Automated hippocampal segmentation in patients with epilepsy: Available free online

Hippocampal sclerosis, a common cause of refractory focal epilepsy, requires hippocampal volumetry for accurate diagnosis and surgical planning. Manual segmentation is time-consuming and subject to interrater/intrarater variability. Automated algorithms perform poorly in patients with temporal lobe epilepsy. We validate and make freely available online a novel automated method

Tamoxifen resistance in early breast cancer: statistical modelling of tissue markers to improve risk prediction

BACKGROUND: For over two decades, the Nottingham Prognostic Index (NPI) has been used in the United Kingdom to calculate risk scores and inform management about breast cancer patients. It is derived using just three clinical variables - nodal involvement, tumour size and grade. New scientific methods now make cost-effective measurement of many biological characteristics of tumour tissue from breast cancer biopsy samples possible. However, the number of potential explanatory variables to be considered presents a statistical challenge. The aim of this study was to investigate whether in ER+ tamoxifen-treated breast cancer patients, biological variables can add value to NPI predictors, to provide improved prognostic stratification in terms of overall recurrence-free survival (RFS) and also in terms of remaining recurrence free while on tamoxifen treatment (RFoT). A particular goal was to enable the discrimination of patients with a very low risk of recurrence. METHODS: Tissue samples of 401 cases were analysed by microarray technology, providing biomarker data for 72 variables in total, from AKT, BAD, HER, MTOR, PgR, MAPK and RAS families. Only biomarkers screened as potentially informative (i.e., exhibiting univariate association with recurrence) were offered to the multivariate model. The multiple imputation method was used to deal with missing values, and bootstrap sampling was used to assess internal validity and refine the model. RESULTS: Neither the RFS nor RFoT models derived included Grade, but both had better predictive and discrimination ability than NPI. A slight difference was observed between models in terms of biomarkers included, and, in particular, the RFoT model alone included HER2. The estimated 7-year RFS rates in the lowest-risk groups by RFS and RFoT models were 95 and 97%, respectively, whereas the corresponding rate for the lowest-risk group of NPI was 89%. CONCLUSION: The findings demonstrate considerable potential for improved prognostic modelling by incorporation of biological variables into risk prediction. In particular, the ability to identify a low-risk group with minimal risk of recurrence is likely to have clinical appeal. With larger data sets and longer follow-up, this modelling approach has the potential to enhance an understanding of the interplay of biological characteristics, treatment and cancer recurrence. British Journal of Cancer (2010) 102, 1503 - 1510. doi:10.1038/sj.bjc.6605627 www.bjcancer.co

How do enamelysin and kallikrein 4 process the 32-kDa enamelin?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74876/1/j.1600-0722.2006.00281.x.pd

The value of repeat neuroimaging for epilepsy at a tertiary referral centre: 16 years of experience.

PURPOSE: Magnetic resonance imaging (MRI) is the investigation of choice for detecting structural lesions that underlie and may accompany epilepsy. Despite advances in imaging technology, 20-30% of patients with refractory focal epilepsy have normal MRI scans. We evaluated the role of repeated imaging with improved MRI technology - an increase in field strength from 1.5T to 3T and superior head coils - in detecting pathology not previously seen. METHODS: Retrospective review of a large cohort of patients attending a tertiary epilepsy referral centre who underwent MRI at 1.5T (1995-2004) and subsequently 3T (2004-2011) with improved head coils. Scan reports were reviewed for the diagnoses and medical notes for the epilepsy classification. RESULTS: 804 patients underwent imaging on both scanners, the majority with focal epilepsy (87%). On repeat scanning at 3T, 37% of scans were normal and 20% showed incidental findings. Positive findings included hippocampal sclerosis (13%), malformations of cortical development (8%), other abnormalities (4%) and previous surgery (18%). A total of 37 (5%) relevant new diagnoses were made on the 3T scans not previously seen at 1.5T. The most common new findings were hippocampal sclerosis, focal cortical dysplasia and dysembryoplastic neuroepithelial tumour. These findings affected patient management with several patients undergoing neurosurgery. CONCLUSIONS: The higher field strength and improved head coils were associated with a clinically relevant increased diagnostic yield from MRI. This highlights the importance of technological advances and suggests that rescanning patients with focal epilepsy and previously negative scans is clinically beneficial

Verticalization of bacterial biofilms

Biofilms are communities of bacteria adhered to surfaces. Recently, biofilms of rod-shaped bacteria were observed at single-cell resolution and shown to develop from a disordered, two-dimensional layer of founder cells into a three-dimensional structure with a vertically-aligned core. Here, we elucidate the physical mechanism underpinning this transition using a combination of agent-based and continuum modeling. We find that verticalization proceeds through a series of localized mechanical instabilities on the cellular scale. For short cells, these instabilities are primarily triggered by cell division, whereas long cells are more likely to be peeled off the surface by nearby vertical cells, creating an "inverse domino effect". The interplay between cell growth and cell verticalization gives rise to an exotic mechanical state in which the effective surface pressure becomes constant throughout the growing core of the biofilm surface layer. This dynamical isobaricity determines the expansion speed of a biofilm cluster and thereby governs how cells access the third dimension. In particular, theory predicts that a longer average cell length yields more rapidly expanding, flatter biofilms. We experimentally show that such changes in biofilm development occur by exploiting chemicals that modulate cell length.Comment: Main text 10 pages, 4 figures; Supplementary Information 35 pages, 15 figure

Guaranteed violation of a Bell inequality without aligned reference frames or calibrated devices

Bell tests---the experimental demonstration of a Bell inequality violation---are central to understanding the foundations of quantum mechanics, underpin quantum technologies, and are a powerful diagnostic tool for technological developments in these areas. To date, Bell tests have relied on careful calibration of the measurement devices and alignment of a shared reference frame between the two parties---both technically demanding tasks in general. Surprisingly, we show that neither of these operations are necessary, violating Bell inequalities with near certainty with (i) unaligned, but calibrated, measurement devices, and (ii) uncalibrated and unaligned devices. We demonstrate generic quantum nonlocality with randomly chosen local measurements on a singlet state of two photons implemented with reconfigurable integrated optical waveguide circuits based on voltage-controlled phase shifters. The observed results demonstrate the robustness of our schemes to imperfections and statistical noise. This new approach is likely to have important applications in both fundamental science and in quantum technologies, including device independent quantum key distribution.Comment: 7 pages, 7 figure

Characterisation of feline renal cortical fibroblast cultures and their transcriptional response to transforming growth factor beta 1

Chronic kidney disease (CKD) is common in geriatric cats, and the most prevalent pathology is chronic tubulointerstitial inflammation and fibrosis. The cell type predominantly responsible for the production of extra-cellular matrix in renal fibrosis is the myofibroblast, and fibroblast to myofibroblast differentiation is probably a crucial event. The cytokine TGF-β1 is reportedly the most important regulator of myofibroblastic differentiation in other species. The aim of this study was to isolate and characterise renal fibroblasts from cadaverous kidney tissue of cats with and without CKD, and to investigate the transcriptional response to TGF-β1

Experimental measurement-based quantum computing beyond the cluster-state model

The paradigm of measurement-based quantum computation opens new experimental avenues to realize a quantum computer and deepens our understanding of quantum physics. Measurement-based quantum computation starts from a highly entangled universal resource state. For years, clusters states have been the only known universal resources. Surprisingly, a novel framework namely quantum computation in correlation space has opened new routes to implement measurement-based quantum computation based on quantum states possessing entanglement properties different from cluster states. Here we report an experimental demonstration of every building block of such a model. With a four-qubit and a six-qubit state as distinct from cluster states, we have realized a universal set of single-qubit rotations, two-qubit entangling gates and further Deutsch's algorithm. Besides being of fundamental interest, our experiment proves in-principle the feasibility of universal measurement-based quantum computation without using cluster states, which represents a new approach towards the realization of a quantum computer.Comment: 26 pages, final version, comments welcom

The deuteron: structure and form factors

A brief review of the history of the discovery of the deuteron in provided. The current status of both experiment and theory for the elastic electron scattering is then presented.Comment: 80 pages, 33 figures, submited to Advances in Nuclear Physic