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Biomedical subjects

S Shalev

Publications and source records attributed to S Shalev.

At least 19 recordsLinked to original sources

Otoacoustic emissions and brainstem evoked potentials in compound carriers of connexin 26 mutations.

This study compares the effects of mutations in the gap junction protein connexin 26 (Cx26), on outer hair cells (OHCs), inner hair cells (IHCs) and auditory nerve/brainstem among carriers of these mutations. One hundred and twenty eight individuals, from a village with widespread consanguinity and congenital deafness, due to three Cx26 mutations, were selected among relatives of deaf persons, and divided into non-carriers, carriers of one mutation, homozygous to one mutation, or compound heterozygous carriers of two different mutations. Distortion product otoacoustic emissions (DPOAEs), auditory brainstem responses (ABRs) and audiometric evaluation were compared in these genetic groups. Hearing loss among homozygotes and compound heterozygotes was comparable and ranged from mild to profound. Most ABRs from these groups showed no responses or partial responses (peaks III, V) with prolonged latencies, but some individuals had all peaks at normal latencies. DPOAEs were absent, except sporadic responses. Carriers of one mutation had significantly smaller DPOAEs compared to non-carriers, although normal pure tone audiograms and ABRs were found in these groups. In conclusion, based on DPOAEs, Cx26 mutations may impact OHC function among carriers of one or two Cx26 mutations. IHC/nerve impairment among homozygotes and compound heterozygotes is variable. OHCs may be more susceptible to Cx26 mutations compared to IHCs and the auditory nerve and brainstem pathway activated by them.

Adolescent↗

The effects of a connexin 26 mutation--35delG--on oto-acoustic emissions and brainstem evoked potentials: homozygotes and carriers.

The purpose of this study was to examine whether outer hair cells (OHCs), inner hair cells and the brainstem auditory pathway are impaired due to a mutation in a gap junction protein, connexin 26 (Cx26), 35delG. Fifty-six individuals, from a village with widespread consanguinity and profound, non-syndromic congenital deafness, due to 35delG mutation, were selected among relatives of deaf people. The individuals were either non-carriers (n=20), heterozygous (n=20) or homozygous (n=16) for the mutation. Distortion product oto-acoustic emissions (DPOAEs) and auditory brainstem evoked potentials (ABEPs) in mutation non-carriers, in heterozygotes (carriers) and in subjects homozygous for the mutation were compared in addition to audiometric evaluation. Most deaf homozygotes had no DPOAEs, except some sporadic responses at 1000, 8000 and 10000 Hz. This was also observed in audiometry which showed profound hearing loss in most cases. Two cases were unique: one had moderate to severe hearing loss and the other had severe to profound hearing loss. A significant difference was found between non-carriers and carriers of 35delG: non-carriers had larger DPOAE responses than heterozygotes at all frequencies. The prevalence of responses got lower with higher frequencies in both groups, but between 6000 and 10000 Hz 50-70% of the carriers had no DPOAE responses, compared to 30-60% of non-carriers. In both groups responses diminished with age, but no significant interaction was found between age and the genetic group. ABEPs among homozygotes were variable: in most homozygotes ABEPs were absent or partial (waves III, V) with prolonged latencies, but two subjects had ABEPs within normal limits, in one ear. ABEPs were normal with no differences between carriers and non-carriers. We suggest that OHC function is affected by the 35delG mutation in Cx26. In addition, the hearing of carriers of this mutation may be impaired at very high frequencies (8000-10000 Hz), which are not assessed in routine audiometry or ABEP testing.

Adolescent↗

Hypotrichosis with juvenile macular dystrophy is caused by a mutation in CDH3, encoding P-cadherin.

Congenital hypotrichosis associated with juvenile macular dystrophy (HJMD; MIM601553) is an autosomal recessive disorder of unknown etiology, characterized by hair loss heralding progressive macular degeneration and early blindness. We used homozygosity mapping in four consanguineous families to localize the gene defective in HJMD to 16q22.1. This region contains CDH3, encoding P-cadherin, which is expressed in the retinal pigment epithelium and hair follicles. Mutation analysis shows in all families a common homozygous deletion in exon 8 of CDH3. These results establish the molecular etiology of HJMD and implicate for the first time a cadherin molecule in the pathogenesis of a human hair and retinal disorder.

Adolescent↗

Clinical use of electronic portal imaging: report of AAPM Radiation Therapy Committee Task Group 58.

AAPM Task Group 58 was created to provide materials to help the medical physicist and colleagues succeed in the clinical implementation of electronic portal imaging devices (EPIDs) in radiation oncology. This complex technology has matured over the past decade and is capable of being integrated into routine practice. However, the difficulties encountered during the specification, installation, and implementation process can be overwhelming. TG58 was charged with providing sufficient information to allow the users to overcome these difficulties and put EPIDs into routine clinical practice. In answering the charge, this report provides; comprehensive information about the physics and technology of currently available EPID systems; a detailed discussion of the steps required for successful clinical implementation, based on accumulated experience; a review of software tools available and clinical use protocols to enhance EPID utilization; and specific quality assurance requirements for initial and continuing clinical use of the systems. Specific recommendations are summarized to assist the reader with successful implementation and continuing use of an EPID.

Biophysical Phenomena↗

Genetic disorders among Palestinian Arabs: 3. Autosomal recessive disorders in a single village.

Autosomal recessive diseases are common in the Arab population of Israel, mostly as a result of the high rate of consanguinity. They represent a major factor in the mortality and morbidity of the population. Since the distribution of genetic disorders in this population is not uniform, the present study was performed to determine the frequency and impact of recessive disorders within a single village. We demonstrate the existence of at least 19 autosomal recessive disorders in a village of about 8,600 inhabitants chosen at random. Since most of the disorders were chronic, the prevalence of recessive conditions in the village at the time of the study was at least 1/70, leading to a very high burden to the population and the health services.

Arabs↗

Prenatal diagnosis and carrier detection for molybdenum cofactor deficiency type A in northern Israel using polymorphic DNA markers.

Molybdenum cofactor deficiency (MoCoD) is an autosomal recessive, fatal neurological disorder, characterized by the combined deficiency of sulphite oxidase, xanthine dehydrogenase and aldehyde oxidase. We have recently reported an excessive occurrence of this fatal disorder among segments of the Arab population in Northern Israel suggesting that the true incidence of MoCoD is probably underestimated in this highly inbred population. This lethal disease can be diagnosed prenatally by assay of sulphite oxidase activity in chorionic villus samples in pregnancies of couples who have had previously affected children (obligatory carriers). However, to date, there is no biochemical assay for carrier detection among the population at risk. Recently we demonstrated the linkage of a MoCoD gene to an 8-cM region on chromosome 6p21.3 in two consanguineous Israeli-Arab unrelated kindreds. The description of the MOCS1 gene that maps to the same region and which carries multiple mutations in MoCoD type A followed this finding. We describe here one additional kindred of Arab-Israeli origin, which is also linked to the MOCS1 locus, and demonstrate the feasibility of prenatal diagnosis and carrier detection using microsatellite markers in selected families when mutations are unknown. A complete correlation between the biochemical and DNA assays was found in a total of six samples (five chorionic villus and one amniocyte culture sample) obtained from the three MoCoD families.

Chorionic Villi↗

Image Storage Requirements for Treatment Planning and Verification.

Digital imaging techniques are becoming increasingly accepted in radiation therapy, and they bring significant advantages when compared with film, especially the ease of storage and retrieval. A simple model is proposed for the estimation of digital data storage requirements in a typical department of radiation therapy. The model assumes that 100 patients are undergoing treatment at any given time, and their computed tomography (CT) images, treatment plans, digitized simulator films, and portal images are to be available at short notice ("on-line"). Off-line archival image storage is required after the completion of treatment, for 1,000 patients per year. Reasonable assumptions are postulated regarding image sizes and acquisition rates, and on-line storage requirements are estimated to be up to 300 megabytes (MB) for CT data, 170 MB for treatment plans, 200 MB for digitized simulator films, and 500 MB for digitized port films. If electronic portal imaging is used instead of port films, the on-line requirement becomes about 2 gigabytes (GB) for verification images, and 20 GB if portal movies are to be archived. Off-line storage requirements are a factor of ten larger. It is suggested that data compression may reduce these requirements by up to a factor of 20.

Journal Article↗

Pelvic irradiation of the obese patient: a treatment strategy involving megavoltage simulation and intratreatment setup corrections.

This study involves a fractionated course of external radiation therapy for a 42 year old female weighing 150 kg, diagnosed with stage IIb cancer of the cervix. The patient could not be simulated in the conventional sense due to weight restrictions on the simulator couch, and body casts or molds were impractical. Using an on-line portal imaging device, treatment fields were established during the first session, and intratreatment verification was used before every subsequent treatment to measure and, when necessary, to correct the patient setup. Two courses of treatment were prescribed with a total dose of 60 Gy delivered by a four field box technique (A/P, P/A, and two lateral fields). Out of a total of 108 treatment fields monitored, 12 anterior fields and 1 posterior field were corrected (exclusive of the first, or simulation fraction). Without corrections, 10% of the initial setup displacements would have had displacements greater than 10 mm, 21% greater than 7 mm, and 41% greater than 5 mm. With the application of intratreatment corrections, only 2% of the displacements were greater than 10 mm, 11% were greater than 7 mm, and 32% were greater than 5 mm. It was also found that the second field treated in a parallel opposed pair (i.e., anterior/posterior or left/right lateral) had lower setup displacements and did not require verification or correction.

Adult↗

A quality control test for electronic portal imaging devices.

A quality control (QC) test suitable for routine daily use has been developed for video based electronic portal imaging devices. It provides an objective and quantitative test for acceptable image quality on the basis of the high contrast spatial resolution and the contrast-to-noise ratio (CNR). The test uses a phantom consisting of five sets of high-contrast rectangular bar patterns with spatial frequencies of 0.1, 0.2, 0.25, 0.4, and 0.75 lp/mm. Data obtained during a one month calibration period were used to determine a critical frequency fc for the relative square wave modulation transfer function and a critical contrast-to-noise ratio (CNRc). Subsequent measurements indicating significant deviations from these critical values result in warning messages to the operator indicating potential problems in system performance. Measurements over a period of two years show that the QC test provides a sensitive indication of imaging performance.

Biophysical Phenomena↗

Assessing radiation and light field congruence with a video based electronic portal imaging device.

Projected light fields are used on treatment simulators and teletherapy treatment units to delineate the size and position of the radiation beam. Any discrepancy between these fields will lead to a systematic field placement error, with possibly serious implications with regard to the accuracy of the delivered dose distribution in the patient. Conventionally, film has been used for regular quality control tests of light and radiation field congruence, but this is a time consuming method and is not suitable for daily checks. A new method is described that uses a specially designed test phantom, a video-based electronic portal imaging device and a personal computer to test for radiation and light field congruence on treatment accelerators. This method consists of aligning the test phantom in the light field of a treatment linac and acquiring an electronic portal image. A computer program then automatically analyzes the image and determines the degree of congruence between the two fields. The final result of the test is a go, warning, or no go decision depending on the extent of misalignment between the light and radiation fields. Two algorithms were tested for reproducibility (<0.4 mm), sensitivity to noise (<0.2 mm), and positional accuracy (<0.4 mm) and are shown to give results comparable to the conventional film method. Daily testing of field congruence over a period of 84 days demonstrated differences in the results determined by the two algorithms of less than 0.1 +/- 0.2 mm (standard deviation) at 6 MV and 0.22 +/- 0.13 mm at 23 MV. Routine testing is possible as the effort and time required are minimal, and the test can be performed during daily routine start-up procedures.

Algorithms↗

Thick phosphor screens for on-line portal imaging.

Gd2O2S phosphor screens between 250 and 1000 mg/cm2 thick were evaluated for use in megavoltage imaging systems. The phosphor layers were placed on brass plates ranging from 1 to 5 mm thick, each with and without an optical back reflector (white paint). Light output and spatial resolution were measured at 6- and 23-MV x-ray energies. Light output was found to increase linearly with phosphor thickness up to 500 mg/cm2, reaching a plateau at 1000 mg/cm2. Spatial resolution [modulation transfer function (MTF)] decreased exponentially with phosphor thickness up to 750 mg/cm2, where a minimum was reached. The variation of MTF with phosphor thickness was found to obey a simple empirical relation.

Gadolinium↗

Optimization of metal/phosphor screens for on-line portal imaging.

Studies were conducted to determine the optimal metal/phosphor screen for on-line video verification of radiation treatment portals. Screens were evaluated for luminance and spatial resolution as a function of composition and thickness at 6- and 23-MV x-ray energies. A new video technique was used to determine modulation transfer functions. Gd2O2S was found to be the most efficient (brightest) phosphor for this application. Luminance was found to vary linearly with phosphor thickness up to a thickness of 500 mg/cm2. Metal plates made of iron, brass, copper, lead, and sintered tungsten of various thicknesses were also tested for luminance and resolution with Gd2O2S phosphor. Brightness peaked at about 2-mm thickness for most metals. Significant contributions to the brightness were found to come from x rays interacting with the phosphor itself.

Evaluation Studies as Topic↗

Pseudocorrelation: a fast, robust, absolute, grey-level image alignment algorithm.

A new image alignment algorithm--pseudocorrelation--has been developed based on the application of Monte Carlo techniques to the calculation of a cross-correlation integral for grey-scale images. It has many advantages over cross-correlation: it is at least a factor of 10 faster than fast-Fourier-transform-based cross-correlation, and requires 8 times less memory. Its high speed allows for the search space of geometric transformations between images to include magnification and rotation as well as translations without the search time becoming too long. It allows noise to be taken into account, making calculation of a robust, absolute probability of good alignment possible. It is relatively insensitive to differences in quality between images. This article describes the pseudocorrelation algorithm in detail and presents the results of tests of the effects of contrast enhancement, resolution differences, and noise on the algorithm's performance. These tests show that the algorithm is well suited to the task of automated alignment of very low contrast images from video electronic portal imaging devices.

Algorithms↗

Noise analysis in real-time portal imaging. I. Quantization noise.

The limit at which quantization noise becomes dominant in video-based real-time portal imaging has been studied. Quantization noise due to truncation in integer frame averaging is shown to be dominant over the input analog-to-digital converter (A/D) quantization noise, unless image addition is used in video-based real-time portal imaging systems. Portal images acquired with the Newvicon camera by averaging more than 64 frames are found to be dominated by the quantization noise due to truncation. It has shown that the signal-to-noise ratio (SNR) is limited to 886.8 when using an 8-bit A/D with digital frame averaging, but higher values can be achieved with digital frame addition. It is also shown that digital frame addition together with 16-bit processing can achieve higher contrast resolution than digital frame averaging and 8-bit processing.

Gadolinium↗

The objective evaluation of alternative treatment plans. III: The quantitative analysis of dose volume histograms.

The computer program OSCAR evaluates dose-volume histograms in a consistent way for use in 3-dimensional treatment planning. Based on a dose prescription specified by a radiation oncologist, the technique provides a quantitative and easily understood visual analysis of a proposed dose distribution. Rapid, reliable, and consistent choices can be made between alternative treatment plans, and if necessary the results of OSCAR calculations can be used to guide the design of a plan that will be closer to the required prescription. The method is well suited to use in the definition of treatment protocols. The use of OSCAR is demonstrated by applying it to the evaluation of alternative volumetric treatment plans for ca lung. The results demonstrate the importance of using corrections for inhomogeneous tissue density in the calculation of 3-dimensional dose distributions.

Computer Graphics↗