Qualitative analysis of barriers and facilitators encountered by HIV patients in an ART adherence programme.

Background Medication adherence is a complex, dynamic and changing behaviour that is affected by a variety of factors, including the patient's beliefs and life circumstances. Studies have highlighted barriers to medication adherence (e.g., unmanaged side effects or a lack of social support), as well as facilitators of medication adherence (e.g., technical simplicity of treatment and psychological acceptance of the disease). Since August 2004, in Lausanne (Switzerland), physicians have referred patients who are either experiencing or are at risk of experiencing problems with their HIV antiretroviral treatment (ART) to a routine interdisciplinary ART adherence programme. This programme consists of multifactorial intervention including electronic drug monitoring (MEMS(TM)). Objective This study's objective was to identify the barriers and facilitators encountered by HIV patients with suboptimal medication adherence (≤90 % adherence over the study period). Setting The community pharmacy of the Department of Ambulatory Care and Community Medicine in Lausanne (Switzerland). Method The study consisted of a retrospective, qualitative, thematic content analysis of pharmacists' notes that were taken during semi-structured interviews with patients and conducted as part of the ART adherence programme between August 2004 and May 2008. Main outcome measure Barriers and facilitators encountered by HIV patients. Results Barriers to and facilitators of adherence were identified for the 17 included patients. These factors fell into three main categories: (1) cognitive, emotional and motivational; (2) environmental, organisational and social; and (3) treatment and disease. Conclusion The pharmacists' notes revealed that diverse barriers and facilitators were discussed during medication adherence interviews. Indeed, the results showed that the 17 non-adherent patients encountered barriers and benefited from facilitators. Therefore, pharmacists should inquire about all factors, regardless of whether they have a negative or a positive impact on medication adherence, and should consider all dimensions of patient adherence. The simultaneous strengthening of facilitators and better management of barriers may allow healthcare providers to tailor care to a patient's specific needs and support each individual patient in improving his medication-related behaviour.

Meta-analysis of heat- and chemically upregulated chaperone genes in plant and human cells.

Molecular chaperones are central to cellular protein homeostasis. In mammals, protein misfolding diseases and aging cause inflammation and progressive tissue loss, in correlation with the accumulation of toxic protein aggregates and the defective expression of chaperone genes. Bacteria and non-diseased, non-aged eukaryotic cells effectively respond to heat shock by inducing the accumulation of heat-shock proteins (HSPs), many of which molecular chaperones involved in protein homeostasis, in reducing stress damages and promoting cellular recovery and thermotolerance. We performed a meta-analysis of published microarray data and compared expression profiles of HSP genes from mammalian and plant cells in response to heat or isothermal treatments with drugs. The differences and overlaps between HSP and chaperone genes were analyzed, and expression patterns were clustered and organized in a network. HSPs and chaperones only partly overlapped. Heat-shock induced a subset of chaperones primarily targeted to the cytoplasm and organelles but not to the endoplasmic reticulum, which organized into a network with a central core of Hsp90s, Hsp70s, and sHSPs. Heat was best mimicked by isothermal treatments with Hsp90 inhibitors, whereas less toxic drugs, some of which non-steroidal anti-inflammatory drugs, weakly expressed different subsets of Hsp chaperones. This type of analysis may uncover new HSP-inducing drugs to improve protein homeostasis in misfolding and aging diseases.

Magnetic resonance imaging correlates of first-episode psychosis in young adult male patients: combined analysis of grey and white matter.

Background: Several patterns of grey and white matter changes have been separately described in young adults with first-episode psychosis. Concomitant investigation of grey and white matter densities in patients with first-episode psychosis without other psychiatric comorbidities that include all relevant imaging markers could provide clues to the neurodevelopmental hypothesis in schizophrenia. Methods: We recruited patients with first-episode psychosis diagnosed according to the DSM-IV-TR and matched controls. All participants underwent magnetic resonance imaging (MRI). Voxel-based morphometry (VBM) analysis and mean diffusivity voxel-based analysis (VBA) were used for grey matter data. Fractional anisotropy and axial, radial and mean diffusivity were analyzed using tract-based spatial statistics (TBSS) for white matter data. Results: We included 15 patients and 16 controls. The mean diffusivity VBA showed significantly greater mean diffusivity in the first-episode psychosis than in the control group in the lingual gyrus bilaterally, the occipital fusiform gyrus bilaterally, the right lateral occipital gyrus and the right inferior temporal gyrus. Moreover, the TBSS analysis revealed a lower fractional anisotropy in the first-episode psychosis than in the control group in the genu of the corpus callosum, minor forceps, corticospinal tract, right superior longitudinal fasciculus, left middle cerebellar peduncle, left inferior longitudinal fasciculus and the posterior part of the fronto-occipital fasciculus. This analysis also revealed greater radial diffusivity in the first-episode psychosis than in the control group in the right corticospinal tract, right superior longitudinal fasciculus and left middle cerebellar peduncle. Limitations: The modest sample size and the absence of women in our series could limit the impact of our results. Conclusion: Our results highlight the structural vulnerability of grey matter in posterior areas of the brain among young adult male patients with first-episode psychosis. Moreover, the concomitant greater radial diffusivity within several regions already revealed by the fractional anisotropy analysis supports the idea of a late myelination in patients with first-episode psychosis.

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.

Pseudogenes in the ENCODE regions: consensus annotation, analysis of transcription, and evolution.

Arising from either retrotransposition or genomic duplication of functional genes, pseudogenes are "genomic fossils" valuable for exploring the dynamics and evolution of genes and genomes. Pseudogene identification is an important problem in computational genomics, and is also critical for obtaining an accurate picture of a genome's structure and function. However, no consensus computational scheme for defining and detecting pseudogenes has been developed thus far. As part of the ENCyclopedia Of DNA Elements (ENCODE) project, we have compared several distinct pseudogene annotation strategies and found that different approaches and parameters often resulted in rather distinct sets of pseudogenes. We subsequently developed a consensus approach for annotating pseudogenes (derived from protein coding genes) in the ENCODE regions, resulting in 201 pseudogenes, two-thirds of which originated from retrotransposition. A survey of orthologs for these pseudogenes in 28 vertebrate genomes showed that a significant fraction ( approximately 80%) of the processed pseudogenes are primate-specific sequences, highlighting the increasing retrotransposition activity in primates. Analysis of sequence conservation and variation also demonstrated that most pseudogenes evolve neutrally, and processed pseudogenes appear to have lost their coding potential immediately or soon after their emergence. In order to explore the functional implication of pseudogene prevalence, we have extensively examined the transcriptional activity of the ENCODE pseudogenes. We performed systematic series of pseudogene-specific RACE analyses. These, together with complementary evidence derived from tiling microarrays and high throughput sequencing, demonstrated that at least a fifth of the 201 pseudogenes are transcribed in one or more cell lines or tissues.

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.