Diagnostic accuracy for different strategies of image-guided breast intervention in cases of nonpalpable breast lesions

To find out whether ultrasound-guided fine-needle aspiration (FNA) and ultrasound and stereotactic-guided large core needle biopsy (LCNB) are reliable alternatives to needle-localised open breast biopsy (NLBB) in daily practice, we performed a retrospective study and evaluated the validity of these methods. In all, 718 women with 749 nonpalpable breast lesions from three Dutch Hospitals were included, and the validity of the various methods for diagnosis was assessed. This was carried out according to a method described by Burbank and Parker for evaluating the quality of an image-guided breast intervention. We compared our results with the outcome of the COBRA study. Overall, all diagnostic strategies (NLBB, FNA, LCNB ultrasound and stereotactic guided) show comparable agreement rates. However, the miss rates differ: 2% for NLBB, 3% for COBRA (LCNB in study setting), 5% for FNA and 8-12% for LCNB in practice. Fine-needle aspiration was nonconclusive in 29%, and shows an overestimation for DCIS in 9%. The DCIS underestimate rate in NLBB was 8%. For the assessment of lesions consisting of microcalcifications only and to exclude malignancy in all other lesions, a 14-gauge needle should be used. Ultrasound-guided intervention can be performed in a large percentage of nonpalpable lesions. Lesions consisting only of microcalcifications on mammography need special attention

Class IA PI3Kinase Regulatory Subunit, p85α, Mediates Mast Cell Development through Regulation of Growth and Survival Related Genes

Stem cell factor (SCF) mediated KIT receptor activation plays a pivotal role in mast cell growth, maturation and survival. However, the signaling events downstream from KIT are poorly understood. Mast cells express multiple regulatory subunits of class 1A PI3Kinase (PI3K) including p85α, p85β, p50α, and p55α. While it is known that PI3K plays an essential role in mast cells; the precise mechanism by which these regulatory subunits impact specific mast cell functions including growth, survival and cycling are not known. We show that loss of p85α impairs the growth, survival and cycling of mast cell progenitors (MCp). To delineate the molecular mechanism (s) by which p85α regulates mast cell growth, survival and cycling, we performed microarray analyses to compare the gene expression profile of MCps derived from WT and p85α-deficient mice in response to SCF stimulation. We identified 151 unique genes exhibiting altered expression in p85α-deficient cells in response to SCF stimulation compared to WT cells. Functional categorization based on DAVID bioinformatics tool and Ingenuity Pathway Analysis (IPA) software relates the altered genes due to lack of p85α to transcription, cell cycle, cell survival, cell adhesion, cell differentiation, and signal transduction. Our results suggest that p85α is involved in mast cell development through regulation of expression of growth, survival and cell cycle related genes

The PROgnostic Value of unrequested Information in Diagnostic Imaging (PROVIDI) Study: rationale and design

We describe the rationale for a new study examining the prognostic value of unrequested findings in diagnostic imaging. The deployment of more advanced imaging modalities in routine care means that such findings are being detected with increasing frequency. However, as the prognostic significance of many types of unrequested findings is unknown, the optimal response to such findings remains uncertain and in many cases an overly defensive approach is adopted, to the detriment of patient-care. Additionally, novel and promising image findings that are newly available on many routine scans cannot be used to improve patient care until their prognostic value is properly determined. The PROVIDI study seeks to address these issues using an innovative multi-center case-cohort study design. PROVIDI is to consist of a series of studies investigating specific, selected disease entities and clusters. Computed Tomography images from the participating hospitals are reviewed for unrequested findings. Subsequently, this data is pooled with outcome data from a central population registry. Study populations consist of patients with endpoints relevant to the (group of) disease(s) under study along with a random control sample from the cohort. This innovative design allows PROVIDI to evaluate selected unrequested image findings for their true prognostic value in a series of manageable studies. By incorporating unrequested image findings and outcomes data relevant to patients, truly meaningful conclusions about the prognostic value of unrequested and emerging image findings can be reached and used to improve patient-care

Polymorphism and magnetic properties of Li2MSiO4 (M 5 Fe, Mn) cathode materials

Transition metal-based lithium orthosilicates (Li2MSiO4,M=Fe, Ni, Co, Mn) are gaining a wide interest as cathode materials for lithium-ion batteries. These materials present a very complex polymorphism that could affect their physical properties. In this work, we synthesized the Li2FeSiO4 and Li2MnSiO4 compounds by a sol-gel method at different temperatures. The samples were investigated by XRPD, TEM, 7Li MAS NMR, and magnetization measurements, in order to characterize the relationships between crystal structure and magnetic properties. High-quality 7Li MAS NMR spectra were used to determine the silicate structure, which can otherwise be hard to study due to possible mixtures of different polymorphs. The magnetization study revealed that the Neel temperature does not depend on the polymorph structure for both iron and manganese lithium orthosilicates

Inter-scan reproducibility of coronary calcium measurement using Multi Detector-Row Computed Tomography (MDCT)

Purpose: To assess inter-scan reproducibility of coronary calcium measurements obtained from Multi Detector-Row CT (MDCT) images and to evaluate whether this reproducibility is affected by different measurement protocols, slice thickness, cardiovascular risk factors and/or technical variables. Design: Cross-sectional study with repeated measurements. Materials and methods: The study population comprised 76 healthy women. Coronary calcium was assessed in these women twice in one session using 16-MDCT (Philips Mx 8000 IDT 16). Images were reconstructed with 1.5 mm slice thickness and 3.0 mm slice thickness. The 76 repeated scans were scored. The Agatston score, a volume measurement and a mass measurement were assessed. Reproducibility was determined by estimation of mean, absolute, relative difference, the weighted kappa value for agreement and the Intra-class correlation coefficient (ICCC). Results: Fifty-five participants (72.4%) had a coronary calcification of more than zero in Agatston (1.5 mm slice thickness). The reproducibility of coronary calcium measurements between scans in terms of ranking was excellent with Intra-class correlation coefficients of >0.98, and kappa values above 0.80. The absolute difference in calcium score between scans increased with increasing calcium levels, indicating that measurement error increases with increasing calcium levels. However, no relation was found between the mean difference in scores and calcium levels, indicating that the increase in measurement error is likely to result in random misclassification in calcium score. Reproducibility results were similar for 1.5 mm slices and for 3.0 mm slices, and equal for Agatston, volume and mass measurements. Conclusion: Inter-scan reproducibilility of measurement of coronary calcium using images from MDCT is excellent, irrespective of slice thickness and type of calcium parameter

Cas9 gRNA engineering for genome editing, activation and repression

We demonstrate that by altering the length of Cas9-associated guide RNA(gRNA) we were able to control Cas9 nuclease activity and simultaneously perform genome editing and transcriptional regulation with a single Cas9 protein. We exploited these principles to engineer mammalian synthetic circuits with combined transcriptional regulation and kill functions governed by a single multifunctional Cas9 protein.National Human Genome Research Institute (U.S.) (P50 HG005550)United States. Department of Energy (DE-FG02-02ER63445)Wyss Institute for Biologically Inspired EngineeringUnited States. Army Research Office (DARPA W911NF-11-2-0054)National Science Foundation (U.S.)United States. National Institutes of Health (5R01CA155320-04)United States. National Institutes of Health (P50 GM098792)National Cancer Institute (U.S.) (5T32CA009216-34)Massachusetts Institute of Technology. Department of Biological EngineeringHarvard Medical School. Department of GeneticsDefense Threat Reduction Agency (DTRA) (HDTRA1-14-1-0006

Aortic root dimension changes during systole and diastole: evaluation with ECG-gated multidetector row computed tomography

Cardiac pulsatility and aortic compliance may result in aortic area and diameter changes throughout the cardiac cycle in the entire aorta. Until this moment these dynamic changes could never be established in the aortic root (aortic annulus, sinuses of Valsalva and sinotubular junction). The aim of this study was to visualize and characterize the changes in aortic root dimensions during systole and diastole with ECG-gated multidetector row computed tomography (MDCT). MDCT scans of subjects without aortic root disease were analyzed. Retrospectively, ECG-gated reconstructions at each 10% of the cardiac cycle were made and analyzed during systole (30–40%) and diastole (70–75%). Axial planes were reconstructed at three different levels of the aortic root. At each level the maximal and its perpendicular luminal dimension were measured. The mean dimensions of the total study group (n = 108, mean age 56 ± 13 years) do not show any significant difference between systole and diastole. The individual dimensions vary up to 5 mm. However, the differences range between minus 5 mm (diastolic dimension is greater than systolic dimensions) and 5 mm (vice versa). This variability is independent of gender, age, height and weight. This study demonstrated a significant individual dynamic change in the dimensions of the aortic root. These results are highly unpredictable. Most of the healthy subjects have larger systolic dimensions, however, some do have larger diastolic dimensions

Cost-effectiveness of stereotactic large-core needle biopsy for nonpalpable breast lesions compared to open-breast biopsy

This paper demonstrates that the introduction of large-core needle biopsy (LCNB) replacing needle-localised breast biopsy (NLBB) for nonpalpable (screen-detected) breast lesions could result in substantial cost savings at the expense of a possible slight increase in breast cancer mortality. The cost-effectiveness of LCNB and NLBB was estimated using a microsimulation model. The sensitivity of LCNB (0.97) and resource use and costs of LCNB and NLBB were derived from a multicentre consecutive cohort study among 973 women who consented in getting LCNB and NLBB, if LCNB was negative. Sensitivity analyses were performed. Replacing NLBB with LCNB would result in approximately six more breast cancer deaths per year (in a target population of 2.1 million women), or in 1000 extra life-years lost from breast cancer (effect over 100 years). The total costs of management of breast cancer (3% discounted) are estimated at £4676 million with NLBB; introducing LCNB would save £13 million. The incremental cost-effectiveness ratio of continued NLBB vs LCNB would be £12 482 per additional life-year gained (3% discounted); incremental costs range from £-21 687 (low threshold for breast biopsy) to £74 378 (high sensitivity of LCNB)

Extraction and sensitive detection of toxins A and B from the human pathogen Clostridium difficile in 40 seconds using microwave-accelerated metal-enhanced fluorescence.

Clostridium difficile is the primary cause of antibiotic associated diarrhea in humans and is a significant cause of morbidity and mortality. Thus the rapid and accurate identification of this pathogen in clinical samples, such as feces, is a key step in reducing the devastating impact of this disease. The bacterium produces two toxins, A and B, which are thought to be responsible for the majority of the pathology associated with the disease, although the relative contribution of each is currently a subject of debate. For this reason we have developed a rapid detection assay based on microwave-accelerated metal-enhanced fluorescence which is capable of detecting the presence of 10 bacteria in unprocessed human feces within 40 seconds. These promising results suggest that this prototype biosensor has the potential to be developed into a rapid, point of care, real time diagnostic assay for C. difficile