Empirical Bayes accomodation of batch-effects in microarray data using identical replicate reference samples: application to RNA expression profiling of blood from Duchenne muscular dystrophy patients

<p>Abstract</p> <p>Background</p> <p>Non-biological experimental error routinely occurs in microarray data collected in different batches. It is often impossible to compare groups of samples from independent experiments because batch effects confound true gene expression differences. Existing methods can correct for batch effects only when samples from all biological groups are represented in every batch.</p> <p>Results</p> <p>In this report we describe a generalized empirical Bayes approach to correct for cross-experimental batch effects, allowing direct comparisons of gene expression between biological groups from independent experiments. The proposed experimental design uses identical reference samples in each batch in every experiment. These reference samples are from the same tissue as the experimental samples. This design with tissue matched reference samples allows a gene-by-gene correction to be performed using fewer arrays than currently available methods. We examine the effects of non-biological variation within a single experiment and between experiments.</p> <p>Conclusion</p> <p>Batch correction has a significant impact on which genes are identified as differentially regulated. Using this method, gene expression in the blood of patients with Duchenne Muscular Dystrophy is shown to differ for hundreds of genes when compared to controls. The numbers of specific genes differ depending upon whether between experiment and/or between batch corrections are performed.</p

Handler beliefs affect scent detection dog outcomes

Our aim was to evaluate how human beliefs affect working dog outcomes in an applied environment. We asked whether beliefs of scent detection dog handlers affect team performance and evaluated relative importance of human versus dog influences on handlers’ beliefs. Eighteen drug and/or explosive detection dog/handler teams each completed two sets of four brief search scenarios (conditions). Handlers were falsely told that two conditions contained a paper marking scent location (human influence). Two conditions contained decoy scents (food/toy) to encourage dog interest in a false location (dog influence). Conditions were (1) control; (2) paper marker; (3) decoy scent; and (4) paper marker at decoy scent. No conditions contained drug or explosive scent; any alerting response was incorrect. A repeated measures analysis of variance was used with search condition as the independent variable and number of alerts as the dependent variable. Additional nonparametric tests compared human and dog influence. There were 225 incorrect responses, with no differences in mean responses across conditions. Response patterns differed by condition. There were more correct (no alert responses) searches in conditions without markers. Within marked conditions, handlers reported that dogs alerted more at marked locations than other locations. Handlers’ beliefs that scent was present potentiated handler identification of detection dog alerts. Human more than dog influences affected alert locations. This confirms that handler beliefs affect outcomes of scent detection dog deployments

Total thyroidectomy: Complications and technique

During the 27-year period from 1957 to 1984, four hundred thirty patients underwent total thyroidectomies for malignant or benign disease of the thyroid gland at our institutions. Thyroid cancer was found in 83.4% of cases, and 47.2% of these had concomitant lymph node dissections. Transient recurrent laryngeal nerve injury occurred in 6.2% of the entire series. Permanent unilateral vocal cord paralysis occurred in 2.5% of the patients operated on, although only 1 patient (0.45%) sustained this complication in the past 14 years. No patient had permanent bilateral vocal cord paralysis. Transient hypoparathyroidism was seen in 16.8% of patients with permanent hypoparathyroidism occurring in 4.0%. The incidence of permanent hypoparathyroidism fell to 2.7% during the past 14 years and was directly related to the extent of thyroid cancer found at operation. Postoperative complications decrease with the experience of the surgeon and increase with reoperations and extensive disease. Total thyroidectomy continues to be our treatment of choice for thyroid cancer. Au cours d'une période de 27 ans de 1957 à 1984, quatre cent trente patients ont subi une thyroïdectomie totale dans notre établissement pour des lésions bénignes ou malignes du corps thyroïdien. Dans 83.4% des cas il s'agit d'un carcinome thyroïdien, nécessitant chez 47.2% d'entre eux un curage ganglionnaire associé. On observe une atteinte transitoire du nerf récurrent laryngé dans 6.2% des cas sur la totalité de la série. Une paralysie permanente unilatérale des cordes vocales survient chez 2.5% des patients opérés, alors que durant les 14 dernières années un seul patient présente cette complication. Aucun des cas de paralysie bilatérale permanente des cordes vocales n'est observé. Une hypoparathyroïdie transitoire est constatée chez 16.8% des patients avec hypoparathyroïdie définitive dans 4.0% des cas. L'incidence de l'hypoparathyroïdisme définitif tombe à 2.7% au cours des 14 dernières années et est directement liée à l'extension du cancer thyroïdien constaté lors de l'intervention. Les complications postopératoires diminuent avec l'expérience du chirurgien et augmentent lors des réinterventions et l'extension des lésions. La thyroïdectomie totale demeure pour les auteurs le traitement de choix du cancer thyroïdien. En el lapso de los 27 años entre 1957 y 1984, cuatro cientos treinta pacientes fueron sometidos a tiroidectomía total por enfermedad maligna o benigna de la glándula tiroides en nuestras instituciones. Cáncer tiroideo fue hallado en 83.4% de los casos, y 47.2% de éstos tuvieron disecciones ganglionares concomitantes. Lesión transitoria del nervio recurrente laríngeo ocurrió en el 6.2% de la serie total. Parálisis permanente unilateral de la cuerda vocal ocurrió en 2.5% de los pacientes operados, mientras sólo un paciente (0.45%) presentó esta complicación en los últimos 14 años. Ningún paciente presento parálisis bilateral permanente de las cuerdas vocales. Hipoparatiroidismo transitorio fue observado en 16.8% de los pacientes, y el hipoparatiroidismo permanente ocurrió en el 4.0%. La incidencia de hipoparatiroidismo permanente descendió a 2.7% en los ültimos 14 años y apareció directamente relacionado con la extensión del cancer tiroideo hallada en la operación. Las complicaciones postoperatorias disminuyen en relación a la experiencia del cirujano y se incrementan con las reoperaciones y con la enfermedad muy extensa. La tiroidectomía total continúa siendo nuestra forma preferida de tratamiento para cáncer tiroideo.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41277/1/268_2005_Article_BF01655238.pd

Albúm cervantino aragonés de los trabajos literarios y artísticos con que se ha celebrado en Zaragoza y Pedrola el III Centenario de la edición príncipe del Quijote

"Las estampas sueltas se tiraron por J. Blass, por fotograbados de Laporta" ColofónCopia digital. Zaragoza : Diputación General de Aragón, 201

Development of Photonic Crystal Fiber Based Gas/ Chemical Sensors

The development of highly-sensitive and miniaturized sensors that capable of real-time analytes detection is highly desirable. Nowadays, toxic or colorless gas detection, air pollution monitoring, harmful chemical, pressure, strain, humidity, and temperature sensors based on photonic crystal fiber (PCF) are increasing rapidly due to its compact structure, fast response and efficient light controlling capabilities. The propagating light through the PCF can be controlled by varying the structural parameters and core-cladding materials, as a result, evanescent field can be enhanced significantly which is the main component of the PCF based gas/chemical sensors. The aim of this chapter is to (1) describe the principle operation of PCF based gas/ chemical sensors, (2) discuss the important PCF properties for optical sensors, (3) extensively discuss the different types of microstructured optical fiber based gas/ chemical sensors, (4) study the effects of different core-cladding shapes, and fiber background materials on sensing performance, and (5) highlight the main challenges of PCF based gas/ chemical sensors and possible solutions

Case report: hypoglycemia due to a novel activating glucokinase variant in an adult – a molecular approach

We present a case of an obese 22-year-old man with activating GCK variant who had neonatal hypoglycemia, re-emerging with hypoglycemia later in life. We investigated him for asymptomatic hypoglycemia with a family history of hypoglycemia. Genetic testing yielded a novel GCK missense class 3 variant that was subsequently found in his mother, sister and nephew and reclassified as a class 4 likely pathogenic variant. Glucokinase enables phosphorylation of glucose, the rate-limiting step of glycolysis in the liver and pancreatic β cells. It plays a crucial role in the regulation of insulin secretion. Inactivating variants in GCK cause hyperglycemia and activating variants cause hypoglycemia. Spleen-preserving distal pancreatectomy revealed diffuse hyperplastic islets, nuclear pleomorphism and periductular islets. Glucose stimulated insulin secretion revealed increased insulin secretion in response to glucose. Cytoplasmic calcium, which triggers exocytosis of insulin-containing granules, revealed normal basal but increased glucose-stimulated level. Unbiased gene expression analysis using 10X single cell sequencing revealed upregulated INS and CKB genes and downregulated DLK1 and NPY genes in β-cells. Further studies are required to see if alteration in expression of these genes plays a role in the metabolic and histological phenotype associated with glucokinase pathogenic variant. There were more large islets in the patient’s pancreas than in control subjects but there was no difference in the proportion of β cells in the islets. His hypoglycemia was persistent after pancreatectomy, was refractory to diazoxide and improved with pasireotide. This case highlights the variable phenotype of GCK mutations. In-depth molecular analyses in the islets have revealed possible mechanisms for hyperplastic islets and insulin hypersecretion

Is IP-10 a Better Biomarker for Active and Latent Tuberculosis in Children than IFNγ?

Background: The blood based interferon-gamma release assays (IGRA) for the diagnosis of tuberculosis do not discriminate between active TB disease and latent TB infection (LTBI). The search for distinguishing biomarkers therefore continues, as the accurate diagnosis of tuberculosis is particularly challenging in children. IFN-c-inducible protein 10 (IP-10/CXCL10) has recently been evaluated as a marker for active TB in adults with promising results. Aim: To investigate this new biomarker for active TB and LTBI in paediatrics. Method: We measured IP-10 levels using ELISA in supernatants of whole blood samples stimulated with TB-specificantigens and negative control antigen. Results: IP-10 is produced in high levels following mycobacterial antigen stimulation in active TB (n = 17) and LTBI (n = 16) compared to controls (n = 16) and to IFN-c. The baseline levels of IP-10 are increased in active TB and in LTBI, but there is no significant difference of stimulated levels of IP-10 between active TB and LTBI. Conclusions: IP-10 is a biomarker for tuberculosis in children. However like IFNc, IP-10 also does not distinguish between active TB and LTBI

A metagenomic portrait of the microbial community responsible for two decades of bioremediation of poly-contaminated groundwater

Biodegradation of pollutants is a sustainable and cost-effective solution to groundwater pollution. Here, we investigate microbial populations involved in biodegradation of poly-contaminants in a pipeline for heavily contaminated groundwater. Groundwater moves from a polluted park to a treatment plant, where an aerated bioreactor effectively removes the contaminants. While the biomass does not settle in the reactor, sediment is collected afterwards and used to seed the new polluted groundwater via a backwash cycle. The pipeline has successfully operated since 1999, but the biological components in the reactor and the contaminated park groundwater have never been described. We sampled seven points along the pipeline, representing the entire remediation process, and characterized the changing microbial communities using genome-resolved metagenomic analysis. We assembled 297 medium- and high-quality metagenome-assembled genome sequences representing on average 46.3% of the total DNA per sample. We found that the communities cluster into two distinct groups, separating the anaerobic communities in the park groundwater from the aerobic communities inside the plant. In the park, the community is dominated by members of the genus Sulfuricurvum, while the plant is dominated by generalists from the order Burkholderiales. Known aromatic compound biodegradation pathways are four times more abundant in the plant-side communities compared to the park-side. Our findings provide a genome-resolved portrait of the microbial community in a highly effective groundwater treatment system that has treated groundwater with a complex contamination profile for two decades

Association study of genetic variants of pro-inflammatory chemokine and cytokine genes in systemic lupus erythematosus

BACKGROUND: Several lines of evidence suggest that chemokines and cytokines play an important role in the inflammatory development and progression of systemic lupus erythematosus. The aim of this study was to evaluate the relevance of functional genetic variations of RANTES, IL-8, IL-1α, and MCP-1 for systemic lupus erythematosus. METHODS: The study was conducted on 500 SLE patients and 481 ethnically matched healthy controls. Genotyping of polymorphisms in the RANTES, IL-8, IL-1α, and MCP-1 genes were performed using a real-time polymerase chain reaction (PCR) system with pre-developed TaqMan allelic discrimination assay. RESULTS: No significant differences between SLE patients and healthy controls were observed when comparing genotype, allele or haplotype frequencies of the RANTES, IL-8, IL-1α, and MCP-1 polymorphisms. In addition, no evidence for association with clinical sub-features of SLE was found. CONCLUSION: These results suggest that the tested functional variation of RANTES, IL-8, IL-1α, and MCP-1 genes do not confer a relevant role in the susceptibility or severity of SLE in the Spanish population