This dissertation presents two complete neural interface systems to address two key challenges:evading the brain's foreign body response to achieve long probe longevity,and scaling wireless, implantable systems to high channel counts.The first,a self-contained, 0.125 mm2, 4-channel wireless recording system, achieves an  unprecedented level of miniaturization.The second system achieves an unprecedented level of integration, combining 64 recording channels, 16 stimulation channels, and neural data compression onto a single 4.78 mm2 IC. Furthermore, the IC achieves substantial improvements in power and area versus state-of-the-art. 

关键词：神经接口；脑机接口；无线传感器；神经传感器

查看摘要 索取原文[80页]

CXCR4 and its chemokine ligand CXCL12 are potential targets for molecular therapy of ovarian cancer. Receptor CXCR4 is expressed by ovarian cancer cells in approximately 50% of patients. High levels of CXCL12 are present in ascites of patients with ovarian cancer, providing a local source of chemokine ligand in the tumor microenvironment. CXCL12 signaling through CXCR4 activates pathways that could promote tumor growth, invasion, metastasis, and resistance to chemotherapy. To advance clinical translation of CXCR4 inhibitors for therapy of ovarian cancer, we developed molecular imaging reporters for CXCR4 signaling that can be used for cell-based assays and real-time imaging studies in mouse xenograft models of ovarian cancer. After validating that these reporters correspond with biochemical measures of CXCL12-CXCR4 signaling, we used optical imaging to quantify pharmacodynamics of therapy for CXCR4 targeted inhibitors in mice with ovarian cancer. Treatment studies established that inhibiting CXCR4 prolonged survival of mice with ovarian cancer and potentially could improve treatment efficacy of a standard chemotherapeutic drug, cisplatin.

关键词：细胞(生物学),化疗药物,临床医学;卵巢癌;生物化学;增长(生理学);图像;抑制;分子;肿瘤;光学图像;患者;药理学;电阻(生物学);感觉器官;治疗;光学成像;趋化因子

查看摘要 索取原文[20页]

We have obtained continuing approval from our Institutional Review Board and Conflict of Interest (COI) Committees. Dr. Sassani has assisted Dr. David Liang and Dr. Esther Bowie in data collection. All observers are masked. Nevertheless, at the request of our COI Committee he does not participate in data analysis or interpretation. We completed testing in 4 volunteers in each of the once daily and 4 times daily, 1 x 10-6 M cohorts; four times daily, 1 x 10-6, 5 x 10- 6, and 1 x 10-5 M dosages of topical Naltrexone in Vigamox eyedrops. Due to a pharmacy error, one additional cohort of 4 individuals was treated at a lower than scheduled dose of 5 X 10-6M and this cohort had to be repeated at the higher dosage of 1 x 10-5M, thereby further delaying the research. No significant untoward side effects were noted in any groups of volunteers. Although this officially is our Final Report, we are committed to completing the terms of our original grant. Therefore, we have recruited our final cohort of volunteers and within one week will have treated them with the four times daily, 5 x 10-5 M Naltrexone dosage. Thus, we will have completed the protocol fully.

关键词：剂量;眼疾;医药;药店;冲突;家常便饭;数据采集;数据处理;错误;眼睛;观察家;角膜磨损;眼药水;阿片拮抗物;角膜伤口愈合;阿片样物质;治疗

查看摘要 索取原文[89页]

Chronic pain is among the most prevalent health problems in the United States today, affecting 10% of the population and costing the U.S. billions of dollars each year in health care expenses, lost income, and lost productivity. Genetic differences among individuals in pain response physiology are partially responsible for observed variation in chronic pain development and maintenance. To identify genes affecting inter-individual variability in chronic pain response we are using a state of the art reference population of laboratory mice (Diversity Outbred mice). Diversity Outbred (DO) mice are a unique population of laboratory mice designed to maximize allelic variation throughout the genome (Churchill, Gatti et al 2012). Each DO mouse is genetically unique. Unlike fully inbred strains, cohorts of DO mice approximate the levels of genetic (allelic) diversity found in human populations. The levels of segregating phenotypic and allelic diversity in DO mice allow for high precision for mapping regions of the genome that condition complex traits. Identifying genes whose allelic variants condition susceptibility to chronic pain development will further our understanding of the molecular mechanisms underlying chronic pain. This information, in turn, promises to facilitate improved methods for individualized chronic pain treatment and prevention.

关键词：遗传学;疼痛;响应(生物学);基因;健康;医疗服务;分子性质;预防医学;慢性疼痛敏感性;痛苦遗传学;多样性

查看摘要 索取原文[9页]

Despite multiple therapeutic efforts targeting a variety of underlying pathogenic mechanisms, approaches to cure the mouse the models amyotrophic lateral sclerosis (ALS) have failed. With the exception of Riluzole (the only drug approved by the FDA for treatment of ALS), we have been unsuccessful at translating promising results from pre-clinical mouse trials to effective pharmacotherapies for ALS patients. One of the problems in finding highly efficacious treatments in ALS may derive from the so far underestimated issue of disease-driven pharmacoresistance mediated by the multi-drug resistance (mdr) efflux transporter, P-glycoprotein (P-gp). These are proteins that are present at the blood and spinal cord brain barrier whose function is to protect the brain from xenobiotics including drugs. These proteins actively pump out from the nervous system (CNS) foreign substances. We have shown that in ALS, both in patients and in the ALS mice, there is an increased expression and activity of these efflux transporter P-gps and hypothesized that one of the problem in treating ALS derives from a disease-driven acquired pharmacoresistance due to increased P-gps. Riluzole, which only has a modest effect in patients, is a Pg-p substarate. Thus, it is plausible that administration of Riluzole in combination with a P-gp inhibitor could improve its therapeutic outcome. With this proposal we test the hypothesis that co- administration of Riluzole with a potent P-gp inhibitor (Elacridar) will enhance Riluzole bioavailability and therefore will improve its therapeutic efficacy the SOD1-G93A ALS mice.

关键词：中枢神经系统;临床医学;药物耐受性;药物;脑;化疗;主机(生物学);假设;神经系统;病理;蛋白质;电阻(生物学);脊髓;测试和评估,Als(肌萎缩性脊髓侧索硬化症);利鲁唑;药物释放交易

查看摘要 索取原文[7页]

The study is designed to evaluate the utility of levels of two phospholipids in serum as a marker of past drinking behavior across month-level time horizons, in an attempt to improve ability to measure alcohol quantity consumed and associated damage better than can be done with ethyl alcohol level measures and other existing tests that only measure very recent exposure and poorly reflect quantity consumed. This will be achieved by correlating detailed questionnaire data on alcohol consumption with serum phospholipid levels in subjects not selected for alcohol abuse (part I) and subjects under alcohol abuse treatment (part II). The Department of Defense-funded study will conduct Part I at the VA hospital and Part II at the Fairbanks treatment facility. Part I involves a single study session (n=280), while Part II will involve serial blood draws and phospholipid measures at several treatment visits (n=60). The study is open to 280 subjects for Part I, and 60 subjects for part II. Part I has 179 consented, and 18 screen fails; Part II has 33 consented (one withdrew from the study) and 8 screen fails. The study is currently active and analysis has not been completed. Since the inception of the study, we have not experienced any problems with subjects recruitment. To date, we have recruited 197 subjects into Part I of the study and 41 subjects into part II.

关键词：酗酒;磷脂;饮酒;醇类;行为;血;血清;消费;损害;乙自由基;医院;标志;测量;医学研究;数量;问卷调查;技巧;示踪研究;生物标志物

查看摘要 索取原文[13页]

Disease-causing microorganisms that have become resistant to drug therapy are an increasing cause of burn, wound, blast and bone infections, with many traditional antimicrobial agents becoming ineffective. Our main hypothesis is that predatory prokaryotes could serve as a novel therapeutic agent to control wound-related bacterial infections. In a previous study, we confirmed that predatory bacteria Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus are able to prey on a wide range of pathogens including bacteria isolated from Wounded Warriors. The aim of this proposal is to address key questions regarding the safety and efficacy of predatory bacteria and investigating predator prey interactions and resistance. Using enrichment culturing techniques we have verified that no genetically stable predation resistant phenotype developed in K. pneumoniae and A. baumannii host cells following sequential predation by B. bacteriovorus. Furthermore, sequential predation by M. aeruginosavorus also did not yield host resistance. Our data also confirmed that the predators do not breach their host specificity and attack previously resistant bacteria. Additional enrichment experiments did not produce predators which exhibit enhance predation on a selected host but did yield predators which were acclimated to attack at elevated temperatures.

关键词：抗菌药物;细菌;创伤和损伤;攻击;细菌性疾病;杀菌剂;细胞(生物学);主机(生物学);假设;传染病;交互作用;范围(极端);耐药性;安全;治疗;产量;食肉细菌;生物防除;伤口感染

查看摘要 索取原文[23页]

No abstract available.

关键词：传染病;军事人员;抗体;文职人员;革兰氏阴性细菌;住院;人类免疫缺陷病毒;医疗筛查;败血症;医疗监测

查看摘要 索取原文[29页]

The findings described in the two case reports of malaria on pages 8 to 9 of this issue of the MSMR illustrate what has been previously reported about the frequently prolonged latent period between exposure to Korean strains of Plasmodium vivax and the subsequent clinical presentation with overt malaria (see pages 8-14).1 Both cases experienced delays of at least fi ve months (since leaving Korea) and as long as 10 months (since their likely exposure to malaria vectors) before the onset of their symptoms. Review of their electronic health records uncovered no evidence of prior clinical symptomatology consistent with malaria. Th e length of the latency period may have some basis not only in the strain of P. vivax, but also in the relative youth and general excellent physical condition of these two soldiers. Moreover, it is possible that mild symptomatology was not reported by the soldiers or observed in clinic.

关键词：临床医学;诊断(医学);接触(生理学);疟疾;军队人员;健康;医学;门诊诊所,间日疟原虫;记录;报告;监测

查看摘要 索取原文[21页]

Tobacco is a highly addictive substance with well-documented health risks. Although great progress has been made in reducing and preventing tobacco use in the United States, the rates of cigarette use and dependence remain high in certain subpopulations, including those with substance use disorders. For example, 2011 data show that an estimated 22 percent of U.S. adults are current cigarette smokers, whereas smoking prevalence rates for those in substance abuse treatment exceeded 70 percent between 2005 and 2009. The negative health effects of tobacco use among alcohol- and drug dependent individuals can be substantial. Individuals in substance abuse treatment smoke more heavily than the general population, and consequently are more likely to suffer from tobacco-related morbidity, including cardiopulmonary problems, emphysema, and cancer, than are smokers in the general population. One study of substance abuse treatment clients found that tobacco use caused more deaths than the alcohol or drug use that brought them to treatment; specifically, the rate of death among tobacco users was nearly 1.5 times the rate of death from other addiction-related causes.

关键词：吸烟;卫生服务;癌;心肺疾病,肺气肿;健康影响;发病率;人口;预防医学;烟草;治疗项目;烟草戒烟

查看摘要 索取原文[7页]