Horizontal transmission of porcine circovirus type 2 (PCV2)

Porcine circovirus type 2 (PCV2) is a small, non-enveloped, circular, single stranded DNA virus of economic importance in the swine industry worldwide. The focus of this dissertation was to investigate different aspects of horizontal transmission including the use of serology to accurately detect infection, the infectivity and amount of PCV2 present in various secretions and excretions following experimental or natural PCV2 infection, the use of disinfectants in the prevention of PCV2 transmission on livestock trailers, the potential for spread of infectious PCV2 in spray-dried plasma, and evaluation of disinfection protocol of a swine facility following a natural PCV2 outbreak. Results of the first study indicated that evaluated ELISAs had area under the receiver operating curve values greater than 0.94, detected both anti-PCV2a and -2b antibodies with no differentiation, and did cross react with anti-PCV1 antibodies in infected animals. The second study determined that PCV2 exposure (natural or experimental) results in a chronic infection and PCV2 is shed in similar amounts by nasal, oral and fecal routes. In addition, PCV2 DNA present in excretions, secretions or on mechanical vectors is infectious to nayve pigs and therefore important for PCV2 transmission. The third study determined that although PCV2 DNA was detected on trailer surfaces by PCR following three different disinfection protocols, PCV2 was not transmitted to nayve animals exposed to the contaminated trailers. The fourth study provided direct evidence that an experimental spray-drying process was not effective in inactivating PCV2 and it is therefore possible that spray-dried porcine plasma from pigs could represent a biosecurity risk for the industry. The final study showed that the combination of a multistep disinfection protocol with an improved, strict biosecurity plan can result in establishment of a PCV2 nayve herd and this status can be maintained for up to 10 months (300 days)

Evaluation of porcine respiratory and reproductive syndrome virus (PRRSV) ante-mortem diagnostic techniques

Objective. The specific objective of this thesis was to address the U.S. pork industry\u27s need for evaluation of alternative ante-mortem diagnostic samples for PRRSV. To accomplish this objective, three trials were untaken with the following goals: (1) Develop a sampling protocol for the blood swab method. (2) Analyze the diagnostic accuracies of the blood swab, the capillary tube and the jugular sampling methods on two standard PRRS diagnostic tests: quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) and ELISA in known positive and negative animals. (3) Analyze the diagnostic accuracy of the blood swab method for ELISA testing in commercial finishing swine.;Trial one. Trial 1 showed that under laboratory conditions, the Fisherbrand swabs absorbed a significantly higher volume of blood than the Puritan swabs. Trial 2 showed that when the 20g x 1/2&inches; needle was used, significantly more blood was absorbed than when the 25g x 5/8&inches; needle was used regardless of the swab type. Trial 3 confirmed that when the 20g x 1/2&inches; needle was used, the swab absorbed significantly more blood. Trial two. For qRT-PCR testing, the sensitivity and specificity for all sampling methods ranged from 93%--100% for weeks 1--3 PI. Results of ELISA testing depended on cut-off selection. Optimization of ELISA S/P cut-off points for swab sample data was substantially lower (S/P ratio of 0.08 +/- 0.05) than the industry standard (S/P ratio of 0.4). Trial three. The sensitivity and specificity of the swab sampling method was 22.3% (95% probability intervals = 16.0%, 29.2%) and 94.3% (80.1%, 99.8%) respectively when an S/P ratio cut-off of 0.4 was used. The sensitivity and specificity were 94% (89.8%, 97.2%) and 93.5% (77.8%, 99.8%) respectively when an S/P ratio cut-off of 0.08 was used.;Implications. (1) Fisherbrand swabs absorb a significantly greater blood volume (167mul) then Puritan swabs (142mul) under ideal sampling conditions. (2) Under field conditions, the Fisherbrand swabs absorbed numerically less blood (118mul) then under laboratory conditions (167mul). (3) A Fisherbrand swab and a 20g x 1/2&feet; needle combination would be the best diagnostic sample for sows and finisher pigs when collection time is less than 15 seconds. (4) The capillary tube method suffers from neither inadequate volume nor differences in sample type collected (as compared to the blood swab method). This study indicated that the capillary sampling method can be used with ELISA and real-time qRT-PCR testing with diagnostic accuracy equal to the jugular sampling method. The total expense for the capillary sampling method was {dollar}1.44/sample ({dollar}0.94/tube in product and {dollar}0.50/sample in labor cost (calculated for 3 minutes at {dollar}10/hr)). In comparison, the total cost of the jugular sample was {dollar}0.91/sample. (5) Early diagnosis (weeks 1--3 PI) of PRRSV infected nursery pigs using real-time qRT-PCR under study conditions can be equivalently accomplished using the capillary, swab, or jugular sampling methods. (6) No change in cut-off values for qRT-PCR data dichotomization is necessary for data obtained via any of the sampling methods. (7) The diagnostic accuracy of PRRSV ELISA was poor for the swab sampling method when an S/P ration cut-off of 0.4 was utilized (sensitivity ranged from 20%--55.6% over weeks 2--7 PI). (8) When optimal cut-off values are employed, as determined by AUC analysis, all sampling methods are capable of achieving very high diagnostic accuracy on PRRSV ELISA testing. These cut-off values may not be clinically useful. (9) Under commercial (field) conditions, the sensitivity of the swab sampling method was low (22.3%) for ELISA results dichotomized at an S/P ratio of 0.4. (10) The sensitivity of the swab method improved when a lower S/P cut-off was used (94%) indicating this method may have application in routine ELISA diagnostic monitoring programs. (11) In comparison to the jugular sampling method, the sensitivity and specificity of the swab method is lower when used in commercial settings; this will result in more false negative and false positive test results. (12) Under the assumptions of the partial budget, the jugular sampling method would cost a 1000-head sow operation {dollar}0.15/pig produced while the swab sampling method would cost {dollar}0.36/pig produced. (Abstract shortened by UMI.

Plasma concentrations of sodium salicylate in nursery pigs treated orally

Objectives: To determine stability of acetylsalicylic acid (ASA) and sodium salicylate (SS) stock solutions, and to determine plasma concentrations of SS in swine after administration in drinking water. Materials and methods: Stock solutions of liquid ASA and SS products were placed in a nursery environment for 24 hours (Trial One). Salicylate concentrations were measured at 0, 8, 16, and 24 hours using high pressure liquid chromatography (HPLC). In Trial Two, SS was metered into the drinking water of four groups of pigs in a commercial nursery, at stock solution concentrations of 2268 mg per L (T1), 4913 mg per L (T2), 9827 mg per L (T3), and 19,654 mg per L (T4). Controls received nonmedicated water. Plasma salicylate concentrations in 10 pigs per group were measured at 0, 24, 60, and 72 hours. Results: Salicylate concentration ranges of stock solutions in Trial One were 4.04 to 4.61 g per L (ASA) and 8.19 to 9.34 g per L (SS). In Trial Two, mean plasma salicylate concentration ranges for treated groups over the 72-hour study were 0.17 to 0.41 mg per L (T1), 0.03 to 1.28 mg per L (T2), 0.44 to 1.41 mg per L (T3), and 0.62 to 7.22 mg per L (T4). Mean concentrations increased at 24 hours post study initiation, then decreased for all treated groups at 60 hours. Implications: Solubilities of ASA and SS products differ. Sodium salicylate administered via a water-medication system reaches measurable plasma concentrations in nursery pigs. Consistency of dosing may be variable

Evaluation of alternative antemortem diagnostic samples for porcine reproductive and respiratory syndrome virus

Objective: To assess the diagnostic accuracy of two minimally invasive methods of blood collection and a reference method. Materials and methods: Blood samples were collected from 30 pigs at 7 and 8 weeks of age. Fifteen pigs were then inoculated with porcine reproductive and respiratory syndrome virus (PRRSV) VR-2332 and 15 remained uninoculated. Pigs were sampled weekly for 7 weeks post inoculation (PI) using a reference sample (jugular vein sample) and two index samples (whole blood from the auricular vein collected either with a sterile polyester swab or using a capillary tube system). All samples were tested by quantitative reverse transcriptase-polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) using established protocols. Continuous sample data for the three sampling methods were compared by analysis of the area under the receiver-operating characteristic curve. Results: Sensitivity and specificity of qPCR testing for all samples ranged from 93% to 100% for weeks 1 through 3 PI. Results of ELISA testing depended on cutoff selection. Optimized ELISA sample:positive (S:P) ratio cutoffs for swab-sample data were significantly lower (mean S:P ratio cutoff = 0.08, SD = 0.05) than the industry standard (0.4). When the industry standard cutoff of 0.4 was utilized, swab-sample sensitivity ranged from 20.0% to 55.6% over weeks 2 through 7 PI. Implications: Diagnosis of viremic animals using qPCR can be equivalently accomplished using any of the sampling methods. PRRS ELISA status can be determined using any of the sampling methods if an alternative S:P ratio cutoff is used

Going Multimodal: Programmatic, Curricular, and Classroom Change

AS THE STUDENTS NOTE IN this epigraph, we do not live in a monomodal world. Rather, we experience the world and communicate through multiple modalities. To confine students to learning in only one mode, typically the textual mode in first-year writing courses, indeed limits, students\u27 understanding and creative potential-a point that has reemerged in considerations of education and the teaching of writing..

Healthy and Safe Neighborhoods

Final project for URSP688L: Planning Technologies (Fall 2015). University of Maryland, College Park.For this project the Healthy and Safe Neighborhoods group worked with Baltimore’s Southwest Partnership (SWP) to create mapping resources for their seven partnering neighborhoods. The primary focus was to investigate the health and safety of Southwest Baltimore’s current neighborhood using the most recent ACS (American Community Survey) and Census Data as well as open source data provided by the City and the SWP, to determine if certain conditions influence one another. Like much of Baltimore, the Partnership’s neighborhoods have been isolated and neglected due to white flight, racially restrictive zoning, redlining, and “decades of disinvestment.”1 By using GIS mapping to visualize the neighborhood conditions and GIS analysis to pinpoint areas of opportunity and concern, we hope to help SWP focus their resources to attract new residents and investment, particularly from its neighboring partners and anchor institutions. Recently planners have used GIS to map areas of opportunity and spatial mismatch where, for example, employment needs do not match resident skills. Using crime data provided by the SWP and the City, this report compares street conditions and demographics in Southwest Baltimore with contributing factors or variables that would affect the neighborhoods’ health and safety. The following variables were mapped: racial demographics, median household income, vacant houses, crime density by type and time of day, urban tree canopy, street conditions, street lights, and illegal dumping sites. Analysis showed that the neighborhood trends reflected issues facing Baltimore City as a whole, so the study area was expanded to provide context and draw comparisons between the City and the SWP area. Both Baltimore City and the SWP area have overlapping clusters of aging infrastructure, low income, crime, and vacancies abutting areas of wealth and security. In the end, the limiting factors on the analysis were due to incomplete data sets, which SWP recognizes and continues to build.The Southwest Partnership (SWP), Baltimor

Acceptability of Aggression Among Children Who Reside With Substance-Abusing Parents: The Influence of Behavioral Dysregulation, Exposure to Neighborhood Violence, and Interparental Violence

The present study examined how interparental violence, neighborhood violence, behavioral regulation during parental conflict, and age predicted beliefs about the acceptability of aggression and the acceptance of retaliation against an aggressive peer among youths. Participants were 110 families (mothers, fathers, and children) in which one or both parents met criteria for substance use disorder. Results of a bootstrapped multivariate regression model revealed higher exposure to neighborhood violence predicted greater acceptability of general aggression, whereas higher father-to-mother violence perpetration predicted lower acceptability of general aggression. Higher exposure to neighborhood violence, behavioral dysregulation during parental conflict, and older child age predicted greater approval of retaliation toward an aggressive peer. Findings are interpreted as related to the cognitive-contextual framework

2017 Research & Innovation Day Program

A one day showcase of applied research, social innovation, scholarship projects and activities.https://first.fanshawec.ca/cri_cripublications/1004/thumbnail.jp

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570