Ischemic preconditioning attenuates portal venous plasma concentrations of purines following warm liver ischemia in man

Background/Aims: Degradation of adenine nucleotides to adenosine has been suggested to play a critical role in ischemic preconditioning (IPC). Thus, we questioned in patients undergoing partial hepatectomy whether (i) IPC will increase plasma purine catabolites and whether (ii) formation of purines in response to vascular clamping (Pringle maneuver) can be attenuated by prior IPC. Methods: 75 patients were randomly assigned to three groups: group I underwent hepatectomy without vascular clamping; group II was subjected to the Pringle maneuver during resection, and group III was preconditioned (10 min ischemia and 10 min reperfusion) prior to the Pringle maneuver for resection. Central, portal venous and arterial plasma concentrations of adenosine, inosine, hypoxanthine and xanthine were determined by high-performance liquid chromatography. Results: Duration of the Pringle maneuver did not differ between patients with or without IPC. Surgery without vascular clamping had only a minor effect on plasma purine transiently increased. After the Pringle maneuver alone, purine plasma concentrations were most increased. This strong rise in plasma purines caused by the Pringle maneuver, however, was significantly attenuated by IPC. When portal venous minus arterial concentration difference was calculated for inosine or hypoxanthine, the respective differences became positive in patients subjected to the Pringle maneuver and were completely prevented by preconditioning. Conclusion: These data demonstrate that (i) IPC increases formation of adenosine, and that (ii) the unwanted degradation of adenine nucleotides to purines caused by the Pringle maneuver can be attenuated by IPC. Because IPC also induces a decrease of portal venous minus arterial purine plasma concentration differences, IPC might possibly decrease disturbances in the energy metabolism in the intestine as well. Copyright (C) 2005 S. Karger AG, Basel

SMT-based Model Checking for Recursive Programs

We present an SMT-based symbolic model checking algorithm for safety verification of recursive programs. The algorithm is modular and analyzes procedures individually. Unlike other SMT-based approaches, it maintains both "over-" and "under-approximations" of procedure summaries. Under-approximations are used to analyze procedure calls without inlining. Over-approximations are used to block infeasible counterexamples and detect convergence to a proof. We show that for programs and properties over a decidable theory, the algorithm is guaranteed to find a counterexample, if one exists. However, efficiency depends on an oracle for quantifier elimination (QE). For Boolean Programs, the algorithm is a polynomial decision procedure, matching the worst-case bounds of the best BDD-based algorithms. For Linear Arithmetic (integers and rationals), we give an efficient instantiation of the algorithm by applying QE "lazily". We use existing interpolation techniques to over-approximate QE and introduce "Model Based Projection" to under-approximate QE. Empirical evaluation on SV-COMP benchmarks shows that our algorithm improves significantly on the state-of-the-art.Comment: originally published as part of the proceedings of CAV 2014; fixed typos, better wording at some place

Corynebacterium lipophiloflavum sp. nov. isolated from a patient with bacterial vaginosis

A unique coryneform bacterium was isolated from a patient with bacterial vaginosis. Chemotaxonomical investigations demonstrated that the unknown bacterium belonged to the genus Corynebacterium. The yellow-pigmented, slightly lipophilic, oxidative, urea-hydrolyzing bacterium could be phenotypically readily differentiated from the other members of the genus Corynebacterium. Comparative 16S rRNA gene analysis revealed that the bacterium represented a new subline within the genus Corynebacterium for which the name Corynebacterium lipophiloflavum sp. nov. is proposed. The type strain is CCUG 37336 (DSM 44291

Efficient Interpolation for the Theory of Arrays

Existing techniques for Craig interpolation for the quantifier-free fragment of the theory of arrays are inefficient for computing sequence and tree interpolants: the solver needs to run for every partitioning $(A, B)$ of the interpolation problem to avoid creating $AB$-mixed terms. We present a new approach using Proof Tree Preserving Interpolation and an array solver based on Weak Equivalence on Arrays. We give an interpolation algorithm for the lemmas produced by the array solver. The computed interpolants have worst-case exponential size for extensionality lemmas and worst-case quadratic size otherwise. We show that these bounds are strict in the sense that there are lemmas with no smaller interpolants. We implemented the algorithm and show that the produced interpolants are useful to prove memory safety for C programs.Comment: long version of the paper at IJCAR 201

Differentially Testing Soundness and Precision of Program Analyzers

In the last decades, numerous program analyzers have been developed both by academia and industry. Despite their abundance however, there is currently no systematic way of comparing the effectiveness of different analyzers on arbitrary code. In this paper, we present the first automated technique for differentially testing soundness and precision of program analyzers. We used our technique to compare six mature, state-of-the art analyzers on tens of thousands of automatically generated benchmarks. Our technique detected soundness and precision issues in most analyzers, and we evaluated the implications of these issues to both designers and users of program analyzers

Using a runway paradigm to assess the relative strength of rats' motivations for enrichment objects

Laboratory animals should be provided with enrichment objects in their cages; however, it is first necessary to test whether the proposed enrichment objects provide benefits that increase the animals’ welfare. The two main paradigms currently used to assess proposed enrichment objects are the choice test, which is limited to determining relative frequency of choice, and consumer demand studies, which can indicate the strength of a preference but are complex to design. Here, we propose a third methodology: a runway paradigm, which can be used to assess the strength of an animal’s motivation for enrichment objects, is simpler to use than consumer demand studies, and is faster to complete than typical choice tests. Time spent with objects in a standard choice test was used to rank several enrichment objects in order to compare with the ranking found in our runway paradigm. The rats ran significantly more times, ran faster, and interacted longer with objects with which they had previously spent the most time. It was concluded that this simple methodology is suitable for measuring rats’ motivation to reach enrichment objects. This can be used to assess the preference for different types of enrichment objects or to measure reward system processes

Efficacy of tigecycline for the treatment of complicated intraabdominal infections in real-life clinical practice from five european observational studies

Objectives: Tigecycline is a broad-spectrum antibiotic approved for the treatment of complicated intra-abdominal infections (cIAIs). The efficacy of tigecycline when administered as monotherapy or in combination with other antibacterials in the treatment of cIAIs in routine clinical practice is described. Patients and methods: Individual patient-level data were pooled from five European observational studies (July 2006 to October 2011). Results: A total of 785 cIAI patients who received tigecycline were included (mean age 63.1+14.0 years). Of these, 56.6% were in intensive care units, 65.6% acquired their infection in hospital, 88.1% had at least one comorbidity and 65.7% had secondary peritonitis. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores at the beginning of treatment were 16.9+7.6 (n=614) and 7.0+4.2 (n=108), respectively, indicating high disease severity. Escherichia coli (41.8%), Enterococcus faecium (40.1%) and Enterococcus faecalis (21.1%) were the most frequently isolated pathogens; 49.1% of infections were polymicrobial and 17.5% were due to resistant pathogens. Overall, 54.8% (n=430) received tigecycline as monotherapy and 45.2% (n=355) as combination therapy for a mean duration of 10.6 days. Clinical response rates at the end of treatment were 77.4% for all patients (567/733), 80.6% for patients who received tigecycline as monotherapy (329/408), 75.2% for patients with a nosocomial infection (354/471), 75.8% for patients with an APACHE II score .15 (250/330) and 54.2% (32/59) for patients with a SOFA score =7. Conclusions: In these real-life studies, tigecycline, alone and in combination, achieved favourable clinical response rates in patients with cIAI with a high severity of illness

Corynebacterium lipophiloflavum sp. nov. isolated from a patient with bacterial vaginosis

A unique coryneform bacterium was isolated from a patient with bacterial vaginosis. Chemotaxonomical investigations demonstrated that the unknown bacterium belonged to the genus Corynebacterium. The yellow-pigmented, slightly lipophilic, oxidative, urea-hydrolyzing bacterium could be phenotypically readily differentiated from the other members of the genus Corynebacterium. Comparative 16S rRNA gene analysis revealed that the bacterium represented a new subline within the genus Corynebacterium for which the name Corynebacterium lipophiloflavum sp. nov. is proposed. The type strain is CCUG 37336 (DSM 44291

Urinary tract infection in men

Uri nary tract in fec tion in men Ab stract. Ob jec tive: To ex plore the prev alence and mi cro bi ol ogy of uri nary tract in fection (UTI) in symp tom atic men in a pri mary care set ting and to de ter mine the ap pro pri ateness of pa tient man age ment of these con ditions by the gen eral prac ti tio ners. Meth ods: A cross-sec tional sur vey was car ried out matching doc u men ta tion of symp toms and man agement with urine cul ture and re sults of sus cep tibil ity tests. All pa tients pre sent ing with symptoms typ i cal for a UTI in 36 teach ing gen eral prac tices in the area of Göttingen, Ger many, were el i gi ble for en rol ment in the study. 15% (n = 90) of all pa tients were adult men. Gen eral prac ti tio ners (GPs) were in structed to man age pa tients as usual. Pa tient char ac ter is tics, dipstick tests and treat ment were matched with results of urine cul tures and sus cep ti bil ity testing. Re sults: Men pre sent ing with symp toms in dic a tive of UTI were pre dom i nantly el derly (me dian age 61 years) and 41% had ad di tional risk fac tors. An ti bi ot ics were pre scribed for 36%, but these were not well-tar geted. Urine cul ture re vealed UTI in 60%, of which half had low col ony counts (23% of all pa tients) or multi ple bac te rial growth (7%); 40% had ster ile urine. Dip stick tests proved un help ful: leu kocytes and ni trite had sen si tiv i ties of 54% and 38%, specificities of 55% and 84%, pos i tive pre dic tive val ues of 65% and 78% and neg ative pre dic tive val ues of 44% and 46%, re spectively. Re sis tance lev els were 53% for amoxicillin and cefaclor, 28% for cefixim, 22% for ciprofloxacin, 34% for both trimethoprim as in di vid ual sub stance and the com bi na tion with sulfamethoxazole (cotrimoxazole) and 25% for ni tro fu ran toin. Con clusion: Men with symp toms in dic a tive of a UTI should not be treated em pir i cally. A urine culture and antibiogram should be ob tained before a treat ment de ci sion is made. A low-count UTI was com mon and should not be con sidered nor mal