Precondition Inference via Partitioning of Initial States

Precondition inference is a non-trivial task with several applications in program analysis and verification. We present a novel iterative method for automatically deriving sufficient preconditions for safety and unsafety of programs which introduces a new dimension of modularity. Each iteration maintains over-approximations of the set of \emph{safe} and \emph{unsafe} \emph{initial} states. Then we repeatedly use the current abstractions to partition the program's \emph{initial} states into those known to be safe, known to be unsafe and unknown, and construct a revised program focusing on those initial states that are not yet known to be safe or unsafe. An experimental evaluation of the method on a set of software verification benchmarks shows that it can solve problems which are not solvable using previous methods.Comment: 19 pages, 8 figure

Karlstadter Positionspapier zum Schutz der Ackerwildkräuter. Erarbeitet von den Teilnehmerinnen und Teilnehmern der "Tagung zum Schutz der Ackerwildflora" am 25./26.6.2004 in Karlstadt am Main

Der Erhalt von Ackerwildkräutern, die historisch erst mit der Landbewirtschaftung in Mitteleuropa heimisch geworden sind, ist eine Kulturaufgabe, damit auch künftige Generationen die Arten- und Farbenvielfalt in der Kulturlandschaft erleben können

The impact of COVID-19 infection, the pandemic and its associated control measures on patients with Pompe disease

Background: Patients with Pompe disease, a rare metabolic myopathy, were thought to be at increased risk of severe COVID-19 disease during the pandemic. In addition, the lockdown may have affected their regular treatment. Objective: To assess the perceived effect of COVID-19 infection and of the pandemic on the treatment, and physical and mental health of patients with Pompe disease. Methods: Patients with Pompe disease over 16 years of age participated in an international, cross-sectional, online survey (September 20, 2022–November 7, 2022). The questionnaire, available in eight languages, consisted of 89 questions divided into 3 parts: (A) severity of Pompe disease, (B) COVID-19 precautions and infection(s) and (C) effects of the COVID-19 pandemic. Results: Among 342 respondents, originating from 25 different countries, 47.6% experienced one or more COVID-19 infections. While most recovered within 4 weeks (69.7%) and only eight patients needed to be admitted to the hospital, 42.2% of patients experienced an impact of the infection on their overall condition, respiratory status and/or mobility status. More severely affected patients took more stringent control measures. The pandemic additionally caused interruptions in medical care in many patients (56.0%) and 17.2% of patients experienced interruptions of enzyme replacement therapy. The pandemic also affected many patients’ disease severity (27.7%), mental health (55.4%) and feeling of loneliness (43.4%). Conclusion: COVID-19 infection(s) and the pandemic affected the treatment, physical health and mental health of patients with Pompe disease, emphasizing the importance of continued patient centered care during a difficult time such as the COVID-19 pandemic.</p

Why are the 2-oxoacid dehydrogenase complexes so large? Generation of an active trimeric complex

The four-component polypeptides of the 2-oxoacid dehydrogenase complex from the thermophilic archaeon Thermoplasma acidophilum assemble to give an active multienzyme complex possessing activity with the branched-chain 2-oxoacids derived from leucine, isoleucine and valine, and with pyruvate. The dihydrolipoyl acyl-transferase (E2) core of the complex is composed of identical trimer-forming units that assemble into a novel 42-mer structure comprising octahedral and icosahedral geometric aspects. From our previously determined structure of this catalytic core, the inter-trimer interactions involve a tyrosine residue near the C-terminus secured in a hydrophobic pocket of an adjacent trimer like a ball-and-socket joint. In the present study, we have deleted the five C-terminal amino acids of the E2 polypeptide (IIYEI) and shown by equilibrium centrifugation that it now only assembles into a trimeric enzyme. This was confirmed by SAXS analysis, although this technique showed the presence of approximately 20% hexamers. The crystal structure of the trimeric truncated E2 core has been determined and shown to be virtually identical with the ones observed in the 42-mer, demonstrating that removal of the C-terminal anchor does not significantly affect the individual monomer or trimer structures. The truncated E2 is still able to bind both 2-oxoacid decarboxylase (E1) and dihydrolipoamide dehydrogenase (E3) components to give an active complex with catalytic activity similar to the native multienzyme complex. This is the first report of an active mini-complex for this enzyme, and raises the question of why all 2-oxoacid dehydrogenase complexes assemble into such large structures.</jats:p

First Cultivation and Characterization of Mycobacterium ulcerans from the Environment

Mycobacterium ulcerans infection, or Buruli ulcer, is the third most common mycobacteriosis of humans worldwide, after tuberculosis and leprosy. Buruli ulcer is a neglected, devastating, necrotizing disease, sometimes producing massive, disfiguring ulcers, with huge social impact. Buruli ulcer occurs predominantly in impoverished, humid, tropical, rural areas of Africa, where the incidence has been increasing, surpassing tuberculosis and leprosy in some regions. Besides being a disease of the poor, Buruli ulcer is a poverty-promoting chronic infectious disease. There is strong evidence that M. ulcerans is not transmitted person to person but is an environmental pathogen transmitted to humans from its aquatic niches. However, until now M. ulcerans has not been isolated in pure culture from environmental sources. This manuscript describes the first isolation, to our knowledge, of M. ulcerans in pure culture from an environmental source. This strain, which is highly virulent for mice, has microbiological features typical of African strains of M. ulcerans and was isolated from an aquatic insect from a Buruli ulcer–endemic area in Benin, West Africa. Our findings support the concept that M. ulcerans is a pathogen of humans with an aquatic environmental niche and will have positive consequences for the control of this neglected and socially important tropical disease

Benchmarked performance charts using principal components analysis to improve the effectiveness of feedback for audit data in HIV care

Abstract Background Feedback tools for clinical audit data that compare site-specific results to average performance over all sites can be useful for quality improvement. Proposed tools should be simple and clearly benchmark the site’s performance, so that a relevant action plan can be directly implemented to improve patient care services. We aimed to develop such a tool in order to feedback data to UK HIV clinics participating in the 2015 British HIV Association (BHIVA) audit assessing compliance with the 2011 guidelines for routine investigation and monitoring of adult HIV-1- infected individuals. Methods HIV clinic sites were asked to provide data on a random sample of 50–100 adult patients attending for HIV care during 2014 and/or 2015 by completing a self-audit spreadsheet. Outcomes audited included the proportion of patients with recorded resistance testing, viral load monitoring, adherence assessment, medications, hepatitis testing, vaccination management, risk assessments, and sexual health screening. For each outcome we benchmarked the proportion for a specific site against the average performance. We produced performance charts for each site using boxplots for the outcomes. We also used the mean and differences from the mean performance to produce a dashboard for each site. We used principal components analysis to group correlated outcomes and simplify the dashboard. Results The 106 sites included in the study provided information on a total of 7768 patients. Outcomes capturing monitoring of treatment of HIV-infection showed high performance across the sites, whereas testing for hepatitis, and risk assessment for cardiovascular disease and smoking, management of flu vaccination, sexual health screening, and cervical cytology for women were very variable across sites. The principal components analysis reduced the original 12 outcomes to four factors that represented HIV care, hepatitis testing, other screening tests, and resistance testing. These provided simplified measures of adherence to guidelines which were presented as a 4 bar dashboard of performance. Conclusion Our dashboard performance charts provide easily digestible visual summaries of locally relevant audit data that are benchmarked against the overall mean and can be used to improve feedback to HIV services. Feedback from clinicians indicated that they found these charts acceptable and useful