Metastases or benign adrenal lesions in patients with histopathological verification of lung cancer: Can CT texture analysis distinguish?

INTRODUCTION: Distant metastases are found in the many of patients with lung cancer at time of diagnosis. Several diagnostic tools are available to distinguish between metastatic spread and benign lesions in the adrenal gland. However, all require additional diagnostic steps after the initial CT. The purpose of this study was to evaluate if texture analysis of CT-abnormal adrenal glands on the initial CT correctly differentiates between malignant and benign lesions in patients with confirmed lung cancer. MATERIALS AND METHODS: In this retrospective study 160 patients with endoscopic ultrasound-guided biopsy from the left adrenal gland and a contrast-enhanced CT in portal venous phase were assessed with texture analysis. A region of interest encircling the entire adrenal gland was used and from this dataset the slice with the largest cross section of the lesion was analyzed individually. RESULTS: Several texture parameters showed statistically significantly difference between metastatic and benign lesions but with considerable between-groups overlaps in confidence intervals. Sensitivity and specificity were assessed using ROC-curves, and in univariate binary logistic regression the area under the curve ranged from 36 % (Kurtosis 0.5) to 69 % (Entropy 2.5) compared to 73 % in the best fitting model using multivariate binary logistic regression. CONCLUSION: In lung cancer patients with abnormal adrenal gland at imaging, adrenal gland texture analyses appear not to have any role in discriminating benign from malignant lesions

PILER-CR: Fast and accurate identification of CRISPR repeats

BACKGROUND: Sequencing of prokaryotic genomes has recently revealed the presence of CRISPR elements: short, highly conserved repeats separated by unique sequences of similar length. The distinctive sequence signature of CRISPR repeats can be found using general-purpose repeat- or pattern-finding software tools. However, the output of such tools is not always ideal for studying these repeats, and significant effort is sometimes needed to build additional tools and perform manual analysis of the output. RESULTS: We present PILER-CR, a program specifically designed for the identification and analysis of CRISPR repeats. The program executes rapidly, completing a 5 Mb genome in around 5 seconds on a current desktop computer. We validate the algorithm by manual curation and by comparison with published surveys of these repeats, finding that PILER-CR has both high sensitivity and high specificity. We also present a catalogue of putative CRISPR repeats identified in a comprehensive analysis of 346 prokaryotic genomes. CONCLUSION: PILER-CR is a useful tool for rapid identification and classification of CRISPR repeats. The software is donated to the public domain. Source code and a Linux binary are freely available at

SHRiMP: Accurate Mapping of Short Color-space Reads

The development of Next Generation Sequencing technologies, capable of sequencing hundreds of millions of short reads (25–70 bp each) in a single run, is opening the door to population genomic studies of non-model species. In this paper we present SHRiMP - the SHort Read Mapping Package: a set of algorithms and methods to map short reads to a genome, even in the presence of a large amount of polymorphism. Our method is based upon a fast read mapping technique, separate thorough alignment methods for regular letter-space as well as AB SOLiD (color-space) reads, and a statistical model for false positive hits. We use SHRiMP to map reads from a newly sequenced Ciona savignyi individual to the reference genome. We demonstrate that SHRiMP can accurately map reads to this highly polymorphic genome, while confirming high heterozygosity of C. savignyi in this second individual. SHRiMP is freely available at http://compbio.cs.toronto.edu/shrimp

Probing the local nature of excitons and plasmons in few-layer MoS₂

Excitons and plasmons are the two most fundamental types of collective electronic excitations occurring in solids. Traditionally, they have been studied separately using bulk techniques that probe their average energetic structure over large spatial regions. However, as the dimensions of materials and devices continue to shrink, it becomes crucial to understand how these excitations depend on local variations in the crystal- and chemical structure on the atomic scale. Here, we use monochromated low-loss scanning-transmission-electron-microscopy electron-energy-loss spectroscopy, providing the best simultaneous energy and spatial resolution achieved to-date to unravel the full set of electronic excitations in few-layer MoS₂ nanosheets over a wide energy range. Using first-principles, many-body calculations we confirm the excitonic nature of the peaks at ~ 2 and ~ 3 eV in the experimental electron-energy-loss spectrum and the plasmonic nature of higher energy-loss peaks. We also rationalise the non-trivial dependence of the electron-energy-loss spectrum on beam and sample geometry such as the number of atomic layers and distance to steps and edges. Moreover, we show that the excitonic features are dominated by the long wavelength (q = 0) components of the probing field, while the plasmonic features are sensitive to a much broader range of q-vectors, indicating a qualitative difference in the spatial character of the two types of collective excitations. Our work provides a template protocol for mapping the local nature of electronic excitations that open new possibilities for studying photo-absorption and energy transfer processes on a nanometer scale

Interaction Between the a3 Region of Factor VIII and the TIL'E’ Domains of the von Willebrand Factor

The von Willebrand factor (VWF) and coagulation factor VIII (FVIII) are intricately involved in hemostasis. A tight, noncovalent complex between VWF and FVIII prolongs the half-life of FVIII in plasma, and failure to form this complex leads to rapid clearance of FVIII and bleeding diatheses such as hemophilia A and von Willebrand disease (VWD) type 2N. High-resolution insight into the complex between VWF and FVIII has so far been strikingly lacking. This is particularly the case for the flexible a3 region of FVIII, which is imperative for high-affinity binding. Here, a structural and biophysical characterization of the interaction between VWF and FVIII is presented with focus on two of the domains that have been proven pivotal for mediating the interaction, namely the a3 region of FVIII and the TIL’E’ domains of VWF. Binding between the FVIII a3 region and VWF TIL’E’ was here observed using NMR spectroscopy, where chemical shift changes were localized to two β-sheet regions on the edge of TIL’E’ upon FVIII a3 region binding. Isothermal titration calorimetry and NMR spectroscopy were used to characterize the interaction between FVIII and TIL’E’ as well as mutants of TIL’E’, which further highlights the importance of the β-sheet region of TIL’E’ for high-affinity binding. Overall, the results presented provide new insight into the role the FVIII a3 region plays for complex formation between VWF and FVIII and the β-sheet region of TIL’E’ is shown to be important for FVIII binding. Thus, the results pave the way for further high-resolution insights into this imperative complex

Extremal and nonextremal Kerr/CFT correspondences

I rederive the Kerr/CFT correspondence without first taking the near-horizon extremal Kerr limit. This method extends easily to nonextremal black holes, for which the temperature and central charge behave poorly at the horizon but the entropy remains finite. A computation yields one-half of the standard Bekenstein-Hawking entropy, with hints that the other half may be related to a conformal field theory at the inner horizon. I then present an alternative approach, based on a stretched Killing horizon, in which the full entropy is obtained and the temperature and central charge remain well-behaved even in the nonextremal case.Comment: v3: missing term restored in eqn. (A.10) for central term; does not affect conclusions of this paper, but important in other context

Auditory temporal resolution of a wild white-beaked dolphin (Lagenorhynchus albirostris)

Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Journal of Comparative Physiology A: Neuroethology, Sensory, Neural, and Behavioral Physiology 195 (2009): 375-384, doi:10.1007/s00359-009-0415-x.Adequate temporal resolution is required across taxa to properly utilize amplitude modulated acoustic signals. Among mammals, odontocete marine mammals are considered to have relatively high temporal resolution, which is a selective advantage when processing fast traveling underwater sound. However, multiple methods used to estimate auditory temporal resolution have left comparisons among odontocetes and other mammals somewhat vague. Here we present the estimated auditory temporal resolution of an adult male white-beaked dolphin, (Lagenorhynchus albirostris), using auditory evoked potentials and click stimuli. Ours is the first of such studies performed on a wild dolphin in a capture-and-release scenario. The white-beaked dolphin followed rhythmic clicks up to a rate of approximately 1125-1250 Hz, after which the modulation rate transfer function (MRTF) cut-off steeply. However, 10% of the maximum response was still found at 1450 Hz indicating high temporal resolution. The MRTF was similar in shape and bandwidth to that of other odontocetes. The estimated maximal temporal resolution of white-beaked dolphins and other odontocetes was approximately twice that of pinnipeds and manatees, and more than ten-times faster than humans and gerbils. The exceptionally high temporal resolution abilities of odontocetes are likely due primarily to echolocation capabilities that require rapid processing of acoustic cues.We wish to thank the Danish Natural Science Research Council for major financial support (grant no. 272-05-0395)

Low hospital admission rates for respiratory diseases in children

BACKGROUND: Population-based data on hospital admissions for children aged 0-17 years concerning all respiratory diseases are scarce. This study examined hospital admissions in relation to the preceding consultations in general practice in this age group. METHODS: Data on children aged 0-17 years with respiratory diseases included in the Second Dutch National Survey of General Practice (DNSGP-2) were linked to all hospital admissions in the Dutch National Medical Registration. Admission rates for respiratory diseases were calculated. Data were analysed using multivariate logistic regression. RESULTS: Of all 79,272 children within the DNSGP-2, 1.8% were admitted to hospital for any respiratory diagnosis. The highest admission rates per 1000 children were for chronic disease of tonsils and adenoids (12.9); pneumonia and influenza (0.97); and asthma (0.92). Children aged 0-4 years and boys were admitted more frequently. Of children with asthma, 2.3% were admitted for respiratory diseases. For asthma, admission rates varied by urbanisation level: 0.47/1000 children/year in cities with ≤ 30,000 inhabitants, 1.12 for cities with ≥ 50,000 inhabitants, and 1.73 for the three largest cities (p = 0.002). Multivariate logistic regression showed that within two weeks after a GP consultation, younger age (OR 0.81, 95% CI 0.76-0.88) and more severe respiratory diseases (5.55, 95% CI 2.99-8.11) predicted hospital admission. CONCLUSIONS: Children in the general population with respiratory diseases (especially asthma) had very low hospital admission rates. In urban regions children were more frequently admitted due to respiratory morbidity. For effectiveness studies in a primary care setting, hospital admission rates should not be used as quality end-point

A Study to investigate the role of p27 and Cyclin E immunoexpression as a prognostic factor in early breast carcinoma

<p>Abstract</p> <p>Background</p> <p>Cyclin E and p27 expression is easy to assess in human tissues by standard immunohistochemical techniques. Immunohistochemistry is cost effective, relatively easy to perform and will play more of a role in the future management of cancer. The aim of this study was to investigate the role of p27 and cyclin E immunoexpression as a prognostic factor in early breast carcinoma.</p> <p>Methods</p> <p>Cyclin E and p27 immunohistochemistry was performed on sixty six cases of breast carcinoma submitted over a five year period to the Division of Anatomical Pathology, Groote Schuur hospital; Whittaker and Associates; and PathCare. All tumours included in this study were less than 5 cm in diameter (pT1 and pT2 stage) and all the patients had wide local excisions performed. Follow up information was obtained from patient folders in the Department of Radiation Oncology.</p> <p>Results</p> <p>There was no significant association of cyclin E and p27 expression with distant metastasis free survival (MFS) for all invasive carcinomas in contrast to grade, lymph node spread and vascular invasion. However, there was a statistically significant direct association of cyclin E with distant metastases in all invasive carcinomas, in the subgroup of infiltrating duct carcinomas (IDC) and in the node negative group when cyclin E was stratified as negative and positive (low/high). In this study of early breast carcinoma, only 9/66 cases showed cyclin E expression. Of these, four patients had distant metastases, one patient had a local recurrence and four patients were alive at last follow-up. Furthermore, cyclin E expression was significantly associated with grade, lymph node spread, oestrogen receptor status and histological type. None of the lobular carcinomas showed cyclin E positivity and only one case of lobular carcinoma presented with distant metastases.</p> <p>59/66 cases were positive (low/high) for p27 while seven cases were negative, 22 cases showed low expression and 37 cases demonstrated high p27 expression.</p> <p>p27 was significantly associated with oestrogen receptor status only for all invasive carcinomas and in the IDC group. There was no statistical relationship between p27 and cyclin E, but 50 (76%) tumours with positive p27 expression were negative for cyclin E. There were similar results for the invasive ductal carcinoma subgroup.</p> <p>Conclusion</p> <p>This study shows that p27 and cyclin E are not good independent prognostic markers for early breast carcinoma in contrast to grade, lymph node spread and vascular invasion for all invasive carcinomas. However, cyclin E provides some prognostic value as there is a direct statistical association with the development of distant metastases. Many previous studies have correlated overexpression of cyclin E with an aggressive course. The inverse relationship between p27 and cyclin E expression which has been reported in the literature has been highlighted, but this was not statistically significant. Most cases showed positive p27 expression and negative Cyclin E expression. This may be due to the early stage of the disease.</p

Limits on WWZ and WW\gamma couplings from p\bar{p}\to e\nu jj X events at \sqrt{s} = 1.8 TeV

We present limits on anomalous WWZ and WW-gamma couplings from a search for WW and WZ production in p-bar p collisions at sqrt(s)=1.8 TeV. We use p-bar p -> e-nu jjX events recorded with the D0 detector at the Fermilab Tevatron Collider during the 1992-1995 run. The data sample corresponds to an integrated luminosity of 96.0+-5.1 pb^(-1). Assuming identical WWZ and WW-gamma coupling parameters, the 95% CL limits on the CP-conserving couplings are -0.33<lambda<0.36 (Delta-kappa=0) and -0.43<Delta-kappa<0.59 (lambda=0), for a form factor scale Lambda = 2.0 TeV. Limits based on other assumptions are also presented.Comment: 11 pages, 2 figures, 2 table