Site Suitability Analysis for an Intermountain Solid Waste Facility: A Study for Cache County, Utah

The goal of this project was to analyze Cache County for potential sanitary landfill sites covering the period 2020 to 2120. The county population and per capita solid waste were estimated. The minimum landfill size was then calculated. A geographic information system (GIS) was used for data storage and vii analysis. Relevant data were gathered. Areas which would not support a landfill were eliminated. Remaining sites were rated as having slight, moderate, or severe restrictions for use as an area method sanitary landfill based on the Natural Resource Conservation Service (NRCS) Sanitary Facility Report, and the NRCS Soil Interpretations Rating Guide. Seventeen sites were designated as sites for further evaluation. A landfill ranking system giving a primary and/or secondary rating to data items was developed. Nine prime sites had one secondary (.,a ting. These sites should be more closely investigated to determine which are the best potential sites. (136 pages

Development of quantitative suspension array assays for six immunoglobulin isotypes and subclasses to multiple Plasmodium falciparum antigens

Background Quantitative suspension arrays are powerful immunoassays to measure antibodies against multiple antigens in large numbers of samples in a short time and using few microliters. To identify antigen targets of immunity for vaccine development against complex microbes like Plasmodium falciparum, such technology allows the characterization of the magnitude and antigenic specificity of Ig isotypes and subclasses that are important for functional responses. However, standardized assays are not widely available. Methods We developed six quantitative suspension array assays to measure IgG1, IgG2, IgG3, IgG4, IgM and IgE specific to multiple P. falciparum antigens. Secondary and tertiary antibodies, as well as human purified antibodies for standard curves, were tested among several commercially available sources. Positive and negative controls included plasmas from malaria hyper-immune African adults and from malaria-naïve European adults, respectively. Reagents were selected and optimal antibody and test sample dilutions established according to sensitivity, specificity and performance of the standard curves. The variability between replicates and plates was assessed with 30 test samples and controls. Results Assays were able to detect P. falciparum antigen-specific antibodies for all isotypes and subclasses in samples from malaria-exposed individuals, with low background signal in blank wells. Levels detected in malaria-naïve individuals were overall low except for IgM. For the IgG2 and IgE assays, a triple sandwich was required for sensitivity. Standard curves with 5-parameter logistic fit were successfully obtained in all assays. The coefficients of variation for measurements performed in different days were all <30%, and <5% when comparing duplicates from the same plate. Conclusion The isotype/subclass assays developed here were sensitive, specific, reproducible and of adequate quantification dynamic range. They allow performing detailed immuno-profiling to large panels of P. falciparum antigens to address naturally- and vaccine-induced Ig responses and elucidate correlates of malaria protection, and could also be applied to other antigenic panels

Spontaneous splenic rupture in Waldenstrom's macroglobulinemia: a case report

<p>Abstract</p> <p>Introduction</p> <p>We report the case of a patient with Waldenstrom's macroglobulinemia complicated by spontaneous splenic rupture.</p> <p>Case presentation</p> <p>A 49-year-old Caucasian woman was referred to our emergency department by her general practitioner following a three-week history of malaise, night sweats, six kilograms of weight loss, intermittent nausea and vomiting, progressive upper abdominal pain and easy bruising. On the fourth day following her admission, she had a rapid clinical deterioration, with subsequent radiological investigations revealing a splenic rupture. Her morphology, biochemistry, flow cytometry and histology were strongly suggestive of Waldenstrom's macroglobulinemia.</p> <p>Conclusions</p> <p>Spontaneous splenic rupture is not an expected complication of low-grade lymphoplasmacytic lymphomas, such as Waldenstrom's macroglobulinemia. To the best of our knowledge, this is the only reported case of early spontaneous splenic rupture due to Waldenstrom's macroglobulinemia. Our case highlights that despite the typical disease course of low-grade hematological malignancies, signs and symptoms of imminent splenic rupture should be considered when formulating a clinical assessment.</p

Trends in Suicide Among Youth Aged 10 to 19 Years in the United States, 1975 to 2016

IMPORTANCE Suicide is a leading cause of death among youth aged 10 to 19 years in the United States, with rates traditionally higher in male than in female youth. Recent national mortality data suggest this gap may be narrowing, which warrants investigation. OBJECTIVE To investigate trends in suicide rates among US youth aged 10 to 19 years by age group, sex, race/ethnicity, and method of suicide. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study using period trend analysis of US suicide decedents aged 10 to 19 years from January 1, 1975, to December 31, 2016. Data were analyzed for periods defined by statistically significant changes in suicide rate trends. Suicide rates were calculated using population estimates. MAIN OUTCOMES AND MEASURES Period trends in suicide rates by sex and age group were assessed using joinpoint regression. Incidence rate ratios (IRRs) were estimated using negative binomial regression comparing male and female suicide rates within periods. RESULTS From 1975 to 2016, we identified 85 051 youth suicide deaths in the United States (68 085 male [80.1%] and 16 966 female [19.9%]) with a male to female IRR of 3.82 (95% CI, 3.35-4.35). Following a downward trend until 2007, suicide rates for female youth showed the largest significant percentage increase compared with male youth (12.7% vs 7.1% for individuals aged 10-14 years; 7.9% vs 3.5% for individuals aged 15-19 years). The male to female IRR decreased significantly across the study period for youth aged 10 to 14 years (3.14 [95% CI, 2.74-3.61] to 1.80 [95% CI, 1.53-2.12]) and 15 to 19 years (4.15 [95% CI, 3.79-4.54] to 3.31 [95% CI, 2.96-3.69]). Significant declining trends in the male to female IRR were found in non-Hispanic white youth aged 10 to 14 years (3.27 [95% CI, 2.68- 4.00] to 2.04 [95% CI, 1.45-2.89]) and non-Hispanic youth of other races aged 15 to 19 years (4.02 [95% CI, 3.29-4.92] to 2.35 [95% CI, 2.00-2.76]). The male to female IRR for firearms increased significantly for youth aged 15 to 19 years (χ2 = 7.74; P = .02 for sex × period interaction). The male to female IRR of suicide by hanging or suffocation decreased significantly for both age groups (10-14 years: χ2 = 88.83; P \u3c .001 for sex × period interaction and 15-19 years: χ2 = 82.15; P \u3c .001 for sex × period interaction). No significant change was found in the male to female IRR of suicide by poisoning across the study period. CONCLUSIONS AND RELEVANCE A significant reduction in the historically large gap in youth suicide rates between male and female individuals underscores the importance of interventions that consider unique differences by sex. Future research examining sex-specific factors associated with youth suicide is warranted

Chronic Exposure to Malaria Is Associated with Inhibitory and Activation Markers on Atypical Memory B Cells and Marginal Zone-Like B Cells

In persistent infections that are accompanied by chronic immune activation, such as human immunodeficiency virus, hepatitis C virus, and malaria, there is an increased frequency of a phenotypically distinct subset of memory B cells lacking the classic memory marker CD27 and showing a reduced capacity to produce antibodies. However, critical knowledge gaps remain on specific B cell changes and immune adaptation in chronic infections. We hypothesized that expansion of atypical memory B cells (aMBCs) and reduction of activated peripheral marginal zone (MZ)-like B cells in constantly exposed individuals might be accompanied by phenotypic changes that would confer a tolerogenic profile, helping to establish tolerance to infections. To better understand malaria-associated phenotypic abnormalities on B cells, we analyzed peripheral blood mononuclear cells from 55 pregnant women living in a malaria-endemic area of Papua Nueva Guinea and 9 Spanish malaria-naïve individuals using four 11-color flow cytometry panels. We assessed the expression of markers of B cell specificity (IgG and IgM), activation (CD40, CD80, CD86, b220, TACI, and CD150), inhibition (PD1, CD95, and CD71), and migration (CCR3, CXCR3, and CD62l). We found higher frequencies of active and resting aMBC and marked reduction of MZ-like B cells, although changes in absolute cell counts could not be assessed. Highly exposed women had higher PD1+-, CD95+-, CD40+-, CD71+-, and CD80+-activated aMBC frequencies than non-exposed subjects. Malaria exposure increased frequencies of b220 and proapoptotic markers PD1 and CD95, and decreased expression of the activation marker TACI on MZ-like B cells. The increased frequencies of inhibitory and apoptotic markers on activated aMBCs and MZ-like B cells in malaria-exposed adults suggest an immune-homeostatic mechanism for maintaining B cell development and function while simultaneously downregulating hyperreactive B cells. This mechanism would keep the B cell activation threshold high enough to control infection but impaired enough to tolerate it, preventing systemic inflammation

Next-generation sequencing reveals large connected networks of intra-host HCV variants

Background: Next-generation sequencing (NGS) allows for sampling numerous viral variants from infected patients. This provides a novel opportunity to represent and study the mutational landscape of Hepatitis C Virus (HCV) within a single host. Results: Intra-host variants of the HCV E1/E2 region were extensively sampled from 58 chronically infected patients. After NGS error correction, the average number of reads and variants obtained from each sample were 3202 and 464, respectively. The distance between each pair of variants was calculated and networks were created for each patient, where each node is a variant and two nodes are connected by a link if the nucleotide distance between them is 1. The work focused on large components having > 5% of all reads, which in average account for 93.7% of all reads found in a patient. The distance between any two variants calculated over the component correlated strongly with nucleotide distances (r = 0.9499; p = 0.0001), a better correlation than the one obtained with Neighbour-Joining trees (r = 0.7624; p = 0.0001). In each patient, components were well separated, with the average distance between (6.53%) being 10 times greater than within each component (0.68%). The ratio of nonsynonymous to synonymous changes was calculated and some patients (6.9%) showed a mixture of networks under strong negative and positive selection. All components were robust to in silico stochastic sampling; even after randomly removing 85% of all reads, the largest connected component in the new subsample still involved 82.4% of remaining nodes. In vitro sampling showed that 93.02% of components present in the original sample were also found in experimental replicas, with 81.6% of reads found in both. When syringe-sharing transmission events were simulated, 91.2% of all simulated transmission events seeded all components present in the source. Conclusions: Most intra-host variants are organized into distinct single-mutation components that are: well separated from each other, represent genetic distances between viral variants, robust to sampling, reproducible and likely seeded during transmission events. Facilitated by NGS, large components offer a novel evolutionary framework for genetic analysis of intra-host viral populations and understanding transmission, immune escape and drug resistance

Thermal Emission of WASP-14b Revealed with Three Spitzer Eclipses

Exoplanet WASP-14b is a highly irradiated, transiting hot Jupiter. Joshi et al. calculate an equilibrium temperature Teq of 1866 K for zero albedo and reemission from the entire planet, a mass of 7.3 +/- 0.5 Jupiter masses and a radius of 1.28 +/- 0.08 Jupiter radii. Its mean density of 4.6 g/cm3 is one of the highest known for planets with periods less than 3 days. We obtained three secondary eclipse light curves with the Spitzer Space Telescope. The eclipse depths from the best jointly fit model are $0.224\%$ +/- $0.018\%$ at 4.5 {\mu}m and $0.181\%$ +/- $0.022\%$ at 8.0 {\mu}m. The corresponding brightness temperatures are 2212 +/- 94 K and 1590 +/- 116 K. A slight ambiguity between systematic models suggests a conservative 3.6 {\mu}m eclipse depth of $0.19\%$ +/- $0.01\%$ and brightness temperature of 2242 +/- 55 K. Although extremely irradiated, WASP-14b does not show any distinct evidence of a thermal inversion. In addition, the present data nominally favor models with day night energy redistribution less than $~30\%$. The current data are generally consistent with oxygen-rich as well as carbon-rich compositions, although an oxygen-rich composition provides a marginally better fit. We confirm a significant eccentricity of e = 0.087 +/- 0.002 and refine other orbital parameters.Comment: 16 pages, 16 figure

Modeling the effect of lockdown timing as a COVID‑19 control measure in countries with differing social contacts

The application, timing, and duration of lockdown strategies during a pandemic remain poorly quantified with regards to expected public health outcomes. Previous projection models have reached conflicting conclusions about the effect of complete lockdowns on COVID-19 outcomes. We developed a stochastic continuous-time Markov chain (CTMC) model with eight states including the environment (SEAMHQRD-V), and derived a formula for the basic reproduction number, R0, for that model. Applying the R 0 formula as a function in previously-published social contact matrices from 152 countries, we produced the distribution and four categories of possible R 0 for the 152 countries and chose one country from each quarter as a representative for four social contact categories (Canada, China, Mexico, and Niger). The model was then used to predict the effects of lockdown timing in those four categories through the representative countries. The analysis for the effect of a lockdown was performed without the influence of the other control measures, like social distancing and mask wearing, to quantify its absolute effect. Hypothetical lockdown timing was shown to be the critical parameter in ameliorating pandemic peak incidence. More importantly, we found that well-timed lockdowns can split the peak of hospitalizations into two smaller distant peaks while extending the overall pandemic duration. The timing of lockdowns reveals that a “tunneling” effect on incidence can be achieved to bypass the peak and prevent pandemic caseloads from exceeding hospital capacity

Early detection of Mycobacterium avium subsp. paratuberculosis infection in cattle with multiplex-bead based immunoassays

Johne’s Disease (JD), caused by Mycobacterium avium subspecies paratuberculosis (MAP), results in significant economic loss to livestock production. The early detection of MAP infection in animals with extant serological assays has remained challenging due to the low sensitivity of commercially available ELISA tests, a fact that has hampered the development of effective JD control programs. Our recent protein microarray-based studies identified several promising candidate antigens that are immunogenic during different stages of MAP infection. To evaluate these antigens for use in diagnostic assays and reliably identify animals with MAP infection, a multiplex (Luminex®) assay was developed using color-coded flourescent beads coupled to 6 MAP recombinant proteins and applied to screen 180 serum and 90 milk samples from cows at different stages of MAP infection including negative (NL), fecal test positive/ELISA negative (F+E-), and fecal positive/ELISA positive (F+E+). The results show that while serum antibody reactivities to each of the 6 anti-gens were highest in F+E+ group, antibody reactivity to three of the six antigens were identified in the F+E- group, suggesting that these three antigens are expressed and provoke antibody responses during the early infection stages with MAP. Further, antibodies against all six antigens were elevated in milk samples from both the F+E- and F+E+ groups in comparison to the NL group (