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Levee systems are designed to reduce the risk of water-related natural hazards (e.g., flooding) in areas behind levees. Most levees in the U.S. are designed to protect people and facilities against the impacts of the 100-year floods. However, the current climate change is increasing the probability of the occurrence of 500-year flood events that in turn increases the likelihood of economic loss, environmental damage, and fatality that disproportionately impacts communities of color and low-income groups facing socio-economic inequities in leveed areas. The increased frequency and intensity of flooding is putting extra pressure on emergency responders that often require diverse, multi-dimensional data originating from different sources to make sound decisions. Currently, the integration of these heterogeneous data acquired by diverse sensors and emergency agencies about environmental, hydrological, and demographic indicators requires costly and complex programming and analysis that hinder rapid disaster management efforts. Our domain ‘Levee System Ontology (LSO)’ resolves the data integration and software interoperability issues by semantically modeling the static aspects, dynamic processes, and information content of the levee systems by extending the well-structured, top-level Basic Formal Ontology (BFO) and mid-level Common Core Ontologies (CCO). LSO’s class and property names follow the terminology of the National Levee Database (NLD), allowing data scientists using NLD data to constrain their classifications based on the knowledge represented in LSO. In addition to modeling the information related to the characteristics and status of the structural components of the levee system, LSO represents the residual risk in leveed areas, economic and environmental losses, and damage to facilities in case of breaching and/or overtopping of levees. LSO enables reasoning to infer components and places along levees and floodwalls where the system requires inspection, maintenance, and repair based on the status of system components. The ontology also represents the impact of flood management activities on different groups of people from an environmental justice perspective, based on the principles of DEI (diversity, equity, inclusion) as defined by the U.N. Sustainable Development Goals.

Introduction: Cardiac point-of-care ultrasound (c-POCUS) is an increasingly implemented diagnostic tool with the potential to guide clinical management. We sought to characterize and analyze the existing c-POCUS literature with a focus on the temporal trends and differences across specialties. Methods: A literature search for c-POCUS and related terms was conducted using Ovid (MEDLINE and Embase) and Web of Science databases through 2020. Eligible publications were classified by publication type and topic, author specialty, geographical region of senior author, and journal specialty. Results: The initial search produced 1761 potential publications. A strict definition of c-POCUS yielded a final total of 574 cardiac POCUS manuscripts. A yearly increase in c-POCUS publications was observed. Nearly half of publications were original research (48.8%) followed by case report or series (22.8%). Most publications had an emergency medicine senior author (37.5%), followed by cardiology (20.2%), anesthesiology (12.2%), and critical care (12.2%). The proportion authored by emergency medicine and cardiologists has decreased over time while those by anesthesiology and critical care has generally increased, particularly over the last decade. First authorship demonstrated a similar trend. Articles were published at similar numbers in emergency medicine journals (23.0%) and cardiology journals (19.9%). Conclusion: The annual number of c-POCUS publications has steadily increased over time reflecting the increased recognition and utilization of c-POCUS. This study can help inform clinicians of the current state of c-POCUS and augment the discussion surrounding barriers to continued adoption across all specialties.

In group-living species, particularly cooperative breeders, all group members contribute to various behaviours but there is considerable variation between and within individuals in their contributions. While it is well established that there is variation due to differences in the costs and benefits for individuals of different sex, age and dominance status, shorter-term social, internal and environmental factors are also likely to be important. Sentinel behaviour, where individuals adopt a raised position to scan for danger while groupmates forage, offers an opportunity to test hypotheses about context-dependent differences in contributions to group behaviour. Here we used field experiments to manipulate the conspecific audience, satiation state and perceived danger level of dwarf mongooses, Helogale parvula, to investigate how sentinel contributions are modulated by individual context. In addition to standard measures of sentinel behaviour (likelihood of becoming a sentinel, number of bouts, bout duration), we considered within-bout behaviour in terms of surveillance calls and attentiveness (head-scanning rate and distraction levels). We found that the presence of a neighbouring forager (audience) decreased sentinel contributions, while individuals increased their sentinel investment when satiated and experiencing an increased danger level. Changes in head-scanning rate provided evidence for an interaction between the effect of satiation and danger levels, demonstrating that sentinel attentiveness was influenced by changes in context. Our results demonstrate that sentinel behaviour is strongly context dependent, with effects seen in initial bout and bout quantity decisions, as well as within-bout characteristics, and that individual contributions to group behaviours can vary depending on social, internal and environmental factors.

Out-group conflict is rife in the natural world, occurring from primates to ants. Traditionally, research on this aspect of sociality has focused on the interactions between groups and their conspecific rivals, investigating contest function and characteristics, which group members participate and what determines who wins. In recent years, however, there has been increasing interest in the consequences of out-group conflict. In this review, we first set the scene by outlining the fitness consequences that can arise immediately to contest participants, as well as a broader range of delayed, cumulative and third-party effects of out-group conflict on survival and reproductive success. For the majority of the review, we then focus on variation in these fitness consequences of out-group conflict, describing known examples both between species and between populations, groups and individuals of the same species. Throughout, we suggest possible reasons for the variation, provide examples from a diverse array of taxa, and suggest what is needed to advance this burgeoning area of social evolution. This article is part of the theme issue ‘Intergroup conflict across taxa’.

Most stimulants used to treat attention-deficit/hyperactivity disorder are administered in the morning and absorbed in the upper gastrointestinal tract. DR/ER-MPH (formerly HLD200), an evening-dosed delayed-release and extended-release methylphenidate, is predicted to be absorbed in the proximal colon. The pharmacokinetic (PK) profile of DR/ER-MPH is characterized by an 8- to 10-hour delay in initial methylphenidate absorption and a subsequent gradual increase in plasma concentration, followed by a slow decline. To examine the relationship of absorption site to pharmacokinetics, the DR/ER-MPH formulation was altered to release methylphenidate in the small intestine and distal colon. The 3 formulations were administered in an open-label, 3-way, crossover study in healthy adults (N = 18). Compared with the small intestine formulation, the PK profile of the proximal colon (DR/ER-MPH) formulation exhibited a longer delay before initial methylphenidate absorption, decreased peak methylphenidate concentration, increased time to peak concentration, and decreased bioavailability; these characteristics were amplified in the distal colon formulation. Safety profiles fell within the expectations for methylphenidate products. Modeled PK profiles were similar between the small intestine formulation and a morning-dosed extended-release methylphenidate (both predicted to release methylphenidate in the upper gastrointestinal tract), providing additional evidence that the PK profile of DR/ER-MPH is shaped by colonic absorption.

Conflict between rival groups is rife in nature. While recent work has begun exploring the behavioural consequences of this intergroup conflict, studies have primarily considered just the 1–2 h immediately after single interactions with rivals or their cues. Using a habituated population of wild dwarf mongooses (Helogale parvula), we conducted week-long manipulations to investigate longer-term impacts of intergroup conflict. Compared to a single presentation of control herbivore faeces, one rival-group faecal presentation (simulating a territorial intrusion) resulted in more within-group grooming the following day, beyond the likely period of conflict-induced stress. Repeated presentations of outsider cues led to further changes in baseline behaviour by the end of the week: compared to control weeks, mongooses spent less time foraging and foraged closer to their groupmates, even when there had been no recent simulated intrusion. Moreover, there was more baseline territorial scent-marking and a higher likelihood of group fissioning in intrusion weeks. Consequently, individuals gained less body mass at the end of weeks with repeated simulated intrusions. Our experimental findings provide evidence for longer-term, extended and cumulative, effects of an elevated intergroup threat, which may lead to fitness consequences and underpin this powerful selective pressure.

This qualitative study aimed to explore the experiences of low-income pet guardians in accessing veterinary care during COVID-19. Participants were recruited through a purposive sampling method: 12 individuals who applied to and met the low-income threshold to access support for veterinary fees from the Vancouver Humane Society (VHS) were invited for semi-structured in-depth telephone interviews. Participants indicated that they experienced pandemic-related barriers related to and compounded by their low-income status. Their experiences fit into three categories: the barriers to accessing veterinary care pre-and peri-COVID-19, the emotional impact of compounding barriers related to accessing veterinary care during COVID-19, and the human-animal bond and resilience in the context of COVID-19. Drawing on the One Health, One Welfare approach, we argue that veterinary and animal services should evaluate and improve their support services, particularly programs developed for low-income pet guardians. Based on the participants' recommendations, we propose that veterinary and animal services prepare for future disaster situations by increasing their financial capacity to support people needing assistance, undergoing training to better work with people experiencing financial and emotional stress, and providing easily accessible resources to better distribute knowledge about animal needs and available financial assistance programming. The suggestions are intended to benefit animals, their guardians, and both veterinary and animal service sector workers.

Anthropogenic noise is an increasingly widespread pollutant, with a rapidly burgeoning literature demonstrating impacts on humans and other animals. However, most studies have simply considered if there is an effect of noise, examining the overall cohort response. Although substantial evidence exists for intraspecific variation in responses to other anthropogenic disturbances, this possibility has received relatively little experimental attention with respect to noise. Here, we used field-based playbacks with dwarf mongooses (Helogale parvula) to test how traffic noise affects vigilance behavior and to examine potential variation between individuals of different age class, sex, and dominance status. Foragers exhibited a stronger immediate reaction and increased their subsequent vigilance (both that on the ground and as a sentinel) in response to traffic-noise playback compared with ambient-sound playback. Traffic-noise playback also resulted in sentinels conducting longer bouts and being more likely to change post height or location than in ambient-sound playback. Moreover, there was evidence of variation in noise responses with respect to age class and dominance status but not sex. In traffic noise, foraging pups were more likely to flee and were slower to resume foraging than adults; they also tended to increase their vigilance more than adults. Dominants were more likely than subordinates to move post during sentinel bouts conducted in traffic-noise trials. Our findings suggest that the vigilance–foraging trade-off is affected by traffic noise but that individuals differ in how they respond. Future work should, therefore, consider intrapopulation response variation to understand fully the population-wide effects of this global pollutant.

Recently there has been a significant progression in the understanding of molecular mutations driving biochemical and cellular signaling changes leading to survival and proliferation of leukemia cells in patients with acute myeloid leukemia (AML). Preclinical studies have demonstrated a mutated enzyme in the citric acid cycle, isocitrate dehydrogenase (IDH), leads to the production of an oncogenic metabolite R-2-hydroxy-glutarate (R-2-HG). This causes the arrest in the differentiation of hematopoietic stem cells leading to the promotion of leukemia. Inhibitors of the IDH enzyme have been shown in preclinical studies to reduce the production of R-2-HG, resulting in terminal differentiation of leukemia blast cells. In recent phase I and II trials, the IDH2 inhibitor enasidenib has shown clinical activity in patients with relapsed and refractory (R/R) AML. This review will describe the preclinical and clinical developments of enasidenib and its Food and Drug Administration approval in R/R AML, treatment recommendations and management will be outlined.

50 Background: Educating staff on new anticancer medications is imperative for patient safety. Infusion nurses at Dana Farber Cancer Institute (DFCI) satellite infusion centers were surveyed on their comfort level administering newer oncology drugs. Results revealed only 57% of nurses were “extremely comfortable or somewhat comfortable,” while 32% of nurses were “somewhat uncomfortable or very uncomfortable.” This project aimed to increase percentage of nurses at the satellites indicating they are “extremely comfortable” or “somewhat comfortable” from baseline of 57% to ≥75%. Methods: An interdisciplinary team including pharmacy, medical oncology, and nursing was formed to analyze workflows around new drug onboarding, staff education, and satellite communication. The team utilized Plan-Do-Study-Act (PDSA) cycle methodology. Tools included process maps and fishbone to identify areas of improvement. Intervention development tools included a Pareto chart and a priority matrix. Results were analyzed using statistical process control charts. Results: PDSA cycle 1 consisted of making the pharmacy driven education sheet, At-A-Glance (AAG), more accessible for new drugs. AAGs for drugs approved by the FDA in the previous 18 months were posted on the DFCI pharmacy intranet page. Nurses were educated on how to access AAG weekly. For PDSA cycle 2, the survey was modified to target individual nurses administering new drugs rather than all nurses. A “Nursing consideration” section was added to the AAG template and workflow developed; Navigation and review of AAG was added to nursing competency. Monthly nursing/pharmacy huddles were established to optimize communication. These interventions increased the percentage of nurses indicating they are “extremely comfortable” or “somewhat comfortable” to ≥75% which was sustainable through PDSA cycle 2 (see Table). Conclusions: Making an easy-to-use nursing education resource accessible improved nursing comfort level. There were challenges with nursing survey due to COVID-19 surge and staff shortages. Routine huddles are essential for sustainability.[Table: see text]

Over 1 million dogs are imported into the United States and roughly 340,000 dogs into the United Kingdom yearly. Although the official number of dogs arriving to Canada is currently unknown, local animal professionals estimate that thousands of dogs are imported into Canada each year. Dog importation may be increasing globally while regulation and surveillance are still limited, resulting in concerns for the health and welfare of imported dogs. To date, few studies have investigated how the source location of dogs influences the owner-dog relationship. The current report presents two independent studies that were conducted to assess whether owners of imported dogs reported a poorer owner-dog relationships compared to owners of Canadian-born dogs. In both studies, an online survey was distributed to dog owners (Study 1: n = 803; Study 2: n = 878) in British Columbia, Canada, containing questions on various aspects of the owner-dog relationship. The first study included questions from the Lexington Attachment to Pets Scale, Canine Behavioral Assessment and Research Questionnaire, Human-Animal Bond questionnaire, Monash Dog Owner Relationship Scale, and constructed questions about training methods, expectations, and health. The second study was comprised of original questions assessing difficult behaviour, training practices, health, attachment, and perceived level of burden of owning a dog. Both studies found no evidence of a poorer owner-dog relationship in non-Canadian-sourced dogs. In fact, owners of Canadian-sourced dogs used harsh training methods more frequently and had higher expectations for their dog. While no signs of poorer owner-dog relationship in non-Canadian-sourced dogs were found, future research should continue the investigation of age, health, and backgrounds of incoming dogs.

The research aims to explore COVID-19 health and safety protocol impacts on companion animal guardians living with (dis)abilities relating to veterinary medical and behavioral service access. The COVID-19 global public health crisis has impacted almost all international communities, however, vulnerable and marginalized groups have been disproportionately affected. Within the human–companion animal domain, COVID-19-driven societal impacts (e.g., social, health, and economic) not only boomed with new companion animal guardians, but also negatively influenced guardians’ access to veterinary services. Although studies have examined guardian-related COVID-19-specific challenges, there is a paucity of concentration on vulnerable populations, such as persons with disabilities (PWDs). Responding to this research deficit, this study recruited twelve companion animal guardians to participate in semi-structured in-depth interviews, and eight (67%) of the twelve participants self-identified as PWDs. From a PWD perspective, this research reveals three pandemic-triggered primary barriers, preventing PWDs from pursuing veterinary services: (1) service affordability, (2) assistance program feasibility, and (3) veterinary service accessibility. This article argues that PWD-driven approaches could improve existing assistance and support programs to address PWDs’ unique requirements, promoting a healthy human–animal bond.

Variant acute promyelocytic leukemia (vAPL) is a rare leukemia characterized by rearrangement between RARα and a non-PML partner gene. This type of leukemia can be difficult to recognize by histomorphologic evaluation, particularly in patients with few or no Auer rods, and by flow cytometry, but it can be identified by distinct cytogenetic features. Herein, we report on a patient with vAPL with t(11;17)(q23;q21) who presented an initial diagnostic challenge. Detailed flow cytometry findings are presented for this rare entity. Our case study also presents novel treatment (chemotherapy in combination with venetoclax) chosen based on mechanistic data from preclinical studies.

Background: Focused cardiac ultrasound (FCU) is widely used by healthcare providers to answer specific questions about cardiac structure and function at the bedside. Currently, no widely accepted FCU image acquisition checklist exists to assess learners with varying skill levels from different specialties. Objective: The primary objective of this project was to develop a consensus-based FCU image acquisition checklist using a multispecialty group of point-of-care ultrasound (POCUS) experts. Methods: The essential components of an FCU examination were identified on the basis of published recommendations from echocardiography and international ultrasound societies. A checklist of the essential components of an FCU examination was drafted. A panel of POCUS experts from different medical specialties in the United States and Canada was convened to vote on each checklist item by answering two questions: 1) Is this item important to include in a checklist of essential FCU skills applicable to any medical specialty? and 2) Should the learner be required to successfully complete this item to be considered competent? A modified Delphi approach was used to assess the level of agreement for each checklist item during four rounds of voting. Checklist items that achieved an agreement of 80% or greater were included in the final checklist. Results: Thirty-one POCUS experts from seven different medical specialties voted on sixty-five items to be included in the FCU image acquisition assessment tool. The majority of POCUS experts (61%) completed all four rounds of voting. During the first round of voting, 59 items reached consensus, and after revision and revoting, an additional 3 items achieved 80% or greater consensus. A total of 62 items were included in the final checklist, and 57 items reached consensus as a requirement for demonstration of competency. Conclusion: We have developed a multispecialty, consensus-based FCU image acquisition checklist that may be used to assess the skills of learners from different specialties. Future steps include studies to develop additional validity evidence for the use of the FCU assessment tool and to evaluate its utility for the translation of skills into clinical practice.

e19016 Background: The standard remission induction regimen for medically fit patients with AML consists of a backbone of cytarabine & an anthracycline (“7+3” therapy). However, the choice & dose of the anthracycline varies between institutions & practitioner preference, particularly in patients with favorable risk cytogenetics. Gemtuzumab ozogamicin (GO) may improve outcomes in this patient population but is associated with increased toxicities. Methods: We performed a retrospective analysis on medically fit patients ≥ 18 yo with favorable risk AML from 2015-2020 treated with 7+3 at the University of Virginia. Patients were stratified based on standard dose (45 or 60 mg/m2 daunorubicin) (SD) vs higher dose (90 mg/m2 daunorubicin or 12 mg/m2 idarubicin) (HD) of anthracycline vs the addition of GO. Measures included rates of remission, EFS, RFS, and OS as well as rates of treatment-related complications. Results: In total, 58 patients were identified, of which 33 received induction with SD, 19 received HD, & 6 received GO. The majority (75%) of patients were < 60 years old & 93% had de novo AML. The rates of complete remission in the SD, HD & GO groups were 90.9%, 89.5% & 100%, respectively (p = 0.57). EFS at 2-years was 43.9%, 36.7%, & 66.7%, respectively (p = 0.85). RFS at 2-years was 53.0%, 39.0%, & 100%, respectively (p = 0.18). OS at 2-years was similar between all groups (58.9%, 56.9%, & 66.7%, p = 0.92). The rate & duration of cytopenias after induction were similar among all groups (median duration 29 days), however cytopenias were more common in the GO group following consolidation. The rates of major bleeding, admission to the intensive care unit (ICU), and new onset cardiomyopathy (EF < 50%) were higher in the GO group (major bleeding: 0% in SD, 5.3% in HD, 33.3% in GO; ICU admission: 12.1% in SD, 21.1% in HD, 33.3% in GO; cardiomyopathy: 12.1% in SD, 26.3% in HD, 33.3% in GO). The rate of infection, liver dysfunction, & acute renal injury were similar among all groups. No patients developed veno-occlusive disease. Conclusions: Patients receiving GO had a trend toward improved EFS & RFS, however with a similar OS at the expense of higher rates of cytopenias, major bleeding, ICU admission, & cardiotoxicity. Patients receiving HD had a trend toward worse outcomes than those who received SD. A major limitation of our study is the small sample size & single institution experience, however multi-institutional analysis is ongoing for further investigation.[Table: see text]

e19015 Background: The prognosis of adult patients with acute lymphoblastic leukemia (ALL) has improved with the adoption of pediatric-inspired chemotherapy regimens. PEGylated asparaginase (PEG-Asp) is essential to these regimens. Although PEG-Asp is associated with an increased risk of coagulopathy, venous thromboembolism, and depletion of antithrombin III (AT3), there is limited data evaluating the risk of thrombosis and bleeding and optimal antithrombotic interventions in these patients are unknown. Methods: We performed a single-center retrospective study of patients ≥ 18 years-old who received PEG-Asp for B- or T-ALL at the University of Virginia between 2015 and 2020. The primary outcomes were the incidence of thrombosis and bleeding events. All patients received prophylactic AT3 repletion for activity level

Introduction Early formal instruction in procedural skills may increase the frequency with which residents perform procedures in the clinical setting. This workshop trained internal medicine residents in ultrasound skills and manual skills required to perform procedures common on medicine wards and required for board eligibility. Methods Since 2016, our internal medicine residency program has executed three annual half-day workshops for interns during orientation, before clinical duties began. Prior to the workshop, we directed interns to relevant educational resources in the form of online modules and videos. At the workshop, trainees rotated in small groups through facilitated stations to learn basics of procedural ultrasound and to practice manual tasks performed during paracentesis, thoracentesis, lumbar puncture, and peripheral intravenous catheter placement. We administered questionnaires before and immediately after the workshop and used Wilcoxon signed rank tests to compare self-assessed independence and confidence. Results Two hundred four interns with little prior procedural training participated in the workshop. Most participants (85%) indicated that orientation was the best timing for this training experience when compared to later options. Confidence and independence increased for ultrasound-marked thoracentesis, paracentesis, and peripheral intravenous catheters and for lumbar puncture without ultrasound. Discussion This internal medicine intern orientation workshop on procedures and procedural ultrasound was well received and increased participants’ confidence and sense of independence. This publication contains materials needed to reproduce the training experience.

This study compares the intellectual quality and inclusivity of Aboriginal and Torres Strait Islander content in the NSW 2003 Stage 5 History syllabus and the NSW 2012 Stage 5 History syllabus. The significance of this analysis lies in the impact of the Australian Curriculum (AC) Aboriginal and Torres Strait Islander Cross Curriculum Priority (CCP) introduced into the NSW 2012 Stage 5 History syllabus. The purpose of this priority is to improve student engagement with Aboriginal and Torres Strait Islander histories and cultures (BOSTES, 2012). This study identifies the level of intellectual quality by coding cognitive processes with knowledge dimensions and the level of inclusivity by coding the CCP themes with the continuum of history concepts for each syllabus. Analysis revealed that the level of intellectual quality and the level of inclusivity of both syllabi are in the lower range thus operating at a surface level of knowledge and understanding. We therefore argue that the paucity of intellectual rigour and in-depth understandings about Aboriginal and Torres Strait Islander histories, cultures and peoples will fail to redress the tokenistic and misinformed understandings of Indigenous cultures that permeate the Australian schooling institution, whilst simultaneously failing to meet the intended requirements of the AC.

225 Background: Between June and December 2019, hematology-oncology patients admitted for elective chemotherapy at Memorial Regional Hospital had a median delay of 10 hours to initiate chemotherapy infusion from time of admission. This contributes to increased cost to the healthcare system and patient dissatisfaction. By September 2020, elective inpatient median time from admission to chemotherapy initiation at Memorial Regional Hospital will be reduced by 20%. Methods: Multidisciplinary team formed to evaluate the time from admission to initiation of chemotherapy for patients who are electively admitted for chemotherapy in 8 Central based on time stamps available in the electronic health records. Patients electively admitted by a non MCI oncologist were excluded. Data collections included time stamp between each process from admission to administration of 1st chemotherapy. Longest time lapse between each process was counted as an occurrence/contributor to delay. Top 80% contributors identified from Pareto chart allowed team to identify countermeasures. Priority Matrix of implementation in PDSA cycle based on highest impact and ease of implementation. Statistical process control chart was developed. Results: (see table). Conclusions: PDSA Cycle 1, obtaining labs 24-48 hours prior to admission, resulted in a 10% reduction in chemotherapy initiation time. PDSA Cycle 2, enhancing “ok to treat” communication, resulted in a further reduction of time to treatment. The combination of PDSA Cycle 1 & 2 resulted in a 40% reduction in time to chemotherapy initiation, exceeding the planned aim of 20%. Balance measures reflected no reduction in the mean number of overnight stays between baseline and PDSA Cycle 2 (4 nights) that could contribute to a decreased cost. Results and recommendations to adopt at all inpatient oncology departments within the healthcare system will be presented to leadership for support. Data automation through collaborative efforts with information technology is in process to assist with continuous monitoring. Future state, the quality improvement tools gained from ASCO QTP will be utilized to evaluate and improve workflow issues in the outpatient oncology setting. Nationally recognized organizations are encouraged to propose a benchmark for admission time to first chemotherapy administration based on the evaluation of current available data. Additional studies are needed to evaluate chemotherapy treatment delays in other settings.[Table: see text]

Despite growing evidence that males often associate in all-male groups, there has been no review of male savannah elephant Loxodonta africana social relationships or of the use of vocal communication within these male groups. We assess the evidence for all-male group formation and for the use of vocal communication by males throughout the savannah elephant range of southern and eastern Africa, as well as in ex-situ studies of captive animals. We derived data from two quantitative reviews of the published literature, for associations and for vocalisations, respectively. We supplemented these structured reviews with searches for books and of bibliographies. We compiled evidence from 30 studies on associative groups, and found that group size was the most commonly reported variable (mean group size reported 2–4.9; range reported 2–40 when excluding studies that included lone males). We found 22 studies reporting evidence of vocal communication in males. A total of four studies were retrieved from both searches, indicating that these areas of research may overlap. We found that male elephants are frequently reported to be in groups, throughout their range and over time, although the groups are small: median group size was three. The diversity of male savannah elephant group sizes may indicate the behavioural flexibility of the species. It could also represent a lack of studies focusing on males. We found a paucity of research on male vocal communication (5% of studies were concentrated solely on male bioacoustics), particularly in natural settings, and few studies reported the social context or role of male vocal signals outside of musth. We see great scope for future research at the important intersection between male elephant associations and vocal communication, including research on the role of vocalisations in mediating all-male associations.

The risk of venous thromboembolism (VTE) is increased in individuals with cancer, particularly in those with multiple myeloma. The immunomodulatory agents (IMiDs) thalidomide, lenalidomide and pomalidomide are commonly used to treat multiple myeloma and other hematologic malignancies and are associated with increased risk of VTE. Current National Comprehensive Cancer Network (NCCN) guidelines (v.1.2016) on cancer-associated VTE utilize a risk assessment model based on a few small studies to guide VTE prophylaxis for multiple myeloma patients being treated with an IMiD (Palumbo, et al. Leukemia, 2008). Aspirin is recommended for lower risk patients while prophylactic-dose low molecular weight heparin or therapeutic warfarin are recommended for higher risk patients. The use of direct oral anticoagulants (DOACs) for cancer-associated VTE is currently under investigation (Raskob, et al. Lancet Haematol, 2016). Little is known about their role in VTE prophylaxis in patients on IMiDs. The purpose of this study was to explore the use of DOACs in patients receiving IMiDs. We performed a retrospective chart review of all patients at the University of Virginia Health System who received an IMiD and who were taking either a DOAC or warfarin between January 1, 2010 and December 31, 2015. DOACs included dabigatran, rivaroxaban, and apixaban. IMiDs included lenalidomide, thalidomide, and pomalidomide. The primary endpoint was to assess the safety of DOACs as compared to warfarin, and the secondary endpoint was to assess their efficacy. We collected baseline patient information, as well as diagnosis, IMiD, anticoagulant, antiplatelet agent and dose, duration of treatment, concurrent antineoplastic therapies, and thrombotic risk factors. We utilized the NCCN definitions of individual and myeloma-related thrombotic risk factors. Many patients had changes in their IMiD or anticoagulation. Thus, separate encounters were collected, where an encounter was the combination of an IMiD agent and dose, the anticoagulant, the antiplatelet agent (if any), and the thrombotic risk profile for that time period. Descriptive analyses were performed on all encounters in both groups. Rates of bleeding and thrombotic events were calculated. There were 21 discrete patients in the DOAC group and 16 in the warfarin group. Characteristics and outcomes are described in Table 1. There were four non-major bleeding events in the DOAC group; two of the four bleeding events occurred while on concomitant aspirin therapy. The patient with hematuria stopped anticoagulation and cystoscopy revealed bladder cancer. The other patients did not change or stop therapy. There were six bleeding events in the warfarin group: two were major and four were non-major. The two major events were gastrointestinal bleeding (GIB) and a subarachnoid hemorrhage (SAH). Neither event occurred while on concomitant antiplatelet therapy. The GIB required cessation of therapy, hospitalization, and transfusions. The INR at the time is unknown. The SAH was preceded by a fall while INR was in therapeutic range. Both major and two of the non-major bleeding events occurred in the same patient at different time points and accounted for most of the warfarin-related bleeding events. There was one thrombotic event in the DOAC group. The patient had a non-ST segment elevation myocardial infarction (NSTEMI) while on prophylactic-dose rivaroxaban. She was not on concomitant antiplatelet therapy. Arterial thrombotic events are not typically seen with IMiDs, and the NSTEMI was thought to be related to the recent initiation of carfilzomib. There were no thrombotic events in the warfarin group. This was a retrospective, single-institution study assessing the safety and efficacy of DOACs as compared to warfarin in patients on IMiDs. In our study, all bleeding events in the DOAC group were non-major, while patients on warfarin experienced both major and non-major bleeds. Only one thrombotic event was recorded in the DOAC group. DOACs may represent an attractive alternative to warfarin for VTE prophylaxis in these patients, given no need for routine monitoring and fewer dietary restrictions. Prospective studies in this population are warranted. Disclosures No relevant conflicts of interest to declare.

Most drugs used in standard regimens for acute lymphoblastic leukemia (ALL) were developed more than 30 years ago. Since that time, several new drugs have been developed and incorporated into ALL treatment. In spite of this, novel therapeutic approaches are still needed to improve outcomes for high-risk or relapsed ALL. This manuscript discusses newer treatment strategies, including purine nucleoside analogs, monoclonal antibodies, antibody drug conjugates, mammalian target of rapamycin (mTOR) inhibitors, proteasome inhibitors, histone deacetylase (HDAC) inhibitors, hypomethylating agents, spleen tyrosine kinase inhibitors, Bruton's tyrosine kinase (BTK) inhibitors, Janus kinase-signal transducer and activator of transcription (JAK-STAT) inhibitors, anti-programmed cell death protein (anti-PD-1) antibodies, mitogen-activated protein kinase (MEK) inhibitors, CXCR4 antagonists, poly (ADP-ribose) polymerase (PARP) inhibitors, and FMS-like tyrosine kinase 3 (FLT3) inhibitors. Additionally, this manuscript discusses the impact of diagnostic approaches on management of ALL. Specifically, minimal residual disease is increasingly felt to be important and will likely dramatically impact the care of ALL patients in the near future.

Familial intrahepatic cholestasis 1 (FIC1) deficiency is caused by a mutation in the ATP8B1 gene. Partial external biliary diversion (PEBD) is pursued to improve pruritus and arrest disease progression. Our aim is to describe clinical variability after PEBD in FIC1 disease.We performed a single-center, retrospective review of genetically confirmed FIC1 deficient patients who received PEBD. Clinical outcomes after PEBD were cholestasis, pruritus, fat-soluble vitamin supplementation, growth, and markers of disease progression that included splenomegaly and aspartate aminotransferase-to-platelet ratio index.Eight patients with FIC1 disease and PEBD were included. Mean follow-up was 32 months (range 15-65 months). After PEBD, total bilirubin was2 mg/dL in all patients at 8 months after surgery, but 7 of 8 subsequently experienced a total of 15 recurrent cholestatic events. Subjective assessments of pruritus demonstrated improvement, but itching exacerbation occurred during cholestatic episodes. High-dose fat-soluble vitamin supplementation persisted, with increases needed during cholestatic episodes. Weight z scores improved (-3.4 to -1.65, P 0.01). Splenomegaly did not worsen or develop and 1 patient developed an aminotransferase-to-platelet ratio index score of0.7 suggesting development of fibrosis 24 months after PEBD.Clinical variability is evident among genetically defined FIC1 deficient patients after PEBD, even among those with identical mutations. Recurrent, self-limited episodes of cholestasis and pruritus are reminiscent of the benign recurrent intrahepatic cholestasis phenotype. Despite diversion of bile from the intestinal lumen, weight gain improved while fat-soluble vitamin requirements persisted. Significant progression of liver disease was not evident during follow-up.

Many hands can build a house; it takes trust to make that house a home. Trust has two main components: credibility (worthiness based on preparation and past performance) and empathy (the ability to understand and share another person's values). CHEST has maintained its credibility and empathy as the global leader in clinical pulmonary, critical care, and sleep medical education. It follows that the leader in chest clinical education would also be the home of the clinician-educator. You are that educator.

We describe a case of acute liver failure and myopericarditis due to herpes simplex virus–1 (HSV-1) in an immunocompetent adult. We estimate that, at the height of viremia, the patient contained a quantity of HSV-1 virions approaching that of human cells. The patient recovered with acyclovir that was dose-adjusted for neurotoxicity and developed a vigorous anti-HSV-1 T-cell response.

In social species, conspecific outsiders present various threats to groups and their members. These out-group threats are predicted to affect subsequent within-group interactions (e.g., affiliation and aggression) and individual behavior (e.g., foraging and vigilance decisions). However, experimental investigations of such consequences are rare, especially in natural conditions. We used field-based call playbacks and fecal presentations on habituated wild dwarf mongooses (Helogale parvula)—a cooperatively breeding, territorial species—to examine postinteraction responses to the simulated threat of a rival group. Dwarf mongooses invested more in grooming of groupmates, foraged closer together, and more regularly acted as sentinels (a raised guard) after encountering indicators of rival-group presence compared to control conditions. These behavioral changes likely arise from greater anxiety and, in the case of increased vigilance, the need to seek additional information about the threat. The influence of an out-group threat lasted at least 1 h but individuals of different dominance status and sex responded similarly, potentially because all group members suffer costs if a contest with rivals is lost. Our results provide field-based experimental evidence from wild animals that out-group threats can influence within-group behavior and decision making, and suggest the need for greater consideration of the lasting impacts of social conflict., Threats from rival groups can lead to changes in within-group behavior. Using call playbacks and fecal presentations to simulate the presence of rivals, we show that wild dwarf mongooses groom groupmates for longer, forage closer together, and more regularly act as sentinels (raised guards) after encountering indicators of an out-group threat. These behavioral changes likely arise from greater anxiety and, in the case of sentinel behavior, the need to seek additional information about the threat.

There are no national standards for time between patient arrival and the initiation of scheduled chemotherapy (time to chemotherapy [TTC]). Delays in this process have a negative impact on patient care and the use of health care resources. At the University of Virginia Cancer Center, mean TTC in 2015 was 12.1 hours and mean length of stay (LOS) was 5.45 days at baseline. We formed a multidisciplinary team that participated in ASCO’s Quality Training Program. We aimed to improve TTC by 10% over 6 months. We used Plan-Do-Study-Act (PDSA) cycles as quality improvement (QI) models and used XmR charts to evaluate the interventions. The first PDSA cycle involved amending the chemotherapy consent process; mean TTC and LOS improved to 9.3 hours and 4.65 days, respectively. The second PDSA cycle involved shifting pharmacist review of chemotherapy orders to before admission rather than after patient arrival. Mean TTC remained at 9.4 hours (net 22% improvement from baseline) and LOS improved to 4.33 days (net 21% improvement). Our team surpassed the 10% improvement goal for TTC. This QI project faced a few limitations. Our baseline data set was a retrospective cohort review. In addition, oncology patients have a wide range of individual clinical needs that may have an impact on TTC. Delays in TTC have an impact on oncologic care at many medical centers. Our project highlights the need for guidance on this issue. We recommend that other institutions form multidisciplinary teams and also use QI tools to assess delays and implement changes.

BACKGROUND & AIMS: In celiac disease (CeD), gluten induces immune activation, leading to enteropathy. TAK-101, gluten protein (gliadin) encapsulated in negatively charged poly(dl-lactide-co-glycolic acid) nanoparticles, is designed to induce gluten-specific tolerance. METHODS: TAK-101 was evaluated in phase 1 dose escalation safety and phase 2a double-blind, randomized, placebo-controlled studies. Primary endpoints included pharmacokinetics, safety, and tolerability of TAK-101 (phase 1) and change from baseline in circulating gliadinspecific interferon-γ–producing cells at day 6 of gluten challenge, in patients with CeD (phase 2a). Secondary endpoints in the phase 2a study included changes from baseline in enteropathy (villus height to crypt depth ratio [Vh:Cd]), and frequency of intestinal intraepithelial lymphocytes and peripheral gut-homing T cells. RESULTS: In phase 2a, 33 randomized patients completed the 14-day gluten challenge. TAK-101 induced an 88% reduction in change from baseline in interferon-γ spot-forming units vs placebo (2.01 vs 17.58, P = .006). Vh:Cd deteriorated in the placebo group (−0.63, P = .002), but not in the TAK-101 group (−0.18, P = .110), although the intergroup change from baseline was not significant (P = .08). Intraepithelial lymphocyte numbers remained equal. TAK-101 reduced changes in circulating α4β7(+)CD4(+) (0.26 vs 1.05, P = .032), αEβ7(+)CD8(+) (0.69 vs 3.64, P = .003), and γδ (0.15 vs 1.59, P = .010) effector memory T cells. TAK-101 (up to 8 mg/kg) induced no clinically meaningful changes in vital signs or routine clinical laboratory evaluations. No serious adverse events occurred. CONCLUSIONS: TAK-101 was well tolerated and prevented gluten-induced immune activation in CeD. The findings from the present clinical trial suggest that antigen-specific tolerance was induced and represent a novel approach translatable to other immune-mediated diseases. ClinicalTrials.gov identifiers: NCT03486990 and NCT03738475.