Artificial Neural Networks are mathematical models resembling the brain behavior. They have the ability to "learn" from the "environment" and produce responses as a consequence of this learning process. They were broadly used in medicine both as a classification model as well as a prediction tool. In hemodialysis they were used for molecular modeling in the estimation of equilibrated urea concentration, as a monitoring strategy for online treatment analysis and also for bed side models for hemodialysis adequacy evaluation. In this chapter the basic concepts of artificial neural models are introduced and a complete application in equilibrated urea estimation in hemodialized patients is presented.

关键词：血液透析；分子建模；均衡尿素浓度；人工神经网络

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Although peritoneal dialysis was first developed in the early 20th century, there are still many challenges that need to be addressed by bioengi-neers working with nephrologists. The peritoneal dialysis catheter sets up a foreign body reaction in the cavity and often becomes infected; new polymers are needed to minimize the resulting inflammation. New osmotic agents are needed to substitute for glucose that sets up a "diabetic state" in the cavity that leads to peritoneal sclerosis. New technology that can be worn by the mobile patient and that provides continuous dialysis is an exciting development that presents significant challenges to the design engineer. Computational biology attempts to quantitatively integrate the findings in clinical studies, genomics, proteomics, metabolomics to move health care toward "personalized medicine" in order to predict outcomes and to improve care of the individual patient.

关键词：腹膜透析导管腔；异物反应；新聚合物；渗透剂；糖尿病状态；腹膜硬化

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The current study involves a head to head comparison of the reliability and clinical validity of four neurocognitive assessment tools (NCAT s) for the acute neurocognitive assessment, tracking cognitive recovery, and informing clinical management after mild traumatic brain injury (mTBI). The specific NCAT s under study include: the Automated Neuropsychiatric Assessment Metric (ANAM), AXON Sports, Defense Automated Neurobehavioral Assessment (DANA), and Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT). The study design involves both a Sports Concussion Arm and Civilian mTBI Arm. Both study arms are fully operational with data collection underway, with steady progress toward recruitment of mTBI/concussion participants and controls. In the first phase of data collection, we have enrolled more than 400 athletes in the baseline study phase, and 38 injured and control participants in the postinjury protocol. A new online e-consent platform developed as part of this project has been highly effective. Obstacles to recruitment in the civilian mTBI (hospital emergency dept.) arm have been identified and alternate strategies developed. Overall, the study is on target with respect to statement of work, timeline and budget. With ongoing recruitment of injured and control participants, we anticipate having informative data on our specific aims relevant to the NCAT s as part of future annual reports.

关键词：创伤性脑损伤;预算;临床医学;认知;数据采集;精神障碍;可靠性;神经认知评估

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The overall goal of this project is to determine the underlying mechanisms for the neurological symptoms associated with Gulf War Illness. The central hypothesis is that subthreshold exposures to organophosphates-OPs (defined as exposures not associated with acute signs of toxicity) may have adversely affected axonal transport and/or myelin integrity in affected individuals. We are studying two OPs, a representative insecticide that was used in the first gulf war, chlorpyrifos (CPF), and a representative, nerve agent, diisopropylfluorophosphate (DFP) in rats. The first year of this proposal has been dedicated to Specific Aim No. 1: which has been designed to evaluate OP effects on axonal transport in the living rat brain using manganese-enhanced magnetic resonance imaging (MEMRI) of the optic nerve axonal projections from the retina to the superior colliculus. The following procedures have been conducted to date (N=4-6): (1) baseline MRI scans; (2) daily injections of vehicle or chlorpyrifos (3.0-18.0 mg/kg) x 14 days; (3) a second MRI scan on the day following the last drug injection; (4) a third scan after a 4 week (OP-free) washout period. For each animal, a separate 6 hour and 24 hour scan was performed after Mg2+ eye injection. The data analyzed to date appear to support our hypothesis that repeated OP exposure leads to persistent impairments in axonal transport in the brain of living animals.

关键词：大脑;药物;对立;疾病;注射(医学);磁共振成像;哺乳动物;神经,神经病学;有机磷;视网膜,症状和体征;战争

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The purpose of this research project is to develop new approaches that can impact early diagnosis of breast cancer, post-biopsy analysis, lymph node examinations, and drug delivery studies. The scope of this training involves optimizing Raman instrumentation and methods for efficient illumination and collection of Raman scattered light originating from deep within breast tissue. Experiments encompass designing tissue phantoms using Intralipid , dyes/pigments, inclusions, and agarose gel to quantitatively characterize the instruments capabilities and performance. Additionally, we conduct spectroscopy on tissue biopsies to correlate spectral bands with healthy and diseased breast tissue. Observed spectral changes are compared to infrared images and H&E/HIS-stained images to relate observed biochemical changes to histology. The Raman data will be used to generate and train classification algorithms for automated histopathology as a starting point for in vivo work at the culmination of this training program. This report outlines progress for year 1 of the 3 year training program. In the approved statement of work 5 tasks were stated. All 5 tasks were successfully completed. We now have a working relationship with local clinicians. We have built-up a comprehensive database consisting of micrographs and IR spectral images for identify breast tissue histology and tissue chemistry. We have acquired Raman measurements on biopsied tissue. We have identified Raman spectral bands that can be used for distinguishing between different tissue types and have applied those Raman spectral bands to achieve cell-level contrast in Raman spectral images. Additionally, we have used clinical observations and interaction with clinicians to develop a conceptual design for a Raman Tomography instrument aimed at breast cancer screening. Finally for Raman tomographic reconstruction, we have evaluated existing diffuse optical tomography algorithms specifically for Raman measurements and have ad.

关键词：带光谱;活检;乳腺癌;癌症筛查;临床医学;分娩;扩散;疾病;药物;酶;凝胶;组织学;组织病理学;体内分析;红外图像;红外成像;仪表;光散射;淋巴结;乳腺;节点;光学性质;颜料;拉曼成像;拉曼光谱,拉曼光谱,拉曼成像;组织(生物学);断层;透射光谱透射率

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Inverse planning is at the heart of prostate Volumetric Modulated Arc Therapy (VMAT) treatment procedure and critically determines its level of success. As practiced now, the capacity of VMAT is greatly underutilized because of inferior computing performance of existing optimization methods. An alternative mathematical approach that improves both the efficiency and the efficacy is needed and is the center of this research. We propose to develop a new innovative inverse planning tool, based on the novel idea of superiorization, to replace the classical constrained optimization approaches employed in clinics today for prostate VMAT cases. Year 1 of the training award focused on formulating the VMAT problem as a constrained superiorization problem and on the development of a framework of fast converging inverse planning algorithms. Empty solution sets and infeasibility constraints that often exist in real-world applications were incorporated into the model. The new framework was proven mathematically and its efficacy was demonstrated when it was compared to a classical optimization method. The superiorization methodology was Implemented, tested and evaluated on a previously treated prostate case where good initial results were obtained.

关键词：算法;临床医学;效率;反演;数学模型;模型;调制;优化;患者;规划;前列腺癌,前列腺;Vmat(体积调制电弧疗法)

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Dependable and efficient diagnosis of Bacillus anthracis has long been a major concern for caregivers. Nonspecific symptoms during early illness often misguide the diagnosis; thereby jeopardize the proper therapeutic intervention. It is, therefore, crucial to understand the initial events that take place in a host soon after the onset of infection. The present study examines the transcriptional profile of human peripheral blood mononuclear cells (PBMCs) challenged by B. anthracis (BA) spores in vitro, and cultured for 2 hrs, 4hrs, 6 hrs, 8 hrs and 24 hrs, respectively. Transcriptomic assays support the past findings and identify novel targets for diagnosis and anthrax therapy. We observe rapid elevation of a number of transcripts encoding genes for cytokines, chemokines, and other uptake receptors, concurrently with onset of infection. Delayed responses to the BA include gradual attenuation of the genes linked with pathogenic uptake, such as MyD88 and TLR4, putatively extending the duration of host vulnerability. The signs of altering host defenses, nevertheless are evident immediately after the exposure to the B. anthracis spores. The pathogenic insult selectively induces some of the key genes for apoptotic pathways regulated by the toll-like receptors and the caspase cascade; and suppresses the transcripts related to the p38MAPK- dependent pathways. The T-cell receptors and CD3-mediated antigenic recognition processes are possibly restrained, and the expression of CD79, a B-cell committed CD marker, is suppressed. Overall, BA challenges both innate and adaptive immunity processes and their key interfaces during the early course of infection. We identified several early targets across the networks and pathways, primarily related to chemotaxis and apoptosis of immune cells that can potentially facilitate development of next generation anthrax prevention strategies.

关键词：炭疽杆菌;血细胞;趋化因子;文化(生物学);细胞因子;脱氧核糖核的酸;诊断(医学);Dna(脱氧核糖核的酸);基因表达;基因;主机响应;体外分析;微阵列;Pbmc(外周血单核细胞);Pcr(聚合酶链反应);受体网站(生理学);核醣核酸酸;Rna隔离;Rna(核醣核酸酸),症状和体征;孢子;转录组分析

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The overall goal of this research project is to develop and implement a conceptually innovative strategy for extrinsic regulation of the androgen receptor (AR) to target the transcriptional misregulation mediated by this receptor in prostate cancer. This strategy utilizes bifunctional molecules that simultaneously interact with AR and with components of the chromatin remodeling machinery. In the second year of funding, a paper outlining the early stages of the study was accepted for publication. Additionally, thorough characterization of HDAC inhibitor-based structures revealed that localizing HDACs to promoters via AR leads is not efficacious. However, targeting an epigenetic reader, Brd4, lead to robust and reliable extrinsic control of full- length nuclear receptor function. In the final year of funding, this latter model will be fully extended in the prostate cancer system.

关键词：雄激素受体;雄激素;控制;功能;原因抑制剂;核医学;前列腺癌,前列腺;受体网站(生理学);感觉器官;目标

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To understand the risks of lung disease faced by soldiers, USACEHR has studied a rat model of lung disease after instillation of dust or silica. After exposure, lung pathology was measured and we identified the proteins and microRNAs that were released into the lung lavage fluid at different times after exposure so that the markers could be correlated with the observed pathology. In this model silica affected the lung more than dust from Iraq, and we reported the proteins and microRNAs we found in lavage fluid after either treatment. The candidate biomarkers we found came from lavage fluid which is relatively accessible. The markers we found can now be compared to markers from human clinical specimens. This work is underway via a collaboration with the STAMPEDE project at BAMC.

关键词：支气管灌洗液;清洁;临床医学疾病,尘埃,尘埃滴注法;接触(生理学);肺癌;肺损伤;微rna生物标志物;病理学;蛋白生物标志物;蛋白质;肺功能;大鼠;二氧化硅;创伤和损伤

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Common injuries sustained by war fighters in Iraq and Afghanistan result from blast and shrapnel wounds which cause extensive damage to skin, bones, and nerves. The management of damaged peripheral nerves is challenging for patients and surgeons. Peripheral nerve transection injuries may fail to regenerate even when managed surgically. These injuries are associated with long term disability and impaired function. Nerve guidance conduits have been developed for use in surgery to bridge the gap between transected nerve ends and to support nerve regeneration. A team of scientist and clinicians at Wake Forest School of Medicine has developed a keratin biomaterial hydrogel that can be used as luminal filler in nerve guidance conduits to facilitate nerve regeneration. Studies in mice, rabbits, and nonhuman primates have established the feasibility of this keratin hydrogel to promote nerve regeneration. A Phase I prospective, randomized trial is designed to compare nerve regeneration in patients sustaining peripheral nerve injuries treated either with keratin hydrogel and a nerve conduit or with a nerve conduit alone. The clinical trial will be initiated as soon as the FDA provides an IND for the keratin biomaterial hydrogel.

关键词：临床研究;可行性研究;无能力;伊拉克;角质化;医学研究;军事人员;神经;患者;周围神经系统;随机变量;再生(生理学);手术;创伤;创伤和损伤

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