273 research outputs found
Effect of various normalization methods on Applied Biosystems expression array system data
BACKGROUND: DNA microarray technology provides a powerful tool for characterizing gene expression on a genome scale. While the technology has been widely used in discovery-based medical and basic biological research, its direct application in clinical practice and regulatory decision-making has been questioned. A few key issues, including the reproducibility, reliability, compatibility and standardization of microarray analysis and results, must be critically addressed before any routine usage of microarrays in clinical laboratory and regulated areas can occur. In this study we investigate some of these issues for the Applied Biosystems Human Genome Survey Microarrays. RESULTS: We analyzed the gene expression profiles of two samples: brain and universal human reference (UHR), a mixture of RNAs from 10 cancer cell lines, using the Applied Biosystems Human Genome Survey Microarrays. Five technical replicates in three different sites were performed on the same total RNA samples according to manufacturer's standard protocols. Five different methods, quantile, median, scale, VSN and cyclic loess were used to normalize AB microarray data within each site. 1,000 genes spanning a wide dynamic range in gene expression levels were selected for real-time PCR validation. Using the TaqMan(® )assays data set as the reference set, the performance of the five normalization methods was evaluated focusing on the following criteria: (1) Sensitivity and reproducibility in detection of expression; (2) Fold change correlation with real-time PCR data; (3) Sensitivity and specificity in detection of differential expression; (4) Reproducibility of differentially expressed gene lists. CONCLUSION: Our results showed a high level of concordance between these normalization methods. This is true, regardless of whether signal, detection, variation, fold change measurements and reproducibility were interrogated. Furthermore, we used TaqMan(® )assays as a reference, to generate TPR and FDR plots for the various normalization methods across the assay range. Little impact is observed on the TP and FP rates in detection of differentially expressed genes. Additionally, little effect was observed by the various normalization methods on the statistical approaches analyzed which indicates a certain robustness of the analysis methods currently in use in the field, particularly when used in conjunction with the Applied Biosystems Gene Expression System
Magnetism, FeS colloids, and Origins of Life
A number of features of living systems: reversible interactions and weak
bonds underlying motor-dynamics; gel-sol transitions; cellular connected
fractal organization; asymmetry in interactions and organization; quantum
coherent phenomena; to name some, can have a natural accounting via
interactions, which we therefore seek to incorporate by expanding the horizons
of `chemistry-only' approaches to the origins of life. It is suggested that the
magnetic 'face' of the minerals from the inorganic world, recognized to have
played a pivotal role in initiating Life, may throw light on some of these
issues. A magnetic environment in the form of rocks in the Hadean Ocean could
have enabled the accretion and therefore an ordered confinement of
super-paramagnetic colloids within a structured phase. A moderate H-field can
help magnetic nano-particles to not only overcome thermal fluctuations but also
harness them. Such controlled dynamics brings in the possibility of accessing
quantum effects, which together with frustrations in magnetic ordering and
hysteresis (a natural mechanism for a primitive memory) could throw light on
the birth of biological information which, as Abel argues, requires a
combination of order and complexity. This scenario gains strength from
observations of scale-free framboidal forms of the greigite mineral, with a
magnetic basis of assembly. And greigite's metabolic potential plays a key role
in the mound scenario of Russell and coworkers-an expansion of which is
suggested for including magnetism.Comment: 42 pages, 5 figures, to be published in A.R. Memorial volume, Ed
Krishnaswami Alladi, Springer 201
A large age for the pulsar B1757-24 from an upper limit on its proper motion
The "characteristic age" of a pulsar usually is considered to approximate its true age, but this assumption has led to some puzzling results, including the fact that many pulsars with small characteristic ages have no associated supernova remnants. The pulsar B1757-24 is located just beyond the edge of a supernova remnant; the properties of the system indicate that the pulsar was born at the centre of the remnant, but that it has subsequently overtaken the expanding blast-wave. With a characteristic age of 16,000 yr, this implies an expected proper motion by the pulsar of 63-80 milliarcsec per year. Here we report observations of the nebula surrounding the pulsar which limit its proper motion to less than 25 mas/yr, implying a minimum age of 39,000 yr. A more detailed analysis argues for a true age as great as 170,000 yr, significantly larger than the characteristic age. From this result and other discrepancies associated with pulsars, we conclude that characteristic ages seriously underestimate the true ages of pulsars
Modeling transitions in body composition: the approach to steady state for anthropometric measures and physiological functions in the Minnesota human starvation study
The Mediterranean diet for Polish infants: a losing struggle or a battle still worth fighting?
The Mediterranean diet is well known for its health-promoting effects. Among its key ingredients, olive oil is the most characteristic. Processing industries have been successfully manufacturing and marketing jarred baby foods with the use of vegetable oils, including olive oil, as well as other sources of visible fat. We aimed to survey manufacturer claims concerning added fat in jarred infant foods supplied to the Polish market. A total of 124 kinds of infant foods from six suppliers were analyzed. Corn, canola, and soybean oil occupied the first three positions, respectively, in rank order of vegetable oils used in jarred baby foods. In our sample, only one type of ready-to-eat jars with vegetables contained olive oil. 11% of products contained cow milk butter or cream. 61% of jarred “dinners” contained poultry or fish, which are typical sources of animal protein in the Mediterranean diet. Given that commercial baby foods currently available in the Polish market contain no olive oil, we advocate considering home preparation of infant foods with the use of visible fat. Medical professionals should encourage food manufacturers to return to the concepts of the Mediterranean diet for young consumers, aimed at long-term health
Association of Escherichia coli O157:H7 tir polymorphisms with human infection
<p>Abstract</p> <p>Background</p> <p>Emerging molecular, animal model and epidemiologic evidence suggests that Shiga-toxigenic <it>Escherichia coli </it>O157:H7 (STEC O157) isolates vary in their capacity to cause human infection and disease. The translocated intimin receptor (<it>tir</it>) and intimin (<it>eae</it>) are virulence factors and bacterial receptor-ligand proteins responsible for tight STEC O157 adherence to intestinal epithelial cells. They represent logical genomic targets to investigate the role of sequence variation in STEC O157 pathogenesis and molecular epidemiology. The purposes of this study were (1) to identify <it>tir </it>and <it>eae </it>polymorphisms in diverse STEC O157 isolates derived from clinically ill humans and healthy cattle (the dominant zoonotic reservoir) and (2) to test any observed <it>tir </it>and <it>eae </it>polymorphisms for association with human (vs bovine) isolate source.</p> <p>Results</p> <p>Five polymorphisms were identified in a 1,627-bp segment of <it>tir</it>. Alleles of two <it>tir </it>polymorphisms, <it>tir </it>255 T>A and repeat region 1-repeat unit 3 (RR1-RU3, presence or absence) had dissimilar distributions among human and bovine isolates. More than 99% of 108 human isolates possessed the <it>tir </it>255 T>A T allele and lacked RR1-RU3. In contrast, the <it>tir </it>255 T>A T allele and RR1-RU3 absence were found in 55% and 57%, respectively, of 77 bovine isolates. Both polymorphisms associated strongly with isolate source (p < 0.0001), but not by pulsed field gel electrophoresis type or by <it>stx</it>1 and <it>stx</it>2 status (as determined by PCR). Two <it>eae </it>polymorphisms were identified in a 2,755-bp segment of 44 human and bovine isolates; 42 isolates had identical <it>eae </it>sequences. The <it>eae </it>polymorphisms did not associate with isolate source.</p> <p>Conclusion</p> <p>Polymorphisms in <it>tir </it>but not <it>eae </it>predict the propensity of STEC O157 isolates to cause human clinical disease. The over-representation of the <it>tir </it>255 T>A T allele in human-derived isolates vs the <it>tir </it>255 T>A A allele suggests that these isolates have a higher propensity to cause disease. The high frequency of bovine isolates with the A allele suggests a possible bovine ecological niche for this STEC O157 subset.</p
Cisplatin-DNA adduct formation in patients treated with cisplatin-based chemoradiation: lack of correlation between normal tissues and primary tumor
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69595.pdf (publisher's version ) (Closed access)PURPOSE: In this study, the formation of cisplatin-DNA adducts after concurrent cisplatin-radiation and the relationship between adduct-formation in primary tumor tissue and normal tissue were investigated. METHODS: Three intravenous cisplatin-regimens, given concurrently with radiation, were studied: daily low-dose (6 mg/m(2)) cisplatin, weekly 40 mg/m(2), three-weekly 100 mg/m(2). A (32)P-postlabeling technique was used to quantify adducts in normal tissue [white blood cells (WBC) and buccal cells] and tumor. RESULTS: Normal tissue samples for adduct determination were obtained from 63 patients and tumor biopsies from 23 of these patients. Linear relationships and high correlations were observed between the levels of two guanosine- and adenosine-guanosine-adducts in normal and tumor tissue. Adduct levels in tumors were two to five times higher than those in WBC (P<0.001). No significant correlations were found between adduct levels in normal tissues and primary tumor biopsies, nor between WBC and buccal cells. CONCLUSIONS: In concurrent chemoradiotherapy schedules, cisplatin adduct levels in tumors were significantly higher than in normal tissues (WBC). No evidence of a correlation was found between adduct levels in normal tissues and primary tumor biopsies. This lack of correlation may, to some extent, explain the inconsistencies in the literature regarding whether or not cisplatin-DNA adducts can be used as a predictive test in anticancer platinum therapy
Oxford Phase 3 unicompartmental knee arthroplasty: medium-term results of a minimally invasive surgical procedure
PURPOSE: In the last decade, a major increase in the use of and interest in unicompartmental knee arthroplasty (UKA) has developed. The Oxford Phase 3 UKA is implanted with a minimally invasive technique using newly developed instruments. The objective of this prospective study was to evaluate the outcome of UKA in patients with medial osteoarthritis of the knee in a high-volume unit. METHODS: Two-hundred and forty-four UKAs were performed with a minimally invasive approach. The median age was 72 (43-91) years. The median follow-up was 4.2 years (range 1-10.4 years). Fourteen patients died, and nine were considered to be lost to follow-up, but all had a well-functioning prosthesis in situ until their last follow-up. Pain, function and health-related quality of life were evaluated pre- and postoperatively using patient- and assessor-based outcome scores, as well as radiographic evidence. RESULTS: The mean Knee Society knee and function scores, WOMAC-scores, Oxford-score and VAS pain and satisfaction all improved. Nine knees required revision. Eleven patients required an additional arthroscopic procedure due to persisting pain secondary to intra-articular pathology, and four patients required manipulation under anaesthesia because of limited range of motion. The 7-year cumulative survival rate of the arthroplasty was 94.4%. A low incidence (21%) of a radiolucent line beneath the tibial component was observed at 5 years of follow-up. CONCLUSION: This study showed a high survival rate of the Oxford Phase 3 UKA. Patient satisfaction and functional performance were also very high. Major complication rate was low; in addition, the incidence of radiolucency under the tibial component, when compared to present literature, was low. When strict indication criteria are followed, excellent, durable, and in our opinion reliable, results can be expected for this procedur
Measuring emotional and social wellbeing in Aboriginal and Torres Strait Islander populations: an analysis of a Negative Life Events Scale
Aboriginal and Torres Strait Islander Australians experience widespread socioeconomic disadvantage and health inequality. In an attempt to make Indigenous health research more culturally-appropriate, Aboriginal and Torres Strait Islander Australians have called for more attention to the concept of emotional and social wellbeing (ESWB). Although it has been widely recognised that ESWB is of crucial importance to the health of Aboriginal and Torres Strait Islander peoples, there is little consensus on how to measure in Indigenous populations, hampering efforts to better understand and improve the psychosocial determinants of health. This paper explores the policy and political context to this situation, and suggests ways to move forward. The second part of the paper explores how scales can be evaluated in a health research setting, including assessments of endorsement, discrimination, internal and external reliability
A phase II randomized trial comparing radiotherapy with concurrent weekly cisplatin or weekly paclitaxel in patients with advanced cervical cancer
<p>Abstract</p> <p>Purpose/Objective</p> <p>This is a prospective comparison of weekly cisplatin to weekly paclitaxel as concurrent chemotherapy with standard radiotherapy for locally advanced cervical carcinoma.</p> <p>Materials/Methods</p> <p>Between May 2000 and May 2004, 31 women with FIGO stage IB2-IVA cervical cancer or with postsurgical pelvic recurrence were enrolled into this phase II study and randomized to receive on a weekly basis either 40 mg/m<sup>2 </sup>Cisplatin (group I; 16 patients) or 50 mg/m<sup>2 </sup>paclitaxel (group II; 15 patients) concurrently with radiotherapy. Median total dose to point A was 74 Gy (range: 66-92 Gy) for group I and 66 Gy (range: 40-98 Gy) for group II. Median follow-up time was 46 months.</p> <p>Results</p> <p>Patient and tumor characteristics were similar in both groups. The mean number of chemotherapy cycles was also comparable with 87% and 80% of patients receiving at least 4 doses in groups I and II, respectively. Seven patients (44%) of group I and 8 patients (53%) of group II developed tumor recurrence. The Median Survival time was not reached for Group I and 53 months for group II. The proportion of patients surviving at 2 and 5 years was 78% and 54% for group I and 73% and 43% for group II respectively.</p> <p>Conclusions</p> <p>This small prospective study shows that weekly paclitaxel does not provide any clinical advantage over weekly cisplatin for concurrent chemoradiation for advanced carcinoma of the cervix.</p
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