Influencing factors and clinical significance of the metastatic lymph nodes ratio in gastric adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>To investigate influencing factors of the metastatic lymph nodes ratio (MLR) and whether it is related to survival in patients with gastric adenocarcinoma.</p> <p>Methods</p> <p>We retrospectively evaluated the clinical features of 121 patients with gastric adenocarcinoma enrolled in our hospital between 2000 and 2007. The receiver operating characteristic (ROC) curve was used to determine the cutoff of the MLR, and CK20 immunohistochemical staining was used to detect micrometastasis of the lymph nodes.</p> <p>Results</p> <p>The areas under the ROC curve of MLR used to predict the death of 3-year and 5-year postoperative patients were 0.826 ± 0.053 and 0.896 ± 0.046. Thus MLR = 30.95% and MLR = 3.15% were designated as cutoffs. The MLR was then classified into three groups: MLR₁(MLR<3.15%); MLR₂(3.15% ≤ MLR ≤ 30.95%); and MLR₃(MLR>30.95%). We found that patients with a higher MLR demonstrated a much poorer survival period after radical operation than those patients with a lower MLR (P = 0.000). The COX model showed that MLR was an independent prognostic factor (P = 0.000). The MLR could also discriminate between subsets of patients with different 5-year survival periods within the same N stage (P < 0.05). The MLR has been shown to be 34.7% (242/697) by HE staining and 43.5% (303/697) by CK staining (P = 0.001). The clinicopathological characteristics of lymph vessel invasion and the depth of invasion could significantly affect the MLR.</p> <p>Conclusion</p> <p>MLR is an independent prognostic factor in gastric cancer. The combined ROC curve with MLR is an effective strategy to produce a curve to predict the 3-year and 5-year survival rates.</p

Structured Text Retrieval Models

Structured text retrieval models provide a formal definition or mathematical framework for querying semistructured textual databases. A textual database contains both content and structure. The content is the text itself, and the structure divides the database into separate textual parts and relates those textual parts by some criterion. Often, textual databases can be represented as marked up text, for instance as XML, where the XML elements define the structure on the text content. Retrieval models for textual databases should comprise three parts: 1) a model of the text, 2) a model of the structure, and 3) a query language [4]: The model of the text defines a tokenization into words or other semantic units, as well as stop words, stemming, synonyms, etc. The model of the structure defines parts of the text, typically a contiguous portion of the text called element, region, or segment, which is defined on top of the text modelâ\u80\u99s word tokens. The query language typically defines a number of operators on content and structure such as set operators and operators like â\u80\u9ccontaining â\u80\u9d and â\u80\u9ccontained-by â\u80\u9d to model relations between content and structure, as well as relations between the structural elements themselves. Using such a query language, the (expert) user can for instance formulate requests like â\u80\u9cI want a paragraph discussing formal models near to a table discussing the differences between databases and information retrievalâ\u80\u9d. Here, â\u80\u9cformal models â\u80\u9d and â\u80\u9cdifferences between databases and information retrieval â\u80\u9d should match the content that needs to be retrieved from the database, whereas â\u80\u9cparagraph â\u80\u9d and â\u80\u9ctable â\u80\u9d refer to structural constraints on the units to retrieve. The features, structuring power, and the expressiveness of the query languages of several models for structured text retrieval are discussed below. HISTORICAL BACKGROUND The STAIRS system (Storage and Information Retrieval System), which was developed at IBM already in the late 1950â\u80\u99s allowed querying both content and structure. Much like todayâ\u80\u99s On-line Public Access Catalogues, it wa

Investigation of the use of meshfree methods for haptic thermal management of design and simulation of MEMS

This thesis presents a novel approach of using haptic sensing technology combined with virtual environment (VE) for the thermal management of Micro-Electro-Mechanical-Systems (MEMS) design. The goal is to reduce the development cycle by avoiding the costly iterative prototyping procedure. In this regard, we use haptic feedback with virtua lprototyping along with an immersing environment. We also aim to improve the productivity and capability of the designer to better grasp the phenomena operating at the micro-scale level, as well as to augment computational steering through haptic channels. To validate the concept of haptic thermal management, we have implemented a demonstrator with a user friendly interface which allows to intuitively "feel" the temperature field through our concept of haptic texturing. The temperature field in a simple MEMS component is modeled using finite element methods (FEM) or finite difference method (FDM) and the user is able to feel thermal expansion using a combination of different haptic feedback. In haptic application, the force rendering loop needs to be updated at a frequency of 1Khz in order to maintain continuity in the user perception. When using FEM or FDM for our three-dimensional model, the computational cost increases rapidly as the mesh size is reduced to ensure accuracy. Hence, it constrains the complexity of the physical model to approximate temperature or stress field solution. It would also be difficult to generate or refine the mesh in real time for CAD process. In order to circumvent the limitations due to the use of conventional mesh-based techniques and to avoid the bothersome task of generating and refining the mesh, we investigate the potential of meshfree methods in the context of our haptic application. We review and compare the different meshfree formulations against FEM mesh based technique. We have implemented the different methods for benchmarking thermal conduction and elastic problems. The main work of this thesis is to determine the relevance of the meshfree option in terms of flexibility of design and computational charge for haptic physical model

IMPROVING QUANTITATIVE TREATMENT RESPONSE MONITORING WITH DEFORMABLE IMAGE REGISTRATION

Quantitative imaging with 18F-FDG PET/CT has the potential to provide an in vivo assessment of response to radiotherapy (RT). However, comparing tissue tracer uptake in longitudinal studies is often confounded by variations in patient setup and potential treatment induced gross anatomic changes. These variations make true response monitoring for the same anatomic volume a challenge, not only for tumors, but also for normal organs-at-risk (OAR). The central hypothesis of this study is that more accurate image registration will lead to improved quantitation of tissue response to RT with 18F-FDG PET/CT. Employing an in-house developed “demons” based deformable image registration algorithm, pre-RT tumor and parotid gland volumes can be more accurately mapped to serial functional images. To test the hypothesis, specific aim 1 was designed to analyze whether deformably mapping tumor volumes rather than aligning to bony structures leads to superior tumor response assessment. We found that deformable mapping of the most metabolically avid regions improved response prediction (P\u3c0.05). The positive predictive power for residual disease was 63% compared to 50% for contrast enhanced post-RT CT. Specific aim 2 was designed to use parotid gland standardized uptake value (SUV) as an objective imaging biomarker for salivary toxicity. We found that relative change in parotid gland SUV correlated strongly with salivary toxicity as defined by the RTOG/EORTC late effects analytic scale (Spearman’s ρ = -0.96, P\u3c0.01). Finally, the goal of specific aim 3 was to create a phenomenological dose-SUV response model for the human parotid glands. Utilizing only baseline metabolic function and the planned dose distribution, predicting parotid SUV change or salivary toxicity, based upon specific aim 2, became possible. We found that the predicted and observed parotid SUV relative changes were significantly correlated (Spearman’s ρ = 0.94, P\u3c0.01). The application of deformable image registration to quantitative treatment response monitoring with 18F-FDG PET/CT could have a profound impact on patient management. Accurate and early identification of residual disease may allow for more timely intervention, while the ability to quantify and predict toxicity of normal OAR might permit individualized refinement of radiation treatment plan designs

Standardization on Purification process of VEERAM: A Comparative Analysis

One of the most important aspects of siddha system is purification of the raw materials before using them for medicine. In this scientific era, it is very essential to determine changes in the material during the process of purification. Standardization is necessary to ensure the availability of the uniform product in all part of the world. Thus today standardization is very essential to focus on our system of medicine for practice. Based on the above rationale the present study was carried out with an aim to standardize the purification of Veeram based on some qualitative and quanitative analysis as per PLIM guidelines. Veeram which is one of the mineral compound mentioned in the Siddha literatures to treat major illness. From the above study report, purification process of Veeram is more important and high lightened to analyse change its complicated form into more easily acceptable form. Raw Veeram, Padigaram, Soodan was procured from the reputed country shop in Nagercoil and Kariuppu was purchased from local market in Tirunelveli. The raw drug was authenticated by experts of PG Gunapadam department, Government Siddha Medical College, Palayamkottai. Milagu was purchased from local market in Sattur and authenticated by Botanist, Government Siddha Medical College, Palayamkottai. Then the raw drug Veeram was divided into three equal quantities of 35g. One of the part of the raw drug was taken and powdered well and kept as such labelled as V1. The other two part of the raw drug Veeram was subjected to purification process by two methods. After the completion of purification procedure, the treated Veeram was powdered and labelled as V2, which is purified by method I and V3, which is purified by method II. The qualitative and quantitative analyses were done for V1, V2 and V3. The physicochemical analysis of V1, V2 and V3 reveals the changes in colour and pH. The change in loss of drying from before to after purification process depicts the extensive shelf life of the drug. After purification V2 lost its 17.14g% weight and sample V3 lost its 42.85g% weight and qualitatively indicated that the concentration of mercury was reduced better on compared with sample V1. From the extraction value, it was concluded that water is a better solvent of extraction than Alcohol. In chemical analysis revealed the presence of Carbonate, Sodium, Calcium, Ferrous Iron, Sulphate, Chloride and Mercury in all the three samples V1, V2 and V3. The presence of Silicate was found in V1 and V3. Absence in V2.Aluminium was present in the Sample V1 and V3 which was absent in the sample V2. This indicated that some chemical compounds disappeared after purification. In ICP-OES, elements such as Arsenic, Aluminium, Cadmium, Copper, Nickel and Lead were found below detection limit in all samples. Mercury was reduced after purification in both V2 & V3. It was confirmed that mercury level found to be decreased after purification of Veeram. In FTIR, V1 shows Alkyl halide C-I stretch, Alkyl halide C-Cl stretch, Alkyl halide C-F stretch, Alkene C-H, Amide C=O stretch, Acid O-H, Water (O-H stretch). Compared with V1, the FTIR spectra of purified sample V2 shows in addition of functional groups such as Alkanes and phenols. Sample V3 shows in addition of functional groups such as amines, Carboxylic acid and phenols. FTIR spectrum of sample V2 and sample V3 indicates either the formation of new organo mercuric compounds or presence of some organic compounds originally present in the herbal preparation used for the process of purification. It also confirmed the existance of Mercury chloride in purified veeram. SEM analysis depicted the changes in particle size range before and after purification. Among V1, V2 and V3 drugs, V1 batch of drugs shows smaller particle sizes compared to V2 and V3. X-ray diffraction of the samples inform the genuinity and stability of the formulation, with respect to the standard reference materials. The elemental composition of V1 showed the presence of Mercuric chloride (HgCl2) along with Sodium Mercury (II) Trichloride Dihydrate in small proportion. After purification in both V2 and V3, Mercury sulphide (HgS) is also present along with compounds of V1. Thus it can be postulate that the purification procedures as mentioned in Siddha literature help to remove the toxic effect without interfering its therapeutic efficacy. It may reduce the effect of toxic substance in the drug. The study stresses the need of purification process of the drug before going to preparation of medicines with strong evidence. Information obtained from these studies can be used as markers in the identification and statndardization of this mineral. CONCLUSION: From the study, the speciation analysis of Unpurified Veeram (V1) showed the presence of Mercuric chloride (HgCl2) along with Sodium Mercury (II) Trichloride Dihydrate in small proportion. Purification performed by both the methods resulted in addition of Mercury sulphide (HgS) along with compounds of V1. Siddha system insists on Purification before using them in the pharmaceutical preparations. This is the preliminary important procedure in preparing a medicine. The present study is an attempt to establish the scientific basis of purification for Veeram. The aim of purification is to minimize the toxic effect of the drug and enhance the potency and safe of a drug. The changes found in Veeram after purification indicates the necessity of purification. Hence it can be concluded that the concept of purification procedure as mentioned in Siddha text provides contemporary evidence with a good scientific background. These explorations will definitely help to set a standard procedure for purification of Veeram in futur

Nephrotic Syndrome and Glomerular Basement Membrane: Genetic Defect of the Laminin α5 Chain

Nephrotic syndrome is a heterogeneous group of disorders characterised by renal and extra-renal manifestations. Classic symptoms of nephrotic syndrome include severe proteinuria, hypoalbumiaemia, oedema and hyperlipidaemia. Genetic studies of hereditary forms of nephrotic syndrome have led to the identification of proteins playing a crucial role in slit diaphragm signalling, regulation of actin cytoskeleton dynamics and cell-matrix interactions. The laminin α5 chain is a 404 kDa protein essential for embryonic development and, in association with laminin β2 and laminin γ1, it is a major component of the glomerular basement membrane. Mutations in LAMB2 are associated with Pierson’s syndrome and mutations in LAMA5 have recently been identified in paediatric patients affected by nephrotic syndrome. As part of the MRC Harwell Ageing Screen, a large-scale ENU mutagenesis screen, a novel missense mutation (E884G) was identified in the gene Lama5. Homozygous mice showed a nephrotic phenotype including a severe proteinuria that preceded histological and ultrastructural changes. Further investigation using in vitro studies, extensive proteomics analysis and investigation of integrin activation, revealed a possible impact of the causative mutation on protein folding. Data suggest that changes in protein structure lead to a reduced secretion, integrin β1 activation, and agrin expression ultimately resulting in possible instability of the podocyte actin cytoskeleton

The relationship between quality of life (EORTC QLQ C-30) and survival and treatment in patients with gastro-oesophageal cancer.

Gastro-oesophageal cancer is the third commonest cause of cancer death in the UK. Each year, there are approximately 16,500 new cases diagnosed and over 13,000 deaths attributable to the disease. Overall survival is poor with the majority of patients presenting with advanced, inoperable disease and less than 15% surviving 5 years, therefore ensuring the best quality of life is paramount for these patients. The traditional end points of tumour response, toxicity and survival are limited in discerning differences between the various treatments for gastro-oesophageal cancer. Irrespective of treatment, the majority of patients with advanced disease do not achieve a response to treatment or an increased survival. Consequently, in the last decade, there has been considerable interest in including some measure of quality of life in the assessment of patients with cancer and their continuing aftercare, as it provides information on the patient’s perception of their health and the effectiveness and side effects of their treatment. Quality of life has been an implied outcome since the earlier days of health care. In 1947, the World Health Organisation defined health as “a state of complete physical, mental and social well-being and not merely the absence of disease”. The first scale to quantify patient’s activity level and capability was developed in 1948 by Karnofsky. Since that time, numerous scales have been developed to assess an individual’s physical, psychological and social response to disease and its treatment. The aim of this thesis is to examine the baseline relationship between clinico-pathological characteristics and quality of life in gastro-oesophageal cancer patients and to further assess the long-term effect of treatment (surgery, oncological treatment or supportive care). For this study we have used the EORTC QLQ-C30, the ECOG performance status scale and the dysphagia score. In Chapter 2, an assessment of quality of life, clinical and pathological variables was undertaken on 152 patients. This study demonstrated there were major differences in quality of life and symptom scores with increasing stage of disease. In particular, social functioning, fatigue, appetite loss and global quality of life were all impaired with increasing tumour stage. As might be expected in view of these associations, the majority of quality of life and symptom scores predicted survival on univariate analysis. It was of interest, however, that appetite loss remained an independently significant prognostic factor even after adjustment for TNM stage and treatment. Furthermore in the present study C-reactive protein concentrations were available in 94 (62%) patients, at the time of quality of life assessment. An elevated C-reactive protein concentration was associated with increased appetite loss and when included in the multivariate analysis, an elevated C-reactive protein concentration was independently associated with poorer cancer specific survival. However, even those patients without an elevated C-reactive protein concentration, reported some appetite loss and the independent prognostic value of appetite loss remained, thus confirming the importance of appetite loss in the multifactorial nature of weight loss and poor outcome in these patients. The effect of treatment on aspects of quality of life including appetite loss has rarely been examined. Furthermore, there are, to our knowledge, no studies which have examined the effect of surgery on quality of life beyond 3 years. Therefore in Chapter 3 we examined the effect of treatment (surgery, oncological treatment or supportive care) on quality of life (EORTC QLQ-C30) for up to fours years post treatment in 160 patients. Patients who underwent surgery had, at study entry, better global quality life including better physical and role functioning and less fatigue and appetite loss compared with those patients who did not receive surgery. Furthermore, the effect of oesophageal surgery on global quality of life appeared to be more profound and persistent. In contrast, in patients with inoperable disease, the poor quality of life measures at study entry remained poor on follow-up whether patients received oncological input or supportive care. In conclusion, the results of the present studies have indicated that appetite loss is important in determining quality of life in gastro-oesophageal cancer patients and is independently associated with poor survival. Furthermore, the effect of surgery has a long lasting and profound effect on quality of life in this cohort of patients