Towards self-verification in finite difference code generation

Code generation from domain-specific languages is becoming increasingly popular as a method to obtain optimised low-level code that performs well on a given platform and for a given problem instance. Ensuring the correctness of generated codes is crucial. At the same time, testing or manual inspection of the code is problematic, as the generated code can be complex and hard to read. Moreover, the generated code may change depending on the problem type, domain size, or target platform, making conventional code review or testing methods impractical. As a solution, we propose the integration of formal verification tools into the code generation process. We present a case study in which the CIVL verification tool is combined with the Devito finite difference framework that generates optimised stencil code for PDE solvers from symbolic equations. We show a selection of properties of the generated code that can be automatically specified and verified during the code generation process. Our approach allowed us to detect a previously unknown bug in the Devito code generation tool

Conformational fingerprinting with Raman spectroscopy reveals protein structure as a translational biomarker of muscle pathology

\ua9 2024 The Royal Society of Chemistry.Neuromuscular disorders are a group of conditions that can result in weakness of skeletal muscles. Examples include fatal diseases such as amyotrophic lateral sclerosis and conditions associated with high morbidity such as myopathies (muscle diseases). Many of these disorders are known to have abnormal protein folding and protein aggregates. Thus, easy to apply methods for the detection of such changes may prove useful diagnostic biomarkers. Raman spectroscopy has shown early promise in the detection of muscle pathology in neuromuscular disorders and is well suited to characterising the conformational profiles relating to protein secondary structure. In this work, we assess if Raman spectroscopy can detect differences in protein structure in muscle in the setting of neuromuscular disease. We utilise in vivo Raman spectroscopy measurements from preclinical models of amyotrophic lateral sclerosis and the myopathy Duchenne muscular dystrophy, together with ex vivo measurements of human muscle samples from individuals with and without myopathy. Using quantitative conformation profiling and matrix factorisation we demonstrate that quantitative ‘conformational fingerprinting’ can be used to identify changes in protein folding in muscle. Notably, myopathic conditions in both preclinical models and human samples manifested a significant reduction in α-helix structures, with concomitant increases in β-sheet and, to a lesser extent, nonregular configurations. Spectral patterns derived through non-negative matrix factorisation were able to identify myopathy with a high accuracy (79% in mouse, 78% in human tissue). This work demonstrates the potential of conformational fingerprinting as an interpretable biomarker for neuromuscular disorders

Singlet oxygen luminescence as an in vivo photodynamic therapy dose metric: validation in normal mouse skin with topical amino-levulinic acid

Although singlet oxygen (1O2) has long been proposed as the primary reactive oxygen species in photodynamic therapy (PDT), it has only recently been possible to detect it in biological systems by its luminescence at 1270 nm. Having previously demonstrated this in vitro and in vivo, we showed that cell survival was strongly correlated to the 1O2 luminescence in cell suspensions over a wide range of treatment parameters. Here, we extend this to test the hypothesis that the photobiological response in vivo is also correlated with 1O2 generation, independent of individual treatment parameters. The normal skin of SKH1-HR hairless mice was sensitised with 20% amino-levulinic acid-induced protoporophyrin IX and exposed to 5, 11, 22 or 50 J cm−2 of pulsed 523 nm light at 50 mW cm−2, or to 50 J cm−2 at 15 or 150 mW cm−2. 1O2 luminescence was measured during treatment and the photodynamic response of the skin was scored daily for 2 weeks after treatment. As observed by other authors, a strong irradiance dependence of the PDT effect was observed. However, in all cases the responses increased with the 1O2 luminescence, independent of the irradiance, demonstrating for the first time in vivo an unequivocal mechanistic link between 1O2 generation and photobiological response

A hypothetico-deductive approach to assessing the social function of chemical signalling in a non-territorial solitary carnivore

The function of chemical signalling in non-territorial solitary carnivores is still relatively unclear. Studies on territorial solitary and social carnivores have highlighted odour capability and utility, however the social function of chemical signalling in wild carnivore populations operating dominance hierarchy social systems has received little attention. We monitored scent marking and investigatory behaviour of wild brown bears Ursus arctos, to test multiple hypotheses relating to the social function of chemical signalling. Camera traps were stationed facing bear ‘marking trees’ to document behaviour by different age sex classes in different seasons. We found evidence to support the hypothesis that adult males utilise chemical signalling to communicate dominance to other males throughout the non-denning period. Adult females did not appear to utilise marking trees to advertise oestrous state during the breeding season. The function of marking by subadult bears is somewhat unclear, but may be related to the behaviour of adult males. Subadults investigated trees more often than they scent marked during the breeding season, which could be a result of an increased risk from adult males. Females with young showed an increase in marking and investigation of trees outside of the breeding season. We propose the hypothesis that females engage their dependent young with marking trees from a young age, at a relatively ‘safe’ time of year. Memory, experience, and learning at a young age, may all contribute towards odour capabilities in adult bears

A Possible Mechanism for the Suppression of Plasmodium berghei Development in the Mosquito Anopheles gambiae by the Microsporidian Vavraia culicis

BACKGROUND: Microsporidian parasites of mosquitoes offer a possible way of controlling malaria, as they impede the development of Plasmodium parasites within the mosquito. The mechanism involved in this interference process is unknown. METHODOLOGY: We evaluated the possibility that larval infection by a microsporidian primes the immune system of adult mosquitoes in a way that enables a more effective anti-Plasmodium response. To do so, we infected 2-day old larvae of the mosquito Anopheles gambiae with one of 4 isolates of the microsporidian Vavraia culicis and reared one group as an uninfected control. Within each treatment, we fed half the adult females on a mix of P. berghei ookinetes and blood and inoculated the other half with a negatively charged CM-25 Sephadex bead to evaluate the mosquitoes' melanisation response. CONCLUSIONS: The microsporidian-infected mosquitoes were less likely to harbour oocysts (58.5% vs. 81.8%), harboured fewer oocysts (8.9 oocysts vs. 20.7 oocysts) if the malaria parasite did develop and melanised the Sephadex bead to a greater degree (73% vs. 35%) than the controls. While the isolates differed in the number of oocysts and in the melanisation response, the stimulation of the immune response was not correlated with either measure of malaria development. Nevertheless, the consistent difference between microsporidian-infected and -uninfected mosquitoes--more effective melanisation and less successful infection by malaria--suggests that microsporidians impede the development of malaria by priming the mosquito's immune system

Evaluating the impact of MEDLINE filters on evidence retrieval: study protocol

<p>Abstract</p> <p>Background</p> <p>Rather than searching the entire MEDLINE database, clinicians can perform searches on a filtered set of articles where relevant information is more likely to be found. Members of our team previously developed two types of MEDLINE filters. The 'methods' filters help identify clinical research of high methodological merit. The 'content' filters help identify articles in the discipline of renal medicine. We will now test the utility of these filters for physician MEDLINE searching.</p> <p>Hypothesis</p> <p>When a physician searches MEDLINE, we hypothesize the use of filters will increase the number of relevant articles retrieved (increase 'recall,' also called sensitivity) and decrease the number of non-relevant articles retrieved (increase 'precision,' also called positive predictive value), compared to the performance of a physician's search unaided by filters.</p> <p>Methods</p> <p>We will survey a random sample of 100 nephrologists in Canada to obtain the MEDLINE search that they would first perform themselves for a focused clinical question. Each question we provide to a nephrologist will be based on the topic of a recently published, well-conducted systematic review. We will examine the performance of a physician's unaided MEDLINE search. We will then apply a total of eight filter combinations to the search (filters used in isolation or in combination). We will calculate the recall and precision of each search. The filter combinations that most improve on unaided physician searches will be identified and characterized.</p> <p>Discussion</p> <p>If these filters improve search performance, physicians will be able to search MEDLINE for renal evidence more effectively, in less time, and with less frustration. Additionally, our methodology can be used as a proof of concept for the evaluation of search filters in other disciplines.</p

Comparative efficacy and safety of biosimilar infliximab and other biological treatments in ankylosing spondylitis: systematic literature review and meta-analysis.

OBJECTIVES: To compare the efficacy and safety of infliximab-biosimilar with other biological drugs for the treatment of active ankylosing spondylitis (AS). METHODS: Systematic literature review for randomized controlled trials (RCTs) with adalimumab, etanercept, golimumab, infliximab and infliximab-biosimilar in AS was performed and indirect meta-analysis (Bayesian mixed treatment comparison) was carried out. The proportion of patients reaching 20 % improvement by the assessment of Spondyloarthritis International Society response criteria (ASAS20) at weeks 12 and 24 was used as efficacy endpoints, and the occurrence of serious adverse events at week 24 was applied to compare the safety of the biologicals. RESULTS: Altogether, 13 RCTs, identified by the systematic literature search, were included in the analysis. Results on the ASAS20 efficacy endpoint were reported for week 12 in 12 RCTs involving 2,395 patients, and for week 24 in 5 RCTs comprising 1,337 patients. All the five biological agents proved to be significantly superior to placebo. Infliximab showed the highest odds ratio (OR) of 7.2 (95 % CI 3.68-13.19) compared to placebo, followed by infliximab-biosimilar with OR 6.25 (95 % CI 2.55-13.14), both assessed at week 24. No significant difference was found between infliximab-biosimilar and other biological treatments regarding their efficacy and safety. CONCLUSIONS: This is the first study which includes a biosimilar drug in the meta-analysis of biological treatments in AS. The results have proven the similar efficacy and safety profile of infliximab-biosimilar treatment compared to other biologicals

The metabolic basis of adolescent idiopathic scoliosis: 2011 report of the “metabolic” workgroup of the Fondation Yves Cotrel

OBJECTIVE: The purpose of this review is to elucidate the metabolic processes involved in the pathogenesis of adolescent idiopathic scoliosis (AIS) in light of research by the present authors as well as current literature. METHODS: Pathogenetic mechanism

Error determination in the photogrammetric assessment of shoreline changes

The evaluation of error or uncertainty in shoreline change studies is an issue of prime importance for providing an adequate framework for calculated rates of change and to allow the establishment of threshold values above which the rates would be significant. In this note, a practical, easy-to-use method is presented to estimate error involved in the calculation of shoreline changes on aerial photographs, including the three most used types of shoreline indicators: high water line, dune/cliff toe and cliff top. This approach takes into account the specific characteristics of each shoreline proxy, such as relief in the case of the cliff top or tidal oscillations in the case of the high water line. At the same time it includes the error components that are independent from the proxy, basically related to the technical aspects of the process such as photo scanning and georeferencing. A practical example of application of the method is provided for several types of data inputs, based on shoreline changes around the Bay of Cádiz (SW Spain)