SARS-CoV-2 incidence, seroprevalence, and antibody dynamics in a rural, population-based cohort: March 2020 - July 2022.

Studies of SARS-CoV-2 incidence are important for response to continued transmission and future pandemics. We followed a rural community cohort with broad age representation with active surveillance for SARS-CoV-2 identification from November 2020 through July 2022. Participants provided serum specimens at regular intervals and following SARS-CoV-2 infection or vaccination. We estimated the incidence of SARS-CoV-2 infection identified by study RT-PCR, electronic health record documentation or self-report of a positive test, or serology. We also estimated the seroprevalence of SARS-CoV-2 spike and nucleocapsid antibodies measured by ELISA. Overall, 65% of the cohort had ≥1 SARS-CoV-2 infection by July 2022, and 19% of those with primary infection were reinfected. Infection and vaccination contributed to high seroprevalence, 98% (95% CI: 95%, 99%) of participants were spike or nucleocapsid seropositive at the end of follow-up. Among those seropositive, 82% were vaccinated. Participants were more likely to be seropositive to spike than nucleocapsid following infection. Infection among seropositive individuals could be identified by increases in nucleocapsid, but not spike, ELISA optical density values. Nucleocapsid antibodies waned more quickly after infection than spike antibodies. High levels of SARS-CoV-2 population immunity, as found in this study, are leading to changing epidemiology necessitating ongoing surveillance and policy evaluation.

The role of complement in kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

Uncontrolled complement activation can cause or contribute to glomerular injury in multiple kidney diseases. Although complement activation plays a causal role in atypical hemolytic uremic syndrome and C3 glomerulopathy, over the past decade, a rapidly accumulating body of evidence has shown a role for complement activation in multiple other kidney diseases, including diabetic nephropathy and several glomerulonephritides. The number of available complement inhibitor therapies has also increased during the same period. In 2022, Kidney Diseases: Improving Global Outcomes (KDIGO) convened a Controversies Conference, "The Role of Complement in Kidney Disease," to address the expanding role of complement dysregulation in the pathophysiology, diagnosis, and management of various glomerular diseases, diabetic nephropathy, and other forms of hemolytic uremic syndrome. Conference participants reviewed the evidence for complement playing a primary causal or secondary role in progression for several disease states and considered how evidence of complement involvement might inform management. Participating patients with various complement-mediated diseases and caregivers described concerns related to life planning, implications surrounding genetic testing, and the need for inclusive implementation of effective novel therapies into clinical practice. The value of biomarkers in monitoring disease course and the role of the glomerular microenvironment in complement response were examined, and key gaps in knowledge and research priorities were identified.

NCCN Guidelines® Insights: Kidney Cancer, Version 2.2024.

The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients with renal cell carcinoma (RCC). These NCCN Guidelines Insights focus on the systemic therapy options for patients with advanced RCC and summarize the new clinical data evaluated by the NCCN panel for the recommended therapies in Version 2.2024 of the NCCN Guidelines for Kidney Cancer.

Temperature-Pressure Swing Process for Reactive Carbon Capture and Conversion to Methanol: Techno-Economic Analysis and Life Cycle Assessment.

A model was developed to conduct techno-economic analysis (TEA) and life cycle assessment (LCA) for reactive carbon capture (RCC) and conversion of carbon dioxide (CO2) to methanol. This RCC process is compared to a baseline commercialized flue gas CO2 hydrogenation process. An ASPEN model was combined with existing TEA and LCA models into a larger TEA/LCA framework in Python. From preliminary experimental data, the model found a levelized cost of $0.79/kg methanol for the baseline process and $0.99/kg for the RCC process. The cradle-to-gate carbon intensity of the baseline process was 0.50 kg-CO2e/kg-methanol, compared to 0.55 kg-CO2e/kg-methanol for the RCC process. However, water consumption for RCC (10.21 kg-H2O/kg-methanol) is greatly reduced compared to the baseline (12.89 kg-H2O/kg-methanol). Future improvements in hydrogen electrolysis costs will benefit the RCC. A target H2/methanol mass ratio of 0.26 was developed for RCC laboratory experiments to reduce methanol cost below the baseline. If a ratio of 0.24 can be achieved, a levelized cost of $0.76/kg methanol is projected, with a carbon intensity of 0.42 kg-CO2e/kg-methanol.

Post-recovery health domain scores among outpatients by SARS-CoV-2 testing status during the pre-Delta period.

BACKGROUND: Symptoms of COVID-19 including fatigue and dyspnea, may persist for weeks to months after SARS-CoV-2 infection. This study compared self-reported disability among SARS-CoV-2-positive and negative persons with mild to moderate COVID-19-like illness who presented for outpatient care before widespread COVID-19 vaccination. METHODS: Unvaccinated adults with COVID-19-like illness enrolled within 10 days of illness onset at three US Flu Vaccine Effectiveness Network sites were tested for SARS-CoV-2 by molecular assay. Enrollees completed an enrollment questionnaire and two follow-up surveys (7-24 days and 2-7 months after illness onset) online or by phone to assess illness characteristics and health status. The second follow-up survey included questions measuring global health, physical function, fatigue, and dyspnea. Scores in the four domains were compared by participants' SARS-CoV-2 test results in univariate analysis and multivariable Gamma regression. RESULTS: During September 22, 2020 - February 13, 2021, 2712 eligible adults were enrolled, 1541 completed the first follow-up survey, and 650 completed the second follow-up survey. SARS-CoV-2-positive participants were more likely to report fever at acute illness but were otherwise comparable to SARS-CoV-2-negative participants. At first follow-up, SARS-CoV-2-positive participants were less likely to have reported fully or mostly recovered from their illness compared to SARS-CoV-2-negative participants. At second follow-up, no differences by SARS-CoV-2 test results were detected in the four domains in the multivariable model. CONCLUSION: Self-reported disability was similar among outpatient SARS-CoV-2-positive and -negative adults 2-7 months after illness onset.

Controlling posture to see the world: The integration of visual task demands and postural sway in sitting and standing infants.

Our ability to integrate posture with visually demanding tasks is a critical aspect of motor behavior flexibility. When looking at a small object, excessive body movements impair an individual's ability to visually attend to the object. To overcome this problem, we adjust our postural sway to successfully focus on the object. The goal of the current study was to assess whether infants also adjust postural sway when engaged in a challenging visual task. The participants, 19 independently sitting infants (Sitters) and 21 newly independently standing infants (Standers), sat or stood on a force plate while viewing differently sized images displayed on a monitor (smaller images: 8 × 6.5 cm or 3 × 3 cm; larger images: 13 × 16 cm or 13 × 13 cm). Regardless of image size, Standers were less stable than Sitters with larger sway areas and faster sway velocities. Both Sitters and Standers adjusted sway area but not sway velocity, based on image size. Sitters and Standers differed in how they controlled sway dynamics. Standers but not Sitters altered sway dynamics based on image size. Overall, infants used posture-specific adaptive control strategies to make fine-grained adjustments based on image size. The development of the ability to integrate posture with a visually demanding task further emphasizes the capability of advanced complex motor behaviors during infancy, enabling infants to flexibly attend to important aspects of their environment at different postural positions.

Utilizing a patient advocacy-led clinical network to engage diverse, community-based sites in implementation-effectiveness research.

BACKGROUND: Increased engagement with community-based practices is a promising strategy for increasing clinical trials access of diverse patient populations. In this study we assessed the ability to utilize a patient-advocacy organization led clinical network to engage diverse practices as field sites for clinical research. METHODS: GO2 for Lung Cancer led recruitment efforts of 17 field sites from their Centers of Excellence in Lung Cancer Screening Network for participation in an implementation-effectiveness trial focused on smoking cessation integration into screening programs for lung cancer. Sites were engaged by one of three methods: 1) Pre-Grant submission of letters of support, 2) a non-targeted study information dissemination campaign to network members, and 3) proactive, targeted outreach to specific centers informed by previously submitted network member data. Detailed self-reported information on barriers to participation was collected from centers that declined to join the study. RESULTS: Of 17 total field sites, 16 were recruited via the targeted outreach campaign and 1 via pre-grant letter of support submission. The sites covered 13 states and 4 United States geographic regions, were varied in annual screening volumes and years of screening program experience and were predominantly community-based practices (10 of 17 sites). The most reported reason (by 33% of sites) for declining to participate as a field site was inadequate staffing bandwidth for trial activities. This was especially true in community-based programs among which it was reported by 45% as a reason for declining. CONCLUSIONS: Our results suggest that this model of field site recruitment leveraging an existing partnership between an academic research team and an informal clinical network maintained by a disease-specific patient advocacy organization can result in engagement of diverse, community-based field sites. Additionally, reported barriers to participation by sites indicate that solutions centered around providing additional resources to enable greater capacity for site staff may increase community-practice participation in research.

Real-world analysis of the relationships between smoking, lung cancer stigma, and emotional functioning.

INTRODUCTION: People diagnosed with lung cancer experience high rates of distress, which can be compounded by the stigma of the disease. This study assessed a real-world population to understand patient-reported emotional functioning, types of stigma experienced, and relationship with smoking history. METHODS: Questionnaires using validated survey tools assessing demographics, smoking history, stigma, and quality of life (EORTC QLQ-C30 Emotional Functioning Scale) were analyzed from 539 global participants in the Lung Cancer Registry between November 2019 and July 2022. The associations between smoking history and self-reported internalized and perceived stigma and constrained disclosure of lung cancer diagnosis, as well as the potential impact of stigma on emotional functioning, were examined using multivariable logistic regression models. RESULTS: Among the broad geographic mix of study participants, all types of lung cancer stigma were associated with decreased emotional functioning due to a combination of factors including depression, anxiety, stress, and irritability. Participants who reported a history of current or former smoking experienced higher levels of internalized stigma and perceived stigma. Constrained disclosure about a diagnosis was common, associated with decreased emotional functioning, and not related to a history of smoking. Smoking status itself was not associated with reduced emotional functioning, implicating the role of stigma in distress. CONCLUSIONS: In this study, all types of lung cancer stigma were associated with clinically important decreases in emotional functioning. This impact was not dependent on smoking history. Internalized and perceived stigma were associated with the presence of a smoking history. These findings have implications for proper psychosocial care of people diagnosed with lung cancer.

Optimising recovery after perineal trauma: Implementation of an evidence-based patient-centred care and clinical practice guideline.

BACKGROUND: Perineal trauma and pain can affect the quality of life of women who experience vaginal birth. AIM: To investigate the effect of perineal care and pain management on women's postpartum recovery. METHODS: This was a Quasi-experimental study. In Phase 1 women were treated using our old postnatal perineal care management guideline. In Phase 2 an updated guideline was introduced (regular administration of icepacks and analgesia during the first 24-48 h postpartum). During Phase 1, pregnant women planning a vaginal birth completed a baseline questionnaire. Those who sustained perineal trauma completed a survey at 24-48 h, seven days and 12 weeks after birth. In Phase 2 we continued recruiting participants, using the same procedure, and investigated the efficacy of pain relief approaches using the new guideline. RESULTS: In Phase 1, 111 women (Group 1), and Phase 2, 146 women (Group 2) were recruited. No statistically significant differences were found between the two groups in terms of the women's pain catastrophising, their partner's responses to pain behaviours, or birth outcomes. At 24-48 h and seven days postpartum, women in Group 2 were less likely than women in Group 1 to be bothered by back or perineal pain, headache, sleeping difficulties and dizziness (p < 0.05). More women in Group 2 received regular paracetamol and perineal icepacks during their hospital stay, with less use of oxycodone in Group 2 than Group 1. CONCLUSION: The implementation of the guideline's recommendations was associated with decrease back and perineal pain, headache, sleeping difficulties and dizziness during the first seven days postpartum.

Factors Associated with PrEP Stigma Among Gay, Bisexual, and Other Men Who Have Sex with Men (gbMSM): A Systematic Review.

Gay, bisexual, and other men who have sex with men (gbMSM) are disproportionately affected by HIV. While pre-exposure prophylaxis (PrEP) is highly effective at preventing HIV acquisition, uptake of PrEP among gbMSM is low, which may in part be due to stigma associated with PrEP use. This systematic review aimed to explore experiences of PrEP stigma and to identify factors associated with this. Four databases were searched for papers including terms relating to (i) gbMSM, (ii) PrEP, and (iii) stigma, with narrative synthesis used to analyze results. After screening, 70 studies were included in the final analysis. Experiences of PrEP stigma were found to be characterized by a number of stereotypes and came from a range of sources. Five categories of factors were associated with stigma: (i) healthcare-related factors, (ii) cultural and contextual factors, (iii) sociodemographic factors, (iv) peer-discussion, and (v) psychosocial factors. These findings suggest that stigma can be a common experience for gbMSM. However, some are more at risk than others. Interventions aimed at reducing PrEP stigma may be useful in increasing uptake.

Assessment of heart-substructures auto-contouring accuracy for application in heart-sparing radiotherapy for lung cancer.

Objectives: We validated an auto-contouring algorithm for heart substructures in lung cancer patients, aiming to establish its accuracy and reliability for radiotherapy (RT) planning. We focus on contouring an amalgamated set of subregions in the base of the heart considered to be a new organ at risk, the cardiac avoidance area (CAA), to enable maximum dose limit implementation in lung RT planning. Methods: The study validates a deep-learning model specifically adapted for auto-contouring the CAA (which includes the right atrium, aortic valve root, and proximal segments of the left and right coronary arteries). Geometric, dosimetric, quantitative, and qualitative validation measures are reported. Comparison with manual contours, including assessment of interobserver variability, and robustness testing over 198 cases are also conducted. Results: Geometric validation shows that auto-contouring performance lies within the expected range of manual observer variability despite being slightly poorer than the average of manual observers (mean surface distance for CAA of 1.6 vs 1.2 mm, dice similarity coefficient of 0.86 vs 0.88). Dosimetric validation demonstrates consistency between plans optimized using auto-contours and manual contours. Robustness testing confirms acceptable contours in all cases, with 80% rated as "Good" and the remaining 20% as "Useful." Conclusions: The auto-contouring algorithm for heart substructures in lung cancer patients demonstrates acceptable and comparable performance to human observers. Advances in knowledge: Accurate and reliable auto-contouring results for the CAA facilitate the implementation of a maximum dose limit to this region in lung RT planning, which has now been introduced in the routine setting at our institution.

Antibody response to sequential vaccination with cell culture, recombinant, or egg-based influenza vaccines among U.S. adults.

The immune response to inactivated influenza vaccines (IIV) is influenced by multiple factors, including hemagglutinin content and egg-based manufacturing. Only two US-licensed vaccines are manufactured without egg passage: cell culture-based inactivated vaccine (ccIIV) and recombinant vaccine (RIV). We conducted a randomized open-label trial in central Wisconsin during the 2018-19 and 2019-20 seasons to compare immunogenicity of sequential vaccination. Participants 18-64 years old were randomized 1:1:1 to receive RIV, ccIIV or IIV in strata defined by number of influenza vaccine doses in the prior 3 years. They were revaccinated with the same product in year two. Paired serum samples were tested by hemagglutination inhibition against egg-adapted and cell-grown vaccine viruses. Serologic endpoints included geometric mean titer (GMT), mean fold rise, and percent seroconversion. There were 373 participants randomized and vaccinated in 2018-19; 332 were revaccinated in 2019-20. In 2018-19, RIV and ccIIV were not more immunogenic than IIV against A/H1N1. The post-vaccination GMT against the cell-grown 3C.2a A/H3N2 vaccine virus was higher for RIV vs IIV (p = .001) and RIV vs ccIIV (p = .001). The antibody response to influenza B viruses was similar across study arms. In 2019-20, GMT against the cell-grown 3C.3a A/H3N2 vaccine virus was higher for RIV vs IIV (p = .03) and for RIV vs ccIIV (p = .001). RIV revaccination generated significantly greater backboosting to the antigenically distinct 3C.2a A/H3N2 virus (2018-19 vaccine strain) compared to ccIIV or IIV. This study adds to the evidence that RIV elicits a superior immunologic response against A/H3N2 viruses compared to other licensed influenza vaccine products.

Ipsilateral and contralateral coadministration of influenza and COVID-19 vaccines produce similar antibody responses.

BACKGROUND: World Health Organisation (WHO) and USA Centers for Disease Control and Prevention (U.S. CDC) recommendations now allow simultaneous administration of COVID-19 and other vaccines. We compared antibody responses after coadministration of influenza and bivalent COVID-19 vaccines in the same (ipsilateral) arm vs. different (contralateral) arms. METHODS: Pre- and post-vaccination serum samples from individuals in the Prospective Assessment of COVID-19 in a Community (PACC) cohort were used to conduct haemaglutination inhibition (HI) assays with the viruses in the 2022-2023 seasonal influenza vaccine and focus reduction neutralisation tests (FRNT) using a BA.5 SARS-CoV-2 virus. The effect of ipsilateral vs. contralateral vaccination on immune responses was inferred in a model that accounted for higher variance in vaccine responses at lower pre-vaccination titers. FINDINGS: Ipsilateral vaccination did not cause higher influenza vaccine responses compared to contralateral vaccination. The response to SARS-CoV-2 was slightly increased in the ipsilateral group, but equivalence was not excluded. INTERPRETATION: Coadministration of influenza and bivalent COVID-19 vaccines in the same arm or different arms did not strongly influence the antibody response to either vaccine. FUNDING: This work was supported by the U.S. CDC (grant number: 75D30120C09259).

Neutralizing Immunity Against Antigenically Advanced Omicron BA.5 in Children After SARS-CoV-2 Infection.

We assessed serum neutralization of Omicron BA.5 in children following SARS-CoV-2 infection during the Delta or Omicron BA.1/BA.2 variant period. Convalescent BA.5 titers were higher following infections during the Omicron BA.1/BA.2 vs Delta variant period, and in vaccinated vs unvaccinated children. Titers against BA.5 did not differ by age group.

Time-Dependent Effects of Clinical Interventions on SARS-CoV-2 Immunity in Patients with Lung Cancer.

In patients with lung cancer (LC), understanding factors that impact the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike antibody (SAb) titers over time is critical, but challenging, due to evolving treatments, infections, vaccinations, and health status. The objective was to develop a time-dependent regression model elucidating individual contributions of factors influencing SAb levels in LC patients using a prospective, longitudinal, multi-institutional cohort study initiated in January 2021. The study evaluated 296 LC patients-median age 69; 55% female; 50% stage IV. Blood samples were collected every three months to measure SAb levels using FDA-approved ELISA. Asymptomatic and unreported infections were documented through measurement of anti-nucleocapsid Ab levels (Meso Scale Discovery). Associations between clinical characteristics and titers were evaluated using a time-dependent linear regression model with a generalized estimating equation (GEE), considering time-independent variables (age, sex, ethnicity, smoking history, histology, and stage) and time-dependent variables (booster vaccinations, SARS-CoV-2 infections, cancer treatment, steroid use, and influenza vaccination). Significant time-dependent effects increasing titer levels were observed for prior SARS-CoV-2 infection (p < 0.001) and vaccination/boosters (p < 0.001). Steroid use (p = 0.043) and chemotherapy (p = 0.033) reduced titer levels. Influenza vaccination was associated with increased SAb levels (p < 0.001), independent of SARS-CoV-2 vaccine boosters. Prior smoking significantly decreased titers in females (p = 0.001). Age showed no association with titers. This GEE-based linear regression model unveiled the nuanced impact of multiple variables on patient anti-spike Ab levels over time. After controlling for the major influences of vaccine and SARS-CoV-2 infections, chemotherapy and steroid use were found to have negatively affected titers. Smoking in females significantly decreased titers. Surprisingly, influenza vaccinations were also significantly associated, likely indirectly, with improved SARS-CoV-2 titers.

Characteristics of Lung Cancer Patients With Asymptomatic or Undiagnosed SARS-CoV-2 Infections.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be spread by individuals unaware they are infected. Such dissemination has heightened ramifications in cancer patients, who may need to visit healthcare facilities frequently, be exposed to immune-compromising therapies, and face greater morbidity from coronavirus disease 2019 (COVID-19). We determined characteristics of (1) asymptomatic, clinically diagnosed, and (2) serologically documented but clinically undiagnosed SARS-CoV-2 infection among individuals with lung cancer. PATIENTS AND METHODS: In a multicenter registry, individuals with lung cancer (regardless of prior SARS-CoV-2 vaccination or documented infection) underwent collection of clinical data and serial blood samples, which were tested for antinucleocapsid protein antibody (anti-N Ab) or IgG (N) levels. We used multivariable logistic regression models to investigate clinical characteristics associated with the presence or absence of symptoms and the presence or absence of a clinical diagnosis among patients with their first SARS-CoV-2 infection. RESULTS: Among patients with serologic evidence or clinically documented SARS-CoV-2 infection, 80/142 (56%) had no reported symptoms at their first infection, and 61/149 (40%) were never diagnosed. Asymptomatic infection was more common among older individuals and earlier-stage lung cancer. In multivariable analysis, non-white individuals with SARS-CoV-2 serologic positivity were 70% less likely ever to be clinically diagnosed (P = .002). CONCLUSIONS: In a multicenter lung cancer population, a substantial proportion of SARS-CoV-2 infections had no associated symptoms or were never clinically diagnosed. Because such cases appear to occur more frequently in populations that may face greater COVID-19-associated morbidity, measures to limit disease spread and severity remain critical.