Design and calibration of a Tonpilz transducer for low frequency medical ultrasound tomography.

The design and performance of a transducer for low frequency ultrasound tomography is presented, motivated by recent research demonstrating that acoustic waves transmitting at frequencies between 10 kHz and 750 kHz penetrate the lungs and may be useful for thoracic imaging. An adaptation of the traditional Tonpilz design was developed, vibrational amplitude and electrical impedance were measured, and an optimal frequency was determined. The design is found to meet the desired mechanical, electrical, and safety specifications. Thus, it was considered a promising option for the target application of pulmonary imaging with ultrasound computed tomography between 50 and 200 kHz; highest efficiency achieved around 125 kHz and 156 kHz, and beam divergence of 40°.

The D-bar method for electrical impedance tomography-demystified.

Electrical impedance tomography (EIT) is an imaging modality where a patient or object is probed using harmless electric currents. The currents are fed through electrodes placed on the surface of the target, and the data consists of voltages measured at the electrodes resulting from a linearly independent set of current injection patterns. EIT aims to recover the internal distribution of electrical conductivity inside the target. The inverse problem underlying the EIT image formation task is nonlinear and severely ill-posed, and hence sensitive to modeling errors and measurement noise. Therefore, the inversion process needs to be regularized. However, traditional variational regularization methods, based on optimization, often suffer from local minima because of nonlinearity. This is what makes regularized direct (non-iterative) methods attractive for EIT. The most developed direct EIT algorithm is the D-bar method, based on Complex Geometric Optics solutions and a nonlinear Fourier transform. Variants and recent developments of D-bar methods are reviewed, and their practical numerical implementation is explained.

Infant cognition includes the potentially human-unique ability to encode embedding.

Human cognition relies on the ability to encode complex regularities in the input. Regularities above a certain complexity level can involve the feature of embedding, defined by nested relations between sequential elements. While comparative studies suggest the cognitive processing of embedding to be human specific, evidence of its ontogenesis is lacking. To assess infants' ability to process embedding, we implemented nested relations in tone sequences, minimizing perceptual and memory requirements. We measured 5-month-olds' brain responses in two auditory oddball paradigms, presenting standard sequences with one or two levels of embedding, interspersed with infrequent deviant sequences violating the established embedding rules. Brain potentials indicate that infants detect embedding violations and thus appear to track nested relations. This shows that the ability to encode embedding may be part of the basic human cognitive makeup, which might serve as scaffolding for the acquisition of complex regularities in language or music.

Portable Pocket colposcopy performs comparably to standard-of-care clinical colposcopy using acetic acid and Lugol's iodine as contrast mediators: an investigational study in Peru.

OBJECTIVE: Our goal was to develop a tele-colposcopy platform for primary-care clinics to improve screening sensitivity and access. Specifically, we developed a low-cost, portable Pocket colposcope and evaluated its performance in a tertiary healthcare centre in Peru. DESIGN AND SETTING: Images of the cervix were captured with a standard-of-care and Pocket colposcope at la Liga Contra el Cáncer in Lima, Peru. POPULATION: Two hundred Peruvian women with abnormal cytology and/or human papillomavirus positivity were enrolled. METHODS: Images were collected using acetic acid and Lugol's iodine as contrast agents. Biopsies were taken as per standard-of-care procedures. MAIN OUTCOME MEASURES: After passing quality review, images from 129 women were sent to four physicians who provided a diagnosis for each image. RESULTS: Physician interpretation of images from the two colposcopes agreed 83.1% of the time. The average sensitivity and specificity of physician interpretation compared with pathology was similar for the Pocket (sensitivity = 71.2%, specificity = 57.5%) and standard-of-care (sensitivity = 79.8%, specificity = 56.6%) colposcopes. When compared with a previous study where only acetic acid was applied to the cervix, results indicated that adding Lugol's iodine as a secondary contrast agent improved the percent agreement between colposcopes for all pathological categories by up to 8.9% and the sensitivity and specificity of physician interpretation compared with pathology by over 6.0 and 9.0%, respectively. CONCLUSIONS: The Pocket colposcope performance was similar to that of a standard-of-care colposcope when used to identify precancerous and cancerous lesions using acetic acid and Lugol's iodine during colposcopy examinations in Peru. TWEETABLE ABSTRACT: The Pocket colposcope performance was similar to that of a standard-of-care colposcope when identifying cervical lesions.

Robust computation in 2D absolute EIT (a-EIT) using D-bar methods with the 'exp' approximation.

OBJECTIVE: Absolute images have important applications in medical electrical impedance tomography (EIT) imaging, but the traditional minimization and statistical based computations are very sensitive to modeling errors and noise. In this paper, it is demonstrated that D-bar reconstruction methods for absolute EIT are robust to such errors. APPROACH: The effects of errors in domain shape and electrode placement on absolute images computed with 2D D-bar reconstruction algorithms are studied on experimental data. MAIN RESULTS: It is demonstrated with tank data from several EIT systems that these methods are quite robust to such modeling errors, and furthermore the artefacts arising from such modeling errors are similar to those occurring in classic time-difference EIT imaging. SIGNIFICANCE: This study is promising for clinical applications where absolute EIT images are desirable but previously thought impossible.

Incorporating a Spatial Prior into Nonlinear D-Bar EIT Imaging for Complex Admittivities.

Electrical Impedance Tomography (EIT) aims to recover the internal conductivity and permittivity distributions of a body from electrical measurements taken on electrodes on the surface of the body. The reconstruction task is a severely ill-posed nonlinear inverse problem that is highly sensitive to measurement noise and modeling errors. Regularized D-bar methods have shown great promise in producing noise-robust algorithms by employing a low-pass filtering of nonlinear (nonphysical) Fourier transform data specific to the EIT problem. Including prior data with the approximate locations of major organ boundaries in the scattering transform provides a means of extending the radius of the low-pass filter to include higher frequency components in the reconstruction, in particular, features that are known with high confidence. This information is additionally included in the system of D-bar equations with an independent regularization parameter from that of the extended scattering transform. In this paper, this approach is used in the 2-D D-bar method for admittivity (conductivity as well as permittivity) EIT imaging. Noise-robust reconstructions are presented for simulated EIT data on chest-shaped phantoms with a simulated pneumothorax and pleural effusion. No assumption of the pathology is used in the construction of the prior, yet the method still produces significant enhancements of the underlying pathology (pneumothorax or pleural effusion) even in the presence of strong noise.

A direct D-bar reconstruction algorithm for recovering a complex conductivity in 2-D.

A direct reconstruction algorithm for complex conductivities in W2,∞ (Ω), where Ω is a bounded, simply connected Lipschitz domain in ℝ2, is presented. The framework is based on the uniqueness proof by Francini [Inverse Problems 20 2000], but equations relating the Dirichlet-to-Neumann to the scattering transform and the exponentially growing solutions are not present in that work, and are derived here. The algorithm constitutes the first D-bar method for the reconstruction of conductivities and permittivities in two dimensions. Reconstructions of numerically simulated chest phantoms with discontinuities at the organ boundaries are included.

2D D-bar reconstructions of human chest and tank data using an improved approximation to the scattering transform.

The D-bar method for electrical impedance tomography requires the computation of an intermediate function known as the scattering transform from the measured data. An approximation to the scattering transform utilizing the standard Green's function for the Laplacian was introduced for the 2D D-bar method in Mueller and Siltanen (2003 SIAM J. Sci. Comp. 24 1232-66) and tested on simple numerically simulated conductivity distributions. In this work, the approximation is implemented for experimental data for the first time. It is tested on both tank and human chest data, and the results demonstrate decreased blurring toward the boundary in the images than in images computed with the t(exp) approximation to the scattering transform.

Initial description of the human NLRP3 promoter.

Mutations in NLRP3 (CIAS1) are identified in a continuum of related inflammatory disorders, known as cryopyrinopathies since NLRP3 codes for the protein cryopyrin. Approximately 40% of patients with classic presentation lack mutations in the coding region of NLRP3 suggesting heterogeneity or epigenetic factors. Cryopyrin is a key regulator of proinflammatory cytokine release. Therefore, variations in the NLRP3 promoter sequence may have effects on disease state in patients with cryopyrinopathies and other inflammatory diseases. In this report, we confirmed three 5'-untranslated region splice forms with two separate transcriptional start sites, and identified potential promoter regions and six new DNA promoter variants. One variant is unique to a mutation negative cryopyrinopathy patient and increases in vitro gene expression. Additional studies can now be performed to further characterize the NLRP3 promoter and sequence variants, which will lead to better understanding of the regulation of NLRP3 expression and its role in disease.

Reconstructions of conductive and insulating targets using the D-bar method on an elliptical domain.

The D-bar algorithm based on A Nachman's 2D global uniqueness proof for the inverse conductivity problem (Nachman 1996 Ann. Math. 143 71-96) is implemented on an elliptical domain. The scattering transform is computed on an ellipse and the complete electrode model (CEM) for the forward problem is computed with the finite element method (FEM) in order to obtain static conductivity reconstructions of conductive and insulating targets in a saline-filled tank. It is demonstrated that the spatial artifacts in the image are significantly reduced when the domain is properly modeled in the reconstruction, as opposed to being modeled as a disk.

Imaging cardiac activity by the D-bar method for electrical impedance tomography.

A practical D-bar algorithm for reconstructing conductivity changes from EIT data taken on electrodes in a 2D geometry is described. The algorithm is based on the global uniqueness proof of Nachman (1996 Ann. Math. 143 71-96) for the 2D inverse conductivity problem. Results are shown for reconstructions from data collected on electrodes placed around the circumference of a human chest to reconstruct a 2D cross-section of the torso. The images show changes in conductivity during a cardiac cycle.

Cross-species comparison of Drosophila male accessory gland protein genes.

Drosophila melanogaster males transfer seminal fluid proteins along with sperm during mating. Among these proteins, ACPs (Accessory gland proteins) from the male's accessory gland induce behavioral, physiological, and life span reduction in mated females and mediate sperm storage and utilization. A previous evolutionary EST screen in D. simulans identified partial cDNAs for 57 new candidate ACPs. Here we report the annotation and confirmation of the corresponding Acp genes in D. melanogaster. Of 57 new candidate Acp genes previously reported in D. melanogaster, 34 conform to our more stringent criteria for encoding putative male accessory gland extracellular proteins, thus bringing the total number of ACPs identified to 52 (34 plus 18 previously identified). This comprehensive set of Acp genes allows us to dissect the patterns of evolutionary change in a suite of proteins from a single male-specific reproductive tissue. We used sequence-based analysis to examine codon bias, gene duplications, and levels of divergence (via dN/dS values and ortholog detection) of the 52 D. melanogaster ACPs in D. simulans, D. yakuba, and D. pseudoobscura. We show that 58% of the 52 D. melanogaster Acp genes are detectable in D. pseudoobscura. Sequence comparisons of ACPs shared and not shared between D. melanogaster and D. pseudoobscura show that there are separate classes undergoing distinctly dissimilar evolutionary dynamics.

Detection and mapping of quantitative trait loci that determine responsiveness of mice to nitrous oxide antinociception.

Exposure to 70% N(2)O evokes a robust antinociceptive effect in C57BL/6 (B6) but not in DBA/2 (D2) inbred mice. This study was conducted to identify quantitative trait loci (QTL) in the mouse genome that might determine responsiveness to N(2)O. Offspring from the F(2) generation bred from B6 and D2 progenitors exhibited a broad range of responsiveness to N(2)O antinociception as determined by the acetic acid-induced abdominal constriction test. QTL analysis was then used to dissect this continuous trait distribution into component loci, and to map them to broad chromosomal regions. To this end, 24 spleens were collected from each of the following four groups: male and female F(2) mice responding to 70% N(2)O in oxygen with 100% response (high-responders); and male and female F(2) mice responding with 0% response (low-responders). Genomic DNA was extracted from the spleens and genotyped with simple sequence length polymorphism MapPairs markers. Findings were combined with findings from the earlier QTL analysis from BXD recombinant inbred mice [Brain Res 725 (1996) 23]. Combined results revealed two significant QTL that influence responsiveness to nitrous oxide on proximal chromosome 2 and distal chromosome 5, and one suggestive QTL on midchromosome 18. The chromosome 2 QTL was evident only in males. A significant interaction was found between a locus on chromosome 6 and another on chromosome 13 with a substantial effect on N(2)O antinociception.

Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome.

Familial cold autoinflammatory syndrome (FCAS, MIM 120100), commonly known as familial cold urticaria (FCU), is an autosomal-dominant systemic inflammatory disease characterized by intermittent episodes of rash, arthralgia, fever and conjunctivitis after generalized exposure to cold. FCAS was previously mapped to a 10-cM region on chromosome 1q44 (refs. 5,6). Muckle-Wells syndrome (MWS; MIM 191900), which also maps to chromosome 1q44, is an autosomal-dominant periodic fever syndrome with a similar phenotype except that symptoms are not precipitated by cold exposure and that sensorineural hearing loss is frequently also present. To identify the genes for FCAS and MWS, we screened exons in the 1q44 region for mutations by direct sequencing of genomic DNA from affected individuals and controls. This resulted in the identification of four distinct mutations in a gene that segregated with the disorder in three families with FCAS and one family with MWS. This gene, called CIAS1, is expressed in peripheral blood leukocytes and encodes a protein with a pyrin domain, a nucleotide-binding site (NBS, NACHT subfamily) domain and a leucine-rich repeat (LRR) motif region, suggesting a role in the regulation of inflammation and apoptosis.

Reconstruction of conductivity changes due to ventilation and perfusion from EIT data collected on a rectangular electrode array.

In this paper we demonstrate that conductivity changes caused by ventilation and perfusion in a human subject can be reconstructed from electrical impedance tomography data collected on a rectangular array of electrodes placed on a subject's chest. Currents are applied on the electrodes and the resulting voltages on the electrodes are measured. A 3D reconstruction algorithm is used to reconstruct the conductivity distribution in the region beneath the array. Time traces of the reconstructed conductivity distribution demonstrate the detected changes in conductivity due to ventilation and perfusion.

Antagonism of nitrous oxide antinociception in mice by intrathecally administered antisera to endogenous opioid peptides.

Previously it was demonstrated that nitrous oxide antinociception in the mouse abdominal constriction test is mediated by kappa-opioid receptors. Since nitrous oxide is thought to cause the neuronal release of endogenous opioid peptide to stimulate opioid receptors, this study was designed to identify the opioid peptides involved, especially in the spinal cord, by determining whether nitrous oxide antinociception can be differentially inhibited by intrathecally (i. t.) administered antisera to different opioid peptides. Male NIH Swiss mice were pretreated i.t. with rabbit antisera to opioid peptides then exposed 24 h later to one of three different concentrations of nitrous oxide in oxygen. Dose-response curves constructed from the data indicated that the antinociceptive effect of nitrous oxide was significantly antagonized by antisera to various dynorphins (DYNs) and methionine-enkephalin (ME), but not by antiserum to beta-endorphin (beta-EP). The AD(50) values for nitrous oxide antinociception were significantly elevated by antisera to DYNs and ME but not beta-EP. These findings of this study support the hypothesis that nitrous oxide antinociception in the mouse abdominal constriction test involves the neuronal release of DYN and ME in the spinal cord.

A reconstruction algorithm for electrical impedance tomography data collected on rectangular electrode arrays.

A three-dimensional reconstruction algorithm in electrical impedance imaging is presented for determining the conductivity distribution beneath the surface of a medium, given surface voltage data measured on a rectangular array of electrodes. Such an electrode configuration may be desirable for using electrical impedence tomography to detect tumors in the human breast. The algorithm is based on linearizing the conductivity about a constant value. Here, we describe a simple implementation of the algorithm on a four-electrode--by-four-electrode array and the reconstructions obtained from numerical and experimental tank data. The results demonstrate significantly better spatial resolution in the plane of the electrodes than with respect to depth.

Returning to work through job accommodation: a case study.

1. As more people live longer and more active lives the likelihood of experiencing a disability during one's career increases. Although the unemployment rate among people with disabilities is high, workers with disabilities are becoming more common. 2. Effective job accommodation costs only a small fraction of the hundreds of thousands of dollars that would otherwise be paid out in disability benefits and insurance premiums, or wasted in litigation. 3. Job accommodation planning should begin as early as possible in the disability process and include the active involvement of the individual with the disability and appropriate clinicians, as well as the supervisor and coworkers. 4. Successful accommodation is the result of teamwork, The occupational health professional is often the coordinator of a number of internal and external resources in the job accommodation process. Tools are available for sharing information among all those involved in the accommodation process, without compromise of confidential medical or business information.

Assistive technology and universal design in the workplace.

The terms assistive technology and universal design challenge designers, engineers, and technologists to consider the broadest possible use for the things they create, to make assistive technology as useful to nondisabled persons as to those with disabilities, and to make the products and environments we design as usable as possible for everyone, regardless of age or ability.

Nitrous oxide antinociception in BXD recombinant inbred mouse strains and identification of quantitative trait loci.

Among inbred mouse strains, DBA/2 mice are unique because of their poor responsiveness to nitrous oxide (N2O) antinociception. As a first step towards identifying candidate genes involved in determining antinociceptive responsiveness to N2O, male mice from the DBA/2 strain, the more responsive C57BL/6 strain, their B6D2F1 offspring, and 22 BXD recombinant inbred (RI) strains derived from DBA/2 and C57BL/6 mice were exposed to N2O and evaluated using the acetic acid abdominal constriction test. When exposed to 70% N2O, C57BL/6, DBA/2 and B6D2F1 mice exhibited antinociceptive responses of 78, 22 and 55%, respectively. The BXD RI strains demonstrated varying degrees of responsiveness to N2O. Cluster analysis revealed one cluster of 16 strains approximating the C57BL/6 progenitor (61.9-100% antinociceptive response to 70% N2O) and another of six strains around the DBA/2 progenitor (9.1-40% antinociceptive response to 70% N2O). The robust strain differences permitted screening the strain means with 1492 marker loci previously mapped in BXD RI strains. Using a QTL analysis specifically tailored to existing mouse RI strains, we found associations at the 0.01 level on seven chromosomes with the most promising marker loci being Il2ra, Hbb, Hmg1rs7 and Gsl5 on chromosomes 2, 7, 16 and 19, respectively (P < 0.002).