Phase 3 Safety and Efficacy of AZD1222 (ChAdOx1 nCoV-19) Covid-19 Vaccine.

BACKGROUND: The safety and efficacy of the AZD1222 (ChAdOx1 nCoV-19) vaccine in a large, diverse population at increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United States, Chile, and Peru has not been known. METHODS: In this ongoing, double-blind, randomized, placebo-controlled, phase 3 clinical trial, we investigated the safety, vaccine efficacy, and immunogenicity of two doses of AZD1222 as compared with placebo in preventing the onset of symptomatic and severe coronavirus disease 2019 (Covid-19) 15 days or more after the second dose in adults, including older adults, in the United States, Chile, and Peru. RESULTS: A total of 32,451 participants underwent randomization, in a 2:1 ratio, to receive AZD1222 (21,635 participants) or placebo (10,816 participants). AZD1222 was safe, with low incidences of serious and medically attended adverse events and adverse events of special interest; the incidences were similar to those observed in the placebo group. Solicited local and systemic reactions were generally mild or moderate in both groups. Overall estimated vaccine efficacy was 74.0% (95% confidence interval [CI], 65.3 to 80.5; P<0.001) and estimated vaccine efficacy was 83.5% (95% CI, 54.2 to 94.1) in participants 65 years of age or older. High vaccine efficacy was consistent across a range of demographic subgroups. In the fully vaccinated analysis subgroup, no severe or critical symptomatic Covid-19 cases were observed among the 17,662 participants in the AZD1222 group; 8 cases were noted among the 8550 participants in the placebo group (<0.1%). The estimated vaccine efficacy for preventing SARS-CoV-2 infection (nucleocapsid antibody seroconversion) was 64.3% (95% CI, 56.1 to 71.0; P<0.001). SARS-CoV-2 spike protein binding and neutralizing antibodies increased after the first dose and increased further when measured 28 days after the second dose. CONCLUSIONS: AZD1222 was safe and efficacious in preventing symptomatic and severe Covid-19 across diverse populations that included older adults. (Funded by AstraZeneca and others; ClinicalTrials.gov number, NCT04516746.).

First-in-human study of oleclumab, a potent, selective anti-CD73 monoclonal antibody, alone or in combination with durvalumab in patients with advanced solid tumors.

BACKGROUND: CD73 upregulation in tumors leads to local immunosuppression. This phase I, first-in-human study evaluated oleclumab (MEDI9447), an anti-CD73 human IgG1λ monoclonal antibody, alone or with durvalumab in patients with advanced colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), or epidermal growth factor receptor-mutant non-small-cell lung cancer (NSCLC). METHODS: Patients received oleclumab 5-40 mg/kg (dose-escalation) or 40 mg/kg (dose-expansion) intravenously every 2 weeks (Q2W), alone (escalation only) or with durvalumab 10 mg/kg intravenously Q2W. RESULTS: 192 patients were enrolled, 66 during escalation and 126 (42 CRC, 42 PDAC, 42 NSCLC) during expansion. No dose-limiting toxicities occurred during escalation. In the monotherapy and combination therapy escalation cohorts, treatment-related adverse events (TRAEs) occurred in 55 and 54%, respectively, the most common being fatigue (17 and 25%). In the CRC, PDAC, and NSCLC expansion cohorts, 60, 57, and 45% of patients had TRAEs, respectively; the most common were fatigue (15%), diarrhea (9%), and rash (7%). Free soluble CD73 and CD73 expression on peripheral T cells and tumor cells showed sustained decreases, accompanied by reduced CD73 enzymatic activity in tumor cells. Objective response rate during escalation was 0%. Response rates in the CRC, PDAC, and NSCLC expansion cohorts were 2.4% (1 complete response [CR]), 4.8% (1 CR, 1 partial response [PR]), and 9.5% (4 PRs), respectively; 6-month progression-free survival rates were 5.4, 13.2, and 16.0%. CONCLUSIONS: Oleclumab ± durvalumab had a manageable safety profile, with pharmacodynamic activity reflecting oleclumab's mechanism of action. Evidence of antitumor activity was observed in tumor types that are generally immunotherapy resistant. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT02503774; date of registration, July 17, 2015.

Assessing COVID-19 testing strategies in K-12 schools in underserved populations: study protocol for a cluster-randomized trial.

BACKGROUND: Since March 2020, COVID-19 has disproportionately impacted communities of color within the United States. As schools have shifted from virtual to in-person learning, continual guidance is necessary to understand appropriate interventions to prevent SARS-CoV-2 transmission. Weekly testing of students and staff for SARS-CoV-2 within K-12 school setting could provide an additional barrier to school-based transmission, especially within schools unable to implement additional mitigation strategies and/or are in areas of high transmission. This study seeks to understand the role that weekly SARS-CoV-2 testing could play in K-12 schools. In addition, through qualitative interviews and listening sessions, this research hopes to understand community concerns and barriers regarding COVID-19 testing, COVID-19 vaccine, and return to school during the COVID-19 pandemic. METHODS/DESIGN: Sixteen middle and high schools from five school districts have been randomized into one of the following categories: (1) Weekly screening + symptomatic testing or (2) Symptomatic testing only. The primary outcome for this study will be the average of the secondary attack rate of school-based transmission per case. School-based transmission will also be assessed through qualitative contact interviews with positive contacts identified by the school contact tracers. Lastly, new total numbers of weekly cases and contacts within a school-based quarantine will provide guidance on transmission rates. Qualitative focus groups and interviews have been conducted to provide additional understanding to the acceptance of the intervention and barriers faced by the community regarding SARS-CoV-2 testing and vaccination. DISCUSSION: This study will provide greater understanding of the benefit that weekly screening testing can provide in reducing SARS-CoV-2 transmission within K-12 schools. Close collaboration with community partners and school districts will be necessary for the success of this and similar studies. TRIAL REGISTRATION: NCT04875520 . Registered May 6, 2021.

The impact of responsible fatherhood programs on parenting, psychological well-being, and financial outcomes: A randomized controlled trial.

The objective of this study was to examine differences in parenting, psychological well-being, and economic outcomes between fathers receiving two different programs offered by Fathers & Families Support Center for economically disadvantaged fathers: (a) Family Formation (FF), a 6-week/240-h program focused on economic stability/mobility, responsible fatherhood, and healthy relationships, with case management and legal services; (b) Economic Stability (ES), a 4-week/80-h program focused only on economic stability with limited case management and legal services. A randomized controlled trial (RCT) was used to compare fathers in FF (n = 350) vs. ES (n = 342). Surveys were administered at enrollment and 3- and 12-months postintervention. Linear and generalized linear mixed models were used to assess changes in program outcomes over time and across study groups. Four hundred and eighty-two fathers responded to either follow-up survey (251 FF, 231 ES). Nearly all (98%) were non-white (93% Black, 5% other/mixed race) and were on average 34 years old. Approximately 46% attended ≥75% of program sessions (FF 48% vs. ES 44%). Both FF and ES groups experienced improvements in parenting, psychological well-being, and financial outcomes after the programs, but changes in outcomes over time did not differ significantly by program. The lack of difference in outcomes between fathers in FF and ES groups could be due to a similar core focus on employment-related curriculum for both groups. Gaining financial stability could have contributed to positive improvements in other fatherhood domains. Implications for future research and practice are discussed herein.

El objetivo de este estudio fue analizar las diferencias en la crianza, el bienestar psicológico y los resultados económicos entre padres que recibían dos programas diferentes ofrecidos por el Centro de Apoyo a los Padres y las Familias (Fathers & Familiares Support Center) para padres desfavorecidos económicamente: (a) Formación de una Familia (Family Formation, FF), un programa de 6 semanas/240 horas centrado en la estabilidad/movilidad económica, la paternidad responsable y las relaciones saludables, con gestión de casos y servicios legales; (b) Estabilidad Económica (Economic Stability, ES), un programa de 4 semanas/80 horas centrado solamente en la estabilidad económica con poca gestión de casos y servicios legales. Se usó un ensayo controlado aleatorizado para comparar a los padres de FF (n=350) con los de ES (n=342). Se realizaron encuestas en la inscripción y a los 3 y a los 12 meses posteriores a la intervención. Se usaron modelos lineales y modelos mixtos lineales generalizados para evaluar los cambios en los resultados de los programas con el tiempo y entre los grupos de estudio. 482 padres respondieron a cada encuesta de seguimiento (251 FF, 231 ES). Casi todos (el 98 %) eran de color (el 93 % negros, el 5 % de otra raza o de raza mestiza) y tenían, en promedio, 34 años. Aproximadamente el 46 % asistió a más del 75 % de las sesiones de los programas (el 48 % de FF frente al 44 % de ES). Tanto el grupo de FF como el de ES tuvieron mejoras en la crianza, en el bienestar psicológico y en los resultados económicos después de los programas, pero los cambios en los resultados con el tiempo no variaron significativamente por programa. La falta de diferencia en los resultados entre los padres del grupo de FF y los del grupo de ES podría deberse a un enfoque principal similar en un currículo relacionado con el empleo para ambos grupos. La adquisición de estabilidad económica podría haber contribuido a mejoras positivas en otras áreas de la paternidad. Se comentan las consecuencias para la futura investigación y la práctica.

The HIV-1 Tat Protein Enhances Splicing at the Major Splice Donor Site.

Transcription of the HIV-1 proviral DNA and subsequent processing of the primary transcript results in the production of a large set of unspliced and differentially spliced viral RNAs. The major splice donor site (5'ss) that is located in the untranslated leader of the HIV-1 transcript is used for the production of all spliced RNAs, and splicing at this site has to be tightly regulated to allow the balanced production of all viral RNAs and proteins. We demonstrate that the viral Tat protein, which is known to activate viral transcription, also stimulates splicing at the major 5'ss. As for the transcription effect, Tat requires the viral long terminal repeat promoter and the trans-acting responsive RNA hairpin for splicing regulation. These results indicate that HIV-1 transcription and splicing are tightly coupled processes through the coordinated action of the essential Tat protein.IMPORTANCE The HIV-1 proviral DNA encodes a single RNA transcript that is used as RNA genome and packaged into newly assembled virus particles. This full-length RNA is also used as mRNA for the production of structural and enzymatic proteins. Production of other essential viral proteins depends on alternative splicing of the primary transcript, which yields a large set of differentially spliced mRNAs. Optimal virus replication requires a balanced production of all viral RNAs, which means that the splicing process has to be strictly regulated. We show that the HIV-1 Tat protein, a factor that is well known for its transcription activating function, also stimulates splicing. Thus, Tat controls not only the level of the viral RNA but also the balance between spliced and unspliced RNAs.

Dietary pattern and risk of hodgkin lymphoma in a population-based case-control study.

Classic Hodgkin lymphoma (cHL) has few known modifiable risk factors, and the relationship between diet and cHL risk is unclear. We performed the first investigation of an association between dietary pattern and cHL risk in 435 cHL cases and 563 population-based controls from Massachusetts and Connecticut (1997-2000) who completed baseline diet questionnaires. We identified 4 major dietary patterns ("vegetable," "high meat," "fruit/low-fat dairy," "desserts/sweets") using principal components analysis. We computed multivariable odds ratios and 95% confidence intervals for associations of dietary pattern score (quartiles) with younger-adult (age <50 years), older-adult (age ≥50 years), and overall cHL risk. Secondary analyses examined associations by histological subtype and tumor Epstein-Barr virus (EBV) status. A diet high in desserts/sweets was associated with younger-adult (odds ratio(quartile 4 vs. quartile 1) = 1.60, 95% confidence interval: 1.05, 2.45; Ptrend = 0.008) and EBV-negative, younger-adult (odds ratio = 2.11, 95% confidence interval: 1.31, 3.41; Ptrend = 0.007) cHL risk. A high meat diet was associated with older-adult (odds ratio = 3.34, 95% confidence interval: 1.02, 10.91; Ptrend = 0.04) and EBV-negative, older-adult (odds ratio = 4.64, 95% confidence interval: 1.03, 20.86; Ptrend = 0.04) cHL risk. Other dietary patterns were not clearly associated with cHL. We report the first evidence for a role of dietary pattern in cHL etiology. Diets featuring high intake of meat or desserts and sweets may increase cHL risk.

Human immunodeficiency virus type 1 splicing at the major splice donor site is controlled by highly conserved RNA sequence and structural elements.

Human immunodeficiency virus type 1 (HIV-1) splicing has to be strictly controlled to ensure the balanced production of the unspliced and all differently spliced viral RNAs. Splicing at the major 59 splice site (59ss) that is used for the synthesis of all spliced RNAs is modulated by the local RNA structure and binding of regulatory SR proteins. Here, we demonstrate that the suboptimal sequence complementarity between this 59ss and U1 small nuclear RNA (snRNA) also contributes to prevent excessive splicing. Analysis of a large set of HIV-1 sequences revealed that all three regulatory features of the 59ss region (RNA structure, SR protein binding and sequence complementarity with U1 snRNA) are highly conserved amongst virus isolates, which supports their importance. Combined mutations that destabilize the local RNA structure, remove binding sites for inhibitory SR proteins and optimize the U1 snRNA complementarity resulted in almost complete splicing and accordingly reduced virus replication.

HIV-1 splicing is controlled by local RNA structure and binding of splicing regulatory proteins at the major 5' splice site.

The 5' leader region of the human immunodeficiency virus 1 (HIV-1) RNA genome contains the major 5' splice site (ss) that is used in the production of the many spliced viral RNAs. This splice-donor (SD) region can fold into a stable stem-loop structure and the thermodynamic stability of this RNA hairpin influences splicing efficiency. In addition, splicing may be modulated by binding of splicing regulatory (SR) proteins, in particular SF2/ASF (SRSF1), SC35 (SRSF2), SRp40 (SRSF5) and SRp55 (SRSF6), to sequence elements in the SD region. The role of RNA structure and SR protein binding in splicing control was previously studied by functional analysis of mutant SD sequences. The interpretation of these studies was complicated by the fact that most mutations simultaneously affect both structure and sequence elements. We therefore tried to disentangle the contribution of these two variables by designing more precise SD region mutants with a single effect on either the sequence or the structure. The current analysis indicates that HIV-1 splicing at the major 5'ss is modulated by both the stability of the local RNA structure and the binding of splicing regulatory proteins.

Serum IgA to Epstein-Barr virus early antigen-diffuse identifies Hodgkin's lymphoma.

Hodgkin's lymphoma is associated with immune dysregulation. Immune impairment often results in aberrant immune responses and lytic reactivation of ubiquitous Herpesviruses, such as Epstein-Barr virus (EBV) in mucosal tissues. Accordingly, the specificity of IgA to EBV early lytic antigens, which are important for reactivation, was evaluated to determine Hodgkin's lymphoma-specific sero-reactive patterns. Sera from 42 patients with Hodgkin's lymphoma were compared to sera from 17 patients with infectious mononucleosis (IM), another EBV-related condition that often presents in a similar manner; and to sera from 15 healthy EBV-seropositive subjects. Flow cytometry analysis demonstrated that like IM sera, most Hodgkin's lymphoma sera contained IgA that labeled cells expressing EBV early lytic antigens whereas healthy EBV-seropositive sera did not. Further evaluation to distinguish Hodgkin's lymphoma from IM showed that IgA in most Hodgkin's lymphoma, irrespective of the presence of EBV in primary tumors, detected only modified forms of EBV lytic Early Antigen-Diffuse (EA-D) while IM sera detected the un-modified form as well, further supporting the presence of immune dysregulation in Hodgkin's lymphoma patients. This IgA pattern distinguished Hodgkin's lymphoma from IM sera with a sensitivity of 92.9%, specificity 100%, positive predictive value 100%, and negative predictive value 85%. Our findings lay the groundwork for additional scientific and clinical investigation, particularly into the potential for developing Hodgkin's lymphoma-associated diagnostic and prognostic biomarkers.

Atypical prediagnosis Epstein-Barr virus serology restricted to EBV-positive Hodgkin lymphoma.

An altered anti-Epstein-Barr virus (EBV) serologic profile preceding diagnosis is associated with an increased risk of Hodgkin lymphoma. It is unknown whether this atypical pattern predicts Hodgkin lymphoma risk further subdivided by determination of EBV in tumor cells. A nested case-control study of 128 incident Hodgkin lymphoma cases and 368 matched controls from active-duty military personnel with archived serum in the US Department of Defense Serum Repository was conducted to determine whether a panel of anti-EBV antibody titers differed in EBV(+) and EBV(-) Hodgkin lymphoma. Among 40 EBV(+) Hodgkin lymphoma cases and matched controls, statistically significant increased risks were associated with elevated anti-EBV VCA IgG antibody titers (relative risk = 3.1; 95% confidence interval [CI], 1.1-8.7), and an anti-EBNA-1/anti-EBNA-2 antibody ratio ≤ 1.0 versus > 1.0 (relative risk = 4.7; 95% CI, 1.6-13.8). In contrast, no significant associations were found among 88 EBV(-) Hodgkin lymphoma cases relative to their matched controls. In case-case analysis, EBV(+) disease was significantly associated with a low anti-EBNA-1/anti-EBNA-2 antibody ratio. This distinctive serologic response to EBV latent antigens, indicative of immune dysfunction in other clinical settings, is associated with an increased risk of developing EBV(+) but not EBV(-) Hodgkin lymphoma.

Evaluation of participant recruitment methods to a rare disease online registry.

Internet communication advances provide new opportunities to assemble individuals with rare diseases to online patient registries from wide geographic areas for research. However, there is little published information on the efficacy of different recruitment methods. Here we describe recruitment patterns and the characteristics of individuals with the self-identified autosomal dominant genetic disorder neurofibromatosis type 1 (NF1) who participated in an online patient registry during the 1-year period from 1/1/2012 to 12/31/2012. We employed four main mechanisms to alert potential participants to the registry: (1) Facebook and Google advertising, (2) government and academic websites, (3) patient advocacy groups, and (4) healthcare providers. Participants reported how they first heard about the registry through an online questionnaire. During the 1-year period, 880 individuals participated in the registry from all 50 U.S. States, the District of Columbia, Puerto Rico, and 39 countries. Facebook and Google were reported as referral sources by the highest number of participants (n=550, 72% Facebook), followed by healthcare providers (n=74), and government and academic websites (n=71). The mean participant age was 29±18 years and most participants reported White race (73%) and female sex (62%) irrespective of reported referral source. Internet advertising, especially through Facebook, resulted in efficient enrollment of large numbers of individuals with NF1. Our study demonstrates the potential utility of this approach to assemble individuals with a rare disease from across the world for research studies.

COVID-19 Related Facilitators and Barriers to In-Person Learning for Children With Intellectual and Development Disabilities: A Follow-Up.

BACKGROUND: Students with intellectual and developmental disabilities (IDD) and the staff who support them were largely in-person during the 2021-2022 school year, despite their continued vulnerability to infection with SARS-CoV-2. This qualitative study aimed to understand continued perceptions of weekly SARS-CoV-2 screening testing of students and staff amidst increased availability of vaccinations. METHODS: Twenty-three focus groups were held with school staff and parents of children with IDD to examine the perceptions of COVID-19 during the 2021-2022 school year. Responses were analyzed using a directed thematic content analysis approach. RESULTS: Four principal themes were identified: strengths and opportunities of school- and district-level mitigation policies; experience at school with the return to in-person learning; facilitators and barriers to participation in SARS-CoV-2 screening testing; and perceptions of SARS-CoV-2 testing in light of vaccine availability. IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: Despite the increased availability of vaccines, school staff and families agreed that saliva-based SARS-CoV-2 screening testing helped increase comfort with in-person learning as long as the virus was present in the community. CONCLUSION: To keep children with IDD in school during the pandemic, families found SARS-CoV-2 screening testing important. Clearly communicating school policies and mitigation strategies facilitated peace of mind and confidence in the school district.

Social media adoption in local health departments nationwide.

OBJECTIVES: We examined whether characteristics of local health departments (LHD) and their geographic region were associated with using Facebook and Twitter. We also examined the number of tweets per month for Twitter accounts as an indicator of social media use by LHDs. METHODS: In 2012, we searched for Facebook and Twitter accounts for 2565 LHDs nationwide, and collected adoption date and number of connections for each account. Number of tweets sent indicated LHD use of social media. LHDs were classified as innovators, early adopters, or nonadopters. Characteristics of LHDs were compared across adoption categories, and we examined geographic characteristics, connections, and use. RESULTS: Twenty-four percent of LHDs had Facebook, 8% had Twitter, and 7% had both. LHDs serving larger populations were more likely to be innovators, tweeted more often, and had more social media connections. Frequency of tweeting was not associated with adoption category. There were differences in adoption across geographic regions, with western states more likely to be innovators. Innovation was also higher in states where the state health department adopted social media. CONCLUSIONS: Social media has the potential to aid LHDs in disseminating information across the public health system. More evidence is needed to develop best practices for this emerging tool.

Local health department use of twitter to disseminate diabetes information, United States.

INTRODUCTION: Diabetes may affect one-third of US adults by 2050. Adopting a healthful diet and increasing physical activity are effective in preventing type 2 diabetes and decreasing the severity of diabetes-related complications. Educating and informing the public about health problems is a service provided by local health departments (LHDs). The objective of this study was to examine how LHDs are using social media to educate and inform the public about diabetes. METHODS: In June 2012 we used NVivo 10 to collect all tweets ever posted from every LHD with a Twitter account and identified tweets about diabetes. We used a 2010 National Association of County and City Health Officials survey to compare characteristics of LHDs that tweeted about diabetes with those that did not. Content analysis was used to classify each tweet topic. RESULTS: Of 217 LHDs with Twitter accounts, 126 had ever tweeted about diabetes, with 3 diabetes tweets being the median since adopting Twitter. LHDs tweeting about diabetes were in jurisdictions with larger populations and had more staff and higher spending than LHDs not tweeting about diabetes. They were significantly more likely to employ a public information specialist and provide programs in diabetes-related areas. There was also a weak positive association between jurisdiction diabetes rate and the percentage of all tweets that were about diabetes (r = .16; P = .049). CONCLUSION: LHDs are beginning to use social media to educate and inform their constituents about diabetes. An understanding of the reach and effectiveness of social media could enable public health practitioners to use them more effectively.

Policy activity and policy adoption in rural, suburban, and urban local health departments.

Public health policy is among the most effective and cost-effective interventions in some areas of public health and is emerging as effective in others. Policy may be especially important for rural communities, where residents face serious health and economic disparities and local health departments (LHDs) lack resources to provide necessary services. Data from the 2008 National Association of County and City Health Officials National Profile of Local Health Departments were used to examine policy activity (eg, policy development; communication with policymakers) and policy adoption in a sample of 454 LHDs. Results indicate policy activity was low in some policy areas for all LHDs and lowest in all policy areas for rural departments. Policy activities had significant positive relationships with policy adoption for land use (φ = 0.31; P < .05); tobacco prevention and control (φ = 0.37; P < .05); indoor air quality (φ = 0.28; P < .05); and nutrition and physical activity (φ = 0.21; P < .05). These relationships differed for rural, suburban, and urban LHDs. Significant positive correlations were also identified between overall levels of policy activity and any policy adoption (r = 0.16-0.27; P < .05). Local health departments should increase participation in policy activity to facilitate public health policy adoption nationwide.

Psychosocial work environment stressors for school staff during the COVID-19 pandemic: Barriers and facilitators for supporting wellbeing.

Introduction: After periods of remote and/or hybrid learning as a result of the COVID-19 global pandemic, the return to in-person learning has been beneficial for both students and teachers, but it has not been without challenges. This study was designed to assess the impact of the return to in-person learning on the school experience, and efforts made to ease the transition in furthering a positive in-person learning environment. Materials and methods: We conducted a series of listening sessions with 4 stakeholder groups: students (n = 39), parents (n = 28), teachers/school staff (n = 41), and a combination of listening sessions and semi-structured interviews with building level and district administrators (n = 12), focusing on in-school experiences during the 2021-2022 school year amidst the COVID-19 pandemic. A primarily deductive qualitative analysis approach was employed to code the data followed by a primarily inductive thematic analysis, followed by thematic aggregation, thus providing depth and identification of nuances in the data. Results: Three main themes emerged around school staff experiences: (1) increased levels of stress and anxiety manifested in key ways, including students' challenges with personal behavior management contributing to increased aggression and staff shortages; (2) school staff described key contributors to stress and anxiety, including feeling excluded from decision making and challenges with clear and consistent communication; and (3) school staff described key facilitators that supported their management of anxiety and stress, including adaptability, heightened attention and resources to wellbeing, and leveraging interpersonal relationships. Discussion: School staff and students faced significant stress and anxiety during the 2021-2022 school year. Further exploration and identification of approaches to mitigate key contributors to increased stress and anxiety for school staff, along with increased opportunities for implementing key facilitators that were identified as important in managing and navigating the increased stress and anxiety offer valuable opportunities for helping to create a supportive work environment for school staff in the future.

COVID-19-Related Facilitators and Barriers to In-Person Learning for Children With Intellectual and Development Disabilities.

BACKGROUND: Schools provide essential functions for children with intellectual and developmental disabilities (IDD), but their vulnerability to infection with SARS-CoV-2 are a barrier to in-person learning. This qualitative study aimed to understand how weekly SARS-CoV-2 screening testing of students and staff could best facilitate in-school learning during the pandemic. METHODS: Thirty-one focus groups were held with school staff and parents of children with IDD to examine the perceptions of COVID-19 during the 2020-2021 school year. Responses were analyzed using a directed thematic content analysis approach. RESULTS: Five principal themes were identified: risks of returning to in-person learning; facilitators and barriers to participation in SARS-CoV-2 screening testing; messaging strategies; and preferred messengers. IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: Staff and families agreed that saliva-based SARS-CoV-2 screening testing helps increase comfort with in-person learning. Screening testing increased family and school staff comfort with in-person learning particularly because many students with special needs cannot adhere to public health guidelines. CONCLUSION: To keep children with IDD in school during the pandemic, families found SARS-CoV-2 screening testing important, particularly for students that cannot adhere to mitigation guidelines.

Antibody titers against EBNA1 and EBNA2 in relation to Hodgkin lymphoma and history of infectious mononucleosis.

A role for Epstein Barr virus (EBV) in Hodgkin lymphoma (HL) pathogenesis is supported by the detection of EBV genome in about one-third of HL cases, but is not well defined. We previously reported that an elevated prediagnosis antibody titer against EBV nuclear antigens (EBNA) was the strongest serologic predictor of subsequent HL. For the present analysis, we measured antibody levels against EBNA components EBNA1 and EBNA2 and computed their titer ratio (anti-EBNA1:2) in serum samples from HL cases and healthy siblings. We undertook this analysis to examine whether titer patterns atypical of well-resolved EBV infection, such as an anti-EBNA1:2 ratio ≤ 1.0, simply reflect history of infectious mononucleosis (IM), an HL risk factor, or independently predict HL risk. Participants were selected from a previous population-based case-control study according to their history of IM. We identified 55 EBV-seropositive persons with a history of IM (IM+; 33 HL cases, 22 siblings) and frequency-matched a comparison series of 173 IM history-negative, EBV-seropositive subjects on HL status, gender, age and year of blood draw (IM-; 105 cases, 58 siblings). In multivariate logistic regression models, an anti-EBNA1:2 ratio ≤ 1.0 was significantly more prevalent in HL cases than siblings (odds ratio, 95% confidence interval = 2.43, 1.05-5.65); similar associations were apparent within the IM+ and IM- groups. EBNA antibodies were not significantly associated with IM history in HL cases or siblings. These associations suggest that chronic or more severe EBV infection is a risk factor for HL, independent of IM history.

Organelle segregation into Plasmodium liver stage merozoites.

The liver stage of the Plasmodium parasite remains one of the most promising targets for intervention against malaria as it is clinically silent, precedes the symptomatic blood stage and represents a bottleneck in the parasite life cycle. However, many aspects of the development of the parasite during this stage are far from understood. During the liver stage, the parasite undergoes extensive replication, forming tens of thousands of infectious merozoites from each invading sporozoite. This implies a very efficient and accurate process of cytokinesis and thus also of organelle development and segregation. We have generated for the first time Plasmodium berghei double-fluorescent parasite lines, allowing visualization of the apicoplast, mitochondria and nuclei in live liver stage parasites. Using these we have seen that in parallel with nuclear division, the apicoplast and mitochondrion become two extensively branched and intertwining structures. The organelles then undergo impressive morphological and positional changes prior to cell division. To form merozoites, the parasite undergoes cytokinesis and the complex process of organelle development and segregation into the forming daughter merozoites could be analysed in detail using the newly generated transgenic parasites.