Measurable Residual FLT3 Internal Tandem Duplication Before Allogeneic Transplant for Acute Myeloid Leukemia.

Importance: Persistence of FLT3 internal tandem duplication (ITD) in adults with acute myeloid leukemia (AML) in first complete remission (CR) prior to allogeneic hematopoietic cell transplant (HCT) is associated with increased relapse and death after transplant, but the association between the level of measurable residual disease (MRD) detected and clinical outcome is unknown. Objective: To examine the association between pre-allogeneic HCT MRD level with relapse and death posttransplant in adults with AML in first CR. Design, Setting, and Participants: In this cohort study, DNA sequencing was performed on first CR blood from patients with FLT3-ITD AML transplanted from March 2013 to February 2019. Clinical follow-up was through May 2022. Data were analyzed from October 2022 to December 2023. Exposure: Centralized DNA sequencing for FLT3-ITD in pre-allogeneic HCT first CR blood using a commercially available kit. Main Outcomes and Measures: The primary outcomes were overall survival and cumulative incidence of relapse, with non-relapse-associated mortality as a competing risk post-allogeneic HCT. Kaplan-Meier estimations (log-rank tests), Cox proportional hazards models, and Fine-Gray models were used to estimate the end points. Results: Of 537 included patients with FLT3-ITD AML from the Pre-MEASURE study, 296 (55.1%) were female, and the median (IQR) age was 55.6 (42.9-64.1) years. Using the variant allele fraction (VAF) threshold of 0.01% or greater for MRD positivity, the results closely aligned with those previously reported. With no VAF threshold applied (VAF greater than 0%), 263 FLT3-ITD variants (median [range] VAF, 0.005% [0.0002%-44%]), and 177 patients (33.0%) with positive findings were identified. Multivariable analyses showed that residual FLT3-ITD was the variable most associated with relapse and overall survival, with a dose-dependent correlation. Patients receiving reduced-intensity conditioning without melphalan or nonmyeloablative conditioning had increased risk of relapse and death at any given level of MRD compared with those receiving reduced-intensity conditioning with melphalan or myeloablative conditioning. Conclusions and Relevance: This study provides generalizable and clinically applicable evidence that the detection of residual FLT3-ITD in the blood of adults in first CR from AML prior to allogeneic HCT is associated with an increased risk of relapse and death, particularly for those with a VAF of 0.01% or greater. While transplant conditioning intensification, an intervention not available to all, may help mitigate some of this risk, alternative approaches will be necessary for this high-risk population of patients who are underserved by the current standard of care.

Analysing dynamic work systems using DynEAST: a demonstration of concept.

The capability of current Ergonomics methods to capture dynamism is limited, stifling our understanding of work-as-done, distributed situational awareness and organisational drift. This paper provides a demonstration of concept of DynEAST; an extension of the EAST framework underpinned by principles from Dynamic Network Analysis, to capture elements of dynamism within work systems. The DynEAST concept is applied to a railway maintenance case study. Case study findings demonstrate how DynEAST outputs can be used to advance our understanding of the aforementioned phenomena and better equip practitioners for current and future Ergonomics challenges.Practitioner summary: This paper introduces the DynEAST method. DynEAST enables HF/E practitioners to model and analyse dynamic features of complex work systems. The development of DynEAST is timely due to the concurrent proliferation of increasingly complex sociotechnical systems and stagnation of HF/E methods development; particularly those able to model systemic dynamism. Abbreviations: DynEAST: dynamic event analysis of systemic teamwork; EAST: dynamic event analysis of systemic teamwork; HF/E: human factors and ergonomics; HF: human factors; DNA: dynamic network analysis; HTA: hierarchal task analysis; CWA: cognitive work analysis; CAST: causal analysis based on system theory; STAMP: system theoretic accident model and processes; FRAM: functional resonance analysis method; SNA: social network analysis; DSA: distributed situational awareness; PPO: possession protection officer; PO: protection officer; RTS: railway track signals; LPA: local possession authority; SMEs: subject matter experts.

The Binary-Based Model (BBM) for Improved Human Factors Method Selection.

OBJECTIVE: This paper presents the Binary-Based Model (BBM), a new approach to Human Factors (HF) method selection. The BBM helps practitioners select the most appropriate HF methodology in relation to the complexity within the target system. BACKGROUND: There are over 200 HF methods available to the practitioner and little guidance to help choose between them. METHOD: The BBM defines a HF "problem space" comprising three complexity attributes. HF problems can be rated against these attributes and located in the "problem space." In addition, a similar HF "approach space" in which 66 predictive methods are rated according to their ability to confront those attributes is defined. These spaces are combined into a "utility space" in which problems and methods coexist. In the utility space, the match between HF problems and methods can be formally assessed. RESULTS: The method space is split into octants to establish broad groupings of methods distributed throughout the space. About 77% of the methods reside in Octant 1 which corresponds to problems with low levels of complexity. This demonstrates that most HF methods are suited to problems in low-complexity systems. CONCLUSION: The location of 77% of the rated methods in Octant 1 indicates that HF practitioners are underserved with methods for analysis of HF problems exhibiting high complexity. APPLICATION: The BBM can be used by multidisciplinary teams to select the most appropriate HF methodology for the problem under analysis. All the materials and analysis are placed in the public domain for modification and consensus building by the wider HF community.

Radical systems thinking and the future role of computational modelling in ergonomics: an exploration of agent-based modelling.

We are teetering on the precipice of the imminent Fourth Industrial Revolution. In this new age, systems are set to become more densely intraconnected and interconnected, and massive sociotechnical systems exhibiting unprecedented levels of complexity will increasingly take hold. At the dawning of this new age, the Ergonomics discipline must reflect on its preparedness for tackling problems in these novel systems. This paper engages in this reflection by putting forth a critical commentary on the implication of these changes on the discipline and discusses the utility of our current methods in this new paradigm. A resulting Radical Systems Thinking in Ergonomics Manifesto is put forward - a set of mandates to guide practitioners and researchers in the development of new methods capable of coping with these imminent challenges. From the manifesto are derived a series of capability requirements for future computational modelling approaches in Ergonomics. Practitioner summary: The goal of this paper was to inspire the Ergonomics community to pursue further applications involving computational modelling approaches such as Agent-Based Modelling. It presents a manifesto for the future of the discipline, and from this the capabilities that future computational modelling approaches need to possess. Abbreviations: 1IR: first industrial revolution; 2IR: second industrial revolution; 3IR: third industrial revolution; 4IR: fourth industrial revolution; ABM: agent based model; AI: artificial intelligence; AoF: allocation of function; CPA: cyber physical attack; CPS: cyber-physical system; CWA: cognitive work analysis; DDoS: distributed denial of service; EAST: event analysis of systemic teamwork; FRAM; functional resonance analysis method; HCI: human-computer interaction; HERA: human error and recovery assessment; HET: human error template; HMC: human-machine cooperation; IoT: internet of things; RSTEM: radical systems thinking in ergonomics manifesto; SAI: situated artificial intelligence; STAMP: systems theoretic accident model and processes; TRACEr: technique for the retrospective and predictive analysis of cognitive errors in air traffic control.

Association of severity of primary open-angle glaucoma with serum vitamin D levels in patients of African descent.

Purpose: To study the relationship between primary open-angle glaucoma (POAG) in a cohort of patients of African descent (AD) and serum vitamin D levels. Methods: A subset of the AD and glaucoma evaluation study III (ADAGES III) cohort, consisting of 357 patients with a diagnosis of POAG and 178 normal controls of self-reported AD, were included in this analysis. Demographic information, family history, and blood samples were collected from all the participants. All the subjects underwent clinical evaluation, including visual field (VF) mean deviation (MD), central cornea thickness (CCT), intraocular pressure (IOP), and height and weight measurements. POAG patients were classified into early and advanced phenotypes based on the severity of their visual field damage, and they were matched for age, gender, and history of hypertension and diabetes. Serum 25-Hydroxy (25-OH) vitamin D levels were measured by enzyme-linked immunosorbent assay (ELISA). The association of serum vitamin D levels with the development and severity of POAG was tested by analysis of variance (ANOVA) and the paired t-test. Results: The 178 early POAG subjects had a visual field MD of better than -4.0 dB, and the 179 advanced glaucoma subjects had a visual field MD of worse than -10 dB. The mean (95% confidence interval [CI]) levels of vitamin D of the subjects in the control (8.02 ± 6.19 pg/ml) and early phenotype (7.56 ± 5.74 pg/ml) groups were significantly or marginally significantly different from the levels observed in subjects with the advanced phenotype (6.35 ± 4.76 pg/ml; p = 0.0117 and 0.0543, respectively). In contrast, the mean serum vitamin D level in controls was not significantly different from that of the subjects with the early glaucoma phenotype (p = 0.8508). Conclusions: In this AD cohort, patients with advanced glaucoma had lower serum levels of vitamin D compared with early glaucoma and normal subjects.

Does a perioperative belladonna and opium suppository improve postoperative pain following robotic assisted laparoscopic radical prostatectomy? Results of a single institution randomized study.

INTRODUCTION: Robotic assisted laparoscopic radical prostatectomy (RALP) is a common treatment for localized prostate cancer. Despite a primary advantage of improved postoperative pain, patients undergoing RALP still experience discomfort. Belladonna, containing the muscarinic receptor antagonists atropine and scopolamine, in combination with opium as a rectal suppository (B & O) may improve post-RALP pain. This study evaluates whether a single preoperative B & O results in decreased postoperative patient-reported pain and analgesic requirements. MATERIALS AND METHODS: Patients undergoing RALP at Virginia Mason Medical Center between November 2008 and July 2009 were offered the opportunity to enter a randomized, double-blind, placebo-controlled trial. Exclusion criteria included: glaucoma, bronchial asthma, convulsive disorders, chronic pain, chronic use of analgesics, or a history of alcohol or opioid dependency. Surgeons were blinded to suppository placement which was administered after induction of anesthesia. All patients underwent a standardized anesthesia regimen. Postoperative pain was assessed by a visual analog scale (VAS) and postoperative narcotic use was calculated in intravenous morphine equivalents. RESULTS: Ninety-nine patients were included in the analysis. The B & O and control groups were not significantly different in terms of age, body mass index, operative time, nerve sparing status or prostatic volume. Postoperative pain was significantly improved during the first two postoperative hours in the B & O group. Similarly, 24-hour morphine consumption was significantly lower in patients who received a B & O. No adverse effects secondary to suppository placement were identified. CONCLUSION: Preoperative administration of B & O suppository results in significantly decreased postoperative pain and 24-hour morphine consumption in patients undergoing RALP.