The use of murine polyclonal anti-idiotypic antibodies as surrogate allergens in the diagnosis of Parthenium hypersensitivity

Background: Anti-idiotypic antibodies (Ab-2), which are the mirror images of idiotypic antibodies (Ab-1), may be useful as diagnostic reagents and for use as immunogen to induce antigen-specific immune responses. Methods and Results: To explore the biologic potential of Ab-2 as diagnostic reagents in allergic diseases, murine mouse (m) Ab-2 were raised by immunizing Balb/c mice with affinity purified rabbit (r) Ab-1 specific for the pollen of Parthenium hysterophorus, an allergenic weed that grows wild on the Indian subcontinent and in Australia, Mexico, and the southern United States. Affinity purified Parthenium-specific human (h)AB-1 could successfully inhibit the binding of mAb-2 to immobilized rAb-1. Further, Balb/c mice immunized with mAb-2 induced Parthenium-specific anti-anti-idiotypic IgE and IgG antibodies. Specificity of the Ab-2 was confirmed by the ability of Parthenium pollen extracts to inhibit the binding of allergen-specific IgE and IgG Ab-1 in the sera of patients with rhinitis to immobilized mAb-2. Parthenium-sensitive patients with rhinitis who had positive results on skin prick tests to Parthenium pollen extracts also responded with a positive skin reaction to mAb-2. Conclusion: Our data demonstrate that Parthenium-specific mAb-2 may be of value as surrogate allergens in allergen standardization and for in vitro diagnosis.

An Adaptive Scheme for Learning the Probability Threshold in Pattern Recognition

The statistical minimum risk pattern recognition problem, when the classification costs are random variables of unknown statistics, is considered. Using medical diagnosis as a possible application, the problem of learning the optimal decision scheme is studied for a two-class twoaction case, as a first step. This reduces to the problem of learning the optimum threshold (for taking appropriate action) on the a posteriori probability of one class. A recursive procedure for updating an estimate of the threshold is proposed. The estimation procedure does not require the knowledge of actual class labels of the sample patterns in the design set. The adaptive scheme of using the present threshold estimate for taking action on the next sample is shown to converge, in probability, to the optimum. The results of a computer simulation study of three learning schemes demonstrate the theoretically predictable salient features of the adaptive scheme.

Pulsatile blood flow in a stenosed arteryâ a theoretical model

Abstract is not available.

Component wave delineation of ECG by filtering in the Fourier domain

A complete solution to the fundamental problem of delineation of an ECG signal into its component waves by filtering the discrete Fourier transform of the signal is presented. The set of samples in a component wave is transformed into a complex sequence with a distinct frequency band. The filter characteristics are determined from the time signal itself. Multiplication of the transformed signal with a complex sinusoidal function allows the use of a bank of low-pass filters for the delineation of all component waves. Data from about 300 beats have been analysed and the results are highly satisfactory both qualitatively and quantitatively.

Use of finite wordlength FIR digital filter structures with improved magnitude and phase characteristics for reduction of muscle noise in EEG signals

One of the main disturbances in EEG signals is EMG artefacts generated by muscle movements. In the paper, the use of a linear phase FIR digital low-pass filter with finite wordlength precision coefficients is proposed, designed using the compensation procedure, to minimise EMG artefacts in contaminated EEG signals. To make the filtering more effective, different structures are used, i.e. cascading, twicing and sharpening (apart from simple low-pass filtering) of the designed FIR filter Modifications are proposed to twicing and sharpening structures to regain the linear phase characteristics that are lost in conventional twicing and sharpening operations. The efficacy of all these transformed filters in minimising EMG artefacts is studied, using SNR improvements as a performance measure for simulated signals. Time plots of the signals are also compared. Studies show that the modified sharpening structure is superior in performance to all other proposed methods. These algorithms have also been applied to real or recorded EMG-contaminated EEG signal. Comparison of time plots, and also the output SNR, show that the proposed modified sharpened structure works better in minimising EMG artefacts compared with other methods considered.

Mutations in WDR62, encoding a centrosomal and nuclear protein, in Indian primary microcephaly families with cortical malformations

Primary microcephaly is an autosomal recessive disorder characterized by smaller than normal brain size and mental retardation. It is genetically heterogeneous with seven loci: MCPH1-MCPH7. We have previously reported genetic analysis of 35 families, including the identification of the MCPH7 gene STIL. Of the 35 families, three families showed linkage to the MCPH2 locus. Recent whole-exome sequencing studies have shown that the WDR62 gene, located in the MCPH2 candidate region, is mutated in patients with severe brain malformations. We therefore sequenced the WDR62 gene in our MCPH2 families and identified two novel homozygous protein truncating mutations in two families. Affected individuals in the two families had pachygyria, microlissencephaly, band heterotopias, gyral thickening, and dysplastic cortex. Using immunofluorescence study, we showed that, as with other MCPH proteins, WDR62 localizes to centrosomes in A549, HepG2, and HaCaT cells. In addition, WDR62 was also localized to nucleoli. Bioinformatics analysis predicted two overlapping nuclear localization signals and multiple WD-40 repeats in WDR62. Two other groups have also recently identified WDR62 mutations in MCPH2 families. Our results therefore add further evidence that WDR62 is the MCPH2 gene. The present findings will be helpful in genetic diagnosis of patients linked to the MCPH2 locus.

Green synthesis of biopolymer-silver nanoparticle nanocomposite: An optical sensor for ammonia detection

Biopolymer used for the production of nanoparticles (NPs) has attracted increasing attention. In the presence article we use aqueous solution of polysaccharide Cyamopsis tetragonaloba commonly known as guar gum (GG), from plants. GG acts as reductive preparation of silver nanoparticles which are found to be <10. nm in size. The uniformity of the NPs size was measured by the SEM and TEM, while a face centered cubic structure of crystalline silver nanoparticles was characterized using powder X-ray diffraction technique. Aqueous ammonia sensing study of polymer/silver nanoparticles nanocomposite (GG/AgNPs NC) was performed by optical method based on surface plasmon resonance (SPR). The performances of optical sensor were investigated which provide the excellent result. The response time of 2-3. s and the detection limit of ammonia solution, 1. ppm were found at room temperature. Thus, in future this room temperature optical ammonia sensor can be used for clinical and medical diagnosis for detecting low ammonia level in biological fluids, such as plasma, sweat, saliva, cerebrospinal liquid or biological samples in general for various biomedical applications in human. © 2012 Elsevier B.V.

A LSQR-type method provides a computationally efficient automated optimal choice of regularization parameter in diffuse optical tomography

Purpose: Developing a computationally efficient automated method for the optimal choice of regularization parameter in diffuse optical tomography. Methods: The least-squares QR (LSQR)-type method that uses Lanczos bidiagonalization is known to be computationally efficient in performing the reconstruction procedure in diffuse optical tomography. The same is effectively deployed via an optimization procedure that uses the simplex method to find the optimal regularization parameter. The proposed LSQR-type method is compared with the traditional methods such as L-curve, generalized cross-validation (GCV), and recently proposed minimal residual method (MRM)-based choice of regularization parameter using numerical and experimental phantom data. Results: The results indicate that the proposed LSQR-type and MRM-based methods performance in terms of reconstructed image quality is similar and superior compared to L-curve and GCV-based methods. The proposed method computational complexity is at least five times lower compared to MRM-based method, making it an optimal technique. Conclusions: The LSQR-type method was able to overcome the inherent limitation of computationally expensive nature of MRM-based automated way finding the optimal regularization parameter in diffuse optical tomographic imaging, making this method more suitable to be deployed in real-time. (C) 2013 American Association of Physicists in Medicine. http://dx.doi.org/10.1118/1.4792459]

Mutation analysis of the SLC4A11 gene in Indian families with congenital hereditary endothelial dystrophy 2 and a review of the literature

Purpose: Congenital hereditary endothelial dystrophy 2 (CHED2) is an autosomal recessive disorder caused by mutations in the solute carrier family 4, sodium borate transporter, member 11 (SLC4A11) gene. The purpose of this study was to identify the genetic cause of CHED2 in six Indian families and catalog all known mutations in the SLC4A11 gene. Methods: Peripheral blood samples were collected from individuals of the families with CHED2 and used in genomic DNA isolation. PCR primers were used to amplify the entire coding region including intron-exon junctions of SLC4A11. Amplicons were subsequently sequenced to identify the mutations. Results: DNA sequence analysis of the six families identified four novel (viz., p.Thr262Ile, p.Gly417Arg, p.Cys611Arg, and p.His724Asp) mutations and one known p.Arg869His homozygous mutation in the SLC4A11 gene. The mutation p.Gly417Arg was identified in two families. Conclusions: This study increases the mutation spectrum of the SLC4A11 gene. A review of the literature showed that the total number of mutations in the SLC4A11 gene described to date is 78. Most of the mutations are missense, followed by insertions-deletions. The present study will be helpful in genetic diagnosis of the families reported here.

Is The Burden of Medical Education Affecting Ethics of Medical Treatment?

A substantial number of medical students in India have to bear an enormous financial burden for earning a bachelor's degree in medicine referred to as MBBS (bachelor of medicine and bachelor of surgery). This degree program lasts for four and one-half years followed by one year of internship. A postgraduate degree, such as MD, has to be pursued separately on completion of a MBBS. Every medical college in India is part of a hospital where the medical students get clinical exposure during the course of their study. All or at least a number of medical colleges in a given state are affiliated to a university that mainly plays a role of an overseeing authority. The medical colleges usually have no official interaction with other disciplines of education such as science and engineering, perhaps because of their independent location and absence of emphasis on medical research. However, many of the medical colleges are adept in imparting high-quality and sound training in medical practices including diagnostics and treatment. The medical colleges in India are generally of two types, i.e., government owned and private. Since only a limited number of seats are available across India in the former category of colleges, only a small fraction of aspiring candidates can find admission in these colleges after performing competitively in the relevant entrance tests. A major advantage of studying in these colleges is the nominal tuition fees that have to be paid. On the other hand, a large majority of would-be medical graduates have to seek admission in the privately run medical institutes in which the tuition and other related fees can be mind boggling when compared to their public counterparts. Except for candidates of exceptionally affluent background, the only alternative for fulfilling the dream of becoming a doctor is by financing one's study through hefty bank loans that may take years to pay back. It is often heard from patients that they are asked by doctors to undergo a plethora of diagnostic tests for apparently minor illnesses, which may financially benefit those prescribing the tests. The present paper attempts to throw light on the extent of disparity in cost of a medical education between state-funded and privately managed medical colleges in India; the average salary of a new medical graduate, which is often ridiculously low when compared to what is offered in entry-level engineering and business jobs; and the possible repercussions of this apparently unjust economic situation regarding the exploitation of patients.

Whole exome sequencing identifies a novel splice-site mutation in ADAMTS17 in an Indian family with Weill-Marchesani syndrome

Purpose: Weill-Marchesani syndrome (WMS) is a rare connective tissue disorder, characterized by short stature, micro-spherophakic lens, and stubby hands and feet (brachydactyly). WMS is caused by mutations in the FBN1, ADAMTS10, and LTBP2 genes. Mutations in the LTBP2 and ADAMTS17 genes cause a WMS-like syndrome, in which the affected individuals show major features of WMS but do not display brachydactyly and joint stiffness. The main purpose of our study was to determine the genetic cause of WMS in an Indian family. Methods: Whole exome sequencing (WES) was used to identify the genetic cause of WMS in the family. The cosegregation of the mutation was determined with Sanger sequencing. Reverse transcription (RT)-PCR analysis was used to assess the effect of a splice-site mutation on splicing of the ADAMTS17 transcript. Results: The WES analysis identified a homozygous novel splice-site mutation c.873+1G>T in a known WMS-like syndrome gene, ADAMTS17, in the family. RT-PCR analysis in the patient showed that exon 5 was skipped, which resulted in the deletion of 28 amino acids in the ADAMTS17 protein. Conclusions: The mutation in the WMS-like syndrome gene ADAMTS17 also causes WMS in an Indian family. The present study will be helpful in genetic diagnosis of this family and increases the number of mutations of this gene to six.

Cancer gene signatures in risk stratification: use in personalized medicine

Cancer is a complex disease which arises due to a series of genetic changes related to cell division and growth control. Cancer remains the second leading cause of death in humans next to heart diseases. As a testimony to our progress in understanding the biology of cancer and developments in cancer diagnosis and treatment methods, the overall median survival time of all cancers has increased six fold one year to six years during the last four decades. However, while the median survival time has increased dramatically for some cancers like breast and colon, there has been only little change for other cancers like pancreas and brain. Further, not all patients having a single type of tumour respond to the standard treatment. The differential response is due to genetic heterogeneity which exists not only between tumours, which is called intertumour heterogeneity, but also within individual tumours, which is called intratumoural heterogeneity. Thus it becomes essential to personalize the cancer treatment based on a specific genetic change in a given tumour. It is also possible to stratify cancer patients into low- and high-risk groups based on expression changes or alterations in a group of genes gene signatures and choose a more suitable mode of therapy. It is now possible that each tumour can be analysed using various high-throughput methods like gene expression profiling and next-generation sequencing to identify its unique fingerprint based on which a personalized or tailor-made therapy can be developed. Here, we review the important progress made in the recent years towards personalizing cancer treatment with the use of gene signatures.

Effects of refractive index mismatch in optical CT imaging of polymer gel dosimeters

Purpose: Proposing an image reconstruction technique, algebraic reconstruction technique-refraction correction (ART-rc). The proposed method takes care of refractive index mismatches present in gel dosimeter scanner at the boundary, and also corrects for the interior ray refraction. Polymer gel dosimeters with high dose regions have higher refractive index and optical density compared to the background medium, these changes in refractive index at high dose results in interior ray bending. Methods: The inclusion of the effects of refraction is an important step in reconstruction of optical density in gel dosimeters. The proposed ray tracing algorithm models the interior multiple refraction at the inhomogeneities. Jacob's ray tracing algorithm has been modified to calculate the pathlengths of the ray that traverses through the higher dose regions. The algorithm computes the length of the ray in each pixel along its path and is used as the weight matrix. Algebraic reconstruction technique and pixel based reconstruction algorithms are used for solving the reconstruction problem. The proposed method is tested with numerical phantoms for various noise levels. The experimental dosimetric results are also presented. Results: The results show that the proposed scheme ART-rc is able to reconstruct optical density inside the dosimeter better than the results obtained using filtered backprojection and conventional algebraic reconstruction approaches. The quantitative improvement using ART-rc is evaluated using gamma-index. The refraction errors due to regions of different refractive indices are discussed. The effects of modeling of interior refraction in the dose region are presented. Conclusions: The errors propagated due to multiple refraction effects have been modeled and the improvements in reconstruction using proposed model is presented. The refractive index of the dosimeter has a mismatch with the surrounding medium (for dry air or water scanning). The algorithm reconstructs the dose profiles by estimating refractive indices of multiple inhomogeneities having different refractive indices and optical densities embedded in the dosimeter. This is achieved by tracking the path of the ray that traverses through the dosimeter. Extensive simulation studies have been carried out and results are found to be matching that of experimental results. (C) 2015 American Association of Physicists in Medicine.

Understanding Medical Device Patenting and Clinical Trials for Product Leadership

Unmet clinical needs remain the primary driving force for innovations in medical devices. While appropriate mechanisms to protect these innovative outcomes are essential, the performance of clinical trials to ensure safety is also mandated before the invention is ready for public use. Literature explaining the relationship between patenting activities and clinical trials of medical devices is scarce. Linking patent ownership to clinical trials may imply product leadership and value chain control. In this paper, we use patent data from Indian Patent Office (IPO), PCT, and data from Clinical Trials Registry of India (CTRI) to identify whether patent assignees have any role in leading as primary sponsors of clinical trials. A total of 42 primary sponsors are identified from the CTRI database in India. Number of patents awarded to these primary sponsors in the particular medical device, total number of patents awarded to the primary sponsor in all technologies, total number of patents in the specific medical device technology provides an indication of leadership and control in the value chain.

Average Overlap for Clustering Incomplete Data using Symmetric Non-Negative Matrix Factorization

Clustering techniques which can handle incomplete data have become increasingly important due to varied applications in marketing research, medical diagnosis and survey data analysis. Existing techniques cope up with missing values either by using data modification/imputation or by partial distance computation, often unreliable depending on the number of features available. In this paper, we propose a novel approach for clustering data with missing values, which performs the task by Symmetric Non-Negative Matrix Factorization (SNMF) of a complete pair-wise similarity matrix, computed from the given incomplete data. To accomplish this, we define a novel similarity measure based on Average Overlap similarity metric which can effectively handle missing values without modification of data. Further, the similarity measure is more reliable than partial distances and inherently possesses the properties required to perform SNMF. The experimental evaluation on real world datasets demonstrates that the proposed approach is efficient, scalable and shows significantly better performance compared to the existing techniques.