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As the cyst ages and the specific antibody concentration decreases pain treatment with laser buy cheap motrin 600mg online, the likelihood of detecting species-specific antibodies also goes down pain treatment journal buy genuine motrin. An assessment of the sensitivity of different assays is thus strongly influenced by the composition of the tested collective hip pain treatment relief buy motrin 600 mg otc. A steady increase in antibody reaction from 78% in the early phase to 91% in the advanced phases can be assumed pain treatment center rochester general hospital generic 400mg motrin visa. In countries like Germany quadriceps pain treatment motrin 600mg on line, where both Echinococcus species are expected pain medication for dogs surgery purchase motrin from india, an assay with a high sensitivity to both species. For both Echinococcus species, a differentiation is most successful when there is a high concentration of genusspecific antibodies. IgM, IgA, and IgE antibodies can be detected during various stages in some patients, however they are not suitable for routine diagnostics. Therefore, the diagnosis is based on the detection of IgG antibodies or whole globulin. Only the complete surgical removal of the lesions containing the larvae produces a rapid drop and disappearance of specific antibodies. In contrast, the disappearance of such antibodies indicates that the larval tissue has died [14]. Antibody detection is also not a suitable method for confirming the clinical suspicion of a reactivation (formation of new cysts). The relevance of a positive or negative serological finding can only be evaluated in conjunction with the clinical finding. An antibody screening is useful for sero-epidemiological studies in endemic regions. It also occurs in countries with a moderate climate, insufficient water treatment and poor hygienic conditions. Transmission occurs fecal-orally through the ingestion of water or food contaminated with cysts. In around 90% of cyst carriers, the intestinal infection is asymptomatic and self-limiting, and the parasites can no longer be detected after around 1 year. Intestinal or extra-intestinal symptoms include: acute, ulcerative to fulminant colitis and bloody stool and/or liver abscesses and, in rare cases, lung involvement. An objective assessment of the different assays is difficult due to the absence of a gold standard for amoebiasis. After specific treatment, IgG antibodies drop and persist at a low level for months to years. Positive serological test results should always be interpreted in conjunction with clinical symptoms and the origin or travel history of the affected individual. In highly endemic regions, a positive serological finding can be expected in up to 84% of the population. Antigen detection in stool: the assays that detect coproantigen should specifically detect E. All of the tests are limited by the fact that the stool samples have to be fresh and processed within 24 hours, or frozen in an unfixed state in order to avoid degradation of the target antigens. However it should be noted that positive results are expected to last longer after a specific treatment than for microscopic tests and should be correspondingly assessed. In contrast to isoenzyme analysis, the sensitivity of such tests is between 80% and 99%, and the specificity is between 86% and 98%. Immunologically based antigen detection tests make sense when an intestinal amoebic infection is specifically suspected or when a microscopic finding is positive so that a differentiation can be made between species. The diagnostic significance of antibody tests is higher in non-endemic regions than in endemic regions. Eight to twelve weeks after infection they begin to excrete immature eggs which are passed with the bile to the 190 stool and ultimately into the environment. The complex reproduction cycle of the pathogen facilitates focal distribution in the endemic regions. The chronic or obstructive phase is characterized by blockage of the bile ducts, cholecystitis, liver abscess or cirrhosis. Detection is laborious (at least 6 tests) and unreliable in low endemic areas since the eggs are excreted irregularly and in low concentrations. Serological tests are a suitable diagnostic tool during the early phase of infection in which considerable liver damage can occur through larva migration when there is a severe infection. Serological tests are also suitable for chronic infections, particularly when there is a low degree of egg excretion. Currently there is no consensus on the best serological test for human fasciolosis which uses a defined antigen. Cross reactivity is possible with Schistosoma, Paragonimus, Clonorchis and other helminths. Details on the development of antibodies in humans after an initial infection are rare. Antigen detection: In order to detect eggs, veterinary tests based on monoclonal antibodies are adapted for human stool samples. They are as sensitive (if not more so) in the chronic phase than microscopic detection using the Kato-Katz method [322]. The infectious larvae are injected during the bite but rarely develop into adult worms (approx. If they are able to develop in the host, the adults can be found either in the lymph nodes and vessels (lymphatic filariasis: Wuchereria bancrofti, Brugia malayi, B. The causative agents of lymphatic filariasis occur in humid regions of Central and South America, Africa and Southeast Asia (W. The rarely pathogenic Mansonella have been detected in humans in central and west Africa (M. A percentage of all filarial infections are subclinical and the infected person remains an asymptomatic microfilaria carrier for years. Serious diseases have been observed in infected individuals in the acute or chronic phase of the infection when they react to the filariae with a strong immune response. In the case of lymphatic filariasis the pathogenic agents are always the adult worms and the antigens secreted by them. The disease can be divided into an early phase, which is characterized by discomfort, fever, chills, recurring attacks of lymphadenitis and lymphangitis, and, in the case of W. In the late stage (chronic-obstructive) a proliferation of the lymphatic endothelia develops that leads to a drainage blockage and to lymphatic obstruction and ultimately to elephantiasis of the limbs (< 5% of those infected) due to a dilatation of the lymph channels. It occurs as a result of a strong immune reaction to microfilaria in the lungs and is characterized by coughing and asthma-like attacks. In the early phase of the infection the reaction manifests as dermatitis with pronounced itching, particularly in those individuals not from an endemic region (tourists, seasonal workers). In the late stage, skin atrophies, loss of skin elasticity and pigment damage occur. The most severe damage develops from an inflammatory reaction to migrating microfilaria in the eye. People in the late phase of the disease have pronounced symptoms, but mostly no blood microfilaria and no specific antibodies (burn-out phase). Antibody detection is useful for asymptomatic and symptomatic individuals from non-endemic or low-endemic regions, or as a screening test for individuals from endemic regions. Since there is no generally recognized gold standard, multiple diagnostic methods should be combined in individual cases. In non-endemic regions, screening tests are one of the only ways to detect anti-Filaria antibodies. The tests exhibit a low species specificity and enable anti-Filaria antibodies to be detected in different filarial infections. They are characterized by a high sensitivity, however a high degree of cross reactivity with other worms, particularly helminths, must be taken into account. A positive antibody test indicates contact with worm antigens, without the possibility of differentiating between exposure and infection (prepatent, active, chronic). The specificity of serological detection methods has been considerably improved through the use of species-specific, recombinant antigens. The recombinant antigen Ov-16 is preferred in the species-specific diagnosis of Onchocerca volvulus, the antigen BmR1 for B. The card tests selectively determine specific IgG4 antibodies against the corresponding recombinant antigens. In contrast to an IgG-based test, the specificity of the test can be considerably improved through this method since the antibodies responsible for the cross reaction between nematodes are absent in the IgG4 subclass. However, the serum concentration of IgG4 antibodies depends on the intensity of the filarial infection. This test concept is well suited for identifying people from an endemic region with an active infection (microfilaria carriers) or with a strong exposure. The currently available test combinations do not achieve a 100% sensitivity and specificity as the results of sero-epidemiological tests illustrate. The quality of the Bm14 test has limitations when determining Brugia or Wuchereria-Mf carriers despite its high sensitivity (> 90%) because of cross reactivity with Onchocerca and Loa antibodies and most likely with other helminths (Ascaris, Strongyloides) as well [350]. It may be possible to improve the diagnostic certainty of future tests through a cocktail of various recombinant antigens. Disease and stage Result of antibody screening and interpretation Lymphatic filariasis 1 Positive Negative (W. Species-specific serological assays are currently not suitable for identifying weak infections and, like screening tests, cannot differentiate between various stages of infection (prepatent, patent, after treatment) and a strong exposure. Wuchereria-specific antibodies (Anti-Bm33, Anti-Bm14) develop for around 3 years in children in endemic regions until microfilaria can be detected in blood [136]. As with experimentally infected primates, when adults are infected for the first time with filaria as travelers, specific serum antibodies are expected to appear a few weeks after infection and thus during the prepatent period [350]. False-negative serological findings are possible in people from endemic regions with a high parasite load and in people with clinical symptoms of a chronic infection in which worm antigens are no longer present (burned-out infection). After treatment, antibodies against Filaria crude antigens and recombinant antigens fall slowly over years making serology unsuitable for monitoring treatment. A positive result indicates an infection, even when blood microfilaria cannot be microscopically detected. Monoclonal antibodies detect the antigen Og4C3 which correlates well to the worm load of adult filaria in the quantitative assay. These tests have not been approved in Germany and are not available for diagnosing patients. Antibody detection has a limited diagnostic significance for individuals from Filaria-endemic regions where a large proportion of the population is seropositive. Even when the serology is negative, antibody detection cannot be used in this target group as the only means of excluding an active or burned-out filarial infection. Leishmania are amastigotes that reproduce intracellularly in the cytoplasm of macrophages and cells of reticuloendothelial systems. These have a special preference for tissue which leads, in the case of disease, to three main clinical syndromes: visceral, cutaneous or mucocutaneous leishmaniosis. The species of Leishmania determines the type and progression of the disease as well as the genetic predisposition and specific immunity status of the infected individual. The disease is progressive and characterized by a high fever (possibly also intermittent), splenomegaly and/or hepatomegaly, and less often by lymphadenopathy, anemia, leucopenia and thrombocytopenia. However, 9 out of 10 infections with visceralizing Leishmania remain asymptomatic. Antibody 195 detection is useful when a visceral infection is suspected since, with this clinical picture, serological tests exhibit good to very good diagnostic properties.

Inadequate vitamin K leads to clotting factor deficiency because this vitamin is important in the synthesis of the clotting factors by the liver pain treatment center memphis buy motrin paypal. Terminology: 1) Haemorrhage enclosed within a tissue or a cavity is knownas hematoma pain solutions treatment center woodstock ga cheap motrin online visa. Hemostasis and Blood Coagulation Hemostasis Definition: Hemostasis is the maintainence of the clot-free state of blood & the prevention of blood loss via the formation of hemostatic plug pain ischial tuberosity treatment order motrin online from canada. Hemostasis depends on three general components: a) Vascular wall b) Platelets c) Coagulation pathways Whenever a vessel is ruptured or severed pain treatment medicine clifton springs ny best buy motrin, hemostasis is achieved by several mechanisms: A pain treatment studies discount 600 mg motrin amex. Eventual growth of fibrous tissue in to the blood clot to close the hole in the vessel permanently advanced pain treatment center ohio cheap motrin online visa. Remark: the student is advised to revise his physiology lecture note on the above topics. Thrombosis Under this topic, we will discuss the definition, pathogenesis, morphology, fates, & clinical significance of thrombi, in this order. Definition: Thrombosis is defined as the formation of a solid or semisolid mass from the constituents of the blood within the vascular system during life. B: Turbulence or Stasis (Alterations in normal blood flow) Under physiologic conditions normal blood flow is laminar, that is, the cellular elements flow centrally in the vessel lumen separated from endothelium by slowing moving clear zone of plasma. Disrupt the laminar flow and bring platelets in to contact with the endothelium b. Retard or make a time lag in the inflow of clotting factor inhibitors and permit the build up of thrombi. A dilated left atrium is a site of stasis & a prime location of thrombus development. C: Hypercoagulablity Definition: Hypercoagulability is any alteration of the coagulation pathway that predisposes to thrombosis. Hypercoagulability is a less common cause of thrombosis & & it can be divided into: 1. Secondary (Acquired) which, in turn, can be categorized into: A: High-risk for hypercoagulablity prolonged bed rest or immobilization Myocardial infarction Tissue damage (surgery, fracture, burns) ancers (Cancers release procoagulant tissue products to cause thrombosis) Prosthetic cardiac valves Disseminated intra vascular coagulation 73 B: Low risk factor for hypercoagulablity A trial fibrillation Cardiomyopathy Nephrotic syndrome Smoking Oral contraceptives Hyperestrogenic state eg. The differences between arterial & venous thrombi are: Arterial thrombi Venous thrombi a) Arise at the site of endothelial injury a) Arise at area of stasis b) Grow in a retrograde fasion, against b) Grow in the direction of blood flow from its site of attachment. B: Embolization: the thrombus may dislodge and travel to other sites in the vasculature. Death of a tissue due to a decreased blood supply or drainage is called infarction. D: Organization and recanalization Organization refers to the ingrowth of endothelial cells, smooth muscle cells, and fibroblasts into the fibrin-rich thrombus. Organization is accompanied by the formation of capillary channels across the thrombus, re-establishing lumen continuity to some extent. The recanalization eventually converts the thrombus into a vasscularized mass of tissue which is later on incorporated as a subendothelial swelling of the vessel wall. Venous Thrombosis (Phlebothrombosis) Venous thrombosis affects veins of the lower extremity in 90% of cases. Superficial venous thrombosis Usually occurs in saphenous venous system, particularly when there are varicosities. This is because deep venous obstruction is rapidly offset or releaved by collateral bypass channels. Pregnancy & puerperal states increase coagulation factors & reduce the synthesis of antithrombotic substances. Migratory thrombophlebitis is a condition that affects various veins throughout the body & is usually of obscure aetiology, but sometimes it is associated with cancer, particularly pancreatic cancer. Arterial Thrombosis the rapid flow of arterial blood prevents the occurrence of thrombosis unless the vessel wall is abnormal. Atheromatous plaques produce turbulence and may ulcerate & cause endothelial injury, both of which can lead to thrombosis. These thrombi may narrow or occlude the lumen of arteries such as the coronary and cerebral arteries. A thrombus develops in the atrium in patients with atrial fibrillation & dilatation superimposed on mitral stenosis. Embolism Definition:An embolus is a detached intravascular solid, liquid or gaseous mass that is carried by blood to sites distant from its point of origin. Causes of embolism: An embolus can arise from: o Thrombus (99% of emboli arise from a thrombus. Such an embolus is called thromboembolus) o Platelets aggregates o Fragment of material from ulcerating atheromatous plaque o Fragment of a tumour o Fat globules o Bubbles of air o Amniotic fluid o Infected foreign material o Bits of bone marrow o Others. Unless otherwise specified, the term embolism should be considered to mean thromboembolism. Such an embolus is derived from a thrombus in the systemic veins or the right side of the heart. The thromboembolus will travel long with the venous return & reach the right side of the heart. Depending on the size of the embolus and on the state of pulumonary circulation, the pulmonary embolism can have the following effects: 1. If the thrombus is large, it may block the outflow tract of the right ventricle or the bifurcation of the main pulumonary trunk (saddle embolus) or both of its branches, causing sudden death by circulatory arrest. Sudden death, right side heart failure (cor pulmonale), or cardiovascular collapse occurs when 60% or more of the pulumonary circulation is obstructed with emboli. If the embolus is very small (as in 60-80% of the cases), the pulmonary emboli will be clinically silent. Embolic obstruction of medium sized arteries manifests as pulmonary haemorrhage but usually does not cause infarction because of dual blood inflow to the area from the bronchial circulation. In turn, two thirds of intracardiac mural thrombi are associated with left ventricular wall infarcts and another quarter with dilated left atria secondary to rheumatic valvular heart disease. The major sites for arteriolar embolization are the lower extremities (75%) & the brain (10%), with the rest lodging in the intestines, kidney, & spleen. The emboli may obstruct the arterial blood flow to the tissue distal to the site of the obstruction. The infarctions, in turn, will lead to different clinical features which vary according to the organ involved. Fat Embolism Fat embolism usually follows fracture of bones and other type of tissue injury. Although traumatic fat embolisms occur usually it is as symptomatic in most cases and fat is removed. But in some severe injuries the fat emboli may cause occlusion of pulmonary or cerebral microvasculature and fat embolism syndrome may result. Fat embolism syndrome typically begins 1 to 3 days after injury during which the raised tissue pressure caused by swelling of damaged tissue forces fat into marrow sinsosoid & veins. The features of this syndrome are a sudden onset of dyspnea, blood stained sputum, taccycardia, mental confusion with neurologic symptoms including irritability & restlessness, sometimes progress to delirium & coma. Air embolism Gas bubbles within the circulation can obstruct vascular flow and cause distal ischemic injury almost as readily as thrombotic masses. Generally, in excesses of 100cc is required to have a clinical effect and 300cc or more may be fatal. The bubbles act like physical obstructions and may coalesce to form a frothy mass sufficiently large to occlude major vessels. Amniotic fluid embolism It is a grave but un common, unpredictable complication of labour which may complicate vaginal delivery, caesarean delivery and abortions. The amniotic fluid containing fetal material enters via the placental bed & the ruptured uterine veins. The onset is characterized by sudden severe dyspnea, cyanosis, hypotensive shock followed by seizure & coma of the labouring mother. As discussed in this & the previous subtopics, the potential consequence of thromboembolic events is ischemic necrosis of distal tissue, known as infarction. Infarction Definition: An infract is an area of ischemic necrosis caused by occlusion of either the arterial supply or venous drainage in a particular tissue. The effect of such a dual blood supply is that if there is obsrtuction of one of the arterial supplies, the other one may offset the rapid occurrence of infarction in these organs unlike the renal & splenic circulations which have end arterial supply. Infarction caused by venous thrombosis is more likely to occur in organs with single venous outflow channels, such as testis &ovary. B: Rate of development occlusion Slowly developing occlusions are less likely to cause infraction since they provide time for the development of collaterals. Neurons undergo irreversible damage when deprived of their blood supply for only 3 to 4 minutes. D: Oxygen content of blood Partial obstruction of the flow of blood in an anaemic or cyanotic patient may lead to tissue infarction. Types of infarcts Infarcts are classified depening on: A) the basis of their colour (reflecting the amount of haemorrhage) into: 1. Anemic (White) infarcts B) the presence or absence of microbial infection into: 1. Red infarcts occur in: a) Venous occlusions as in ovarian torsion b) Loose tissues such as the lung which allow blood to collect in infarct zone. White infarcts occur in: a) Arterial occlusion in organs with a single arterial blood supply. Morphology of infarcts Gross: All infarcts are wedge-shaped with the occluded vessel at the apex and the periphery of the organ forming the base of the wedge. Following inflammation, some of the infarcts may show recovery, however, most are ultimately replaced with scars except in the brain. Microscopy: the dominant histologic feature of infarction is ischemic coagulative necrosis. The brain is an exception to this generalization, where liquifactive necrosis is common. Myocardial infarction Usually results from occlusive thrombosis supervening on ulcerating atheroma of a major coronary artery. Cerebral infarcts May appear as pale or hemorrhagic A fatal increase in intracranial pressure may occur due to swelling of large cerebral infarction, as recent infarcts are raised above the surface since hypoxic cells lack the ability to maintain ionic gradients & they absorb water & swell. Splenic infarcts Conical & sub capsular Initially dark red later turned to be pale. Tissue thromboplastin substance may be derived from a variety of sources such as: A: Massive trauma, severe burns & extensive surgery. B: Obstetric conditions in which thromboplastin derived from the placenta, dead retained fetus, or amniotic fluid may enter the circulation. Endothelial injury: Widespread endothelial injury may result from: Deposition of antigen-antibody complexes as it occurs in systemic lupus erythematosus Extreme temperature eg. This may lead to ischemia of the more severely affected or more vulnerable organs and hemolytic anemia resulting from fragmentation of led cells as they squeeze through the narrowed microvasculature (Microangiopathic haemolytic anaemia). Second, a hemorrhagic diathesis may dominate the clinical picture because of consumption of the coagulation factors and increased fibrinolysis. The onset may be fulminant when caused by endotoxic shock or amniotic fluid embolism or it may be chronic in the case of carcinomatosis or retention of dead fetus. Less often, they may present with acrocyanosis, pre-gangrenous changes in the digits, genitalia, & nose areas where blood flow may be markedly decreased. Shock Definition: Shock is a state in which there is failure of the circulatory system to maintain adequate cellular perfusion resulting in widespread reduction in delivery of oxygen & other nutrients to tissues. In shock, the mean arterial pressure is less than 60 mmHg or the systolic blood pressure is less than 90 mmHg. The end results are hypotension followed by impaired tissue perfusion and cellular hypoxia. Reduction in circulating blood volume results in the reduction of the preload which leads to inadequate left ventricular filling, reflected as decreased left & right ventricular end diastolic volume and pressure. The reduced preload culminates in decreased cardiac out put which leads to widespread tissue perfusion (shock). Causes of hypovolumic shock include: a) Haemorrhage b) Diarrhoea & vomiting c) Burns d) Trauma e) etc the effect of haemorrhage depends on the rate and amount of blood loss. A normal healthy adult can lose 550ml (10%of blood volume) without significant symptoms. But loss of 25% or more of the blood volume (N=1250ml) results in significant hypovolemia. Cardiogenic shock Definition: this is shock that results from severe depression of cardiac performance. Usually shock occurs in this conditioin if 40% of the left ventricular mass & more on the right ventricle is involved by infarction. Aortic stenosis, hypertrophic cardiomyopathy b) Reduction in forward cardiac output E.

Our network architecture was inspired by the Unet and has been modified to increase brain tumor segmentation performance pain treatment peptic ulcer order motrin canada. On the challenge validation dataset treatment of cancer pain guidelines cheap 400mg motrin, our system achieved a mean enhancing tumor pain management for dogs with arthritis order 600mg motrin free shipping, whole tumor pain treatment in osteoporosis purchase 600mg motrin with amex, and tumor core dice score of 0 pain treatment hypnosis discount motrin online amex. However pain treatment for lumbar arthritis discount motrin on line, segmenting brain tumor manually is not only challenging task but also a time-consuming one, favoring therefore, the emergence of computerized approaches. Despite considerable research works and encouraging results in the medical imaging domain, fast and precise 3D computerized brain tumors segmentation remains until now a challenging process and a very difficult task to achieve because brain tumors may appear in any size, shape, location and image intensity [2-5]. The transformations comprise rotation, translation, and horizontal flipping and mirroring. For downsampling, a convolution layer with a 2 x 2 filter and a stride of 2 is applied. At the last layer of the expanding path, a 1 x 1 convolution with the Softmax activation function is used to map the multi-channel feature maps to the desired number of classes. The goal is to find the network parameters (weights and biases) that minimize a loss function. Employing Sensitivity with Specificity can provide a good assessment of the segmentation result. Mean, standard deviation, median and 25th and 75th percentile are given for Dice and Sensitivity metrics in Table 1 and for Specificity and Hausdorff distance in Table 2. In this1 context, we can compare our segmentation results with those of other participants. Also, other interesting perspective consists to use ensemble learning methods, like Stacking and Blending, to improve segmentation performance in tumor core and active tumor regions. The training dataset comprises of 210 high grade glioma volumes and 75 low grade gliomas. The Table 1 lists the features extracted for survival analysis which is further elaborated below. Hence, this feature gives the ratio of volume of the tumor core to the volume of the whole tumor. In images d and e, Green, Yellow & Red represent Edema,Enhancing Tumor and Necrosis present in the lesion. In images d and e, Green, Yellow & Red represent Edema, Enhancing Tumor and Necrosis present in the lesion. The false positives generated by the network were minimized by using 3-D connected component analysis. Spyridon Bakas, Hamed Akbari, Aristeidis Sotiras, Michel Bilello, Martin Rozycki, Justin S Kirby, John B Freymann, Keyvan Farahani, and Christos Davatzikos. Bjoern H Menze, Andras Jakab, Stefan Bauer, Jayashree Kalpathy-Cramer, Keyvan Farahani, Justin Kirby, Yuliya Burren, Nicole Porz, Johannes Slotboom, Roland Wiest, et al. On the other hand time consuming 3D evaluation like segmentation is able to provide precise estimation of a number of valuable spatial characteristics giving us understanding about the course of the disease. Test dataset is split into two parts: validation data proposed methods can be evaluated with throughout the challenge and testing data. The performance of the methods is evaluated using Dice coeficient, Sensitivity, Specificity and Hausdor distance. Above-named challenge made a significant impact on the evolution of computational approaches for tumor segmentation. In the last few years variety of algorithms addressed to solve this problem were proposed. In this paper we present two-stage convolutional neural network based pipeline for brain tumor segmentation. We compare multiple approaches for defining localization network and report their performance. Regression of the spatial characteristics is done using Resnet18 [6] model and Resnet10 model with Difierentiable Spatial to Numeric Transform [11]. We use unet [5, 12] and proposed cascaded unet variant as a second type of algorithms that are able to implicitly estimate values described above. Every convolution uses 3x3x3 kernel and 1x1x1 padding to keep the size of feature map the same. Corresponding feature maps of encoding and decoding parts are linked using skip connections. Cascaded U-net Proposed network is illustrated in figure 3 and consists of three basic blocks. After that we are eliminating outliers and noise by clamping all values to the range from -5 to 5. At the final step we shift brain voxels to the range [0;10] and assign zeros to background. Here we are especially interested in intersection over union and overlap ratio since these two characteristics refiect number of rejected voxels that can possibly be tumor voxels. We implemented and compared difierent localization methods and showed their performance for brain tumor localization. Both methods achieved the same accuracy on validation data provided by organizers, however proposed method showed better performance on local validation. Our four-stage system attempts to follow the layered structure of tumor tissues provided in the annotation protocol. In each segmentation stage we dealt with four major difculties: feature selection, determination of training database used, optimization of classifer performances and image post-processing. The most important advantage of medical imaging is the fact that examination performed non-intrusively. Lefkovits in this article was supported by the Communitas Foundation and the work of L. The segmentation results obtained showed that the tumor region is well detected, but the contours of the whole tumor and the interior tumor tissues are not well delimited. The source of the aforementioned errors could be the choice of training samples used, the unbalanced database provided, and its enormous size. Another defciency in our previous model is that it considered almost any spatial relationship between the tumor tissues, according to the annotation protocol described in [11, 15]. The feature database generation process is identical both for the segmentation (classifcation) and the training phases, as well. Intensity normalization was done by histogram linear transformation in such a way that the frst and third quartiles had predefned values. In voxel-wise segmentation it is necessary to defne a set of intensityand local neighboring features. Each classifer is trained and evaluated on its own feature database during its training process (Fig. The global training consists of four training stages and each stage is composed of the following four steps: 1. Therefore, this large amount of data was handled by taking advantage of the random forest variable importance evaluation. The main idea of the algorithm is to evaluate the variable importance several times on a randomly chosen part of the feature database (Fig. Averaging the variable importances in the iterations the algorithm was able to eliminate the most unimportant 20-40% of variables in each run. In consequence we must obtain a well-defned database for training our random forest classifer. By applying this post-processing step we succeeded to eliminate the most of the false detections and improve the quality of segmentation. This binary classifer was trained on the whole brain in order to delimit the healthy region from the tumoral region. So as to improve these values a region dilation of 3 voxels (with a ball-structuring element) was applied, taking into consideration only the two most important connected regions. In this stage the segmentation with post-processing creates two disjunct regions, considering the tumor zone a connected region inside the healthy tissues. The results obtained after the four stages were uploaded to the leaderboard [5] are presented in Tables 2, 3 and Fig. In each stage we solved the four important issues concerning discriminative models. Our results show that binary classifers are very efcient for the layered segmentation task. The modified U-Net of each stage is implemented as three separate 2D modified U-net for the axial, sagittal and coronal views, followed by fusion operation to include tumor features from all views. With different histological structure, gliomas can be divided into various heterogeneous subregions such as edema, necrotic core, enhancing and non-enhancing tumor core. Accurate segmentation of the tumor sub-region is important for the precise diagnosis and treatment, such as radiotherapy[1, 2, 3]. U-Net has been successfully applied to many biomedical image tasks, and showed good performance on semantic segmentations[7, 8, 9]. For the prediction of patient overall survival, the data is defined in days, storing in the csv file corresponding to each case name. We have adopted a three-stage approach to extract the tumor structures, which consists of whole tumor extraction, tumor core extraction and enhancing tumor extraction. The U-Net is implemented with feature numbers of [64, 128, 256, 512, 1024], separately. During downsampling and upsampling of each layer, we adopt the kernel size of 3 in convolutional layer and kernel size of 2 in max pooling layer. The output of the network has 2 channels, each represents the background and foreground (whole tumor). While in testing stage, testing cases will be feed forwarded through each UNet-Axi, U-Net-Sag and U-Net-Cor, and the results of each view are ensembled with equal weights, followed by a post-processing operation. During post-processing, the final binary labels are fused as the maximum indexes of log-softmax values from the 2 output channels. Besides, the kernel size was set as 3 in convolutional layers and as 2 in pooling layers, the same as in the 2D U-Net. The output of the net is a 3-channel tensor, each channel refers to the probability map of background, tumor core and edema, respectively. Since the region of brain tumor normally correspond to 20% or less of the overall brain tissue, dice coefficient[14, 15, 16] is used as a loss function to train the net, which can be written as: = (1) + where V is the set of voxels in the 3D image, is the softmax value of the voxel. To solve the problem, we design a united dice loss function which also include dice score of edema to revise boundary: = + (2) where is the coefficient of the dice loss of edema region. Subsequently, the 3-channel output of the network was multiplied by the previous whole tumor prediction probability map to remove outside false positive voxels. The final dice is calculated as the average in all procedures, and an average dice score of 0. During training and validating, we have applied data preprocessing and augmentation techniques to increase the segment accuracy. In International Conference on Medical Image Computing and ComputerAssisted Intervention 2015 Oct 5 (pp. The importance of skip connections in biomedical image segmentation[M]//Deep Learning and Data Labeling for Medical Applications. Semantic segmentation is a difficult problem, for it requires algorithms include both multi-level reasoning and the pixel-level accuracy. In recent years, deep convolutional neural networks have achieved many result-breaking results in dense prediction and scientists are still working on proposing new methods to produce more precise boundary. In this paper, a two-stage coarse-tofine model is put forward, of which the first phase is designed to obtain the overall shape of target region and the second one to identify pixel-level details. It requires algorithms not only segment the object out, but also categorize pixels into different classes. Up to now, most of the models proposed for dense prediction problems are adapted from neural networks proposed for natural scene [9]. For example, in an indoor dense prediction problem, when algorithms are required to segment a fork out, there is no need to differentiate each tooth of the fork. Those models are reported to performs better in solving image segmentation problems. Based on those research mentioned above, the second or later neural networks will improve the performance and that improvement could be attributed to better segmentation of details. This method raises questions that whether the second or later neural networks should as complex as the first one. If the first stage is designed to achieve a coarse result and the second stage are designed to polish the output of it, would the structure become more brief and efficientfi In this paper, a two-stage coarse-to-fine model are proposed for semantic segmentation problem. The convolutional neural network of the first stage is designed with pooling operations, so that a large receptive field could be obtained for image reasoning. In the method part of this paper, we will introduce the structure of out model and some details of it.

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One of the natural instincts of most couples is to conceive flawless children free from the burden of any disorder. Especially in Western society, pre-natal screening for genetic impairment is progressively considered as a regular practice (Press, 1997, p. It is also clear that earlier initiation of therapy can make a substantial difference in the outcome of the disease progression (Wang, 2011). However, the universal truth is that genetic screening seems to be accepted as a norm in society today. The use of pre-natal testing has thus become accepted over the past 20 years (Thompson, 1999, p. One of the arguments against screening is the risk of discrimination or stigmatization (De Montalembert, 2005, p. Unanticipated medical tests and evaluations may be conducted on adults with asymptomatic Gaucher disease who have now been identified through screening (Zuckerman, 2007, p. Chadwick et al held that in addition to creating uncertainty and anxiety, some patients might also experience low self-esteem (Chadwick, 1997, p. Some authors like Takala et al suggest that an individual is personally responsible to obtain all relevant information through genetic screening and to decide whether the benefits of gathering this information outweighs the risks (Takala, 2000, p. Data from both carriers and non-carriers are imperative in this instance and societal benefit clearly outweighs the disadvantages to any individual, which is in support of utilitarianism. Knowledge of a predisposition may prevent or ameliorate some of the consequences of the future disease and allow the affected society to make informed choices timeously. Historically, utilitarianism, which was initially proposed by David Hume and later on firmly established by both Jeremy Bentham and John Stuart Mill describes the moral goodness of actions by their consequences (Lea, 2005, p. Bentham was specifically interested in social and political reform, most notably in criminal law. Applied to genetics and subsequently a rare genetic disease like Gaucher disease, utilitarianism broadly supports genetic testing, genetic selection, gene therapy and genetic enhancement of offspring, aiming at enhancing the opportunity of such individuals to enjoy the best lives, but also to lessen the burden on society (Fulda, 2006, p. Prior knowledge of a genetic disease and prevention of parents unknowingly passing on the genetic disorder by not having children may lessen the burden on society that often needs to pay high costs for expensive treatments (Fulda, 2006, p. Through genetic testing and screening and notifying at risk family members may not only delay onset of symptoms through early medical intervention but may also decrease the duration and extent of symptoms (Fulda, 2006). Furthermore, through sufficient preparation and appropriate lifestyle changes this may impact on the quality of life. The principle of beneficence rests on actions done to promote only good and well-being of others. Thus, for utilitarians, the ultimate moral principle is the principle of utility, which is all about pleasure and satisfaction of human needs. This sounds great, since almost everyone would agree that well-being is most certainly a primary end goal for any individual on earth. In contrast with Kantianism, utilitarianism is not about pleasing God or being faithful to abstract rules. Bentham held that since human beings essentially are primarily pain-pleasure organisms, morality and political philosophy should thus hinge on minimizing pain. So, any action is good if it leads to human happiness and bad if it interferes with the happiness of others. Thus, in the end with utilitarianism, the consequences or most importantly, the absolute best outcome for the most people involved, are what matters most. Perhaps a few questions might arise concerning the universal applicability of Utilitarianism. Although happiness seems to be universal, the theoretical model of Utilitarianism seems to be more applicable for public policy than to clinical medical ethics and that barring the very good intentions of utilitarianism the practical case-by-case implementation in each and every instance may be fraught with difficulty. Average utilitarianism depicts choosing the act that capitalises on utility (individual good) per individual; aggregate utilitarianism says select the act that augments the totality of utility across individuals. An argument can also be made that genetic screening could assist by increasing the future prospects of Gaucher disease patients if timeously identified and diagnosed. This may have a major impact on the potential of the individual with regards to their participation in the family and in the community. Fully functioning individuals can also totally participate and compete as normal citizens in all domains of social life (Buchanan, 2000). Persad et al even hold that resource allocation might be dependent on usefulness of a person (Persad, 2009, p. X for instance apply for a job, the underlying threat of Gaucher disease detrimentally influencing her health and wellbeing, might count against her in being successful in her application in obtaining the position, even though this is directly against government policy and infringing on her human rights. Also, as mentioned before, successful treatment with enzyme replacement therapy should enable a Gaucher patient to have a complete and fulfilled life, thus assisting him or her to reaching his or her full potential as an individual, and making a meaningful contribution to society (Masek, 1999, p. Insurance companies will most probably also be more averse to accept a patient with Gaucher disease or even an individual with the probability of inheriting the disease genetically. Insurance rates might be increased dramatically or coverage might be denied altogether (Guttmacher, 2003, p. Genetic screening may not give exact information since the disease course of Gaucher type 1 disease could be unpredictable. Because genetic testing may not supply sufficiently comprehensive information to a patient and the family, these tests may consequently necessitate complex moral decision making. X has been diagnosed with Gaucher disease and the biological father, after proper counselling and informed consent procedures were followed, was subsequently tested and found to be a carrier for Gaucher disease. This is the time period where the embryo grows into a fetus (non-viable) and late-term (viable). If she is between 13 and 20 weeks pregnant, she can get the abortion if (a) her own physical or mental health is at stake, (b) the baby will have severe mental or physical abnormalities, (c) she is pregnant because of incest, (d) she is pregnant because of rape, or (e) she is of the personal opinion that her economic or social situation is sufficient reason for the termination of pregnancy. In particular, massive hepatosplenomegaly may alter normal growth of a fetus during pregnancy. With proper enzyme replacement treatment strategies in place, the patient can have an extremely productive life, both socially and economically. As previously mentioned, in the current scenario, the mother has Gaucher disease and the father is a carrier. With regards to abortion, severe genetic abnormalities pose limited ethical difficulties. While the test for genetic screening of Gaucher disease is simple, accurate and sensitive, it does not predict disease prognosis or severity of clinical manifestations. I contend that maybe we should not only be fascinated with the notion of predictability or non-predictability (genetic testing) of the future traits of a person. Many Gaucher patients have the potential to be highly functional individuals particularly if they are diagnosed early and have adequate access to enzyme replacement therapy are treated timeously and thus have the capacity to live quite happy and fulfilled lives whilst making major economic and societal contributions (Masek, 1999, p. However, maternal discretion to abort during the further progression or later on in the pregnancy is normally insufficient both morally as well as ethically to provide sufficient justification. The expectation of delivering an infant with a chronic, incapacitating and devastating genetic disease generally supplies adequate reason for abortion, however, the contexts unique to Gaucher disease could overturn any forthright conclusions (Gross, 2002). According to Gross et al, when the disease is treatable, fetal best interests may actually mitigate against abortion. A utilitarian approach generally underscores justification for selective abortion. Should a mother decide to terminate a pregnancy due to concerns regarding carrying a fetus with an impairment to term, such a decision would be influenced by the utilitarian approach to moral reasoning. In this instance, according to utilitarian principles, it might be better if the baby dies. Although the appropriate action may not always seem well-defined, the direction the medical action must take is evident. Both the values and wishes of everyone involved should be taken into account when choosing the best possible outcome. When analyzing this situation, careful thought and consideration of all the influencing factors must be considered. Lastly society, particularly with reference to the extra financial resources needed to look after and treat a child afflicted with a disability or a hereditary genetic disease (Kushe, 1985, p.