The realizability of a coding scheme for additive noise channels with feedback

Coding scheme for additive noise channels with feedbac

Pilot study of duloxetine for treatment of aromatase inhibitor‐associated musculoskeletal symptoms

BACKGROUND: Approximately 50% of postmenopausal women with hormone receptor‐positive early stage breast cancer treated with an aromatase inhibitor (AI) develop musculoskeletal symptoms. Standard analgesics are relatively ineffective. Duloxetine is a serotonin norepinephrine reuptake inhibitor with proven efficacy for treatment of multiple chronic pain states. The authors investigated the hypothesis that duloxetine is efficacious for treatment of AI‐associated musculoskeletal symptoms. METHODS: The authors performed a single‐arm, open‐label phase 2 study of duloxetine in postmenopausal women with breast cancer who developed new or worsening pain after treatment with an AI for at least 2 weeks. Patients were treated with duloxetine for 8 weeks (30 mg for 7 days, then 60 mg daily). The primary endpoint was a 30% decrease in average pain score over 8 weeks, and secondary outcomes included change in average and worst pain, pain interference, depression, sleep quality, and hot flashes. Statistical analysis was done with t tests for paired data. RESULTS: Twenty‐one of 29 evaluable patients (72.4%) achieved at least a 30% decrease in average pain, and 18 of 23 patients (78.3%) who completed protocol‐directed treatment continued duloxetine. The mean percentage reduction in average pain severity between baseline and 8 weeks was 60.9% (95% confidence interval [CI], 48.6%‐73.1%), and in maximum pain severity it was 59.9% (95% CI, 47.0‐72.7%). The most common adverse events were grade 1 or 2 fatigue, xerostomia, nausea, and headache. CONCLUSIONS: Duloxetine appears to be effective and well tolerated for treatment of AI‐associated musculoskeletal symptoms. Future randomized, placebo‐controlled studies are warranted. Cancer 2011;. © 2011 American Cancer Society. Bothersome musculoskeletal symptoms affect about half of women with early stage breast cancer treated with aromatase inhibitors. In this pilot clinical trial, treatment with duloxetine appeared to significantly improve pain and functioning, and was relatively well tolerated.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/89530/1/26230_ftp.pd

Detection of Tumor Cell-Specific mRNA in the Peripheral Blood of Patients with Breast Cancer-Evaluation of Several Markers with Real-Time Reverse Transcription-PCR

It is widely known that cells from epithelial tumors, e. g., breast cancer, detach from their primary tissue and enter blood circulation. We show that the presence of circulating tumor cells (CTCs) in samples of patients with primary and metastatic breast cancer can be detected with an array of selected tumor-marker-genes by reverse transcription real-time PCR. The focus of the presented work is on detecting differences in gene expression between healthy individuals and adjuvant and metastatic breast cancer patients, not an accurate quantification of these differences. Therefore, total RNA was isolated from blood samples of healthy donors and patients with primary or metastatic breast cancer after enrichment of mononuclear cells by density gradient centrifugation. After reverse transcription real-time PCR was carried out with a set of marker genes (BCSP, CK8, Her2, MGL, CK18, CK19). B2M and GAPDH were used as reference genes. Blood samples from patients with metastatic disease revealed increased cytokine gene levels in comparison to normal blood samples. Detection of a single gene was not sufficient to detect CTCs by reverse transcription real-time PCR. Markers used here were selected based on a recent study detecting cancer cells on different protein levels. The combination of such a marker array leads to higher and more specific discovery rates, predominantly in metastatic patients. Identification of CTCs by PCR methods may lead to better diagnosis and prognosis and could help to choose an adequate therapy

Simple multi-level microchannel fabrication by pseudo-grayscale backside diffused light lithography

Photolithography of multi-level channel features in microfluidics is laborious and/or costly. Grayscale photolithography is mostly used with positive photoresists and conventional front side exposure, but the grayscale masks needed are generally costly and positive photoresists are not commonly used in microfluidic rapid prototyping. Here we introduce a simple and inexpensive alternative that uses pseudo-grayscale (pGS) photomasks in combination with backside diffused light lithography (BDLL) and the commonly used negative photoresist, SU-8. BDLL can produce smooth multi-level channels of gradually changing heights without use of true grayscale masks because of the use of diffused light. Since the exposure is done through a glass slide, the photoresist is cross-linked from the substrate side up enabling well-defined and stable structures to be fabricated from even unspun photoresist layers. In addition to providing unique structures and capabilities, the method is compatible with the "garage microfluidics" concept of creating useful tools at low cost since pGS BDLL can be performed with the use of only hot plates and a UV transilluminator: equipment commonly found in biology labs. Expensive spin coaters or collimated UV aligners are not needed. To demonstrate the applicability of pGS BDLL, a variety of weir-type cell traps were constructed with a single UV exposure to separate cancer cells (MDA-MB-231, 10-15 ??m in size) from red blood cells (RBCs, 2-8 ??m in size) as well as follicle clusters (40-50 ??m in size) from cancer cells (MDA-MB-231, 10-15 ??m in size)close1

Poliovirus RNA Polymerase Mutation 3D-M394T Results in a Temperature-Sensitive Defect in RNA Synthesis

AbstractMutant ts10 is an RNA-negative temperature-sensitive mutant of Mahoney type 1 poliovirus. Mutant ts10 3Dpolwas purified from infected cells and was shown to be rapidly heat-inactivated at 45° when compared to wild-type polymerase. Sequencing of mutant ts10 genomic RNA revealed a U to C transition at nt 7167 resulting in an amino acid change of methionine 394 of 3Dpolto threonine. The 3D-M394T mutation was engineered into a wild-type infectious clone of poliovirus type 1. The resultant mutant virus, 3D-105, had a temperature-sensitive phenotype in plaque assays. The translation and replication of wild-type, ts10, and 3D-105 virion RNAs were all characterized in HeLa S10 translation-RNA replication reactionsin vitro.The optimum temperatures for the replication of the wild-type and mutant viral RNAs in the HeLa S10 translation-replication reactions were 37 and 34°, respectively. To characterize the temperature-sensitive defect in the replication of the mutant RNA, we used preinitiation RNA replication complexes which were formed in HeLa S10in vitroreactions containing guanidine HCl. Negative-strand RNA synthesis in 3D-M394T mutant preinitiation replication complexes was normal at 34° but was rapidly and irreversibly inhibited at 39.5°. To differentiate between the initiation and elongation steps in RNA replication, we compared the elongation rates in mutant and wild-type replication complexes at 39.5°. The results showed that the elongation rates for nascent negative strands in both the mutant and wild-type replication complexes were identical. Therefore, the results indicate that the heat-sensitive step in negative-strand synthesis exhibited by the 3D-M394T replication complexes is in the initiation of RNA synthesis and not in the elongation of nascent chains

Markers for the identification of late breast cancer recurrence

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited

Head and Neck Squamous Cell Carcinoma Detection and Surveillance: Advances of Liquid Biomarkers

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150578/1/lary27725.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150578/2/lary27725_am.pd