123 research outputs found

    Early Assessment of Acute Renal Rejection Post-transplantation: A Combined Imaging and Clinical Biomarkers Protocol

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    © 2018 IEEE. Non-invasive evaluation of renal transplant function is crucial. Hence, a computer-assisted diagnostic (CAD) system is introduced in this paper to evaluate kidney function post-transplantation. The developed CAD system integrates clinical-based with diffusion weighted (DW) MR image-based biomarkers. The latter are derived from 3D DW-MRIs at multiple strengths and duration of the magnetic field (i.e. b-values). These DW-MRI scans were acquired at multiple geographical areas (Egypt and USA) using different scanner types (GE and Philips). The developed CAD system first segments kidneys using level-sets method and then estimates the DW-MRI image-markers, known as apparent diffusion coefficients (ADCs), from the segmented kidney. Then, the clinical biomarkers (serum creatinine and creatinine clearance) are integrated with the DW-MR image-markers (ADCs) resulted in new integrated markers known as integrated ADCs (IADCs). These IADCs are then used to construct cumulative distribution functions (CDFs) at multiple b-values. Finally, these markers (i.e. CDFs of the IADCs) are used to assess renal transplant status using different classifiers. Our CAD system demonstrates an almost consistent accuracy of 93%, sensitivity of 93%, and specificity of 92% in distinguishing acute rejection (AR) from non-rejection (NR) renal transplants, making the proposed diagnostic platform independent from the geographical area, scanner type, and classifier. These promising preliminary results are of high diagnostic accuracy and suggest that the developed CAD system might be noninvasively able to diagnose renal allograft status

    Computer-Aided Diagnostic System for Early Detection of Acute Renal Transplant Rejection Using Diffusion-Weighted MRI

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    © 1964-2012 IEEE. Objective: Early diagnosis of acute renal transplant rejection (ARTR) is critical for accurate treatment. Although the current gold standard, diagnostic technique is renal biopsy, it is not preferred due to its invasiveness, long recovery time (1-2 weeks), and potential for complications, e.g., bleeding and/or infection. Methods: This paper presents a computer-aided diagnostic (CAD) system for early ARTR detection using (3D + b-value) diffusion-weighted (DW) magnetic resonance imaging (MRI) data. The CAD process starts from kidney tissue segmentation with an evolving geometric (level-set-based) deformable model. The evolution is guided by a voxel-wise stochastic speed function, which follows from a joint kidney-background Markov-Gibbs random field model accounting for an adaptive kidney shape prior and on-going kidney-background visual appearances. A B-spline-based three-dimensional data alignment is employed to handle local deviations due to breathing and heart beating. Then, empirical cumulative distribution functions of apparent diffusion coefficients of the segmented DW-MRI at different b-values are collected as discriminatory transplant status features. Finally, a deep-learning-based classifier with stacked nonnegative constrained autoencoders is employed to distinguish between rejected and nonrejected renal transplants. Results: In our initial \u27leave-one-subject-out\u27 experiment on 100 subjects, 97.0% of the subjects were correctly classified. The subsequent four-fold and ten-fold cross-validations gave the average accuracy of 96.0% and 94.0%, respectively. Conclusion: These results demonstrate the promise of this new CAD system to reliably diagnose renal transplant rejection. Significance: The technology presented here can significantly impact the quality of care of renal transplant patients since it has the potential to replace the gold standard in kidney diagnosis, biopsy

    International Trade Under the Rule of Law Conference

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    The central focus of the conference was the dispute settlement system of the World Trade Organization (WTO), with a view toward exploring the need for a superstructure of international law governing trade and economic cooperation between countries

    No. 5 - International Trade under the Rule of Law: An American Society of International Law Centennial Regional Meeting

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    Organized and sponsored by the Dean Rusk Center and designated an American Society of International Law Centennial Regional Meeting, this conference focused on the Dispute Settlement System (DSS) of the World Trade Organization (WTO) with a view toward discussing the need for a superstructure of international law governing trade and economic cooperation between states

    Smoking status and common carotid artery intima-medial thickness among middle-aged men and women based on ultrasound measurement: a cohort study

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    BACKGROUND: Cigarette smoking is an established causal factor for atherosclerosis. However, the smoking effect on different echogenic components of carotid arterial wall measured by ultrasound is not well elucidated. METHODS: Middle-aged men and women who had IMT measurement ≥ 0.7 mm at baseline and follow-up were included (N = 413, age 40–60 years at baseline in 1995). Intima-media thickness of common carotid artery (CCA-IMT) and its components (echogenic and echolucent layers) were measured at baseline and in the follow-up examination 3 years later. IMT and its components were compared across current, former and never smokers. Individual growth models were used to examine how smoking status was related to the baseline and progression of overall IMT and IMT components. RESULTS: For both men and women, current smoking was associated with thicker echogenic layer than never smokers; former smokers exhibited thinner echogenic layer than current smokers after adjustment for cigarette pack-years. Among women, current smoking was also associated with a thinned echolucent layer that resulted in a non-significant overall association of current smoking with IMT for women. CONCLUSION: Cigarette smoking is associated with carotid artery morphological changes and the association is sex-dependent. The atherogenic effect of smoking appears to be partly reversible among former smokers. IMT measurement alone may not be adequate to detect carotid atherosclerosis associated with cigarette smoking among middle-age women

    No evidence for association between polymorphisms in GRM3 and schizophrenia

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    BACKGROUND: Three studies have previously reported data that were interpreted by the authors as supportive of association between schizophrenia and polymorphisms in the gene encoding the metabotropic glutamate receptor GRM3. METHODS: In a bid to examine this hypothesis, we examined seven SNPs spanning GRM3 in a UK case-control sample (schizophrenic cases n = 674, controls n = 716). These included all SNPs previously reported to be associated, alone or in haplotypes, with schizophrenia in European or European American samples. RESULTS: Our data showed no evidence for association with single markers, or 2, 3, 4 and 5 marker haplotypes, nor did any specific haplotypes show evidence for association according to previously observed patterns. CONCLUSION: Examination of our own data and those of other groups leads us to conclude that at present, GRM3 should not be viewed as a gene for which there is replicated evidence for association with schizophrenia

    Optimizing colorectal cancer screening by race and sex

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    BACKGROUND: Colorectal cancer (CRC) risk varies by race and sex. This study, 1 of 2 microsimulation analyses to inform the 2018 American Cancer Society CRC screening guideline, explored the influence of race and sex on optimal CRC screening strategies. METHODS: Two Cancer Intervention and Surveillance Modeling Network microsimulation models, informed by US incidence data, were used to evaluate a variety of screening methods, ages to start and stop, and intervals for 4 demographic subgroups (black and white males and females) under 2 scenarios for the projected lifetime CRC risk for 40-year-olds: 1) assuming that risk had remained stable since the early screening era and 2) assuming that risk had increased proportionally to observed incidence trends under the age of 40 years. Model-based screening recommendations were based on the predicted level of benefit (life-years gained) and burden (required number of colonoscopies), the incremental burden-to-benefit ratio, and the relative efficiency in comparison with strategies with similar burdens. RESULTS: When lifetime CRC risk was assumed to be stable over time, the models differed in the recommended age to start screening for whites (45 vs 50 years) but consistently recommended screening from the age of 45 years for blacks. When CRC risk was assumed to be increased, the models recommended starting at the age of 45 years, regardless of race and sex. Strategies recommended under both scenarios included colonoscopy every 10 or 15 years, annual fecal immunochemical testing, and computed tomographic colonography every 5 years through the age of 75 years. CONCLUSIONS: Microsimulation modeling suggests that CRC screening should be considered from the age of 45 years for blacks and for whites if the lifetime risk has increased proportionally to the incidence for younger adults

    Acceptability of prison-based take-home naloxone programmes among a cohort of incarcerated men with a history of regular injecting drug use

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    Background: Take-home naloxone (THN) programmes are an evidence-based opioid overdose prevention initiative. Elevated opioid overdose risk following prison release means release from custody provides an ideal opportunity for THN initiatives. However, whether Australian prisoners would utilise such programmes is unknown. We examined the acceptability of THN in a cohort of male prisoners with histories of regular injecting drug use (IDU) in Victoria, Australia. Methods: The sample comprised 380 men from the Prison and Transition Health (PATH) Cohort Study; all of whom reported regular IDU in the 6 months prior to incarceration. We asked four questions regarding THN during the pre-release baseline interview, including whether participants would be willing to participate in prison-based THN. We describe responses to these questions along with relationships between before- and during-incarceration factors and willingness to participate in THN training prior to release from prison. Results: Most participants (81%) reported willingness to undertake THN training prior to release. Most were willing to resuscitate a friend using THN if they were trained (94%) and to be revived by a trained peer (91%) using THN. More than 10 years since first injection (adjusted odds ratio [AOR] 2.22, 95%CI 1.03-4.77), having witnessed an opioid overdose in the last 5 years (AOR 2.53, 95%CI 1.32-4.82), having ever received alcohol or other drug treatment in prison (AOR 2.41, 95%CI 1.14-5.07) and injecting drugs during the current prison sentence (AOR 4.45, 95%CI 1.73-11.43) were significantly associated with increased odds of willingness to participate in a prison THN programme. Not specifying whether they had injected during their prison sentence (AOR 0.37, 95%CI 0.18-0.77) was associated with decreased odds of willingness to participate in a prison THN training. Conclusion: Our findings suggest that male prisoners in Victoria with a history of regular IDU are overwhelmingly willing to participate in THN training prior to release. Factors associated with willingness to participate in prison THN programmes offer insights to help support the implementation and uptake of THN programmes to reduce opioid-overdose deaths in the post-release period

    Changes in Gene Expression and Cellular Architecture in an Ovarian Cancer Progression Model

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    BACKGROUND: Ovarian cancer is the fifth leading cause of cancer deaths among women. Early stage disease often remains undetected due the lack of symptoms and reliable biomarkers. The identification of early genetic changes could provide insights into novel signaling pathways that may be exploited for early detection and treatment. METHODOLOGY/PRINCIPAL FINDINGS: Mouse ovarian surface epithelial (MOSE) cells were used to identify stage-dependent changes in gene expression levels and signal transduction pathways by mouse whole genome microarray analyses and gene ontology. These cells have undergone spontaneous transformation in cell culture and transitioned from non-tumorigenic to intermediate and aggressive, malignant phenotypes. Significantly changed genes were overrepresented in a number of pathways, most notably the cytoskeleton functional category. Concurrent with gene expression changes, the cytoskeletal architecture became progressively disorganized, resulting in aberrant expression or subcellular distribution of key cytoskeletal regulatory proteins (focal adhesion kinase, α-actinin, and vinculin). The cytoskeletal disorganization was accompanied by altered patterns of serine and tyrosine phosphorylation as well as changed expression and subcellular localization of integral signaling intermediates APC and PKCβII. CONCLUSIONS/SIGNIFICANCE: Our studies have identified genes that are aberrantly expressed during MOSE cell neoplastic progression. We show that early stage dysregulation of actin microfilaments is followed by progressive disorganization of microtubules and intermediate filaments at later stages. These stage-specific, step-wise changes provide further insights into the time and spatial sequence of events that lead to the fully transformed state since these changes are also observed in aggressive human ovarian cancer cell lines independent of their histological type. Moreover, our studies support a link between aberrant cytoskeleton organization and regulation of important downstream signaling events that may be involved in cancer progression. Thus, our MOSE-derived cell model represents a unique model for in depth mechanistic studies of ovarian cancer progression
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