Next generation high-power laser facilities are expected to generate hundreds-of-MeV proton beams and operate at multi-Hz repetition rates, presenting opportunities for medical, industrial and scientific applications requiring bright pulses of energetic ions. Characterizing the spectro-spatial profile of these ions at high repetition rates in the harsh radiation environments created by laser–plasma interactions remains challenging but is paramount for further source development. To address this, we present a compact scintillating fiber imaging spectrometer based on the tomographic reconstruction of proton energy deposition in a layered fiber array. Modeling indicates that spatial resolution of approximately 1 mm and energy resolution of less than 10% at proton energies of more than 20 MeV are readily achievable with existing 100 μm diameter fibers. Measurements with a prototype beam-profile monitor using 500 μm fibers demonstrate active readouts with invulnerability to electromagnetic pulses, and less than 100 Gy sensitivity. The performance of the full instrument concept is explored with Monte Carlo simulations, accurately reconstructing a proton beam with a multiple-component spectro-spatial profile.

An investigation into an outbreak of Salmonella Newport infections in Canada was initiated in July 2020. Cases were identified across several provinces through whole-genome sequencing (WGS). Exposure data were gathered through case interviews. Traceback investigations were conducted using receipts, invoices, import documentation, and menus. A total of 515 cases were identified in seven provinces, related by 0–6 whole-genome multi-locus sequence typing (wgMLST) allele differences. The median age of cases was 40 (range 1–100), 54% were female, 19% were hospitalized, and three deaths were reported. Forty-eight location-specific case sub-clusters were identified in restaurants, grocery stores, and congregate living facilities. Of the 414 cases with exposure information available, 71% (295) had reported eating onions the week prior to becoming ill, and 80% of those cases who reported eating onions, reported red onion specifically. The traceback investigation identified red onions from Grower A in California, USA, as the likely source of the outbreak, and the first of many food recall warnings was issued on 30 July 2020. Salmonella was not detected in any tested food or environmental samples. This paper summarizes the collaborative efforts undertaken to investigate and control the largest Salmonella outbreak in Canada in over 20 years.

Climate change is at the forefront of discussions for many companies. Climate change-related disclosures and reporting are important tools and allow stakeholders to understand climate-related risks a company is facing and help various stakeholders to take informed decisions.

The landscape for climate change-related reporting requirements is ever evolving, with a trend from voluntary to mandatory, with many global disclosure standards and requirements influencing local requirements and other related standards.

This paper explores these ideas further, giving a general background to disclosure requirements, discusses greenwashing, details disclosure organisations including TCFD and the ISSB, and provides details on a country level including green taxonomies.

Since the initial publication of A Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals in 2008, the prevention of healthcare-associated infections (HAIs) has continued to be a national priority. Progress in healthcare epidemiology, infection prevention, antimicrobial stewardship, and implementation science research has led to improvements in our understanding of effective strategies for HAI prevention. Despite these advances, HAIs continue to affect ∼1 of every 31 hospitalized patients,1 leading to substantial morbidity, mortality, and excess healthcare expenditures,1 and persistent gaps remain between what is recommended and what is practiced.

The widespread impact of the coronavirus disease 2019 (COVID-19) pandemic on HAI outcomes2 in acute-care hospitals has further highlighted the essential role of infection prevention programs and the critical importance of prioritizing efforts that can be sustained even in the face of resource requirements from COVID-19 and future infectious diseases crises.3

The Compendium: 2022 Updates document provides acute-care hospitals with up-to-date, practical expert guidance to assist in prioritizing and implementing HAI prevention efforts. It is the product of a highly collaborative effort led by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Disease Society of America (IDSA), the Association for Professionals in Infection Control and Epidemiology (APIC), the American Hospital Association (AHA), and The Joint Commission, with major contributions from representatives of organizations and societies with content expertise, including the Centers for Disease Control and Prevention (CDC), the Pediatric Infectious Disease Society (PIDS), the Society for Critical Care Medicine (SCCM), the Society for Hospital Medicine (SHM), the Surgical Infection Society (SIS), and others.

During engineering design, different representations are used to convey information about a systems' components, functionality, spatial layout, and interdependencies. These varying representations may have an impact on the interpretation of a system and consequently the decision-making process. This paper presents a research study that tries to capture these different interpretations by investigating how designers divide a system into subsystem clusters. These subsystem clusters can be considered partitions of a set-in combinatorial mathematics. Given designers' subsystem clusters for three products across three representation modalities, three different analysis methods for finding the most likely partition from observed data are presented. Analysis shows that the Variation of Information analysis method gives the most coherent and consistent results for the search of a most likely cluster. In addition, differences in clustering behaviour are observed based on representation modality. These results show that the way an engineer or designer chooses to represent a system impacts how that system is interpreted, which has implications for the decision-making process during engineering design.

OBJECTIVES/GOALS: Glioblastomas (GBMs) are heterogeneous, treatment-resistant tumors that are driven by populations of cancer stem cells (CSCs). In this study, we perform an epigenetic-focused functional genomics screen in GBM organoids and identify WDR5 as an essential epigenetic regulator in the SOX2-enriched, therapy resistant cancer stem cell niche. METHODS/STUDY POPULATION: Despite their importance for tumor growth, few molecular mechanisms critical for CSC population maintenance have been exploited for therapeutic development. We developed a spatially resolved loss-of-function screen in GBM patient-derived organoids to identify essential epigenetic regulators in the SOX2-enriched, therapy resistant niche. Our niche-specific screens identified WDR5, an H3K4 histone methyltransferase responsible for activating specific gene expression, as indispensable for GBM CSC growth and survival. RESULTS/ANTICIPATED RESULTS: In GBM CSC models, WDR5 inhibitors blocked WRAD complex assembly and reduced H3K4 trimethylation and expression of genes involved in CSC-relevant oncogenic pathways. H3K4me3 peaks lost with WDR5 inhibitor treatment occurred disproportionally on POU transcription factor motifs, required for stem cell maintenance and including the POU5F1(OCT4)::SOX2 motif. We incorporated a SOX2/OCT4 motif driven GFP reporter system into our CSC cell models and found that WDR5 inhibitor treatment resulted in dose-dependent silencing of stem cell reporter activity. Further, WDR5 inhibitor treatment altered the stem cell state, disrupting CSC in vitro growth and self-renewal as well as in vivo tumor growth. DISCUSSION/SIGNIFICANCE: Our results unveiled the role of WDR5 in maintaining the CSC state in GBM and provide a rationale for therapeutic development of WDR5 inhibitors for GBM and other advanced cancers. This conceptual and experimental framework can be applied to many cancers, and can unmask unique microenvironmental biology and rationally designed combination therapies.

Glufosinate resistance in Palmer amaranth (Amaranthus palmeri S. Watson) was recently detected in three accessions from Arkansas, USA. Amaranthus palmeri is the first and only broadleaf weed species resistant to this herbicide, and the resistance mechanism is still unclear. A previous study characterized the glufosinate resistance level in the accessions from Arkansas. A highly glufosinate-resistant accession was further used to investigate the mechanism conferring glufosinate resistance in A. palmeri. Experiments were designed to sequence the herbicide target enzyme cytosolic and chloroplastic glutamine synthetase isoforms (GS1 and GS2, respectively) and quantify copy number and expression. Absorption, translocation, and metabolism of glufosinate using the 14C-labeled herbicide were also evaluated in the resistant and susceptible accessions. The glufosinate-resistant accession had an increase in copy number and expression of GS2 compared with susceptible plants. All accessions showed only one GS1 copy and no differences in expression. No mutations were identified in GS1 or GS2. Absorption (54% to 60%) and metabolism (13% to 21%) were not different between the glufosinate-resistant and glufosinate-susceptible accessions. Most residues of glufosinate (94% to 98%) were present in the treated leaf. Glufosinate translocation to tissues above the treated leaf and in the roots was not different among accessions. However, glufosinate translocation to tissues below the treated leaf (not including roots) was greater in the resistant A. palmeri (2%) compared with the susceptible (less than 1%) accessions. The findings of this paper strongly indicate that gene amplification and increased expression of the chloroplastic glutamine synthetase enzyme are the mechanisms conferring glufosinate resistance in the A. palmeri accession investigated. Thus far, no additional resistance mechanism was observed, but further investigations are ongoing.

This paper investigates the use of ANNs to model human behaviour in design by comparing the predictive capability of ANNs and engineering students. Function structure models of 15 products are used as input for prediction. The type of information provided varied between topology and vocabulary. Analysis of prediction accuracy showed that ANNs perform comparably to students. However, students are more precise with their predictions. Finally, limitations and future work are discussed, with research questions presented for subsequent research.

Although testing is critical in industries, the general approaches of testing in engineering design are under-represented in academia. This research investigates the current state of testing based on design textbooks. The findings suggest there is no clear definition of testing. Testing appears in different design stages with adjacent concepts such as prototyping, experimentation, verification, and validation. The processes of testing and its role within engineering design are ambiguous. Recommendations to design educators are provided, and the limitations of the study are discussed.

OBJECTIVES/GOALS: Several studies compare perioperative parameters and postoperative morphology of open cranial vault remodeling (CVR) and endoscopic-assisted craniectomy (EAC) in the treatment of sagittal craniosynostosis. However, data on neurodevelopmental outcomes comparing these techniques is lacking. METHODS/STUDY POPULATION: Patients with repaired sagittal synostosis were enrolled from a single tertiary care center between five and fifteen years of age. Patients with any craniofacial syndrome (e.g., 22q11.2 deletion) or other medical conditions that could affect neurodevelopment were excluded. Neurodevelopment was measured using the Differential Ability Scale-II (DAS-II). The General Cognitive Ability (GCA) score was the primary outcome measure, describing overall intellectual ability. Secondary outcome measures were measurements of cephalic index (CI) from pre- and postoperative imaging studies. Family socioeconomic status (SES) was estimated using the Hollingshead index (total score, continuous). RESULTS/ANTICIPATED RESULTS: 26 patients [10 CVR (2 Female:8 Male), 16 EAC (6 F:10 M)] were studied. Mean age at repair was greater with CVR than EAC (15.5 ± 8.5 months vs 3.5 ± 1.3 months, respectively, p < 0.001). Mean age at DAS-II testing was 9.0 ± 2.2 years. Patients GCA scores were within the average range relative to test norms (CVR 95.7 ± 15.4 vs EAC 102.6 ± 17.4). After adjusting for SES and preoperative CI, group differences in GCA were modest and statistically nonsignificant (p = 0.646). GCA scores were associated with SES (p = 0.054) but not preop CI (p = 0.479). Differences between CVR and EAC were not statistically significant for any of the imaging parameters (pre and postop CI, pre to postop change in CI, or age at postop imaging; 0.131 <= p <= 0.867). None of the independent variables were significantly associated with postop CI (0.140 <= p <= 0.689). DISCUSSION/SIGNIFICANCE: Interim analysis of the preliminary data suggests no association between surgical procedure and cognitive and morphological outcomes at school-age in patients with sagittal craniosynostosis who underwent CVR versus EAC. Collection of data continues, with the goal to enroll 50 participants in each group by 2022.