A case study of pragmatic measure development of the Treatment Integrity for Elementary Settings self-report measure for teachers.

Introduction: Due to usability, feasibility, and acceptability concerns, observational treatment fidelity measures are often challenging to deploy in schools. Teacher self-report fidelity measures with specific design features might address some of these barriers. This case study outlines a community-engaged, iterative process to adapt the observational Treatment Integrity for Elementary Settings (TIES-O) to a teacher self-report version designed to assess the use of practices to support children's social-emotional competencies in elementary classrooms. Method: Cognitive walkthrough interviews were conducted with teachers to improve the usability of the teacher self-report measure, called the Treatment Integrity for Elementary Schools-Teacher Report (TIES-T). Qualitative content analysis was used to extract themes from the interviews and inform changes to the measure. Results: Increasing clarity and interactive elements in the measure training were the dominant themes, but suggestions for the measure format and jargon were also suggested. Conclusion: The suggested changes resulted in a brief measure, training, and feedback system designed to support the teacher's use of practices to support children's social-emotional competencies in elementary classrooms. Future research with the TIES-T will examine the score reliability and validity of the measure.

Collecting observational data in schools is challenging, so developing teacher self-report measures and involving teachers in the design process is important to help make them easier to use. This paper reports on the development of a teacher self-report measure designed to collect information about the instructional practices teachers deliver to promote positive student behavior.

KRT17High/CXCL8+ tumor cells display both classical and basal features and regulate myeloid infiltration in the pancreatic cancer microenvironment.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is generally divided in two subtypes, classical and basal. Recently, single cell RNA sequencing has uncovered the co-existence of basal and classical cancer cells, as well as intermediary cancer cells, in individual tumors. The latter remains poorly understood; here, we sought to characterize them using a multimodal approach. EXPERIMENTAL DESIGN: We performed subtyping on a single cell RNA sequencing dataset containing 18 human PDAC samples to identify multiple intermediary subtypes. We generated patient-derived PDAC organoids for functional studies. We compared single cell profiling of matched blood and tumor samples to measure changes in the local and systemic immune microenvironment. We then leveraged longitudinally patient-matched blood to follow individual patients over the course of chemotherapy. RESULTS: We identified a cluster of KRT17-high intermediary cancer cells that uniquely express high levels of CXCL8 and other cytokines. The proportion of KRT17High/CXCL8+ cells in patient tumors correlated with intra-tumoral myeloid abundance, and, interestingly, high pro-tumor peripheral blood granulocytes, implicating local and systemic roles. Patient-derived organoids maintained KRT17High/CXCL8+cells and induced myeloid cell migration in an CXCL8-dependent manner. In our longitudinal studies, plasma CXCL8 decreased following chemotherapy in responsive patients, while CXCL8 persistence portended worse prognosis. CONCLUSIONS: Through single cell analysis of PDAC samples we identified KRT17High/CXCL8+ cancer cells as an intermediary subtype, marked by a unique cytokine profile and capable of influencing myeloid cells in the tumor microenvironment and systemically. The abundance of this cell population should be considered for patient stratification in precision immunotherapy.

Analysis of Donor Pancreata Defines the Transcriptomic Signature and Microenvironment of Early Neoplastic Lesions.

The adult healthy human pancreas has been poorly studied given the lack of indication to obtain tissue from the pancreas in the absence of disease and rapid postmortem degradation. We obtained pancreata from brain dead donors, thus avoiding any warm ischemia time. The 30 donors were diverse in age and race and had no known pancreas disease. Histopathologic analysis of the samples revealed pancreatic intraepithelial neoplasia (PanIN) lesions in most individuals irrespective of age. Using a combination of multiplex IHC, single-cell RNA sequencing, and spatial transcriptomics, we provide the first-ever characterization of the unique microenvironment of the adult human pancreas and of sporadic PanIN lesions. We compared healthy pancreata to pancreatic cancer and peritumoral tissue and observed distinct transcriptomic signatures in fibroblasts and, to a lesser extent, macrophages. PanIN epithelial cells from healthy pancreata were remarkably transcriptionally similar to cancer cells, suggesting that neoplastic pathways are initiated early in tumorigenesis. SIGNIFICANCE: Precursor lesions to pancreatic cancer are poorly characterized. We analyzed donor pancreata and discovered that precursor lesions are detected at a much higher rate than the incidence of pancreatic cancer, setting the stage for efforts to elucidate the microenvironmental and cell-intrinsic factors that restrain or, conversely, promote malignant progression. See related commentary by Hoffman and Dougan, p. 1288. This article is highlighted in the In This Issue feature, p. 1275.

Analysis of donor pancreata defines the transcriptomic signature and microenvironment of early pre-neoplastic pancreatic lesions.

The adult healthy human pancreas has been poorly studied given lack of indication to obtain tissue from the pancreas in the absence of disease and rapid postmortem degradation. We obtained pancreata from brain dead donors thus avoiding any warm ischemia time. The 30 donors were diverse in age and race and had no known pancreas disease. Histopathological analysis of the samples revealed PanIN lesions in most individuals irrespective of age. Using a combination of multiplex immunohistochemistry, single cell RNA sequencing, and spatial transcriptomics, we provide the first ever characterization of the unique microenvironment of the adult human pancreas and of sporadic PanIN lesions. We compared healthy pancreata to pancreatic cancer and peritumoral tissue and observed distinct transcriptomic signatures in fibroblasts, and, to a lesser extent, macrophages. PanIN epithelial cells from healthy pancreata were remarkably transcriptionally similar to cancer cells, suggesting that neoplastic pathways are initiated early in tumorigenesis. Statement of significance: The causes underlying the onset of pancreatic cancer remain largely unknown, hampering early detection and prevention strategies. Here, we show that PanIN are abundant in healthy individuals and present at a much higher rate than the incidence of pancreatic cancer, setting the stage for efforts to elucidate the microenvironmental and cell intrinsic factors that restrain, or, conversely, promote, malignant progression.

Twenty-Four-Hour Pulsatile Hemodynamics Predict Brachial Blood Pressure Response to Renal Denervation in the SPYRAL HTN-OFF MED Trial.

BACKGROUND: Renal denervation (RDN) lowers blood pressure (BP), but BP response is variable in individual patients. We investigated whether measures of pulsatile hemodynamics, obtained during 24-hour ambulatory BP monitoring, predict BP drop following RDN. METHODS: From the randomized, sham-controlled SPYRAL HTN-OFF MED Pivotal trial, we performed a post hoc analysis of BP waveforms from 111 RDN patients and 111 sham controls, obtained with a brachial cuff-based sphygmomanometer. Waveforms were acquired during ambulatory BP monitoring at diastolic BP level and processed with validated ARCSolver algorithms to derive hemodynamic parameters (augmentation index; augmentation pressure; backward and forward wave amplitude; estimated aortic pulse wave velocity). We investigated the relationship between averaged 24-hour values at baseline and the change in 24-hour BP at 3 months in RDN patients, corrected for observed trends in the sham group. RESULTS: There was a consistent inverse relationship between baseline augmentation index/augmentation pressure/backward wave amplitude/forward wave amplitude/estimated aortic pulse wave velocity and BP response to RDN: the decrease in 24-hour systolic BP/diastolic BP was 7.8/5.9 (augmentation index), 8.0/6.3 (augmentation pressure), 6.7/5.4 (backward wave amplitude), 5.7/4.7 (forward wave amplitude), and 7.8/5.2 (estimated aortic pulse wave velocity) mm Hg greater for patients below versus above the respective median value (P<0.001 for all comparisons, respectively). Taking augmentation index/augmentation pressure/backward wave amplitude/forward wave amplitude/estimated aortic pulse wave velocity into account, a favorable BP response following RDN, defined as a drop in 24-hour systolic blood pressure of ≥5 mm Hg, could be predicted with an area under the curve of 0.70/0.74/0.70/0.65/0.62 (P<0.001 for all, respectively). CONCLUSIONS: These results suggest that pulsatile hemodynamics, obtained during 24-hour ambulatory BP monitoring, may predict BP response to RDN.

Socioeconomic and environmental predictors of estuarine shoreline hard armoring.

Rising sea levels and growing coastal populations are intensifying interactions at the land-sea interface. To stabilize upland and protect human developments from coastal hazards, landowners commonly emplace hard armoring structures, such as bulkheads and revetments, along estuarine shorelines. The ecological and economic consequences of shoreline armoring have garnered significant attention; however, few studies have examined the extent of hard armoring or identified drivers of hard armoring patterns at the individual landowner level across large geographical areas. This study addresses this knowledge gap by using a fine-scale census of hard armoring along the entire Georgia U.S. estuarine coastline. We develop a parsimonious statistical model that accurately predicts the probability of armoring emplacement at the parcel level based on a set of environmental and socioeconomic variables. Several interacting influences contribute to patterns of shoreline armoring; in particular, shoreline slope and the presence of armoring on a neighboring parcel are strong predictors of armoring. The model also suggests that continued sea level rise and coastal population growth could trigger future increases in armoring, emphasizing the importance of considering dynamic patterns of armoring when evaluating the potential effects of sea level rise. For example, evolving distributions of armoring should be considered in predictions of future salt marsh migration. The modeling approach developed in this study is adaptable to assessing patterns of hard armoring in other regions. With improved understanding of hard armoring distributions, sea level rise response plans can be fully informed to design more efficient scenarios for both urban development and coastal ecosystems.

Oncology Nurse Navigation: Results of the 2016 Role Delineation Study.

BACKGROUND: In 2011, an oncology nurse navigator (ONN) role delineation survey (RDS) was conducted by the Oncology Nursing Society (ONS) when the role was relatively new to oncology. Results did not demonstrate a unique skill set for the ONN; however, since then, the role has expanded. OBJECTIVES: ONS and the Oncology Nursing Certification Corporation partnered in 2016 to complete an RDS of ONNs to redefine the role and determine the need for an ONN certification examination. METHODS: A structured RDS was conducted using a formal consensus-building process. A survey was developed and released to examine the specific tasks, knowledge, and skills for the ONN as well as to determine which role possesses more responsibility for the tasks. FINDINGS: The ONN role is evolving, and more was learned about its key tasks, including differences in the responsibilities of the ONN and the clinical or staff nurse. However, the RDS did not find an adequate difference in the knowledge required by the ONN and the clinical or staff nurse to support the need for a separate ONN certification.

Antibiotic dosing during sustained low-efficiency dialysis: special considerations in adult critically ill patients.

OBJECTIVE: To address issues of antibiotic dosing during sustained low-efficiency dialysis by using available pharmacokinetic data, intermittent and continuous renal replacement therapy dialysis guidelines, and our experience with sustained low-efficiency dialysis. DATA RESOURCES: Published clinical trials, case reports, and reviews of antibiotic dosing in humans during sustained low-efficiency dialysis. DATA EXTRACTION: A search of electronic databases (MEDLINE, PubMed, and Ovid) was conducted by using key words of extended daily dialysis, sustained low-efficiency dialysis, antibiotics, antimicrobial agents, and pharmacokinetics. MEDLINE identified 32 sustained low-efficiency dialysis articles, and PubMed identified 33 articles. All papers describing antibiotic clearance prospectively in patients were considered for this article. DATA SYNTHESIS: We identified nine original research articles and case reports that determined the impact of sustained low-efficiency dialysis on antibiotic clearance in patients. The blood and dialysate flow rates, duration of dialysis, type of filter, and the pharmacokinetic parameters were extracted from each article. If multiple articles on the same drug were published, they were compared for consistency with the aforementioned dialysis parameters and then compared with forms of continuous renal replacement therapy. Antibiotic clearance by sustained low-efficiency dialysis was determined to be similar or higher than continuous renal replacement therapy therapies. The estimated creatinine clearance during sustained low-efficiency dialysis was approximately 60 mL/min to 100 mL/min depending on the blood and dialysate flow rates and the type of filter used. CONCLUSIONS: The potential for significant drug removal during an 8-hr-or-longer sustained low-efficiency dialysis session is evident by the limited number of studies available. Because significant amounts of drug may be removed by sustained low-efficiency dialysis combined with altered pharmacokinetic variables in critically ill patients, the risk for suboptimal drug concentrations and pharmacodynamics must be considered. Appropriate dose and calculation of dosing intervals is essential to provide adequate antibiotic therapy in these patients. It is recommended that institutions who utilize sustained low-efficiency dialysis establish dosing guidelines for all pharmacists and physicians to follow to provide consistent delivery of antibiotics at adequate concentrations.