While COVID-19 vaccines reduce adverse outcomes, post-vaccination SARS-CoV-2 infection remains problematic. We sought to identify community factors impacting risk for breakthrough infections (BTI) ...among fully vaccinated persons by rurality.
We conducted a retrospective cohort study of US adults sampled between January 1 and December 20, 2021, from the National COVID Cohort Collaborative (N3C). Using Kaplan-Meier and Cox-Proportional Hazards models adjusted for demographic differences and comorbid conditions, we assessed impact of rurality, county vaccine hesitancy, and county vaccination rates on risk of BTI over 180 days following two mRNA COVID-19 vaccinations between January 1 and September 21, 2021. Additionally, Cox Proportional Hazards models assessed the risk of infection among adults without documented vaccinations. We secondarily assessed the odds of hospitalization and adverse COVID-19 events based on vaccination status using multivariable logistic regression during the study period.
Our study population included 566,128 vaccinated and 1,724,546 adults without documented vaccination. Among vaccinated persons, rurality was associated with an increased risk of BTI (adjusted hazard ratio aHR 1.53, 95% confidence interval CI 1.42-1.64, for urban-adjacent rural and 1.65, 1.42-1.91, for nonurban-adjacent rural) compared to urban dwellers. Compared to low vaccine-hesitant counties, higher risks of BTI were associated with medium (1.07, 1.02-1.12) and high (1.33, 1.23-1.43) vaccine-hesitant counties. Compared to counties with high vaccination rates, a higher risk of BTI was associated with dwelling in counties with low vaccination rates (1.34, 1.27-1.43) but not medium vaccination rates (1.00, 0.95-1.07). Community factors were also associated with higher odds of SARS-CoV-2 infection among persons without a documented vaccination. Vaccinated persons with SARS-CoV-2 infection during the study period had significantly lower odds of hospitalization and adverse events across all geographic areas and community exposures.
Our findings suggest that community factors are associated with an increased risk of BTI, particularly in rural areas and counties with high vaccine hesitancy. Communities, such as those in rural and disproportionately vaccine hesitant areas, and certain groups at high risk for adverse breakthrough events, including immunosuppressed/compromised persons, should continue to receive public health focus, targeted interventions, and consistent guidance to help manage community spread as vaccination protection wanes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
While the P3 component during target detection and novelty processing has been widely studied, less is known about its underlying network dynamics. A recent cognitive model suggests that ...frontal‐parietal and frontal‐temporal interregional connectivity are related to attention/action selection and target‐related memory updating during the P3, respectively, but empirical work testing this model is lacking. Other work suggests the importance of theta‐ and delta‐band connectivity between the medial frontal cortex and distributed cortical regions during attention, stimulus detection, and response selection processes, and similar dynamics may underlie P3‐related network connectivity. The present study evaluated the functional connectivity elicited during a visual task, which combined oddball target and novelty stimuli, in a sample of 231 same‐sex twins. It was hypothesized that both target and novel conditions would involve theta frontoparietal connectivity and medial frontal theta power, but that target stimuli would elicit the strongest frontotemporal connectivity. EEG time‐frequency analysis revealed greater theta‐band frontoparietal connectivity and medial frontal power during both target and novel conditions compared to standards, which may index conflict/uncertainty resolution processes. Theta‐band frontotemporal connectivity was maximal during the target condition, potentially reflecting context updating or stimulus‐response activation. Delta‐band frontocentral‐parietal connectivity was also strongest following targets, which may be sensitive to response‐related demands. These results suggest the existence of functional networks related to P3 that are differentially engaged by target oddballs and novel distractors. Compared to simple P3 amplitude, network measures may provide a more nuanced view of the neural dynamics during target detection/novelty processing in normative and pathological populations.
Occurrence of emerging organic contaminants (EOCs) in surface water bodies can cause adverse effects on non-target organisms. When surface waters are used as drinking water sources, temporal ...variability in EOC concentrations can potentially impact drinking water quality and human health. To better understand spatiotemporal variability of EOCs in drinking water sources in Central Pennsylvania, EOCs were evaluated in six drinking water sources during a two-year study period (April 2016–June 2018) in the Susquehanna River Basin (SRB). The study was conducted in two phases: Phase I was a spatially distributed sampling approach within the SRB focusing on seven human pharmaceuticals and Phase II was a temporally intensive sampling regime at a single site focusing on a broader range of EOCs. Concentration-discharge relationships were utilized to classify EOC transport dynamics and understand the extent to which hydrologic and anthropogenic factors, such as surface runoff and wastewater effluent, may contribute to EOC occurrence. Overall, EOCs were present at higher concentrations in colder seasons than warmer seasons. Thiamethoxam, a neonicotinoid insecticide, and caffeine exhibited accretion dynamics during high-flow periods, suggesting higher transport during surface runoff events. Human pharmaceuticals known to persist in wastewater effluent were inversely correlated with discharge, indicating dilution characteristics consistent with diminished wastewater signals during high-flow periods. Acetaminophen exhibited near-chemostatic transport dynamics, indicating nonpoint source inputs during high-flow periods. Risk calculations revealed that although EOCs posed medium-to-high risk to aquatic organisms, human health risk through fish consumption was low.
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•Common human pharmaceuticals were detected in >80% of drinking water source samples.•EOCs occurred at higher concentrations in colder rather than warmer months.•Concentration-discharge (C-Q) relationships helped to classify transport dynamics.•C-Q relationships identified likely sources and pathways contributing to EOCs.•Observed EOCs posed high risks to aquatic organisms but not to human health.
Purpose
Rural communities are among the most underserved and resource‐scarce populations in the United States. However, there are limited data on COVID‐19 outcomes in rural America. This study aims ...to compare hospitalization rates and inpatient mortality among SARS‐CoV‐2‐infected persons stratified by residential rurality.
Methods
This retrospective cohort study from the National COVID Cohort Collaborative (N3C) assesses 1,033,229 patients from 44 US hospital systems diagnosed with SARS‐CoV‐2 infection between January 2020 and June 2021. Primary outcomes were hospitalization and all‐cause inpatient mortality. Secondary outcomes were utilization of supplemental oxygen, invasive mechanical ventilation, vasopressor support, extracorporeal membrane oxygenation, and incidence of major adverse cardiovascular events or hospital readmission. The analytic approach estimates 90‐day survival in hospitalized patients and associations between rurality, hospitalization, and inpatient adverse events while controlling for major risk factors using Kaplan‐Meier survival estimates and mixed‐effects logistic regression.
Findings
Of 1,033,229 diagnosed COVID‐19 patients included, 186,882 required hospitalization. After adjusting for demographic differences and comorbidities, urban‐adjacent and nonurban‐adjacent rural dwellers with COVID‐19 were more likely to be hospitalized (adjusted odds ratio aOR 1.18, 95% confidence interval CI, 1.16‐1.21 and aOR 1.29, CI 1.24‐1.1.34) and to die or be transferred to hospice (aOR 1.36, CI 1.29‐1.43 and 1.37, CI 1.26‐1.50), respectively. All secondary outcomes were more likely among rural patients.
Conclusions
Hospitalization, inpatient mortality, and other adverse outcomes are higher among rural persons with COVID‐19, even after adjusting for demographic differences and comorbidities. Further research is needed to understand the factors that drive health disparities in rural populations.
While vaccination is the most important way to combat the SARS-CoV-2 pandemic, there may still be a need for early outpatient treatment that is safe, inexpensive, and currently widely available in ...parts of the world that do not have access to the vaccine. There are in-silico, in-vitro, and in-tissue data suggesting that metformin inhibits the viral life cycle, as well as observational data suggesting that metformin use before infection with SARS-CoV2 is associated with less severe COVID-19. Previous observational analyses from single-center cohorts have been limited by size.
Conducted a retrospective cohort analysis in adults with type 2 diabetes (T2DM) for associations between metformin use and COVID-19 outcomes with an active comparator design of prevalent users of therapeutically equivalent diabetes monotherapy: metformin versus dipeptidyl-peptidase-4-inhibitors (DPP4i) and sulfonylureas (SU). This took place in the National COVID Cohort Collaborative (N3C) longitudinal U.S. cohort of adults with +SARS-CoV-2 result between January 1 2020 to June 1 2021. Findings included hospitalization or ventilation or mortality from COVID-19. Back pain was assessed as a negative control outcome.
6,626 adults with T2DM and +SARS-CoV-2 from 36 sites. Mean age was 60.7 +/- 12.0 years; 48.7% male; 56.7% White, 21.9% Black, 3.5% Asian, and 16.7% Latinx. Mean BMI was 34.1 +/- 7.8kg/m2. Overall 14.5% of the sample was hospitalized; 1.5% received mechanical ventilation; and 1.8% died. In adjusted outcomes, compared to DPP4i, metformin had non-significant associations with reduced need for ventilation (RR 0.68, 0.32-1.44), and mortality (RR 0.82, 0.41-1.64). Compared to SU, metformin was associated with a lower risk of ventilation (RR 0.5, 95% CI 0.28-0.98, p = 0.044) and mortality (RR 0.56, 95%CI 0.33-0.97, p = 0.037). There was no difference in unadjusted or adjusted results of the negative control.
There were clinically significant associations between metformin use and less severe COVID-19 compared to SU, but not compared to DPP4i. New-user studies and randomized trials are needed to assess early outpatient treatment and post-exposure prophylaxis with therapeutics that are safe in adults, children, pregnancy and available worldwide.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The COVID-19 pandemic has demonstrated the need for efficient and comprehensive, simultaneous assessment of multiple combined novel therapies for viral infection across the range of illness severity. ...Randomized Controlled Trials (RCT) are the gold standard by which efficacy of therapeutic agents is demonstrated. However, they rarely are designed to assess treatment combinations across all relevant subgroups. A big data approach to analyzing real-world impacts of therapies may confirm or supplement RCT evidence to further assess effectiveness of therapeutic options for rapidly evolving diseases such as COVID-19.
Gradient Boosted Decision Tree, Deep and Convolutional Neural Network classifiers were implemented and trained on the National COVID Cohort Collaborative (N3C) data repository to predict the patients' outcome of death or discharge. Models leveraged the patients' characteristics, the severity of COVID-19 at diagnosis, and the calculated proportion of days on different treatment combinations after diagnosis as features to predict the outcome. Then, the most accurate model is utilized by eXplainable Artificial Intelligence (XAI) algorithms to provide insights about the learned treatment combination impacts on the model's final outcome prediction.
Gradient Boosted Decision Tree classifiers present the highest prediction accuracy in identifying patient outcomes with area under the receiver operator characteristic curve of 0.90 and accuracy of 0.81 for the outcomes of death or sufficient improvement to be discharged. The resulting model predicts the treatment combinations of anticoagulants and steroids are associated with the highest probability of improvement, followed by combined anticoagulants and targeted antivirals. In contrast, monotherapies of single drugs, including use of anticoagulants without steroid or antivirals are associated with poorer outcomes.
This machine learning model by accurately predicting the mortality provides insights about the treatment combinations associated with clinical improvement in COVID-19 patients. Analysis of the model's components suggests benefit to treatment with combination of steroids, antivirals, and anticoagulant medication. The approach also provides a framework for simultaneously evaluating multiple real-world therapeutic combinations in future research studies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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•Three vernal pools impacted by wastewater irrigation were sampled for estrogens.•A sampling period from April to June 2015 coincided with amphibian metamorphosis.•Estrogens persisted ...throughout the study period and were in nearly 100% of samples.•Only E1 was in the wastewater, yet E1, 17α-E2 17β-E2, E3 and EE2 were in the ponds.•Estrogens were observed at low levels (>1 ng/L) known to impact aquatic ecosystems.
Planned beneficial re-use of water has become an increasingly common conservation practice worldwide, sparking questions about the degree of water treatment needed to mitigate negative environmental impacts. Since the early 1980s, as an alternative to surface discharge, the Pennsylvania State University has spray-irrigated all of its treated wastewater effluent via land application onto an environmental setting known as the “Living Filter” site (∼245 ha). The impacts of spray irrigation on nearby ephemeral wetlands, known as vernal pools, were explored. The pools gain water from both natural rainfall and spray-irrigation of the University’s treated wastewater. The occurrence and persistence of estrogens in three vernal pools were quantified by analyzing >137 water samples collected from the pools over an eight-week period coincident with the development period of native amphibian larvae. Additionally, dissolved oxygen, oxidation-reduction potential, water level, water temperature, electrical conductivity, pH, and rainfall data were measured continuously throughout the study period within each pool. Further, the treated wastewater effluent was sampled during each weekly spray-irrigation event. Estrone was detected in nearly 100% of the vernal pool samples, with concentrations up to 6.2 ng L−1. Additionally, 17α-estradiol was not detected in the wastewater effluent, but was present in 52% of the vernal pool samples. 17β-estradiol, estriol, and 17α-ethinylestradiol were detected in fewer than 10% of the vernal pool samples. The findings of this research have important implications for management practices that can help protect these critical habitats.
It is unclear whether vitamin D benefits inpatients with COVID-19. Objective: To examine the relationship between vitamin D and COVID-19 outcomes. Design: Cohort study. Setting: National COVID Cohort ...Collaborative (N3C) database. Patients: 158,835 patients with confirmed COVID-19 and a sub-cohort with severe disease (n = 81,381) hospitalized between 1 January 2020 and 31 July 2021. Methods: We identified vitamin D prescribing using codes for vitamin D and its derivatives. We created a sub-cohort defined as having severe disease as those who required mechanical ventilation or extracorporeal membrane oxygenation (ECMO), had hospitalization >5 days, or hospitalization ending in death or hospice. Using logistic regression, we adjusted for age, sex, race, BMI, Charlson Comorbidity Index, and urban/rural residence, time period, and study site. Outcomes of interest were death or transfer to hospice, longer length of stay, and mechanical ventilation/ECMO. Results: Patients treated with vitamin D were older, had more comorbidities, and higher BMI compared with patients who did not receive vitamin D. Vitamin D treatment was associated with an increased odds of death or referral for hospice (adjusted odds ratio (AOR) 1.10: 95% CI 1.05−1.14), hospital stay >5 days (AOR 1.78: 95% CI 1.74−1.83), and increased odds of mechanical ventilation/ECMO (AOR 1.49: 95% CI 1.44−1.55). In the sub-cohort of severe COVID-19, vitamin D decreased the odds of death or hospice (AOR 0.90, 95% CI 0.86−0.94), but increased the odds of hospital stay longer >5 days (AOR 2.03, 95% CI 1.87−2.21) and mechanical ventilation/ECMO (AOR 1.16, 95% CI 1.12−1.21). Limitations: Our findings could reflect more aggressive treatment due to higher severity. Conclusion: Vitamin D treatment was associated with greater odds of extended hospitalization, mechanical ventilation/ECMO, and death or hospice referral.
Among the contributors to soil CO2 efflux, there remains uncertainty about the contribution of root activity to the overall soil efflux. Soil water and temperature frequently have been used to ...predict a large portion of the variation in soil CO2 efflux. We hypothesized that fine-root dynamics explain most of the remaining variability in soil CO2 efflux that cannot be explained by soil temperature and water content. We anticipated that seasonal increases in root production, mortality via decomposition, and standing crop would result in corresponding increases in soil CO2 efflux. We tested our hypotheses by collecting and analyzing two years of minirhizotron and soil chamber CO2 flux data from plots distributed throughout the Shale Hills Catchment of the Susquehanna-Shale Hills Critical Zone Observatory in Central Pennsylvania, USA. Here we showed that: (1) seasonal fluctuations in fine-root dynamics yielded only a very small increase in the predictability of soil CO2 efflux; (2) fine-root mortality effects on soil CO2 efflux were strongly tied to soil temperature; (3) fluctuations in fine-root presence or standing mass independent of temperature and moisture had little effect on soil CO2 efflux; and (4) new fine-root length and root length mortality had limited impacts on soil CO2 efflux rates. We conclude that, at least in temperate forests on rocky soils, characterizing fine-root dynamics may provide only limited improvement in the estimation of soil CO2 efflux.
Relatively little attention has been paid to the neural basis of superior memory despite its potential in providing important insight into efforts to improve memory in the general population or to ...offset age-related cognitive decline. The current study reports a rare opportunity to reproduce and isolate specific neural activities directly associated with exceptional memory. To capture the brain processes responsible for superior memory, we returned to a laboratory task and analytic approach used to explore the nature of exceptional memory, namely, digit-span task combined with verbal protocol analysis. One participant with average memory received approximately 50 h of digit-span training and the participant's digit-span increased from normative (8 digits) to exceptional (30 digits). Event-related potentials were recorded while the participant's digit span increased from 19 to 30 digits. Protocol analysis allowed us to identify direct behavioral indices of idiosyncratic encoding processes underlying the superior memory performance. EEG indices directly corresponding to the behavioral indices of encoding processes were identified. The results suggest that the early attention-related encoding processes were reflected in theta and delta whereas the later attention-independent encoding processes were reflected in time-domain slow-wave. This fine-grained approach offers new insights into studying neural mechanism mediating superior memory and the cognitive effort necessary to develop it.
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