The effects of non-linear bromide adsorption on apparent macrodispersivity

Macrodispersivity estimates are crucial in predicting the subsurface transport of contaminants. These predictions have become increasingly important as the number of contaminated sites continues to increase. In addition, the longevity of many contaminants can affect water quality over extended periods of time. Anionic tracers such as bromide and chloride are commonly used as groundwater tracers in dispersivity experiments because they are inexpensive, easily detected, and are commonly believed to behave conservatively. It has been found, however, that anionic tracers do not always behave conservatively; sediments with a net positive surface charge can adsorb some-of the tracer. A weakly non-linear, experimentally derived Freundlich sorption isotherm was found to describe bromide adsorption in sediments from the Savannah River Site in South Carolina. The aim of this research was to quantify the effects of this sorption on apparent dispersivities relative to a conservative tracer. In addition, the effects on apparent dispersivities of injecting different amounts of tracer and omitting tracer concentrations below detection limits were evaluated. Monte Carlo simulations were performed using SUTRA and W ATSUTRA. The models were developed to simulate natural gradient tracer tests. Two types of hydraulic conductivity fields were generated using the Fast Fourier Transform method. One represented a weakly heterogeneous flow field, with physical parameters similar to the Borden aquifer in Ontario, Canada; the other represented a strongly heterogeneous flow field with physical parameters similar to the Columbus aquifer in Mississippi. These hydraulic conductivity fields represent two extremes of aquifer conditions. Forty simulations were performed in this study for eight cases. Five realizations were performed for each case; each realization was simulated for two years. Apparent dispersivities were calculated by the method of moments. Ensemble means were estimated by averaging the apparent longitudinal or horizontal transverse dispersivity values for the five realizations in each case. Null hypothesis testing was performed with a standard t-test to test the significance between the estimates for the ensemble means for various cases. The following simplifying assumptions were used in this research: 1) Sorption according to the Freundlich isotherm was assumed to be a reversible equilibrium process. Thus, desorption followed the same isotherm as adsorption, only with decreasing concentrations, and both adsorption and desorption were rapid in comparison to advective flow. 2) The Freundlich isotherm was constant throughout the model domain. 3) The groundwater model employed was two-dimensional; vertical heterogeneity was not represented. The results indicated the experimentally derived Freundlich isotherm, given the assumptions and limited number of realizations used in this study, did not significantly affect apparent plume dispersivity values. Thus, bromide was not found to be an unsuitable groundwater tracer. The quantity of tracer mass injected and omission of tracer concentrations below detection limits also did not have a significant effect on apparent dispersivity values. It was found that using tracer concentrations below detection level can adversely affect high-order spatial moments; this finding may, however, be unique to SUTRA and W ATSUTRA or similar finite-element programs

Selection Bias Due to Loss to Follow Up in Cohort Studies

Selection bias due to loss to follow up represents a threat to the internal validity of estimates derived from cohort studies. Over the last fifteen years, stratification-based techniques as well as methods such as inverse probability-of-censoring weighted estimation have been more prominently discussed and offered as a means to correct for selection bias. However, unlike correcting for confounding bias using inverse weighting, uptake of inverse probability-of-censoring weighted estimation as well as competing methods has been limited in the applied epidemiologic literature. To motivate greater use of inverse probability-of-censoring weighted estimation and competing methods, we use causal diagrams to describe the sources of selection bias in cohort studies employing a time-to-event framework when the quantity of interest is an absolute measure (e.g. absolute risk, survival function) or relative effect measure (e.g., risk difference, risk ratio). We highlight that whether a given estimate obtained from standard methods is potentially subject to selection bias depends on the causal diagram and the measure. We first broadly describe inverse probability-of-censoring weighted estimation and then give a simple example to demonstrate in detail how inverse probability-of-censoring weighted estimation mitigates selection bias and describe challenges to estimation. We then modify complex, real-world data from the University of North Carolina Center for AIDS Research HIV clinical cohort study and estimate the absolute and relative change in the occurrence of death with and without inverse probability-of-censoring weighted correction using the modified University of North Carolina data. We provide SAS code to aid with implementation of inverse probability-of-censoring weighted techniques

Hypertension Among HIV-infected Patients in Clinical Care, 1996–2013

BACKGROUND: Persons infected with human immunodeficiency virus (HIV) are at higher risk for major cardiovascular disease (CVD) events than uninfected persons. Understanding the epidemiology of major traditional CVD risk determinants, particularly hypertension, in this population is needed. METHODS: The study population included HIV-infected patients participating in the UNC CFAR HIV Clinical Cohort from 1996 to 2013. Annual incidence rates of hypertension were calculated. Multivariable Poisson models were fit to identify factors associated with incident hypertension. RESULTS: 3141 patients contributed 21 956 person-years (PY) of follow-up. Overall, 57% patients were black, 28% were women, and the median age was 35 years. Hypertension age-standardized incidence rates increased from 1.68 cases per 100 PYs in 1996 to 5.35 cases per 100 PYs in 2013 (P < .001). In adjusted analyses, hypertension rates were higher among obese patients (incidence rate ratio [IRR] 1.70, 95% confidence interval [CI], 1.43-2.02), and those with diabetes mellitus (IRR 1.44, 95% CI, 1.14-1.83) and renal insufficiency (IRR 1.36, 95% CI, 1.16-1.61), but lower among patients with a CD4 nadir of ≥500 cells/mm(3) (IRR 0.73, 95% CI, .53-1.01). CONCLUSIONS: The incidence of hypertension increased from 1996 to 2013, alongside increases in traditional hypertension risk determinants. Notably, HIV-related immunosuppression and ongoing viral replication may contribute to an increased hypertension risk. Aggressive CVD risk factor management, early HIV diagnosis, linkage to care, antiretroviral therapy initiation, and durable viral suppression, will be important components of a comprehensive primary CVD prevention strategy in HIV-infected persons

Outpatient Treatment of SARS-CoV-2 Infection to Prevent COVID-19 Progression

As of March 2021, COVID-19 has caused more than 123 million infections, and almost 3 million deaths worldwide. Dramatic advances have been made in vaccine development and non-pharmaceutical interventions to stop the spread of infection. But treatments to stop the progression of disease are limited. A wide variety of "repurposed" drugs explored for treatment of COVID-19 have had little or no benefit. More recently, intravenous monoclonal antibody (mAb) combinations have been authorized by the US FDA for emergency use (EUA) for outpatients with mild to moderate COVID-19 including some active against emerging SARS-COV-2 variants of concern (VOC). Easier to administer therapeutics including intramuscular and subcutaneous mAbs and oral antivirals are in clinical trials. Reliable, safe, effective COVID-19 treatment for early infection in the outpatient setting is of urgent and critical importance. Availability of such treatment should lead to reduced progression of COVID-19

An Integrated Interdisciplinary Faculty-Student Learning Community Focused on Water Issues: A Case Study

In response to a request from a campus student organization, faculty from three fields came together to develop and teach an integrated interdisciplinary course on water issues and social activism. This course, Water as Life, Death, and Power, brought together topics from the fields of anthropology, biology and chemistry to explore water rights, access to clean water, and water treatment methods. Students enrolled in the course developed projects related to a variety of local and global water issues to present real-world solutions at a university-wide student research showcase. This article describes how we organized the learning community, composed of students, faculty, and staff, and outlines the training process of developing a sense of community, content integration, and interdisciplinary teaching techniques. Cathy Willermet is a Professor of Anthropology at Central Michigan University. Eron Drake is the Assistant Director of the Faculty Center for Innovative Teaching at Central Michigan University. Anja Mueller is a Professor of Chemistry at Central Michigan University. Stephen J. Juris is a Professor of Biology at Central Michigan University. Pratik Chhetri is a graduate student and a member of Universities Allied for Essential Medicines (UAEM) at Central Michigan University. Samik Upadhaya is a graduate student and a member of UAEM at Central Michigan University

Rising prevalence of non-B HIV-1 subtypes in North Carolina and evidence for local onward transmission.

HIV-1 diversity is increasing in North American and European cohorts which may have public health implications. However, little is known about non-B subtype diversity in the southern United States, despite the region being the epicenter of the nation's epidemic. We characterized HIV-1 diversity and transmission clusters to identify the extent to which non-B strains are transmitted locally. We conducted cross-sectional analyses of HIV-1 partial pol sequences collected from 1997 to 2014 from adults accessing routine clinical care in North Carolina (NC). Subtypes were evaluated using COMET and phylogenetic analysis. Putative transmission clusters were identified using maximum-likelihood trees. Clusters involving non-B strains were confirmed and their dates of origin were estimated using Bayesian phylogenetics. Data were combined with demographic information collected at the time of sample collection and country of origin for a subset of patients. Among 24,972 sequences from 15,246 persons, the non-B subtype prevalence increased from 0% to 3.46% over the study period. Of 325 persons with non-B subtypes, diversity was high with over 15 pure subtypes and recombinants; subtype C (28.9%) and CRF02_AG (24.0%) were most common. While identification of transmission clusters was lower for persons with non-B versus B subtypes, several local transmission clusters (≥3 persons) involving non-B subtypes were identified and all were presumably due to heterosexual transmission. Prevalence of non-B subtype diversity remains low in NC but a statistically significant rise was identified over time which likely reflects multiple importation. However, the combined phylogenetic clustering analysis reveals evidence for local onward transmission. Detection of these non-B clusters suggests heterosexual transmission and may guide diagnostic and prevention interventions

Amino-terminal alteration of the HLA-A*0201-restricted human immunodeficiency virus pol peptide increases complex stability and in vitro immunogenicity

Initial studies suggested that major histocompatibility complex class I- restricted viral epitopes could he predicted by the presence of particular residues termed anchors. However, recent studies showed that nonanchor positions of the epitopes are also significant for class I binding and recognition by cytotoxic T lymphocytes (CTLs). We investigated if changing nonanchor amino acids could increase class I affinity, complex stability, and T-cell recognition of a natural viral epitope. This concept was tested by using the HLA-A*0201-restricted human immunodeficiency virus type I epitope from reverse transcriptase (pol). Position 1 (P1) amino acid substitutions were emphasized because P1 alterations may not alter the T-cell receptor interaction. The peptide with the P1 substitution of tyrosine for isoleucine (I1Y) showed a binding affinity for HLA-A*0201 similar to that of the wild- type pol peptide in a cell lysate assembly assay. Surprisingly, I1Y significantly increased the HLA-A*0201-peptide complex stability at the cell surface. I1Y sensitized HLA-A*0201-expressing target cells for wild-type pol-specific CTL lysis as well as wild-type pol. Peripheral blood lymphocytes from three HLA-A2 HIV-seropositive individuals were stimulated in vitro with I1Y and wild-type pol. I1Y stimulated a higher wild-type pol-specific CTL response than wild-type pol in all three donors. Thus, I1V may be an 'improved' epitope for use as a CTL-based human immunodeficiency virus vaccine component. The design of improved epitopes has important ramifications for prophylaxis and therapeutic vaccine development