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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.

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.

BackgroundGlioblastoma is an incurable disease with a poor prognosis. For caregivers of people with glioblastoma, the burden of care can be high. Patients often present with different clinical characteristics, which may impact caregiver burden in different ways. This study aimed to evaluate associations between patient clinical characteristics and caregiver burden/quality of life (QoL).MethodsCaregiver-patient dyads were enrolled at 7 academic cancer centers in the United States. Eligible caregiver participants were self-reported as the primary caregiver of an adult living with glioblastoma and completed a caregiver burden survey. Eligible patients were age ≥ 18 years at glioblastoma diagnosis and alive when their respective caregiver entered the study, with the presence of cognitive dysfunction confirmed by the caregiver. Data were analyzed with descriptive statistics and multivariable analyses.ResultsThe final cohort included 167 dyads. Poor patient performance status resulted in patient difficulty with mental tasks, more caregiving tasks, and increased caregiving time. Language problems were reported in patients with left-sided lesions. Patient confusion was negatively associated with all caregiver domains: emotional health, social health, general health, ability to work, confidence in finances, and overall QoL. Better caregiver QoL was observed in patients with frontal lobe lesions versus non-frontal lobe lesions.ConclusionThis study reinforced that patient performance status is a critical clinical factor that significantly affects caregiver burden, caregiving tasks, and caregiver time. Additionally, patient confusion affects multiple facets of caregiver burden/QoL. These results could be used to support guided intervention for caregiver support, customized to the patient experience.

Abstract PURPOSE Standard of care for craniopharyngiomas is surgery with or without radiotherapy (RT). Cohort A of Alliance A071601 evaluated the efficacy of BRAF/MEK inhibition with vemurafenib/cobimetinib in patients with previously untreated papillary craniopharyngiomas (PCP), which carry the BRAF V600E mutation. Cohort B is currently enrolling patients with recurrence after RT. In a correlative analysis, we examined changes in RT volumes after BRAF/MEK therapy in Cohort A. METHODS Previously unirradiated patients with BRAF-mutated PCP were treated with vemurafenib/cobimetinib. Sixteen patients had scans available before starting vemurafenib/cobimetinib (“pre-therapy”) and after completing therapy (“post-therapy”). Two patients went off study treatment after 8 and 9 days due to side-effects and were excluded for this analysis. Gross target volumes (GTV) were contoured on pre-therapy and post-therapy scans. On post-therapy scans, an additional target comprising gross disease and at-risk regions for microscopic residual disease (GTV-micro) was defined and considered the treatment volume. Clinical target volume (CTV) was a 5-mm uniform expansion on pre-therapy GTV and post-therapy GTV-micro. Volumes were independently reviewed by two radiation oncologists. Changes in volumes from pre- versus post-therapy were compared using the Wilcoxon signed rank test. RESULTS In 14 patients evaluated, 57% were female and median age at enrollment was 49.5 years (range 33-83). Median time on treatment was 8.9 months (range 4.0-18.0). Median GTV pre-therapy was 3.8 mL (range 0.2-23.4) versus 0.3 mL (range 0.0-3.2) post-therapy (p=0.0001) and 1.7 mL (range 0.1-8.0) post-therapy GTV-micro (p=0.0001). Median CTV pre-therapy was 13.7 mL (range 2.8-51.8) versus 9.1 mL (range 2.2-27.5) post-therapy (p=0.0001). All tumors abutted the optic chiasm pre-therapy, only 6 did post-therapy. CONCLUSIONS Vemurafenib/cobimetinib resulted in smaller RT volumes. BRAF/MEK inhibitors could reduce RT volumes and spare dose to surrounding normal structures. Enrollment to Cohort B of Alliance A071601 should be considered for patients with recurrent tumors after RT. SUPPORT https://acknowledgments.alliancefound.org

The Transportation Sustainability Research Center (TSRC) at the University of California, Berkeley is pleased to present the results of the Mobility on Demand (MOD) State of the Industry Practitioner Census. The global pandemic has led to a challenging period for the transportation sector. Nevertheless, the industry has shown resilience and innovation. This industry outlook provides information on MOD and Mobility as a Service (MaaS) developments throughout the United States (U.S.) and highlights some industry changes in response to the pandemic.

Advanced air mobility (AAM) is a broad concept enabling consumers access to on-demand air mobility, cargo and package delivery, healthcare applications, and emergency services through an integrated and connected multimodal transportation network. However, a number of challenges could impact AAM’s growth potential, such as autonomous flight, the availability of take-off and landing infrastructure (i.e., vertiports), integration into airspace and other modes of transportation, and competition with shared automated vehicles. This article discusses the results of a demand analysis examining the market potential of two potential AAM passenger markets—airport shuttles and air taxis. The airport shuttle market envisions AAM passenger service to, from, or between airports along fixed routes. The air taxi market envisions a more mature and scaled service that provides on-demand point-to-point passenger services throughout urban areas. Using a multi-method approach comprised of AAM travel demand modeling, Monte Carlo simulations, and constraint analysis, this study estimates that the air taxi and airport shuttle markets could capture a 0.5% mode share. The analysis concludes that AAM could replace non-discretionary trips greater than 45 min; however, demand for discretionary trips would be limited by consumer willingness to pay. This study concludes that AAM passenger services could have a daily demand of 82,000 passengers served by approximately 4000 four- to five-seat aircraft in the U.S., under the most conservative scenario, representing an annual market valuation of 2.5 billion USD.

The Mobility on Demand (MOD) Sandbox Demonstration Program provides a venue through which integrated MOD concepts and strategies, supported through local partnerships, are demonstrated in real-world settings. For the 11 MOD Sandbox Demonstration projects, an independent evaluation was conducted that includes an analysis of project impacts from performance measures provided by the project partners and an assessment of the business models used. This document presents the results from the independent evaluation of the Dallas Area Rapid Transit (DART) First and Last Mile Solution MOD Sandbox Demonstration project. Evaluated were hypotheses that explored project impacts on travel behavior, user experiences, first and last mile to public transit accessibility, service quality for passengers with disabilities, and costs. The project improved first and last mile connectivity to DART transit, increased satisfaction among DART transit users, enhanced service for passengers with disabilities, and increased the geographic scope of DART transit service in the Plano area. In addition, wait and travel times for passengers with and without disabilities reflected similar distributions. The subsidy per rider of GoLink services was lower than the low-ridership fixed-route transit services that it replaced in Plano, but it was not lower than the subsidy for DART fixed-route transit in the overall Dallas region. DART project team members were interviewed to better understand challenges, barriers, successes, and broader lessons learned from the project, representing agency personnel from the offices of Innovation, Service Planning, Scheduling, Paratransit Operations, and Marketing. Lessons learned revealed the importance of having pre-planned, ready-to-go projects with committed partners, flexible contracting terms, metrics for adjusting spatial and temporal service coverage (including terminating service if appropriate), vehicle right-sizing, and understanding customer needs.

The Federal Transit Administration’s (FTA) Mobility on Demand (MOD) Sandbox Program provides a venue through which integrated MOD concepts and strategies, supported through local partnerships, are demonstrated in real-world settings. This case study documents lessons learned from the Chicago Transit Authority (CTA) MOD Sandbox Demonstration, called Ventra–Divvy Integration. The case study is a part of an independent evaluation of the MOD Sandbox Demonstrations sponsored by the USDOT Intelligent Transportation Systems Joint Program Office (ITS JPO) and FTA. The case study includes background on CTA’s MOD Sandbox Demonstration, technical and institutional challenges encountered in the demonstration’s first phase, payment integration and unbanked access as part of the second phase of the demonstration, and discussion of lessons learned and recommended practices identified from this demonstration.

2000 Background: Craniopharyngiomas, a rare brain tumor along the pituitary-hypothalamic axis, can cause significant clinical sequelae. Surgery and radiation, the only effective treatments, can cause significant morbidity. Genetic analysis of craniopharyngiomas revealed that 95% of papillary craniopharyngiomas (PCP) have BRAF V600E mutations (Brastianos et al. Nature Genetics 2014). We evaluated the efficacy of BRAF/MEK inhibition in patients (pts) with previously untreated PCP. Methods: Eligible pts without prior radiation whose PCP screened positively for BRAF mutations were treated with oral vemurafenib/cobimetinib in 28-day cycles. The primary endpoint of response rate (RR) based on centrally determined volumetric data was evaluated in 16 pts, where a partial response was defined as >20% decrease in volume. This single arm, Simon two-stage phase 2 trial had 89% power to detect a true RR of at least 30% (vs. the null RR 5%; alpha=0.04). In this design, 3 or more observed volumetric responses in 16 evaluable pts would be considered promising activity. Results: In the 16 pts evaluated, 56% were female, and the median age was 49.5 years. Median follow-up was 22 months (95% CI: 16-26.5) and median number of treatment cycles was 8. Three patients progressed after therapy was discontinued and none have died. Based on volumetric response criteria, 14 of 15 pts with volumetric data available for central review had response to therapy (93%; 95% CI: 68% to 99.8%). Of 16 patients evaluable based on local review, 15 had response to therapy (93.75%; 95% CI: 70% to 99.8%). The median tumor reduction was -83% (range: -52% to -99%). The one nonresponder received 2 days of treatment before coming off therapy due to toxicity. Median progression-free survival was not reached. Grade 3 toxicities at least possibly related to treatment occurred in 12 pts (rash in 6 pts). Grade 4 toxicities were observed in two pts: hyperglycemia (n=1) and increased CPK (n=1). Three pts discontinued treatment for adverse events. Conclusions: Vemurafenib/cobimetinib resulted in an objective response in all pts who received 1 or more cycles of therapy. Our study indicates that BRAF/MEK inhibitors could be a powerful tool in the treatment of previously untreated PCP and warrants further evaluation in larger studies. A second arm of this study is enrolling pts with progressive PCP after prior radiotherapy. Support: U10CA180821, U10CA180882; U24CA196171, U10CA180868 (NRG); Genentech; https://acknowledgments.alliancefound.org. Clinical trial information: NCT03224767.

Background and aimDirect-acting antivirals (DAAs) have increased hepatitis C virus (HCV) treatment opportunities for vulnerable HIV/HCV coinfected persons. The aim of this study was to identify the frequency of and potential barriers to DAA prescription in HIV/HCV patients during the first few years of DAA availability in the United States.MethodsThe AIDS Healthcare Foundation electronic medical record system was queried to identify all HCV viremic HIV-infected patients in care at AIDS Healthcare Foundation Healthcare centers in January 2015-August 2017 and compare characteristics by receipt of a DAA prescription. Multivariate logistic regression analyses were conducted to examine factors associated with DAA prescription.ResultsOf 826 eligible patients, 355 (43%) were prescribed a DAA; among those not prescribed a DAA, 301 (64%) had well-controlled HIV (HIV RNA ≤ 200 copies per mL). In multivariate logistic regression analysis, patients with a history of substance use (odds ratio [OR], 0.51 [95% confidence interval 0.35-0.73]) or on select HIV antiretroviral regimens were less likely to be prescribed a DAA. Those who had well-controlled HIV (OR, 5.03 [3.06-8.27]), CD4 + T cell count >200 cells per mm3 (OR, 1.85 [1.04-3.30]), estimated glomerular filtration rate >60 mL/min/1.73 m2 (OR, 3.32 [1.08-10.15]), or established care prior to January 2015 (OR, 1.57 [1.08-2.29] were more likely to be prescribed a DAA.ConclusionsIn addition to lack of HIV suppression, select antiretroviral regimens, substance use, and kidney disease appeared to limit DAA prescription in the early interferon-free DAA era. Many were not prescribed DAAs despite HIV suppression. Further research is needed to determine if the observed associations persist today.

This report documents the results of an independent evaluation of the Vermont Agency of Transportation’s (VTrans) OpenTripPlanner (OTP), called Go! Vermont, part of the Federal Transit Administration (FTA) Mobility on Demand (MOD) Sandbox Demonstration program. The project intended to serve as an alternative to other trip planners by including flexible transit options such as route deviation, dial-a-ride, and other demand-responsive alternatives and to analyze web traffic data to determine the level of user activity attracted by Go! Vermont since its launch. The evaluation compared the trip itineraries of Google Maps and the OTP and explored the inclusion of flexible transit options. Eight hypotheses were evaluated, and expert (stakeholder/project partner) interviews highlighted VTrans partnerships with employment services and vocational rehabilitation to leverage the trip planner for improving access to jobs, training, and healthcare for carless and carlite house-holds. Interviewees noted how the trip planner improved how telephone dispatchers and case workers provided transportation information.

Evacuation and response plans require thoughtful strategies that build mandatory evacuation order compliance, reduce vehicular congestion, and increase social equity for disadvantaged populations. However, the novel coronavirus (COVID-19) pandemic coincided with a series of devastating disasters in 2020 that have required mass evacuations, leading to several new compounding effects (i.e., “double the trouble”). Strategies typically used in evacuations (e.g., high-capacity vehicles and public congregate shelters) and movements of people (e.g., evacuees, first responders, and volunteers) could increase the risk of COVID-19 spread and exposure. Moreover, disadvantaged populations who are already disproportionately impacted by disasters and COVID-19 separately could face new challenges in dual crises. To address these new and growing challenges, this playbook employs insights from case studies (n=12), survey data of individuals impacted by public safety power shutoff (PSPS) events (n=210), and expert interviews (n=17). Using these data, the playbook: (i) shares recent lessons learned from case studies of compounding disasters during the pandemic; (ii) offers a primer for the potential compounding impact of PSPS events and disasters; (iii) highlights current considerations in the emergency management and evacuation fields; and (iv) provides a series of actionable checklists to address COVID-19 and a compounding disaster. Relevant stakeholders in disasters and evacuations that should use this playbook include public agencies, first responders, community-based organizations, non-governmental organizations, private mobility companies, public health facilities, and other evacuation stakeholders. The playbook can beadapted for multiple hazards, different local contexts, various agency types, and future pandemics.

Since the early 20th century, inventors have conceptualized “plane cars” and other urban aerial transportation. Emerging innovations in electrification, automation, and other technologies are enabling new opportunities for on-demand air mobility, business models, and aircraft design. Urban air mobility (UAM) envisions a safe, sustainable, affordable, and accessible air transportation system for passenger mobility, goods delivery, and emergency services within or traversing metropolitan areas. This research employed a multi-method approach comprised of 106 interviews with thought leaders and two stakeholder workshops to construct the history, ecosystem, state of the industry, and potential evolution of UAM. The history, current developments, and anticipated milestones of UAM can be classified into six phases: 1) “flying car” concepts from the early 1910s to 1950s, 2) early UAM operations using scheduled helicopter services from the 1950s to 1980s, 3) re-emergence of on-demand services starting in the 2010s, 4) corridor services using vertical take-off and landing (VTOL) envisioned for the 2020s, 5) hub and spoke services, and 6) point-to-point services. In the future, UAM could face several barriers to growth and mainstreaming, such as the existing regulatory environment; community acceptance; and concerns about safety, noise, social equity, and environmental impacts. UAM also could be limited by infrastructure and airspace management needs, as well as business model constraints. The paper concludes with recommendations for future research on sustainability, social and economic impacts, airspace integration, and other topics.