Plasma and cerebrospinal fluid concentrations of linezolid in neurosurgical critically ill patients with proven or suspected central nervous system infections

Linezolid is a valuable treatment option for central nervous system (CNS) infections caused by multidrug-resistant Gram-positive micro-organisms. Data regarding its penetration into the CNS have shown wide variability. The aim of this study was to describe the population pharmacokinetics of linezolid in plasma and cerebrospinal fluid (CSF) in critically ill patients with external CSF drainage and proven or suspected CNS infections. This was an observational pharmacokinetic (PK) study in 11 critically ill patients with proven or suspected CNS infection receiving linezolid. Serial blood and CSF samples were taken and were subject to population PK analysis. The median (interquartile range) of AUC(0-12h) was 47.6 (17.9-58.6) mg h/L in plasma and 21.1(18.8-30.4) mg h/L in CSF, with a median CSF/plasma ratio of 0.77. At pre-dose at steady state, a strong positive correlation was observed between linezolid concentrations in CSF and plasma (Spearman's rho = 0.758; P = 0.011). For a minimum inhibitory concentration (MIC) of 2 mg/L, the median AUC(0-24h)/MIC values in plasma and CSF wer

An artificial intelligence method using FDG PET to predict treatment outcome in diffuse large B cell lymphoma patients

Convolutional neural networks (CNNs) may improve response prediction in diffuse large B-cell lymphoma (DLBCL). The aim of this study was to investigate the feasibility of a CNN using maximum intensity projection (MIP) images from 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) baseline scans to predict the probability of time-to-progression (TTP) within 2 years and compare it with the International Prognostic Index (IPI), i.e. a clinically used score. 296 DLBCL 18F-FDG PET/CT baseline scans collected from a prospective clinical trial (HOVON-84) were analysed. Cross-validation was performed using coronal and sagittal MIPs. An external dataset (340 DLBCL patients) was used to validate the model. Association between the probabilities, metabolic tumour volume and Dmaxbulk was assessed. Probabilities for PET scans with synthetically removed tumors were also assessed. The CNN provided a 2-year TTP prediction with an area under the curve (AUC) of 0.74, outperforming the IPI-based model (AUC = 0.68). Furthermore, high probabilities (> 0.6) of the original MIPs were considerably decreased after removing the tumours (< 0.4, generally). These findings suggest that MIP-based CNNs are able to predict treatment outcome in DLBCL

Systematic review: conservative treatments for secondary lymphedema

<p>Abstract</p> <p>Background</p> <p>Several conservative (i.e., nonpharmacologic, nonsurgical) treatments exist for secondary lymphedema. The optimal treatment is unknown. We examined the effectiveness of conservative treatments for secondary lymphedema, as well as harms related to these treatments.</p> <p>Methods</p> <p>We searched MEDLINE^®, EMBASE^®, Cochrane Central Register of Controlled Trials^®, AMED, and CINAHL from 1990 to January 19, 2010. We obtained English- and non-English-language randomized controlled trials or observational studies (with comparison groups) that reported primary effectiveness data on conservative treatments for secondary lymphedema. For English-language studies, we extracted data in tabular form and summarized the tables descriptively. For non-English-language studies, we summarized the results descriptively and discussed similarities with the English-language studies.</p> <p>Results</p> <p>Thirty-six English-language and eight non-English-language studies were included in the review. Most of these studies involved upper-limb lymphedema secondary to breast cancer. Despite lymphedema's chronicity, lengths of follow-up in most studies were under 6 months. Many trial reports contained inadequate descriptions of randomization, blinding, and methods to assess harms. Most observational studies did not control for confounding. Many studies showed that active treatments reduced the size of lymphatic limbs, although extensive between-study heterogeneity in areas such as treatment comparisons and protocols, and outcome measures, prevented us from assessing whether any one treatment was superior. This heterogeneity also precluded us from statistically pooling results. Harms were rare (< 1% incidence) and mostly minor (e.g., headache, arm pain).</p> <p>Conclusions</p> <p>The literature contains no evidence to suggest the most effective treatment for secondary lymphedema. Harms are few and unlikely to cause major clinical problems.</p

Tumour antigen expression in hepatocellular carcinoma in a low-endemic western area

Background: Identification of tumour antigens is crucial for the development of vaccination strategies against hepatocellular carcinoma (HCC). Most studies come from eastern-Asia, where hepatitis-B is the main cause of HCC. However, tumour antigen expression is poorly studied in low-endemic, western areas where the aetiology of HCC differs. Methods: We constructed tissue microarrays from resected HCC tissue of 133 patients. Expression of a comprehensive panel of cancer-testis (MAGE-A1, MAGE-A3/4, MAGE-A10, MAGE-C1, MAGE-C2, NY-ESO-1, SSX-2, sperm protein 17), onco-fetal (AFP, Glypican-3) and overexpressed tumour antigens (Annexin-A2, Wilms tumor-1, Survivin, Midkine, MUC-1) was determined by immunohistochemistry. Results: A higher prevalence of MAGE antigens was observed in patients with hepatitis-B. Patients with expression of more tumour antigens in general had better HCC-specific survival (P=0.022). The four tumour antigens with high expression in HCC and no, or weak, expression in surrounding tumour-free-liver tissue, were Annexin-A2, GPC-3, MAGE-C1 and MAGE-C2, expressed in 90, 39, 17 and 20% of HCCs, respectively. Ninety-five percent of HCCs expressed at least one of these four tumour antigens. Interestingly, GPC-3 was associated with SALL-4 expression (P=0.001), an oncofetal transcription factor highly expressed in embryonal stem cells. SALL-4 and GPC-3 expression levels were correlated with vascular invasion, poor differentiation and higher AFP levels before surgery. Moreover, patients who co-expressed higher levels of both GPC-3 and SALL-4 had worse HCC-specific survival (P=0.018). Conclusions: We describe a panel of four tumour antigens with excellent coverage and good tumour specificity in a western area, low-endemic for hepatitis-B. The association between GPC-3 and SALL-4 is a novel finding and suggests that GPC-3 targeting may specifically attack the tumour stem-cell compartment

Priabonian (upper Eocene) larger foraminifera from the Helvetic Nappes of the Alps (Western Switzerland): new markers for Shallow Benthic zones 19-20

Here, we revise and update the biostratigraphy of larger foraminiferal assemblages in three sections of the Priabonian Sanetsch Formation in the Helvetic Nappes of the Western Swiss Alps: The Sex Rouge (SE) and the Sanetsch Buvette (SA) sections in the Wildhorn Nappe Complex, and the Col des Essets (ETS) section in the most external Morcles Nappe. In the SE and SA sections, the Tsanfleuron and most of the Pierredar Limestone members of the formation are assigned to SBZ 19 (early Priabonian), while the upper- most part of the formation is assigned to SBZ 20 (late Priabonian). In the external ETS section the entire Sanetsch Formation contains as- semblages characteristic of SBZ 19, suggesting an earlier, middle-late Priabonian onset of the hemipelagic Stad Formation (“Globigerina Marls”). Since it was established in 1998, the Shallow Benthic Zones (SBZ), a biozonation based on larger foraminifera, has been a useful tool in the biostratigraphy of the Paleogene. Biozonation proposals for the late middle-late Eocene are based mainly in biometrical subdivi- sion of lineages of nummulitids and orthophragmines, which requires measurements in oriented sections of isolated specimens. Here, we define previously unreported taxa from the Sanetsch Formation, which are considered characteristic for the Priabonian. They are easy to identify in random sections and thus useful biostratigraphical markers. We also describe a new orthophragminid genus, Virgasterocylina n. gen. (Orbitoclypeidae) characterized by the presence of rods, radial thickenings of calcite along ribs; a new species of Rotorbinella, R. epardi n. sp., and a new genus and new species of difficult suprageneric attribution, Sanetschella indeprensa n. gen., n. sp. We add the new taxa to the larger foraminiferal association characterizing the Priabonian (SBZ 19–20). The revision of the literature, together with our own sample collections revealed that these new taxa occur in Priabonian rocks from different basins in the western Tethys. Virgasterocylina n. gen. also occurs in the Caribbean bioprovince in the middle and upper Eocene. In the western Tethys, Virgasterocylina ferrandezi is subdivided into two subspecies, V. f. ferrandezi (Özcan and Less) and V. f. lessi n. ssp., which characterize the SBZ 19 and 20 biozones respectively

The QALL-ME Framework: A Specifiable-Domain Multilingual Question Answering Architecture.

This paper presents the QALL-ME Framework, a reusable architecture for building multilingual Question Answering (QA) systems working on structured data. The framework is released as free open source software with a set of demo components and extensive documentation. As main characteristics of the QALL-ME Framework we point out: (i) the framework domain portability, achieved by an ontology modelling of the target domain; (ii) the context awareness regarding space and time of the question; (iii) the use of textual entailment engines as the core of the question interpretation; and (iv) the framework’s Service Oriented Architecture, which is realized using interchangeable web services. Furthermore we present a running example to clarify how the framework processes questions as well as a case study that successfully shows a QA application built with the QALL-ME Framework for cinema/movie events in the tourism domain

Spinal cystic echinococcosis - a systematic analysis and review of the literature : part 1. Epidemiology and anatomy

Bone involvement in human cystic echinococcosis (CE) is rare, but affects the spine in approximately 50% of cases. Despite significant advances in diagnostic imaging techniques as well as surgical and medical treatment of spinal CE, our basic understanding of the parasite's predilection for the spine remains incomplete. To fill this gap, we systematically reviewed the published literature of the last five decades to summarize and analyze the currently existing data on epidemiological and anatomical aspects of spinal CE

Major determinants of height development in Turner syndrome (TS) patients treated with GH: Analysis of 987 patients from KIGS

Little is known about factors determining height outcome during GH treatment in Turner syndrome (TS). We investigated 987 TS children within the Kabi International Growth Study (KIGS) who had reached near adult height (NAH) after > 4 y GH treatment (including > 1 y before puberty). Through multiple regression analysis we developed a model for NAH and total gain. Our results were as follows (median): 1) At start, age 9.7 yrs, height (HT) 118.0 cm (0.0 TS SDS), projected adult height 146.1 cm, GH dose 0.27 mg/kg wk; 2) NAH HT 151.0 cm (1.5 TS SDS); 3) Prepubertal gain 21.2 cm (1.6 TS SDS); 4) Pubertal gain 9.4 cm (0.0 TS SDS). NAH correlated (r(2) = 0.67) with (ranked) HT at GH start (+), Is' year responsiveness to GH (+), MPH (+), age at puberty onset (+), age at GH start (-), and dose (+). The same factors explained (R-2 = 0.90) the total HT gain. However, HT at GH start correlated negatively. Karyotype had no influence on outcome. Evidently, height at GH start (the taller, the better), age at GH start (the younger, the better), the responsiveness to GH (the higher, the better) and age at puberty (the later, the better) determine NAH