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The objective of this study was to determine the prevalence of Shiga toxin-producing Escherichia coli (STEC) O157:H7 in colon contents and on carcasses from pigs slaughtered at provincially licensed abattoirs (PLAs) in Alberta, Canada. In 2017, carcass sponge samples and colon content samples were collected from 504 healthy market hogs at 39 PLAs and analyzed for E. coli O157:H7. Carcass samples were also analyzed for E. coli and aerobic colony count (ACC). Nine (1.8%) of 504 carcass samples were confirmed positive for E. coli O157:H7. Seven (1.4%) of 504 colon content samples were confirmed positive for E. coli O157:H7. These positives were found in 5 (12.8%) of 39 PLAs from hogs originating from eight farms. The E. coli O157:H7 isolates recovered from the positive samples (n = 1 isolate per sample) were clonal, as determined by pulsed-field gel electrophoresis. Six E. coli O157:H7 isolates obtained over 8 months from one PLA that only processed hogs and sourced hogs from one farm had indistinguishable pulsed-field gel electrophoresis patterns. All 16 E. coli O157:H7 isolates harbored eae and ehxA and were of stx2a subtype, suggesting that swine can carry E. coli O157:H7 of importance to human health. All carcass sponge swabs (100%) were positive for ACC. E. coli was present in 72% of carcass swabs. Carcasses from PLAs slaughtering both beef and hogs had a numerically higher ACC mean value but not statistically different compared with the carcasses from PLAs slaughtering only swine (2,799 and 610 CFU/cm2, respectively). E. coli showed a similar trend with a mean value of 0.88 CFU/cm2 in PLAs slaughtering both species and 0.26 CFU/cm2 in PLAs slaughtering only swine (P ≤ 0.05). This study provides evidence that healthy market hogs from different producers and farms in Alberta can carry E. coli O157:H7, and some strains of the organism may be able to establish persistence on some swine farms. HIGHLIGHTS

Objective: To examine crash rates over time among 16–17-year-old drivers compared to older drivers. Methods: Data were from a random sample of 854 of the 3,500 study participants in SHRP 2, a U.S. national, naturalistic driving (instrumented vehicle) study. Crashes/10,000 miles by driver age group, 3-month period, and sex were examined within generalized linear mixed models. Results: Analyses of individual differences between age cohorts indicated higher incidence rates in the 16–17-year old cohort relative to older age groups each of the first four quarters (except the first quarter compared to 18–20 year old drivers) with incident rate ratios (IRR) ranging from 1.98 to 18.90, and for the full study period compared with drivers 18–20 (IRR = 1.69, CI = 1.00, 2.86), 21 to 25 (IRR = 2.27, CI = 1.31, 3.91), and 35 to 55 (IRR = 4.00, CI = 2.28, 7.03). Within the 16–17-year old cohort no differences were found in rates among males and females and the decline in rates over the 24-month study period was not significant. Conclusions: The prolonged period of elevated crash rates suggests the need to enhance novice young driver prevention approaches such as Graduated Driver’s Licensing limits, parent restrictions, and post-licensure supervision and monitoring. Practical Applications: Increases are needed in Graduated Driver’s Licensing limits, parent restrictions, and postlicensure supervision and monitoring.

From January to December 2016, Alberta Agriculture and Forestry (AAF) conducted a provincial survey of selected pathogens and indicator organisms on beef carcasses processed at Provincially Licensed Abattoirs (PLAs) in Alberta. The survey was conducted in seven small and medium scale slaughterhouses located in southern and northern Alberta that process beef cattle and cows. Paired samples were collected from the same carcass immediately after hide removal (pre-evisceration n = 401) and at pre-chill (n = 402) after application of a carcass wash and/or anti-microbial interventions. Swab samples were screened for the presence of Shiga toxin-producing Escherichia coli (STEC) O157:H7, six non-O157 STECs (O26, O45, O103, O111, O121 and O145), and Salmonella. In addition, samples were enumerated for indicator organisms (aerobic colony count (ACC), Enterobacteriaceae, coliforms, and generic E. coli). At pre-evisceration, 30 samples (7.4%) were confirmed positive for E. coli O157:H7; 13 samples (3.2%) were confirmed positive for non-O157 STEC; and 7 samples (1.7%) were confirmed positive for Salmonella. Pre-chill swabs had 21 samples (5.2%) positive for E. coli O157:H7, 16 samples (3.9%) positive for non-O157 STEC, and 1 sample (0.2%) positive for Salmonella. At pre-chill the prevalence of Salmonella was significantly lower (P

Purpose To investigate the natural history and genetic associations of drusenoid pigment epithelial detachment (DPED) associated with age-related macular degeneration (AMD). Design Retrospective analysis of a prospective cohort study. Participants Of the 4203 Age-Related Eye Disease Study 2 (AREDS2) participants, 391 eyes (325 participants) had DPED without late AMD at the time of DPED detection. Genetic analyses included 120 white AREDS2 participants and 145 Age-Related Eye Disease Study (AREDS) participants with DPED. Methods Baseline and annual stereoscopic fundus photographs were graded centrally to detect DPED, a well-defined yellow elevated mound of confluent drusen ≥433 μm in diameter, and to evaluate progression rates to late AMD: geographic atrophy (GA) and neovascular (NV)-AMD. Five single nucleotide polymorphisms (CFH [rs10611670], C3 [rs2230199], CFI [rs10033900], C2/CFB [rs114254831], ARMS2 [rs10490924]) and genetic risk score (GRS) group were investigated for association with DPED development. Kaplan–Meier analyses and multivariable proportional hazard regressions were performed. Main Outcome Measures Progression rates to late AMD and decrease of ≥3 lines in visual acuity (VA) from the time of DPED detection; association of rate of DPED development with genotype. Results Mean (standard deviation [SD]) follow-up time from DPED detection was 4.7 (0.9) years. DPED was associated with increased risk of progression to late AMD (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.98–2.82; P Conclusions This study replicates the results of previous natural history studies of eyes with DPED including the high rates of progression to late AMD and vision loss (regardless of progression to late AMD). The genetic associations are consistent with genes associated with AMD progression.

Purpose To analyze the prevalence, incidence, and clinical characteristics of eyes with geographic atrophy (GA) in age-related macular degeneration (AMD), including clinical and genetic factors affecting enlargement. Design Prospective cohort study within a controlled clinical trial. Participants Age-Related Eye Disease Study 2 (AREDS2) participants, aged 50–85 years. Methods Baseline and annual stereoscopic color fundus photographs were evaluated for GA presence and area. Analyses included GA prevalence and incidence rates, Kaplan-Meier rates, mixed-model regression, and multivariable analysis of the square root of GA, area adjusted for covariates, including clinical/imaging characteristics and genotype. Main Outcome Measures (1) Presence or development of GA; (2) change in the square root of GA area over time. Results At baseline, 517 eyes (6.2%) of 411 participants (9.8%) had pre-existing GA (without neovascular AMD), with the following characteristics: 33% central, 67% noncentral; and the following configurations: 36% small, 26% solid/unifocal, 24% multifocal, 9% horseshoe/ring, and 6% indeterminate. Of the remaining 6530 eyes at risk, 1099 eyes (17.3%) of 883 participants developed incident GA without prior neovascular disease during mean follow-up of 4.4 years. The Kaplan-Meier rate of incident GA was 19% of eyes at 5 years. In eyes with incident GA, 4-year risk of subsequent neovascular AMD was 29%. In eyes with incident noncentral GA, 4-year risk of central involvement was 57%. GA enlargement rate (following square root transformation) was similar in eyes with pre-existing GA (0.29 mm/year; 95% confidence interval 0.27–0.30) and incident GA (0.28 mm/year; 0.27–0.30). In the combined group, GA enlargement was significantly faster with noncentrality, multifocality, intermediate baseline size, and bilateral GA (P Conclusions Analyses of AREDS2 data on natural history of GA provide representative data on GA evolution and enlargement. GA enlargement, which was influenced by lesion features, was relentless, resulting in rapid central vision loss. The genetic variants associated with faster enlargement were partially distinct from those associated with risk of incident GA. These findings are relevant to further investigations of GA pathogenesis and clinical trial planning.

Objective Abnormal deposition of the antimicrobial peptide amyloid beta (Aβ) is a characteristic of Alzheimer's Disease (AD). The objective of this study was to elucidate risk factors for brain Aβ in a cohort enriched for human immunodeficiency virus (HIV) and other neurotropic pathogens. Design Cross-sectional cohort study. Methods We examined autopsy brains of 257 donors with a mean age of 52.8 years; 62% were male; and 194 were HIV+ and 63 HIV-. Hyperphosphorylated tau (p-tau) and Aβ were identified in frontal and temporal regions by immunohistochemistry. APOE genotyping was performed. Clinical and neuropathological predictors for Aβ were identified in univariate analyses, and then tested in multivariate regressions. Results Cortical Aβ was identified in 32% of the sample, and active brain infection in 27%. Increased odds of Aβ were seen with increasing age and having an APOE e4 allele; for the overall sample, HIV+ status was protective and brain infection was not a predictor. Within the HIV+ population, predictors for Aβ were duration of HIV disease and APOE alleles, but not age. When HIV disease duration and other HIV parameters were introduced into models for the entire sample, HIV disease duration was equivalent to age as a predictor of Aβ. Conclusion We hypothesize that dual aspects of immune suppression and stimulation in HIV, and beneficial survivor effects in older HIV+ individuals, account for HIV+ status decreasing, and HIV duration increasing, odds of Aβ. Importantly, with HIV, disease duration replaces age as an independent risk for Aβ, suggesting HIV-associated accelerated brain senescence.

The financial sector is entering a new era of rapidly advancing data analytics as deep learning models are adopted into its technology stack. A subset of Artificial Intelligence, deep learning represents a fundamental discontinuity from prior analytical techniques, providing previously unseen predictive powers enabling significant opportunities for efficiency, financial inclusion, and risk mitigation. Broad adoption of deep learning, though, may over time increase uniformity, interconnectedness, and regulatory gaps. This paper maps deep learning’s key characteristics across five possible transmission pathways exploring how, as it moves to a mature stage of broad adoption, it may lead to financial system fragility and economy-wide risks. Existing financial sector regulatory regimes - built in an earlier era of data analytics technology - are likely to fall short in addressing the systemic risks posed by broad adoption of deep learning in finance. The authors close by considering policy tools that might mitigate these systemic risks.

Purpose To evaluate the efficacy and safety of sirolimus, an immunosuppressive drug, for the treatment of age-related macular degeneration (AMD)–associated geographic atrophy (GA). Design Randomized, controlled, single-masked multicenter phase II clinical trial of intravitreal sirolimus versus sham therapy in Age-Related Eye Disease Study 2 (AREDS2) clinical centers. Participants Patients with GA. Methods Participants were assigned randomly to a monthly intravitreal injection of sirolimus (20 μL [440 μg]) or sham treatment. Best-corrected visual acuity (BVCA), spectral-domain OCT, fundus color photography, and fundus autofluorescence (FAF) images were obtained at baseline and every 6 months until visit month 24. Main Outcome Measures Rate of progression of GA (square millimeters per year) measured on color fundus photographs from baseline to 24 months. Secondary outcome measures include change in BVCA, worsening of vision by 3 lines or more, and changes in area of GA measured on FAF and OCT. Results Fifty-two participants (mean age, 79 years) were enrolled, with 27 study eyes assigned to sirolimus from May 2012 through March 2014. The baseline median area of GA was 4.73 disc areas (DA; 12.01 mm 2 ). The mean growth rates of GA detected on color fundus photographs were 2.27 mm 2 (standard deviation [SD], 2.17 mm 2 ) and 1.91 mm 2 (SD, 2.27 mm 2 ) at month 12 and 4.94 mm 2 (SD, 2.96 mm 2 ) and 5.72 mm 2 (SD, 3.97 mm 2 ) at month 24 for the sirolimus and sham groups, respectively. There was no statistically significant difference in the GA growth rates between the 2 treatment groups ( P = 0.33). Median visual acuity changes and incidence of 15-letter loss from baseline were not different between the 2 treatment groups ( P = 0.19). The intervention was stopped early because of sterile endophthalmitis that occurred in 3 participants in the sirolimus group. Participants were followed up for safety until the study was closed in May 2015 because of lack of efficacy. Conclusions Sirolimus did not result in different rates of GA growth in this phase II study. Immunosuppression may be important for some stages of the AMD process, but may not necessarily be the main pathway for the development of GA.

BackgroundCognitive dysfunction in human immunodeficiency virus (HIV) has decreased, but milder forms of HIV-associated neurocognitive disorders (HAND) persist along with motor dysfunction. The HIV Motor Scale (HMS) is a validated tool that captures motor abnormalities on routine neurologic examination and which is associated with cognitive impairment in HIV. In this study, we applied a modified HMS (MHMS) to a nationwide cohort of people with longstanding HIV to characterize and understand the factors contributing to motor dysfunction.MethodsThe National NeuroAIDS Tissue Consortium is a nationwide longitudinal cohort study. Participants undergo regular assessments including neurological examination, neuropsychological testing, and immunovirologic data collection. Data from examinations were used to calculate the MHMS score, which was then correlated with history of AIDS-related central nervous system (CNS) disorders (ARCD; eg, prior CNS opportunistic infection), cerebrovascular disease (CVD), and HAND.ResultsSixty-nine percent of participants showed an abnormality on the MHMS, with 27% classified as severe. Results did not vary based on demographic or immunologic variables. The most common abnormalities seen were gait (54%), followed by coordination (39%) and strength (25%), and these commonly co-occurred. CVD (P = .02), history of ARCD (P = .001), and HAND (P = .001) were all associated with higher (ie, worse) HMS in univariate analyses; CVD and ARCD persisted in multivariate analyses. CVD was also marginally associated with symptomatic HAND.ConclusionsComplex motor dysfunction remains common in HIV and is associated with CVD, ARCD, and to a lesser extent, HAND. Future studies are needed to understand the longitudinal trajectory of HIV-associated motor dysfunction, its neural substrates, and impact on quality of life.

Objective: This research examined the incidence rates of elevated gravitational force events (kinematic risky driving, KRD) among 16- to 17-year-old drivers compared to those of 18- to 20-year-old, 21- to 25-year-old, and 35- to 55-year-old drivers over a 12-month period. Methods: Data were sampled from the Strategic Highway Research Program 2 (SHRP2) naturalistic driving study that recruited a U.S. national sample of study participants. General linear mixed models (GLIMMIX) for recurrent events were used to estimate KRD incident rates for age cohorts in 3-month periods. Results: KRD incidence rates for 16- to 17-year-old drivers were higher than the rates for older drivers at each 3-month period. Analyses of individual differences for the 12-month period indicated that incidence rates for the 16- to 17-year-old group were 1.84 times higher than the rates for 18- to 20-year-old drivers, 2.86 higher than those for 21- to 25-year-old drivers, and 4.92 times higher than those for 35- to 55-year-old drivers. The incident rate for 16- to 17-year-old males was 1.9 times higher than that for same-aged females in the first 3 months and 2.3 times higher over 12 months. Over the study period, KRD rates of 16- to 17-year-old participants declined 24.5% among females and 18.0% among males. Conclusions: KRD rates were higher among younger relative to older, more experienced drivers and did not decline over time, consistent with a protracted period of risky driving behavior. The persistently higher KRD rate among young drivers suggests the need to enhance crash prevention approaches, such as feedback about abrupt maneuvering, to young drivers and their parents.

Author(s): Morgello, Susan; Gensler, Gary; Sherman, Seth; Ellis, Ronald J; Gelman, Benjamin B; Kolson, Dennis L; Letendre, Scott L; Robinson-Papp, Jessica; Rubin, Leah H; Singer, Elyse; Valdes-Sueiras, Miguel; NNTC | Abstract: ObjectivesMultimorbidity and frailty are consequences of aging with HIV, yet not everyone with medical disease is frail. Our objective was to identify factors associated with frailty in a multimorbid HIV-infected cohort.DesignAnalysis of a prospective, observational, longitudinal cohort.MethodsThree hundred and thirty-two participants in the medically advanced National NeuroAIDS Tissue Consortium (NNTC) study were categorized as frail, prefrail, or robust with the Fried Frailty Index. A series of logistic regression analyses (first univariate, then multivariable) were conducted to determine whether medical comorbidities, immunologic and virologic parameters, and/or neuropsychiatric variables predicted increased odds of frailty.ResultsThe mean number of medical comorbidities per participant was 2.7, mean CD4 T-cell count was 530 cells/μl, and 77% had undetectable HIV RNA in blood. Twenty-two percent were frail, 55% prefrail, and 23% robust. Significant predictors of frailty in multivariable analysis were cognitive diagnosis rendered by Frascati criteria, depressive symptoms, diabetes mellitus, chronic obstructive pulmonary disease (COPD), and sex. Men were less likely to be frail than women. Higher odds of frailty were seen with: symptomatic, but not asymptomatic, cognitive impairment (compared with cognitive normals); more depressive symptoms; diabetes mellitus; and COPD.ConclusionNeuropsychiatric illness increased odds of being frail on a predominantly physical/motoric measure, but only when symptomatic. Lack of association with asymptomatic impairment may reflect the importance of functional limitation to frailty, or possibly a unique resilience phenotype. Understanding why sex and symptomatic neuropsychiatric illness are associated with frailty will be important in managing HIV-associated morbidity in aging populations.

Herein we present major updates to the National NeuroAIDS Tissue Consortium (NNTC) database. The NNTC's ongoing multisite clinical research study was established to facilitate access to ante-mortem and post-mortem data, tissues and biofluids for the neurohuman immunodeficiency virus (HIV) research community. Recently, the NNTC has expanded to include data from the central nervous system HIV Antiretroviral Therapy Effects Research (CHARTER) study. The data and biospecimens from CHARTER and NNTC cohorts are available to qualified researchers upon request. Data generated by requestors using NNTC biospecimens and tissues are returned to the NNTC upon the conclusion of requestors' work, and this external, experimental data are annotated and curated in the publically accessible NNTC database, thereby extending the utility of each case. A flexible and extensible database ontology allows the integration of disparate data sets, including external experimental data, clinical neuropsychological and neuromedical testing data, tissue pathology and neuroimaging data.

Traditional site-monitoring techniques are not optimal in finding data fabrication and other nonrandom data distributions with the greatest potential for jeopardizing the validity of study results. TransCelerate BioPharma conducted an experiment testing the utility of statistical methods for detecting implanted fabricated data and other signals of noncompliance.TransCelerate tested statistical monitoring on a data set from a chronic obstructive pulmonary disease (COPD) clinical study with 178 sites and 1554 subjects. Fabricated data were selectively implanted in 7 sites and 43 subjects by expert clinicians in COPD. The data set was partitioned to simulate studies of different sizes. Analyses of vital signs, spirometry, visit dates, and adverse events included distributions of standard deviations, correlations, repeated values, digit preference, and outlier/inlier detection. An interpretation team, including clinicians, statisticians, site monitoring, and data management, reviewed the results and created an algorithm to flag sites for fabricated data.The algorithm identified 11 sites (19%), 19 sites (31%), 28 sites (16%), and 45 sites (25%) as having potentially fabricated data for studies 2A, 2, 1A, and 1, respectively. For study 2A, 3 of 7 sites with fabricated data were detected, 5 of 7 were detected for studies 2 and 1A, and 6 of 7 for study 1. Except for study 2A, the algorithm had good sensitivity and specificity (70%) for identifying sites with fabricated data.We recommend a cross-functional, collaborative approach to statistical monitoring that can adapt to study design and data source and use a combination of statistical screening techniques and confirmatory graphics.

Purpose To develop a clinical eye-specific prediction model for advanced age-related macular degeneration (AMD). Design The Age-Related Eye Disease Study (AREDS) cohort followed up for 8 years served as the training dataset, and the Blue Mountains Eye Study (BMES) cohort followed up for 10 years served as the validation dataset. Participants A total of 4507 AREDS participants (contributing 1185 affected vs. 6992 unaffected eyes) and 2169 BMES participants (contributing 69 affected vs. 3694 unaffected eyes). Methods Using Bayes' theorem in a logistic model, we used 8 baseline predictors—age, sex, education level, race, smoking status, and presence of pigment abnormality, soft drusen, and maximum drusen size—to devise and validate a macular risk scoring system (MRSS). We assessed the performance of the MRSS by calculating sensitivity, specificity, and the area under the receiver operating characteristic curve (i.e., c-index). Main Outcome Measures Advanced AMD. Results The internally validated c-index AREDS (0.88; 95% confidence interval, 0.87–0.89) and the externally validated c-index BMES (0.91; 95% confidence interval, 0.88–0.95) suggested excellent performance of the MRSS. The sensitivity and specificity at the optimal macular risk score cutoff point of 0 were 87.6% and 73.6%, respectively. An application for the iPhone and iPad also was developed as a practical tool for the MRSS. Conclusions The MRSS was developed and validated to provide satisfactory accuracy and generalizability. It may be used to screen patients at risk of developing advanced AMD.

This study determined the prevalence of Salmonella serovars, antimicrobial resistance (AMR) and resistance genes in Salmonella isolated from retail meats purchased in Alberta, Canada. Samples were collected during one year period (May 2007-April 2008) on weekly basis from 19 census divisions in Alberta. A total of 564 samples including chicken (n = 206), turkey (n = 91), beef (n = 134) and pork (n = 133) were purchased. Salmonella were recovered from chicken (40%), turkey (27%) and pork (2%) samples and was not found in ground beef. A total of 21, 8, and 3 different serovars were recovered from chicken, turkey and pork meats, respectively. Salmonella Hadar was most common in chicken whereas S. Heidelberg was common in turkey meat. Overall 29% (32/110) of isolates were susceptible to tested antimicrobials and resistance to ciprofloxacin, amikacin and nalidixic acid was not found in any isolate. Multiresistance (≥2 antimicrobials) was found in 56% of isolates. Resistance to amoxicillin-clavulanic acid (AMC), ceftiofur (TIO), and ceftriaxone (CRO) was found in about 21% of chicken and 25% of turkey isolates. Resistance to either of tetracycline (TET), streptomycin (STR) or ampicillin (AMP) was unconditionally associated with S. Hadar but resistance to either of TET, AMP, AMC, TIO, CRO or cefoxitin was associated with S. Heidelberg. The strA/B (42% isolates), tet(A) (28% isolates), bla(CMY-2) (21% isolates) and bla(TEM) (17% isolates) were the most common resistance genes found. The bla(CMY-2) and bla(TEM) genes were unconditionally associated with S. Heidelberg; tet(A) and strA/B with S. Hadar and tet(B) gene with S. Kentucky. The strA/B genes were not associated with S. Heidelberg. Our data suggests that the prevalence of Salmonella serovars varied by the meat type and that AMR and resistance genes varied by the Salmonella serovars.

Introduction: Human immunodeficiency virus (HIV)-infected patients commonly develop distal symmetric polyneuropathy (DSP). Age, ethnicity, and toxic exposures may influence the risk. In this study we examined the association between substance use, antiretrovirals, ethnicity, and incident neuropathy in an HIV-infected cohort. Methods: Data were obtained from the National NeuroAIDS Tissue Consortium (NNTC), an ongoing, prospective cohort started in 1998. Cox proportional hazards models were used to examine the association of substance use, demographics, neurotoxic antiretrovirals, and laboratory parameters with incident neuropathy in 636 participants who were neuropathy-free at baseline. Results: The cumulative incidence of DSP was 41%. Substance use (P = 0.04), number of substances used (P = 0.04), and longer duration of HIV infection (P = 0.05) were associated with incident DSP, but demographic factors, use of neurotoxic antiretrovirals, and laboratory parameters were not. Conclusions: Substance use and longer duration of HIV infection are risk factors for DSP in HIV-infected patients. Use of multiple substances may be particularly risky. Muscle Nerve, 2012

Purpose Genetic variants CFH and ARMS2/HTRA1 gene regions as well as high-sensitivity C-reactive protein (CRP) levels are related to age-related macular degeneration (AMD). We evaluated their independent and combined effects on risk of AMD, as well as their interactions. Design Case-control study. Participants Subjects with AMD (n = 244) or no or minimal maculopathy (n = 209) in the Age Related Eye Disease Ancillary Study. Methods Risk factors, genotypes, and biomarkers were assessed by questionnaire, direct measurement, and analyses of blood specimens. The independent and joint effects of serum CRP and CFH (rs1061170) and ARMS2/HTRA1 (rs10490924) genotypes were assessed using logistic regression analyses, adjusting for age, gender, education, smoking, body mass index, and vitamin/mineral supplementation. Main Outcome Measures We defined AMD as large drusen, geographic atrophy, or neovascular disease. Results Higher CRP levels were associated with a higher risk of AMD, controlling for genotype and demographic and behavioral risk factors, with odds ratio 2.6 for levels of 3.0 mg/L and above versus below 1.0 mg/L (95% confidence interval, 1.01–6.7). Single nucleotide polymorphisms (SNPs) in both genes were also independently associated with risk of AMD, controlling for the level of CRP and other factors. Presence of both highest level of CRP together with risk genotypes for both SNPs, conferred the highest risk of AMD (OR 5.4, 95% CI 1.4-21.1). Conclusions High-sensitivity CRP and polymorphisms in the CFH and ARMS2/HTRA1 genes are independently associated with risk of AMD. Higher CRP level tends to confer a higher risk of AMD within most genotype groups. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

Recent information suggests that the Age-Related Eye Disease Study (AREDS) supplement, enhanced intake of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), and reducing dietary glycaemic index (dGI) are protective against advanced age-related macular degeneration (AMD).Dietary information was collected at baseline, and fundus photograph grades were obtained during the 8-year trial period from 2924 eligible AREDS AMD trial participants. Using the eye as the unit of analysis and multifailure Cox proportional-hazards regression, the risk of AMD progression was related to dietary intake in the four arms of the trial.Independent of AREDS supplementation, higher intakes of DHA (or =64.0 vs26.0 mg/day) (hazard ratio (HR) = 0.73, 95% confidence interval (CI), 0.57 to 0.94), EPA (or =42.3 vs12.7 mg/day) (HR = 0.74, 95% CI 0.59 to 0.94), and lower dGI (dGI,75.2 vsor =81.5) (HR = 0.76, 95% CI 0.60 to 0.96) were associated with a lower risk for progression to advanced AMD. Participants consuming a lower dGI and higher DHA or EPA had the lowest risk (p value for synergistic interaction0.001). Only participants in the "placebo" (p value for antagonistic interaction = 0.006) benefited from a higher DHA intake against early AMD progression (HR = 0.58, 95% CI 0.37 to 0.92; P(trend) = 0.01).The findings show an association of consuming a diet rich in DHA with a lower progression of early AMD. In addition to the AREDS supplement, a lower dGI with higher intakes of DHA and EPA was associated with a reduced progression to advanced AMD.NCT00000145.

Purpose To assess the risk of advanced age-related macular degeneration (AMD) developing after cataract surgery. Design Cohort study. Participants Four thousand five hundred seventy-seven participants (8050 eyes) from a multicenter, controlled, randomized clinical trial, the Age-Related Eye Disease Study (AREDS). Methods Development of advanced AMD, either neovascular (NV) AMD or geographic atrophy (GA), was evaluated with annual fundus photographs, and history of cataract surgery was assessed every 6 months. Cox proportional hazard models with time-dependent covariates were conducted for NV AMD and GA separately. Main Outcome Measures Neovascular AMD, GA, and central GA (CGA; involving the center of the macula). Results The Cox proportional hazards model of right eyes showed nonsignificant hazard ratios of 1.20 (95% confidence interval [CI], 0.82–1.75) for NV AMD, 0.80 (95% CI, 0.61–1.06) for GA, and 0.87 (95% CI, 0.64–1.18) for CGA. Similar results were obtained for left eyes: 1.07 (95% CI, 0.72–1.58) for NV AMD, 0.94 (95% CI, 0.71–1.25) for GA, and 0.86 (95% CI, 0.63–1.19) for CGA. For participants with advanced AMD in 1 eye (AREDS category 4), the hazard ratios for fellow eyes were 1.08 (95% CI, 0.65–1.72) for NV AMD and 0.98 (95% CI, 0.64–1.49) for CGA. Conclusions The AREDS results showed no clear effect of cataract surgery on the risk of progression to advanced AMD. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Previously there was no available information on the levels of indicator bacteria and the prevalence of pathogens in fresh produce grown in Alberta, Canada. Baseline information on the occurrence and levels of Escherichia coli and the prevalence of foodborne pathogens in selected produce items available to consumers from farmers' and public markets in two large urban centers and surrounding areas in Alberta was obtained. A total of 10 large markets with between 1 and 12 produce vendors and 26 small markets with between 1 and 6 produce vendors were sampled from 21 June to 7 October 2007. Lettuce (128 samples), spinach (59 samples), tomatoes (120 samples), carrots (206 samples), green onions (129 samples), and strawberries (31 samples) were analyzed for E. coli, Salmonella, E. coli O157:H7, and Campylobacter spp. Lettuce, spinach, green onion, and strawberry samples were also tested for the presence of Cryptosporidium spp. Information on whether produce was grown using organic or conventional practices was obtained from the produce vendors. E. coli was isolated from 8.2% of the samples that included lettuce, spinach, carrots, and green onions. The bacterial counts ranged from0.48 to3.04 Log most probable number per g. E. coli was not isolated from tomatoes or strawberries. The percentage of positive samples ranged from 4.4% for carrots to 27.1% for spinach. Salmonella, E. coli O157:H7, and Campylobacter spp. were not isolated from any of the samples. Cryptosporidium was identified by PCR in one sample of spinach (0.6% of the samples).

Accurate detection and classification of aspiration is a critical component of videofluoroscopic swallowing evaluation, the most commonly utilized instrumental method for dysphagia diagnosis and treatment. Currently published literature indicates that interjudge reliability for the identification of aspiration ranges from poor to fairly good depending on the amount of training provided to clinicians. The majority of extant studies compared judgments among clinicians. No studies included judgments made during the use of a postural compensatory strategy. The purpose of this study was to examine the accuracy of judgments made by speech-language pathologists (SLPs) practicing in hospitals compared with unblinded expert judges when identifying aspiration and using the 8-point Penetration/Aspiration Scale. Clinicians received extensive training for the detection of aspiration and minimal training on use of the Penetration/Aspiration Scale. Videofluoroscopic data were collected from 669 patients as part of a large, randomized clinical trial and include judgments of 10,200 swallows made by 76 clinicians from 44 hospitals in 11 states. Judgments were made on swallows during use of dysphagia compensatory strategies: chin-down posture with thin liquids and head-neutral posture with thickened liquids (nectar-thick and honey-thick consistencies). The subject population included patients with Parkinson's disease and/or dementia. Kappa statistics indicate high accuracy for all interventions by SLPs for identification of aspiration (all kappa0.86) and variable accuracy (range = 69-76%) using the Penetration/Aspiration Scale when compared to expert judges. It is concluded that while the accuracy of identifying the presence of aspiration by SLPs is excellent, more extensive training and/or image enhancement is recommended for precise use of the Penetration/Aspiration Scale.

Background: Cross-sectional studies indicate that diets that provide a higher dietary glycemic index (dGI) are associated with a greater risk of age-related macular degeneration (AMD). No prospective studies have addressed this issue. Objective: The objective was to prospectively evaluate the effect of baseline dGI on the progression of AMD. Design: dGI was calculated as the weighted average of GIs from foods and was evaluated as being above or below the sex median (women: 77.9; men: 79.3) for 3977 participants aged 55-80 y (58% women) in the Age-Related Eye Disease Study. The 7232 eligible eyes without advanced AMD were classified into 1 of 3 AMD categories: group 1 (nonextensive small drusen), group 2 (intermediate drusen, extensive small drusen, or pigmentary abnormalities), or group 3 (large drusen or extensive intermediate drusen). With the use of multifailure Cox proportional-hazards regression, we modeled the time to the maximal progression to evaluate the relation between dGI and the risk of AMD. Results: Overall, the multivariate-adjusted risk of progression over 8 y of follow-up (x: 5.4 y) was significantly higher (risk ratio: 1.10; 95% CI: 1.00, 1.20; P = 0.047) in the high-dGI group than in the low-dGI group. The risk of progression for groups 1, 2, and 3 eyes was 5%, 8%, and 17% greater, respectively (P for trend < 0.001). The latter gives an estimate that 7.8% of new advanced AMD cases would be prevented in 5 y if people consumed the low-dGI diet. Conclusion: Persons at risk of AMD progression, especially those at high risk of advanced AMD, may benefit from consuming a smaller amount of refined carbohydrates.

Background: Age-related macular degeneration (AMD) is the major cause of irreversible blindness. AMD appears to share several carbohydrate-related mechanisms and risk factors with diabetes-related diseases, including retinopathy and cardiovascular disease (CVD); however, to date, only one small study has addressed this issue. Objective: The objective was to test the hypothesis that dietary glycemic index (dGI), which has been related to the risk of diabetes and CVD, is associated with the risk and severity of AMD in nondiabetic elderly populations. Design: Dietary information was obtained from 4099 participants aged 55-80 y (56% women) in the Age-Related Eye Disease Study (AREDS). A total of 8125 eligible eyes at baseline were classified into 1 of 5 AMD groups according to the size and extent of drusen, the presence of geographic atrophy, and neovascular changes. We used a generalized estimating approach to evaluate the relations between dGI and risk and severity of AMD with eyes as the unit of analysis. Results: Compared with eyes in the first quintile of dGI, eyes in the fourth and fifth quintiles had a significantly or suggestively higher risk of large drusen, geographic atrophy, and neovascularization. The multivariate-adjusted odds ratios (95% CIs) for the highest quintile were 1.42 (1.09, 1.84), 1.78 (0.81, 3.90), and 1.41 (0.95, 2.08), respectively, of which only the odds ratio for large drusen was significant. A significant positive relation between dGI and severity of AMD was also noted (P for trend < 0.001). There was a 49% increase in the risk of advanced AMD (geographic atrophy plus neovascularization) for persons with a dGI higher than the sex median (women: ≥77.9; men: ≥79.3). This result indicated that 20% of prevalent cases of AMD would have been eliminated if the AREDS participants consumed diets with a dGI below the median. Conclusion: The association between dGI and AMD from the AREDS cross-sectional analysis at baseline suggests that a reduction in the dGI, a modifiable risk factor, may provide a means of diminishing the risk of AMD.

Conventional culture methods have traditionally been considered the "gold standards" for the isolation and identification of foodborne pathogens. However, culture methods are labor-intensive and time-consuming. We have developed a real-time PCR assay for the detection of Salmonella in a variety of food and food-animal matrices. The real-time PCR assay incorporates both primers and hybridization probes based on the sequence of the Salmonella invA gene and uses fluorescent resonance energy transfer technology to ensure highly sensitive and specific results. This method correctly classified 51 laboratory isolates of Salmonella and 28 non-Salmonella strains. The method was also validated with a large number of field samples that consisted of porcine feces and cecal contents, pork carcasses, bovine feces and beef carcasses, poultry cecal contents and carcasses, equine feces, animal feeds, and various food products. The samples (3388) were preenriched in buffered peptone water and then selectively enriched in tetrathionate and Rappaport-Vassiliadis broths. Aliquots of the selective enrichment broths were combined for DNA extraction and analysis by the real-time PCR assay. When compared with the culture method, the diagnostic sensitivity of the PCR assay for the various matrices ranged from 97.1 to 100.0%, and the diagnostic specificity ranged from 91.3 to 100.0%. Kappa values ranged from 0.87 to 1.00, indicating excellent agreement of the real-time PCR assay to the culture method. The reduction in time and labor makes this highly sensitive and specific real-time PCR assay an excellent alternative to conventional culture methods for surveillance and research studies to improve food safety.

Background Liquid aspiration during swallowing has been linked to pneumonia, the most common cause of infectious death in the elderly. This paper examines the key issues in the design and implementation of the first multisite, randomized behavioral trial in dysphagia in an aging population. The study evaluated two commonly used treatments with respect to short-term and long-term management of liquid aspiration and subsequent pneumonia in dysphagic geriatric participants with dementia and/or Parkinson's disease. Methods Discussed are lessons learned during the conduct of this trial and include (1) ethical and methodological design issues, (2) pragmatic implementation of procedures and forms, (3) importance of multiple communication and monitoring strategies, (4) response to funding issues, and (5) changes in staff and facilities. Results In order to complete this trial the researchers were required to provide more support than anticipated in tasks such as completion of regulatory requirements by sites, supplementing site staff to identify potential study participants using a ‘circuit rider’ approach, continued recruitment of new sites and staff throughout the course of the trial, adapting forms and procedures and managing within economic constraints in a changing trial environment. Limitations Many of the challenges faced by the researchers were not anticipated when the study began. Successful strategies are described for these unanticipated difficulties, based on retrospective evaluation. Conclusions Successful conduct of clinical trials in long-term care environments that are heavily impacted by changes extraneous to the trial design and with staff typically new to clinical trials is possible but success depends on logistical flexibility.

A total of 800 meat and poultry products were purchased from the retail marketplace in Edmonton, Alberta, Canada. The products consisted of raw ground beef, chicken legs, pork chops, and ready-to-eat fermented sausage, roast beef, processed turkey breast, chicken wieners, and beef wieners. The samples were analyzed to determine the prevalence of Shiga toxin-producing Escherichia coli, Salmonella, Campylobacter spp., and Listeria monocytogenes. Shiga toxin-producing E. coli 022: H8 was found in one raw ground beef sample. Salmonella and Campylobacter were found in 30 and 62% of raw chicken legs, respectively. L. monocytogenes was found in 52% of raw ground beef, 34% of raw chicken legs, 24% of raw pork chops, 4% of fermented sausages, 3% of processed turkey breast, 5% of beef wieners, and 3% of chicken wieners. The occurrence of pathogens in this study is similar to that in retail products in many other international locales.

Purpose We aimed to visualize the relationship of predominant dietary patterns and their associations with AMD. Methods A total of 8103 eyes from 4088 participants in the baseline Age-Related Eye Disease Study (AREDS) were classified into three groups: control (n = 2739), early AMD (n = 4599), and advanced AMD (n = 765). Using principle component analysis, two major dietary patterns and eight minor dietary patterns were characterized. Applying logistic regression in our analysis, we related dietary patterns to the prevalence of AMD. Qualitative comparative analysis by operating Boolean algebra and drawing Venn diagrams was used to visualize our findings. Results In general, the eight minor patterns were subsets or extensions of either one of the two major dietary patterns (Oriental and Western patterns) and consisted of fewer characteristic foods than the two major dietary patterns. Unlike the two major patterns, which were more strongly associated with both early and advanced AMD, none of the eight minors were associated with early AMD and only four minor patterns, including the Steak pattern (odds ratio comparing the highest to lowest quintile of the pattern score = 1.73 [95% confidence interval: 1.24 to 2.41; Ptrend = 0.02]), the Breakfast pattern (0.60 [0.44 to 0.82]; Ptrend = 0.004]), the Caribbean pattern (0.64 [0.47 to 0.89; Ptrend = 0.009]), and the Peanut pattern (0.64 [0.46 to 0.89; Ptrend = 0.03]), were significantly associated with advanced AMD. Our data also suggested several potential beneficial (peanuts, pizza, coffee, and tea) and harmful (salad dressing) foods for AMD. Conclusions Our data indicate that a diet of various healthy foods may be optimal for reducing AMD risk. The effects of some specific foods in the context of overall diet warrant further study.

Objective: We hypothesized that major American dietary patterns and differences in specific nutrient intakes within the context of the patterns are associated with age-related macular degeneration ...

We hypothesized that major American dietary patterns are associated with risk for age-related macular degeneration (AMD).Cross-sectional study.We classified 8103 eyes in 4088 eligible participants in the baseline Age-Related Eye Disease Study (AREDS). They were classified into control (n = 2739), early AMD (n = 4599), and advanced AMD (n = 765) by the AREDS AMD Classification System. Food consumption data were collected by using a 90-item food frequency questionnaire.Two major dietary patterns were identified by factor (principal component) analysis based on 37 food groups and named Oriental and Western patterns. The Oriental pattern was characterized by higher intake of vegetables, legumes, fruit, whole grains, tomatoes, and seafood. The Western pattern was characterized by higher intake of red meat, processed meat, high-fat dairy products, French fries, refined grains, and eggs. We ranked our participants according to how closely their diets line up with the 2 patterns by calculating the 2 factor scores for each participant. For early AMD, multivariate-adjusted odds ratio (OR) from generalized estimating equation logistic analysis comparing the highest to lowest quintile of the Oriental pattern score was ORE5O = 0.74 (95% confidence interval (CI): 0.59-0.91; Ptrend =0.01), and the OR comparing the highest to lowest quintile of the Western pattern score was ORE5W = 1.56 (1.18-2.06; Ptrend = 0.01). For advanced AMD, the ORA5O was 0.38 (0.27-0.54; Ptrend0.0001), and the ORA5W was 3.70 (2.31-5.92; Ptrend0.0001).Our data indicate that overall diet is significantly associated with the odds of AMD and that dietary management as an AMD prevention strategy warrants further study.

Background Site monitoring and source document verification account for 15%‒30% of clinical trial costs. An alternative is to streamline site monitoring to focus on correcting trial-specific risks identified by central data monitoring. This risk-based approach could preserve or even improve the quality of clinical trial data and human subject protection compared to site monitoring focused primarily on source document verification. Purpose To determine whether a central review by statisticians using data submitted to the Food and Drug Administration (FDA) by clinical trial sponsors can identify problem sites and trials that failed FDA site inspections. Methods An independent Analysis Center (AC) analyzed data from four anonymous new drug applications (NDAs) where FDA had performed site inspections overseen by FDA’s Office of Scientific Investigations (OSI). FDA team members in the OSI chose the four NDAs from among all NDAs with data in Study Data Tabulation Model (SDTM) format. Two of the NDAs had data that OSI had deemed unreliable in support of the application after FDA site inspections identified serious data integrity problems. The other two NDAs had clinical data that OSI deemed reliable after site inspections. At the outset, the AC knew only that the experimental design specified two NDAs with significant problems. FDA gave the AC no information about which NDAs had problems, how many sites were inspected, or how many were found to have problems until after the AC analysis was complete. The AC evaluated randomization balance, enrollment patterns, study visit scheduling, variability of reported data, and last digit reference. The AC classified sites as ‘High Concern’, ‘Moderate Concern’, ‘Mild Concern’, or ‘No Concern’. Results The AC correctly identified the two NDAs with data deemed unreliable by OSI. In addition, central data analysis correctly identified 5 of 6 (83%) sites for which FDA recommended rejection of data and 13 of 15 sites (87%) for which any regulatory deviations were identified during inspection. Of the six sites for which OSI reviewed inspections and found no deviations, the central process flagged four at the lowest level of concern, one at a moderate level, and one was not flagged. Limitations Central data monitoring during the conduct of a trial while data checking was in progress was not evaluated. Conclusion Systematic central monitoring of clinical trial data can identify problems at the same trials and sites identified during FDA site inspections. Central data monitoring in conjunction with an overall monitoring process that adapts to identify risks as a trial progresses has the potential to reduce the frequency of site visits while increasing data integrity and decreasing trial costs compared to processes that are dependent primarily on source documentation.

Purpose To assess the relationship between plasma levels of homocysteine and age-related macular degeneration (AMD). Design Cross-sectional, case-control study. Methods Fasting plasma homocysteine levels were measured at two centers in 934 individuals who were participating in an ancillary study of the Age-Related Eye Disease Study. There were 547 cases and 387 control subjects, who were determined by fundus photography. Conditional logistic regression analyses were conducted to assess the association of homocysteine with AMD. Results Median values of homocysteine were higher among advanced AMD cases (9.51 mmol/l) compared with persons with no AMD (8.81 mmol/l; P = .01). Values of >12 mmol/l vs ≤12 mmol/l were also associated with an increased risk of AMD ( P = .023), when controlled for other covariates. Conclusion Results are consistent with a possible small, independent association between higher homocysteine levels and AMD. Homocysteine may be a modifiable risk factor for AMD.

To determine the current immunization recommendations of practicing pediatric nephrologists, a questionnaire was sent to the members of the North American Pediatric Renal Transplant Cooperative Society. Sixty-two percent of the centers responded. The results of the survey suggest that although consensus for approaching immunization does exist, recommendations do vary from center to center. Virtually all centers recommend standard vaccines [DTP, oral poliovirus (OPV), hepatitis B (Hep B), and Haemophilus influenzae B (Hib)] for their renal insufficiency and dialysis patients. Despite the fact that they are not infectious, standard killed vaccines (DTP, Hep B, Hib) are recommended less frequently for transplanted patients (86%) than their renal insufficiency (98%) and dialysis (near 100%) counterparts. Additionally, OPV and measles/mumps/rubella (MMR), both live viral vaccines, are rarely recommended post transplant. Almost 90% of centers recommend the use of influenza vaccine, while only 60% of centers recommend pneumococcal vaccine for children with renal disease. Over 70% of centers recommend the newly licensed varicella vaccine for patients on dialysis and those with renal insufficiency. Between 5% and 12% of centers recommend live viral vaccines, including OPV, MMR, and varicella vaccine, for immunosuppressed patients post renal transplant.

To develop a clinical eye-specific prediction model for advanced age-related macular degeneration (AMD).The Age-Related Eye Disease Study (AREDS) cohort followed up for 8 years served as the training dataset, and the Blue Mountains Eye Study (BMES) cohort followed up for 10 years served as the validation dataset.A total of 4507 AREDS participants (contributing 1185 affected vs. 6992 unaffected eyes) and 2169 BMES participants (contributing 69 affected vs. 3694 unaffected eyes).Using Bayes' theorem in a logistic model, we used 8 baseline predictors-age, sex, education level, race, smoking status, and presence of pigment abnormality, soft drusen, and maximum drusen size-to devise and validate a macular risk scoring system (MRSS). We assessed the performance of the MRSS by calculating sensitivity, specificity, and the area under the receiver operating characteristic curve (i.e., c-index).Advanced AMD.The internally validated c-indexAREDS (0.88; 95% confidence interval, 0.87-0.89) and the externally validated c-indexBMES (0.91; 95% confidence interval, 0.88-0.95) suggested excellent performance of the MRSS. The sensitivity and specificity at the optimal macular risk score cutoff point of 0 were 87.6% and 73.6%, respectively. An application for the iPhone and iPad also was developed as a practical tool for the MRSS.The MRSS was developed and validated to provide satisfactory accuracy and generalizability. It may be used to screen patients at risk of developing advanced AMD.

Author(s): Gelman, Benjamin B; Lisinicchia, Joshua G; Morgello, Susan; Masliah, Eliezer; Commins, Deborah; Achim, Cristian L; Fox, Howard S; Kolson, Dennis L; Grant, Igor; Singer, Elyse; Yiannoutsos, Constantin T; Sherman, Seth; Gensler, Gary; Moore, David J; Chen, Tiansheng; Soukup, Vicki M | Abstract: ObjectiveReplicating HIV-1 in the brain is present in HIV encephalitis (HIVE) and microglial nodule encephalitis (MGNE) and is putatively linked with HIV-associated neurocognitive disorders (HAND). A cliniconeurovirological correlation was conducted to elucidate the relationship between brain viral load and clinical phenotype. SUBJECTS AND ASSAYS: HIV gag/pol RNA and DNA copies were quantified with reverse transcriptase-polymerase chain reaction or polymerase chain reaction in 148 HAART-era brain specimens. Comparison with HAND, HIVE, and MGNE and correlation with neuropsychological (NP) test scores were done using one-way ANOVA with Tukey-Kramer and Spearman tests, respectively.ResultsBrain HIV RNA was higher in subjects with HAND plus HIVE versus without HAND (delta = 2.48 log10 units, n = 27 versus 36, P l 0.001). In HAND without HIVE or MGNE, brain HIV RNA was not significantly different versus without HAND (P = 0.314). Worse NP scores correlated significantly with higher HIV RNA and interferon responses in brain specimens (P l 0.001) but not with HIV RNA levels in premortem blood plasma (n = 114) or cerebrospinal fluid (n = 104). In subjects with MGNE, brain HIV RNA was slightly higher versus without MGNE (P l 0.01) and much lower versus with HIVE (P l 0.001).ConclusionsBrain HIV RNA and to a lesser extent HIV DNA are correlated with worse NP performance in the 6 months before death. Linkage occurs primarily in patients with HIVE and MGNE, and these patients could obtain added NP improvement by further reducing brain HIV while on HAART. Patients not in those groups are less certain to obtain added NP benefit.

Human immunodeficiency virus (HIV)-infected patients commonly develop distal symmetric polyneuropathy (DSP). Age, ethnicity, and toxic exposures may influence the risk. In this study we examined the association between substance use, antiretrovirals, ethnicity, and incident neuropathy in an HIV-infected cohort.Data were obtained from the National NeuroAIDS Tissue Consortium (NNTC), an ongoing, prospective cohort started in 1998. Cox proportional hazards models were used to examine the association of substance use, demographics, neurotoxic antiretrovirals, and laboratory parameters with incident neuropathy in 636 participants who were neuropathy-free at baseline.The cumulative incidence of DSP was 41%. Substance use (P = 0.04), number of substances used (P = 0.04), and longer duration of HIV infection (P = 0.05) were associated with incident DSP, but demographic factors, use of neurotoxic antiretrovirals, and laboratory parameters were not.Substance use and longer duration of HIV infection are risk factors for DSP in HIV-infected patients. Use of multiple substances may be particularly risky.

Salmonellosis is one of the most common bacterial foodborne diseases of public health concern in industrialized countries. Poultry products are considered an important source of Salmonella-related foodborne disease in humans. This study was undertaken to evaluate the relationship between various management factors including feed withdrawal and transportation time with Salmonella contamination in crops, ceca, and carcasses of broiler chickens at slaughter in Alberta. Using a two-stage sampling procedure, 30 matched crop and cecal samples before evisceration and an additional 30 neck skin samples after final wash of broiler chickens were collected at slaughter. A questionnaire was administered at the time of sampling to collect information on flock management risk factors. Cecal contents were individually screened with Salmonella-specific real-time PCR to detect positive flocks, and all cecal, crop, and neck skin samples from positive flocks were processed further for Salmonella isolation and characterization. The flock prevalence of Salmonella was 57.1% and within-flock prevalence of Salmonella for positive flocks was 17.2, 8.1, and 53.9% for ceca, crops, and neck skins, respectively. Salmonella Hadar was the most common serovar identified from crops, ceca, and neck skins of broiler chickens tested. Longer transport (P = 0.04 for neck skins) and waiting time in-plant (P = 0.04 for crops, P = 0.03 for ceca) were identified as important risk factors for Salmonella contamination of broiler chickens at slaughter. Salmonella contamination of broiler chickens could potentially be minimized by reducing waiting time in-plant for flocks with longer transport time.

Objective To describe the natural history of eyes with drusenoid pigment epithelial detachments (DPEDs) associated with age-related macular degeneration (AMD). Design Multicenter, clinic-based, prospective cohort study. Participants Among 4757 participants enrolled in the Age-Related Eye Disease Study (AREDS), 255 were identified as having DPED in at least 1 eye and having 5 or more years of follow-up after the initial detection of the DPED. Methods Baseline and annual fundus photographs were evaluated for the evolution of the fundus features and the development of advanced AMD in the forms of central geographic atrophy (CGA) or neovascular (NV) AMD. Kaplan–Meier analyses of progression to advanced AMD and of moderate vision loss (≥15 letters compared with baseline) were performed. Main Outcome Measures Rate of progression to advanced AMD and change in visual acuity from baseline (in terms of mean letters lost and proportion losing ≥15 letters). Results A total of 311 eyes (from 255 participants) with DPED were followed for a median follow-up time of 8 years subsequent to the initial detection of a DPED. Of the 282 eyes that did not have advanced AMD at baseline, advanced AMD developed within 5 years in 119 eyes (42%) (19% progressing to CGA and 23% progressing to NV-AMD). In the remaining eyes that did not develop advanced AMD (n=163), progressive fundus changes, typified by the development of calcified drusen and pigmentary changes, were detected. Visual decline was prominent among study eyes, with approximately 40% of all eyes decreasing in visual acuity by ≥15 letters at 5 years follow-up. Mean visual acuity decreased from 76 letters (∼20/30) at baseline to 61 letters (∼20/60) at 5 years. Five-year decreases in mean visual acuity averaged 26 letters for eyes progressing to advanced AMD and 8 letters for non-progressing eyes. Conclusions The natural history of eyes containing DPED is characterized by a high rate of progression to both CGA and NV-AMD. Among eyes not progressing to advanced AMD, progressive development of pigmentary changes and calcified drusen were observed. Decline of visual acuity is a common outcome, with or without progression to advanced forms of AMD. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

Studies that isolated Listeria spp. from the environment of two meat processing facilities were conducted. Samples were collected in the processing environment of the facilities with three different sampling methods (cotton swab, sterile sponge, and composite-ply tissues) to evaluate their ability to recover Listeria spp. A total of 240 samples for each sampling method were collected and tested. The cotton swab method of sampling was significantly (P0.01) less efficient in recovery of Listeria spp. than the sterile-sponge and composite-ply tissue methods, which were similar (P0.05) in their ability to recover Listeria spp. The specificity and sensitivity of four detection methods (conventional culture, Petrifilm Environmental Listeria Plates [ELP], lateral-flow immunoprecipitation [LFI], and automated PCR) were evaluated for identification of Listeria spp. Facilities were visited until a minimum of 100 positive and 100 negative samples per detection method were collected. The LFI and PCR methods were highly sensitive (95.5 and 99.1%, respectively) and specific (100%) relative to the culture method. The ELP method was significantly less efficient (P0.01) than LFI and PCR in detection of Listeria spp., with lower sensitivity (50.6%) and specificity (91.5%). Kappa values indicated excellent agreement of the LFI and PCR assays and moderate agreement of the ELP method to the culture method. Overall, ELP was easy to use but less efficient in detection of Listeria spp. from environmental samples, while the LFI and PCR methods were found to be excellent alternatives to culture, considering performance and time and labor inputs.

Purpose Because foods provide many nutrients that may interact to modify risk for multifactorial diseases such as age-related macular degeneration (AMD), we sought to develop a composite scoring system to summarize the combined effect of multiple dietary nutrients on AMD risk. This has not been done previously. Design Cross-sectional study. Participants From the 4003 participants in the Age-Related Eye Disease Study (AREDS), there were 7,934 eyes included in this study. Methods Considering dietary intakes of vitamins C and E, zinc, lutein/zeaxanthin, docosahexaenoic acid, eicosapentaenoic acid, and low-dietary glycemic index (dGI) from AREDS baseline information, we assigned each nutrient a percentile rank score then summed them into a compound score for each participant. Using eye as the unit of analysis, we evaluated the association between the compound score and risk of prevalent AMD. Validation, fitness, and performance of the model were evaluated using bootstrapping techniques, adjusted quasi-likelihood under the independence model criterion, and the c-index, respectively. Main Outcome Measures Stereoscopic fundus photographs of the macula were taken and graded at baseline using the AREDS protocol and AMD Classification System. Results Our results showed that higher compound scores were associated with lower risk for early AMD, indicated by drusen, and advanced AMD. Validation analyses indicated that these relationships are robust (the average 50-time bootstrapping per quartile odds ratios=0.727, 0.827, and 0.753, respectively, for drusen, and 0.616, 0.536, and 0.572, respectively, for advanced AMD). Model selection analyses suggested that the compound score should be included, but that measures of dietary β-carotene should not be included. Conclusions We found that consuming diets that provide low dGI and higher intakes of these nutrients were associated with the greatest reduction in risk for prevalent drusen and advanced AMD, whereas dietary β-carotene did not affect these relationships. These findings warrant further prospective studies. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

Swallowing disorders are associated with increased morbidity and mortality. An estimated 18 million adults will require care for dysphagia-related malnutrition, dehydration, pneumonia, and reductions in quality of life by 2010 (1-3). Patients with dysphasia have an increased incidence of aspiration pneumonia because the aspirated material is heavily colonized with bacteria. Pneumonia is the most common cause of infectious death in the United States among persons age 65 years or older and the third leading cause of death for persons age 85 years or older (4). One hospital admission for pneumonia is estimated to cost $7166 (5). Rates of hospital discharge for Medicare beneficiaries with pneumonia as a primary diagnosis have increased by 93.5% in the past decade (6), along with length of stay and death rates (4). Liquid aspiration is the most common type of aspiration in elderly persons (1). Relative risk for pneumonia is highest in patients with dementia, followed by those who are institutionalized (7). As many as 50% of patients with parkinsonism are estimated to have dysphagia (8), and one third aspirate silently---that is, with no external sign (such as coughing) to eject material or alert caregivers (9). Many short- and long-term care facilities use thickened liquid diets to treat of aspiration (10). In these diets, thin liquids (for example, water, tea, coffee) are eliminated, even in the absence of efficacy data, at a substantial cost in financial and quality-of-life terms. It costs approximately $200 per month for an individual to drink thickened liquids (11,12). A common alternative to thickened liquids is use of a chin-down posture (13-17). Welch and coworkers (13) noted that posterior shift of anterior pharyngeal structures with the chin-down posture improved airway protection. Whereas previous studies have provided a basis for the widespread clinical use of chin-down posture, none has provided long-term health outcome data. Results from a previously reported portion of this study demonstrated short-term elimination of aspiration during the videofluorographic swallowing evaluation most often with honey-thick liquids, followed by nectar-thick liquids, and finally chin-down position (18). We sought to compare the effectiveness of chin-down posture and thickened liquids (nectar thick and honey thick) on the incidence of pneumonia in participants with dementia or Parkinson disease during 3 months of treatment.

Purpose This study was designed to identify which of 3 treatments for aspiration on thin liquids—chin-down posture, nectar-thickened liquids, or honey-thickened liquids—results in the most successful immediate elimination of aspiration on thin liquids during the videofluorographic swallow study in patients with dementia and/or Parkinson’s disease. Method This randomized clinical trial included 711 patients ages 50 to 95 years who aspirated on thin liquids as assessed videofluorographically. All patients received all 3 interventions in a randomly assigned order during the videofluorographic swallow study. Results Immediate elimination of aspiration on thin liquids occurred most often with honey-thickened liquids for patients in each diagnostic category, followed by nectar-thickened liquids and chin-down posture. Patients with most severe dementia exhibited least effectiveness on all interventions. Patient preference was best for chin-down posture followed closely by nectar-thickened liquids. Conclusion To identify best short-term intervention to prevent aspiration of thin liquid in patients with dementia and/or Parkinson’s disease, a videofluorographic swallow assessment is needed. Evidence-based practice requires taking patient preference into account when designing a dysphagic patient’s management plan. The longer-term impact of short-term prevention of aspiration requires further study.

Purpose To determine the effects of zinc supplementation on plasma thiol metabolites and their redox status in a cohort of patients with age-related macular degeneration (AMD). Design Randomized clinical trial that evaluated the effects of high doses of zinc and antioxidants on plasma biomarkers of oxidative stress. Methods This was an ancillary study of the Age-Related Eye Disease Study (AREDS). Subjects with AMD were randomized to one of four treatment groups: (1) antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta carotene, 15 mg), (2) zinc (80 mg zinc oxide, 2 mg cupric oxide), (3) antioxidants plus zinc, or (4) placebo. At 20 and 80 months after randomization, blood specimens were collected and analyzed for glutathione (GSH), oxidized glutathione (GSSG), cysteine (Cys), and cystine (CySS). Results Although zinc supplementation had no apparent effect on plasma thiol/disulfide redox status at the first blood draw, the group of patients receiving zinc supplementation at the second blood draw had significantly less CySS compared with those not receiving zinc (54.9 vs 64.1 μM; P = .01). There was a time-dependent oxidation of the plasma GHS pool and was not affected by zinc supplementation. Conclusions Because increased CySS level is associated with aging, oxidative stress, and age-related diseases, the apparent prevention of increased CySS by zinc supplementation warrants additional investigation.

Background Little is known about the association between dietary carbohydrates and cataract in nondiabetic persons. Objective The aim was to test whether recent dietary carbohydrate intakes or glycemic index (GI; a measure of carbohydrate intake quality) was associated with the presence of cortical or nuclear opacities. Design A modified Block food-frequency questionnaire was used to obtain dietary information from 3377 participants (aged 60-80 y; 56% were women) in the Age-Related Eye Disease Study (AREDS). Lens status was evaluated by using the AREDS System for Classifying Cataracts. Associations were examined for eyes with only a single, or pure, type of lens opacity by using the generalized estimating approach to logistic regression to account for the lack of independence between the eyes of a person. Results For participants in the highest quartile, dietary GI was associated with a higher prevalence of all pure nuclear opacities [grade >2; odds ratio (OR): 1.29; 95% CI: 1.04, 1.59; P for trend = 0.02] and moderate nuclear opacities (grade > or =4; OR: 1.43; 95% CI: 0.96, 2.14; P for trend = 0.052). The OR in a comparison of the highest with the lowest quartile of intake was 1.27 (95% CI: 0.99, 1.63; P for trend = 0.09) for cortical opacities of any severity (>0% of area opaque), and the OR increased somewhat for moderate cortical opacities (>5% of area opaque; OR: 1.71; 95% CI: 1.00, 2.95; P for trend = 0.056). Conclusions Results from the cross-sectional analysis of AREDS baseline data suggest that dietary glycemic quality and dietary carbohydrate quantity may be associated with prevalent nuclear and cortical opacities, respectively.

Objective We investigated whether age-related macular degeneration risk factors are associated with high-sensitivity C-reactive protein (CRP) and homocysteine (HCY), systemic biomarkers for cardiovascular disease. Methods Subjects with a range of age-related macular maculopathies or no maculopathy at two centers in the United States were evaluated. Risk factors and biomarkers were assessed by questionnaire, direct measurement, or analyses of blood specimens. Results Higher levels of serum antioxidants vitamin C and lutein/zeaxanthin and higher fish intake were associated with lower serum CRP levels, whereas serum vitamin E, smoking, and increased body mass index were associated with increased CRP. Serum vitamin E, serum α-carotene, and dietary intake of antioxidants and vitamin B6 were associated with lower levels of plasma HCY, whereas hypertension was associated with increased HCY. Conclusions C-reactive protein and HCY levels are related to traditional dietary and behavioral factors associated with age-related macular degeneration.

Purpose Determine whether antioxidant supplements alter the plasma glutathione and/or cysteine redox potential in age-related macular degeneration (AMD) patients. Design This was an ancillary study to the Age-Related Eye Disease Study (AREDS), where subset of AREDS subjects at two sites were studied at two time points, an average of 1.7 and 6.7 years after enrollment. Methods Plasma glutathione (GSH), glutathione disulfide (GSSG), cysteine (Cys), and cystine (CySS) were measured by high-performance liquid chromatography, and redox potentials of GSH/GSSG (Eh GSH) and Cys/CySS (Eh Cys) were calculated. The means of the metabolites and redox potentials were compared by repeated-measures analysis of variance for subjects receiving antioxidants and those not receiving antioxidants. Results At the first blood draw, the means for the antioxidant group (n = 153) and no antioxidant group (n = 159) were not significantly different for any of the metabolites or redox potentials. At the second draw, the GSH parameters were not significantly different between the antioxidant (n = 37) and no antioxidant (n = 45) groups; however, mean Cys was significantly higher in the antioxidant group (9.5 vs 7.2 μmol/l, P = .008). Also, mean Eh Cys was significantly more reduced in the antioxidant group (−74 vs −67.3 mV, P = .03). Conclusions The AREDS antioxidant supplements reduced oxidation of Eh Cys but had no effect on GSH. Because Cys is important for cell growth, apoptosis, and immune function, the beneficial effect of antioxidant supplementation on progression to advanced AMD may be partially explained by its effect on Eh Cys and/or its effect on Cys availability.

The prevalence of Salmonella contamination was assessed at five points in a Canadian pork slaughter plant. In the cooler only 0.5% (2/429) carcasses were positive, even though Salmonella were detected in 51.3% of all cecal samples and in the cecum of at least one pig in 91.5% (43/47) lots tested. Hogs held overnight in lairage were significantly more likely to have positive cecal samples. Salmonella was isolated at least once from the truck, holding pen or cecum of hogs from all 31 producers. Four serotypes comprised 70.3% of 299 isolates: Bovismorbificans, Derby, Brandenburg and Agona. PFGE showed several Salmonella strains were identical between fecal samples and carcass swabs. Many strains were different, suggesting resident bacteria or cross contamination during processing may be important in this plant. Processing interventions appear to be successfully minimizing carcass contamination in this plant. Introduction Salmonella is considered the most important food-borne pathogen from pork. Markets are requiring evidence of Salmonella control both during the production of hogs as well as pork processing. The epidemiology of Salmonella contamination is complex and not well understood. Determining the baseline prevalence of Salmonella at several steps in the pork production chain is a first step in developing a control program. Rates of Salmonella contamination on pork carcasses have been shown to vary widely between individual plants in Canada (Quessy et al., 2004). Differences in infection status of incoming hogs and different procedures in each plant play a role in carcass contamination rates. It has been reported that essentially all Salmonella spp. on pork carcasses leaving the kill floor in a slaughter plant arrive in or on the pig (Berends et al., 1997). Hogs from some farms may be chronically infected with high levels of Salmonella spp, while others may rarely be infected (Rajic et al., 2001, Berends et al., 1996). There is a reported positive correlation between the number of animals that carry Salmonella spp. in their feces and the number of contaminated carcasses (Morgan et al., 1987). Cross contamination and infection of animals can occur during lairage, making the relationship between on-farm infection status and carcass contamination less clear. Negative hogs can become infected with Salmonella within a few hours in a contaminated lairage pen. Increasing lairage time has been reported to increase infection and carcass contamination rates (Hurd et al., 2001, Morgan et al., 1997) Lairage and transport have been identified as interventionpoints where carcass contamination rates can be easily reduced (Hurd et al., 2002, Berends et al., 1996). Some authors indicate that the most cost effective place to intervene may be during processing (Berends et al., 1996). Onfarm controls have also been suggested as effective. In order to identify effective intervention points, the sources of contamination must be identified. Pulsed-field gel electrophoresis (PFGE) is one method that may be used to determine genetic relatedness of strains and sources of contamination. The objectives of this study were to determine the prevalence of Salmonella at five steps in the production chain (truck, lairage pen, cecum, carcass before evisceration, carcass in cooler); to describe Salmonella serovar diversity and relatedness at each step; and to identify risk factors for contamination. This processor would like to determine which steps are the most effective in controlling carcass contamination, and whether to focus control efforts on the farm or at the plant. Materials and Methods Hogs were purposively selected to represent the entire slaughter population based on farm of origin, duration of lairage (length of time the hog is rested before slaughter), lot size, and time of slaughter. A lot was defined as a group of hogs from one farm that were shipped together. Nine hogs were systematically selected from each targeted lot. Lots were not mixed during transport, lairage or processing. Sampling was done over three different seasons. Samples consisted of fecal samples from the truck (TF) and holding pens after lairage (HP), cecal contents (CS); and carcass swabs before O R A L P R E S E N T A T IO N S 39 SafePork 2005 evisceration (BE) and in the chilling cooler (CL). TF and HP samples consisted of 5 individual droppings combined into one 25 g sample. The side of the carcass swabbed was alternated between animals. Carcasses were swabbed following the USDA protocol (USDA, 1996) with one modification; the order of swabbing was belly, jowls then ham. Samples were transported in coolers and tested the following day. The entire swab or 10 g fecal/cecal material was enriched in buffered peptone water for 24 hours. 1 mL of this broth was transferred to tetrathionate broth (TB) and 0.1 mL to Rappaport-Vassiliadis (RVB) broth. The TB was incubated at 35 °C and RV at 42 °C for 24 hours. 150 μL of TB and RVB were combined and screened for Salmonella with real-time PCR (R-PCR). R-PCR positive samples were culturally confirmed and three isolates per sample were frozen. One isolate from each CS sample and all three isolates from CL, BE, TF and HP samples were analyzed by pulsed-field gel electrophoresis (PFGE). PFGE was performed using the PulseNet method (CDC, Atlanta, GA). Representative strains from each PFGE profile were sent to the Public Health Agency of Canada laboratory for serotyping. Results Samples were taken from 47 different lots representing 31 different farms. Salmonella was isolated at least once from the truck, holding pen or cecum of hogs from all 31 producers. Thirty-four of the 47 lots tested were held overnight in lairage before slaughter, which is representative of the typical kill at this plant where 75% of hogs are held overnight. There were significantly more positive fecal samples from the pen floor after lairage (82.9%) than from the truck floor upon arrival (40.5%) (p

Background Despite controversy about paying research subjects, little is known about actual practices in the U.S., including what type of studies offer payment, to what type of subjects, and how amounts are determined. Objective To document current U.S. practices regarding payment to research subjects. Methods The protocols and consent forms of 467 studies offering payment to research subjects approved by 11 IRBs across the U.S. were reviewed to analyze how they describe and justify payment to subjects. Results Money was offered in a wide variety of study types, from short term physiologic studies to large clinical trials of therapeutic interventions, to both patient (61%) and healthy (24.4%) subjects or both (14.6%). Dollar amounts varied widely and were infrequently explicitly described as based on time (19%) or procedures (12%). Unexplained variation in dollar amounts occurred in similar studies or in the same (multi-site) study at different sites, and for similar procedures across studies sometimes even within one site. Although the range was wide ($5–$2000), total amounts were usually modest (overall median $155), and almost always described in the consent form (94.4%) and usually as pro-rated (73%). Conclusions Both patient and healthy subjects are offered payment in a wide variety of types of research in the U.S. Variation in the dollar amounts offered is largely unexplained.