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1.
ACS ES T Water ; 2(11): 2094-2104, 2022 Nov 11.
Article in English | MEDLINE | ID: mdl-37552737

ABSTRACT

Congregate living poses one of the highest risk situations for the transmission of respiratory viruses including SARS-CoV-2. University dormitories exemplify such high-risk settings. We demonstrate the value of using building-level SARS-CoV-2 wastewater surveillance as an early warning system to inform when prevalence testing of all building occupants is warranted. Coordinated daily testing of composite wastewater samples and clinical testing in dormitories was used to prompt the screening of otherwise unrecognized infected occupants. We overlay the detection patterns in the context of regular scheduled occupant testing to validate a wastewater detection model. The trend of wastewater positivity largely aligned well with the clinical positivity and epidemiology of dormitory occupants. However, the predictive ability of wastewater-surveillance to detect new positive cases is hampered by convalescent shedding in recovered/noncontagious individuals as they return to the building. Building-level pooled wastewater-surveillance and forecasting is most productive for predicting new cases in low-prevalence instances at the community level. For higher-education facilities and other congregate living settings to remain in operation during a pandemic, a thorough surveillance-based decision-making system is vital. Building-level wastewater monitoring on a daily basis paired with regular testing of individual dormitory occupants is an effective and efficient approach for mitigating outbreaks on university campuses.

2.
Appl Environ Microbiol ; 87(13): e0043321, 2021 06 11.
Article in English | MEDLINE | ID: mdl-33858836

ABSTRACT

Wastewater-based monitoring for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the individual building level could be an efficient, passive means of early detection of new cases in congregate living settings, but this approach has not been validated. Preliminary samples were collected from a hospital and a local municipal wastewater treatment plant. Molecular diagnostic methods were compared side by side to assess feasibility, performance, and sensitivity. Refined sample collection and processing protocols were then used to monitor two occupied dormitory complexes (n = 105 and 66) over 8 weeks. Wastewater results were validated using known case counts from external clinical testing of building occupants. Results confirm that ultracentrifugation from a 24-h composite collection had a sensitivity of 96.2% and a specificity of 100%. However, the method could not distinguish new infectious cases from persistent convalescent shedding of SARS-CoV-2 RNA. If the detection of convalescent shedding is considered a false positive, then the sensitivity is 100% and specificity drops to 45%. It was determined that the proposed approach constitutes a highly sensitive wastewater surveillance method for detecting SARS-CoV-2, but it could not distinguish new infectious cases from persistent convalescent shedding. Future work must focus on approaches to distinguish new infections from convalescent shedding to fully realize the potential of building wastewater as a surveillance tool for congregate living. IMPORTANCE Some of the most severe outbreaks of COVID-19 have taken place in places where persons live together, such as nursing homes. Wastewater testing from individual buildings could be used for frequent pooled surveillance of virus from all occupants, including those who are contagious, with or without symptoms. This work provides a sensitive practical method for detecting infected individuals, as validated in two building complexes housing occupants who underwent frequent clinical testing performed by external entities. Although this sensitive method could be deployed now for pooled surveillance as an early warning system to limit outbreaks, the study shows that the approach will require further refinement to differentiate contagious, newly infected individuals from persons who have persistent viral fragments shedding in their stool outside the contagious period.


Subject(s)
COVID-19/epidemiology , Residential Facilities , SARS-CoV-2/isolation & purification , Wastewater/virology , COVID-19/diagnosis , Humans , Molecular Diagnostic Techniques , Reproducibility of Results , SARS-CoV-2/genetics , Wastewater-Based Epidemiological Monitoring
3.
PLoS One ; 15(5): e0232872, 2020.
Article in English | MEDLINE | ID: mdl-32396548

ABSTRACT

Fish populations globally are susceptible to endangerment through exploitation and habitat loss. We present theoretical simulations to explore how reduced adult survival (age truncation) might affect short-lived freshwater fish species in human-altered contemporary environments. Our simulations evaluate two hypothetical "average fish" and five example fish species of age 1 or age 2 maturity. From a population equilibrium baseline representing a natural, unaltered environment we impose systematic reductions in adult survival and quantify how age truncation affects the causes of variation in population growth rate. We estimate the relative contributions to population growth rate arising from simulated temporal variation in age-specific vital rates and population structure. At equilibrium and irrespective of example species, population structure (first adult age class) and survival probability of the first two adult age classes are the most important determinants of population growth. As adult survival decreases, the first reproductive age class becomes increasingly important to variation in population growth. All simulated examples show the same general pattern of change with age truncation as known for exploited, longer-lived fish species in marine and freshwater environments. This implies age truncation is a general potential concern for fish biodiversity across life history strategies and ecosystems. Managers of short-lived, freshwater fishes in contemporary environments often focus on supporting reproduction to ensure population persistence. However, a strong focus on water management to support reproduction may reduce adult survival. Sustainability management needs a focus on mitigating adult mortality in human-altered ecosystems. A watershed spatial extent embracing land and water uses may be necessary to identify and mitigate causes of age truncation in freshwater species. Achieving higher adult survival will require paradigm transformations in society and government about water management priorities.


Subject(s)
Conservation of Natural Resources/methods , Fishes/growth & development , Animals , Computer Simulation , Ecosystem , Endangered Species , Fisheries , Fresh Water , Human Activities , Humans , Population Growth
4.
Appl Opt ; 57(22): 6565-6571, 2018 Aug 01.
Article in English | MEDLINE | ID: mdl-30117897

ABSTRACT

We report a new framework for a quantitative understanding of optical trapping (OT) particle handling dynamics. We present a novel three-dimensional particle-based model that includes optical, hydrodynamic, and inter-particle forces. This semi-empirical colloid model is based on an open-source simulation code known as LAMMPS (large-scale atomic/molecular massively parallel simulator) and properly recapitulates the full OT force profile beyond the typical linear approximations valid near the trap center. Simulations are carried out with typical system parameters relevant for our experimental holographic optical trapping (HOT) system, including varied particle sizes, trap movement speeds, and beam powers. Furthermore, we present a new experimental method for measuring both the stable and metastable boundaries of the optical force profile to inform or validate the model's underlying force profile. We show that our framework is a powerful tool for accurately predicting particle behavior in a practical experimental OT setup and can be used to characterize and predict particle handling dynamics within any arbitrary OT force profile.

5.
Malar J ; 16(1): 115, 2017 03 13.
Article in English | MEDLINE | ID: mdl-28288639

ABSTRACT

BACKGROUND: Non-human primates, such as the rhesus macaques, are the preferred model for down-selecting human malaria vaccine formulations, but the rhesus model is expensive and does not allow for direct efficacy testing of human malaria vaccines. Transgenic rodent parasites expressing genes of human Plasmodium are now routinely used for efficacy studies of human malaria vaccines. Mice have however rarely predicted success in human malaria trials and there is scepticism whether mouse studies alone are sufficient to move a vaccine candidate into the clinic. METHODS: A comparison of immunogenicity, fine-specificity and functional activity of two Alum-adjuvanted Plasmodium falciparum circumsporozoite protein (CSP)-based vaccines was conducted in mouse and rhesus models. One vaccine was a soluble recombinant protein (CSP) and the other was the same CSP covalently conjugated to the Qß phage particle (Qß-CSP). RESULTS: Mice showed different kinetics of antibody responses and different sensitivity to the NANP-repeat and N-terminal epitopes as compared to rhesus. While mice failed to discern differences between the protective efficacy of CSP versus Qß-CSP vaccine following direct challenge with transgenic Plasmodium berghei parasites, rhesus serum from the Qß-CSP-vaccinated animals induced higher in vivo sporozoite neutralization activity. CONCLUSIONS: Despite some immunologic parallels between models, these data demonstrate that differences between the immune responses induced in the two models risk conflicting decisions regarding potential vaccine utility in humans. In combination with historical observations, the data presented here suggest that although murine models may be useful for some purposes, non-human primate models may be more likely to predict the human response to investigational vaccines.


Subject(s)
Malaria Vaccines/immunology , Plasmodium falciparum/immunology , Protozoan Proteins/immunology , Animals , Female , Immunogenicity, Vaccine , Macaca mulatta , Male , Mice , Mice, Inbred C57BL , Recombinant Proteins/immunology
6.
Accid Anal Prev ; 88: 1-8, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26710265

ABSTRACT

Across the nation, researchers and transportation engineers are developing safety performance functions (SPFs) to predict crash rates and develop crash modification factors to improve traffic safety at roadway segments and intersections. Generalized linear models (GLMs), such as Poisson or negative binomial regression, are most commonly used to develop SPFs with annual average daily traffic as the primary roadway characteristic to predict crashes. However, while more complex to interpret, data mining models such as boosted regression trees have improved upon GLMs crash prediction performance due to their ability to handle more data characteristics, accommodate non-linearities, and include interaction effects between the characteristics. An intersection data inventory of 36 safety relevant parameters for three- and four-legged non-signalized intersections along state routes in Alabama was used to study the importance of intersection characteristics on crash rate and the interaction effects between key characteristics. Four different SPFs were investigated and compared: Poisson regression, negative binomial regression, regularized generalized linear model, and boosted regression trees. The models did not agree on which intersection characteristics were most related to the crash rate. The boosted regression tree model significantly outperformed the other models and identified several intersection characteristics as having strong interaction effects.


Subject(s)
Accidents, Traffic/statistics & numerical data , Environment Design/statistics & numerical data , Models, Statistical , Alabama , Humans , Linear Models , Logistic Models , Models, Theoretical , Poisson Distribution , Safety , Transportation
7.
Clin Vaccine Immunol ; 20(6): 803-10, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23536694

ABSTRACT

Circumsporozoite protein (CSP) of Plasmodium falciparum is a protective human malaria vaccine candidate. There is an urgent need for models that can rapidly down-select novel CSP-based vaccine candidates. In the present study, the mouse-mosquito transmission cycle of a transgenic Plasmodium berghei malaria parasite stably expressing a functional full-length P. falciparum CSP was optimized to consistently produce infective sporozoites for protection studies. A minimal sporozoite challenge dose was established, and protection was defined as the absence of blood-stage parasites 14 days after intravenous challenge. The specificity of protection was confirmed by vaccinating mice with multiple CSP constructs of differing lengths and compositions. Constructs that induced high NANP repeat-specific antibody titers in enzyme-linked immunosorbent assays were protective, and the degree of protection was dependent on the antigen dose. There was a positive correlation between antibody avidity and protection. The antibodies in the protected mice recognized the native CSP on the parasites and showed sporozoite invasion inhibitory activity. Passive transfer of anti-CSP antibodies into naive mice also induced protection. Thus, we have demonstrated the utility of a mouse efficacy model to down-select human CSP-based vaccine formulations.


Subject(s)
Malaria Vaccines/immunology , Malaria/prevention & control , Parasitemia/prevention & control , Protozoan Proteins/immunology , Vaccination/methods , Animals , Antibodies, Protozoan/blood , Culicidae , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Malaria Vaccines/genetics , Malaria Vaccines/isolation & purification , Mice , Mice, Inbred C57BL , Plasmodium berghei/genetics , Plasmodium berghei/immunology , Plasmodium falciparum/genetics , Plasmodium falciparum/immunology , Protozoan Proteins/genetics , Vaccines, Synthetic/genetics , Vaccines, Synthetic/immunology , Vaccines, Synthetic/isolation & purification
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