T2 mapping outperforms normalised FLAIR in identifying hippocampal sclerosis

Rationale Qualitatively, FLAIR MR imaging is sensitive to the detection of hippocampal sclerosis (HS). Quantitative analysis of T2 maps provides a useful objective measure and increased sensitivity over visual inspection of T2-weighted scans. We aimed to determine whether quantification of normalised FLAIR is as sensitive as T2 mapping in detection of HS. Method Dual echo T2 and FLAIR MR images were retrospectively analysed in 27 patients with histologically confirmed HS and increased T2 signal in ipsilateral hippocampus and 14 healthy controls. Regions of interest were manually segmented in all hippocampi aiming to avoid inclusion of CSF. Hippocampal T2 values and measures of normalised FLAIR Signal Intensity (nFSI) were compared in healthy and sclerotic hippocampi. Results HS was identified on T2 values with 100% sensitivity and 100% specificity. HS was identified on nFSI measures with 60% sensitivity and 93% specificity. Conclusion T2 mapping is superior to nFSI for identification of HS

Amyotrophic lateral sclerosis genetic studies: from genome-wide association mapping to genome sequencing

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of obscure etiology. Multiple genetic studies have been conducted to advance our understanding of the disease, employing a variety of techniques such as linkage mapping in families, to genome-wide association studies and sequencing based approaches such as whole exome sequencing and whole genome sequencing and a few epigenetic analyses. While major progress has been made, the majority of the genetic variation involved in ALS is yet to be undefined. The optimal study designs to investigate ALS depend on the genetic model for the disease, and it is likely that different approaches will be required to map genes involved in familial and sporadic disease. The potential approaches and their strengths and weaknesses are discussed

Double Photoionization of Helium

The cross sections for double photoionization of helium and the ratios of double to single ionization have been measured from the double-ionization threshold to 820 eV. The results are in very good agreement with several recent calculations

Assembling evidence for identifying reservoirs of infection

Many pathogens persist in multihost systems, making the identification of infection reservoirs crucial for devising effective interventions. Here, we present a conceptual framework for classifying patterns of incidence and prevalence, and review recent scientific advances that allow us to study and manage reservoirs simultaneously. We argue that interventions can have a crucial role in enriching our mechanistic understanding of how reservoirs function and should be embedded as quasi-experimental studies in adaptive management frameworks. Single approaches to the study of reservoirs are unlikely to generate conclusive insights whereas the formal integration of data and methodologies, involving interventions, pathogen genetics, and contemporary surveillance techniques, promises to open up new opportunities to advance understanding of complex multihost systems

Non-Redundant Spectral Dimensionality Reduction

Spectral dimensionality reduction algorithms are widely used in numerous domains, including for recognition, segmentation, tracking and visualization. However, despite their popularity, these algorithms suffer from a major limitation known as the "repeated Eigen-directions" phenomenon. That is, many of the embedding coordinates they produce typically capture the same direction along the data manifold. This leads to redundant and inefficient representations that do not reveal the true intrinsic dimensionality of the data. In this paper, we propose a general method for avoiding redundancy in spectral algorithms. Our approach relies on replacing the orthogonality constraints underlying those methods by unpredictability constraints. Specifically, we require that each embedding coordinate be unpredictable (in the statistical sense) from all previous ones. We prove that these constraints necessarily prevent redundancy, and provide a simple technique to incorporate them into existing methods. As we illustrate on challenging high-dimensional scenarios, our approach produces significantly more informative and compact representations, which improve visualization and classification tasks

Triggered qutrits for Quantum Communication protocols

A general protocol in Quantum Information and Communication relies in the ability of producing, transmitting and reconstructing, in general, qunits. In this letter we show for the first time the experimental implementation of these three basic steps on a pure state in a three dimensional space, by means of the orbital angular momentum of the photons. The reconstruction of the qutrit is performed with tomographic techniques and a Maximum-Likelihood estimation method. In this way we also demonstrate that we can perform any transformation in the three dimensional space

Oncolytic viruses as therapeutic cancer vaccines

Oncolytic viruses (OVs) are tumor-selective, multi-mechanistic antitumor agents. They kill infected cancer and associated endothelial cells via direct oncolysis, and uninfected cells via tumor vasculature targeting and bystander effect. Multimodal immunogenic cell death (ICD) together with autophagy often induced by OVs not only presents potent danger signals to dendritic cells but also efficiently cross-present tumor-associated antigens from cancer cells to dendritic cells to T cells to induce adaptive antitumor immunity. With this favorable immune backdrop, genetic engineering of OVs and rational combinations further potentiate OVs as cancer vaccines. OVs armed with GM-CSF (such as T-VEC and Pexa-Vec) or other immunostimulatory genes, induce potent anti-tumor immunity in both animal models and human patients. Combination with other immunotherapy regimens improve overall therapeutic efficacy. Coadministration with a HDAC inhibitor inhibits innate immunity transiently to promote infection and spread of OVs, and significantly enhances anti-tumor immunity and improves the therapeutic index. Local administration or OV mediated-expression of ligands for Toll-like receptors can rescue the function of tumor-infiltrating CD8+ T cells inhibited by the immunosuppressive tumor microenvironment and thus enhances the antitumor effect. Combination with cyclophosphamide further induces ICD, depletes Treg, and thus potentiates antitumor immunity. In summary, OVs properly armed or in rational combinations are potent therapeutic cancer vaccines. © 2013 Bartlett et al.; licensee BioMed Central Ltd

Visual Psychophysics and Physiological Optics Handheld Shape Discrimination Hyperacuity Test on a Mobile Device for Remote Monitoring of Visual Function in Maculopathy

PURPOSE. Frequency monitoring of age-related macular degeneration (AMD) and diabetic retinopathy (DR) is crucial for timely intervention. This study evaluated a handheld shape discrimination hyperacuity (hSDH) test iPhone app designed for visual function selfmonitoring in patients with AMD and DR. METHODS. One hundred subjects (27 visually normal, 37 with AMD, and 36 with DR) were included based on clinical documentation and visual acuity of 20/100 or better. The hSDH test was implemented on the iOS platform. A cross-sectional study was conducted to compare the hSDH test with a previously established desktop SDH (dSDH) test and to assess the effect of disease severity on the hSDH test. A user survey was also conducted to assess the usability of the hSDH test on the mobile device. RESULTS. The hSDH test and dSDH test were highly correlated (r ¼ 0.88, P < 0.0001). BlandAltman analysis indicated no significant difference in hSDH and dSDH measurements. Oneway ANOVA indicated that the mean hSDH measurement of the eyes with advanced AMD (n ¼ 16) or with severe to very severe nonproliferative DR (NPDR) (n ¼ 12) was significantly worse than that of the eyes with intermediate AMD (n ¼ 11) or with mild to moderate NPDR (n ¼ 11) (P < 0.0001). Ninety-eight percent of 46 patients (10 with AMD and 36 with DR) who completed the usability survey reported that the hSDH test was easy to use. CONCLUSIONS. This study demonstrated that the hSDH test on a mobile device is comparable to PC-based testing methods. As a mobile app, it is intuitive to use, readily accessible, and sensitive to the severity of maculopathy. It has the potential to provide patients having maculopathy with a new tool to monitor their vision at home