Using a simple 2D steady-state saturated flow and reactive transport model to elucidate denitrification patterns in a hillslope aquifer

In the last 50 years, agricultural intensification has resulted in increasing nutrient losses that threaten the health of the lakes on the volcanic plateau of New Zealand’s North Island. As part of our efforts to understand the transport and transformations of nitrogen in this landscape, the 2D vertical groundwater transport model AquiferSim 2DV was used to simulate water flow, nitrate transport, denitrification, and discharge to surface waters in a hillslope adjacent to a wetland and stream discharging into Lake Taupo, Australasia’s largest lake. AquiferSim 2DV is a steady state model using the finite-difference stream function method for flow modelling and finite-volume mixing cell method for contaminant transport modelling. The ratio of horizontal to vertical hydraulic conductivity must be specified within the aquifer domain, as must effective porosity and denitrification rates. Boundary conditions consist of recharge fluxes and contaminant concentrations, as well as the assumed zone of discharge. Hydrodynamic dispersion is simulated through numerical dispersion, which depends on grid resolution. Denitrification reactions within each computational cell may include both zero-order and first-order rates. All parameters may be spatially heterogeneous. Previous applications of this model have been to essentially horizontal aquifer systems. By contrast, this hillslope system has sloping material layers and a dynamic and sloping water table. Extensions were made to AquiferSim 2DV, including representation of converging/diverging flow, which allowed a 2D steady-state model of this system to be developed. Comparison of model predictions with detailed water level and hydrochemical data from the site, however, showed that the model’s attractive simplicity in this case precluded adequate characterisation of what is essentially a 3D, transient system. While the model produced reasonable agreement with the concentration patterns under an average water table profile, predictions of oxygen and nitrate concentrations under low summer and high spring water table conditions were poor. The seasonal changes reflected an annual recharge pulse of fresh, oxidised water followed by gradual oxygen depletion till the next recharge pulse occurs in the following year, an essentially transient phenomenon which could not be represented using a steady state model. This in itself has provoked fresh thinking about the dynamic nature of flow and chemistry at the site

Predicting Risk of End-Stage Liver Disease in Antiretroviral-Treated HIV/Hepatitis C Virus-Coinfected Patients

Background. End-stage liver disease (ESLD) is an important cause of morbidity among HIV/hepatitis C virus (HCV)-coinfected patients. Quantifying the risk of this outcome over time could help determine which coinfected patients should be targeted for risk factor modification and HCV treatment. We evaluated demographic, clinical, and laboratory variables to predict risk of ESLD in HIV/HCV-coinfected patients receiving antiretroviral therapy (ART). Methods. We conducted a retrospective cohort study among 6,016 HIV/HCV-coinfected patients who received ART within the Veterans Health Administration between 1997 and 2010. The main outcome was incident ESLD, defined by hepatic decompensation, hepatocellular carcinoma, or liver-related death. Cox regression was used to develop prognostic models based on baseline demographic, clinical, and laboratory variables, including FIB-4 and aspartate aminotransferase-to-platelet ratio index, previously validated markers of hepatic fibrosis. Model performance was assessed by discrimination and decision curve analysis. Results. Among 6,016 HIV/HCV patients, 532 (8.8%) developed ESLD over a median of 6.6 years. A model comprising FIB-4 and race had modest discrimination for ESLD (c-statistic, 0.73) and higher net benefit than alternative strategies of treating no or all coinfected patients at relevant risk thresholds. For FIB-4 \u3e3.25, ESLD risk ranged from 7.9% at 1 year to 26.0% at 5 years among non-blacks and from 2.4% at 1 year to 14.0% at 5 years among blacks. Conclusions. Race and FIB-4 provided important predictive information on ESLD risk among HIV/HCV patients. Estimating risk of ESLD using these variables could help direct HCV treatment decisions among HIV/HCV-coinfected patients

HIV RNA, CD4+ Percentage, and Risk of Hepatocellular Carcinoma by Cirrhosis Status.

BackgroundDespite increasing incidence of hepatocellular carcinoma (HCC) among HIV-infected patients, it remains unclear if HIV-related factors contribute to development of HCC. We examined if higher or prolonged HIV viremia and lower CD4+ cell percentage were associated with HCC.MethodsWe conducted a cohort study of HIV-infected individuals who had HIV RNA, CD4+, and CD8+ cell counts and percentages assessed in the Veterans Aging Cohort Study (1999-2015). HCC was ascertained using Veterans Health Administration cancer registries and electronic records. Cox regression was used to determine hazard ratios (HR, 95% confidence interval [CI]) of HCC associated with higher current HIV RNA, longer duration of detectable HIV viremia (≥500 copies/mL), and current CD4+ cell percentage less than 14%, adjusting for traditional HCC risk factors. Analyses were stratified by previously validated diagnoses of cirrhosis prior to start of follow-up.ResultsAmong 35 659 HIV-infected patients, 302 (0.8%) developed HCC over 281 441 person-years (incidence rate = 107.3 per 100 000 person-years). Among patients without baseline cirrhosis, higher HIV RNA (HR = 1.25, 95% CI = 1.12 to 1.40, per 1.0 log10 copies/mL) and 12 or more months of detectable HIV (HR = 1.47, 95% CI = 1.02 to 2.11) were independently associated with higher risk of HCC. CD4+ percentage less than 14% was not associated with HCC in any model. Hepatitis C coinfection was a statistically significant predictor of HCC regardless of baseline cirrhosis status.ConclusionAmong HIV-infected patients without baseline cirrhosis, higher HIV RNA and longer duration of HIV viremia increased risk of HCC, independent of traditional HCC risk factors. This is the strongest evidence to date that HIV viremia contributes to risk of HCC in this group

Provider verification of electronic health record receipt and nonreceipt of direct-acting antivirals for the treatment of hepatitis C virus infection.

PURPOSE: Pharmacoepidemiologic studies using electronic health record data could serve an important role in assessing safety and effectiveness of direct-acting antiviral therapy for chronic hepatitis C virus (HCV) infection, but the validity of these data needs to be determined. We evaluated the accuracy of pharmacy fill records in the national Veterans Health Administration (VA) Corporate Data Warehouse (CDW) as compared to facility-level electronic health record. METHODS: Patients prescribed a direct-acting antiviral regimen at five VA sites between 2014 and 2016 were randomly selected and reviewed. A random sample of patients with chronic HCV infection without evidence of HCV treatment during the study period also underwent chart review. We calculated positive predictive value and negative predictive value overall and by site. RESULTS: Of the 501 patients who received a total of 2416 prescriptions, 494 were validated using data extracted from CDW 6 months after the study period, yielding a positive predictive value of 98.6% (95% confidence interval, 97.6%-99.6%). Of the 100 patients with chronic HCV infection without prescriptions for HCV treatment, 99 were confirmed not to have received antiviral treatment (negative predictive value, 99.0%; 95% confidence interval, 97.1%-100%). CONCLUSIONS: These findings provide assurance to researchers who use national VA CDW data for retrospective cohort studies that the CDW contains accurate information on HCV therapies in the modern treatment era

Dexamethasone in hospitalised coronavirus-19 patients not on intensive respiratory support.

INTRODUCTION: Dexamethasone decreases mortality in coronavirus disease 2019 (COVID-19) patients on intensive respiratory support (IRS) but is of uncertain benefit if less severely ill. We determined whether early (within 48 h) dexamethasone was associated with mortality in patients hospitalised with COVID-19 not on IRS. METHODS: We included patients admitted to Veterans Affairs hospitals between June 7, 2020-May 31, 2021 within 14-days after SARS-CoV-2 positive test. Exclusions included recent prior corticosteroids and IRS within 48 h. We used inverse probability of treatment weights (IPTW) to balance exposed and unexposed groups, and Cox proportional hazards models to determine 90-day all-cause mortality. RESULTS: Of 19 973 total patients (95% men, median age 71, 27% black), 15 404 (77%) were without IRS within 48 h. Of these, 3514/9450 (34%) patients on no oxygen received dexamethasone and 1042 (11%) died; 4472/5954 (75%) patients on low-flow nasal cannula (NC) received dexamethasone and 857 (14%) died. In IPTW stratified models, patients on no oxygen who received dexamethasone experienced 76% increased risk for 90-day mortality (hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.47 to 2.12); there was no association with mortality among patients on NC (HR 1.08, 95% CI 0.86 to 1.36). CONCLUSION: In patients hospitalised with COVID-19, early initiation of dexamethasone was common and was associated with no mortality benefit among those on no oxygen or NC in the first 48 h; instead, we found evidence of potential harm. These real-world findings do not support the use of early dexamethasone in hospitalised COVID-19 patients without IRS

Early incidence of occupational asthma among young bakers, pastry-makers and hairdressers: design of a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Occupational exposures are thought to be responsible for 10-15% of new-onset asthma cases in adults, with disparities across sectors. Because most of the data are derived from registries and cross-sectional studies, little is known about incidence of occupational asthma (OA) during the first years after inception of exposure. This paper describes the design of a study that focuses on this early asthma onset period among young workers in the bakery, pastry making and hairdressing sectors in order to assess early incidence of OA in these "at risk" occupations according to exposure duration, and to identify risk factors of OA incidence.</p> <p>Methods/Design</p> <p>The study population is composed of subjects who graduated between 2001 and 2006 in these sectors where they experience exposure to organic or inorganic allergenic or irritant compounds (with an objective of 150 subjects by year) and 250 young workers with no specific occupational exposure. A phone interview focusing on respiratory and 'Ear-Nose-Throat' (ENT) work-related symptoms screen subjects considered as "possibly OA cases". Subjects are invited to participate in a medical visit to complete clinical and lung function investigations, including fractional exhaled nitric oxide (FE_NO) and carbon monoxide (CO) measurements, and to collect blood samples for IgE (Immunoglobulin E) measurements (total IgE and IgE for work-related and common allergens). Markers of oxidative stress and genetic polymorphisms exploration are also assessed. A random sample of 200 "non-cases" (controls) is also visited, following a nested case-control design.</p> <p>Discussion</p> <p>This study may allow to describ a latent period between inception of exposure and the rise of the prevalence of asthma symptoms, an information that would be useful for the prevention of OA. Such a time frame would be suited for conducting screening campaigns of this emergent asthma at a stage when occupational hygiene measures and adapted therapeutic interventions might be effective.</p> <p>Trial registration</p> <p>Clinical trial registration number is NCT01096537.</p

Genomic Insights Into The Ixodes scapularis Tick Vector Of Lyme Disease

Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects accumulation of repetitive DNA, new lineages of retrotransposons, and gene architecture patterns resembling ancient metazoans rather than pancrustaceans. Annotation of scaffolds representing B57% of the genome, reveals 20,486 protein-coding genes and expansions of gene families associated with tick–host interactions. We report insights from genome analyses into parasitic processes unique to ticks, including host ‘questing’, prolonged feeding, cuticle synthesis, blood meal concentration, novel methods of haemoglobin digestion, haem detoxification, vitellogenesis and prolonged off-host survival. We identify proteins associated with the agent of human granulocytic anaplasmosis, an emerging disease, and the encephalitis-causing Langat virus, and a population structure correlated to life-history traits and transmission of the Lyme disease agent

Genomic Insights Into The Ixodes scapularis Tick Vector Of Lyme Disease

Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects accumulation of repetitive DNA, new lineages of retrotransposons, and gene architecture patterns resembling ancient metazoans rather than pancrustaceans. Annotation of scaffolds representing B57% of the genome, reveals 20,486 protein-coding genes and expansions of gene families associated with tick–host interactions. We report insights from genome analyses into parasitic processes unique to ticks, including host ‘questing’, prolonged feeding, cuticle synthesis, blood meal concentration, novel methods of haemoglobin digestion, haem detoxification, vitellogenesis and prolonged off-host survival. We identify proteins associated with the agent of human granulocytic anaplasmosis, an emerging disease, and the encephalitis-causing Langat virus, and a population structure correlated to life-history traits and transmission of the Lyme disease agent

Groundwater models

This presentation introduces model concepts and terms, demonstrates some models, develops critical awareness of modelling issues, and enables use of published and accepted groundwater models. The regional scale, steady-flow, groundwater model demonstrates the principal behaviour of nitrate contamination from land use, while the stream function approach to contaminant transport addresses questions about response times of effects of land use change. The use of a steady-flow groundwater model for regional scale reduces computation time, which may be important for real-time stakeholder participation

Using stream flow and chemistry data to estimate catchment scale groundwater and nitrate fluxes

Groundwater is the dominant flow path carrying land surface recharge, including dissolved contaminants, to surface waters draining a catchment. The dominance of the groundwater pathway poses a challenge to management of water quality in agricultural catchments, because groundwater quantity and quality are difficult and expensive to monitor, and groundwater assimilative capacity for nitrate is generally unknown. On the other hand, rainfall and evapotranspiration as inputs, and stream flow and nitrate concentration as outputs, can be recorded relatively easily, especially if inexpensive in-stream nitrate sensors can be developed. The eigenmodel approach has previously been used to estimate the land surface area and groundwater discharge contributing to stream flow in a small hill catchment. We extended this approach to explain seasonal patterns of nitrate and silica concentrations observed in the Toenepi Stream, which drains a lowland dairying catchment near Morrinsville, and to estimate the water and nitrate fluxes driving these observations. The resulting model (“StreamGEM”) was calibrated for the four-year period 1 April 2007 to 31 March 2011, and cross-validated using data from the period 1 April 1995 to 31 March 1997. Estimated discharge, nitrate concentration (as nitrate-N) and nitrate load from near-surface, fast groundwater, and slow groundwater flowpaths were then calculated. On an annual basis, stream flow was dominated by discharge from fast, shallow groundwater. In summer however, slow, deeper groundwater dominated both flow and chemistry. The total catchment input load (at the bottom of the root zone) was estimated to be 40 kg N ha⁻¹ y⁻¹ nitrate nitrogen (NO₃-N). Nitrate attenuation in the groundwater components accounted for 20 kg N ha⁻¹ y⁻¹ of this, with the remaining 50% being discharged to the stream. At the catchment scale, nitrate assimilation appears to occur dominantly in the shallower flow near the redox boundary, despite the strongly reduced conditions and much lower nitrate concentrations found in the deeper groundwater. The ability to estimate catchment water and nitrate fluxes from weather and in-stream data offers an inexpensive and potentially widely applicable tool for improved management of New Zealand’s land and water resources. Current research focuses on ascertaining in which type of catchments StreamGEM can be applied successfully