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Microdevice DNA forensics by the simple tandem repeat method.

We review recent experiments on DNA forensics by the simple tandem repeat (STR) method using a 16-lane micromachined device as the active separation element. Separations by linear polyacrylamide matrices show very high data quality metrics when evaluated with statistically significant data sets. Full 16-locus multiplexes are verified on the multilane system. Multi-donor mixed samples are studied in the context of the limits of the laser-induced fluorescence detector and data-reduction software. The microdevice appears to be posed to outperform current capillary arrays in terms of stability and, through specialized sample loading, in the interpretation of complex mixtures.

DNA↗

Expression profiling with oligonucleotide arrays: technologies and applications for neurobiology.

DNA microarrays have been used in applications ranging from the assignment of gene function to analytical uses in prognostics. However, the detection sensitivity, cross hybridization, and reproducibility of these arrays can affect experimental design and data interpretation. Moreover, several technologies are available for fabrication of oligonucleotide microarrays. We review these technologies and performance attributes and, with data sets generated from human brain RNA, present statistical tools and methods to analyze data quality and to mine and visualize the data. Our data show high reproducibility and should allow an investigator to discern biological and regional variability from differential expression. Although we have used brain RNA as a model system to illustrate some of these points, the oligonucleotide arrays and methods employed in this study can be used with cell lines, tissue sections, blood, and other fluids. To further demonstrate this point, we provide data generated from total RNA sample sizes of 200 ng.

Brain↗

Older driver crash rates in relation to type and quantity of travel.

It is a well-established phenomenon that, notwithstanding their overall good crash record, older drivers have a higher than average rate of involvement in injury crashes when the rate is calculated by dividing crash numbers by distance driven. It has been hypothesised that at least some of this higher crash rate is an artefact of the different nature of driving undertaken by many older drivers. For example, driving in congested urban environments provides more opportunities for collisions than driving the same distance on a motorway. However, there have been few opportunities to investigate this theory, as relevant data are difficult to acquire. High-quality data from the New Zealand Travel Survey (1997/1998) were combined with crash data to enable a statistical model to estimate the risk of driver groups under various driving conditions characterised by the type of road used, time of day, day of week, and season of year. Despite elevated crash risks per distance driven compared with middle-aged drivers for most road types, older drivers were as safe as any other age group when driving on motorways. Accounting for the fragility of older drivers and their passengers in the risk estimates for other road types, older drivers appeared to have daytime risks comparable to 25-year-olds and night-time risks as low as any other age group. The driving patterns of older drivers (in terms of when and where they drive) were estimated to minimize their risks in comparison with the driving patterns of other age groups. These results are of interest to both policy makers and transportation planners working against the background of inevitable increases in the number of older drivers as the population ages.

Accidents, Traffic↗

Hurricane effects on a shallow lake ecosystem and its response to a controlled manipulation of water level.

In order to reverse the damage to aquatic plant communities caused by multiple years of high water levels in Lake Okeechobee, Florida (U.S.), the Governing Board of the South Florida Water Management District (SFWMD) authorized a "managed recession" to substantially lower the surface elevation of the lake in spring 2000. The operation was intended to achieve lower water levels for at least 8 weeks during the summer growing season, and was predicted to result in a large-scale recovery of submerged vascular plants. We treated this operation as a whole ecosystem experiment, and assessed ecological responses using data from an existing network of water quality and submerged plant monitoring sites. As a result of large-scale discharges of water from the lake, coupled with losses to evaporation and to water supply deliveries to agriculture and other regional users, the lake surface elevation receded by approximately 1 m between April and June. Water depths in shoreline areas that historically supported submerged plant communities declined from near 1.5 m to below 0.5 m. Low water levels persisted for the entire summer. Despite shallow depths, the initial response (in June 2000) of submerged plants was very limited and water remained highly turbid (due at first to abiotic seston and later to phytoplankton blooms). Turbidity decreased in July and the biomass of plants increased. However, submerged plant biomass did not exceed levels observed during summer 1999 (when water depths were greater) until August. Furthermore, a vascular plant-dominated assemblage (Vallisneria, Potamogeton, and Hydrilla) that occurred in 1999 was replaced with a community of nearly 98% Chara spp. (a macro-alga) in 2000. Hence, the lake"s submerged plant community appeared to revert to an earlier successional stage despite what appeared to be better conditions for growth. To explain this unexpected response, we evaluated the impacts that Hurricane Irene may have had on the lake in the previous autumn. In mid-October 1999, this category 1 hurricane passed just to the south of the lake, with wind velocities over the lake surface reaching 90 km h(-1) at their peak. Output from a three-dimensional hydrodynamic/sediment transport model indicates that during the storm, current velocities in surface waters of the lake increased from near 5 cm s(-1) to as high as 100 cm s(-1). These strong velocities were associated with large-scale uplifting and horizontal transport of fine- grained sediments from the lake bottom. Water quality data collected after the storm confirmed that the hurricane resulted in lake-wide nutrient and suspended solids concentrations far in excess of those previously documented for a 10-year data set. These conditions persisted through the winter months and may have negatively impacted plants that remained in the lake at the end of the 1999 growing season. The results demonstrate that in shallow lakes, unpredictable external forces, such as hurricanes, can play a major role in ecosystem dynamics. In regions where these events are common (e.g., the tropics and subtropics), consideration should be given to how they might affect long-term lake management programs.

Animals↗

Advanced beamline automation for biological crystallography experiments.

An automated crystal-mounting/alignment system has been developed at Lawrence Berkeley National Laboratory and has been installed on three of the protein-crystallography experimental stations at the Advanced Light Source (ALS); it is currently being implemented at synchrotron crystallography beamlines at CHESS, NSLS and the APS. The benefits to using an automounter system include (i) optimization of the use of synchrotron beam time, (ii) facilitation of advanced data-collection techniques, (iii) collection of higher quality data, (iv) reduction of the risk to crystals and (v) exploration of systematic studies of experimental protocols. Developments on the next-generation automounter with improvements in robustness, automated alignment and sample tracking are under way, with an end-to-end data-flow process being developed to allow remote data collection and monitoring.

Automation↗

Analytical methods and database design: implications for transplant researchers, 2005.

Understanding how transplant data are collected is crucial to understanding how the data can be used. The collection and use of Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients (OPTN/SRTR) data continues to evolve, leading to improvements in data quality, timeliness and scope while reducing the data collection burden. Additional ascertainment of outcomes completes and validates existing data, although caveats remain for researchers. We also consider analytical issues related to cohort choice, timing of data submission, and transplant center variations in follow-up data. All of these points should be carefully considered when choosing cohorts and data sources for analysis. The second part of the article describes some of the statistical methods for outcome analysis employed by the SRTR. Issues of cohort and follow-up period selection lead into a discussion of outcome definitions, event ascertainment, censoring and covariate adjustment. We describe methods for computing unadjusted mortality rates and survival probabilities, and estimating covariate effects through regression modeling. The article concludes with a description of simulated allocation modeling, developed by the SRTR for comparing outcomes of proposed changes to national organ allocation policies.

Data Collection↗

Current and future therapeutic approaches in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a lethal form of idiopathic diffuse lung disorders for which no current treatment is effective. The aim of the present study was to systematically review the current status and novel therapies of IPF, with emphasis on controlled trials. The studies selected included randomised controlled trials using drugs alone and/or in combination for the treatment of adults with IPF and meta-analyses, published in English. Abstracts of identified articles were retrieved and articles possibly fulfilling inclusion criteria were retrieved in full. Two reviewers independently assessed trial quality if there were any included studies. Data quality was based on place of publication and relevance to clinical care. There is a lack of good-quality studies regarding the effectiveness of the most used drugs, including corticosteroids and noncorticosteroid immunosuppressive agents. Oral corticosteroids are the usual treatment. Other therapies either alone or in combination with corticosteroids are widely used, including azathioprine, cyclophosphamide and colchicine. Interestingly, clinical trials with novel drugs, mainly antifibrotic, anticytokine and immunoregulatory, are currently being investigated in various trial phases. In conclusion, at present, there are no evidence-based therapies for idiopathic pulmonary fibrosis. Further controlled studies are warranted to improve the evidence base for clinical practice.

Clinical Trials as Topic↗

Evaluation of mercury in urine as an indicator of exposure to low levels of mercury vapor.

We conducted a pooled analysis to investigate the relationship between exposure to elemental mercury in air and resulting urinary mercury levels, specifically at lower air levels relevant for environmental exposures and public health goals (i.e., < 50 microg/m3 down to 1.0 microg/m3). Ten studies reporting paired air and urine mercury data (149 samples total) met criteria for data quality and sufficiency. The log-transformed data set showed a strong correlation between mercury in air and in urine (r = 0.774), although the relationship was best fit by a series of parallel lines with different intercepts for each study R2 = 0.807). Predicted ratios of air to urine mercury levels at 50 microg/m3 air concentration ranged from 1:1 to 1:3, based on the regression line for the studies. Toward the lower end of the data set (i.e., 10 microg/m3), predicted urinary mercury levels encompassed two distinct ranges: values on the order of 20 microg/L and 30-60 microg/L. Extrapolation to 1 microg/m3 resulted in predicted urinary levels of 4-5 and 6-13 microg/L. Higher predicted levels were associated with use of static area air samplers by some studies rather than more accurate personal air samplers. Urinary mercury predictions based primarily on personal air samplers at 1 and 10 microg/m3 are consistent with reported mean (4 microg/L) and upper-bound (20 microg/L) background levels, respectively. Thus, although mercury levels in air and urine are correlated below 50 microg/m3, the impact of airborne mercury levels below 10 microg/m3 is likely to be indistinguishable from background urinary mercury levels.

Biomarkers↗

Excess maternal transmission of type 2 diabetes. The Northern California Kaiser Permanente Diabetes Registry.

OBJECTIVE: To assess excess maternal transmission of type 2 diabetes in a multiethnic cohort. Previous studies have reported higher prevalence of diabetes among mothers of probands with type 2 diabetes than among fathers. This analysis is vulnerable to biases, and this pattern has not been observed in all populations or races. RESEARCH DESIGN AND METHODS: We assessed evidence for excess maternal transmission among 42,533 survey respondents with type 2 diabetes (probands) by calculating the prevalence of diabetes in their siblings and offspring. To assess data quality, we evaluated completeness of family history data provided. Accuracy of family information reported by probands was also evaluated by comparing survey responses in a subsample of 206 probands with family histories modified after further interviews with relatives. RESULTS: Siblings (n = 60,532) of probands with affected mothers had a greater prevalence of diabetes (20%) than those with affected fathers (17%) (P < 0.001 for adjusted odds ratios). Prevalence of diabetes was higher among the offspring (n = 72,087) of female (3.4%) versus male (2.2%) probands (P < 0.001 for adjusted odds ratios). These patterns were evident in all races and both sexes; however, the effect size was clinically insignificant in African-Americans and male offspring. In general, probands provided more complete data about diabetes status for the maternal arm of the pedigree than the paternal arm. Completeness of knowledge was not related to proband sex, but was related to education and race, and inversely to age. Accuracy of proband-reported family history was consistently good (kappa statistics generally > 0.70). CONCLUSIONS: Excess maternal transmission was observed in all races and both sexes, although the size of the excess was negligible in African-Americans and male offspring. Potential reporting and censoring biases are discussed.

Adolescent↗

The roles of bone mineral density, bone turnover, and other properties in reducing fracture risk during antiresorptive therapy.

Osteoporosis is a skeletal disorder characterized by compromised bone strength and increased risk of fracture. Properties related to bone strength include rate of bone turnover, bone mineral density, geometry, microarchitecture, and mean degree of mineralization. These properties (with or without bone density) are sometimes collectively referred to as bone quality. Antiresorptive agents may reduce fracture risk by several separate but interrelated effects on these individual properties. For example, antiresorptive agents have been reported to reduce bone turnover, stabilize or increase bone density, preserve or improve microarchitecture, reduce the number or size of resorption sites, and improve mineralization. Although changes in bone architecture and mineralization are not currently measurable in clinical practice, bone turnover is assessed easily in vivo and affects the other bone properties. Moreover, antiresorptive therapies that produce larger decreases in bone turnover markers together with larger increases in bone mineral density are associated with greater reductions in fracture risk, especially at sites primarily composed of cortical bone such as the hip. Reductions in fracture risk are the most convincing evidence of good bone quality. Data from well-designed randomized clinical trials with up to 10 years of continuous antiresorptive therapy have shown that certain antiresorptive agents effectively reduce fracture risk and (together with extensive preclinical data) suggest no deleterious effects on bone quality.

Bone Density↗

Overview of acrylamide monitoring databases.

Since high acrylamide levels in carbohydrate-rich food were reported in 2002, many research activities were started in order to gain knowledge on occurrence, formation, and prevention of this compound in food products. Among them, monitoring programs were conducted in many countries worldwide by official bodies as well as by the food industry. National and international bodies set up monitoring databases. In 2003, both the European Commission and the World Health Organization posted calls for data and placed their spreadsheets for the submission of data on the Web. The goal of the databases is to collect data for a reliable estimation of the exposure of consumers to acrylamide via the food chain. This paper describes the assessment of the data quality and outlines the composition of the data in the 2 databases, to date.

Acrylamide↗

Practical ethics. What would you do?

Your hospital receives a $1 million donation from a tobacco company executive. The money will be used to make a much-needed technology upgrade that will enable the hospital to report quality data, as well as improve the overall quality of care, a high priority in your community. The donation is from a private individual, but antismoking activists in the community are protesting the gift. The situation is generating a lot of bad publicity for the hospital and is beginning to overshadow recent positive news about improved care. Do you keep the money?

Conflict of Interest↗

The 10 essential activities of the quality assurance unit.

It is certainly my pleasure to be here today. Several months ago, Pat Pomerleau invited me to be on your program. At the time, I had no idea that I would be speaking as Paul Lepore, private citizen, rather than Paul Lepore, regulator and bureaucrat. However, the Food and Drug Administration (FDA) made me an offer I could not refuse and, upon considerable thought, I retired effective September 30, 1994. Immediately, I called Pat for advice on how to deal with my planned presentation before you. Graciously, she said that she did not believe that I would forget all I knew about Good Laboratory Practice (GLP) over 1 weekend and that the Society would love to have me anyway. Today, I intend to discuss the 10 essential activities of a properly functioning quality assurance Unit (GAU). I will summarize the importance of records and documentation to the unit and I will close with some comments on achieving regulatory compliance. My remarks are intended to emphasize that an effective, active quality assurance unit is crucial for ensuring data quality, and that attention paid to day-to-day quality assurance activities will foster regulatory compliance.

Facility Regulation and Control↗

Taste and smell losses in normal aging and disease.

OBJECTIVE: To review the scientific literature on the alterations in the senses of taste and smell in the elderly, including causes, diagnosis, prognosis, and treatment. DATA SOURCES: Original reports and reviews obtained through MEDLINE searches from 1966 through June 1997 using the MeSH headings of "taste," "taste buds," "taste disorders," "taste thresholds," "smell," "odors," "aged," and "aging." Articles frequently cited in reference lists were also included. STUDY SELECTION: All articles were reviewed, tabulated, and summarized. DATA EXTRACTION: Criteria for extraction included data quality and validity, statistical treatment of the data, venue of publication, and relevance to clinical care. CONCLUSION: Losses of taste and smell are common in the elderly and result from normal aging, certain disease states (especially Alzheimer disease), medications, surgical interventions, and environmental exposure. Deficits in these chemical senses cannot only reduce the pleasure and comfort from food, but represent risk factors for nutritional and immune deficiencies as well as adherence to specific dietary regimens. Chemosensory decrements can lead to food poisoning or overexposure to environmentally hazardous chemicals that are otherwise detectable by taste and smell. Use of flavor-enhanced food can increase enjoyment of food and have a positive effect on food intake and immune status.

Aged↗

Profiling providers on use of adjuvant chemotherapy by combining cancer registry and medical record data.

PURPOSE: Treatment information collected by cancer registries can be used to monitor the provision of guideline-recommended chemotherapy to colorectal cancer patients. Incomplete information may bias comparisons of these rates. We developed statistical methods that combine data from a registry and physicians' records to assess hospital quality. DATA: From California Cancer Registry data, we selected all patients (n=12,594) newly diagnosed with stage III colon cancer or stage II or III rectal cancer from 428 hospitals during the years 1994 to 1998. To assess rates and predictors of underreporting of chemotherapy, we surveyed physicians treating 1449 of these patients from 98 hospitals during the years 1996 to 1997. METHODS: Using Bayesian statistical models, we imputed unobserved treatments. We studied the impact of underreporting on provider profiling by comparing rankings, estimates, and credible intervals based only on registry data to those incorporating physician survey data. RESULTS: Analyses that account for incompleteness of reporting yielded wider credible intervals for provider profiles than those that ignored such incompleteness. Among the 109 (25%) hospitals in the highest quartile of chemotherapy rates according to the registry data, 16 were not so classified when incomplete reporting was taken into account. With the more comprehensive model, 12 hospitals could be identified that ranked in the top quartile with probability>0.90. CONCLUSION: Estimates of adjusted hospital chemotherapy rates based solely on cancer registry data overstate the precision of assessments of hospital quality. Using additional information from a physician survey and applying rigorous statistical models, better inferences can be drawn about provider quality.

Adolescent↗

Centralized medical monitoring in phase III clinical trials: the National Surgical Adjuvant Breast and Bowel Project (NSABP) experience.

BACKGROUND: There is a need for data quality assurance procedures in phase III cancer trials. At the National Surgical Adjuvant Breast and Bowel Project (NSABP) 'real-time' systems have been developed for quality assurance and study monitoring: (1) manual review and triage of data forms by data managers at the time of submission; (2) computerized edit checking of all submitted data forms; (3) systematic review of eligibility, treatment compliance and toxicity in the first 100 patients of a new protocol; (4) prospective centralized medical review of all reported serious adverse events, treatment failures, second primary cancers and deaths; (5) quarterly review and approval of study summary data files by project statistician; and (6) on-site auditing. PURPOSE: To assess the utility of an additional final comprehensive review of all patient records to confirm eligibility, disease status and vital status prior to manuscript submission. METHODS: Four phase III NSABP studies, which had been monitored using the triage-based quality assurance program described above, were selected for analysis (n = 7972). Charts for 5965 patients were identified that had not been previously medically reviewed for protocol events of recurrence, second primary cancer or death. Submitted source documents and data forms of these 5965 NSABP patient records underwent medical review to verify patient eligibility, disease status and vital status. RESULTS: This final comprehensive review found no additional treatment failures or deaths, identified seven additional cases of ineligibility, was time-intensive requiring enormous use of expensive resources, and was therefore judged not to add significantly to the integrity of the database. LIMITATIONS: Our findings are influenced by the procedures the NSABP employs for quality assurance and study monitoring for Phase III clinical trials and may have limited generalizability to other settings. CONCLUSION: In the presence of multiple quality assurance and data monitoring systems, the rare discrepancies found between the data forms and source documentation does not support the routine use of a final comprehensive chart review for phase III trials at the NSABP Biostatistical Center.

Breast Neoplasms↗

[The quality of hospital discharge data in the Venice general hospital: methods and evaluation in the development of the Diagnosis Related Groups System].

In this paper the A.A. illustrate the methodology and development of an evaluation programme of hospital discharge medical records data base quality to implement the DRG system. The work was organized into three phases: the first to analyze the quality base level, the second to sensitize the medical doctors to SDO coding through a Medical Managers Department tutorial action; the third to measure the results of a random sample. The A.A. realized a raise in the compilation level between the two analises, particularly as regards the trascription of surgical procedures and/or diagnostic and therapeutic procedures passed from 39.9% at 64.1%, and a greater correctness in the primary diagnosis coding passed from 69.9% at 83.3% and in the surgical procedures and/or diagnostic and therapeutic procedures (coding) passed from 88.7% at 93.7%.

Electronic Data Processing↗

Listening to seniors: successful approaches to data collection and program development.

This paper provides guidelines for high quality data collection with community-residing older adults with illustrations drawn from the authors' practice. A mixed-method approach is described as a means to obtain the highest quality information from the sample. This approach combines focus groups and interviews along with mailed, closed-ended surveys to access both the "depth" of the seniors' responses as well as the "breadth" of responses; that is, the qualitative aspects provide the opportunity to identify and define relevant issues in the voices of respondents, while mailed surveys provide the kind of coverage necessary to make accurate predictions to the larger population of community-residing seniors.

Activities of Daily Living↗