Trovafloxacin in treatment of rabbits with experimental meningitis caused by high-level penicillin-resistant Streptococcus pneumoniae

The fluoroquinolone trovafloxacin was bactericidal (0.47 +/- 0.23 delta log10 CFU/ml x h after 10 mg/kg of body weight and 0.78 +/- 0.15 delta log10 CFU/ml x h after 30 mg/kg) in the treatment of experimental meningitis caused by a highly penicillin-resistant (MIC and minimum bactericidal concentration = 4 and 4 microg/ml) strain of Streptococcus pneumoniae. Combinations with ampicillin and rifampin were indifferent compared to single drugs.

High level of extracellular potassium and its correlates after severe head injury: relationship to high intracranial pressure

OBJECT: Disturbed ionic and neurotransmitter homeostasis are now recognized as probably the most important mechanisms contributing to the development of secondary brain swelling after traumatic brain injury (TBI). Evidence obtained in animal models indicates that posttraumatic neuronal excitation by excitatory amino acids leads to an increase in extracellular potassium, probably due to ion channel activation. The purpose of this study was therefore to measure dialysate potassium in severely head injured patients and to correlate these results with measurements of intracranial pressure (ICP), patient outcome, and levels of dialysate glutamate and lactate, and cerebral blood flow (CBF) to determine the role of ischemia in this posttraumatic ion dysfunction. METHODS: Eighty-five patients with severe TBI (Glasgow Coma Scale Score < 8) were treated according to an intensive ICP management-focused protocol. All patients underwent intracerebral microdialyis. Dialysate potassium levels were analyzed using flame photometry, and dialysate glutamate and dialysate lactate levels were measured using high-performance liquid chromatography and an enzyme-linked amperometric method in 72 and 84 patients, respectively. Cerebral blood flow studies (stable xenon computerized tomography scanning) were performed in 59 patients. In approximately 20% of the patients, dialysate potassium values were increased (dialysate potassium > 1.8 mM) for 3 hours or more. A mean amount of dialysate potassium greater than 2 mM throughout the entire monitoring period was associated with ICP above 30 mm Hg and fatal outcome, as were progressively rising levels of dialysate potassium. The presence of dialysate potassium correlated positively with dialysate glutamate (p < 0.0001) and lactate (p < 0.0001) levels. Dialysate potassium was significantly inversely correlated with reduced CBF (p = 0.019). CONCLUSIONS: Dialysate potassium was increased after TBI in 20% of measurements. High levels of dialysate potassium were associated with increased ICP and poor outcome. The simultaneous increase in dialysate potassium, together with dialysate glutamate and lactate, supports the concept that glutamate induces ionic flux and consequently increases ICP, which the authors speculate may be due to astrocytic swelling. Reduced CBF was also significantly correlated with increased levels of dialysate potassium. This may be due to either cell swelling or altered vasoreactivity in cerebral blood vessels caused by higher levels of potassium after trauma. Additional studies in which potassium-sensitive microelectrodes are used are needed to validate these ionic events more clearly.

PyGirl Generating Whole-System VMs from high-level models using PyPy

Virtual machines emulating hardware devices are generally implemented in low-level languages and using a low-level style for performance reasons. This trend results in largely difficult to understand, difficult to extend and unmaintainable systems. As new general techniques for virtual machines arise, it gets harder to incorporate or test these techniques because of early design and optimization decisions. In this paper we show how such decisions can be postponed to later phases by separating virtual machine implementation issues from the high-level machine-specific model. We construct compact models of whole-system VMs in a high-level language, which exclude all low-level implementation details. We use the pluggable translation toolchain PyPy to translate those models to executables. During the translation process, the toolchain reintroduces the VM implementation and optimization details for specific target platforms. As a case study we implement an executable model of a hardware gaming device. We show that our approach to VM building increases understandability, maintainability and extendability while preserving performance.

PyGirl: Generating Whole-System VMs from High-Level Prototypes Using PyPy

Virtual machines (VMs) emulating hardware devices are generally implemented in low-level languages for performance reasons. This results in unmaintainable systems that are difficult to understand. In this paper we report on our experience using the PyPy toolchain to improve the portability and reduce the complexity of whole-system VM implementations. As a case study we implement a VM prototype for a Nintendo Game Boy, called PyGirl, in which the high-level model is separated from low-level VM implementation issues. We shed light on the process of refactoring from a low-level VM implementation in Java to a high-level model in RPython. We show that our whole-system VM written with PyPy is significantly less complex than standard implementations, without substantial loss in performance.

High level methods for scene exploration

Virtual worlds exploration techniques are used in a wide variety of domains — from graph drawing to robot motion. This paper is dedicated to virtual world exploration techniques which have to help a human being to understand a 3D scene. An improved method of viewpoint quality estimation is presented in the paper, together with a new off-line method for automatic 3D scene exploration, based on a virtual camera. The automatic exploration method is working in two steps. In the first step, a set of “good” viewpoints is computed. The second step uses this set of points of view to compute a camera path around the scene. Finally, we define a notion of semantic distance between objects of the scene to improve the approach.

High-Level Modeling of Multimodal Interaction Techniques Using NiMMiT

The past few years, multimodal interaction has been gaining importance in virtual environments. Although multimodality renders interacting with an environment more natural and intuitive, the development cycle of such an application is often long and expensive. In our overall field of research, we investigate how modelbased design can facilitate the development process by designing environments through the use of highlevel diagrams. In this scope, we present ‘NiMMiT’, a graphical notation for expressing and evaluating multimodal user interaction; we elaborate on the NiMMiT primitives and demonstrate its use by means of a comprehensive example.

Possible role of Cdx2 in the serrated pathway of colorectal cancer characterized by BRAF mutation, high-level CpG Island methylator phenotype and mismatch repair-deficiency

Colorectal cancer is a heterogeneous disease at the histomorphological, clinical and molecular level. Approximately 20% of cases may progress through the "serrated" pathway characterized by BRAF mutation and high-level CpG Island Methylator Phenotype (CIMP). A large subgroup are additionally microsatellite instable (MSI) and demonstrate significant loss of tumor suppressor Cdx2. The aim of this study is to determine the specificity of Cdx2 protein expression and CpG promoter hypermethylation for BRAF(V600E) and high-level CIMP in colorectal cancer. Cdx2, Mlh1, Msh2, Msh6, and Pms2 were analyzed by immunohistochemistry using a multi-punch tissue microarray (TMA; n = 220 patients). KRAS and BRAF(V600E) mutation analysis, CDX2 methylation and CIMP were investigated. Loss of Cdx2 was correlated with larger tumor size (P = 0.0154), right-sided location (P = 0.0014), higher tumor grade (P < 0.0001), more advanced pT (P = 0.0234) and lymphatic invasion (P = 0.0351). Specificity was 100% for mismatch repair (MMR)-deficiency (P < 0.0001), 92.2% (P < 0.0001) for BRAF(V600E) and 91.8% for CIMP-high. Combined analysis of BRAF(V600E) /CIMP identified Cdx2 loss as sensitive (80%) and specific (91.5%) for mutation/high status. These results were validated on eight well-established colorectal cancer cell lines. CDX2 methylation correlated with BRAF(V600E) (P = 0.0184) and with Cdx2 protein loss (P = 0.0028). These results seem to indicate that Cdx2 may play a role in the serrated pathway to colorectal cancer as underlined by strong relationships with BRAF(V600E) , CIMP-high and MMR-deficiency. Whether this protein can only be used as a "surrogate" marker, or is functionally involved in the progression of these tumors remains to be elucidated.

Glacial Lake Wright, a High-Level Antarctic Lake During the LGM and Early Holocene

We report evidence of a large proglacial lake (Glacial Lake Wright) that existed in Wright Valley in the McMurdo Dry Valleys region of Antarctica at the last glacial maximum (LGM) and in the early Holocene. At its highstands, Glacial Lake Wright would have stretched 50 km and covered c. 210 km(2). Chronology for lake-level changes comes from 30 AMS radiocarbon dates of lacustrine algae preserved in deltas, shorelines, and glaciolacustrine deposits that extend up to 480 m above present-day lakes. Emerging evidence suggests that Glacial Lake Wright was only one of a series of large lakes to occupy the McMurdo Dry Valleys and the valleys fronting the Royal Society Range at the LGM. Although the cause of such high lake levels is not well understood, it is believed to relate to cool, dry conditions which produced fewer clouds, less snowfall, and greater amounts of absorbed radiation, leading to increased meltwater production.

Chromosomally and extrachromosomally mediated high-level gentamicin resistance in Streptococcus agalactiae

Streptococcus agalactiae (group B Streptococcus, GBS) is a leading cause of sepsis in neonates. The rate of invasive GBS disease in non-pregnant adults also continues to climb. Aminoglycosides alone have little or no effect on GBS, but synergistic killing with penicillin has been shown in vitro. High-level gentamicin resistance (HLGR) in GBS isolates, however, leads to loss of a synergistic effect. We therefore performed a multicentre study to determine the frequency of HLGR GBS isolates and to elucidate the molecular mechanisms leading to gentamicin resistance. From eight centres in four countries, 1128 invasive and colonizing GBS isolates were pooled and investigated for the presence of HLGR. We identified two strains that displayed HLGR (BSU1203 and BSU452), both of which carried the aacA-aphD gene, typically conferring HLGR. Though, only one strain (BSU1203) also carried the previously described chromosomal gentamicin resistance transposon, designated Tn3706. In the other strain (BSU452), plasmid purification and subsequent DNA sequencing resulted in the detection of plasmid pIP501 carrying a remnant of a Tn3 family transposon. Its ability to confer HLGR was proven by transfer into an Enterococcus faecalis isolate. Conversely, loss of HLGR was documented after curing both GBS BSU452 and the transformed E. faecalis strain from the plasmid. This is the first report showing a plasmid mediated HLGR in GBS. Thus, in our clinical GBS isolates HLGR is mediated both chromosomally and extrachromosomally.

High-level characteristics of or-and independent and-parallelism in prolog

Although studies of a number of parallel implementations of logic programming languages are now available, their results are difficult to interpret due to the multiplicity of factors involved, the effect of each of which is difficult to sepárate. In this paper we present the results of a high-level simulation study of or- and independent and-parallelism with a wide selection of Prolog programs that aims to determine the intrinsic amount of parallelism, independently of implementation factors, thus facilitating this separation. We expect this study will be instrumental in better understanding and comparing results from actual implementations, as shown by some examples provided in the paper. In addition, the paper examines some of the issues and tradeoffs associated with the combination of and- and or-parallelism and proposes reasonable solutions based on the simulation data obtained.

Towards high-level execution primitives for and-parallelism: preliminary results

Most implementations of parallel logic programming rely on complex low-level machinery which is arguably difflcult to implement and modify. We explore an alternative approach aimed at taming that complexity by raising core parts of the implementation to the source language level for the particular case of and-parallelism. Therefore, we handle a signiflcant portion of the parallel implementation mechanism at the Prolog level with the help of a comparatively small number of concurrency-related primitives which take care of lower-level tasks such as locking, thread management, stack set management, etc. The approach does not eliminate altogether modiflcations to the abstract machine, but it does greatly simplify them and it also facilitates experimenting with different alternatives. We show how this approach allows implementing both restricted and unrestricted (i.e., non fork-join) parallelism. Preliminary experiments show that the amount of performance sacriflced is reasonable, although granularity control is required in some cases. Also, we observe that the availability of unrestricted parallelism contributes to better observed speedups.