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1.  Comparative effectiveness of fish oil versus fenofibrate, gemfibrozil, and atorvastatin on lowering triglyceride levels among HIV-infected patients in routine clinical care 
Objective
The goal of this study was to compare the effectiveness of fish oil, fenofibrate, gemfibrozil, and atorvastatin on reducing triglyceride (TG) levels among a large cohort of HIV-infected patients in clinical care.
Design
Retrospective observational cohort study
Methods
The primary endpoint was absolute change in TG levels measured using the last TG value pre-treatment and the first TG value post-treatment. A pre-post quasi-experimental design was used to estimate the change in TG due to initiating fish oil. Linear regression models examined the comparative effectiveness of treatment with fish oil versus gemfibrozil, fenofibrate, or atorvastatin for TG reduction. Models were adjusted for baseline differences in age, sex, race, CD4+ cell count, diabetes, body mass index, protease inhibitor use, and time between TG measures.
Results
A total of 493 patients (mean age 46 years; 95% male) were included (46 receiving gemfibrozil, 80 fenofibrate, 291 atorvastatin, 76 fish oil) with a mean baseline TG of 347 mg/dL. New use of fish oil decreased TG (ΔTG -45 mg/dL 95% Confidence interval (CI):-80 to -11) in the pre-post study. Compared with fish oil (reference), fibrates were more effective (ΔTG -66; 95% CI:-120 to -12) in reducing TG levels, whereas atorvastatin was not (ΔTG -39; 95% CI:-86 to 9).
Conclusion
In HIV-infected patients in routine clinical care, fish oil is less effective than fibrates (but not atorvastatin) at lowering triglyceride values. Fish oil may still represent an attractive alternative for patients with moderately elevated triglycerides particularly among patients who may not want or tolerate fibrates.
doi:10.1097/QAI.0b013e3182a60e82
PMCID: PMC4112457  PMID: 23892238
fish oil; triglycerides; dyslipidemia; fibrates; HIV
2.  Factors influencing Breast Cancer Screening in Low-Income African Americans in Tennessee 
Journal of community health  2014;39(5):943-950.
This study examined demographic and lifestyle factors that influenced decisions and obstacles to being screened for breast cancer in low-income African Americans in three urban Tennessee cities. As part of the Meharry Community Networks Program (CNP) needs assessment, a 123-item community survey was administered to assess demographic characteristics, health care access and utilization, and screening practices for various cancers in low-income African Americans. For this study, only African American women 40 years and older (n=334) were selected from the Meharry CNP community survey database. There were several predictors of breast cancer screening such as marital status and having health insurance (P< .05). Additionally, there were associations between obstacles to screening and geographic region such as transportation and not having enough information about screenings (P< .05). Educational interventions aimed at improving breast cancer knowledge and screening rates should incorporate information about obstacles and predictors to screening.
doi:10.1007/s10900-014-9834-x
PMCID: PMC4165808  PMID: 24554393
3.  Expression of the BMP Receptor Alk3 in the Second Heart Field is Essential for Development of the Dorsal Mesenchymal Protrusion and Atrioventricular Septation 
Circulation research  2013;112(11):10.1161/CIRCRESAHA.112.300821.
Rationale
The Dorsal Mesenchymal Protrusion (DMP) is a prong of mesenchyme derived from the Second Heart Field (SHF) located at the venous pole of the developing heart. Recent studies have shown that perturbation of its development is associated with the pathogenesis of atrioventricular septal defect (AVSD). Although the importance of the DMP to AV septation is now established, the molecular and cellular mechanisms underlying its development are far from fully understood. Prior studies have demonstrated that bone morphogenetic protein (BMP) signaling is essential for proper formation of the AV endocardial cushions and the cardiac outflow tract. A role for BMP signaling in regulation of DMP development remained to be elucidated.
Objective
To determine the role of BMP signaling in DMP development.
Methods and Results
Conditional deletion of the BMP receptor Alk3 from venous pole SHF cells leads to impaired formation of the DMP and a completely penetrant phenotype of ostium primum defect, a hallmark feature of AVSDs. Analysis of mutants revealed decreased proliferative index of SHF cells and, consequently, reduced number of SHF cells at the cardiac venous pole. In contrast, volume and expression of markers associated with proliferation and active BMP/TGFβ signaling was not significantly altered in the AV cushions of SHF-Alk3 mutants.
Conclusions
BMP signaling is required for expansion of the SHF-derived DMP progenitor population at the cardiac venous pole. Perturbation of Alk3-mediated BMP signaling from the SHF results in impaired development of the DMP and ostium primum defects.
doi:10.1161/CIRCRESAHA.112.300821
PMCID: PMC3822333  PMID: 23584254
DMP; AVSD; Alk3; BMP; ASD
4.  Predictors of Undiagnosed Herpes Simplex Virus Type 2 Seropositivity Among Persons Attending an HIV Care Clinic 
Sexually transmitted diseases  2012;39(11):857-859.
We evaluated herpes simplex virus type 2 (HSV-2) seropositivity in an HIV clinic–based population with CD4 lymphocytes counts ≥250 cells/μL and no previous knowledge of HSV-2 infection by history of serology. We demonstrate that although the seroprevalence of HSV-2 is higher in this HIV-infected population, predictors of HSV-2 seropositivity are similar to those in the general population.
doi:10.1097/OLQ.0b013e318264929c
PMCID: PMC3941199  PMID: 23064534
5.  Evaluating the dosimetric effect of treatment-induced changes in virally mediated head and neck cancer patients 
Introduction
Patients with virally mediated head and neck cancer (VMHNC) often present with advanced nodal disease that is highly radioresponsive as demonstrated by tumour and nodal regression during treatment. The resultant changes may impact on the planned dose distribution and so adversely affect the therapeutic ratio. The aim of this study was to evaluate the dosimetric effect of treatment-induced anatomical changes in VMHNC patients who had undergone a replan.
Methods
Thirteen patients with virally mediated oropharyngeal or nasopharyngeal cancer who presented for definitive radiotherapy between 2005 and 2010 and who had a replan generated were investigated. The dosimetric effect of anatomical changes was quantified by comparing dose–volume histograms (DVH) of primary and nodal gross target volumes and organs at risk (OAR), including spinal cord and parotid glands, from the original plan and a comparison plan.
Results
Eleven three-dimensional conformal radiation therapy (3DCRT) and two intensity modulated radiation therapy (IMRT) plans were evaluated. Dose to the spinal cord and brainstem increased by 4.1% and 2.6%, respectively. Mean dose to the parotid glands also increased by 3.5%. In contrast, the dose received by 98% of the primary and nodal gross tumour volumes decreased by 0.15% and 0.3%, respectively, when comparing the initial treatment plan to the comparison plan.
Conclusion
In this study, treatment-induced anatomical changes had the greatest impact on OAR dose with negligible effect on the dose to nodal gross tumour volumes. In the era of IMRT, accounting for treatment-induced anatomical changes is important as focus is placed on minimizing the acute and long-term side effects of treatment.
doi:10.1002/jmrs.30
PMCID: PMC4175821
Head and neck cancer; HPV-16; planning; radiation therapy
6.  Phase IIa Study of the Immunogenicity and Safety of the Novel Staphylococcus aureus Vaccine V710 in Adults with End-Stage Renal Disease Receiving Hemodialysis 
Bacteremia is the second leading cause of death in patients with end-stage renal disease who are on hemodialysis. A vaccine eliciting long-term immune responses against Staphylococcus aureus in patients on chronic hemodialysis may reduce the incidence of bacteremia and its complications in these patients. V710 is a vaccine containing iron surface determinant B (IsdB), a highly conserved S. aureus surface protein, which has been shown to be immunogenic in healthy subjects. In this blinded phase II immunogenicity study, 206 chronic hemodialysis patients between the ages of 18 and 80 years old were randomized to receive 60 μg V710 (with or without adjuvant), 90 μg V710 (with adjuvant), or a placebo in various combinations on days 1, 28, and 180. All 201 vaccinated patients were to be followed through day 360. The primary hypothesis was that at least 1 of the 3 groups receiving 2 V710 doses on days 1 and 28 would have a ≥2.5 geometric mean fold rise (GMFR) in anti-IsdB IgG titers over the baseline 28 days after the second vaccination (day 56). At day 56, all three groups receiving 2 doses of V710 achieved a ≥2.5 GMFR in anti-IsdB antibodies compared to the baseline (P values of <0.001 for all 3 groups), satisfying the primary immunogenicity hypothesis. None of the 33 reported serious adverse experiences were considered vaccine related by the investigators. V710 induced sustained antibody responses for at least 1 year postvaccination in patients on chronic hemodialysis.
doi:10.1128/CVI.00034-12
PMCID: PMC3428394  PMID: 22837094
7.  Cyclic Nucleotide Gated Channels 7 and 8 Are Essential for Male Reproductive Fertility 
PLoS ONE  2013;8(2):e55277.
The Arabidopsis thaliana genome contains 20 CNGCs, which are proposed to encode cyclic nucleotide gated, non-selective, Ca2+-permeable ion channels. CNGC7 and CNGC8 are the two most similar with 74% protein sequence identity, and both genes are preferentially expressed in pollen. Two independent loss-of-function T-DNA insertions were identified for both genes and used to generate plant lines in which only one of the two alleles was segregating (e.g., cngc7-1+/−/cngc8-2−/− and cngc7-3−/−/cngc8-1+/−). While normal pollen transmission was observed for single gene mutations, pollen harboring mutations in both cngc7 and 8 were found to be male sterile (transmission efficiency reduced by more than 3000-fold). Pollen grains harboring T-DNA disruptions of both cngc7 and 8 displayed a high frequency of bursting when germinated in vitro. The male sterile defect could be rescued through pollen expression of a CNGC7 or 8 transgene including a CNGC7 with an N-terminal GFP-tag. However, rescue efficiencies were reduced ∼10-fold when the CNGC7 or 8 included an F to W substitution (F589W and F624W, respectively) at the junction between the putative cyclic nucleotide binding-site and the calmodulin binding-site, identifying this junction as important for proper functioning of a plant CNGC. Using confocal microscopy, GFP-CNGC7 was found to preferentially localize to the plasma membrane at the flanks of the growing tip. Together these results indicate that CNGC7 and 8 are at least partially redundant and provide an essential function at the initiation of pollen tube tip growth.
doi:10.1371/journal.pone.0055277
PMCID: PMC3570425  PMID: 23424627
8.  Vaginal mesh – the controversy 
Pelvic organ prolapse is a condition that can cause significant symptoms that affect a woman's quality of life. It is the result of defects in the supporting structures of the vagina and, depending on the location and size, can alter the functions of the organs contained within the female pelvis. Approximately 11% of women will undergo surgical intervention for their prolapse or for incontinence in their lifetime. Unfortunately, one third of these will require reoperation for failed procedures. Pelvic floor surgeons have sought to improve these outcomes. Based largely on the success of midurethral slings (MUS), transvaginal mesh has been implanted, and commercial kits developed with the intent of improving these outcomes. In 2008, the Food and Drug Administration (FDA) issued a Public Health Notification in response to possible increased adverse events associated with the use of mesh compared to traditional repairs. The 2011 update required that further study be conducted for the use of transvaginal mesh. In this article, we wish to discuss the background of mesh use and the evolution of the public health warnings, and focus on future prospects.
doi:10.3410/M4-21
PMCID: PMC3506218  PMID: 23189090
9.  On the Assessment of Monte Carlo Error in Simulation-Based Statistical Analyses 
The American statistician  2009;63(2):155-162.
Statistical experiments, more commonly referred to as Monte Carlo or simulation studies, are used to study the behavior of statistical methods and measures under controlled situations. Whereas recent computing and methodological advances have permitted increased efficiency in the simulation process, known as variance reduction, such experiments remain limited by their finite nature and hence are subject to uncertainty; when a simulation is run more than once, different results are obtained. However, virtually no emphasis has been placed on reporting the uncertainty, referred to here as Monte Carlo error, associated with simulation results in the published literature, or on justifying the number of replications used. These deserve broader consideration. Here we present a series of simple and practical methods for estimating Monte Carlo error as well as determining the number of replications required to achieve a desired level of accuracy. The issues and methods are demonstrated with two simple examples, one evaluating operating characteristics of the maximum likelihood estimator for the parameters in logistic regression and the other in the context of using the bootstrap to obtain 95% confidence intervals. The results suggest that in many settings, Monte Carlo error may be more substantial than traditionally thought.
doi:10.1198/tast.2009.0030
PMCID: PMC3337209  PMID: 22544972
Bootstrap; Jackknife; Replication
10.  Consistency of Mycobacterium tuberculosis-Specific Interferon-Gamma Responses in HIV-1-Infected Women during Pregnancy and Postpartum 
Background. We determined the consistency of positive interferon-gamma (IFN-γ) release assays (IGRAs) to detect latent TB infection (LTBI) over one-year postpartum in HIV-1-infected women. Methods. Women with positive IGRAs during pregnancy had four 3-monthly postpartum IGRAs. Postpartum change in magnitude of IFN-γ response was determined using linear mixed models. Results. Among 18 women with positive pregnancy IGRA, 15 (83%) had a subsequent positive IGRA; 9 (50%) were always positive, 3 (17%) were always negative, and 6 (33%) fluctuated between positive and negative IGRAs. Women with pregnancy IGRA IFN-γ>8 spot forming cells (SFCs)/well were more likely to have consistent postpartum IGRA response (odds ratio: 10.0; 95% confidence interval (CI): 0.9–117.0). Change in IFN-γ response over postpartum was 10.2 SFCs/well (95% CI: −1.5–21.8 SFCs/well). Conclusion. Pregnancy positive IGRAs were often maintained postpartum with increased consistency in women with higher baseline responses. There were modest increases in magnitude of IGRA responses postpartum.
doi:10.1155/2012/950650
PMCID: PMC3312220  PMID: 22496602
12.  Latent TB detection by interferon gamma release assay (IGRA) in pregnancy predicts active TB and mortality in HIV-1 infected women and their children 
The Journal of infectious diseases  2010;202(12):1826-1835.
Background
We evaluated the prognostic utility of interferon-gamma release assays (IGRAs) for active tuberculosis (TB) and mortality in Kenyan HIV-1 infected women and their infants.
Methods
Prevalence and correlates of Mycobacterium tuberculosis-specific T-SPOT.TB IGRA positivity were determined during pregnancy in a historical cohort of HIV-1 infected women. Hazard ratios, adjusted for baseline maternal CD4 count (aHRCD4) were calculated for associations between IGRA positivity and risk of active TB and mortality over 2-year postpartum follow-up in women and their infants.
Results
Of 333 women tested, 52 (15.6%) had indeterminate IGRAs. Of the remaining 281 women, 120 (42.7%) had positive IGRAs, which were associated with a 4.5-fold increased risk of active TB [aHRCD4: 4.5; 95% confidence interval (CI): 1.1–18.0; p=0.03]. Among immunosuppresed women (CD4<250 cell/mm3), positive IGRAs were associated with increased risk of maternal mortality (aHRCD4: 3.5; 95% CI: 1.02–12.1; p=0.045), maternal active TB or mortality (aHRCD4: 5.2; 95% CI: 1.7–15.6; p=0.004) and infant active TB or mortality, overall (aHRCD4: 3.0; 95% CI: 1.0–8.9; p= 0.05) and in HIV-1 exposed uninfected infants (aHRCD4: 7.3; 95% CI: 1.6–33.5; p =0.01).
Conclusions
Positive IGRAs in HIV-1 infected pregnant women were associated with postpartum active TB and mortality in mothers and their infants.
doi:10.1086/657411
PMCID: PMC3058232  PMID: 21067370
Latent tuberculosis infection; HIV-1; women; infants; T-SPOT.TB; IGRA
13.  Latent Tuberculosis Detection by Interferon γ Release Assay during Pregnancy Predicts Active Tuberculosis and Mortality in Human Immunodeficiency Virus Type 1-Infected Women and Their Children 
The Journal of Infectious Diseases  2010;202(12):1826-1835.
Background. We evaluated the prognostic usefulness of interferon γ release assays (IGRAs) for active tuberculosis and mortality in Kenyan human immunodeficiency virus type 1 (HIV-1)-infected women and their infants.
Methods. Prevalence and correlates of Mycobacterium tuberculosis-specific T-SPOT.TB IGRA positivity were determined during pregnancy in a historical cohort of HIV-1-infected women. Hazard ratios, adjusted for baseline maternal CD4 cell count (aHRCD4), were calculated for associations between IGRA positivity and risk of active tuberculosis and mortality over 2-year postpartum follow-up among women and their infants.
Results. Of 333 women tested, 52 (15.6%) had indeterminate IGRA results. Of the remaining 281 women, 120 (42.7%) had positive IGRA results, which were associated with a 4.5-fold increased risk of active tuberculosis (aHRCD4, 4.5; 95% confidence interval [CI], 1.1–18.0; P = .030). For immunosuppressed women (CD4 cell count, <250 cells/µL), positive IGRA results were associated with increased risk of maternal mortality (aHRCD4, 3.5; 95% CI, 1.02–12.1; ), maternal active tuberculosis or mortality (aHRCD4 P = .045 , 5.2; 95% CI, 1.7–15.6; P = .004), and infant active tuberculosis or mortality overall (aHRCD4, 3.0; 95% CI, 1.0–8.9; P = .05) and among HIV-1-exposed uninfected infants (aHRCD4, 7.3; 95% CI, 1.6–33.5; P = .01).
Conclusions. Positive IGRA results for HIV-1-infected pregnant women were associated with postpartum active tuberculosis and mortality among mothers and their infants.
doi:10.1086/657411
PMCID: PMC3058232  PMID: 21067370
14.  Evaluation of the TREX1 gene in a large multi-ancestral lupus cohort 
Genes and immunity  2011;12(4):270-279.
Systemic Lupus Erythematosus (SLE) is a prototypic autoimmune disorder with a complex pathogenesis in which genetic, hormonal and environmental factors play a role. Rare mutations in the TREX1 gene, the major mammalian 3′-5′ exonuclease, have been reported in sporadic SLE cases. Some of these mutations have also been identified in a rare pediatric neurologic condition featuring an inflammatory encephalopathy known as Aicardi-Goutières syndrome (AGS). We sought to investigate the frequency of these mutations in a large multi-ancestral cohort of SLE cases and controls.
Methods
Forty single-nucleotide polymorphisms (SNPs), including both common and rare variants, across the TREX1 gene were evaluated in ∼8370 patients with SLE and ∼7490 control subjects. Stringent quality control procedures were applied and principal components and admixture proportions were calculated to identify outliers for removal from analysis. Population-based case-control association analyses were performed. P values, false discovery rate q values, and odds ratios with 95% confidence intervals were calculated.
Results
The estimated frequency of TREX1 mutations in our lupus cohort was 0.5%. Five heterozygous mutations were detected at the Y305C polymorphism in European lupus cases but none were observed in European controls. Five African cases incurred heterozygous mutations at the E266G polymorphism and, again, none were observed in the African controls. A rare homozygous R114H mutation was identified in one Asian SLE patient whereas all genotypes at this mutation in previous reports for SLE were heterozygous. Analysis of common TREX1 SNPs (MAF >10%) revealed a relatively common risk haplotype in European SLE patients with neurologic manifestations, especially seizures, with a frequency of 58% in lupus cases compared to 45% in normal controls (p=0.0008, OR=1.73, 95% CI=1.25-2.39). Finally, the presence or absence of specific autoantibodies in certain populations produced significant genetic associations. For example, a strong association with anti-nRNP was observed in the European cohort at a coding synonymous variant rs56203834 (p=2.99E-13, OR=5.2, 95% CI=3.18-8.56).
Conclusion
Our data confirm and expand previous reports and provide additional support for the involvement of TREX1 in lupus pathogenesis.
doi:10.1038/gene.2010.73
PMCID: PMC3107387  PMID: 21270825
15.  Multiple imputation for missing cardiac magnetic resonance imaging data: Results from the Multi-Ethnic Study of Atherosclerosis (MESA) 
The Canadian Journal of Cardiology  2009;25(7):e232-e235.
BACKGROUND:
Cardiac magnetic resonance imaging (MRI) is a non-invasive technique used to accurately and reproducibly measure biological parameters such as left ventricular mass. However, some subjects either refuse or are unable to complete testing, and the impact of excluding these missing data from predictive models is unknown.
METHODS:
Multiple imputation was applied to cardiac MRI data that were previously analyzed using a complete case approach. The model variables – 10 traditional cardiovascular risk factors and five sociodemographic variables – were used as a basis for imputation. Men and women were imputed separately. The primary focus was assessing the change in the cardiovascular predictors of left ventricular geometry and systolic function.
RESULTS:
Although 27% of participants were missing cardiac MRI data, multiple imputation returned results similar to those of a complete case analysis. These results were robust to the point of including additional variables in the imputation analysis above and beyond the model variables. The degree of variance explained by the models increased marginally but the statistical inference was altered for only two predictors out of 53 cardiovascular risk factors using multiple imputation.
DISCUSSION:
The results suggest that the cardiac MRI data in the Multi-Ethnic Study of Atherosclerosis (MESA) do not substantively change when missing data are handled using multiple imputation. Future analyses of cardiac MRI data may consider the complete case approach to be adequate despite the high rate of missing data in this population.
PMCID: PMC2723032  PMID: 19584978
Comparison of methods; Complete case; Magnetic resonance imaging; Multiple imputation
16.  ITGAM coding variant (rs1143679) influences the risk of renal disease, discoid rash, and immunologic manifestations in lupus patients with European ancestry 
Annals of the rheumatic diseases  2009;69(7):1329-1332.
Purpose
We hypothesized that the coding variant (R77H), rs1143679, within ITGAM could predict specific clinical manifestations associated with lupus.
Method
To assess genetic association, 2366 lupus cases and 2931 unaffected controls with European ancestry were analyzed. Lupus patients were coded by the presence or absence of individual ACR criteria. Logistic regression and Pearson chi-square tests were used to assess statistical significance.
Results
First, for overall case-control analysis, we detected highly significant (p=2.22×10−21, OR=1.73) association. Second, using case-only analysis we detected significant association with renal criteria (p=0.0003), discoid rash (p=0.02), and immunologic criteria (p=0.04). Third, we compared them with healthy controls, the association became stronger for renal (p=4.69×10−22, OR=2.15), discoid (p=1.77×10−14, OR=2.03), and immunologic (p=3.49×10−22, OR = 1.86) criteria. Risk allele frequency increased from 10.6% (controls) to 17.0% (lupus), 20.4% (renal), 18.1% (immunologic), and 19.5% (discoid).
Conclusion
These results demonstrated a strong association between the risk allele (A) at rs1143679 and renal disease, discoid rash, and immunological manifestations of lupus.
doi:10.1136/ard.2009.120543
PMCID: PMC2891778  PMID: 19939855
17.  Determining an Optimal Testing Strategy for Infants at Risk for Mother-to-child Transmission of HIV-1 During the Late Postnatal Period 
AIDS (London, England)  2008;22(17):2341-2346.
Objectives
To determine the optimal time for a second HIV-1 nucleic acid amplification assay to detect late postnatal transmission of HIV-1 (first negative test at 4–8 weeks of age) in resource limited settings.
Design
A longitudinal analysis of data from HPTN 024
Methods
Children born to HIV-1 infected mothers enrolled in the HIV Prevention Trial Network trial 024 (HPTN 024) were tested for HIV-1 infection at six intervals within the first year of life. Mothers and infants received nevirapine prophylaxis. We estimated the probability of being alive and having a positive test in each interval after 4–8 weeks and at 30 days post-weaning, conditional on having acquired HIV during the late postnatal period. The interval with the highest probability was taken to be the optimal visit interval.
Results
A total of 1609 infants from HPTN 024 had at least one HIV-1 diagnostic test and were included in the analysis. We found that testing at one month after weaning or 12 months of age (whichever comes first), identified 81% of those infected during the late postnatal period (after 4–8 weeks) through breastfeeding. In total, 93% (95% CI: 89,98) of all infected infants would be detected if tests were performed at these two time points.
Conclusions
In resource-limited settings, HIV-1 PCR testing at 4–8 weeks followed by a second test at one month after weaning or at one year of age (whichever comes first), led to the identification of the vast majority of HIV-1 infected infants.
doi:10.1097/QAD.0b013e328317cc15
PMCID: PMC2760032  PMID: 18981773
HIV infant diagnosis; late postnatal transmission; breast feeding
18.  Antibody Response to Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Nonstructural Proteins and Implications for Diagnostic Detection and Differentiation of PRRSV Types I and II▿  
To further characterize the humoral immune response of pigs to porcine reproductive and respiratory syndrome virus (PRRSV), direct enzyme-linked immunosorbent assays (ELISA) were used to study the kinetics of antibody responses directed against PRRSV nonstructural proteins in pigs experimentally exposed to the virus. The highest immunoreactivities were against nsp1, nsp2, and nsp7. Using the recombinant nsp7 as an antigen, we validated a dual ELISA for the simultaneous detection and differentiation of serum antibodies against type I and type II PRRSV. Receiver operating characteristic analysis based on 1,334 known-positive and 1,357 known-negative samples showed good specificity (98.3% to type I and 99.3% to type II) and sensitivity (97.4% for type I and 99.8% for type II). To differentiate type I and type II PRRSV, 470 sera originating from experimentally inoculated pigs were tested, and positive sera were correctly differentiated in 469 of 470 samples. The capability of the nsp7 dual ELISA to detect serum antibody responses from pigs infected with various genetically different field strains was determined. The nsp7 dual ELISA possessed 97.6% agreement with the Idexx HerdChek PRRS 2XR ELISA. In further testing of Idexx ELISA suspected false-positive samples, the nsp7 dual ELISA resolved 98% of the samples as negative. Taken together, these results indicate that the nsp7 dual ELISA can be used as a differential test for PRRSV serology with high levels of sensitivity and specificity. This ELISA offers an additional tool for routine or follow-up diagnostics, as well as having substantial value in epidemiological surveys and outbreak investigations.
doi:10.1128/CVI.00483-08
PMCID: PMC2681581  PMID: 19261778
19.  Role of NCCN in Integrating Cancer Clinical Practice Guidelines into the Healthcare Debate 
Many new drugs and drugs in the pipeline are referred to as targeted therapy. Targeted therapies have revolutionized the care of certain cancers, such as chronic myelogenous leukemia, but for other common malignancies, such as colon cancer, the impact on survival has been more modest. These seemingly incremental improvements coupled with the high cost of targeted therapy have focused the debate about the cost of healthcare squarely on oncology. Clinical practice guidelines are a common baseline starting point for this debate. Guidelines reflect clinical evidence and expert judgment, which is necessary to fill in the gaps when clinical evidence is not yet available or is evolving quickly. In addition, clinical guidelines inform other key aspects of oncology care, such as establishing a standard of care, which can then be translated into quality measures. Guidelines can also be reformatted to create an oncology drug compendium or rewritten to provide patient information.
PMCID: PMC4114028  PMID: 25126208

Results 1-20 (20)