Miracle-dz/UniFAR-FTUs huggingface dataset:
Model-Driven Trace Diagnostics for Pattern-based Temporal Specifications

Offline trace checking tools check whether a specification holds on a log of events recorded at run time; they yield a verification verdict (typically a boolean value) when the checking process ends. When the verdict is false, a software engineer needs to diagnose the property violations found in the trace in order to understand their cause and, if needed, decide for corrective actions to be performed on the system. However, a boolean verdict may not be informative enough to perform trace diagnostics, since it does not provide any useful information about the cause of the violation and because a property can be violated for multiple reasons. The goal of this paper is to provide a practical and scalable solution to solve the trace diagnostics problem, in the settings of model-driven trace checking of temporal properties expressed in TemPsy, a pattern-based specification language. The main contributions of the paper are: a model-driven approach for trace diagnostics of pattern-based temporal properties expressed in TemPsy, which relies on the evaluation of OCL queries on an instance of a trace metamodel; the implementation of this trace diagnostics procedure in the TemPsy-Report tool; the evaluation of the scalability of TemPsy-Report, when used for the diagnostics of violations of real properties derived from a case study of our industrial partner. The results show that TemPsy-Report is able to collect diagnostic information from large traces (with one million events) in less than ten seconds; TemPsy-Report scales linearly with respect to the length of the trace and keeps approximately constant performance as the number of violations increases.
The Role of Vitamin D in CKD Stages 3 to 4: Report of a Scientific Workshop Sponsored by the National Kidney Foundation.

Deficiency of 25-hydroxyvitamin D (25[OH]D) is common in patients with chronic kidney disease stages 3 and 4 and is associated with poor outcomes. However, the evaluation and management of vitamin D deficiency in nephrology remains controversial. This article reports on the proceedings from a "controversies conference" on vitamin D in chronic kidney disease that was sponsored by the National Kidney Foundation. The report outlines the deliberations of the 3 work groups that participated in the conference. Until newer measurement methods are widely used, the panel agreed that clinicians should classify 25(OH)D "adequacy" as concentrations > 20ng/mL without evidence of counter-regulatory hormone activity (ie, elevated parathyroid hormone). The panel also agreed that 25(OH)D concentrations < 15ng/mL should be treated irrespective of parathyroid hormone level. Patients with 25(OH)D concentrations between 15 and 20ng/mL may not require treatment if there is no evidence of counter-regulatory hormone activity. The panel agreed that nutritional vitamin D (cholecalciferol, ergocalciferol, or calcifediol) should be supplemented before giving activated vitamin D compounds. The compounds need further study evaluating important outcomes that observational studies have linked to low 25(OH)D levels, such as progression to end-stage kidney disease, infections, fracture rates, hospitalizations, and all-cause mortality. We urge further research funding in this field.
Breath of Life: The Respiratory Vagal Stimulation Model of Contemplative Activity

Contemplative practices, such as meditation and yoga, are increasingly popular among the general public and as topics of research. Beneficial effects associated with these practices have been found on physical health, mental health and cognitive performance. However, studies and theories that clarify the underlying mechanisms are lacking or scarce. This theoretical review aims to address and compensate this scarcity. We will show that various contemplative activities have in common that breathing is regulated or attentively guided. This respiratory discipline in turn could parsimoniously explain the physical and mental benefits of contemplative activities through changes in autonomic balance. We propose a neurophysiological model that explains how these specific respiration styles could operate, by phasically and tonically stimulating the vagal nerve: respiratory vagal nerve stimulation (rVNS). The vagal nerve, as a proponent of the parasympathetic nervous system (PNS), is the prime candidate in explaining the effects of contemplative practices on health, mental health and cognition. We will discuss implications and limitations of our model.
Targeting Exercise Interventions to Patients With Cancer in Need: An Individual Patient Data Meta-Analysis

Background Exercise effects in cancer patients often appear modest, possibly because interventions rarely target patients most in need. This study investigated the moderator effects of baseline values on the exercise outcomes of fatigue, aerobic fitness, muscle strength, quality of life (QoL), and self-reported physical function (PF) in cancer patients during and post-treatment. Methods Individual patient data from 34 randomized exercise trials (n = 4519) were pooled. Linear mixed-effect models were used to study moderator effects of baseline values on exercise intervention outcomes and to determine whether these moderator effects differed by intervention timing (during vs post-treatment). All statistical tests were two-sided. Results Moderator effects of baseline fatigue and PF were consistent across intervention timing, with greater effects in patients with worse fatigue (Pinteraction = .05) and worse PF (Pinteraction = .003). Moderator effects of baseline aerobic fitness, muscle strength, and QoL differed by intervention timing. During treatment, effects on aerobic fitness were greater for patients with better baseline aerobic fitness (Pinteraction = .002). Post-treatment, effects on upper (Pinteraction < .001) and lower (Pinteraction = .01) body muscle strength and QoL (Pinteraction < .001) were greater in patients with worse baseline values. Conclusion Although exercise should be encouraged for most cancer patients during and post-treatments, targeting specific subgroups may be especially beneficial and cost effective. For fatigue and PF, interventions during and post-treatment should target patients with high fatigue and low PF. During treatment, patients experience benefit for muscle strength and QoL regardless of baseline values; however, only patients with low baseline values benefit post-treatment. For aerobic fitness, patients with low baseline values do not appear to benefit from exercise during treatment.
Can certain factors for recurrence of placenta-mediated pregnancy complications be identified after an initial small-for-gestational-age birth?

Abstract Introduction: After a small-for-gestational-age (SGA) birth, recurrence of placenta-mediated pregnancy complications (PMPCs) is a cause for anxiety when contemplating another pregnancy. We sought to identify factors potentially associated with this recurrence. Material and methods: This retrospective single-center observational study was conducted in a tertiary maternity unit between 1 January 2010 and 31 December 2017. We included all women having experienced a non-syndromic SGA birth and who were subsequently monitored for at least one other pregnancy in our institution. PMPCs were defined as recurrent SGA births, three consecutive first-trimester miscarriages, or preeclampsia. Results: Ninety-four women were included over a 7-year study period. Recurrent PMPCs were recorded in 30 (32%) cases, of which 29 featured recurrent SGA births. None of the following characteristics were significantly associated with recurrence: presence of preeclampsia during the initial pregnancy (six [20%] versus 25 [39%] cases in the recurrent PMPCs and non-recurrent PMPCs groups, respectively; p = .11), results of the histopathologic placental examination or thrombophilia screen, or implemented treatment during subsequent pregnancies. Conclusions: PMPCs recur frequently. No risk factor for recurrence was identified in our study. Results of etiologic assessments and treatments implemented after an initial SGA birth should therefore not modify level of clinical and ultrasound monitoring provided during subsequent pregnancies.Rationale: Recurrence of placenta-mediated pregnancy complications is a cause for anxiety when contemplating another pregnancy. We did not identify any risk factor after an initial small-for-gestational-age birth in our study; surveillance should therefore not be modified by the etiologic assessments’ results.
Integration of genomics, high throughput drug screening, and personalized xenograft models as a novel precision medicine paradigm for high risk pediatric cancer

ABSTRACT Pediatric high grade gliomas (HGG) are primary brain malignancies that result in significant morbidity and mortality. One of the challenges in their treatment is inter- and intra-tumoral heterogeneity. Precision medicine approaches have the potential to enhance diagnostic, prognostic and/or therapeutic information. In this case study we describe the molecular characterization of a pediatric HGG and the use of an integrated approach based on genomic, in vitro and in vivo testing to identify actionable targets and treatment options. Molecular analysis based on WGS performed on initial and recurrent tumor biopsies revealed mutations in TP53, TSC1 and CIC genes, focal amplification of MYCN, and copy number gains in SMO and c-MET. Transcriptomic analysis identified increased expression of MYCN, and genes involved in sonic hedgehog signaling proteins (SHH, SMO, GLI1, GLI2) and receptor tyrosine kinase pathways (PLK, AURKA, c-MET). HTS revealed no cytotoxic efficacy of SHH pathway inhibitors while sensitivity was observed to the mTOR inhibitor temsirolimus, the ALK inhibitor ceritinib, and the PLK1 inhibitor BI2536. Based on the integrated approach, temsirolimus, ceritinib, BI2536 and standard therapy temozolomide were selected for further in vivo evaluation. Using the PDX animal model (median survival 28 days) we showed significant in vivo activity for mTOR inhibition by temsirolimus and BI2536 (median survival 109 and 115.5 days respectively) while ceritinib and temozolomide had only a moderate effect (43 and 75.5 days median survival respectively). This case study demonstrates that an integrated approach based on genomic, in vitro and in vivo drug efficacy testing in a PDX model may be useful to guide the management of high risk pediatric brain tumor in a clinically meaningful timeframe.
Immunological Tolerance and Function: Associations Between Intestinal Bacteria, Probiotics, Prebiotics, and Phages

Post-birth there is a bacterial assault on all mucosal surfaces. The intestinal microbiome is an important participant in health and disease. The pattern of composition and concentration of the intestinal microbiome varies greatly. Therefore, achieving immunological tolerance in the first 3–4 years of life is critical for maintaining health throughout a lifetime. Probiotic bacteria are organisms that afford beneficial health effects to the host and in certain instances may protect against the development of disease. The potential benefits of modifying the composition of the intestinal microbial cohort for therapeutic benefit is evident in the use in high risks groups such as premature infants, children receiving antibiotics, rotavirus infections in non-vaccinated children and traveler's diarrhea in adults. Probiotics and prebiotics are postulated to have immunomodulating capabilities by influencing the intestinal microbial cohort and dampening the activity of pathobiont intestinal microbes, such as Klebsiella pneumonia and Clostridia perfringens. Lactobacilli and Bifidobacteria are examples of probiotics found in the large intestine and so far, the benefits afforded to probiotics have varied in efficacy. Most likely the efficacy of probiotic bacteria has a multifactorial dependency, namely on a number of factors that include agents used, the dose, the pattern of dosing, and the characteristics of the host and the underlying luminal microbial environment and the activity of bacteriophages. Bacteriophages, are small viruses that infect and lyse intestinal bacteria. As such it can be posited that these viruses display an effective local protective control mechanism for the intestinal barrier against commensal pathobionts that indirectly may assist the host in controlling bacterial concentrations in the gut. A co-operative activity may be envisaged between the intestinal epithelia, mucosal immunity and the activity of bacteriophages to eliminate pathobiots, highlighting the potential role of bacteriophages in assisting with maintaining intestinal homeostasis. Hence bacteriophage local control of inflammation and immune responses may be an additional immunological defense mechanism that exploits bacteriophage–mucin glycoprotein interactions that controls bacterial diversity and abundance in the mucin layers of the gut. Moreover, and importantly the efficacy of probiotics may be dependent on the symbiotic incorporation of prebiotics, and the abundance and diversity of the intestinal microbiome encountered. The virome may be an important factor that determines the efficacy of some probiotic formulations.
Attitudes towards faecal immunochemical testing in patients at increased risk of colorectal cancer: an online survey of GPs in England

Background There is increasing interest in using a quantitative faecal immunochemical test (FIT) to rule out colorectal cancer (CRC) in patients with high-risk symptoms in primary care. Aim This study aimed to investigate GPs’ attitudes and willingness to use a FIT over an urgent 2-week wait (2WW) referral. Design and setting A cross-sectional online survey involving 1024 GPs working across England. Method Logistic regression models were used to explore the likelihood of GPs using a FIT instead of a 2WW referral, and reported using odds ratios (ORs) and 95% confidence intervals (95% CIs). Results Just over one-third of GPs (n = 365) preferred to use a FIT as a rule-out test over a 2WW referral. GPs were more willing if they were: aged 36–45 years (OR 1.59 [95% CI = 1.04 to 2.44]); 46–55 years (OR 1.99 [95% CI = 1.14 to 3.47]); thought a FIT was highly accurate (OR 1.63 [95% CI = 1.16 to 2.29]); thought patients would benefit compared with having a colonoscopy (OR 2.02 [95% CI = 1.46 to 2.79]); and were highly confident about discussing the benefits of a FIT (OR 2.14 [95% CI = 1.46 to 3.16]). GPs were less willing if they had had >10 urgent referrals in the past year (OR 0.62 [95% CI = 0.40 to 0.94]) and thought that longer consultations would be needed (OR 0.61 [95% CI = 0.44 to 0.83]). Conclusion The study findings suggest that the acceptability of using a FIT as a rule-out test in primary care is currently low, with less than half of GPs who perceived the test to be accurate preferring it over colonoscopy. Any potential guideline changes recommending a FIT in patients with high-risk symptoms, instead of urgent referral to rule out CRC, are likely to require intensive supporting educational outreach to increase GP confidence in the accuracy and application of a FIT in this context.
Modularizing and layering metamodels with the modular EMF designer

Metamodels are used in model-driven engineering and model-driven software development to define domain specific languages. Over time, they tend to evolve and grow in complexity to encompass new features. If a modular approach is not taken into account and metamodels are extended intrusively, they can become difficult to maintain and to extend. With the increased complexity, it often becomes even more challenging to modularize the metamodels. However, even though modularity is an established concept in the realm of software engineering, existing metamodeling tools barely address the challenges of modular metamodeling. In this work, we approach the problem from a graphical perspective. We propose a tool that assists the modeler in designing and refactoring metamodels in a modular way. It allows the modeler to explicitly organize metamodels in a layered architecture where each layer has a certain degree of abstraction. The tool detects cyclical dependencies between metamodels and violations to layering and provides key insights about how metamodels depend on each other. By that means, modular metamodeling is encouraged and modularizing metamodels is greatly facilitated.
Porphyrias and photosensitivity: pathophysiology for the clinician

ABSTRACT Porphyrias are disorders caused by defects in the biosynthetic pathway of heme. Their manifestations can be divided into three distinct syndromes, each attributable to the accumulation of three distinct classes of molecules. The acute neurovisceral syndrome is caused by the accumulation of the neurotoxic porphyrin precursors, delta aminolevulinic acid, and porphobilinogen; the syndrome of immediate painful photosensitivity is caused by the lipid-soluble protoporphyrin IX and, the syndrome of delayed blistering photosensitivity, caused by the water-soluble porphyrins, uroporphyrin, and coproporphyrin. Porphyrias can manifest with one, or with a combination, of these syndromes, depending on whether one or more types of molecules are being accumulated. Iron plays a significant role in some of these conditions, as evidenced by improvements in both clinical manifestations and laboratory parameters, following iron depletion in porphyria cutanea tarda, or iron administration in some cases of X-linked erythropoietic protoporphyria. While the pathophysiology of a specific type of porphyrias, the protoporphyrias, appears to favor the administration of zinc, results so far have been conflicting, necessitating further studies in order to assess its potential benefit. The pathways involved in each disease, as well as insights into their pathobiological processes are presented, with an emphasis on the development of photosensitivity reactions.
Eine Theorie sozial-normativer Mediennutzung

Mediennutzung findet heute mehr als früher im sozialen Raum statt: Erstens können Rezipientinnen und Rezipienten ihre eigenen Mediennutzungspräferenzen über soziale Netzwerkseiten (SNS), wie Facebook oder Twitter, darstellen (Good, 2013; Liu, 2007; Uski & Lampinen, 2016); zweitens können sie auf SNS beobachten, welche Medieninhalte ihre Freundinnen und Freunde gerne lesen, sehen und teilen (Pempek, Yermolayeva, & Calvert, 2009); und drittens können sie über SNS oder Instant Messaging-Dienste, wie WhatsApp, direkt mit ihren Freundinnen und Freunden interagieren (Pempek et al., 2009). Alle drei Spezifika der Medienentwicklung verweisen auf die Bedeutung sozialer Normen (Johnson, 2014): Die Möglichkeit der medialen Sichtbarmachung von Mediennutzungspräferenzen macht diese anfälliger für den Einfluss sozialer Normen (Uski & Lampinen, 2016), die Beobachtung der Mediennutzung von Bezugspersonen beeinflusst die Bildung sozialer Normen (Litt & Stock, 2011; Walther et al., 2010) und die medial vermittelte soziale Interaktion stellt in ihrer massenhaften Verbreitung einen neuen Gegenstand der Mediennutzung dar, der von einer Betrachtung aus sozial-normativer Perspektive profitiert. Angesichts dieser Medienentwicklungen drängt sich die Frage auf, wie soziale Normen und Mediennutzung zusammenhängen und ob soziale Normen für unterschiedliche Arten von Mediennutzung unterschiedlich (stark) wirken. Diese Frage ist umso relevanter, als gängige Mediennutzungstheorien, wie das SESAM1-Modell (Knobloch-Westerwick, 2015), der Uses-and-Gratifications-Ansatz (U&G; Katz, Blumler, & Gurevitch, 1973) oder die Social Cognitive Theory of Media Selection (SCT; LaRose, 2009; LaRose & Eastin, 2004), sozial-normative Einflussfaktoren nur indirekt modellieren. Sie berücksichtigen zwar soziale Konzepte, wie die so-
Observations on Madness and Melancholy, &c.

"T^he first edition of this excellent work was published in 1798. *It has been held in such high estimation by the profession, (as its intrinsic merits deserved), that the intelligent author has been induced to submit the present edition to the public notice, as a corrected copy of the former, though it is enriched with considerable additions, which the extensive scope of Bethlem Hospital has furnished, and with remarks which a cultivated
Vulnerability of Amazonian forests to repeated droughts

Extreme droughts have been recurrent in the Amazon over the past decades, causing socio-economic and environmental impacts. Here, we investigate the vulnerability of Amazonian forests, both undisturbed and human-modified, to repeated droughts. We defined vulnerability as a measure of (i) exposure, which is the degree to which these ecosystems were exposed to droughts, and (ii) its sensitivity, measured as the degree to which the drought has affected remote sensing-derived forest greenness. The exposure was calculated by assessing the meteorological drought, using the standardized precipitation index (SPI) and the maximum cumulative water deficit (MCWD), which is related to vegetation water stress, from 1981 to 2016. The sensitivity was assessed based on the enhanced vegetation index anomalies (AEVI), derived from the newly available Moderate Resolution Imaging Spectroradiometer (MODIS)/Multi-Angle Implementation of Atmospheric Correction algorithm (MAIAC) product, from 2003 to 2016, which is indicative of forest's photosynthetic capacity. We estimated that 46% of the Brazilian Amazon biome was under severe to extreme drought in 2015/2016 as measured by the SPI, compared with 16% and 8% for the 2009/2010 and 2004/2005 droughts, respectively. The most recent drought (2015/2016) affected the largest area since the drought of 1981. Droughts tend to increase the variance of the photosynthetic capacity of Amazonian forests as based on the minimum and maximum AEVI analysis. However, the area showing a reduction in photosynthetic capacity prevails in the signal, reaching more than 400 000 km2 of forests, four orders of magnitude larger than areas with AEVI enhancement. Moreover, the intensity of the negative AEVI steadily increased from 2005 to 2016. These results indicate that during the analysed period drought impacts were being exacerbated through time. Forests in the twenty-first century are becoming more vulnerable to droughts, with larger areas intensively and negatively responding to water shortage in the region. This article is part of a discussion meeting issue ‘The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications’.
Experimental validation of the suitability of virtualization-based replication for fault tolerance in real-time control of electric grids

Real-time control systems (RTCSs) perform complex control and require low response times. They typically use third-party software libraries and are deployed on generic hardware, which suffer from delay faults that can cause serious damage. To improve availability and latency, the controllers in RTCSs are replicated on physical nodes. As physical replication is expensive, we study the alternative of exploiting virtualization technology to run multiple virtual replicas on the same physical node. As virtual replicas share the same resources, the delay faults they experience might be correlated, which would make such a replication method unsuitable. We conduct several experiments with an RTCS for electric grids, with multiple virtual replicas of its controller. We find that although the delay of a virtual machine is higher than of a physical machine, the correlation between high delays among the virtual replicas is insignificant, causing an overall improved availability. We conclude that virtual replication is indeed applicable to certain RTCSs, as it can improve reliability without added cost.