A Fabry-Pérot interferometer with wire-grid polarizers as beamsplitters at terahertz frequencies.

The design of a compact Fabry-Pérot interferometer (FPi) and results of the experimental studies carried out using the device are presented. Our FPi uses freestanding wire-grid polarizers (WGPs) as beamsplitters and is suitable for use at terahertz (THz) frequencies. The FPi was studied at the LUCX facility, KEK, Japan, and an 8 MeV linear electron accelerator was used to generate coherent Smith-Purcell radiation. The FPi was designed to be easy to align and reposition for experiments at linear accelerator facilities. All of the components used were required to have a flat or well understood frequency response in the THz range. The performance of the FPi with WGPs was compared to that of a Michelson interferometer and the FPi is seen to perform well. The effectiveness of the beamsplitters used in the FPi is also investigated. Measurements made with the FPi using WGPs, the preferred beamsplitters, are compared to measurements made with the FPi using silicon wafers as alternative beamsplitters. The FPi performs well with both types of beamsplitter in the frequency range used (0.3-0.5 THz). The successful measurements taken with the FPi demonstrate a compact and adaptable interferometer that is capable of analyzing THz radiation over a broad frequency range. The scheme is particularly well suited for polarization studies of THz radiation produced in an accelerator environment.

VHA Corporate Data Warehouse height and weight data: opportunities and challenges for health services research.

Within the Veterans Health Administration (VHA), anthropometric measurements entered into the electronic medical record are stored in local information systems, the national Corporate Data Warehouse (CDW), and in some regional data warehouses. This article describes efforts to examine the quality of weight and height data within the CDW and to compare CDW data with data from warehouses maintained by several of VHA's regional groupings of healthcare facilities (Veterans Integrated Service Networks [VISNs]). We found significantly fewer recorded heights than weights in both the CDW and VISN data sources. In spite of occasional anomalies, the concordance in the number and value of records in the CDW and the VISN warehouses was generally 97% to 99% or greater. Implausible variation in same-day and same-year heights and weights was noted, suggesting measurement or data-entry errors. Our work suggests that the CDW, over time and through validation, has become a generally reliable source of anthropometric data. Researchers should assess the reliability of data contained within any source and apply strategies to minimize the impact of data errors appropriate to their study population.

HLA-A, -B, -C, and -DRB1 allele and haplotype frequencies distinguish Eastern European Americans from the general European American population.

Sequence-based typing was used to identify human leukocyte antigen (HLA)-A, -B, -C, and -DRB1 alleles from 558 consecutively recruited US volunteers with Eastern European ancestry for an unrelated hematopoietic stem cell registry. Four of 31 HLA-A alleles, 29 HLA-C alleles, 59 HLA-B alleles, and 42 HLA-DRB1 alleles identified (A*0325, B*440204, Cw*0332, and *0732N) are novel. The HLA-A*02010101g allele was observed at a frequency of 0.28. Two-, three-, and four-locus haplotypes were estimated using the expectation-maximization algorithm. The highest frequency extended haplotypes (A*010101g-Cw*070101g-B*0801g-DRB1*0301 and A*03010101g-Cw*0702-B*0702-DRB1*1501) were observed at frequencies of 0.04 and 0.03, respectively. Linkage disequilibrium values (Dij') of the constituent two-locus haplotypes were highly significant for both extended haplotypes (P values were less than 8 x 10(-10)) but were consistently higher for the more frequent haplotype. Balancing selection was inferred to be acting on all the four loci, with the strongest evidence of balancing selection observed for the HLA-C locus. Comparisons of the A-C-B haplotypes and DRB1 frequencies in this population with those for African, European, and western Asian populations showed high degrees of identity with Czech, Polish, and Slovenian populations and significant differences from the general European American population.

14th International HLA and Immunogenetics Workshop: report of progress in methodology, data collection, and analyses.

The Biostatistics Component of the 13th International Histocompatibility Workshop (IHWS) developed the PyPop (Python for Population Genomics) software framework for high-throughput analysis and quality control (QC) assessments of highly polymorphic genotype data. Since its initial release, the software has had several new analysis modules added to it. These additions, combined with improved data filtering and QC modules, facilitate analyses of data at different levels (allele, haplotype, amino acid sequence, and nucleotide sequence). Since the 13th IHWS, much of the human leukocyte antigen (HLA) data from the workshop, QCed via PyPop and other methods, have been made publicly available through the Major Histocompatibility Complex database web site at the National Center for Biotechnology Information (http://ncbi.nih.gov/mhc/). The Anthropology/Human Genetic Diversity component (AHGDC) data have been used in a variety of studies. Prugnolle et al. used this data to corroborate a model of pathogen-driven selection as a factor related to high levels of diversity at HLA loci. Using a comparative genomics approach contrasting results for HLA and non-HLA markers, Meyer et al. analyzed a subset of the 13th IHWS AHGDC data and showed that HLA loci show detectable signs of both natural selection and the demographic history of populations.

PyPop update--a software pipeline for large-scale multilocus population genomics.

Population genetic statistics from multilocus genotype data inform our understanding of the patterns of genetic variation and their implications for evolutionary studies, generally, and human disease studies in particular. In any given population one can estimate haplotype frequencies, identify deviation from Hardy-Weinberg equilibrium, test for balancing or directional selection, and investigate patterns of linkage disequilibrium. Existing software packages are oriented primarily toward the computation of such statistics on a population-by-population basis, not on comparisons among populations and across different statistics. We developed PyPop (Python for Population Genomics) to facilitate the analyses of population genetic statistics across populations and the relationships among different statistics within and across populations. PyPop is an open-source framework for performing large-scale population genetic analyses on multilocus genotype data. It computes the statistics described above, among others. PyPop deploys a standard Extensible Markup Language (XML) output format and can integrate the results of multiple analyses on various populations that were performed at different times into a common output format that can be read into a spreadsheet. The XML output format allows PyPop to be embedded as part of a larger analysis pipeline. Originally developed to analyze the highly polymorphic genetic data of the human leukocyte antigen region of the human genome, PyPop has applicability to any kind of multilocus genetic data. It is the primary analysis platform for analyzing data collected for the Anthropological component of the 13th and 14th International Histocompatibility Workshops. PyPop has also been successfully used in studies by our group, with collaborators, and in publications by several independent research teams.

HLA-A, -B, -C, -DRB1 allele and haplotype frequencies in an African American population.

Sequence-based typing was used to identify human leukocyte antigen (HLA)-A, -B, -C, and -DRB1 alleles from 564 consecutively recruited African American volunteers for an unrelated hematopoietic stem cell registry. The number of known alleles identified at each locus was 42 for HLA-A, HLA-B 67, HLA-C 33, and HLA-DRB1 44. Six novel alleles (A*260104, A*7411, Cw*0813, Cw*1608, Cw*1704, and DRB1*130502) not observed in the initial sequence-specific oligonucleotide probe testing were characterized. The action of balancing selection, shaping more 'even' than expected allele frequency distributions, was inferred for all four loci and significantly so for the HLA-A and DRB1 loci. Two-, three-, and four-locus haplotypes were estimated using the expectation maximization algorithm. Comparisons with other populations from Africa and Europe suggest that the degree of European admixture in the African American population described here is lower than that in other African American populations previously reported, although HLA-A:B haplotype frequencies similar to those in previous studies of African American individuals were also noted.

Differentiation between African populations is evidenced by the diversity of alleles and haplotypes of HLA class I loci.

The allelic and haplotypic diversity of the HLA-A, HLA-B, and HLA-C loci was investigated in 852 subjects from five sub-Saharan populations from Kenya (Nandi and Luo), Mali (Dogon), Uganda, and Zambia. Distributions of genotypes at all loci and in all populations fit Hardy-Weinberg equilibrium expectations. There was not a single allele predominant at any of the loci in these populations, with the exception of A*3002 [allele frequency (AF) = 0.233] in Zambians and Cw*1601 (AF = 0.283) in Malians. This distribution was consistent with balancing selection for all class I loci in all populations, which was evidenced by the homozygosity F statistic that was less than that expected under neutrality. Only in the A locus in Zambians and the C locus in Malians, the AF distribution was very close to neutrality expectations. There were six instances in which there were significant deviations of allele distributions from neutrality in the direction of balancing selection. All allelic lineages from each of the class I loci were found in all the African populations. Several alleles of these loci have intermediate frequencies (AF = 0.020-0.150) and seem to appear only in the African populations. Most of these alleles are widely distributed in the African continent and their origin may predate the separation of linguistic groups. In contrast to native American and other populations, the African populations do not seem to show extensive allelic diversification within lineages, with the exception of the groups of alleles A*02, A*30, B*57, and B*58. The alleles of human leukocyte antigen (HLA)-B are in strong linkage disequilibrium (LD) with alleles of the C locus, and the sets of B/C haplotypes are found in several populations. The associations between A alleles with C-blocks are weaker, and only a few A/B/C haplotypes (A*0201-B*4501-Cw*1601; A*2301-B*1503-Cw*0202; A*7401-B* 1503-Cw*0202; A*2902-B*4201-Cw*1701; A*3001-B*4201-Cw*1701; and A*3601-B*5301-Cw*0401) are found in multiple populations with intermediate frequencies [haplotype frequency (HF) = 0.010-0.100]. The strength of the LD associations between alleles of HLA-A and HLA-B loci and those of HLA-B and HLA-C loci was on average of the same or higher magnitude as those observed in other non-African populations for the same pairs of loci. Comparison of the genetic distances measured by the distribution of alleles at the HLA class I loci in the sub-Saharan populations included in this and other studies indicate that the Luo population from western Kenya has the closest distance with virtually all sub-Saharan population so far studied for HLA-A, a finding consistent with the putative origin of modern humans in East Africa. In all African populations, the genetic distances between each other are greater than those observed between European populations. The remarkable current allelic and haplotypic diversity in the HLA system as well as their variable distribution in different sub-Saharan populations is probably the result of evolutionary forces and environments that have acted on each individual population or in their ancestors. In this regard, the genetic diversity of the HLA system in African populations poses practical challenges for the design of T-cell vaccines and for the transplantation medical community to find HLA-matched unrelated donors for patients in need of an allogeneic transplant.

The association of diabetes and glucose control with surgical-site infections among cardiothoracic surgery patients.

OBJECTIVE: To assess the importance of diabetes, diabetes control, hyperglycemia, and previously undiagnosed diabetes in the development of surgical-site infections (SSIs) among cardiothoracic surgery patients. SETTING: A 540-bed tertiary-care university-affiliated hospital. DESIGN: Prospective cohort and case-control studies. PATIENTS: All patients having cardiothoracic surgery between November 1998 and September 1999 were eligible for participation. One thousand patients had preoperative hemoglobin A1c determinations. Seventy-four patients with SSIs were identified. RESULTS: Diabetes (odd ratio [OR], 2.76; P<.001) and postoperative hyperglycemia (OR, 2.02; P=.007) were independently associated with development of SSIs. Among known diabetics, elevated hemoglobin A1c values were not associated with a statistically significantly increased risk of infection; the mean A1c value was 8.44% among those with infections compared with 7.80% for those without (P=.09). Forty-two (6%) of 700 patients without prior diabetes history had evidence of undiagnosed diabetes; their infection rate was comparable to that of known diabetics (3/42 [7%] vs 17/300 [6%]; P=.72). An additional 30% of nondiabetics had elevated hemoglobin A1c determinations or perioperative hyperglycemia. CONCLUSIONS: Postoperative hyperglycemia and previously undiagnosed diabetes are associated with development of SSIs among cardiothoracic surgery patients. Screening for diabetes and hyperglycemia among patients having cardiothoracic surgery may be warranted to prevent postoperative and chronic complications of this metabolic abnormality.

Structures of two RNA domains essential for hepatitis C virus internal ribosome entry site function.

Translation of the hepatitis C virus (HCV) polyprotein is initiated at an internal ribosome entry site (IRES) element in the 5' untranslated region of HCV RNA. The HCV IRES element interacts directly with the 40S subunit, and biochemical experiments have implicated RNA elements near the AUG start codon as required for IRES-40S subunit complex formation. The data we present here show that two RNA stem loops, domains IIId and IIIe, are involved in IRES-40S subunit interaction. The structures of the two RNA domains were solved by NMR spectroscopy and reveal structural features that may explain their role in IRES function.

Developing a suicide prevention strategy based on the perspectives of people with brain injuries.

OBJECTIVE: To develop a service-relevant, suicide prevention strategy based on the perspectives of people with brain injuries and their family members. DESIGN: Structured interview-based, qualitative case design. SETTING: Interviews were conducted in the context of community-based brain injury rehabilitation service delivery. PARTICIPANTS: Ten persons with moderate to severe brain injuries who exhibited suicidal orientations and four family member/carers of these participants. RESULTS: Qualitative analysis of interview transcripts revealed a number of relevant themes. The primary theme was that informal relationships play a key role in preventing suicide. Secondary themes included the potential role of specialist brain injury rehabilitation services in suicide prevention and the need for provision of more information about brain injury to family and friends to promote understanding. CONCLUSIONS: Some discrepancy was noted between the perspectives of people with brain injuries and family members. The need for multiple strategies to respond to suicide risk was reinforced. Service-relevant resources (suicide risk screen, contract, and brochure) have been developed and included in service delivery.

Predictors of patient entry into alcohol treatment after initial diagnosis.

To improve the quality of care for alcohol-related disorders, key transitions in the continuum of care, including treatment entry, must be fully understood. The purpose of this study was to investigate identifiable predictors of patient entry into a substance-use treatment program following the initial diagnosis of an alcohol-related disorder on a medical or surgical inpatient unit. An administrative computerized database was used to identify the sample for this study. Inpatient and outpatient records were obtained from the Little Rock VAMC/DHCP. Predictors of patient entry into treatment within six months of the initial diagnosis of an alcohol related disorder included age younger than than 60 (odds ratio [OR] = 4.6), not married (OR = 1.7), primary diagnosis of an alcohol-related disorder (OR = 7.7), diagnosis of a comorbid drug (OR = 4.3) or psychiatric disorder (OR = 3.6), diagnosis by a medical as opposed to a surgical specialty (OR = 6.0), and African American (OR = 1.7).

The feasibility of using automated data to assess guideline-concordant care for schizophrenia.

This study examines the feasibility of using automated computer data versus written medical record data to identify patients receiving guideline concordant treatment for schizophrenia. Central elements of care derived from published practice guidelines for schizophrenia were examined for a convenience sample of 28 patients who received acute inpatient treatment. The results showed that automated data were superior to medical record data for identifying some elements of guideline-concordant treatment. Not only were the elements of care examined in this study clinically significant and within the current capabilities of the existing computer information system, but they are also likely related to patient outcomes. Implications for clinical care, future research, and health care quality improvement efforts are discussed.

Identifying patterns of disruptive behavior in long-term care residents.

OBJECTIVES: To determine the frequency, timing, and pattern of 45 operationalized disruptive behaviors (DB) in older people in long-term care units. DESIGN: Nursing staff collected prospective descriptive data over 21 consecutive shifts for each patient to document prevalence, frequency, and co-occurrences of DBs. SETTING: All of the eight long-term care units and one acute/admission unit of a large Veterans Administration Medical Center (VAMC). Each 40-bed unit had patients with varying levels of cognitive impairment and skilled nursing needs. PARTICIPANTS: The sample consisted of 240 hospitalized VA patients with a mean age of 72.8 (SD = 8.6) years and mean length of stay of 4.02 (SD = 8.6) years. Residents had dementia, a psychiatric diagnosis, or mixed dementia and psychiatric diagnoses. MEASUREMENTS: The Disruptive Behavior Scale (DBS), an instrument designed for collecting patient-level data on 45 separate DBs. RESULTS: In a 24-hour period, the average frequency was 3.6 DBs per subject. We found that 41.2% of DB occurred during the day shift, 39.2% during the evening shift, and 19.6% during the night shift. In 32% of observed occurrences, only one DB occurred within the hour. In the remaining 68% of observations, two or more DBs occurred within the same hour. We found two behaviors, Does Not Follow Directions and Excessive Motor Activity, to occur with multiple behaviors in multiple categories. Several characteristic patterns were noted; e.g., physically aggressive behaviors rarely co-occurred with verbal DBs. Physically nonaggressive behaviors seemed to occur most frequently with other physically nonaggressive behaviors and, to a lesser extent, with verbal DBs. CONCLUSIONS: These findings lend support to the existence of patterns of DBs in long-term care patients, a useful step toward targeting interventions early in the behavioral sequence.

Geographic market areas for psychiatric and medical outpatient treatment.

The research objective was to measure the variation in the size of a facility's market areas across different diagnostic categories. Specifically, the market area radii for outpatient psychiatric services are compared to the radii for outpatient medical services. Data were collected from the outpatient clinics of the Little Rock Veterans Administration Medical Center. Visits were categorized into 100 diagnostic groups. The market radius for each diagnostic group was defined as the 75th quartile of the distribution of distances traveled. All psychiatric diagnostic groups had significantly (p < 0.05) smaller market area radii than the overall sample radius. The average market area radius across psychiatric illnesses was 62.2 miles, which was significantly (p < 0.05) smaller than the average radius across medical illnesses (90.6 miles). Results suggest that rural patients with mental illness may not receive adequate care and that specialized outreach programs may need to be developed to better serve this population.

Specific binding of an exonic splicing enhancer by the pre-mRNA splicing factor SRp55.

Purine-rich exonic splicing enhancers (ESEs) have been identified in many alternatively spliced exons. Alternative splicing of several ESE-containing exons has been shown to depend on subsets of the SR protein family of pre-mRNA splicing factors. In this report, we show that purified SR protein family member SRp55 by itself binds a 30-nt ESE-containing exon, the alternatively spliced exon 5 of avian cardiac troponin T. We show that purified SRp55 binds specifically to this RNA sequence with an apparent Kd of 60 nM as assayed by gel mobility retardation experiments. Mutations in the exon 5 sequence that increase or decrease exon 5 inclusion in vivo and in vitro have correspondingly different affinities for SRp55 in our assays. The exon 5 sequence contains two purine-rich motifs, common to many ESEs, and both are required for SRp55 binding. Hill plot analysis of binding titration reactions indicates that there is a cooperative binding of at least two SRp55 proteins to the exon sequence. Chemical modification interference studies using kethoxal show that SRp55 binding to exon 5 requires the N1 and/or the N2 of almost every G residue in the exon. Dimethylsulfate modification interference studies indicate that none of the N1 positions of A residues in the exon are important for binding. We postulate that SRp55 may recognize both primary sequence and RNA secondary structural elements within pre-mRNA.

Sexual abuse of children. The detection of semen on skin.

OBJECTIVE: The detection of semen on the skin of children who present within 72 hours of an episode of sexual assault is critical to medical, forensic, and legal personnel. The Wood's Lamp, a UV light that causes semen to fluoresce, and four forensic laboratory techniques were compared to determine their sensitivity and decline in sensitivity over time. DESIGN: A descriptive study. PARTICIPANTS: Eleven adult female volunteers. MEASUREMENTS/MAIN RESULTS: Semen was placed on the skin of the volunteers. Samples of the dried semen were assessed during a 28-hour period with the Wood's Lamp, microscopy, the acid phosphatase assay, and two assays for the prostatic protein p30 (counterimmunoelectrophoresis and enzyme-linked immunosorbent assay). The intensity of the Wood's Lamp fluorescence of semen diminished dramatically by 28 hours; in contrast, the fluorescence of urine persisted up to 80 hours. Over time, the p30-enzyme-linked immunosorbent assay technique was more sensitive than microscopy, the acid phosphatase assay, and p30-counterimmunoelectrophoresis in detecting semen on skin. CONCLUSIONS: The Wood's Lamp is not a sensitive screening tool and should be used with caution. To improve the detection of sexual abuse in children, we recommend that the p30-enzyme-linked immunosorbent assay be used because of its potential as a more sensitive assay than those in current clinical use.