challenge before and after one infusion. Thermographic measurements included area under the rewarming curve (AUC) and maximum rewarming temperature (MAX). Before and during another infusion, each patient underwent monitoring of finger skin temperature by two methods: continuous thermocouple recording (the standard method) and mobile phone thermography. Results All cold challenge summary measures (including AUC and MAX) increased after iloprost (most not significantly). However, when the response curves were modelled after averaging across fingers (linear mixed models, three versions), significant change was detected. For example, with Model 1 (no interaction between period and time) temperature was on average 1.67 (95% CI 1.49 to 1.85, p<0.001)OC higher post-iloprost. Mobile phone and thermocouple temperature measurements showed a strong estimated latent correlation (0.88 [95% CI 0.81 to 0.92]). The estimated increases/hour were 0.25 (95% CI 0.05 to 0.45)OC for the thermocouple and 0.36 (0.13 to 0.60)OC for mobile phone thermography. Conclusions Our pilot study suggests that (a) thermographic response to a cold challenge is sensitive to change and (b) mobile phone thermography could bring feasibility to thermographic parameters as outcome measures in later phase, large-scale, community-based clinical trials of RP