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Intratumoral TLR9 agonists and anti-PD-1 provide durable clinical responses and broad immune activation. To evaluate efficacy and mechanisms of action of this combined treatment, we conducted a single-arm phase 2 neoadjuvant study of TLR9 agonist vidutolimod combined with anti-PD-1 nivolumab (vidu/nivo) in patients with high-risk resectable melanoma. In 30 evaluable patients, 57% (17/30) had major pathologic response (pR), with eight grade 3 treatment-related adverse events. pR was associated with lower residual viable tumor, necrosis, and melanophagocytosis with increased CD8+ tumor-infiltrating lymphocytes and plasmacytoid dendritic cells (pDCs) in the tumor microenvironment and increased frequencies of Ki67+ CD8+ and CD4+ T cells, pDCs, and monocytes peripherally. Gene signatures associated with pR included increased pDC density, macrophage activation, and phagocytosis engulfment. Gut microbial signatures in pR were enriched for Gram-negative bacteria belonging to the Bacteroidaceae and Enterobacteriaceae families and to the small subgroup of Gram-negative Firmicutes. Our findings support that combined vidu/nivo treatment stimulates a broad antitumor immune response and is associated with a distinct baseline gut microbiome composition.

After publication of this supplement [1, 2], it was brought to our attention that due to an error authors were missing in the following abstracts. This has now been included in this correction.

Multiplex IF (mIF) provides a detailed characterization of spatial relationships and complex cell phenotypes in the tumor microenvironment. However, the data-analysis and visualization is complex and time-consuming. Here, we developed a platform to analyze mIF data through flow cytometry workflows (image cytometry), while maintaining spatial information, and applied it to tissue microarrays of metastatic melanoma specimens (n=93; 6-plex mIF panel: PD-1, PD-L1, CD163, CD8, FoxP3, Sox10/S100). Then, we used a UMAP-based approach driven by cell-to-cell distances (rather than fluorescence intensity) to display and analyze geographic organization and cell interactions. Our pipeline provided equivalent results to the digital pathology gold standard with faster run times (5-fold reduction) and higher reproducibility. We identified key prognostic immune variables, including CD8PD1Low and CD8PD1Neg cells which associated with longer overall survival (OS, both p

California State University East Bay (CSUEB), opened in 1959 with 300 students on one campus. Since then, it has grown to serve over 14,000 students on three campuses. The motto of our university is “Per Aspera Ad Astra”, or “Through Adversity to the Stars”. This is an apt motto given that our university is the most racially and ethnically diverse campus in the continental United States (The Chronicle of Higher Education, 2014), and 61% of our undergraduate students are the first in their families to earn a college degree (Office of Institutional Research, personal communication, March 9, 2015). Our students are also highly diverse in terms of age, ability status, parenting experience, immigration background, sexual orientation, gender, religion, and much more. Though the diversity of our campus provides ample opportunities for faculty, staff, and students to be exposed to multiple perspectives, we have learned that intentional efforts are required to build an inclusive, accessible, and responsive community. This article describes strategies we have employed over the past five years across three broad areas: (a) support for student learning, engagement, and retention; (b) professional development; and (c) policies around inclusion and access. Preliminary evaluation of these efforts suggests that we have made significant progress in building an inclusive campus that supports student learning, respects all members of the campus community, and facilitates our continuing engagement in this work.

Information on the prevalence of deleterious BRCA1 and BRCA2 (BRCA1/2) mutations in clinic-based populations of Black women is limited. In order to address this gap, we performed a retrospective study to determine the prevalence of deleterious BRCA1/2 mutations, predictors of having a mutation, and acceptance of risk-reducing surgeries in Black women. In an urban unselected clinic-based population, we evaluated 211 self-identified Black women who underwent genetic counseling for hereditary breast–ovarian cancer syndrome. BRCA1/2 mutations were identified in 13.4 % of the participants who received genetic testing. Younger age at diagnosis, higher BRCA-PRO score, significant family history, and diagnosis of triple-negative breast cancer were associated with identification of a BRCA1/2 mutation. Of the affected patients found to have a deleterious mutation, almost half underwent prophylactic measures. In our study population, 1 in 7 Black women who underwent genetic testing harbored a deleterious BRCA1/2 mutation independent of age at diagnosis or family history.

CASE: Marcus is a 10-year-old boy who was followed by his pediatrician for several years. She knows him as a socially engaged, active athlete, playing soccer and baseball, out-going, and a good student. He has been in good health without a significant medical history.At the beginning of this academic year, a new student was placed in Marcus's fourth grade class. This student is disruptive, impulsive, and abusive. He has frequent violent outbursts, yelling, kicking, and throwing objects, including recently throwing a desk across the room. The school has made efforts to manage this student. The teacher sets up behavior contracts, and the school has temporarily suspended the child; however, the school is unable to remove the child from the classroom. Many students, including Marcus, have been significantly affected by this disruption.Marcus describes the classroom environment as "tense." He reports he is never sure what is going to make the student "so mad." Over the last 3-4 months, Marcus developed nightmares, enuresis, and trichotillomania. The hair pulling is the most distressing feature for both Marcus and his parents. Marcus acknowledges that he is usually unaware of the behavior at first but then finds the sensation is relaxing. Afterward, he is typically embarrassed by the behavior. There is a family history of anxiety in both parents.He has been seeing a psychologist with some mild improvement in his enuresis. However, the hair pulling has not improved and has worsened. They were seeking additional advice regarding the next steps. Language: en

A previously healthy 21-month-old female was brought by a personal car to a community hospital after her father accidently backed up a pickup truck over her. A truck tire reportedly slowly ran over the patient’s abdomen and legs. No loss of consciousness or other injuries were reported. At the community hospital, the patient was found to be hemodynamically stable with appropriate respiratory effort accompanied by a healthy cry. She had a plain film of the chest that was significant for no significant intrathoracic injury but showed a right humerus fracture. She did not have any computed tomography (CT) imaging because it was presumed that she would be transferred to the regional trauma center for definitive trauma evaluation and care. The patient received two 20-mL/kg boluses of normal saline and weight-based dosing of ondansetron and remained immobilized on a pediatric backboard. The local air medical transport team was requested for transfer of the patient to a regional pediatric trauma center for continued treatment of additional presumed traumatic injuries. When the flight team arrived, they noted that the patient was agitated with a waxing and waning mental status. Her Glasgow Coma Scale was estimated at 10, but the patient was moving all extremities without neurologic deficit and responding to verbal stimuli. Although the patient was maintaining her airway, she repeatedly vomited and was noted to become increasingly dyspneic with increased work of breathing despite clear lung sounds bilaterally and normal oxygen saturation. The patient was also noted to be tachycardic with heart rates between 150 and 198 beats/min. She was noted to have delayed capillary refill, weak brachial pulses, pale skin, and hypotensive readings as low as 54/48. Additionally, she was noted to have a distended, diffusely tender, taught abdomen.

“Hot” or “difficult” classroom moments occur when a student's provocative comment elevates emotions in the classroom and creates an uncomfortable tension. Faculty typically feel unprepared to address these volatile moments, and faculty developers and department chairs are faced with the challenge of boosting faculty confidence and helping instructors build the skills to navigate these unexpected moments. This article examines how case studies can be used to help instructors anticipate difficult moments, practice potential responses, and learn from the collective wisdom of their colleagues. Two case studies based on difficult moments in service-learning courses are included.

This paper describes a qualitative study in which midwives’ perceptions of high and low quality interactions between midwives and breast-feeding mothers were elicited. Questionnaires using a critical incident technique were distributed to all the midwives in a maternity service in the North of England. Structured analysis of 16 responses (40%) led to the development of four major themes: communication, support by health professionals, inaccuracy/inconsistency of advice and breast-feeding policy. The case for further education of midwives to improve their self-awareness and communication skills is presented along with recommendations related to resource allocation and policy development.

We study the population cycles of the Monarch butterfly using one of the simplest systems incorporating both migration and local dynamics. The annual migration of the Monarch involves four generations. Members of Generations 1-3 (occasionally 4) migrate from the over-wintering site in Central Mexico to breeding grounds that extend as far north as the Northern United States and Southern Canada. A portion of the Generation 3 and all members of the Generation 4 butterflies begin their return to the over-wintering grounds in August through October where they enter reproductive diapause for several months. We developed a simple discrete-time island chain model in which different fecundity functions are used to model the reproductive strategies of each generation. The fecundity functions are selected from broad classes of functions that capture the effects of either contest or scramble intraspecific competition in the Monarch population. The objectives of our research are multiple and include the study of the generationally dependent intraspecific competition and its effect on the pool size of migrants as well as the persistence of the overall butterfly populations. The stage structure used in modeling the Monarch butterfly dynamics and their generationally dependent reproductive strategies naturally support fluctuating patterns and multiple attractors. The implications of these fluctuations and attractors on the long-term survival of the Monarch butterfly population are explored.