Electronic Reference Library Phase I Report, 1999

This report describes the first phase in a project to develop an electronic reference library (ERL) to help Iowa transportation officials efficiently access information in critical and heavily used documents. These documents include Standard Specifications for Bridge and Highway Construction (hereinafter called Standard Specifications), design manuals, standard drawings, the Construction Manual, and Material Instruction Memoranda (hereinafter called Material IMs). Additional items that could be included to enhance the ERL include phone books, letting dates, Internet links, computer programs distributed by the Iowa Department of Transportation (DOT), and local specifications, such as the Urban Standard Specifications of Public Improvements. All cross-references should be hyper linked, and a search engine should be provided. Revisions noted in the General Supplemental Specifications (hereinafter called the Supplemental Specifications) should be incorporated into the text of the Standard Specifications. The Standard Specifications should refer to related sections of other documents, and there should be reciprocal hyper links in those other documents. These features would speed research on critical issues and save staff time. A master plan and a pilot version were both developed in this first phase of the ERL.

Intermittent atrial tachycardia facilitates atrial fibrillation by a shortening of activation recovery interval

Introduction: We recently observed in a chronic ovine model that a shortening of action potential duration (APD) as assessed by the activation recovery interval (ARI) may be a mechanism whereby pacing-induced atrial tachycardia (PIAT) facilitates atrial fibrillation (AF), mediated by a return to 1:1 atrial capture after the effective refractory period has been reached. The aim of the present study is to evaluate the effect of long term intermittent burst pacing on ARI before induction of AF.Methods: We specifically developed a chronic ovine model of PIAT using two pacemakers (PM) each with a right atrial (RA) lead separated by ∼2cm. The 1st PM (Vitatron T70) was used to record a broadband unipolar RA EGM (800 Hz, 0.4 Hz high pass filter). The 2nd was used to deliver PIAT during electrophysiological protocols at decremental pacing CL (400 beats, from 400 to 110ms) and long term intermittent RA burst pacing to promote electrical remodeling (5s of burst followed by 2s of sinus rhythm) until onset of sustained AF. ARI was defined as the time difference between the peak of the atrial repolarization wave and the first atrial depolarization. The mean ARIs of paired sequences (before and after remodeling), each consisting of 20 beats were compared.Results: As shown in the figure, ARIs (n=4 sheep, 46 recordings) decreased post remodeling compared to baseline (86±19 vs 103±12 ms, p<0.05). There was no difference in atrial structure as assessed by light microscopy between control and remodeled sheep.Conclusions: Using standard pacemaker technology, atrial ARIs as a surrogate of APDs were successfully measured in vivo during the electrical remodeling process leading to AF. The facilitation of AF by PIAT mimicking salvos from pulmonary veins is heralded by a significant shortening of ARI.

Reference values of fat-free and fat masses by bioelectrical impedance analysis in 3393 healthy subjects.

Determination of fat-free mass (FFM) and fat mass (FM) is of considerable interest in the evaluation of nutritional status. In recent years, bioelectrical impedance analysis (BIA) has emerged as a simple, reproducible method used for the evaluation of FFM and FM, but the lack of reference values reduces its utility to evaluate nutritional status. The aim of this study was to determine reference values for FFM, FM, and %FM by BIA in a white population of healthy subjects, to observe the changes in these values with age, and to develop percentile distributions for these parameters. Whole-body resistance of 1838 healthy white men and 1555 women, aged 15-64 y, was determined by using four skin electrodes on the right hand and foot. FFM and FM were calculated according to formulas validated for the subject groups and analyzed for age decades. This is the first study to present BIA-determined age- and sex-specific percentiles for FFM, FM, and %FM for healthy subjects, aged 15-64 y. Mean FM and %FM increased progressively in men and after age 45 y in women. The results suggest that any weight gain noted with age is due to a gain in FM. In conclusion, the data presented as percentiles can serve as reference to evaluate the normality of body composition of healthy and ill subject groups at a given age.

Identification of reference genes for expression analysis by real-time quantitative PCR in drought-stressed soybean

The objective of this work was to validate, by quantitative PCR in real time (RT-qPCR), genes to be used as reference in studies of gene expression in soybean in drought-stressed trials. Four genes commonly used in soybean were evaluated: Gmβ-actin, GmGAPDH, GmLectin and GmRNAr18S. Total RNA was extracted from six samples: three from roots in a hydroponic system with different drought intensities (0, 25, 50, 75 and 100 minutes of water stress), and three from leaves of plants grown in sand with different soil moistures (15, 5 and 2.5% gravimetric humidity). The raw cycle threshold (Ct) data were analyzed, and the efficiency of each primer was calculated for an overall analysis of the Ct range among the different samples. The GeNorm application was used to evaluate the best reference gene, according to its stability. The GmGAPDH was the least stable gene, with the highest mean values of expression stability (M), and the most stable genes, with the lowest M values, were the Gmβ-actin and GmRNAr18S, when both root and leaves samples were tested. These genes can be used in RT-qPCR as reference gene for expression analysis.

Lipid and lipoprotein profile in HIV-infected patients treated with lopinavir/ritonavir as a component of the first combination antiretroviral therapy.

We characterized lipid and lipoprotein changes associated with a lopinavir/ritonavir-containing regimen. We enrolled previously antiretroviral-naive patients participating in the Swiss HIV Cohort Study. Fasting blood samples (baseline) were retrieved retrospectively from stored frozen plasma and posttreatment (follow-up) samples were collected prospectively at two separate visits. Lipids and lipoproteins were analyzed at a single reference laboratory. Sixty-five patients had two posttreatment lipid profile measurements and nine had only one. Most of the measured lipids and lipoprotein plasma concentrations increased on lopinavir/ritonavir-based treatment. The percentage of patients with hypertriglyceridemia (TG >150 mg/dl) increased from 28/74 (38%) at baseline to 37/65 (57%) at the second follow-up. We did not find any correlation between lopinavir plasma levels and the concentration of triglycerides. There was weak evidence of an increase in small dense LDL-apoB during the first year of treatment but not beyond 1 year (odds ratio 4.5, 90% CI 0.7 to 29 and 0.9, 90% CI 0.5 to 1.5, respectively). However, 69% of our patients still had undetectable small dense LDL-apoB levels while on treatment. LDL-cholesterol increased by a mean of 17 mg/dl (90% CI -3 to 37) during the first year of treatment, but mean values remained below the cut-off for therapeutic intervention. Despite an increase in the majority of measured lipids and lipoproteins particularly in the first year after initiation, we could not detect an obvious increase of cardiovascular risk resulting from the observed lipid changes.

The role of interval nodes in sentinel lymph node mapping and dissection for melanoma patients.

In sentinel node (SN) biopsy, an interval SN is defined as a lymph node or group of lymph nodes located between the primary melanoma and an anatomically well-defined lymph node group directly draining the skin. As shown in previous reports, these interval SNs seem to be at the same metastatic risk as are SNs in the usual, classic areas. This study aimed to review the incidence, lymphatic anatomy, and metastatic risk of interval SNs. METHODS: SN biopsy was performed at a tertiary center by a single surgical team on a cohort of 402 consecutive patients with primary melanoma. The triple technique of localization was used-that is, lymphoscintigraphy, blue dye, and gamma-probe. Otolaryngologic melanoma and mucosal melanoma were excluded from this analysis. SNs were examined by serial sectioning and immunohistochemistry. All patients with metastatic SNs were recommended to undergo a radical selective lymph node dissection. RESULTS: The primary locations of the melanomas included the trunk (188), an upper limb (67), or a lower limb (147). Overall, 97 (24.1%) of the 402 SNs were metastatic. Interval SNs were observed in 18 patients, in all but 2 of whom classic SNs were also found. The location of the primary was truncal in 11 (61%) of the 18, upper limb in 5, and lower limb in 2. One patient with a dorsal melanoma had drainage exclusively in a cervicoscapular area that was shown on removal to contain not lymph node tissue but only a blue lymph channel without tumor cells. Apart from the interval SN, 13 patients had 1 classic SN area and 3 patients 2 classic SN areas. Of the 18 patients, 2 had at least 1 metastatic interval SN and 2 had a classic SN that was metastatic; overall, 4 (22.2%) of 18 patients were node-positive. CONCLUSION: We found that 2 of 18 interval SNs were metastatic: This study showed that preoperative lymphoscintigraphy must review all known lymphatic areas in order to exclude an interval SN.

Pediatric reference intervals for plasma free and total metanephrines established with a parametric approach: Relevance to the diagnosis of neuroblastoma.

BACKGROUND: Urine catecholamines, vanillylmandelic, and homovanillic acid are recognized biomarkers for the diagnosis and follow-up of neuroblastoma. Plasma free (f) and total (t) normetanephrine (NMN), metanephrine (MN) and methoxytyramine (MT) could represent a convenient alternative to those urine markers. The primary objective of this study was to establish pediatric centile charts for plasma metanephrines. Secondarily, we explored their diagnostic performance in 10 patients with neuroblastoma. PROCEDURE: We recruited 191 children (69 females) free of neuroendocrine disease to establish reference intervals for plasma metanephrines, reported as centile curves for a given age and sex based on a parametric method using fractional polynomials models. Urine markers and plasma metanephrines were measured in 10 children with neuroblastoma at diagnosis. Plasma total metanephrines were measured by HPLC with coulometric detection and plasma free metanephrines by tandem LC-MS. RESULTS: We observed a significant age-dependence for tNMN, fNMN, and fMN, and a gender and age-dependence for tMN, fNMN, and fMN. Free MT was below the lower limit of quantification in 94% of the children. All patients with neuroblastoma at diagnosis were above the 97.5th percentile for tMT, tNMN, fNMN, and fMT, whereas their fMN and tMN were mostly within the normal range. As expected, urine assays were inconstantly predictive of the disease. CONCLUSIONS: A continuous model incorporating all data for a given analyte represents an appealing alternative to arbitrary partitioning of reference intervals across age categories. Plasma metanephrines are promising biomarkers for neuroblastoma, and their performances need to be confirmed in a prospective study on a large cohort of patients. Pediatr Blood Cancer 2015;62:587-593. © 2015 Wiley Periodicals, Inc.

Minor protease inhibitor mutations at baseline do not increase the risk for a virological failure in HIV-1 subtype B infected patients.

BACKGROUND: Minor protease inhibitor (PI) mutations often exist as polymorphisms in HIV-1 sequences from treatment-naïve patients. Previous studies showed that their presence impairs the antiretroviral treatment (ART) response. Evaluating these findings in a larger cohort is essential. METHODS: To study the impact of minor PI mutations on time to viral suppression and time to virological failure, we included patients from the Swiss HIV Cohort Study infected with HIV-1 subtype B who started first-line ART with a PI and two nucleoside reverse transcriptase inhibitors. Cox regression models were performed to compare the outcomes among patients with 0 and ≥ 1 minor PI mutation. Models were adjusted for baseline HIV-1 RNA, CD4 cell count, sex, transmission category, age, ethnicity, year of ART start, the presence of nucleoside reverse transcriptase inhibitor mutations, and stratified for the administered PIs. RESULTS: We included 1199 patients of whom 944 (78.7%) received a boosted PI. Minor PI mutations associated with the administered PI were common: 41.7%, 16.1%, 4.7% and 1.9% had 1, 2, 3 or ≥ 4 mutations, respectively. The time to viral suppression was similar between patients with 0 (reference) and ≥ 1 minor PI mutation (multivariable hazard ratio (HR): 1.1 [95% confidence interval (CI): 1.0-1.3], P = .196). The time to virological failure was also similar (multivariable HR:.9 [95% CI:.5-1.6], P = .765). In addition, the impact of each single minor PI mutation was analyzed separately: none was significantly associated with the treatment outcome. CONCLUSIONS: The presence of minor PI mutations at baseline has no effect on the therapy outcome in HIV infected individuals.

Patient doses in CT examinations in Switzerland: implementation of national diagnostic reference levels.

Diagnostic reference levels (DRLs) were established for 21 indication-based CT examinations for adults in Switzerland. One hundred and seventy-nine of 225 computed tomography (CT) scanners operated in hospitals and private radiology institutes were audited on-site and patient doses were collected. For each CT scanner, a correction factor was calculated expressing the deviation of the measured weighted computed tomography dose index (CTDI) to the nominal weighted CTDI as displayed on the workstation. Patient doses were corrected by this factor providing a realistic basis for establishing national DRLs. Results showed large variations in doses between different radiology departments in Switzerland, especially for examinations of the petrous bone, pelvis, lower limbs and heart. This indicates that the concept of DRLs has not yet been correctly applied for CT examinations in clinical routine. A close collaboration of all stakeholders is mandatory to assure an effective radiation protection of patients. On-site audits will be intensified to further establish the concept of DRLs in Switzerland.

Fluorescence flow cytometer to determine urine particle reference intervals in doping control samples.

Background: Urine is still the matrix of choice to fight against doping, because it can be collected non-invasively during anti-doping tests. Most of the World Anti-Doping Agency's accredited laboratories have more than 20 years experience in analyzing this biological fluid and the majority of the compounds listed in the 2010 Prohibited List - International Standard are eliminated through the urinary apparatus. Storing and transporting urine samples for doping analyses does not include a specific protocol to prevent microbial and thermal degradation. The use of a rapid and reliable screening method could enable determine reference intervals for urine specimens in doping control samples and evaluate notably the prevalence of microbial contamination known to be responsible for the degradation of chemical substances in urine.Methods: The Sysmex(R) UF-500i is a recent urine flow cytometer analyzer capable of quantifying BACT and other urinary particles such as RBC, WBC, EC, DEBRIS, CAST, PATH. CAST, YLC, SRC as well as measuring urine conductivity. To determine urine anti-doping reference intervals, 501 samples received in our laboratory over a period of two months were submitted to an immediate examination. All samples were collected and then transported at room temperature. Analysis of variance was performed to test the effects of factors such as gender, test type [in-competition, out-of-competition] and delivery time.Results: The data obtained showed that most of the urine samples were highly contaminated with bacteria. The other urine particles were also very different according to the factors.Conclusions: The Sysmex(R) UF-500i was capable of providing a snapshot of urine particles present in the samples at the time of the delivery to the laboratory. These particles, BACT in particular, gave a good idea of the possible microbial degradation which had and/or could have occurred in the sample. This information could be used as the first quality control set up in WADA (World Anti-Doping Agency) accredited laboratories to determine if steroid profiles, endogenous and prohibited substances have possibly been altered. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Influence of the implanted pulse generator as reference electrode in finite element model of monopolar deep brain stimulation.

Electrical deep brain stimulation (DBS) is an efficient method to treat movement disorders. Many models of DBS, based mostly on finite elements, have recently been proposed to better understand the interaction between the electrical stimulation and the brain tissues. In monopolar DBS, clinically widely used, the implanted pulse generator (IPG) is used as reference electrode (RE). In this paper, the influence of the RE model of monopolar DBS is investigated. For that purpose, a finite element model of the full electric loop including the head, the neck and the superior chest is used. Head, neck and superior chest are made of simple structures such as parallelepipeds and cylinders. The tissues surrounding the electrode are accurately modelled from data provided by the diffusion tensor magnetic resonance imaging (DT-MRI). Three different configurations of RE are compared with a commonly used model of reduced size. The electrical impedance seen by the DBS system and the potential distribution are computed for each model. Moreover, axons are modelled to compute the area of tissue activated by stimulation. Results show that these indicators are influenced by the surface and position of the RE. The use of a RE model corresponding to the implanted device rather than the usually simplified model leads to an increase of the system impedance (+48%) and a reduction of the area of activated tissue (-15%).

Différences induites par la définition des périodes diurnes et nocturnes sur la pression artérielle et le dipping lors d'une mesure ambulatoire de la pression artérielle [Effects of nighttime and daytime interval definition on blood pressure and dipping in patients referred for ambulatory blood pressure measurement].

Ambulatory blood pressure monitoring (ABPM) has become indispensable for the diagnosis and control of hypertension. However, no consensus exists on how daytime and nighttime periods should be defined. OBJECTIVE: To compare daytime and nighttime blood pressure (BP) defined by an actigraph and by body position with BP resulting from arbitrary daytime and nighttime periods. PATIENTS AND METHOD: ABPM, sleeping periods and body position were recorded simultaneously using an actigraph (SenseWear Armband(®)) in patients referred for ABPM. BP results obtained with the actigraph (sleep and position) were compared to the results obtained with fixed daytime (7a.m.-10p.m.) and nighttime (10p.m.-7a.m.) periods. RESULTS: Data from 103 participants were available. More than half of them were taking antihypertensive drugs. Nocturnal BP was lower (systolic BP: 2.08±4.50mmHg; diastolic BP: 1.84±2.99mmHg, P<0.05) and dipping was more marked (systolic BP: 1.54±3.76%; diastolic BP: 2.27±3.48%, P<0.05) when nighttime was defined with the actigraph. Standing BP was higher (systolic BP 1.07±2.81mmHg; diastolic BP: 1.34±2.50mmHg) than daytime BP defined by a fixed period. CONCLUSION: Diurnal BP, nocturnal BP and dipping are influenced by the definition of daytime and nighttime periods. Studies evaluating the prognostic value of each method are needed to clarify which definition should be used.

Statistical reference criteria for adaptive signal processing in digital communications

A general criterion for the design of adaptive systemsin digital communications called the statistical reference criterionis proposed. The criterion is based on imposition of the probabilitydensity function of the signal of interest at the outputof the adaptive system, with its application to the scenario ofhighly powerful interferers being the main focus of this paper.The knowledge of the pdf of the wanted signal is used as adiscriminator between signals so that interferers with differingdistributions are rejected by the algorithm. Its performance isstudied over a range of scenarios. Equations for gradient-basedcoefficient updates are derived, and the relationship with otherexisting algorithms like the minimum variance and the Wienercriterion are examined.

GENCODE: producing a reference annotation for ENCODE.

BACKGROUND: The GENCODE consortium was formed to identify and map all protein-coding genes within the ENCODE regions. This was achieved by a combination of initial manual annotation by the HAVANA team, experimental validation by the GENCODE consortium and a refinement of the annotation based on these experimental results. RESULTS: The GENCODE gene features are divided into eight different categories of which only the first two (known and novel coding sequence) are confidently predicted to be protein-coding genes. 5' rapid amplification of cDNA ends (RACE) and RT-PCR were used to experimentally verify the initial annotation. Of the 420 coding loci tested, 229 RACE products have been sequenced. They supported 5' extensions of 30 loci and new splice variants in 50 loci. In addition, 46 loci without evidence for a coding sequence were validated, consisting of 31 novel and 15 putative transcripts. We assessed the comprehensiveness of the GENCODE annotation by attempting to validate all the predicted exon boundaries outside the GENCODE annotation. Out of 1,215 tested in a subset of the ENCODE regions, 14 novel exon pairs were validated, only two of them in intergenic regions. CONCLUSION: In total, 487 loci, of which 434 are coding, have been annotated as part of the GENCODE reference set available from the UCSC browser. Comparison of GENCODE annotation with RefSeq and ENSEMBL show only 40% of GENCODE exons are contained within the two sets, which is a reflection of the high number of alternative splice forms with unique exons annotated. Over 50% of coding loci have been experimentally verified by 5' RACE for EGASP and the GENCODE collaboration is continuing to refine its annotation of 1% human genome with the aid of experimental validation.