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BACKGROUND: In 2022-2023, 15- and 20-valent pneumococcal conjugate vaccines (PCV15/PCV20) were recommended for infants. We aimed to estimate the incidence of outpatient visits and antibiotic prescriptions in US children (≤17 years) from 2016-2019 for acute otitis media, pneumonia, and sinusitis associated with PCV15- and PCV20-additional (non-PCV13) serotypes to quantify PCV15/20 potential impacts. METHODS: We estimated the incidence of PCV15/20-additional serotype-attributable visits and antibiotic prescriptions as the product of all-cause incidence rates, derived from national health care surveys and MarketScan databases, and PCV15/20-additional serotype-attributable fractions. We estimated serotype-specific attributable fractions using modified vaccine-probe approaches incorporating incidence changes post-PCV13 and ratios of PCV13 versus PCV15/20 serotype frequencies, estimated through meta-analyses. RESULTS: Per 1000 children annually, PCV15-additional serotypes accounted for an estimated 2.7 (95% confidence interval, 1.8-3.9) visits and 2.4 (95% CI, 1.6-3.4) antibiotic prescriptions. PCV20-additional serotypes resulted in 15.0 (95% CI, 11.2-20.4) visits and 13.2 (95% CI, 9.9-18.0) antibiotic prescriptions annually per 1000 children. PCV15/20-additional serotypes account for 0.4% (95% CI, 0.2%-0.6%) and 2.1% (95% CI, 1.5%-3.0%) of pediatric outpatient antibiotic use. CONCLUSIONS: Compared with PCV15-additional serotypes, PCV20-additional serotypes account for > 5 times the burden of visits and antibiotic prescriptions. Higher-valency PCVs, especially PCV20, may contribute to preventing pediatric pneumococcal respiratory infections and antibiotic use.

Carpooling allows travelers to share a ride to a common destination and can include several forms of sharing a ride, such as casual carpooling and real-time carpooling. Because carpooling reduces the number of automobiles needed by travelers, it is often associated with numerous societal benefitsincluding:1) reductions in energy consumption and emissions, 2) congestion mitigation, and 3) reduced parking infrastructure demand. In recent years, economic, environmental, and social forces coupled with technological innovations are encouraging shared and pooled services. Shared mobility is changing how people travel and is having a transformative impact on mobility. This chapter reviews key trends impacting the mobility marketplace including the growth of shared mobility and key demographic indicators, such as an aging population and Millennials entering the workforce. For decades, carpooling has been used as a strategy by numerous public agencies and employers as a strategy to address a range of climate, environmental, and congestion mitigation goals, while simultaneously increasing roadway and parking capacity. This chapter discusses how employers and public agencies can support carpooling.

Microtransit is a technology-enabled transit service that typically employs shuttles or vans (Figure 1) to provide on-demand transportation with dynamic routing. While many rides are dispatched and paid via a smartphone, many services also provide a telephone booking option. A few services accept cash payment and street hails (similar to taxis). Variations of microtransit can include fixed schedules and routes and larger or smaller vehicles. Typically, microtransit services are operated by or provided on behalfof a government entity or nonprofit organization, although privately operated microtransit programs also might exist.

Throughout the U.S., app-based gig drivers provide valuable services for courier network services (CNS) like Instacart, Uber Eats and DoorDash, and transportation network companies (TNCs) such as Uber and Lyft. In California, gig labor classification is governed among other things by Assembly Bill 5 (AB 5), which passed in 2019, and Proposition 22 (Prop 22) adopted in 2020. AB 5 established the ABC Test for worker classification in California labor law. The ABC Test results in most app-based drivers being classified as employees, who are due full labor rights and benefits in California. However, gig drivers were exempted from the ABC Test when California voters approved Prop 22. As a result, under Prop 22, most CNS and TNC drivers in California are classified as independent contractors. Understanding the nuances of California labor law as it applies to app-based gig drivers is critical to addressing areas such as: worker flexibility, the need for high-quality jobs, and driver pay variability due to the lack of transparency with algorithm-based platforms. To better understand evolving CNS and TNC labor policy, we conducted interviews with experts (n=8) across the U.S. representing labor, academia, and regulators between June 2022 to February 2024 and examined policy approaches of other cities and states on this issue.

Shared micromobility (bikesharing and scooter sharing) experienced market growth since 2021, rebounding from the pandemic across markets in the US, Mexico, and Canada. In partnership with the North American Bikeshare and Scootershare Association (NABSA) and Toole Design, researchers at the Transportation Sustainability Research Center (TSRC) at UC Berkeley have collaborated on the data collection and analysis of the shared micromobility industry metrics through a series of annual reports beginning in 2019. This includes a series of operator and agency surveys.1 Most recently, TSRC researchers collaborated on an Operator Survey (n=29) and an Agency Survey (n=52), distributed between January 2023 and June 2023, of all known shared micromobility operators and agencies as part of the 2022 state-of-the-industry report. Similar surveys were deployed in January 2022 and May 2022. These surveys include questions about shared micromobility systems2 operating within those agency jurisdictions and operator markets.

Advanced air mobility (AAM) is a broad concept that enables consumers access to air mobility, goods delivery, and emergency services through an integrated and connected multimodal transportation network. AAM can provide short-range urban, suburban, and rural flights of about 50-miles and mid-range regional flights up to a several hundred miles. State law delegates responsibility for oversight in aviation primarily to the California Department of Transportation (Caltrans). This white paper presents an overview of the state of the market, such as the aircraft under development and forecast market growth and discusses factors that could facilitate the development of AAM or pose risks to its deployment or to the public, including the safety and the regulatory environment, airspace and air traffic management, security, environmental impacts, weather, infrastructure and multimodal integration, workforce and economic development, social equity, and community engagement and social acceptance. It concludes by recommending actions that Caltrans and other state agencies can take to facilitate the development of AAM.

The human brain represents one of the most complex biological systems, containing billions of neurons interconnected through trillions of synapses. Inherent to the brain is a biochemical complexity involving ions, signaling molecules, and peptides that regulate neuronal activity and allow for short- and long-term adaptations. Large-scale and noninvasive imaging techniques, such as fMRI and EEG, have highlighted brain regions involved in specific functions and visualized connections between different brain areas. A major shortcoming, however, is the need for more information on specific cell types and neurotransmitters involved, as well as poor spatial and temporal resolution. Recent technologies have been advanced for neuronal circuit mapping and implemented in behaving model organisms to address this. Here, we highlight strategies for targeting specific neuronal subtypes, identifying, and releasing signaling molecules, controlling gene expression, and monitoring neuronal circuits in real-time in vivo Combined, these approaches allow us to establish direct causal links from genes and molecules to the systems level and ultimately to cognitive processes.

PURPOSE: To evaluate the performance of a biopsy decision support algorithmic model, the intelligent-augmented breast cancer risk calculator (iBRISK), on a multicenter patient dataset. MATERIALS AND METHODS: iBRISK was previously developed by applying deep learning to clinical risk factors and mammographic descriptors from 9700 patient records at the primary institution and validated using another 1078 patients. All patients were seen from March 2006 to December 2016. In this multicenter study, iBRISK was further assessed on an independent, retrospective dataset (January 2015-June 2019) from three major health care institutions in Texas, with Breast Imaging Reporting and Data System (BI-RADS) category 4 lesions. Data were dichotomized and trichotomized to measure precision in risk stratification and probability of malignancy (POM) estimation. iBRISK score was also evaluated as a continuous predictor of malignancy, and cost savings analysis was performed. RESULTS: The iBRISK models accuracy was 89.5%, area under the receiver operating characteristic curve (AUC) was 0.93 (95% CI: 0.92, 0.95), sensitivity was 100%, and specificity was 81%. A total of 4209 women (median age, 56 years [IQR, 45-65 years]) were included in the multicenter dataset. Only two of 1228 patients (0.16%) in the low POM group had malignant lesions, while in the high POM group, the malignancy rate was 85.9%. iBRISK score as a continuous predictor of malignancy yielded an AUC of 0.97 (95% CI: 0.97, 0.98). Estimated potential cost savings were more than $420 million. CONCLUSION: iBRISK demonstrated high sensitivity in the malignancy prediction of BI-RADS 4 lesions. iBRISK may safely obviate biopsies in up to 50% of patients in low or moderate POM groups and reduce biopsy-associated costs.Keywords: Mammography, Breast, Oncology, Biopsy/Needle Aspiration, Radiomics, Precision Mammography, AI-augmented Biopsy Decision Support Tool, Breast Cancer Risk Calculator, BI-RADS 4 Mammography Risk Stratification, Overbiopsy Reduction, Probability of Malignancy (POM) Assessment, Biopsy-based Positive Predictive Value (PPV3) Supplemental material is available for this article. Published under a CC BY 4.0 license.See also the commentary by McDonald and Conant in this issue.

IntroductionYoung adults with HIV (YWH) experience worse clinical outcomes than adults and have high rates of substance use (SU) and mental illness that impact their engagement in care and adherence to antiretroviral therapy (ART). The intervention for Virologic Suppression in Youth (iVY) aims to address treatment engagement/adherence, mental health (MH) and SU in a tailored manner using a differentiated care approach that is youth friendly. Findings will provide information about the impact of iVY on HIV virological suppression, MH and SU among YWH who are disproportionately impacted by HIV and at elevated risk for poor health outcomes.Methods and analysisThe iVY study will test the effect of a technology-based intervention with differing levels of resource requirements (ie, financial and personnel time) in a randomised clinical trial with an adaptive treatment strategy among 200 YWH (18-29 years old). The primary outcome is HIV virological suppression measured via dried blood spot. This piloted and protocolised intervention combines: (1) brief weekly sessions with a counsellor via a video-chat platform (video-counselling) to discuss MH, SU, HIV care engagement/adherence and other barriers to care; and (2) a mobile health app to address barriers such as ART forgetfulness, and social isolation. iVY has the potential to address important, distinct and changing barriers to HIV care engagement (eg, MH, SU) to increase virological suppression among YWH at elevated risk for poor health outcomes.Ethics and disseminationThis study and its protocols have been approved by the University of California, San Francisco Institutional Review Board. Study staff will work with a Youth Advisory Panel to disseminate results to YWH, participants and the academic community.Trial registration numberNCT05877729.

Despite lower user costs, only 20% to 40% of transportation network company (TNC) users select a pooled, or shared, ride option. Why are existing TNC users not selecting the pooled option or using TNCs to connect to public transit, and what role do built environment features and incentives play in their decision? This study explores the factors that influence TNC user decisions through a multi-method approach comprising photovoice small group discussions and a workshop. Between March 2021 and May 2021, 15 San Francisco Bay Area TNC users shared photographs they took of TNC pick-up locations through two-to-three-person guided small group discussions. The photos revealed that users prefer waiting in retail or in well-lit, good-visibility locations. Participants’ primary concern was personal safety, particularly female users who may take additional precautions when walking to pick-up locations and waiting for and taking rides. In July 2021, 12 photovoice participants and 5 stakeholders provided feedback on key findings from the photography discussions. The pooling improvement strategies identified include the following: designated TNC stops with lighting and marked pick-up areas; enhanced in-app safety features; TNC partnerships with employers and retailers to incentivize riders; and mode transfer discounts for connecting TNCs to public transit. The findings suggest that safety related to the built environment plays an outsized role in a TNC user’s decision to pool or connect to public transit, and the out-of-vehicle portion of the TNC trip should be equally considered when developing policies to increase pooling.

BACKGROUND: Craniopharyngiomas, primary brain tumors of the pituitary-hypothalamic axis, can cause clinically significant sequelae. Treatment with the use of surgery, radiation, or both is often associated with substantial morbidity related to vision loss, neuroendocrine dysfunction, and memory loss. Genotyping has shown that more than 90% of papillary craniopharyngiomas carry BRAF V600E mutations, but data are lacking with regard to the safety and efficacy of BRAF-MEK inhibition in patients with papillary craniopharyngiomas who have not undergone previous radiation therapy. METHODS: Eligible patients who had papillary craniopharyngiomas that tested positive for BRAF mutations, had not undergone radiation therapy previously, and had measurable disease received the BRAF-MEK inhibitor combination vemurafenib-cobimetinib in 28-day cycles. The primary end point of this single-group, phase 2 study was objective response at 4 months as determined with the use of centrally determined volumetric data. RESULTS: Of the 16 patients in the study, 15 (94%; 95% confidence interval [CI], 70 to 100) had a durable objective partial response or better to therapy. The median reduction in the volume of the tumor was 91% (range, 68 to 99). The median follow-up was 22 months (95% CI, 19 to 30) and the median number of treatment cycles was 8. Progression-free survival was 87% (95% CI, 57 to 98) at 12 months and 58% (95% CI, 10 to 89) at 24 months. Three patients had disease progression during follow-up after therapy had been discontinued; none have died. The sole patient who did not have a response stopped treatment after 8 days owing to toxic effects. Grade 3 adverse events that were at least possibly related to treatment occurred in 12 patients, including rash in 6 patients. In 2 patients, grade 4 adverse events (hyperglycemia in 1 patient and increased creatine kinase levels in 1 patient) were reported; 3 patients discontinued treatment owing to adverse events. CONCLUSIONS: In this small, single-group study involving patients with papillary craniopharyngiomas, 15 of 16 patients had a partial response or better to the BRAF-MEK inhibitor combination vemurafenib-cobimetinib. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT03224767.).

Curb space has been traditionally designed for private vehicle parking, public transit, and passenger and commercial loading. However, in recent years, a growing number of newservices and activities have increased the demand for limited curb space, including passenger pick-up and drop-off; last-mile delivery (e.g., courier network services, personal delivery devices); electric vehicle (EV) charging; micromobility parking and use (e.g., personally owned and shared bikes and scooters); and carsharing services. The curb serves a variety of functions such as vehicle and device storage (including personally owned and shared vehicles and devices), outdoor dining and retail, greenspace, and other uses. These changes are contributing to a notable shift in how people access and use the curb, and how public agencies plan, prioritize, and manage curbside interactions.

Aviation is undergoing rapid change due to advancements in technology, new business models, changing consumer preferences, and other trends. These trends are poised to change the way people travel by air. Advanced air mobility (AAM) is a broad concept focusing on leveraging these trends to include routine aviation mobility in urban, suburban, and rural communities. NASA envisions AAM as safe, sustainable, accessible, and affordable aviation for transformational local and intraregional missions. But it’s worth noting that this vision, AAM associated terms, and even the definition of AAM will also continue to mature. The AAM Coordination and Leadership Act defines the terms “advanced air mobility” and “AAM” as a transportation system that transports people and property by air be-tween two points using aircraft with advanced technologies, including electric aircraft or electric vertical take-off and landing aircraft, in both con-trolled and uncontrolled airspace. AAM includes moving light, time-critical packages by small uncrewed air systems – informally known as “drones.” These packages could include medical supplies to isolated areas or sensors to inspect pipelines or rail tracks. AAM also includes the movement of people and cargo within com-munities, whether this is transporting rural patients to the hospital, passengers to the airport, or packages to a central distribution point where they could be delivered with the mail in electric vehicles. AAM includes regional travel too short or lacking demand for existing air travel, but too long for an easy ground trip. AAM is made possible through integrated and connected multimodal infrastructure and data networks. Infrastructure networks will include existing transportation structures such as roads, airports, and train and bus stations and new AAM infrastructure such as vertiports. Data networks include new equipment, such as navigational aids, connections, such as satellite frequencies, and data such as, local weather observations.

Chimeric antigen receptor T cell (CAR-T) therapies are Food and Drug Administration (FDA)-approved for patients with triple refractory multiple myeloma (MM). Real-world access to CAR-T therapy remains challenging owing to supply chain limitations impacting manufacturing. The goal of this study was to evaluate the extent of this issue and how major centers are handling the challenges of CAR-T manufacturing slot allocation. MM CAR-T physician leaders at each CAR-T treatment center across the United States were surveyed. We received responses from 17 of 20 centers. A median of 1 slot is allocated per month per center, and the median number of patients per center on the waitlist since the FDAs approval of idecabtagene vicleucel is 20 (range, 5 to 100). As a result, patients remain on the waitlist for a median of 6 months (range, 2 to 8 months) prior to leukapheresis. For patient selection, all centers reported using a committee of experienced CAR-T physicians to ensure consistency. To ensure transparency, 15 centers make selection criteria, selection timelines, and priority scores readily available for CAR-T providers. Centers also reported using ethical values for selection: (1) equal treatment: time spent on waiting list (n = 12); (2) priority to the worst-off: limited therapeutic options (n = 14), MM burden (n = 11), high Hematopoietic Cell Transplantation Comorbidity Index (n = 5); (3) maximize benefit: most likely to complete apheresis (n = 13) or infusion (n = 13) or to achieve response (n = 8); and (4) social value: younger patients (n = 3). Maximizing benefit was considered the most important criterion by 10 centers. This study is the first attempt to evaluate existing issues with CAR-T access for patients with MM and the variability and challenges in patient selection. Integrating ethical resource allocation strategies, similar to those described here, into formal institutional policies would help streamline access to CAR-T therapy and protect the needs of both current and future patients and physicians.

Advanced air mobility (AAM) is a broad concept enabling consumers access to air mobility, cargo and package delivery, healthcare applications, and emergency services through an integrated and connected multimodal transportation network. AAM includes local use cases of about a 50-mile radius in rural or urban areas and intraregional use cases of up to approximately 500 miles that occur within or between urban and rural areas. The Future of Aviation Conference: Advancing Aerial Mobility through Technology, Sustainability, and On-Demand Flight was held in person at the San Francisco International Airport from August 2 to 5, 2022. The conference commenced with an AAM 101 workshop hosted by the Community Air Mobility Initiative (CAMI) on August 2nd. The full conference program began on August 3rd. This event advanced key research and policy discussions around environmental impacts, safety, security, equity, multimodal integration, and the role of government.

PURPOSE: Patients with progressive or recurrent meningiomas have limited systemic therapy options. Focal adhesion kinase (FAK) inhibition has a synthetic lethal relationship with NF2 loss. Given the predominance of NF2 mutations in meningiomas, we evaluated the efficacy of GSK2256098, a FAK inhibitor, as part of the first genomically driven phase II study in recurrent or progressive grade 1-3 meningiomas. PATIENTS AND METHODS: Eligible patients whose tumors screened positively for NF2 mutations were treated with GSK2256098, 750 mg orally twice daily, until progressive disease. Efficacy was evaluated using two coprimary end points: progression-free survival at 6 months (PFS6) and response rate by Macdonald criteria, where PFS6 was evaluated separately within grade-based subgroups: grade 1 versus 2/3 meningiomas. Per study design, the FAK inhibitor would be considered promising in this patient population if either end point met the corresponding decision criteria for efficacy. RESULTS: Of 322 patients screened for all mutation cohorts of the study, 36 eligible and evaluable patients with NF2 mutations were enrolled and treated: 12 grade 1 and 24 grade 2/3 patients. Across all grades, one patient had a partial response and 24 had stable disease as their best response to treatment. In grade 1 patients, the observed PFS6 rate was 83% (10/12 patients; 95% CI, 52 to 98). In grade 2/3 patients, the observed PFS6 rate was 33% (8/24 patients; 95% CI, 16 to 55). The study met the PFS6 efficacy end point both for the grade 1 and the grade 2/3 cohorts. Treatment was well tolerated; seven patients had a maximum grade 3 adverse event that was at least possibly related to treatment with no grade 4 or 5 events. CONCLUSION: GSK2256098 was well tolerated and resulted in an improved PFS6 rate in patients with recurrent or progressive NF2-mutated meningiomas, compared with historical controls. The criteria for promising activity were met, and FAK inhibition warrants further evaluation for this patient population.

BackgroundYoung adults have a disproportionately high rate of HIV infection, high rates of attrition at all stages of the HIV care continuum, and an elevated probability of disease progression and transmission. Tracking and monitoring objective measures of antiretroviral therapy (ART) adherence in real time is critical to bolster the accuracy of research data, support adherence, and improve clinical outcomes. However, adherence monitoring often relies on self-reported and retrospective data or requires additional effort from providers to understand individual adherence patterns. In this study, we will monitor medication-taking using a real-time objective measure of adherence that does not rely on self-report or healthcare providers for measurement.MethodsThe Youth Ending the HIV Epidemic (YEHE) study will pilot a novel automated directly observed therapy-conditional economic incentive (aDOT-CEI) intervention to improve ART adherence among youth with HIV (YWH) in California and Florida who have an unsuppressed HIV viral load. The aDOT app uses facial recognition to record adherence each day, and then economic incentives are given based on a participant's confirmed adherence. We will enroll participants in a 3-month pilot study to assess the feasibility and acceptability of the aDOT-CEI intervention using predefined metrics. During and after the trial, a subsample of the pilot participants and staff/providers from participating AIDS Healthcare Foundation (AHF) clinics will participate in individual in-depth interviews to explore intervention and implementation facilitators and barriers.DiscussionYEHE will provide data on the use of an aDOT-CEI intervention to improve adherence among YWH who are not virologically suppressed. The YEHE study will document the feasibility and acceptability and will explore preliminary data to inform a trial to test the efficacy of aDOT-CEI. This intervention has the potential to effectively improve ART adherence and virologic suppression among a key population experiencing health disparities.Trial registrationThe trial registration number is NCT05789875.

Background: Technology-based directly observed therapy (DOT) is more cost-effective and efficient compared with in-person monitoring visits for medication adherence. While some evidence shows these technologies are feasible and acceptable, there is limited evidence collating information across medical conditions or in the context of HIV prevention, care, and treatment.Objectives: We conducted a scoping review to understand the current evidence on the acceptability, feasibility, and efficacy of digital DOT to improve medication adherence and, specifically, to determine if digital DOT had been used to improve adherence for HIV prevention, care, and treatmentMethods: We searched the electronic databases PubMed, Embase, and the Web of Science in January 2021 for any published studies with terms related to digital technologies and DOT. We included peer-reviewed studies in any population, from any country, for any outcome, and excluded conference abstracts. We included three types of digital DOT interventions: synchronous DOT, asynchronous DOT, and automated DOT. We provide an assessment of the current evidence, gaps in literature, and opportunities for intervention development regarding the use digital DOT to improve antiretroviral therapy (ART) adherence, specifically in the field of HIV.Results: We identified 28 studies that examined digital DOT. All studies found digital DOT to be acceptable and feasible. Patients using digital DOT had higher rates of treatment completion, observed doses, and adherence compared with in-person DOT, although data were limited on adherence. Only one study examined HIV prevention, and none examined ART adherence for HIV treatment.Conclusions: Digital DOT is acceptable and feasible but has not been used to remotely monitor and support ART adherence for people living with HIV.

Transportation network companies (TNCs) are changing the way people travel by providing dynamic, on-demand mobility that can supplement public transit and personal vehicle use. Early research suggests that TNCs have the potential to expand access and mobility for underserved communities. Yet aspects of the way TNCs operate have come under scrutiny as pricing algorithms and the choices of human drivers have resulted in a number of inequities and biases in cost and service levels across various socio-demographic groups (e.g., minorities, women, people with disabilities). TNCs present opportunities to increase individual mobility and access, butthey can exacerbate existing inequities and increase VMT, congestion, and emissions. This study led to several key findings regarding TNC customer interest in using pooled rides; consideration of other modes; insights into how disability status, race, ethnicity, gender, and sexuality can influence transportation decision-making; and desired improvements to make transportation more affordable, convenient, reliable, and safer.

Transportation Network Companies (TNCs) enable travelers to order and pay for rides on-demand using an online application that connects them with drivers using their personal vehicles. While these modes present opportunities to increase individual mobility and access, they also can worsen congestion and increase vehicle emissions. Researchers explored factors impacting the willingness to use pooled TNCs and identified strategies/policies that could be employed to reduce congestion from TNC use. Researchers conducted a literature review, interviews with TNC experts, semi-structured interviews with lower-income, non-White TNC users, and small group discussions with lower-income, non-White TNC users. This research resulted in several key findings including the importance of travel time in the decision to pool, greater focus on meeting the needs of people with disabilities, key operational and safety drawbacks of public transportation(e.g., delayed vehicles, harassment onboard), and the importance of personal safety in transportation decision-making. These findings informed several policy options to better understand how TNC benefits can be maximized while minimizing their negative externalities, such as congestion and vehicle emissions.