Impact of Shifting University Policies During the COVID-19 Pandemic on Self-Reported Employee Social Networks.

Objectives: To ascertain if faculty and staff were the link between the two COVID-19 outbreaks in a rural university county, and if the local university's COVID-19 policies affected contact rates of their employees across all its campuses. Methods: We conducted two anonymous, voluntary online surveys for faculty and staff of a PAC-12 university on their contact patterns both within and outside the university during the COVID-19 pandemic. One was asked when classes were virtual, and another when classes were in-person but masking. Participants were asked about the individuals they encountered, the type and location of the interactions, what COVID-19 precautions were taken - if any, as well as general questions about their location and COVID-19. Results: We received 271 responses from the first survey and 124 responses from the second. The first survey had a median of 3 contacts/respondent, with the second having 7 contacts/respondent (p<0.001). During the first survey, most contacts were family contacts (Spouse, Children), with the second survey period having Strangers and Students having the most contact (p<0.001). Over 50% of the first survey contacts happened at their home, while the second survey had 40% at work and 35% at home. Both respondents and contacts masked 42% and 46% of the time for the two surveys respectively (p<0.01). Conclusion: For future pandemics, it would be wise to take employees into account when trying to plan for the safety of university students, employees, and surrounding communities. The main places to be aware of and potentially push infectious disease precautions would be on campus, especially confined spaces like offices or small classrooms, and the home, as these tend to be the largest areas of non-masked close contact.

Healthcare Worker Staffing Ratios Affect Methicillin-Resistant Staphylococcus aureus Acquisition.

Importance: This study addresses the pressing clinical question of how variations in physician and nursing staffing levels influence methicillin-resistant Staphylococcus aureus (MRSA) rates, providing essential insights for optimizing staff allocation and improving patient outcomes in critical care settings. Objective: The main objective is to assess whether variations in staffing ratios and workload conceptualization significantly alter the rates of MRSA acquisitions in the ICU setting. Design: This simulation-based study utilizes stochastic compartmental mathematical modeling to explore the impact of staffing ratios and workload conceptualization on MRSA acquisitions in ICUs. Derived from a previously published model, the analysis involves running year-long stochastic simulations for each scenario 1000 times, varying nurse-to-patient ratios and intensivist staffing levels under infinite and finite workload conceptualizations. Our baseline model was a 3:1 nurse ratio with one intensivist. Main Outcome: MRSA acquisitions in ICUs, measured as median acquisitions per 1000 person-years. Results: Under baseline conditions, our model had a median of 8.2 MRSA acquisitions per 1000 person-years. Varying patient-to-nurse ratios and intensivist numbers showed substantial impacts. For infinite models, a 2:1 nurse ratio resulted in a 21% decrease, while a 1:1 nurse ratio led to a 65% reduction. Finite models demonstrated even larger effects, with a 48% decrease when having a 2:1 ratio, and an 83% reduction with a 1:1 nurse ratio. Reducing patient-to-nurse ratios in finite models increased acquisitions exponentially with a 348% increase for a 6:1 ratio. Intensivist variations had modest impacts. Conclusions and Relevance: Our study highlights the crucial role of optimizing staffing levels in ICUs for effective MRSA infection control. While intensivist variations have modest effects, bolstering nursing ratios significantly reduces MRSA acquisitions, underscoring the need for tailored staffing strategies, and recognizing the nuanced impact of workload conceptualization. Our findings offer practical insights for refining staffing protocols, emphasizing the dynamic nature of healthcare-associated infection outcomes.

Patient-reported outcomes at three months after pancreatic surgery for benign and malignant diseases - A prospective observational study.

BACKGROUND/OBJECTIVES: Pancreatic surgery may have a long-lasting effect on patients' health status and quality of life (QoL). We aim to evaluate patient-reported outcomes (PRO) 3 months after pancreatic surgery. METHODS: Patients scheduled for pancreatic surgery were enrolled in a prospective trial at five German centers. Patients completed PRO questionnaires (EQ-5D-5L, EORTC QLQ-PAN26, patient-reported happiness, and HADS-D), we report the first follow-up 3 months after surgery as an interim analysis. Statistical testing was performed using R software. RESULTS: From 2019 to 2022 203 patients were enrolled, a three-month follow-up questionnaire was available in 135 (65.5 %). 77 (57.9 %) underwent surgery for malignant disease. Patient-reported health status (EQ-5D-5L) was impaired in 4/5 dimensions (mobility, self-care, usual activities, pain, discomfort) for patients with malignant and 3/5 dimensions (mobility, self-care, usual activities) for patients with benign disease 3 months after surgery (p < 0.05). Patients with malignant disease reported an increase in depressive symptoms, patients with benign disease had a decrease in anxiety symptoms (HADS-D; depression: 5.00 vs 6.51, p = 0.002; anxiety: 8.04 vs. 6.34, p = 0.030). Regarding pancreatic-disease-specific symptoms (EORTC-QLQ-PAN26), patients with malignant disease reported increased problems with taste, weight loss, weakness in arms and legs, dry mouth, body image and troubling side effects at three months. Patients with benign disease indicated more weakness in arms and legs, troubling side effects but less future worries at three months. CONCLUSION: Patient-reported outcomes of patients undergoing pancreatic surgery for benign vs. malignant disease show important differences. Patients with malignant tumors report more severely decreased quality of life 3 months postoperatively than patients with benign tumors.

Assessment of seasonal forecasting errors of the ECMWF system in the eastern Indian Ocean.

The interannual variability of the Equatorial Eastern Indian Ocean (EEIO) is highly relevant for the climate anomalies on adjacent continents and affects global teleconnection patterns. Yet, this is an area where seasonal forecasting systems exhibit large errors. Here we investigate the reasons for these errors in the ECMWF seasonal forecasting system SEAS5 using tailored diagnostics and a series of numerical experiments. Results indicate that there are two fundamental and independent sources of forecast errors in the EEIO. The first one is of atmospheric nature and is largely related with too strong and stable easterly atmospheric circulation present in the equatorial Indian Ocean. This induces an easterly bias which leaves the coupled model predominantly in a state with a shallow thermocline and cold SSTs in the EEIO. The second error is of oceanic origin, associated with a too shallow thermocline, which enhances the SST errors arising from errors in the wind. Ocean initial conditions, which depend on both the quality of the assimilation and the ocean model, play an important role in this context. Nevertheless, it is found that the version of the ocean model used for the forecast can also play a non-negligible role at the seasonal time scales, by amplifying or damping the subsurface errors in the initial conditions. Errors in the EEIO are regime-dependent, having different causes in the warm (deep thermocline) regime with strong atmospheric convection and in the cold (shallow thermocline) regime. Errors also exhibit decadal variations, which challenges the calibration methods used in seasonal forecasts. Supplementary Information: The online version contains supplementary material available at 10.1007/s00382-023-06985-3.

Thyroglossal Duct Cyst Infection Caused by Neisseria gonorrhoeae: An Unusual Complication of Pharyngeal Gonorrhea.

ABSTRACT: Neisseria gonorrhoeae is a human obligate pathogen whose clinical expression of disease ranges from localized genital infection to involvement of extragenital sites such as the conjunctiva and throat. We describe the second case of a thyroglossal duct abscess due to N. gonorrhoeae, an uncommon complication of pharyngeal gonococcal infection. The fortuitous occurrence in the same individual of these 2 conditions that both exhibit an occult clinical presentation likely accounts for rarity of this infection. We discuss the pertinent gonococcal and host factors that underlie the clinical manifestations of this infection. A particular focus is the fundamental role that the binding of the gonococcal opacity-associated protein to the ubiquitous human carcinoembryonic cell adhesion molecule plays in the pathogenesis of pharyngeal gonorrhea.

Differences in history-taking skills between male and female chiropractic student interns.

OBJECTIVE: The purpose of this study was to determine if there was a difference in history-taking skills between male and female chiropractic student interns. METHODS: This study included 2040 patient histories collected by student interns over a 3-year period. Students were assessed by chiropractic college clinicians on reasoning (ability to derive clinically relevant information using a mnemonic for taking a history), communication, and professionalism using a modified Dreyfus model scoring system on a 1-4 scale (1 = novice, 4 = proficient). Ordinal dependent variables were scores for reasoning, communication, and professionalism. The categorical independent variable was sex of the student intern (male or female). A Mann-Whitney U test was used to compare for differences in nonparametric dependent variables by the sex of the students. RESULTS: The Mann-Whitney U test revealed that communication scores were greater for female chiropractic interns compared with male chiropractic interns (p < .001, with a small effect size (r = -.08). There was no statistically significant effect for sex on reasoning (p = .263) or professionalism (p = .098). CONCLUSION: Female chiropractic student interns scored higher than male interns on communication skills during a history-taking patient encounter. This supports the trend seen among female medical school students and physicians that women score higher than men on communication-related assessments.

Interactions between the sex of the clinician grader and the sex of the chiropractic student intern on spinal manipulation assessment grade.

OBJECTIVE: The purpose of this project was to determine if there was any relationship between the sex of the clinician grader and the sex of the chiropractic student intern on student spinal manipulation assessment grades. METHODS: Twelve thousand six hundred and thirty-one supervised patient adjustments by student interns were analyzed over a 3-year data collection window. Student interns were assessed by multiple male and female clinicians in a teaching clinic using a modified Dreyfus model scoring system on a 1-4 scale (1 = novice, 4 = proficient). A Mann-Whitney U test was used to compare the relationship between grader sex and student grade as well as student sex and student grade. RESULTS: Sex of the grader had a statistically significant effect on spinal manipulation assessment grade, p < .001, with male clinician graders assigning average scores of 2.81 ± 0.39 (mean ± SD) and female clinician graders scores of 3.01 ± 0.52, r = .18. Sex of the student had a statistically significant but negligible (r = .08) effect on spinal manipulation assessment grade, p < .001, with male students averaging slightly higher scores (2.93 ± 0.47) than females (2.86 ± 0.44) on the modified Dreyfus scale. CONCLUSION: Male clinicians tended to assign lower grades on spinal manipulation assessments than female clinicians. Male students on average received slightly higher scores than female students on spinal manipulation assessments.

Elevated Total Serum Immunoglobulin A Levels in Patients with Suspicion for Celiac Disease.

Patients with classic symptoms of celiac disease are often initially tested for serum tissue transglutaminase-immunoglobulin A (tTG-IgA) and total serum immunoglobulin A (IgA) levels concurrently, as IgA deficiency can lead to falsely low tTG-IgA. There are no guidelines for incidental findings of elevated total serum IgA when testing for celiac disease. In our study, we described the proportion of patients with suspicion of celiac disease who had elevated total serum IgA and the factors that may be associated with these findings. We studied the management of these patients with incidental findings of elevated total serum IgA to identify its clinical significance. To investigate, we performed a retrospective chart review of patients who underwent celiac disease serologic testing at a single clinic from January 2017 to June 2022. We reported further laboratory workup and follow-up for patients with incidental findings of elevated total serum IgA by board-certified immunologists. In our chart review, 848 patients were identified, 85 (10.0%) of whom were found to be negative for celiac disease but had elevated total serum IgA levels (median IgA 351 mg/dL, interquartile range 324-382). Out of 85 patients, 73 were further evaluated by immunologists, with 55 patients undergoing additional laboratory workup. None were diagnosed with specific immunologic conditions. Male sex was identified as associated with elevated total serum IgA findings, and constipation was found in a statistically significant greater frequency of patients with normal total serum IgA rather than elevated total serum IgA. To provide external validation of our findings, we created a second patient cohort within the Stanford Research Repository database. Out of 33,875 patients identified, a similarly high proportion of patients were negative for celiac disease but had elevated total serum IgA levels (9.3%, 3140 patients). In this separate patient cohort, male sex was also identified as being associated with elevated total serum IgA. Our study also provides preliminary evidence that patients with incidental findings of elevated total serum IgA may not need further management or workup, as these abnormalities may not be clinically relevant without other clinical suspicions.

Multivalent Scaffolds to Promote B cell Tolerance.

Autoimmune diseases are characterized by aberrant immune responses toward self-antigens. Current treatments lack specificity, promoting adverse effects by broadly suppressing the immune system. Therapies that specifically target the immune cells responsible for disease are a compelling strategy to mitigate adverse effects. Multivalent formats that display numerous binding epitopes off a single scaffold may enable selective immunomodulation by eliciting signals through pathways unique to the targeted immune cells. However, the architecture of multivalent immunotherapies can vary widely, and there is limited clinical data with which to evaluate their efficacy. Here, we set forth to review the architectural properties and functional mechanisms afforded by multivalent ligands and evaluate four multivalent scaffolds that address autoimmunity by altering B cell signaling pathways. First, we address both synthetic and natural polymer backbones functionalized with a variety of small molecule, peptide, and protein ligands for probing the effects of valency and costimulation. Then, we review nanoparticles composed entirely from immune signals which have been shown to be efficacious. Lastly, we outline multivalent liposomal nanoparticles capable of displaying high numbers of protein antigens. Taken together, these examples highlight the versatility and desirability of multivalent ligands for immunomodulation and illuminate strengths and weaknesses of multivalent scaffolds for treating autoimmunity.

Identification of risk factors and mosquito vectors associated with dengue virus infection in American Samoa, 2017.

INTRODUCTION: The first outbreak of dengue in American Samoa was reported in 1911. Sporadic outbreaks have been reported since, as were outbreaks of other pathogens transmitted by Aedes species mosquitoes including Ross River, chikungunya, and Zika viruses. During an outbreak of dengue virus-type 2 (DENV-2) in 2016-2018, we conducted household-based cluster investigations to identify population-specific risk factors associated with infection and performed entomologic surveillance to determine the relative abundance of Ae. aegypti and Ae. polynesiensis. METHODS AND FINDINGS: We contacted dengue patients who had tested positive for DENV infection and offered them as well as their household members participation in household-based cluster investigations. For those that accepted participation, we also offered participation to residents of households within a 50-meter radius of each case-patient's home. Questionnaires were administered and serum specimens collected for testing by RT-PCR and anti-DENV IgM ELISA. Adult female mosquitoes were aspirated from inside and outside participating households and tested by RT-PCR. We analyzed characteristics associated with DENV infection in bivariate analyses. A total of 226 participants was enrolled from 91 households in 20 clusters. Median age of participants was 34 years (range: <1-94), and 56.2% were female. In total, 7 (3.2%) participants had evidence of DENV infection by IgM ELISA (n = 5) or RT-PCR (n = 2). Factors significantly associated with DENV infection were reporting a febrile illness in the past three months (prevalence ratio: 7.5 [95% confidence interval: 1.9-29.8]) and having a household septic tank (Fisher's Exact Test, p = 0.004). Of 93 Ae. aegypti and 90 Ae. polynesiensis females collected, 90% of Ae. aegypti were collected inside homes whereas 83% of Ae. polynesiensis were collected outside homes. DENV nucleic acid was not detected in any mosquito pools. Sequencing of the DENV-2 from patient specimens identified the Cosmopolitan genotype of DENV-2 and was most closely related to virus detected in the Solomon Islands during 2016. CONCLUSIONS: This investigation demonstrated that dengue is a continuing risk in American Samoa. Increased frequency of infection among residents with a septic tank suggests a need to investigate whether septic tanks serve as larval habitats for mosquito vectors of DENV in American Samoa. Future efforts should also evaluate the role of Ae. polynesiensis in DENV transmission in the wild.

Collaborative Training as a Conduit to Build Knowledge in Black Birth Workers.

BACKGROUND: Black women have worse birthing outcomes in part due to perceived racism. Therefore, mistrust between Black birthing people and their obstetric providers is profound. Black birthing people may use doulas to support and advocate throughout their pregnancy. OBJECTIVE: The objective of this study was to create a structured didactic training between community doulas and institutional obstetric providers to address common pregnancy complications that disproportionately affect Black women. STUDY DESIGN: The collaborative training session was a 2-h-long session jointly developed by a community doula, Maternal/Fetal Medicine physician, and a nurse midwife. The doulas (n = 12) took a pre- and post-test assessment before and after collaborative training. The scores were averaged, and we calculated student t tests between the pre- and post-assessment. A p-value of < 0 .05 was significant. RESULTS: All twelve participants who completed this training session identified as Black cisgender women. The mean score correct of the pretest results was 55.25%. The initial percent correct for post-birth warning signs, hypertension in pregnancy, and gestational diabetes mellitus/ breastfeeding sections were 37.5%, 72.9%, and 75%, respectively. Following training, the percent correct per section increased to 92.7%, 81.3%, and 100% respectively. The mean score of correct answers on the post-test increased to 91.92% (p < 0.01). CONCLUSION: An educational framework that leverages community and institutional partnerships between doulas and institutional obstetric providers can bridge the gap to improve knowledge of community partners and increase trust of Black birth workers.

Soluble antigen arrays improve the efficacy and safety of peptide-based tolerogenic immunotherapy.

Autoantigen-specific immunotherapy using peptides offers a more targeted approach to treat autoimmune diseases, but the limited in vivo stability and uptake of peptides impedes clinical implementation. We previously showed that multivalent delivery of peptides as soluble antigen arrays (SAgAs) efficiently protects against spontaneous autoimmune diabetes in the non-obese diabetic (NOD) mouse model. Here, we compared the efficacy, safety, and mechanisms of action of SAgAs versus free peptides. SAgAs, but not their corresponding free peptides at equivalent doses, efficiently prevented the development of diabetes. SAgAs increased the frequency of regulatory T cells among peptide-specific T cells or induce their anergy/exhaustion or deletion, depending on the type of SAgA (hydrolysable (hSAgA) and non-hydrolysable 'click' SAgA (cSAgA)) and duration of treatment, whereas their corresponding free peptides induced a more effector phenotype following delayed clonal expansion. Moreover, the N-terminal modification of peptides with aminooxy or alkyne linkers, which was needed for grafting onto hyaluronic acid to make hSAgA or cSAgA variants, respectively, influenced their stimulatory potency and safety, with alkyne-functionalized peptides being more potent and less anaphylactogenic than aminooxy-functionalized peptides. Both SAgA variants significantly delayed anaphylaxis compared to their respective free peptides. The anaphylaxis, which occurred in NOD mice but not in C57BL/6 mice, was dose-dependent but did not correlate with the production of IgG1 or IgE against the peptides. We provide evidence that SAgAs significantly improve the efficacy and safety of peptide-based immunotherapy.

Feasibility of an Open Dialogue-Inspired Approach for Young Adults with Psychosis in a Public Hospital System.

The objective was to determine the feasibility of an Open Dialogue-inspired approach in a metropolitan, public hospital setting with predominately African American participants. Participants were ages 18-35, experienced psychosis within the past month, and involved at least one support person in their care. We evaluated domains of feasibility including implementation, adaptation, practicality, acceptability, and limited-efficacy. An organizational change model (Addressing Problems Through Organizational Change) facilitated implementation. Clinicians received three trainings and ongoing supervision. Network meetings were successfully implemented with good self-reported fidelity to principles of dialogic practice. Some adaptations (less frequent meetings and no home visits) were necessary. A subset of individuals completed research assessments over 12 months. Qualitative interviews with participants suggested the intervention was acceptable. Symptom and functional outcomes were preliminary but trended toward improvement. Implementation was feasible with relatively brief training, organizational change processes, and context-specific adaptations. Lessons learned can assist in planning a larger research study.

Understanding Pandemic Solidarity: Mutual Support During the First COVID-19 Lockdown in the United Kingdom.

Throughout the COVID-19 pandemic, the concept of solidarity has been invoked frequently. Much interest has centred around how citizens and communities support one another during times of uncertainty. Yet, empirical research which accounts and understands citizen's views on pandemic solidarity, or their actual practices has remained limited. Drawing upon the analysis of data from 35 qualitative interviews, this article investigates how residents in England and Scotland enacted, understood, or criticised (the lack of) solidarity during the first national lockdown in the United Kingdom in April 2020-at a time when media celebrated solidarity as being at an all-time high. It finds that although solidarity was practiced by some people, the perceived lack of solidarity was just as pronounced. We conclude that despite frequent mobilisations of solidarity by policy makers and other public actors, actual practices of solidarity are poorly understood-despite the importance of solidarity for public health and policy.

Nationally Subsidized Continuous Glucose Monitoring: A Cost-effectiveness Analysis.

OBJECTIVE: The Continuous Glucose Monitoring (CGM) Initiative recently introduced universal subsidized CGM funding for people with type 1 diabetes under 21 years of age in Australia. We thus aimed to evaluate the cost-effectiveness of this CGM Initiative based on national implementation data and project the economic impact of extending the subsidy to all age-groups. RESEARCH DESIGN AND METHODS: We used a patient-level Markov model to simulate disease progression for young people with type 1 diabetes and compared government-subsidized access to CGM with the previous user-funded system. Three years of real-world clinical input data were sourced from analysis of the Australasian Diabetes Data Network and National Diabetes Services Scheme registries. Costs were considered from the Australian health care system's perspective. An annual discount rate of 5% was applied to future costs and outcomes. Uncertainty was evaluated with probabilistic and deterministic sensitivity analyses. RESULTS: Government-subsidized CGM funding for young people with type 1 diabetes compared with a completely user-funded model resulted in an incremental cost-effectiveness ratio (ICER) of AUD 39,518 per quality-adjusted life-year (QALY) gained. Most simulations (85%) were below the commonly accepted willingness-to-pay threshold of AUD 50,000 per QALY gained in Australia. Sensitivity analyses indicated that base-case results were robust, though strongly impacted by the cost of CGM devices. Extending the CGM Initiative throughout adulthood resulted in an ICER of AUD 34,890 per QALY gained. CONCLUSIONS: Providing subsidized access to CGM for people with type 1 diabetes was found to be cost-effective compared with a completely user-funded model in Australia.

Democratic research: Setting up a research commons for a qualitative, comparative, longitudinal interview study during the COVID-19 pandemic.

The sudden and dramatic advent of the COVID-19 pandemic led to urgent demands for timely, relevant, yet rigorous research. This paper discusses the origin, design, and execution of the SolPan research commons, a large-scale, international, comparative, qualitative research project that sought to respond to the need for knowledge among researchers and policymakers in times of crisis. The form of organization as a research commons is characterized by an underlying solidaristic attitude of its members and its intrinsic organizational features in which research data and knowledge in the study is shared and jointly owned. As such, the project is peer-governed, rooted in (idealist) social values of academia, and aims at providing tools and benefits for its members. In this paper, we discuss challenges and solutions for qualitative studies that seek to operate as research commons.

ATP Hydrolysis Coordinates the Activities of Two Motors in a Dimeric Chromatin Remodeling Enzyme.

ATP-dependent chromatin remodelers are essential enzymes that restructure eukaryotic genomes to enable all DNA-based processes. The diversity and complexity of these processes arethe complexity of the enzymes that carry them out, making remodelers a challenging class of molecular motors to study by conventional methods. Here we use a single molecule biophysical assay to overcome some of these challenges, enabling a detailed mechanistic dissection of a paradigmatic remodeler reaction, that of sliding a nucleosome towards the longer DNA linker. We focus on how two motors of a dimeric remodeler coordinate to accomplish such directional sliding. We find that ATP hydrolysis by both motors promotes coordination, suggesting a role for ATP in resolving the competition for directional commitment. Furthermore, we show an artificially constitutive dimer is no more or less coordinated, but is more processive, suggesting a cell could modulate a remodeler's oligomeric state to modulate local chromatin dynamics.

A collaborative comparison of international pediatric diabetes registries.

BACKGROUND: An estimated 1.1 million children and adolescents aged under 20 years have type 1 diabetes worldwide. Principal investigators from seven well-established longitudinal pediatric diabetes registries and the SWEET initiative have come together to provide an international collaborative perspective and comparison of the registries. WORK FLOW: Information and data including registry characteristics, pediatric participant clinical characteristics, data availability and data completeness from the Australasian Diabetes Data Network (ADDN), Danish Registry of Childhood and Adolescent Diabetes (DanDiabKids), Diabetes prospective follow-up registry (DPV), Norwegian Childhood Diabetes Registry (NCDR), National Paediatric Diabetes Audit (NPDA), Swedish Childhood Diabetes Registry (Swediabkids), T1D Exchange Quality Improvement Collaborative (T1DX-QI), and the SWEET initiative was extracted up until 31 December 2020. REGISTRY OBJECTIVES AND OUTCOMES: The seven diabetes registries and the SWEET initiative collectively show data of more than 900 centers and around 100,000 pediatric patients, the majority with type 1 diabetes. All share the common objectives of monitoring treatment and longitudinal outcomes, promoting quality improvement and equality in diabetes care and enabling clinical research. All generate regular benchmark reports. Main differences were observed in the definition of the pediatric population, the inclusion of adults, documentation of CGM metrics and collection of raw data files as well as linkage to other data sources. The open benchmarking and access to regularly updated data may prove to be the most important contribution from registries. This study describes aspects of the registries to enable future collaborations and to encourage the development of new registries where they do not exist.