Cancer Patients Missing Pain Score Information:- Application with Imputation Techniques

Background: Methods for handling missing data in clinical research have been getting more attentions over last few years. Contemplation of missing data in any study is vital as they may lead to considerable biases and can have an impact on the power of the study. Objective: This manuscript is dedicated to present different techniques to handle missing observations obtained from repeatedly measured pain score data on palliative cancer. Methods: This problem caused by subjects drop out before completion of the study. The reason for dropout or withdrawal may be related to study (e.g., adverse event, death, unpleasant study procedures, lack of improvement) or unrelated to the study (e.g., moving away, unrelated disease). The dropout might be very common on studies on palliative cancer patients. The Palliative treatment is designed to relieve symptoms, and improve the quality of life and can be used at any stage of an illness if there are troubling symptoms, such as pain or sickness. Results: The mean(SD) of observed pain score was 3.638(3.156) whereas the imputed mean values were 3.615(2.980), 3.618(2.954), 3.577(2.892), 3.560(2.999) and 3.627(2.949) respectively for the imputation methods regression, predictive mean matching, propensity score, EM algorithm and MCMC methods for pain score values at visit3.  Interpretation and Conclusion: The EM algorithm shows the least percentage change from observed values in both visits followed by predictive mean matching method and MCMC methods. The multiple imputation techniques have few advantages; the imputed values are drawsfrom a distribution, so they inherently contain some variation by introducing an additional form of error in the parameter estimates across the imputation &nbsp

Clinico-physiological profile of patients of pulmonary impairment after tuberculosis at a tertiary care centre

Background: Pulmonary tuberculosis (TB) is a unique infectious disease that more often results in permanent structural changes in the lung parenchyma. It is by virtue of these changes that the patients even after bacteriological cure continue to suffer the after effects of the disease. Objective of study was to assess the clinico-physiological profile of patients of pulmonary impairment after tuberculosis (PIAT) attending S. N. Medical College, Agra, Uttar Pradesh, India.Methods: Over the time period of 2 years, 350 patients of healed pulmonary tuberculosis were identified and studied about their clinico-physiological profile. This profile included age, sex, category of treatment, pulmonary function test pattern, exercising capacity, exercise tolerance and quality of life.Results: It was found that majority of the patients were males, >60 years of age and had taken Category-II treatment. Most of the patients were having an obstructive pattern on PFT, poor exercise tolerance and exercise capacity and a poor quality of life.Conclusions: Patients of healed pulmonary TB continue to experience respiratory symptoms owing to the permanent anatomical changes in the lung conferred by the disease

Quantification of Parasite Load in Clinical Samples of Leishmaniasis Patients: IL-10 Level Correlates with Parasite Load in Visceral Leishmaniasis

A rapid and accurate method to detect and quantify Leishmania parasite is urgently needed to facilitate early diagnosis of Leishmaniasis and monitoring of antileishmania therapy. In this study, real-time assay was applied to estimate parasite load in clinical samples of visceral leishmaniasis (VL) and post kala-azar dermal leishmaniasis (PKDL) patients. The mean parasite load in blood of VL patients (n = 31) was 8,372 parasites/ml, while the mean parasite load in bone marrow aspirate (BMA) was 194,962 parasites/million nucleated cells (n = 12). Parasite load was undetectable after treatment with amphotericin B (n = 9) in VL, while a residual parasite burden was detected in 2 of 6 patients following treatment with sodium antimony gluconate. Further, circulating levels of IFN-γ, TNF-α, IL-10, IL-6, IL-4 and IL-2 were analysed in VL patients (n = 29) by Cytometric Bead Array to evaluate correlation with parasitic load. Interestingly, IL-10 levels correlated significantly with parasite load (r = 0.82, P<0.0001). The mean parasite load in dermal lesions of PKDL patients was 9,502 parasites/µg tissue DNA at pre-treatment stage (n = 25), with no detectable parasites after therapy (n = 5). Parasite burden was distinctly higher (P<0.0001) in nodular lesions (n = 12) (19,586 parasites/µg tissue DNA) compared to papular/macular lesions (n = 13, 193 parasites/µg tissue DNA). Further, chronic PKDL lesions showed significantly (P = 0.0166) higher parasite load in comparison with acute lesions. Results indicate that chronic, nodular cases constitute the major parasite reservoir for anthroponotic transmission. Our results establish that the high parasite load in VL is strongly correlated with a high level of IL-10, implicating IL-10 as a marker of disease severity. The assay is applicable for diagnosis as well as prognosis of both VL and PKDL, providing a simple molecular tool to monitor the efficacy of antileishmanial drugs or vaccines

DESIGN AND OPTIMIZATION OF ELECTROSTATIC PRECIPITATOR USING FINITE ELEMENT ANALYSIS TOOL

ABSTRACT An electrostatic precipitator is designed to trap and remove dust particles from the exhaust gas. The computer aided design and finite element analysis of electrostatic precipitator cone structure has been carried out. For static structure analysis two models (Model A and Model B) is being considered having horizontal and vertical stiffener arrangement. As per ISO (IS 808: 1989, Edition 4.1) standard for stiffeners, the various sizes of stiffeners are analyzed for electrostatic precipitator cone structure. The deformation of Model A cone structure and Model B cone structure is analyzed with various stiffener arrangements with allowable deformation 39mm. From analysis it is observed that deformation goes on decrease as weight of electrostatic precipitator cone structure increase. Also it is interestingly noted that maximum deflection region in each case of model is at centre of face having maximum surface area

Anatomic variations of superficial peroneal nerve: clinical implications of a cadaver study

Superficial peroneal nerve and its branches are frequently at risk for iatrogenic damage. Although different studies on anatomical variations of superficial peroneal nerve are available in the medical literature, such reports are rare from India. Hence the present study was undertaken on Indian population. A total of 60 specimens of inferior extremities from 30 properly embalmed and formalin fixed cadavers were dissected and examined for the location and course of the superficial peroneal nerve including number, level, course and distributions of branches. The superficial peroneal nerve in 28.3% specimens was located in the anterior compartment of the leg. In 8.3% specimens the superficial peroneal nerve branched before piercing between the peroneus longus and extensor digitorum longus muscle whereas in 11.7% specimens it branched after piercing the aforementioned muscles and before piercing the deep fascia. In 41 out of 60 specimens the sensory division of superficial peroneal nerve branched into the medial dorsal cutaneous nerve and intermediate dorsal cutaneous nerve distal to its emergence from the deep fascia and proximal to its relation to the extensor retinaculum. In 20 out of 60 specimens the accessory deep peroneal nerve, an additional branch from the sensory division of superficial peroneal nerve, through its course in the anterior compartment of the leg passed deep to the extensor retinaculum and supplied the ankle and the dorsum of foot. Hopefully the present study will help in minimizing iatrogenic damage to the superficial peroneal nerve and its branches while performing arthroscopy, local anesthetic block, surgical approach to the fibula, open reduction and internal fixation of lateral malleolar fractures, application of external fixators, elevation of a fasciocutaneous or fibular flaps for grafting, surgical decompression of neurovascular structures, or miscellaneous surgery on leg, foot and ankle

Prediction of FAD interacting residues in a protein from its primary sequence using evolutionary information

Background: Flavin binding proteins (FBP) plays a critical role in several biological functions such as electron transport system (ETS). These flavoproteins contain very tightly bound, sometimes covalently, flavin adenine dinucleotide (FAD) or flavin mono nucleotide (FMN). The interaction between flavin nucleotide and amino acids of flavoprotein is essential for their functionality. Thus identification of FAD interacting residues in a FBP is an important step for understanding their function and mechanism. Results: In this study, we describe models developed for predicting FAD interacting residues using 15, 17 and 19 window pattern. Support vector machine (SVM) based models have been developed using binary pattern of amino acid sequence of protein and achieved maximum accuracy 69.65% with Mathew's Correlation Coefficient (MCC) 0.39 and Area Under Curve (AUC) 0.773. The performance of these models have been improved significantly from 69.65% to 82.86% with MCC 0.66 and AUC 0.904, when evolutionary information is used as input in SVM. The evolutionary information was generated in form of position specific score matrix (PSSM) profile by using PSI-BLAST at e-value 0.001. All models were developed on 198 non-redundant FAD binding protein chains containing 5172 FAD interacting residues and evaluated using fivefold cross-validation technique. Conclusion: This study suggests that evolutionary information of 17 amino acid patterns perform best for FAD interacting residues prediction. We also developed a web server which predicts FAD interacting residues in a protein which is freely available for academics

Identification of NAD interacting residues in proteins

Background: Small molecular cofactors or ligands play a crucial role in the proper functioning of cells. Accurate annotation of their target proteins and binding sites is required for the complete understanding of reaction mechanisms. Nicotinamide adenine dinucleotide (NAD+ or NAD) is one of the most commonly used organic cofactors in living cells, which plays a critical role in cellular metabolism, storage and regulatory processes. In the past, several NAD binding proteins (NADBP) have been reported in the literature, which are responsible for a wide-range of activities in the cell. Attempts have been made to derive a rule for the binding of NAD+ to its target proteins. However, so far an efficient model could not be derived due to the time consuming process of structure determination, and limitations of similarity based approaches. Thus a sequence and non-similarity based method is needed to characterize the NAD binding sites to help in the annotation. In this study attempts have been made to predict NAD binding proteins and their interacting residues (NIRs) from amino acid sequence using bioinformatics tools. Results: We extracted 1556 proteins chains from 555 NAD binding proteins whose structure is available in Protein Data Bank. Then we removed all redundant protein chains and finally obtained 195 non-redundant NAD binding protein chains, where no two chains have more than 40% sequence identity. In this study all models were developed and evaluated using five-fold cross validation technique on the above dataset of 195 NAD binding proteins. While certain type of residues are preferred (e.g. Gly, Tyr, Thr, His) in NAD interaction, residues like Ala, Glu, Leu, Lys are not preferred. A support vector machine (SVM) based method has been developed using various window lengths of amino acid sequence for predicting NAD interacting residues and obtained maximum Matthew's correlation coefficient (MCC) 0.47 with accuracy 74.13% at window length 17. We also developed a SVM based method using evolutionary information in the form of position specific scoring matrix (PSSM) and obtained maximum MCC 0.75 with accuracy 87.25%. Conclusion: For the first time a sequence-based method has been developed for the prediction of NAD binding proteins and their interacting residues, in the absence of any prior structural information. The present model will aid in the understanding of NAD+ dependent mechanisms of action in the cell. To provide service to the scientific community, we have developed a user-friendly web server, which is available from URL http://www.imtech.res.in/raghava/nadbinder/

Special and inclusive education in the Republic of Ireland: reviewing the literature from 2000 to 2009

Provision for pupils with special educational needs in Ireland has undergone considerable change and review in the first decade of the twenty first century. In response to international demands for a more equitable education system which recognises diversity and considers how schools might address the needs of pupils who have been previously marginalised, Irish legislation has focused upon the development of inclusive schooling. Researchers during this period have endeavoured to understand how responses to the demand for greater inclusion have impacted upon the perceived need for change. This paper reviews the research literature for this period and identifies four key themes under which research has been conducted. The literature pertaining to these themes is explored and a possible agenda for future researchers identifie

Foxp3 and IL-10 Expression Correlates with Parasite Burden in Lesional Tissues of Post Kala Azar Dermal Leishmaniasis (PKDL) Patients

Post kala azar dermal leishamniasis (PKDL), an unusual dermatosis develops in 5–15% of apparently cured visceral leishmaniasis cases in India and in about 60% of cases in Sudan. PKDL cases assume importance since they constitute a major human reservoir for the parasite. Inadequate treatment of VL, genetics, nutrition and immunological mechanisms that allow renewed multiplication of latent parasites or reinfection predispose to PKDL. Immunopathogenesis of PKDL is poorly understood. IL-10 is widely accepted as an immuno-suppressive cytokine and produced by diverse cell populations including, B cells, macrophages and CD4+ T cells. Natural T regulatory (nTreg) cells are subpopulation of CD4+ T cells that inhibit the response of other T cells. In this study we reported the accumulation of nTreg cells in lesion tissues of PKDL patients. Further correlation of Treg markers and IL-10 with parasite load in lesion tissues suggested a role of IL-10 and Treg in parasite establishment or persistence. Further studies are warranted to explore antigen specific IL-10 source in lesion tissues and unravel the concerted induction or accumulation of Treg in PKDL