Gefitinib and High-Dose Fractionated Radiotherapy for Carcinomatous Encephalitis from Non-Small Cell Lung Carcinoma

Carcinomatous encephalitis is a rapidly fatal form of metastasis caused by miliary spread of systemic cancer into the brain parenchyma. The diagnostic criteria and optimal treatment for this disease are not well defined. We report a patient with rapid neurologic deterioration from carcinomatous encephalitis from lung adenocarcinoma. She was treated with gefitinib and high-dose fractionated whole brain radiotherapy, and eventually improved neurologically and was discharged home on hospital day 48. Gefitinib and high-dose fractionated radiotherapy may have synergistic activity in patients with carcinomatous encephalitis from non-small cell lung cancer having favorable prognostic factors. More importantly, timely recognition of this disease and the use of large fraction radiation therapy are necessary to control rapid neurologic deterioration

Sashimi plots: Quantitative visualization of RNA sequencing read alignments

We introduce Sashimi plots, a quantitative multi-sample visualization of mRNA sequencing reads aligned to gene annotations. Sashimi plots are made using alignments (stored in the SAM/BAM format) and gene model annotations (in GFF format), which can be custom-made by the user or obtained from databases such as Ensembl or UCSC. We describe two implementations of Sashimi plots: (1) a stand-alone command line implementation aimed at making customizable publication quality figures, and (2) an implementation built into the Integrated Genome Viewer (IGV) browser, which enables rapid and dynamic creation of Sashimi plots for any genomic region of interest, suitable for exploratory analysis of alternatively spliced regions of the transcriptome. Isoform expression estimates outputted by the MISO program can be optionally plotted along with Sashimi plots. Sashimi plots can be used to quickly screen differentially spliced exons along genomic regions of interest and can be used in publication quality figures. The Sashimi plot software and documentation is available from: http://genes.mit.edu/burgelab/miso/docs/sashimi.htmlComment: 2 figure

Precise B, B_s and B_c meson spectroscopy from full lattice QCD

We give the first accurate results for $B$ and $B_s$ meson masses from lattice QCD including the effect of $u$, $d$ and $s$ sea quarks, and we improve an earlier value for the $B_c$ meson mass. By using the Highly Improved Staggered Quark action for $u/d$, $s$ and $c$ quarks and NRQCD for the $b$ quarks, we are able to achieve an accuracy in the masses of around 10 MeV. Our results are: $m_B$ = 5.291(18) GeV, $m_{B_s}$ = 5.363(11) GeV and $m_{B_c}$ = 6.280(10) GeV. Note that all QCD parameters here are tuned from other calculations, so these are parameter free tests of QCD against experiment. We also give scalar, $B_{s0}^*$, and axial vector, $B_{s1}$, meson masses. We find these to be slightly below threshold for decay to $BK$ and $B^*K$ respectively.Comment: 22 pages, 19 figure

The role of brevican in glioma: promoting tumor cell motility in vitro and in vivo

Background: Malignant glioma is a common primary tumor of the central nervous system. Brevican, an abundant extracellular matrix component in the adult brain, plays a critical role in the process of glioma. The mechanisms for the highly invasive behavior of gliomas are still poorly understood. The aim of this study was to examine whether brevican is a predictor of glioma and its roles in glioma cell motility. Methods: In this study, immunohistochemistry staining for brevican expression was performed in malignant gliomas and benign controls. We also explored the effects of brevican on cell adhesion and migration in brevican-overexpressed cells. Knockdown of brevican expression was achieved by stable transfection of U251 cells transduced with a construct encoding a short hairpin DNA directed against the brevican gene, which correspondingly, down-regulated the proliferation, invasion and spread of brevican-expressing cells. Moreover, the role of brevican in the growth and progression of glioma was demonstrated by in vivo studies. Results: Our results provide evidence for the molecular and cellular mechanisms that may underlie the motility-promoting role of brevican in the progression of glioma. The role of brevican as a target for immunotherapy might be taken into consideration in future studies. Conclusions: This study suggests that expression of brevican is associated with glioma cell adhesion, motility and tumor growth, and also is related to glioma cell differentiation, therefore it may be a marker for malignance degree of gliom

Study on Incentives for Glaucoma Medication Adherence (SIGMA): study protocol for a randomized controlled trial to increase glaucoma medication adherence using value pricing

BACKGROUND: Many glaucoma patients do not adhere to their medication regimens because they fail to internalize the (health) costs of non-adherence, which may not occur until years or decades later. Behavioural economic theory suggests that adherence rates can be improved by offering patients a near-term benefit. Our proposed strategy is to offer adherence-contingent rebates on medication and check-up costs. This form of value pricing (VP) ensures that rebates are granted only to those most likely to benefit. Moreover, by leveraging loss aversion, rebates are expected to generate a stronger behavioural response than equivalent financial rewards. METHODS/DESIGN: The main objective of the Study on Incentives for Glaucoma Medication Adherence (SIGMA) is to test the VP approach relative to usual care (UC) in improving medication adherence. SIGMA is a randomized, controlled, open-label, single-centre superiority trial with two parallel arms. A total of 100 non-adherent (Morisky Medication Adherence Scale ≤6) glaucoma patients from the Singapore National Eye Centre are block-randomized (blocking factor: single versus multiple medications users) into the VP and UC arms in a 1:1 ratio. The treatment received by VP patients will be strictly identical to that received by UC patients, with the only exception being that VP patients can earn either a 50 % or 25 % rebate on their glaucoma-related healthcare costs conditional on being adherent on at least 90 % or 75 % of days as measured by a medication event monitoring system. Masking the arm allocation will be precluded by the behavioural nature of the intervention but blocking size will not be disclosed to protect concealment. The primary outcome is the mean change from baseline in percentage of adherent days at month 6. A day will be counted as adherent when the patients take all their medication(s) within the appropriate dosing windows. DISCUSSION: This trial will provide evidence on whether adherence-contingent rebates can improve medication adherence among non-adherent glaucoma patients, and more generally whether this approach represents a promising strategy to cost-effectively improve chronic disease management. TRIAL REGISTRATION: NCT02271269 . Registered on 19 October 2014

Response Assessment of NovoTTF-100A Versus Best Physician\u27s Choice Chemotherapy in Recurrent Glioblastoma

The NovoTTF-100A device emits frequency-tuned alternating electric fields that interfere with tumor cell mitosis. In phase III trial for recurrent glioblastomas, NovoTTF-100A was shown to have equivalent efficacy and less toxicity when compared to Best Physician\u27s Choice (BPC) chemotherapy. We analyzed the characteristics of responders and nonresponders in both cohorts to determine the characteristics of response and potential predictive factors. Tumor response and progression were determined by Macdonald criteria. Time to response, response duration, progression-free survival (PFS) ± Simon-Makuch correction, overall survival (OS), prognostic factors, and relative hazard rates were compared between responders and nonresponders. Median response duration was 7.3 versus 5.6 months for NovoTTF-100A and BPC chemotherapy, respectively (P = 0.0009). Five of 14 NovoTTF-100A responders but none of seven BPC responders had prior low-grade histology. Mean cumulative dexamethasone dose was 35.9 mg for responders versus 485.6 mg for nonresponders in the NovoTTF-100A cohort (P \u3c 0.0001). Hazard analysis showed delayed tumor progression in responders compared to nonresponders. Simon-Makuch-adjusted PFS was longer in responders than in nonresponders treated with NovoTTF-100A (P = 0.0007) or BPC chemotherapy (P = 0.0222). Median OS was longer for responders than nonresponders treated with NovoTTF-100A (P \u3c 0.0001) and BPC chemotherapy (P = 0.0235). Pearson analysis showed strong correlation between response and OS in NovoTTF-100A (P = 0.0002) but not in BPC cohort (P = 0.2900). Our results indicate that the response characteristics favor NovoTTF-100A and data on prior low-grade histology and dexamethasone suggest potential genetic and epigenetic determinants of NovoTTF-100A response

Global Vision Impairment Due to Uncorrected Presbyopia

Objectives: To evaluate the personal and community burdens of uncorrected presbyopia. Methods: We used multiple population-based surveys to estimate the global presbyopia prevalence, the spectacle coverage rate for presbyopia, and the community perception of vision impairment caused by uncorrected presbyopia. For planning purposes, the data were extrapolated for the future using population projections extracted from the International Data Base of the US Census Bureau. Results: It is estimated that there were 1.04 billion people globally with presbyopia in 2005, 517 million of whom had no spectacles or inadequate spectacles. Of these, 410 million were prevented from performing near tasks in the way they required. Vision impairment from uncorrected presbyopia predominantly exists (94%) in the developing world. Conclusions: Uncorrected presbyopia causes widespread, avoidable vision impairment throughout the world. Alleviation of this problem requires a substantial increase in the number of personnel trained to deliver appropriate eye care together with the establishment of sustainable, affordable spectacle delivery systems in developing countries. In addition, given that people with presbyopia are at higher risk for permanently sight-threatening conditions such as glaucoma and diabetic eye disease, primary eye care should include refraction services as well as detection and appropriate referral for these and other such conditions

Analysis of physical characteristics of Tumor Treating Fields for human glioblastoma

Abstract Tumor Treating Fields (TTFields) therapy is an approved treatment that has known clinical efficacy against recurrent and newly diagnosed glioblastoma. However, the distribution of the electric fields and the corresponding pattern of energy deposition in the brain are poorly understood. To evaluate the physical parameters that may influence TTFields, postacquisition MP‐RAGE, T1 and T2 MRI sequences from a responder with a right parietal glioblastoma were anatomically segmented and then solved using finite‐element method to determine the distribution of the electric fields and rate of energy deposition at the gross tumor volume (GTV) and other intracranial structures. Electric field–volume histograms (EVH) and specific absorption rate–volume histograms (SARVH) were constructed to numerically evaluate the relative and/or absolute magnitude volumetric differences between models. The electric field parameters EAUC, VE 150, E95%, E50%, and E20%, as well as the SAR parameters SARAUC, VSAR 7.5, SAR 95%, SAR 50%, and SAR 20%, facilitated comparisons between models derived from various conditions. Specifically, TTFields at the GTV were influenced by the dielectric characteristics of the adjacent tissues as well as the GTV itself, particularly the presence or absence of a necrotic core. The thickness of the cerebrospinal fluid on the convexity of the brain and the geometry of the tumor were also relevant factors. Finally, the position of the arrays also influenced the electric field distribution and rate of energy deposition in the GTV. Using EVH and SARVH, a personalized approach for TTFields treatment can be developed when various patient‐related and tumor‐related factors are incorporated into the planning procedure