Background: We evaluated vorasidenib (VOR), a dual inhibitor of mIDH1/2, in patients with mIDH1/2 glioma (Phase 3; NCT04164901). Methods: Patients with residual/recurrent grade 2 mIDH1/2 oligodendroglioma or astrocytoma were enrolled (age ≥12; Karnofsky Performance Score ≥80; measurable non-enhancing disease; surgery as only prior treatment; not in immediate need of chemoradiotherapy). Patients were stratified by 1p19q status and baseline tumor size and randomized 1:1 to VOR 40 mg or placebo (PBO) daily in 28-day cycles. Endpoints included imaging-based progression-free survival (PFS), time to next intervention (TTNI), tumor growth rate (TGR), health-related quality of life (HRQoL), neurocognition and seizure activity. Results: 331 patients were randomized (VOR, 168; PBO, 163). The median age was 40.0 years. 172 and 159 patients had histologically confirmed oligodendroglioma and astrocytoma, respectively. Treatment with VOR significantly improved PFS and TTNI. Median PFS: VOR, 27.7 mos; PBO, 11.1 mos (P=0.000000067). Median TTNI: VOR, not reached; PBO, 17.8 mos (P=0.000000019). Treatment with VOR resulted in shrinkage of tumor volume. Post-treatment TGR: VOR, -2.5% (95% CI: -4.7, -0.2); PBO, 13.9% (95% CI: 11.1, 16.8). HRQoL and neurocognition were preserved and seizure control was maintained. VOR had a manageable safety profile. Conclusions: VOR was effective in mIDH1/2 diffuse glioma not in immediate need of chemoradiotherapy.

This method abstract details the Green School Program, piloted across three schools in maritime Fijian islands, addresses critical issues faced by Fijian and Pacific Island communities. These encompass malnutrition, food security, health hazards, and the urgency of integrating traditional knowledge, governance, and social-ecological systems approaches into creating healthier school environments. Non communicable diseases have emerged as a pervasive concern within Pacific Island communities, creating a challenge for public health systems, driven greatly by dietary habits(1). This complex health landscape underscores the need to safeguard traditional knowledge and agri-food practices and develop neo-traditional approaches to local food systems(2). Furthermore, the Green School Program recognizes the essential role of schools as community hubs, enabling enhancing heathy school environments by embracing traditional wisdom and sustainable farming practices and foods, ultimately empowering communities to address these multifaceted challenges(3). Developing the school environment as a sustainable setting for governance framework led by women and the school administration, rooted in traditional knowledge and practices. Additionally, it aims to design facilities that support efficient organic farming while integrating these into school activities. Economic sustainability through the sale of surplus farm products, as well as the enhancement of sustainable land-use management, health, wellbeing, and cultural identity. The program unfolds within a distinctive community-based framework with the establishment of robust governance, with a notable emphasis on the leadership of women and mothers who play a pivotal role in steering the green school initiative and ensuring community ownership. Collaborative governance spans multiple stakeholders, including school management, community-based school committees, youth groups, women groups, and traditional leaders. This inclusive engagement ensures both shared responsibility in program design and ownership during implementation phases. Sustainable facilities are strategically designed to include biodigesters, water storage and irrigation systems, composting, organic fertilizers, and seedling nurseries, enhancing the program’s capacity to create healthier school food environments while embracing traditional practices and values. The program has witnessed the active engagement of women in governance roles, promoting community unity and ownership. Traditional knowledge integration has enhanced crop diversity and sustainability. Economic sustainability has been achieved through surplus farm product sales, reducing dependency on external funding sources. Health improvements are evident, with reduced exposure to indoor air pollution from open fires. Cultural identity preservation and increased student engagement are also notable outcomes. The Green School Program’s holistic approach, rooted in traditional knowledge and sustainable practices, has yielded positive outcomes in governance, agriculture, nutritional food security, health, and cultural identity preservation. The program’s success demonstrates the potential for community-based initiatives to address critical issues and empower remote island communities. These results provide valuable insights into sustainable development approaches that prioritize community wellbeing and cultural heritage preservation in similar contexts.

While mentors can learn general strategies for effective mentoring, existing mentorship curricula do not comprehensively address how to support marginalized mentees, including LGBTQIA+ mentees. After identifying best mentoring practices and existing evidence-based curricula, we adapted these to create the Harvard Sexual and Gender Minority Health Mentoring Program. The primary goal was to address the needs of underrepresented health professionals in two overlapping groups: (1) LGBTQIA+ mentees and (2) any mentees focused on LGBTQIA+ health. An inaugural cohort (N = 12) of early-, mid-, and late-career faculty piloted this curriculum in spring 2022 during six 90-minute sessions. We evaluated the program using confidential surveys after each session and at the program’s conclusion as well as with focus groups. Faculty were highly satisfied with the program and reported skill gains and behavioral changes. Our findings suggest this novel curriculum can effectively prepare mentors to support mentees with identities different from their own; the whole curriculum, or parts, could be integrated into other trainings to enhance inclusive mentoring. Our adaptations are also a model for how mentorship curricula can be tailored to a particular focus (i.e., LGBTQIA+ health). Ideally, such mentor trainings can help create more inclusive environments throughout academic medicine.

The coronavirus disease 2019 (COVID-19) pandemic has placed significant burden on healthcare systems. We compared Clostridioides difficile infection (CDI) epidemiology before and during the pandemic across 71 hospitals participating in the Canadian Nosocomial Infection Surveillance Program. Using an interrupted time series analysis, we showed that CDI rates significantly increased during the COVID-19 pandemic.

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) led to a significant disease burden and disruptions in health systems. We describe the epidemiology and transmission characteristics of early coronavirus disease 2019 (COVID-19) cases in Bavaria, Germany. Cases were reverse transcription polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infections, reported from 20 January−19 March 2020. The incubation period was estimated using travel history and date of symptom onset. To estimate the serial interval, we identified pairs of index and secondary cases. By 19 March, 3546 cases were reported. A large proportion was exposed abroad (38%), causing further local transmission. Median incubation period of 256 cases with exposure abroad was 3.8 days (95%CI: 3.5–4.2). For 95% of infected individuals, symptom onset occurred within 10.3 days (95%CI: 9.1–11.8) after exposure. The median serial interval, using 53 pairs, was 3.5 days (95%CI: 3.0–4.2; mean: 3.9, s.d.: 2.2). Travellers returning to Germany had an important influence on the spread of SARS-CoV-2 infections in Bavaria in early 2020. Especially in times of low incidence, public health agencies should identify holiday destinations, and areas with ongoing local transmission, to monitor potential importation of SARS-CoV-2 infections. Travellers returning from areas with ongoing community transmission should be advised to quarantine to prevent re-introductions of COVID-19.

Viral pneumonia is an important cause of death and morbidity among infants worldwide. Transmission of non-influenza respiratory viruses in households can inform preventative interventions and has not been well-characterised in South Asia. From April 2011 to April 2012, household members of pregnant women enrolled in a randomised trial of influenza vaccine in rural Nepal were surveyed weekly for respiratory illness until 180 days after birth. Nasal swabs were tested by polymerase chain reaction for respiratory viruses in symptomatic individuals. A transmission event was defined as a secondary case of the same virus within 14 days of initial infection within a household. From 555 households, 825 initial viral illness episodes occurred, resulting in 79 transmission events. The overall incidence of transmission was 1.14 events per 100 person-weeks. Risk of transmission incidence was associated with an index case age 1–4 years (incidence rate ratio (IRR) 2.35; 95% confidence interval (CI) 1.40–3.96), coinfection as initial infection (IRR 1.94; 95% CI 1.05–3.61) and no electricity in household (IRR 2.70; 95% CI 1.41–5.00). Preventive interventions targeting preschool-age children in households in resource-limited settings may decrease the risk of transmission to vulnerable household members, such as young infants.

This case study examined the hypothesis that longer outdoor time results in normal vision and refractive status, using unique genetically informative kinships. The participants were the members of 29-year-old doubly exchanged monozygotic male twin pairs from Bogotá, Colombia, in South America. Comprehensive ophthalmological examinations, including uncorrected and corrected visual acuity, refraction and keratometry, and visual life history interviews were undertaken; all examinations were conducted by two ophthalmologists blind to the hypothesis, relatedness, and rearing status of the four participants. Normal uncorrected vision and refractive status were present in the two rural-raised, unrelated brothers, relative to their urban-raised counterparts. Uncorrected visual acuities were 20/160 and 20/200 for the city-raised twins and 20/20 and 20/30 for the country-raised twins. Premature birth, low birth weight, computer use, and reading time could not explain these differences. It was concluded that time spent outdoors appears to be a significant factor in the development of myopia, reinforcing extant findings via a novel experimental approach.

The Principal INvestigator Development and Resources (PINDAR) program was developed at the NYU-H+H Clinical and Translational Science Award (CTSA) hub in response to a perceived need for focused good clinical practice (GCP) training designed specifically for principal investigators (PIs) performing human subject research. PINDAR is a novel 6-hour, instructor lead, participatory, in-person course for PIs developed de novo, piloted, and implemented. One hundred and seventeen faculty PIs participated in PINDAR from November 2016 through September 2018. All obtained mutual recognition for ICH E6 GCP training from TransCelerate Biopharma. PINDAR was well received by participant PIs, and feedback surveys have revealed a high degree of satisfaction with the program. Other CTSA hubs and research-intensive health systems should consider adopting a similar course focused on GCP for PIs.

Cyber Operational Risk: Cyber risk is routinely cited as one of the most important sources of operational risks facing organisations today, in various publications and surveys. Further, in recent years, cyber risk has entered the public conscience through highly publicised events involving affected UK organisations such as TalkTalk, Morrisons and the NHS. Regulators and legislators are increasing their focus on this topic, with General Data Protection Regulation (“GDPR”) a notable example of this. Risk actuaries and other risk management professionals at insurance companies therefore need to have a robust assessment of the potential losses stemming from cyber risk that their organisations may face. They should be able to do this as part of an overall risk management framework and be able to demonstrate this to stakeholders such as regulators and shareholders. Given that cyber risks are still very much new territory for insurers and there is no commonly accepted practice, this paper describes a proposed framework in which to perform such an assessment. As part of this, we leverage two existing frameworks – the Chief Risk Officer (“CRO”) Forum cyber incident taxonomy, and the National Institute of Standards and Technology (“NIST”) framework – to describe the taxonomy of a cyber incident, and the relevant cyber security and risk mitigation items for the incident in question, respectively.Summary of Results: Three detailed scenarios have been investigated by the working party:

• ∙ Employee leaks data at a general (non-life) insurer: Internal attack through social engineering, causing large compensation costs and regulatory fines, driving a 1 in 200 loss of £210.5m (c. 2% of annual revenue).

• ∙ Cyber extortion at a life insurer: External attack through social engineering, causing large business interruption and reputational damage, driving a 1 in 200 loss of £179.5m (c. 6% of annual revenue).

• ∙ Motor insurer telematics device hack: External attack through software vulnerabilities, causing large remediation / device replacement costs, driving a 1 in 200 loss of £70.0m (c. 18% of annual revenue).

• ∙ While the presented scenarios are deemed material at this point in time, the threat landscape moves fast and could render specific narratives and calibrations obsolete within a short-time frame.

• ∙ There is a lack of historical data to base certain scenarios on and therefore a high level of subjectivity is used to calibrate them.

• ∙ No attempt has been made to make an allowance for seasonality of renewals (a cyber event coinciding with peak renewal season could exacerbate cost impacts)

• ∙ No consideration has been given to the impact of the event on the share price of the company.

• ∙ Correlation with other risk types has not been explicitly considered.

OBJECTIVES/SPECIFIC AIMS: One of the key difficulties in predicting allergenic pollen exposures has been a lack of information on source plant location and abundance. However, the increasing availability of spatially explicit data from remote sensing offers new opportunities to create comprehensive inventories of allergenic pollen producing plants. METHODS/STUDY POPULATION: In this study, we use a spatially oriented field survey to map common ragweed (Ambrosia artemisiifolia) in Detroit, MI, USA. We then combine this with remote sensing imagery and LiDAR to predict ragweed presence and potential pollen production across 344 km2 of Detroit. Finally, we compare this with measurements of airborne pollen concentrations collected throughout the city. RESULTS/ANTICIPATED RESULTS: Our initial results show that ragweed is present in ~2% of the city, and its presence and abundance are strongly associated with demolished building (p<0.001). The uneven distribution of ragweed plants across the city leads to substantially higher pollen concentrations in neighborhoods where more buildings have been recently demolished. DISCUSSION/SIGNIFICANCE OF IMPACT: Our approach offers an effective way to quantify allergenic pollen production, airborne concentrations, and exposures across a large metropolitan area. This in turn provides insight on how to best reduce airborne pollen concentrations: in this case, by changing post-demolition land management practices.

A case–case-control investigation (N = 255 patients) explored the epidemiology of carbapenem-resistant Pseudomonas aeruginosa (CRPA). Recent exposure to carbapenems and a rapidly fatal condition should prompt practitioners to shorten delays in initiating appropriate therapy, which can adversely impact CRPA outcomes, as opposed to the isolated impact of the carbapenem resistance determinant.

Background: A previously healthy 26 year-old male presented with confusion and recurrent hypoglycemia (blood glucose lows of 2.5 mmol/L) while on vacation in Las Vegas. He denied substance or heavy alcohol use and the toxicology screen was negative. He was transferred home to Winnipeg for further care and was found to have only patchy memories of his trip and the days leading up to the trip, consistent with mixed anterograde and retrograde amnesia. MoCA score at presentation was 16/30 with points lost on orientation, delayed recall and visuospatial-executive tasks. MRI revealed T2 hyperintensities and diffusion abnormalities in bilateral hippocampi and globus pallidi. Electroencephalography showed triphasic waves. The patient was found to have a pancreatic insulinoma, which was surgically resected. In follow-up nine weeks later he was near his cognitive baseline, though he had ongoing difficulties with delayed recall. Repeat MRI showed improvement but not resolution of hippocampal and pallidal signal change, with mild hippocampal atrophy.

Neuropathological and animal studies have shown that structures most sensitive to hypoglycemic neural injury include the hippocampus, basal ganglia, and neocortex. The clinical and radiographic findings in this case illustrate an unusual presentation of insulinoma and the effects of hypoglycemia on the brain. Methods: N/A Results: N/A Conclusions: N/A

This work is part of the interlaboratory collaboration to study the stability of organic solar cells containing PCDTBT polymer as a donor material. The varieties of the OPV devices with different device architectures, electrode materials, encapsulation, and device dimensions were prepared by seven research laboratories. Sets of identical devices were aged according to four different protocols: shelf lifetime, laboratory weathering under simulated illumination at ambient temperature, laboratory weathering under simulated illumination, and elevated temperature (65 °C) and daylight outdoor weathering under sunlight. The results generated in this study allow us to outline several general conclusions related to PCDTBT-based bulk heterojunction (BHJ) solar cells. The results herein reported can be considered as practical guidance for the realization of stabilization approaches in BHJ solar cells containing PCDTBT.