Photodynamic Diagnosis of Non-muscle-invasive Bladder Cancer with Hexaminolevulinate Cystoscopy: A Meta-analysis of Detection and Recurrence Based on Raw Data.

BACKGROUND: Studies on hexaminolevulinate (HAL) cystoscopy report improved detection of bladder tumours. However, recent meta-analyses report conflicting effects on recurrence. OBJECTIVE: To assess available clinical data for blue light (BL) HAL cystoscopy on the detection of Ta/T1 and carcinoma in situ (CIS) tumours, and on tumour recurrence. DESIGN, SETTING, AND PARTICIPANTS: This meta-analysis reviewed raw data from prospective studies on 1345 patients with known or suspected non-muscle-invasive bladder cancer (NMIBC). INTERVENTION: A single application of HAL cystoscopy was used as an adjunct to white light (WL) cystoscopy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We studied the detection of NMIBC (intention to treat [ITT]: n=831; six studies) and recurrence (per protocol: n=634; three studies) up to 1 yr. DerSimonian and Laird's random-effects model was used to obtain pooled relative risks (RRs) and associated 95% confidence intervals (CIs) for outcomes for detection. RESULTS AND LIMITATIONS: BL cystoscopy detected significantly more Ta tumours (14.7%; p<0.001; odds ratio [OR]: 4.898; 95% CI, 1.937-12.390) and CIS lesions (40.8%; p<0.001; OR: 12.372; 95% CI, 6.343-24.133) than WL. There were 24.9% patients with at least one additional Ta/T1 tumour seen with BL (p<0.001), significant also in patients with primary (20.7%; p<0.001) and recurrent cancer (27.7%; p<0.001), and in patients at high risk (27.0%; p<0.001) and intermediate risk (35.7%; p=0.004). In 26.7% of patients, CIS was detected only by BL (p<0.001) and was also significant in patients with primary (28.0%; p<0.001) and recurrent cancer (25.0%; p<0.001). Recurrence rates up to 12 mo were significantly lower overall with BL, 34.5% versus 45.4% (p=0.006; RR: 0.761 [0.627-0.924]), and lower in patients with T1 or CIS (p=0.052; RR: 0.696 [0.482-1.003]), Ta (p=0.040; RR: 0.804 [0.653-0.991]), and in high-risk (p=0.050) and low-risk (p=0.029) subgroups. Some subgroups had too few patients to allow statistically meaningful analysis. Heterogeneity was minimised by the statistical analysis method used. CONCLUSIONS: This meta-analysis confirms that HAL BL cystoscopy significantly improves the detection of bladder tumours leading to a reduction of recurrence at 9-12 mo. The benefit is independent of the level of risk and is evident in patients with Ta, T1, CIS, primary, and recurrent cancer.

Genotype-phenotype analysis of Jervell and Lange-Nielsen syndrome in six families from Saudi Arabia.

We sought to explore the genotype-phenotype of Jervell and Lange-Nielsen syndrome (JLNS) patients in Saudi Arabia. We have also assessed the plausible effect of consanguinity into the pathology of JLNS. Six families with at least one JLNS-affected member attended our clinic between 2011 and 2013. Retrospective and prospective clinical data were collected and genetic investigation was performed. Pathogenic mutations in the KCNQ1 gene were detected in all JLNS patients. The homozygous mutations detected were Leu273Phe, Asp202Asn, Ile567Thr, and c.1486_1487delCT and compound heterozygous mutations were c.820_ 830del and c.1251+1G>T. All living JLNS patients except one had a QTc of >500 ms and a history of recurrent syncope. β-Blockers abolished the cardiac-related events in all patients except two siblings with homozygous Ile567Thr mutation. Four of the six mutations were originally reported in autosomal dominant long QT syndrome (LQTS) patients. Eighty percent of the heterozygote mutation carriers showed prolongation of QTc, but majority of these reported no symptoms attributable to arrhythmias. Mutations detected in this study will be advantageous in tribe and region-specific cascade screening of LQTS in Saudi Arabia.

A randomised controlled clinical trial and gait analysis of fixed- and mobile-bearing total knee replacements with a five-year follow-up.

This study compared the outcome of total knee replacement (TKR) in adult patients with fixed- and mobile-bearing prostheses during the first post-operative year and at five years' follow-up, using gait parameters as a new objective measure. This double-blind randomised controlled clinical trial included 55 patients with mobile-bearing (n = 26) and fixed-bearing (n = 29) prostheses of the same design, evaluated pre-operatively and post-operatively at six weeks, three months, six months, one year and five years. Each participant undertook two walking trials of 30 m and completed the EuroQol questionnaire, Western Ontario and McMaster Universities osteoarthritis index, Knee Society score, and visual analogue scales for pain and stiffness. Gait analysis was performed using five miniature angular rate sensors mounted on the trunk (sacrum), each thigh and calf. The study population was divided into two groups according to age (≤ 70 years versus > 70 years). Improvements in most gait parameters at five years' follow-up were greater for fixed-bearing TKRs in older patients (> 70 years), and greater for mobile-bearing TKRs in younger patients (≤ 70 years). These findings should be confirmed by an extended age controlled study, as the ideal choice of prosthesis might depend on the age of the patient at the time of surgery.

Image Analysis of PCC and AC Pavements Using SEM Images, HR-346, 1994

The major objective of this work was to evaluate the potential of image analysis for characterizing air voids in Portland cement Concrete (PCC), voids and constituents of Asphalt Concrete (AC) and aggregate gradation in AC. Images for analysis were obtained from a scanning electron microscope (SEM). Sample preparation techniques are presented that enhance signal differences so that backscattered electron (BSE) imaging, which is sensitive to atomic number changes, can be effectively employed. Work with PCC and AC pavement core samples has shown that the low vacuum scanning electron microscope (LVSEM) is better suited towards rapid analyses. The conventional high vacuum SEM can also be used for AC and PCC analyses but some distortion within the sample matrix will occur. Images with improved resolution can be obtained from scanning electron microscope (SEM) backscatter electron (BSE) micrographs. In a BSE image, voids filled with barium sulfate/resin yield excellent contrast in both PCC and AC. There is a good correlation between percent of air by image analysis and linear traverse.

Total Cost of Transportation Analysis of Road and Highway Issues, HR-388, 2002

In the administration, planning, design, and maintenance of road systems, transportation professionals often need to choose between alternatives, justify decisions, evaluate tradeoffs, determine how much to spend, set priorities, assess how well the network meets traveler needs, and communicate the basis for their actions to others. A variety of technical guidelines, tools, and methods have been developed to help with these activities. Such work aids include design criteria guidelines, design exception analysis methods, needs studies, revenue allocation schemes, regional planning guides, designation of minimum standards, sufficiency ratings, management systems, point based systems to determine eligibility for paving, functional classification, and bridge ratings. While such tools play valuable roles, they also manifest a number of deficiencies and are poorly integrated. Design guides tell what solutions MAY be used, they aren't oriented towards helping find which one SHOULD be used. Design exception methods help justify deviation from design guide requirements but omit consideration of important factors. Resource distribution is too often based on dividing up what's available rather than helping determine how much should be spent. Point systems serve well as procedural tools but are employed primarily to justify decisions that have already been made. In addition, the tools aren't very scalable: a system level method of analysis seldom works at the project level and vice versa. In conjunction with the issues cited above, the operation and financing of the road and highway system is often the subject of criticisms that raise fundamental questions: What is the best way to determine how much money should be spent on a city or a county's road network? Is the size and quality of the rural road system appropriate? Is too much or too little money spent on road work? What parts of the system should be upgraded and in what sequence? Do truckers receive a hidden subsidy from other motorists? Do transportation professions evaluate road situations from too narrow of a perspective? In considering the issues and questions the author concluded that it would be of value if one could identify and develop a new method that would overcome the shortcomings of existing methods, be scalable, be capable of being understood by the general public, and utilize a broad viewpoint. After trying out a number of concepts, it appeared that a good approach would be to view the road network as a sub-component of a much larger system that also includes vehicles, people, goods-in-transit, and all the ancillary items needed to make the system function. Highway investment decisions could then be made on the basis of how they affect the total cost of operating the total system. A concept, named the "Total Cost of Transportation" method, was then developed and tested. The concept rests on four key principles: 1) that roads are but one sub-system of a much larger 'Road Based Transportation System', 2) that the size and activity level of the overall system are determined by market forces, 3) that the sum of everything expended, consumed, given up, or permanently reserved in building the system and generating the activity that results from the market forces represents the total cost of transportation, and 4) that the economic purpose of making road improvements is to minimize that total cost. To test the practical value of the theory, a special database and spreadsheet model of Iowa's county road network was developed. This involved creating a physical model to represent the size, characteristics, activity levels, and the rates at which the activities take place, developing a companion economic cost model, then using the two in tandem to explore a variety of issues. Ultimately, the theory and model proved capable of being used in full system, partial system, single segment, project, and general design guide levels of analysis. The method appeared to be capable of remedying many of the existing work method defects and to answer society's transportation questions from a new perspective.

Total Cost of Transportation Analysis of Road and Highway Issues, HR-388, Supplement, 2002

Supplement to HR-388 - "Total Cost of Transportation Analysis of Road and Highway Issues"

Total Cost of Transportation Analysis of Road and Highway Issues, TR-477, Phase 2, 2003

A prior project, HR-388, (which was entitled "Total Cost of Transportation analysis of road and highway issues"), explored the use of a total economic cost basis for evaluation of road based transportation issues. It was conducted as a proof-of-concept effort between 1996 and 2002, with the final report presented in May 2002. TR-477 rebuilt the analytical model using current data, then performed general, system level, county level, and road segment level analyses. The results are presented herein and will be distributed to all county engineers for information and local use.

Total Cost of Transportation Analysis of Road and Highway Issues, TR-477, Phase 2 Supplement, 2003

Please see TR-477 Phase 2 Final Report -- http://publications.iowa.gov/id/eprint/20041

Faunistic analysis of Carabidae and Staphylinidae (Coleoptera) in five agroecosystems in northeastern São Paulo state, Brazil

The objective of this study was to determined species composition and community structure of Carabidae and Staphylinidae in five areas of forest fragment and soybean/corn crops or orange orchard, from December 2004 to May 2007. Beetles were captured in pitfall traps distributed along two parallel transects of 200 m in length, placed across crop land/forest boundary fragment, with 100 m each. The Shannon-Wiener diversity and evenness indexes and Morisita similarity index were calculated. The carabids Abaris basistriatus Chaudoir, Calosoma granulatum Perty, Megacephala brasiliensis Kirby, Odontochila nodicornis (Dejean) and Selenophorus seriatoporus Putzeys. are dominant and are widely distributed in northeastern São Paulo state, Brazil. Point-scale species diversity was greatest at the transition between forest fragment and cultivated area. The carabid and staphylinid communities of the forest fragment were more similar to the community of orange orchard than that of soybean/corn crops.

Quantitative genetic analysis of methylxanthines and phenolic compounds in mate progenies

The objective of this work was to determine the contents of methylxanthines, caffeine and theobromine, and phenolic compounds, chlorogenic and caffeic acids, in 51 mate progenies (half-sib families) and estimate the heritability of genetic parameters. Mate progenies were from five Brazilian municipalities: Pinhão, Ivaí, Barão de Cotegipe, Quedas do Iguaçu, and Cascavel. The progenies were grown in the Ivaí locality. The contents of the compounds were obtained by high performance liquid chromatography (HPLC). The estimation of genetic parameters by the restricted maximum likelihood (REML) and the prediction of genotypic values via best linear unbiased prediction (BLUP) were obtained by the Selegen - REML/BLUP software. Caffeine (0.248-1.663%) and theobromine (0.106-0.807%) contents were significantly different (p<0.05) depending on the region of origin, with high individual heritability (ĥ²>0.5). The two different progeny groups determined for chlorogenic (1.365-2.281%) and caffeic (0.027-0.037%) acid contents were not significantly different (p<0.05) depending on the locality of origin. Individual heritability values were low to medium for chlorogenic (ĥ²<0.4) and caffeic acid (ĥ²<0.3). The content of the compounds and the values of genetic parameters could support breeding programs for mate.

Cross-validation of methods used for analysis of MTBE and other gasoline components in groundwater.

Head space gas chromatography with flame-ionization detection (HS-GC-FID), ancl purge and trap gas chromatography-mass spectrometry (P&T-GC-MS) have been used to determine methyl-tert-butyl ether (MTBE) and benzene, toluene, and the ylenes (BTEX) in groundwater. In the work discussed in this paper measures of quality, e.g. recovery (94-111%), precision (4.6 - 12.2%), limits of detection (0.3 - 5.7 I~g L 1 for HS and 0.001 I~g L 1 for PT), and robust-ness, for both methods were compared. In addition, for purposes of comparison, groundwater samples from areas suffering from odor problems because of fuel spillage and tank leakage were analyzed by use of both techniques. For high concentration levels there was good correlation between results from both methods.

On-line desorption of dried blood spots coupled to hydrophilic interaction/reversed-phase LC/MS/MS system for the simultaneous analysis of drugs and their polar metabolites.

An assay for the simultaneous analysis of pharmaceutical compounds and their metabolites from micro-whole blood samples (i.e. 5 microL) was developed using an on-line dried blood spot (on-line DBS) device coupled with hydrophilic interaction/reversed-phase (HILIC/RP) LC/MS/MS. Filter paper is directly integrated to the LC device using a homemade inox desorption cell. Without any sample pretreatment, analytes are desorbed from the paper towards an automated system of valves linking a zwitterionic-HILIC column to an RP C18 column. In the same run, the polar fraction is separated by the zwitterionic-HILIC column while the non-polar fraction is eluted on the RP C18. Both fractions are detected by IT-MS operating in full scan mode for the survey scan and in product ion mode for the dependant scan using an ESI source. The procedure was evaluated by the simultaneous qualitative analysis of four probes and their relative phase I and II metabolites spiked in whole blood. In addition, the method was successfully applied to the in vivo monitoring of buprenorphine metabolism after the administration of an intraperitoneal injection of 30 mg/kg on adult female Wistar rat.

Functional analysis of cis- and trans-acting elements of the Candida albicans CDR2 promoter with a novel promoter reporter system.

Azole resistance in Candida albicans can be mediated by the upregulation of the ATP binding cassette transporter genes CDR1 and CDR2. Both genes are regulated by a cis-acting element called the drug-responsive element (DRE), with the consensus sequence 5'-CGGAWATCGGATATTTTTTT-3', and the transcription factor Tac1p. In order to analyze in detail the DRE sequence necessary for the regulation of CDR1 and CDR2 and properties of TAC1 alleles, a one-hybrid system was designed. This system is based on a P((CDR2))-HIS3 reporter system in which complementation of histidine auxotrophy can be monitored by activation of the reporter system by CDR2-inducing drugs such as estradiol. Our results show that most of the modifications within the DRE, but especially at the level of CGG triplets, strongly reduce CDR2 expression. The CDR2 DRE was replaced by putative DREs deduced from promoters of coregulated genes (CDR1, RTA3, and IFU5). Surprisingly, even if Tac1p was able to bind these putative DREs, as shown by chromatin immunoprecipitation, those from RTA3 and IFU5 did not functionally replace the CDR2 DRE. The one-hybrid system was also used for the identification of gain-of-function (GOF) mutations either in TAC1 alleles from clinical C. albicans isolates or inserted in TAC1 wild-type alleles by random mutagenesis. In all, 17 different GOF mutations were identified at 13 distinct positions. Five of them (G980E, N972D, A736V, T225A, and N977D) have already been described in clinical isolates, and four others (G980W, A736T, N972S, and N972I) occurred at already-described positions, thus suggesting that GOF mutations can occur in a limited number of positions in Tac1p. In conclusion, the one-hybrid system developed here is rapid and powerful and can be used for characterization of cis- and trans-acting elements in C. albicans.

Average performance analysis of circular and hyperbolic geolocation

A comparative performance analysis of four geolocation methods in terms of their theoretical root mean square positioning errors is provided. Comparison is established in two different ways: strict and average. In the strict type, methods are examined for a particular geometric configuration of base stations(BSs) with respect to mobile position, which determines a givennoise profile affecting the respective time-of-arrival (TOA) or timedifference-of-arrival (TDOA) estimates. In the average type, methodsare evaluated in terms of the expected covariance matrix ofthe position error over an ensemble of random geometries, so thatcomparison is geometry independent. Exact semianalytical equationsand associated lower bounds (depending solely on the noiseprofile) are obtained for the average covariance matrix of the positionerror in terms of the so-called information matrix specific toeach geolocation method. Statistical channel models inferred fromfield trials are used to define realistic prior probabilities for therandom geometries. A final evaluation provides extensive resultsrelating the expected position error to channel model parametersand the number of base stations.