Fault detection, identification and accommodation techniques for unmanned airborne vehicles

Unmanned Airborne Vehicles (UAV) are assuming prominent roles in both the commercial and military aerospace industries. The promise of reduced costs and reduced risk to human life is one of their major attractions, however these low-cost systems are yet to gain acceptance as a safe alternate to manned solutions. The absence of a thinking, observing, reacting and decision making pilot reduces the UAVs capability of managing adverse situations such as faults and failures. This paper presents a review of techniques that can be used to track the system health onboard a UAV. The review is based on a year long literature review aimed at identifying approaches suitable for combating the low reliability and high attrition rates of today’s UAV. This research primarily focuses on real-time, onboard implementations for generating accurate estimations of aircraft health for fault accommodation and mission management (change of mission objectives due to deterioration in aircraft health). The major task of such systems is the process of detection, identification and accommodation of faults and failures (FDIA). A number of approaches exist, of which model-based techniques show particular promise. Model-based approaches use analytical redundancy to generate residuals for the aircraft parameters that can be used to indicate the occurrence of a fault or failure. Actions such as switching between redundant components or modifying control laws can then be taken to accommodate the fault. The paper further describes recent work in evaluating neural-network approaches to sensor failure detection and identification (SFDI). The results of simulations with a variety of sensor failures, based on a Matlab non-linear aircraft model are presented and discussed. Suggestions for improvements are made based on the limitations of this neural network approach with the aim of including a broader range of failures, while still maintaining an accurate model in the presence of these failures

Glycogen synthase kinase-3 regulation of chromatin segregation and cytokinesis in mouse preimplantation embryos

Glycogen synthase kinase-3 (GSK-3) is a highly conserved serine/threonine protein kinase implicated in diverse cellular processes. Activity of GSK-3 is essential for meiotic chromatin segregation in oocytes, yet expression and/or function of GSK-3 have not been reported in mammalian preimplantation embryos. Objectives of this study were to characterize GSK-3 protein expression/phosphorylation in mouse preimplantation embryos, to assess the effect of GSK-3 activity inhibition on early mitotic events, and to differentiate nuclear and cytoplasmic anomalies in GSK-3 inhibited embryos. Both GSK-3 isoforms were expressed during embryo development, with a differential expression of Α versus Β. Phosphorylation of GSK-3Α/Β at residues Y279/Y216 indicated constitutive activation throughout preimplantation development. Phosphorylation at N-terminal residues S21/S9 indicated inhibition of GSK-3Α/Β activity that was differentially regulated during early development; both Α and Β isoforms were phosphorylated during early divisions, whereas at the blastocyst stage, only Β was phosphorylated. Cytoplasmic microinjection of zygotes with anti-GSK-3Α/Β antibody significantly compromised embryonic development past the two-cell stage compared to controls. Reversibility of developmental block was tested via pharmacological inhibitors of GSK-3, lithium chloride (LiCl) and alsterpaullone. Similar to immunoneutralization, significantly fewer zygotes cultured with either LiCl or alsterpaullone developed past the two-cell stage compared to controls and this mitotic block was not reversible. Inhibition of GSK-3 activity significantly compromised timing of pronuclear membrane breakdown and mitosis initiation, nuclear development, and cytokinesis. Inhibition of GSK-3 also resulted in abnormal chromatin segregation, evidenced by incomplete karyokinesis and micronuclei formation. These results suggest that GSK-3 activity is critical for early preimplantation embryonic development. Mol. Reprod. Dev. © 2006 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55901/1/20495_ftp.pd

Longitudinal patterns of antidepressant prescribing in primary care in the UK: comparison with treatment guidelines

The objective of this study was to determine whether patients beginning therapy on the most common tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) differed in their likelihood of having antidepressant treatment that was consistent with recommended treatment guidelines in the UK. An analytical file constructed from a large general practitioner medical records database (DIN-LINK) from the UK for the years 1992-97 was constructed. A total of 16 204 patients with a new episode of antidepressant therapy who initiated therapy on one of the most often prescribed TCAs (amitriptyline, dothiepin, imipramine and lofepramine) or SSRIs (fluoxetine, paroxetine and sertraline) were analysed. A dichotomous measure was defined to indicate whether subjects were prescribed at least 120 days of antidepressant therapy at an adequate average daily dose within the first 6 months after initiation of therapy. Only 6.0% of patients initiating therapy on aTCA and 32.9% of patients initiating therapy on a SSRI were prescribed antidepressant treatment that was consistent with treatment guidelines. After controlling for observable characteristics, patients who initiated therapy on a SSRI were much more likely (odds ratio=7.473, p<0.001) to have a prescribed average daily dose and duration consistent with recommended treatment guidelines within the first 6 months of initiating therapy than were patients who initiated therapy on a TCA. These findings suggest that initial antidepressant selection is an important determinant of whether the subsequent course of treatment is consistent with current national guidelines for the treatment of depression in the UK.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68732/2/10.1177_026988119901300204.pd

Pilot and feasibility study of serum chemokines as markers to distinguish prostatic disease in men with low total serum PSA

BACKGROUND The incidence and prevalence of both benign prostatic hypertrophy (BPH) and prostate cancer (PCa) increase with the aging process. Our laboratory recently showed that the chemokines CXCL5 and CXCL12, which normally function as inflammatory mediators, are secreted at higher levels by aging prostate stromal fibroblasts and elicit proliferative responses from both prostate stromal fibroblast and epithelial cells. Because both CXCL5 and CXCL12 are secreted molecules, we hypothesized that their levels in patient serum might serve as biomarkers to distinguish between BPH and PCa. METHODS Serum CXCL5 and CXCL12 levels were determined using sandwich ELISAs for 51 men demonstrating low serum PSA values of ≤10 ng/ml who underwent diagnostic needle biopsy for the detection of PCa. The bivariate relationship of circulating chemokine levels, age, and disease status in the prostate was tested using the Wilcoxon rank-sum test. Results Total serum CXCL12 levels were significantly higher for men who were biopsy positive compared to those who were biopsy negative for cancer and histological prostatitis ( P  = 0.050). Among men who were biopsy negative for PCa, total serum CXCL5 levels were inversely associated with prostate volume and were significantly higher in men with concomitant BPH and histological prostatitis compared to those without evidence of prostatic disease ( P  < 0.003). CONCLUSIONS The results of this pilot and feasibility study suggest that serum or plasma CXCL5 and CXCL12 levels may potentially distinguish between BPH and PCa among patients presenting with low serum PSA, and may be useful toward facilitating decisions to perform diagnostic needle biopsy in this patient population. Prostate 68: 442–452, 2008. © 2008 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/57914/1/20717_ftp.pd

Ambulatory Surgery Centers and Their Intended Effects on Outpatient Surgery

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113726/1/hesr12278.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/113726/2/hesr12278-sup-0001-AppendixSA1.pd

A screening tool for clinically relevant urinary incontinence

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111206/1/nau22564.pd

Investigating a genetic link between Alzheimer’s Disease and CADASIL related Cerebral Small Vessel Disease

Monogenic forms of Alzheimer’s disease (AD) have been identified through mutations in genes such as APP, PSEN1, and PSEN2, whilst other genetic markers such as the APOE ε carrier allele status have been shown to increase the likelihood of having the disease. Mutations in these genes are not limited to AD, as APP mutations can also cause an amyloid form of cerebral small vessel disease (CSVD) known as cerebral amyloid angiopathy, whilst PSEN1 and PSEN2 are involved in NOTCH3 signalling, a process known to be dysregulated in the monogenic CSVD, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). The overlap between AD genes and causes of CSVD led to the hypothesis that mutations in other genes within the PANTHER AD–presenilin pathway may be novel causes of CSVD in a cohort of clinically suspicious CADASIL patients without a pathogenic NOTCH3 mutation. To investigate this, whole exome sequencing was performed on 50 suspected CADASIL patients with no NOTCH3 mutations, and a targeted gene analysis was completed on the PANTHER. ERN1 was identified as a novel candidate CSVD gene following predicted pathogenic gene mutation analysis. Rare variant burden testing failed to identify an association with any gene; however, it did show a nominally significant link with ERN1 and TRPC3. This study provides evidence to support a genetic overlap between CSVD and Alzheimer’s disease.</p

Genetic polymorphisms in CYP17 , CYP3A4 , CYP19A1 , SRD5A2 , IGF-1 , and IGFBP-3 and prostate cancer risk in African-American men: The Flint Men's Health Study

BACKGROUND Association studies have examined the significance of several candidate genes based on biological pathways relevant to prostate carcinogenesis, including both the androgen and insulin-like growth factor pathways. Clinical and epidemiologic evidence suggest that androgens, specifically testosterone and dihydrotestosterone (DHT) are important not only in normal prostate growth but in the pathogenesis of prostate cancer. Similarly, the insulin-like growth factor-1 (IGF-1) signaling pathway regulates both cellular proliferation and apoptosis. Therefore, genes involved in the biosynthesis, activation, metabolism and degradation of androgens and the stimulation of mitogenic and antiapoptotic activities of prostate epithelial cells represent important candidates for affecting the development and progression of prostate cancer. METHODS Using resources from the Flint Men's Health Study, a population-based case control study of African-American men aged 40–79, we evaluated the associations between selected single-nucleotide polymorphisms (SNPs) in the CYP17 , CYP3A4 , CYP19A1 , SDR5A2 , IGF1 , and IGFBP3 genes and prostate cancer diagnosis in 473 men (131 prostate cancer cases and 342 disease-free controls). RESULTS We found a significant association between prostate cancer and selected CYP17 SNP genotypes, with the heterozygous genotype conferring decreased risk. Suggestive evidence for association between IGF1 SNPs and prostate cancer were also found. No significant associations were observed between SNPs in the other genes and prostate cancer. CONCLUSIONS These findings suggest that variation in or around CYP17 and/or IGF1 may be associated with prostate cancer development in the African-American population. Additional studies are needed to determine whether these polymorphisms are indeed associated with prostate cancer risk in African Americans. Prostate 68: 296–305, 2008. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/57913/1/20696_ftp.pd

Measuring health-related quality of life outcomes in bladder cancer patients using the Bladder Cancer Index (BCI)

BACKGROUND. Health-related quality of life (HRQOL) has not been adequately measured in bladder cancer. A recently developed reliable and disease-specific quality of life instrument (Bladder Cancer Index, BCI) was used to measure urinary, sexual, and bowel function and bother domains in patients with bladder cancer managed with several different interventions, including cystectomy and endoscopic-based procedures. METHODS. Patients with bladder cancer were identified from a prospective bladder cancer outcomes database and contacted as part of an Institutional Review Board-approved study to assess treatment impact on HRQOL. HRQOL was measured using the BCI across stratified treatment groups. Bivariate and multivariable analyses adjusted for age, gender, income, education, relationship status, and follow-up time were performed to compare urinary, bowel, and sexual domains between treatment groups. RESULTS. In all, 315 bladder cancer patients treated at the University of Michigan completed the BCI in 2004. Significant differences were seen in mean BCI function and bother scores between cystectomy and native bladder treatment groups. In addition, urinary function scores were significantly lower among cystectomy patients treated with continent neobladder compared with those treated with ileal conduit (all pairwise P < .05). CONCLUSIONS. The BCI is responsive to functional and bother differences in patients with bladder cancer treated with different surgical approaches. Significant differences between therapy groups in each of the urinary, bowel, and sexual domains exist. Among patients treated with orthotopic continent urinary diversion, functional impairments related to urinary incontinence and lack of urinary control account for the low observed urinary function scores. Cancer 2007. © 2007 American Cancer Society.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55989/1/22556_ftp.pd