In rifampicin-resistant TB, bedaquiline-containing regimens reduced unfavorable status vs. a control regimen at 132 wk.

GIM/FP/GP: [Formula: see text] Infectious Disease: [Formula: see text] Pulmonology: [Formula: see text].

and constitute a gene regulatory network essential for the development of functional proprioceptors.

Coordinated animal locomotion depends on the development of functional proprioceptors. While early cell-fate determination processes are well characterized, little is known about the terminal differentiation of cells within the proprioceptive lineage and the genetic networks that control them. In this work we describe a gene regulatory network consisting of three transcription factors-Prospero (Pros), D-Pax2, and Delilah (Dei)-that dictates two alternative differentiation programs within the proprioceptive lineage in .

Acoustic component programming in children with cochlear implants using electrocochleography.

Objective: Objective measurements improve reliability and effectiveness of hearing assessment and cochlear implant (CI) programming in young children. In CI recipients with acoustic hearing in the implanted ear, electrocochleography (ECochG) can be conducted using intracochlear electrodes. The cochlear microphonic (CM) portion of ECochG has been shown to correlate with pure-tone audiometric thresholds in adult and paediatric CI recipients.

Comparison of Pure-Tone Thresholds and Cochlear Microphonics Thresholds in Pediatric Cochlear Implant Patients.

Objectives: In adult cochlear implant patients, conventional audiometry is used to measure postoperative residual hearing which requires active listening and patient feedback. However, audiological measurements in pediatric cochlear implant patients are both challenging as well as time consuming. Intracochlear electrocochleography (ECOG) offers an objective and a time-efficient method to measure frequency-specific cochlear microphonic or difference thresholds (CM/DIF) thresholds that closely approximate auditory thresholds in adult cochlear implant patients.

Selective peripheral nerve recordings from nerve cuff electrodes using convolutional neural networks.

Objective: Recording and stimulating from the peripheral nervous system are becoming important components in a new generation of bioelectronics systems. Although neurostimulation has seen a history of successful chronic applications in humans, peripheral nerve recording in humans chronically remains a challenge. Multi-contact nerve cuff electrode configurations have the potential to improve recording selectivity.

Classification of naturally evoked compound action potentials in peripheral nerve spatiotemporal recordings.

Peripheral neural signals have the potential to provide the necessary motor, sensory or autonomic information for robust control in many neuroprosthetic and neuromodulation applications. However, developing methods to recover information encoded in these signals is a significant challenge. We introduce the idea of using spatiotemporal signatures extracted from multi-contact nerve cuff electrode recordings to classify naturally evoked compound action potentials (CAP).

Adverse mental health outcomes in a population-based cohort of survivors of childhood cancer.

Background: The elevated risk for physical late effects in childhood cancer survivors (CCS) is well documented, but their risk for mental health problems is less well described.

Methods: The authors assembled a cohort of all 5-year CCS who were diagnosed before age 18 years and treated in an Ontario pediatric cancer center between 1987 and 2008. Patients were matched to population controls and linked to health administration databases.

The Impact of Anisotropy on the Accuracy of Conductivity Imaging: A Quantitative Validation Study.

We present a quantitative validation study to assess the accuracy of low-frequency conductivity imaging methods, based on a testing current measured using Current Density Imaging (CDI). We tested the proposed procedure to study the influence of tissue anisotropy on the accuracy of conductivity reconstruction methods, using a finite element model of anisotropic brain tissue. Simulations were carried out for three different levels of tissue anisotropy to compare the results obtained by our recently developed anisotropic conductivity method with those obtained by our well-established conductivity method that assumes isotropic conductivity.

Use of spatiotemporal templates for pathway discrimination in peripheral nerve recordings: a simulation study.

Objective: Extraction of information from the peripheral nervous system can provide control signals in neuroprosthetic applications. However, the ability to selectively record from different pathways within peripheral nerves is limited. We investigated the integration of spatial and temporal information for pathway discrimination in peripheral nerves using measurements from a multi-contact nerve cuff electrode.

A newly identified type of attachment cell is critical for normal patterning of chordotonal neurons.

This work describes unknown aspects of chordotonal organ (ChO) morphogenesis revealed in post-embryonic stages through the use of new fluorescently labeled markers. We show that towards the end of embryogenesis a hitherto unnoticed phase of cell migration commences in which the cap cells of the ventral ChOs elongate and migrate towards their prospective attachment sites. This migration and consequent cell attachment generates a continuous zigzag line of proprioceptors, stretching from the ventral midline to a dorsolateral position in each abdominal segment.

FV-162 is a novel, orally bioavailable, irreversible proteasome inhibitor with improved pharmacokinetics displaying preclinical efficacy with continuous daily dosing.

Approved proteasome inhibitors have advanced the treatment of multiple myeloma but are associated with serious toxicities, poor pharmacokinetics, and most with the inconvenience of intravenous administration. We therefore sought to identify novel orally bioavailable proteasome inhibitors with a continuous daily dosing schedule and improved therapeutic window using a unique drug discovery platform. We employed a fluorine-based medicinal chemistry technology to synthesize 14 novel analogs of epoxyketone-based proteasome inhibitors and screened them for their stability, ability to inhibit the chymotrypsin-like proteasome, and antimyeloma activity in vitro.

Deconstructing the complexity of regulating common properties in different cell types: lessons from the delilah gene.

To understand development we need to understand how transcriptional regulatory mechanisms are employed to confer different cell types with their unique properties. Nonetheless it is also critical to understand how such mechanisms are used to confer different cell types with common cellular properties, such as the ability to adhere to the extracellular matrix. To decode how adhesion is regulated in cells stemming from different pedigrees we analyzed the regulatory region that drives the expression of Dei, which is a transcription factor that serves as a central determinant of cell adhesion, particularly by inducing expression of βPS-integrin.

Multiscale properties of weighted total variation flow with applications to denoising and registration.

Images consist of structures of varying scales: large scale structures such as flat regions, and small scale structures such as noise, textures, and rapidly oscillatory patterns. In the hierarchical (BV, L(2)) image decomposition, Tadmor, et al. (2004) start with extracting coarse scale structures from a given image, and successively extract finer structures from the residuals in each step of the iterative decomposition.

Multiscale registration of real-time and prior MRI data for image-guided cardiac interventions.

Recently, there is a growing interest in using magnetic resonance imaging (MRI) to guide interventional procedures due to its excellent soft tissue contrast and lack of ionizing radiation compared to traditional radiographic guidance. One of these applications is the use of MRI to guide radio frequency ablation of anatomic substrates, within the left ventricle, responsible for ventricular tachycardia. However, different MRI acquisition schemes have significant tradeoffs between image quality and acquisition time.

The mammalian-membrane two-hybrid assay (MaMTH) for probing membrane-protein interactions in human cells.

Cell signaling, one of key processes in both normal cellular function and disease, is coordinated by numerous interactions between membrane proteins that change in response to stimuli. We present a split ubiquitin-based method for detection of integral membrane protein-protein interactions (PPIs) in human cells, termed mammalian-membrane two-hybrid assay (MaMTH). We show that this technology detects stimulus (hormone or agonist)-dependent and phosphorylation-dependent PPIs.

Experimental implementation of a new method of imaging anisotropic electric conductivities.

This paper presents the first experiment of imaging anisotropic impedance using a novel technique called Diffusion Tensor Current Density Impedance Imaging (DTCD-II). A biological anisotropic tissue phantom was constructed and an experimental implementation of the new method was performed. The results show that DT-CD-II is an effective way of non-invasively measuring anisotropic conductivity in biological media.

Visualization of proprioceptors in Drosophila larvae and pupae.

Proprioception is the ability to sense the motion, or position, of body parts by responding to stimuli arising within the body. In fruitflies and other insects proprioception is provided by specialized sensory organs termed chordotonal organs (ChOs). Like many other organs in Drosophila, ChOs develop twice during the life cycle of the fly.

Retrocochlear hearing loss in infants: a case study of juvenile pilocytic astrocytoma.

Objective: The purpose of this paper was to describe a child with brainstem juvenile pilocytic astrocytoma (JPA) and associated auditory symptoms.

Design: Case study of a 5-year-old female who presented with a complaint of headaches, accompanied with a history of symptoms that could be associated with a left unilateral congenital auditory neuropathy. She was later diagnosed with a large, left-sided posterior fossa mass determined to be a JPA.

Spatial regulation of cell adhesion in the Drosophila wing is mediated by Delilah, a potent activator of βPS integrin expression.

In spite of our conceptual view of how differential gene expression is used to define different cell identities, we still do not understand how different cell identities are translated into actual cell properties. The example discussed here is that of the fly wing, which is composed of two main cell types: vein and intervein cells. These two cell types differ in many features, including their adhesive properties.

Polar decomposition radio-frequency current density imaging.

Polar Decomposition Radio-frequency Current Density Imaging (PD-RFCDI) is an imaging technique that non-invasively measures RF current density components inside a sample using MRI. Previous PD-RFCDI implementations suffer from the strict constraint on the amount of applied current as well as severe interference from the unwanted induced current. This work proposes solutions to both problems which successfully remove the current constraints of PD-RFCDI.

Radio-frequency current density imaging based on a 180 (°) sample rotation with feasibility study of full current density vector reconstruction.

Radio-frequency current density imaging (RF-CDI) is a technique that noninvasively measures current density distributions at the Larmor frequency utilizing magnetic resonance imaging. Previously implemented RF-CDI methods reconstruct the applied current density component J(z) along the static magnetic field of the imager [(B)\vec](0) (the z direction) based on the assumption that the z-directional change of the magnetic field component H(z) can be ignored compared to J(z). However, this condition may be easily violated in biomedical applications.

A key role for ATF3 in regulating mast cell survival and mediator release.

Activating transcription factor 3 (ATF3) is a basic leucine zipper transcription factor that plays a regulatory role in inflammation, cell division, and apoptosis. Mast cells (MCs) initiate many inflammatory responses and have a central role in allergy and allergic diseases. We report here that ATF3 has a central role in MC development and function.

Electrical conductivity imaging using MRI measurement of the magnetic field vector.

Current density and electrical conductivity imaging research at the University of Toronto is reviewed. Methods for imaging live animals at low frequency are described and contrasted with EIT and other MRI based techniques. New work on imaging at radio frequencies is presented and future work directions are discussed.

Multislice radio-frequency current density imaging.

Radio-frequency current density imaging (RF-CDI) is an imaging technique that noninvasively measures current density distribution at the Larmor frequency utilizing magnetic resonance imaging (MRI). Previously implemented RF-CDI techniques were only able to image a single slice transverse to the static magnetic field B(0) . This paper describes the first realization of a multislice RF-CDI sequence on a 1.

Current density impedance imaging.

Current density impedance imaging (CDII) is a new impedance imaging technique that can noninvasively measure the conductivity distribution inside a medium. It utilizes current density vector measurements which can be made using a magnetic resonance imager (MRI) (Scott , 1991). CDII is based on a simple mathematical expression for inverted Delta sigma / sigma = inverted Delta ln sigma, the gradient of the logarithm of the conductivity sigma, at each point in a region where two current density vectors J1 and J2 have been measured and J1 x J2 not equal 0.