Reducing false-positive biopsies: a pilot study to reduce benign biopsy rates for BI-RADS 4A/B assessments through testing risk stratification and new thresholds for intervention

The aim of this study is to evaluate Breast Imaging Reporting and Data Systems (BI-RADS) 4A/B subcategory risk estimates for ductal carcinoma in situ (DCIS) and invasive cancer (IC), determining whether changing the proposed cutoffs to a higher biopsy threshold could safely increase cancer-to-biopsy yields while minimizing false-positive biopsies. A prospective clinical trial was performed to evaluate BI-RADS 4 lesions from women seen in clinic between January 2006 and March 2007. An experienced radiologist prospectively estimated a percent risk-estimate for DCIS and IC. Truth was determined by histopathology or 4-year follow-up negative for malignancy. Risk estimates were used to generate receiver-operating characteristic (ROC) curves. Biopsy rates, cancer-to-biopsy yields, and type of malignancies missed were then calculated across postulated risk thresholds. A total of 124 breast lesions were evaluated from 213 women. An experienced radiologist gave highly accurate risk estimates for IC, DCIS alone, or the combination with an area under ROC curve of 0.91 (95 % CI 0.84–0.99) (p < 0.001), 0.81 (95 % CI 0.69–0.93) (p = 0.011), and 0.89 (95 % CI 0.83–0.95) (p < 0.001), respectively. The cancer-to-biopsy yield was 30 %. Three hypothetical thresholds for intervention were analyzed: (1) DCIS or IC ≥ 10 %; (2) DCIS ≥ 50 % or IC ≥ 10 %; and (3) IC ≥ 10 %, which translated to 22, 48, and 56 % of biopsies avoided; cancer-to-biopsy yields of 36, 47, and 46 %; and associated chance of missing an IC of 0, 1, and 2 %, respectively. Expert radiologists estimate risk of IC and DCIS with a high degree of accuracy. Increasing the cut off point for recommending biopsy, substituting with a short-term follow-up protocol with biopsy if any change, may safely reduce the number of false-positive biopsies

Facile Synthesis of High Quality Graphene Nanoribbons

Graphene nanoribbons have attracted attention for their novel electronic and spin transport properties1-6, and because nanoribbons less than 10 nm wide have a band gap that can be used to make field effect transistors. However, producing nanoribbons of very high quality, or in high volumes, remains a challenge. Here, we show that pristine few-layer nanoribbons can be produced by unzipping mildly gas-phase oxidized multiwalled carbon nanotube using mechanical sonication in an organic solvent. The nanoribbons exhibit very high quality, with smooth edges (as seen by high-resolution transmission electron microscopy), low ratios of disorder to graphitic Raman bands, and the highest electrical conductance and mobility reported to date (up to 5e2/h and 1500 cm2/Vs for ribbons 10-20 nm in width). Further, at low temperature, the nanoribbons exhibit phase coherent transport and Fabry-Perot interference, suggesting minimal defects and edge roughness. The yield of nanoribbons was ~2% of the starting raw nanotube soot material, which was significantly higher than previous methods capable of producing high quality narrow nanoribbons1. The relatively high yield synthesis of pristine graphene nanoribbons will make these materials easily accessible for a wide range of fundamental and practical applications.Comment: Nature Nanotechnology in pres

Categorical Dimensions of Human Odor Descriptor Space Revealed by Non-Negative Matrix Factorization

In contrast to most other sensory modalities, the basic perceptual dimensions of olfaction remain unclear. Here, we use non-negative matrix factorization (NMF) – a dimensionality reduction technique – to uncover structure in a panel of odor profiles, with each odor defined as a point in multi-dimensional descriptor space. The properties of NMF are favorable for the analysis of such lexical and perceptual data, and lead to a high-dimensional account of odor space. We further provide evidence that odor dimensions apply categorically. That is, odor space is not occupied homogenously, but rather in a discrete and intrinsically clustered manner. We discuss the potential implications of these results for the neural coding of odors, as well as for developing classifiers on larger datasets that may be useful for predicting perceptual qualities from chemical structures

An observational study of patient characteristics associated with the mode of admission to acute stroke services in North East, England

Objective Effective provision of urgent stroke care relies upon admission to hospital by emergency ambulance and may involve pre-hospital redirection. The proportion and characteristics of patients who do not arrive by emergency ambulance and their impact on service efficiency is unclear. To assist in the planning of regional stroke services we examined the volume, characteristics and prognosis of patients according to the mode of presentation to local services. Study design and setting A prospective regional database of consecutive acute stroke admissions was conducted in North East, England between 01/09/10-30/09/11. Case ascertainment and transport mode were checked against hospital coding and ambulance dispatch databases. Results Twelve acute stroke units contributed data for a mean of 10.7 months. 2792/3131 (89%) patients received a diagnosis of stroke within 24 hours of admission: 2002 arrivals by emergency ambulance; 538 by private transport or non-emergency ambulance; 252 unknown mode. Emergency ambulance patients were older (76 vs 69 years), more likely to be from institutional care (10% vs 1%) and experiencing total anterior circulation symptoms (27% vs 6%). Thrombolysis treatment was commoner following emergency admission (11% vs 4%). However patients attending without emergency ambulance had lower inpatient mortality (2% vs 18%), a lower rate of institutionalisation (1% vs 6%) and less need for daily carers (7% vs 16%). 149/155 (96%) of highly dependent patients were admitted by emergency ambulance, but none received thrombolysis. Conclusion Presentations of new stroke without emergency ambulance involvement were not unusual but were associated with a better outcome due to younger age, milder neurological impairment and lower levels of pre-stroke dependency. Most patients with a high level of pre-stroke dependency arrived by emergency ambulance but did not receive thrombolysis. It is important to be aware of easily identifiable demographic groups that differ in their potential to gain from different service configurations

High Electromechanical Response of Ionic Polymer Actuators with Controlled-Morphology Aligned Carbon Nanotube/Nafion Nanocomposite Electrodes

Author Manuscript 2011 October 8Recent advances in fabricating controlled-morphology vertically aligned carbon nanotubes (VA-CNTs) with ultrahigh volume fraction create unique opportunities for markedly improving the electromechanical performance of ionic polymer conductor network composite (IPCNC) actuators. Continuous paths through inter-VA-CNT channels allow fast ion transport, and high electrical conduction of the aligned CNTs in the composite electrodes lead to fast device actuation speed (>10% strain/second). One critical issue in developing advanced actuator materials is how to suppress the strain that does not contribute to the actuation (unwanted strain) thereby reducing actuation efficiency. Here, experiments demonstrate that the VA-CNTs give an anisotropic elastic response in the composite electrodes, which suppresses the unwanted strain and markedly enhances the actuation strain (>8% strain under 4 V). The results reported here suggest pathways for optimizing the electrode morphology in IPCNCs using ultrahigh volume fraction VA-CNTs to further enhanced performance.United States. Army Research Office (Grant W911NF-07-1-0452)National Institutes of Health (U.S.) (Grant R01-EY018387-02)United States. Multidisciplinary University Research Initiativ

The effect of phytosphingosine isolated from Asterina pectinifera on cell damage induced by mite antigen in HaCaT cell and antibacterial activity against Staphylococcus aureus

The current study was to investigate the positive protective effects of phytosphingosine (PS) against mite antigen and Staphylococcus aureus, etiological causes of an atopic dermatitis. To achieve this aim, PS was isolated from starfish, Asterina pectinifera, using high-performance liquid chromatography and was elucidated with nuclear magnetic resonance spectrometry. In the present experiment, PS, which ranged from 1 to 5 &#181;M could protect the HaCaT cell against injuries caused by stimulation to 10 &#181;g/ml mite antigen for 1 h, followed by incubation with serum-free medium for 24 h, which resembled the excitotoxin in vivo system. Furthermore, PS which was isolated from starfish could significantly inhibit the growth of S. aureus. In conclusion, this study demonstrated the protective effect of PS on excitotoxic damage against mite antigen and S. aureus through suppressing the excessive disruption of differentiation and exhibiting antibacterial capacity. This result implicated that the application of PS isolated from starfish might be a promising therapeutic option of atopic dermatitis

The regulatory subunit of PKA-I remains partially structured and undergoes β-aggregation upon thermal denaturation

Background: The regulatory subunit (R) of cAMP-dependent protein kinase (PKA) is a modular flexible protein that responds with large conformational changes to the binding of the effector cAMP. Considering its highly dynamic nature, the protein is rather stable. We studied the thermal denaturation of full-length RIα and a truncated RIα(92-381) that contains the tandem cyclic nucleotide binding (CNB) domains A and B. Methodology/Principal Findings: As revealed by circular dichroism (CD) and differential scanning calorimetry, both RIα proteins contain significant residual structure in the heat-denatured state. As evidenced by CD, the predominantly α-helical spectrum at 25°C with double negative peaks at 209 and 222 nm changes to a spectrum with a single negative peak at 212-216 nm, characteristic of β-structure. A similar α→β transition occurs at higher temperature in the presence of cAMP. Thioflavin T fluorescence and atomic force microscopy studies support the notion that the structural transition is associated with cross-β-intermolecular aggregation and formation of non-fibrillar oligomers. Conclusions/Significance: Thermal denaturation of RIα leads to partial loss of native packing with exposure of aggregation-prone motifs, such as the B' helices in the phosphate-binding cassettes of both CNB domains. The topology of the β-sandwiches in these domains favors inter-molecular β-aggregation, which is suppressed in the ligand-bound states of RIα under physiological conditions. Moreover, our results reveal that the CNB domains persist as structural cores through heat-denaturation. © 2011 Dao et al

Raman bands of double-wall carbon nanotubes: comparison with single- and triple-wall carbon nanotubes, and influence of annealing and electron irradiation

We compare the G and G2D bands of single-, double- and triple-wall carbon nanotubes (CNTs). We observe that the band shape is sensitive to the number of walls of the CNTs. For single-wall carbon nanotubes (SWCNTs), the G band is composed of two distinct contributions G+ and G-, while the G band for double-wall nanotubes is composed of one band with two main contributions from the inner and the outer tube. The G2D band can be fitted with one Lorentzian for single-wall tubes, while two distinct contributions are observed for double-wall carbon nanotubes (DWCNTs). Considerable variations of the G2D band are found with similar first order Raman spectra. Annealing influences the D- and RBM-band intensities. Electron irradiation has the effect of decreasing the G- and D-band wavenumbers but does not enhance the D-band intensity considerably. The down-shifts of the G- and D-band wavenumbers are correlated and are the same for two excitation wavelengths. This is consistent with the scattering of phonons around the K-point