2-C-Hydro­xymethyl-2,3-O-iso­propyl­idene-d-ribono-1,5-lactam. Corrigendum

Corrigendum to Acta Cryst. (2004), E60, o909–o910

Construction of the descriptive system for the assessment of quality of life AQoL-6D utility instrument

BackgroundMulti attribute utility (MAU) instruments are used to include the health related quality of life (HRQoL) in economic evaluations of health programs. Comparative studies suggest different MAU instruments measure related but different constructs. The objective of this paper is to describe the methods employed to achieve content validity in the descriptive system of the Assessment of Quality of Life (AQoL)-6D, MAU instrument.MethodsThe AQoL program introduced the use of psychometric methods in the construction of health related MAU instruments. To develop the AQoL-6D we selected 112 items from previous research, focus groups and expert judgment and administered them to 316 members of the public and 302 hospital patients. The search for content validity across a broad spectrum of health states required both formative and reflective modelling. We employed Exploratory Factor Analysis and Structural Equation Modelling (SEM) to meet these dual requirements.Results and DiscussionThe resulting instrument employs 20 items in a multi-tier descriptive system. Latent dimension variables achieve sensitive descriptions of 6 dimensions which, in turn, combine to form a single latent QoL variable. Diagnostic statistics from the SEM analysis are exceptionally good and confirm the hypothesised structure of the model.ConclusionsThe AQoL-6D descriptive system has good psychometric properties. They imply that the instrument has achieved construct validity and provides a sensitive description of HRQoL. This means that it may be used with confidence for measuring health related quality of life and that it is a suitable basis for modelling utilities for inclusion in the economic evaluation of health programs.<br /

How to combine CTA, 99mTc-WBC SPECT/CT, and [18F]FDG PET/CT in patients with suspected abdominal vascular endograft infections?

Purpose - We aimed at comparing Tc-99m-HMPAO white blood cells (Tc-99m-WBC) scintigraphy, 18fluorine-fluorodeoxyglucose ([F-18]FDG) positron emission tomography/computed tomography (PET/CT) and CT angiography (CTA) in patients with suspected abdominal vascular graft or endograft infection (VGEI). Moreover, we attempted to define a new visual score for interpreting [F-18]FDG PET/CT scans aiming at increasing its specificity. Methods - We prospectively compared Tc-99m-WBC SPECT/CT, [F-18]FDG PET/CT, and CTA in 26 patients with suspected abdominal VGEI. WBC scans were performed and interpreted according to EANM recommendations. [F-18]FDG PET/CT studies were assessed with both qualitative (Sah's scale and new visual score) and semi-quantitative analyses. CTA images were interpreted according to MAGIC criteria. Microbiology, histopathology or a clinical follow-up of at least 24 months were used to achieve final diagnosis. Results - Eleven out of 26 patients were infected. [F-18]FDG PET/CT showed 100% sensitivity and NPV, with both scoring systems, thus representing an efficient tool to rule out the infection. The use of a more detailed scoring system provided statistically higher specificity compared to the previous Sah's scale (p = 0.049). Tc-99m-WBC SPECT/CT provided statistically higher specificity and PPV than [F-18]FDG PET/CT, regardless the interpretation criteria used and it can be, therefore, used in early post-surgical phases or to confirm or rule out a PET/CT finding. Conclusions - After CTA, patients with suspected late VGEI should perform a [F-18]FDG PET/CT given its high sensitivity and NPV. However, given its lower specificity, positive results should be confirmed with Tc-99m-WBC scintigraphy. The use of a more detailed scoring system reduces the number of Tc-99m-WBC scans needed after [F-18]FDG PET/CT. Nevertheless, in suspected infections within 4 months from surgery, Tc-99m-WBC SPECT/CT should be performed as second exam, due to its high accuracy in differentiating sterile inflammation from infection

Class II phosphoinositide 3-kinase C2 beta regulates a novel signaling pathway involved in breast cancer progression

It is now well established that the enzymes phosphoinositide 3-kinases (PI3Ks) have a key role in the development and progression of many cancer types and indeed PI3Ks inhibitors are currently being tested in clinical trials. Although eight distinct PI3K isoforms exist, grouped into three classes, most of the evidence currently available are focused on one specific isoform with very little known about the potential role of the other members of this family in cancer. Here we demonstrate that the class II enzyme PI3K-C2β is overexpressed in several human breast cancer cell lines and in human breast cancer specimens. Our data indicate that PI3K-C2β regulates breast cancer cell growth in vitro and in vivo and that PI3K-C2β expression in breast tissues is correlated with the proliferative status of the tumor. Specifically we show that downregulation of PI3K-C2β in breast cancer cell lines reduces colony formation, induces cell cycle arrest and inhibits tumor growth, in particular in an estrogen-dependent in vivo xenograft. Investigation of the mechanism of the PI3K-C2β-dependent regulation of cell cycle progression and cell growth revealed that PI3K-C2β regulates cyclin B1 protein levels through modulation of microRNA miR-449a levels. Our data further demonstrate that downregulation of PI3K-C2β inhibits breast cancer cell invasion in vitro and breast cancer metastasis in vivo. Consistent with this, PI3K-C2β is highly expressed in lymph-nodes metastases compared to matching primary tumors. These data demonstrate that PI3K-C2β plays a pivotal role in breast cancer progression and in metastasis development. Our data indicate that PI3K-C2β may represent a key molecular switch that regulates a rate-limiting step in breast tumor progression and therefore it may be targeted to limit breast cancer spread

multicenter intraindividual comparison of single dose gadobenate dimeglumine and double dose gadopentetate dimeglumine for mr angiography of the supra aortic arteries the supra aortic value study

BACKGROUND AND PURPOSE: Gadobenate dimeglumine has markedly higher R1 relaxivity compared to gadopentetate dimeglumine meaning that lower doses can be used to achieve similar contrast enhancement. Our aim was to prospectively compare single-dose gadobenate dimeglumine with double-dose gadopentetate dimeglumine for contrast-enhanced MRA of the supra-aortic vasculature. MATERIALS AND METHODS: Forty-six patients (37 men, 9 women; mean age, 63.5 ± 10.1 years) with known or suspected steno-occlusive disease of the supra-aortic vessels underwent 2 identical CE-MRA examinations at 1.5T. Contrast agents were administered in randomized order, with the 2-fold greater volume of gadopentetate dimeglumine injected at a 2 times faster rate. Image assessment was performed by 3 independent blinded readers for vessel anatomic delineation, detection/exclusion of pathology, and global preference. Diagnostic performance (sensitivity, specificity, accuracy, PPV, and NPV) for detection of ≥60% stenosis was determined for 39/46 patients who underwent preinterventional DSA. Data were analyzed by using the Wilcoxon signed-rank, McNemar, and Wald tests in terms of the noninferiority of single-dose gadobenate dimeglumine compared with double-dose gadopentetate dimeglumine. Quantitative enhancement (signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR)) was also compared. RESULTS: All images were technically adequate. No differences (P = 1.0) were noted by any reader for any qualitative parameter. All readers considered single-dose gadobenate dimeglumine and double-dose gadopentetate dimeglumine equivalent in at least 42/46 patients (91.3% three-reader agreement) for all parameters. Nonsignificant superiority for gadobenate dimeglumine was reported for all diagnostic performance indicators (sensitivity: 82.7%–88.5% versus 75.0%–80.8%; specificity: 96.4%–98.6% versus 94.6%–98.6%; accuracy: 94.6%–96.1% versus 92.4%–94.9%; PPV: 81.5%–91.5% versus 73.7%–90.7%; NPV: 96.8%–97.8% versus 95.4%–96.4%). No differences (P > .05) in quantitative enhancement were noted. CONCLUSIONS: The image quality and diagnostic performance achieved with 0.1-mmol/kg gadobenate dimeglumine is at least equivalent to that achieved with 0.2-mmol/kg gadopentetate dimeglumine

Implant placement in patients under treatment with rivaroxaban: A retrospective clinical study

The management of patients under treatment with Direct Oral Anticoagulants (DOACs) has led clinicians to deal with two clinical issues, such as the hemorrhagic risk in case of non-interruption or the risk of thromboembolism in case of suspension of the treatment. The primary aim of this retrospective study was to evaluate the incidence of perioperative bleeding events and healing complications in patients who were under treatment with Rivaroxaban and who received dental implants and immediate prosthetic restoration. Patients treated with Rivaroxaban (Xarelto 20 mg daily) and who needed implant rehabilitation were selected. Four to six implants were placed in mandibular healed sites or fresh extraction sockets. All patients, in agreement with their physicians, interrupted the medication for 24 h and received implants and immediate restorations. Twelve patients and 57 implants were analyzed in the study. No major postoperative bleeding events were reported. Three patients (25%) presented slight immediate postoperative bleeding controlled with compression only. The implant and prosthetic survival rate were both 100% after 1 year. Within the limitations of this study, multiple implant placement with an immediate loading can be performed without any significant complication with a 24 h discontinuation of Rivaroxaban, in conjunction with the patient’s physician

Bridging and downstaging treatments for hepatocellular carcinoma in patients on the waiting list for liver transplantation

Several therapeutic procedures have been proposed as bridging treatments for patients with hepatocellular carcinoma (HCC) awaiting liver transplantation (LT). The most used treatments include transarterial chemoembolization and radiofrequency ablation. Surgical resection has also been successfully used as a bridging procedure, and LT should be considered a rescue treatment in patients with previous HCC resection who experience tumor recurrence or post-treatment severe decompensation of liver function. The aims of bridging treatments include decreasing the waiting list dropout rate before transplantation, reducing HCC recurrence after transplantation, and improving post-transplant overall survival. To date, no data from prospective randomized studies are available; however, for HCC patients listed for LT within the Milan criteria, prolonging the waiting time over 6-12 mo is a risk factor for tumor spread. Bridging treatments are useful in containing tumor progression and decreasing dropout. Furthermore, the response to pre-LT treatments may represent a surrogate marker of tumor biological aggressiveness and could therefore be evaluated to prioritize HCC candidates for LT. Lastly, although a definitive conclusion can not be reached, the experiences reported to date suggest a positive impact of these treatments on both tumor recurrence and post-transplant patient survival. Advanced HCC may be downstaged to achieve and maintain the current conventional criteria for inclusion in the waiting list for LT. Recent studies have demonstrated that successfully downstaged patients can achieve a 5-year survival rate comparable to that of patients meeting the conventional criteria without requiring downstaging. © 2013 Baishideng Publishing Group Co., Limited. All rights reserved

The identification of informative genes from multiple datasets with increasing complexity

Background In microarray data analysis, factors such as data quality, biological variation, and the increasingly multi-layered nature of more complex biological systems complicates the modelling of regulatory networks that can represent and capture the interactions among genes. We believe that the use of multiple datasets derived from related biological systems leads to more robust models. Therefore, we developed a novel framework for modelling regulatory networks that involves training and evaluation on independent datasets. Our approach includes the following steps: (1) ordering the datasets based on their level of noise and informativeness; (2) selection of a Bayesian classifier with an appropriate level of complexity by evaluation of predictive performance on independent data sets; (3) comparing the different gene selections and the influence of increasing the model complexity; (4) functional analysis of the informative genes. Results In this paper, we identify the most appropriate model complexity using cross-validation and independent test set validation for predicting gene expression in three published datasets related to myogenesis and muscle differentiation. Furthermore, we demonstrate that models trained on simpler datasets can be used to identify interactions among genes and select the most informative. We also show that these models can explain the myogenesis-related genes (genes of interest) significantly better than others (P < 0.004) since the improvement in their rankings is much more pronounced. Finally, after further evaluating our results on synthetic datasets, we show that our approach outperforms a concordance method by Lai et al. in identifying informative genes from multiple datasets with increasing complexity whilst additionally modelling the interaction between genes. Conclusions We show that Bayesian networks derived from simpler controlled systems have better performance than those trained on datasets from more complex biological systems. Further, we present that highly predictive and consistent genes, from the pool of differentially expressed genes, across independent datasets are more likely to be fundamentally involved in the biological process under study. We conclude that networks trained on simpler controlled systems, such as in vitro experiments, can be used to model and capture interactions among genes in more complex datasets, such as in vivo experiments, where these interactions would otherwise be concealed by a multitude of other ongoing events

Spatial migration of temporal earthquake clusters driven by the transfer of differential stress between neighbouring fault/shear-zone structures

Uncertainty concerning the processes responsible for slip-rate fluctuations associated with temporal clustering of surface faulting earthquakes is a fundamental, unresolved issue in tectonics, because strain-rates accommodated by fault/shear-zone structures are the key to understanding the viscosity structure of the crust and seismic hazard. We constrain the timing and amplitude of slip-rate fluctuations that occurred on three active normal faults in central Italy over a time period of 20–30 kyrs, using in situ 36Cl cosmogenic dating of fault planes. We identify five periods of rapid slip on individual faults lasting a few millennia, separated time periods of up to 10 millennia with low or zero slip-rate. The rapid slip pulses migrated across the strike between the faults in two waves from SW to NE. We replicate this migration with a model where rapid slip induces changes in differential stress that drive changes in strain-rate on viscous shear zones that drive slip-rate variability on overlying brittle faults. Earthquakes increase the differential stress and strain-rate on underlying shear zones, which in turn accumulate strain, re-loading stress onto the overlying brittle fault. This positive feedback produces high strain-rate episodes containing several large magnitude surface faulting earthquakes (earthquake clusters), but also reduce the differential stress on the viscous portions of neighbouring fault/shear-zones slowing the occurrence of large-magnitude surface faulting earthquakes (earthquake anticlusters). Shear-zones on faults experiencing anticlusters continue to accumulate viscous strain at a lowered rate, and eventually this loads the overlying brittle fault to failure, initiating a period of rapid slip through the positive feedback process described above, and inducing lowered strain-rates onto neighbouring fault/shear-zones. We show that these patterns of differential stress change can replicate the measured earthquake clustering implied by the 36Cl data. The stress changes are related to the fault geometry in terms of distance and azimuth from the slipping structure, implying that (a) strain-rate and viscosity fluctuations for studies of continental rheology, and (b) slip-rates for seismic hazard purposes are to an extent predictable given knowledge of the fault system geometry