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BackgroundPrior to the COVID-19 pandemic, US hospitals relied on static projections of future trends for long-term planning and were only beginning to consider forecasting methods for short-term planning of staffing and other resources. With the overwhelming burden imposed by COVID-19 on the health care system, an emergent need exists to accurately forecast hospitalization needs within an actionable timeframe. ObjectiveOur goal was to leverage an existing COVID-19 case and death forecasting tool to generate the expected number of concurrent hospitalizations, occupied intensive care unit (ICU) beds, and in-use ventilators 1 day to 4 weeks in the future for New Mexico and each of its five health regions. MethodsWe developed a probabilistic model that took as input the number of new COVID-19 cases for New Mexico from Los Alamos National Laboratory’s COVID-19 Forecasts Using Fast Evaluations and Estimation tool, and we used the model to estimate the number of new daily hospital admissions 4 weeks into the future based on current statewide hospitalization rates. The model estimated the number of new admissions that would require an ICU bed or use of a ventilator and then projected the individual lengths of hospital stays based on the resource need. By tracking the lengths of stay through time, we captured the projected simultaneous need for inpatient beds, ICU beds, and ventilators. We used a postprocessing method to adjust the forecasts based on the differences between prior forecasts and the subsequent observed data. Thus, we ensured that our forecasts could reflect a dynamically changing situation on the ground. ResultsForecasts made between September 1 and December 9, 2020, showed variable accuracy across time, health care resource needs, and forecast horizon. Forecasts made in October, when new COVID-19 cases were steadily increasing, had an average accuracy error of 20.0%, while the error in forecasts made in September, a month with low COVID-19 activity, was 39.7%. Across health care use categories, state-level forecasts were more accurate than those at the regional level. Although the accuracy declined as the forecast was projected further into the future, the stated uncertainty of the prediction improved. Forecasts were within 5% of their stated uncertainty at the 50% and 90% prediction intervals at the 3- to 4-week forecast horizon for state-level inpatient and ICU needs. However, uncertainty intervals were too narrow for forecasts of state-level ventilator need and all regional health care resource needs. ConclusionsReal-time forecasting of the burden imposed by a spreading infectious disease is a crucial component of decision support during a public health emergency. Our proposed methodology demonstrated utility in providing near-term forecasts, particularly at the state level. This tool can aid other stakeholders as they face COVID-19 population impacts now and in the future.

BackgroundAlthough there are a number of advantages to using the internet to recruit and enroll participants into Web-based research studies, these advantages hinge on data validity. In response to this concern, researchers have provided recommendations for how best to screen for fraudulent survey entries and to handle potentially invalid responses. Yet, the majority of this previous work focuses on screening (ie, verification that individual met the inclusion criteria) and validating data from 1 individual, and not from 2 people who are in a dyadic relationship with one another (eg, same-sex male couple; mother and daughter). Although many of the same data validation and screening recommendations for Web-based studies with individual participants can be used with dyads, there are differences and challenges that need to be considered. ObjectiveThis paper aimed to describe the methods used to verify and validate couples’ relationships and data from a Web-based research study, as well as the associated lessons learned for application toward future Web-based studies involving the screening and enrollment of couples with dyadic data collection. MethodsWe conducted a descriptive evaluation of the procedures and associated benchmarks (ie, decision rules) used to verify couples’ relationships and validate whether data uniquely came from each partner of the couple. Data came from a large convenience sample of same-sex male couples in the United States, who were recruited through social media venues for a Web-based, mixed methods HIV prevention research study. ResultsAmong the 3815 individuals who initiated eligibility screening, 1536 paired individuals (ie, data from both partners of a dyad) were assessed for relationship verification; all passed this benchmark. For data validation, 450 paired individuals (225 dyads) were identified as fraudulent and failed this benchmark, resulting in a total sample size of 1086 paired participants representing 543 same-sex male couples who were enrolled. The lessons learned from the procedures used to screen couples for this Web-based research study have led us to identify and describe four areas that warrant careful attention: (1) creation of new and replacement of certain relationship verification items, (2) identification of resources needed relative to using a manual or electronic approach for screening, (3) examination of approaches to link and identify both partners of the couple, and (4) handling of bots. ConclusionsThe screening items and associated rules used to verify and validate couples’ relationships and data worked yet required extensive resources to implement. New or updating some items to verify a couple’s relationship may be beneficial for future studies. The procedures used to link and identify whether both partners were coupled also worked, yet they call into question whether new approaches are possible to help increase linkage, suggesting the need for further inquiry.

BackgroundThere is a need to develop innovative and accessible dyadic interventions that provide male couples with the behavioral skills to manage the risk of HIV transmission within their relationship. ObjectiveWe conducted a pilot randomized controlled trial (RCT) to assess the feasibility and acceptability of the electronic health (eHealth) HIV prevention toolkit intervention to encourage seroconcordant negative male couples in the United States to establish and adhere to a sexual agreement (SA). MethodsEligible, consented couples were randomly assigned to the intervention or education control and followed up for 6 months, with assessments occurring every 3 months after baseline. Acceptability items were assessed at both follow-up assessments. Descriptive and comparative statistics summarized cohort characteristics, relationship dynamics, and SA outcomes for the entire cohort and by trial arm. To examine the association between couples’ relationship dynamics and their establishment of an SA over time and by trial arm, multilevel logistic regression analyses were performed with a random intercept to account for correlations of repeated measurements of relationship dynamics at months 3 and 6; the odds ratio (OR) of establishment of an SA and the corresponding 95% confidence interval were then reported. ResultsOverall, 7959 individuals initiated screening. Reasons for individual ineligibility varied. An electronic algorithm was used to assess couple-level eligibility, which identified 1080 ineligible and 266 eligible dyads. Eligible couples (n=149) were enrolled in the pilot RCT: 68 received the intervention and 81 received the education control. Retention was 71.5% (213/298 partnered men) over the 6 months. Participants reported high acceptability of the intervention along with some areas for improvement. A significantly higher proportion of couples who received the intervention established an SA at 6 months compared with those who received the education control (32/43, 74% vs 27/50, 54%; P=.05). The OR of establishing an SA for couples in the intervention versus those in the control condition was greater than 2 when controlling for a number of different relationship dynamics. In addition, the odds of establishing an SA increased by 88% to 322% for each unit increase in a variety of averaged relationship dynamic scores; the opposite result was found for dynamics of stigma. Differences between trial arms for SA type and adherence were nonsignificant at each assessment. However, changes in these 2 SA aspects were noted over time. The average number of items couples included in their SA was 18, and about one-fourth to one-third of couples included HIV prevention items. ConclusionsThe findings demonstrate strong evidence for the acceptability and feasibility of the eHealth toolkit as a brief, stand-alone, couples-based HIV prevention intervention. These findings support the need to update the toolkit and evaluate it in a larger clinical trial powered for efficacy. Trial RegistrationClinicalTrials.gov NCT02494817; http://clinicaltrials.gov/ct2/show/NCT02494817

BackgroundThe recognition of the role of primary partners in HIV transmission has led to a growth in dyadic-focused HIV prevention efforts. The increasing focus on male couples in HIV research has been paralleled by an increase in the development of interventions aimed at reducing HIV risk behaviors among male couples. The ability to accurately assess the efficacy of these interventions rests on the ability to successfully enroll couples into HIV prevention research. ObjectiveThis study aimed to explore factors associated with successful dyadic engagement in Web-based HIV prevention research using recruitment and enrollment data from a large sample of same-sex male couples recruited online from the United States. MethodsData came from a large convenience sample of same-sex male couples in the United States, who were recruited through social media venues for a Web-based, mixed method HIV prevention research study. The analysis examined the demographic factors associated with successful dyadic engagement in research, measured as both members of the dyad meeting eligibility criteria, consenting for the study, and completing all study processes. ResultsAdvertisements generated 221,258 impressions, resulting in 4589 clicks. Of the 4589 clicks, 3826 individuals were assessed for eligibility, of which 1076 individuals (538/1913, 28.12% couples) met eligibility criteria and were included in the study. Of the remaining 2740 ineligible participants, 1293/3826 (33.80%) were unlinked because their partner did not screen for eligibility, 48/2740 (1.75%) had incomplete partner data because at least one partner did not finish the survey, 22/2740 (0.80%) were ineligible because of 1 partner not meeting the eligibility criteria. Furthermore, 492/3826 (12.86%) individuals were fraudulent. The likelihood of being in a matched couple varied significantly by race and ethnicity, region, and relationship type. Men from the Midwest were less likely to have a partner who did not complete the survey. Men with college education and those who labeled their relationships as husband or other (vs boyfriend) were more likely to have a partner who did not complete the survey. ConclusionsThe processes used allowed couples to independently progress through the stages necessary to enroll in the research study, while limiting opportunities for coercion, and resulted in a large sample with relative diversity in demographic characteristics. The results underscore the need for additional considerations when recruiting and enrolling, relative to improving the methods associated with these research processes.

BackgroundMany men who have sex with men (MSM) use apps to connect with and meet other MSM. Given that these apps are often used to arrange sexual encounters, it is possible that apps may be suitable venues for messages and initiatives related to HIV prevention such as those to increase HIV testing rates among this population. ObjectiveThe purpose of this study was to assess willingness to use a new app for reminders of when to be tested for HIV infection among a sample of MSM in London who use apps to arrange sexual encounters. MethodsBroadcast advertisements targeted users of a popular social-networking app for MSM in London. Advertisements directed users to a Web-based survey of sexual behaviors and sexual health needs. Willingness to use apps for reminders of when to be tested for HIV was assessed. In addition, participants responded to items assessing recent sexual behaviors, substance use, and demographic characteristics. Exploratory analyses were undertaken to examine differences in willingness to use an app by demographic and behavioral characteristics. ResultsBroadcast advertisements yielded a sample of 169 HIV-negative MSM. Overall, two-thirds (108/169, 63.9%) reported willingness to use an app to remind them when to be tested for HIV. There were no significant differences in willingness to use these apps based on demographic characteristics, but MSM who reported recent binge drinking and recent club drug use more frequently reported willingness to use this app compared to their nonusing counterparts. ConclusionsMSM in this sample are willing to use a new app for HIV testing reminders. Given the high levels of willingness to use them, these types of apps should be developed, evaluated, and made available for this population.

BackgroundAlthough gay, bisexual, and other men who have sex with men (MSM) are disproportionately affected by human immunodeficiency virus (HIV) infection, few test for HIV at regular intervals. Smartphone apps may be an ideal tool to increase regular testing among MSM. However, the success of apps to encourage regular testing among MSM will depend on how frequently the apps are downloaded, whether they continue to be used over months or years, and the degree to which such apps are tailored to the needs of this population. ObjectiveThe primary objectives of this study were to answer the following questions. (1) What features and functions of smartphone apps do MSM believe are associated with downloading apps to their mobile phones? (2) What features and functions of smartphone apps are most likely to influence MSM’s sustained use of apps over time? (3) What features and functions do MSM prefer in an HIV testing smartphone app? MethodsWe conducted focus groups (n=7, with a total of 34 participants) with a racially and ethnically diverse group of sexually active HIV-negative MSM (mean age 32 years; 11/34 men, 33%, tested for HIV ≥10 months ago) in the United States in Miami, Florida and Minneapolis, Minnesota. Focus groups were digitally recorded, transcribed verbatim, and deidentified for analysis. We used a constant comparison method (ie, grounded theory coding) to examine and reexamine the themes that emerged from the focus groups. ResultsMen reported cost, security, and efficiency as their primary reasons influencing whether they download an app. Usefulness and perceived necessity, as well as peer and posted reviews, affected whether they downloaded and used the app over time. Factors that influenced whether they keep and continue to use an app over time included reliability, ease of use, and frequency of updates. Poor performance and functionality and lack of use were the primary reasons why men would delete an app from their phone. Participants also shared their preferences for an app to encourage regular HIV testing by providing feedback on test reminders, tailored testing interval recommendations, HIV test locator, and monitoring of personal sexual behaviors. ConclusionsMobile apps for HIV prevention have proliferated, despite relatively little formative research to understand best practices for their development and implementation. The findings of this study suggest key design characteristics that should be used to guide development of an HIV testing app to promote regular HIV testing for MSM. The features and functions identified in this and prior research, as well as existing theories of behavior change, should be used to guide mobile app development in this critical area.

Adoptive immunotherapy with Tregs is a promising approach for preventing or treating type 1 diabetes. Islet Antigen-specific Tregs have more potent therapeutic effects than polyclonal cells, but their low frequency is a barrier for clinical application. To generate Tregs that recognize islet antigens, we engineered a chimeric antigen receptor (CAR) derived from a monoclonal antibody with specificity for the insulin B chain 10-23 peptide presented in the context of the I[A.sup.g7] MHC class II allele present in NOD mice. Peptide specificity of the resulting InsB-g7 CAR was confirmed by tetramer staining and T cell proliferation in response to recombinant or islet-derived peptide. The InsB-g7 CAR redirected NOD Treg specificity such that insulin B 10-23-peptide stimulation enhanced suppressive function, measured via reduction of proliferation and IL-2 production by BDC2.5 T cells and CD80 and CD86 expression on dendritic cells. Cotransfer of InsB-g7 CAR Tregs prevented adoptive transfer diabetes by BDC2.5 T cells in immunodeficient NOD mice. In WT NOD mice, InsB-g7 CAR Tregs prevented spontaneous diabetes. These results show that engineering Treg specificity for islet antigens using a T cell receptor-like CAR is a promising therapeutic approach for the prevention of autoimmune diabetes., Introduction Autoimmune type 1 diabetes (T1D) is caused by T cell-mediated destruction of the insulin-producing [beta] cells of the islets of Langerhans in the pancreas. Tregs, defined by expression of [...]

AbstractBackground: Black men who have sex with men (BMSM) face multiple minority stressors (e.g., homophobia, racism, and presumed HIV status) that may indirectly erode their confidence in pursuing HIV testing uptake through exacerbating alcohol use disorder (AUD). Objectives: Using cross-sectional data from 203 community-based BMSM (71.4% as homosexual with a mean age of 26 years) living in a Southern US city, we conducted a causal mediation and moderation analysis to investigate in/direct pathways linking minority stressors, AUD risk, and self-efficacy of HIV testing, including how resilience may moderate these associations. Results: Our mediation analysis revealed that AUD risk accounted for 32.1% of the total effect of internalized homonegativity (βtotal effect = -0.424; SE=0.071; p<0.001), 28.6% of the total effect of experienced homophobia (βtotal effect = -0.684; SE=0.122; p<0.001), and 15.3% of the total effect of perceived HIV stigma (βtotal effect = -0.361; SE=0.164; p<0.05) on HIV testing self-efficacy. Resilience significantly moderated the associations of experienced homophobia (β = -0.049; SE=0.011; p<0.001), internalized homonegativity (β = -0.065; SE=0.027; p<0.01), and perceived HIV stigma (β = -0.034; SE=0.013; p<0.05) with AUD risk. Resilience also significantly moderated the associations of experienced homophobia (β = -0.073; SE=0.021; p<0.01), internalized homonegativity (β = -0.082; SE=0.012; p<0.001), perceived HIV stigma (β = -0.037; SE=0.039; p<0.05), and AUD risk (β = -0.021; SE=0.015; p<0.05) with HIV testing self-efficacy. Conclusions: Our study provides important implications in identifying multilevel sources for building resilience among BMSM to buffer the effects of minority stress on AUD risk and improve HIV testing outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Several studies have noted sexual minority disparities in tobacco smoking; however, few studies have examined the role of intimate partners in these different smoking behaviors among sexual minority men and women. Furthermore, few studies distinguish between intermittent and daily smokers. Thus, this study sought to examine whether perceptions of their partner's smoking behaviors were associated with their own smoking behaviors in a sample of sexual minority adults in romantic relationships. Method: In total, 898 participants (413 sexual minority females and 485 sexual minority males) completed a one-time online anonymous survey. Results: Approximately one third of the sample reported smoking, with 21.2% daily smokers and 9.8% intermittent smokers. Multinomial regression results revealed that for both sexual minority females and males having a partner who was a daily or intermittent smoker was associated with an increased odds of being a daily smoker, whereas having a partner who was an intermittent smoker was associated with an increased odds of being an intermittent smoker. Conclusions: These findings provide valuable information on the need to attend to romantic partners and consider tailored programming to account for different smoking patterns and partners' potential role in reinforcing smoking.

Influenza viruses pose a significant burden on global human health. Influenza has a broad cellular tropism in the airway, but how infection of different epithelial cell types impacts replication kinetics and burden in the airways is not fully understood. Using primary human airway cultures, which recapitulate the diverse epithelial cell landscape of the human airways, we investigated the impact of cell type composition on virus tropism and replication kinetics. Cultures were highly diverse across multiple donors and 30 independent differentiation conditions and supported a range of influenza replication. Although many cell types were susceptible to influenza, ciliated and secretory cells were predominantly infected. Despite the strong tropism preference for secretory and ciliated cells, which consistently make up 75% or more of infected cells, only ciliated cells were associated with increased virus production. Surprisingly, infected secretory cells were associated with overall reduced virus output. The disparate response and contribution to influenza virus production could be due to different pro-and antiviral interferon-stimulated gene signatures between ciliated and secretory populations, which were interrogated with single-cell RNA sequencing. These data highlight the heterogeneous outcomes of influenza virus infections in the complex cellular environment of the human airway and the disparate impacts of infected cell identity on multiround burst size, even among preferentially infected cell types. [ABSTRACT FROM AUTHOR]

Context.--The need for appropriate specimen use for ancillary testing has become more commonplace in the practice of pathology. This, coupled with improvements in technology, often provides less invasive methods of testing, but presents new challenges to appropriate specimen collection and handling of these small specimens, including thoracic small biopsy and cytology samples. Objective.--To develop a clinical practice guideline including recommendations on how to obtain, handle, and process thoracic small biopsy and cytology tissue specimens for diagnostic testing and ancillary studies. Methods.--The College of American Pathologists convened an expert panel to perform a systematic review of the literature and develop recommendations. Core needle biopsy, touch preparation, fine-needle aspiration, and effusion specimens with thoracic diseases including malignancy, granulomatous process/sarcoidosis, and infection (eg, tuberculosis) were deemed within scope. Ancillary studies included immunohistochemistry and immunocytochemistry, fluorescence in situ hybridization, mutational analysis, flow cytometry, cytogenetics, and microbiologic studies routinely performed in the clinical pathology laboratory. The use of rapid on-site evaluation was also covered. Results.--Sixteen guideline statements were developed to assist clinicians and pathologists in collecting and processing thoracic small biopsy and cytology tissue samples. Conclusions.--Based on the systematic review and expert panel consensus, thoracic small specimens can be handled and processed to perform downstream testing (eg, molecular markers, immunohistochemical biomarkers), core needle and fine-needle techniques can provide appropriate cytologic and histologic specimens for ancillary studies, and rapid on-site cytologic evaluation remains helpful in appropriate triage, handling, and processing of specimens. doi: 10.5858/arpa.2020-0119-CP, With the advances in minimally invasive sampling techniques, the ability to provide a diagnosis and perform multiple ancillary studies on limited-volume tissue samples, including small biopsy and cytology specimens, has [...]

Semantic judgements involve the use of general knowledge about the world in specific situations. Such judgements are typically associated with activity in a number of brain regions that include the left inferior frontal gyrus (IFG). However, previous studies showed activity in brain regions associated with mentalizing, including the right temporoparietal junction (TPJ), in semantic judgements that involved social knowledge. The aim of the present study was to investigate if social and non‐social semantic judgements are dissociated using a combination of fMRI and repetitive TMS. To study this, we asked participants to estimate the percentage of exemplars in a given category that shared a specified attribute. Categories could be either social (i.e., stereotypes) or non‐social (i.e., object categories). As expected, fMRI results (n = 26) showed enhanced activity in the left IFG that was specific to non‐social semantic judgements. However, statistical evidence did not support that repetitive TMS stimulation (n = 19) to this brain region specifically disrupted non‐social semantic judgements. Also as expected, the right TPJ showed enhanced activity to social semantic judgements. However, statistical evidence did not support that repetitive TMS stimulation to this brain region specifically disrupted social semantic judgements. It is possible that the causal networks involved in social and non‐social semantic judgements may be more complex than expected. [ABSTRACT FROM AUTHOR]