Search

Striking disparities in access to radiation therapy (RT) exist, especially among racial and ethnic-minority patients. We analyzed census block group data to evaluate differences in travel distance to RT as a function of race and ethnicity, socioeconomic status, and rurality.The Directory of Radiotherapy Centers provided the addresses of facilities containing linear accelerators for RT. We classified block groups as majority (≥ 50%) American Indian/Alaska Native (AI/AN), black, white, Asian, no single racial majority, or Hispanic regardless of race. We used the Area Deprivation Index to classify deprivation and Rural-Urban Commuting Area codes to classify rurality. Generalized linear mixed models tested associations between these factors and distance to nearest RT facility.Median distance to nearest RT facility was 72 miles in AI/AN-majority block groups, but 4 to 7 miles in block groups with non-AI/AN majorities. Multivariable models estimated that travel distances in AI/AN-majority block groups were 39 to 41 miles longer than in areas with non-AI/AN majorities. Travel distance was 1.3 miles longer in the more deprived areas versus less deprived areas and 16 to 32 miles longer in micropolitan, small town, and rural areas versus metropolitan areas.Cancer patients in block groups with AI/AN-majority populations, nonmetropolitan location, and low socioeconomic status experience substantial travel disparities in access to RT. Future research with more granular community- and individual-level data should explore the many other known barriers to access to cancer care and their relationship to the barriers posed by distance to RT care.

Discontinuation of the contingency between a response and its reinforcer sometimes produces a temporary increase in the response before its rate decreases, a phenomenon called the extinction burst. Prior clinical and basic studies on the prevalence of the extinction burst provide highly disparate estimates. Existing theories on the extinction burst fail to account for the dynamic nature of this phenomenon, and the basic behavioral processes that control response bursting remain poorly understood. In this paper, we first review the basic and applied literature on the extinction burst. We then describe a recent refinement of the concatenated matching law called the temporally weighted matching law that appears to resolve the above-mentioned issues regarding the extinction burst. We present illustrative translational data based conceptually on the model. Finally, we discuss specific recommendations derived from the temporally weighted matching law regarding procedures clinicians could implement to potentially mitigate or prevent extinction bursts.

Resurgence following expanded-operant treatments (i.e., increasing the number or variability of alternative responses to problem behavior) has been the focus of numerous studies over the last five years. Researchers have evaluated several techniques for expanding the operant such as serial-, lag-, and concurrent-training procedures. Given the increasing number of recent studies on the topic, the various forms of training used, and the variability in outcomes, it is critical to review this area of research and identify clear future directions. Our brief review identified 10 published studies and eight unpublished theses or dissertations on this topic; however, only three published studies directly evaluated expanded-operant treatments as a strategy for relapse mitigation. All three studies evaluated serial-training procedures, and results across the studies were inconsistent. We summarize the findings of each study and provide recommendations for future research.

Clonal hematopoiesis of indeterminate potential(CHIP) is a recognized consequence of aging and a precursor to myelodysplastic syndrome and acute myeloid leukemia which independently increases all-cause mortality in adults. Childhood cancer survivors experience a phenomenon of accelerated aging with increased all-cause mortality; however, the mechanism of this is not known and the prevalence of CHIP not well defined. We prospectively studied 305 pediatric and young adult childhood cancer survivors to determine the prevalence of clonal hematopoiesis(CH). Targeted next-generation sequencing analysis of peripheral blood mononuclear cells elucidated the prevalence of CH (VAF >1%) at a rate of ∼6%, approaching that of adults >50-70 years and much higher than previously reported. This is the first prospective study of CH in pediatric and young adult survivors of childhood cancer and highlights the importance of further investigation to better understand how CH may contribute to treatment-related myeloid neoplasms and other late effects.

Background and Purpose: The spectrum of brain infarction in patients with embolic stroke of undetermined source (ESUS) has not been well characterized. Our objective was to define the frequency and pattern of brain infarcts detected by magnetic resonance imaging (MRI) among patients with recent ESUS participating in a clinical trial. Methods: In the NAVIGATE ESUS trial (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source), an MRI substudy was carried out at 87 sites in 15 countries. Participants underwent an MRI using a specified protocol near randomization. Images were interpreted centrally by those unaware of clinical characteristics. Results: Among the 918 substudy cohort participants, the mean age was 67 years and 60% were men with a median (interquartile range) of 64 (26–115) days between the qualifying ischemic stroke and MRI. On MRI, 855 (93%) had recent or chronic brain infarcts that were multiple in 646 (70%) and involved multiple arterial territories in 62% (401/646). Multiple brain infarcts were present in 68% (510/755) of those without a history of stroke or transient ischemic attack before the qualifying ESUS. Prior stroke/transient ischemic attack ( P 0 ( P P =0.01) were associated with multiple infarcts. Topographically, large and/or cortical infarcts were present in 89% (757/855) of patients with infarcts, while in 11% (98/855) infarcts were exclusively small and subcortical. Among those with multiple large and/or cortical infarcts, 57% (251/437) had one or more involving a different vascular territory from the qualifying ESUS. Conclusions: Most patients with ESUS, including those without prior clinical stroke or transient ischemic attack, had multiple large and/or cortical brain infarcts detected by MRI, reflecting a substantial burden of clinical stroke and covert brain infarction. Infarcts most frequently involved multiple vascular territories. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02313909.

Most studies examine treatment relapse by programming contextual changes with perfect treatment integrity or with omission errors in the absence of a context change (i.e., all alternative responses placed on extinction). Recently, Mitteer et al. (2018) examined caregiver behavior in response to a confederate playing the role of a child with destructive behavior, providing the opportunity for researchers to empirically derive reinforcement schedules and test caregiver error patterns within future relapse tests with children. The present study represents a pilot demonstration of methods for reverse translating findings from caregivers to relapse preparations with children. We used a human-operant arrangement with three children with autism spectrum disorder in which they (a) emitted a target response (i.e., pad touch) for a preferred item in a home-like context, (b) emitted an alternative response (e.g., card touch) for the item in a clinic context while the target response was extinguished, and (c) experienced a relapse test in which the experimenter programmed the same low-rate omission and commission errors that caregivers made in the prior study within the home-like context. During the relapse test, target responding approximated or exceeded baseline ranges for all cases, and alternative behavior extinguished for two of the three cases. We discuss how researchers might incorporate similar translation processes in future relapse research.

Clinicians frequently prescribe functional communication training (FCT) as a treatment for severe destructive behavior. Recent research has shown that FCT treatments are susceptible to treatment relapse in the form of resurgence of destructive behavior when individuals contact periods in which reinforcers are unavailable. Results of preliminary studies suggest that teaching multiple response alternatives can mitigate the resurgence of target behavior. The current evaluation serves as a preliminary study in which we used a laboratory arrangement to evaluate the effects of a novel approach to training multiple alternative responses on the resurgence of target behavior. Findings showed that multiple-response training did not decrease resurgence of target responding consistently; however, it increased the total amount of target and alternative responding observed during the resurgence phase and decreased the overall probability of the target response.

Although much has been written on the importance of translational research for bridging the continuum of basic science to clinical practice, few authors have described how such work can be carried out practically when working with patient populations in the context of ongoing clinical service delivery, where the priorities for patient care can sometimes conflict with the methods and goals of translational research. In this article, we explore some of the considerations for conducting this type of work while balancing clinical responsibilities that ensure high-quality patient care. We also discuss strategies we have found to jointly facilitate translational research and improve routine, clinical service delivery. A primary goal of this article is to encourage others working in applied settings to contribute to the increasingly important role that translational research plays in our science and practice by helping to better characterize and potentially lessen or remove barriers that may have impeded such investigations in the past.

We replicated and extended Mitteer, Greer, Fisher, and Cohrs (2018) by examining the effects of a video model on inputting data into GraphPad Prism, which is a necessary skill for graph construction. We used a concurrent multiple-probe-across-behavior design with two behavior technicians to assess data-input and graphing skills separately prior to and during access to relevant video models. We evaluated the generality of the training procedures by assessing both skills during data-input-plus-graphing sessions without access to the video models. The video models resulted in mastery of data-input and graphing skills when assessed individually. We observed training effects generalize to data-input-plus-graphing sessions once behavior technicians experienced all relevant video models. These results suggest that individuals should view both data-input and graphing video models prior to depicting single-case design data in Prism but that these skills can maintain at high levels of accuracy without continued access to the training materials.

More than 15% of radiotherapy clinics fail external audits with anthropomorphic phantoms conducted by Imaging and Radiation Oncology Core-Houston (IROC-H) while passing other industry-standard quality assurance (QA) tests. We seek to evaluate the predicted impact of such failed plans on outcomes for patients treated with stereotactic body radiation therapy (SBRT) for lung tumors.We conducted a retrospective study of 55 patients treated with SBRT for lung tumors with prescription BEDA leaf tip offset value of -1.0 mm decreased the fraction of plans receiving a PTV BEDSimulated treatment plans with modest MLC leaf offsets result in lung SBRT plans that significantly under-dose tumor or exceed OAR constraints. These dosimetric endpoints translate to significant detriments in TCP. These simulated plans mimic planning systems that pass internal QA measures but fail independent phantom-based tests, underscoring the need for enhanced quality assurance including external audits of TPS.

The development of therapies to eliminate the latent HIV-1 reservoir is hampered by our incomplete understanding of the biomolecular mechanism governing HIV-1 latency. To further complicate matters, recent single-cell RNA sequencing (scRNA-seq) studies reported extensive heterogeneity between latently HIV-1-infected primary T cells, implying that latent HIV-1 infection can persist in greatly differing host cell environments. We show here that transcriptomic heterogeneity is also found between latently infected T cell lines, which allowed us to study the underlying mechanisms of intercell heterogeneity at high signal resolution. Latently infected T cells exhibited a dedifferentiated phenotype, characterized by the loss of T cell-specific markers and gene regulation profiles reminiscent of hematopoietic stem cells (HSC). These changes had functional consequences. As reported for stem cells, latently HIV-1-infected T cells efficiently forced lentiviral superinfections into a latent state and favored glycolysis. As a result, metabolic reprogramming or cell redifferentiation destabilized latent infection. Guided by these findings, data mining of single-cell RNA-seq data of latently HIV-1-infected primary T cells from patients revealed the presence of similar dedifferentiation motifs. More than 20% of the highly detectable genes that were differentially regulated in latently infected cells were associated with hematopoietic lineage development (e.g., HUWE1, IRF4, PRDM1, BATF3, TOX, ID2, IKZF3, and CDK6) or were hematopoietic markers (SRGN; hematopoietic proteoglycan core protein). The data add to evidence that the biomolecular phenotype of latently HIV-1-infected cells differs from that of normal T cells and strategies to address their differential phenotype need to be considered in the design of therapeutic cure interventions. IMPORTANCE HIV-1 persists in a latent reservoir in memory CD4 T cells for the lifetime of a patient. Understanding the biomolecular mechanisms used by the host cells to suppress viral expression will provide essential insights required to develop curative therapeutic interventions. Unfortunately, our current understanding of these control mechanisms is still limited. By studying gene expression profiles, we demonstrated that latently HIV-1-infected T cells have a dedifferentiated T cell phenotype. Software-based data integration allowed the identification of drug targets that would redifferentiate viral host cells and, by extension, destabilize latent HIV-1 infection events. The importance of the presented data lies within the clear demonstration that HIV-1 latency is a host cell phenomenon. As such, therapeutic strategies must first restore proper host cell functionality to accomplish efficient HIV-1 reactivation.

Translation of promising procedures for mitigating treatment relapse has received considerable attention recently from researchers across the basic-applied continuum. One procedure that has demonstrated mixed support involves increasing the duration of treatment as a strategy for blunting resurgence. In a recent translational study, Greer et al. (2020) failed to detect a mitigation effect of increased treatment duration on the resurgence of destructive behavior. However, design limitations may have been responsible. The present study corrected these limitations by (a) employing a sequential design to decrease the possibility of multiple-treatment interference, (b) evaluating more treatment durations, (c) arranging treatments of fixed durations, and (d) conducting treatments of more extreme duration in a different clinical sample. Despite these improvements in experimental rigor and the testing of more extreme boundary conditions, the present study also failed to detect a mitigation effect of increased treatment duration. Likely explanations are discussed.

Science evolves from prior approximations of its current form. Interest in changes in species over time was not a new concept when Darwin made his famous voyage to the Galapagos Islands; concern with speciation stretches back throughout the history of modern thought. Behavioral science also does and must evolve. Such change can be difficult, but it can also yield great dividends. The focus of the current special section is on a common mutation that appears to have emerged across these areas and the critical features that define an emerging research area-applied quantitative analysis of behavior (AQAB). In this introduction to the "Special Issue on Applications of Quantitative Methods," we will outline some of the common characteristics of research in this area, an exercise that will surely be outdated as the research area continues to progress. In doing so, we also describe how AQAB is relevant to theory, behavioral pharmacology, applied behavior analysis, and health behaviors. Finally, we provide a summary for the articles that appear in this special issue. The authors of these papers are all thinking outside the Skinner box, creating new tools and approaches, and testing them against relevant data. If we can keep up this evolution of methods and ideas, behavior analysis will regain its place at the head of the table!

As a component of reinforcer schedule thinning following functional communication training, multiple schedules of reinforcement produce desirable rates and patterns of communication responses as an alternative response to destructive behavior. However, reinforcement schedule thinning is a gradual process that can take many sessions to obtain therapeutic goals. The desired outcome is that manding occurs only during signaled intervals of reinforcement with a sufficiently lean terminal schedule of reinforcement availability and low rates of destructive behavior. The purposes of this study were to (a) evaluate an assessment for informing the initial duration of extinction for alternative responding, (b) evaluate the utility of competing stimuli during extinction for alternative responding, and (c) assess a method for fading the availability of competing stimuli. With these procedures, all 4 participants experienced terminal schedules of reinforcement with rapid, robust reductions in destructive behavior soon after baseline. We discuss the implications and directions for future research.

Background Infliximab has transformed the management of Inflammatory Bowel Disease (IBD) however it has a significant cost burden. Additionally, demand on our IBD day case infusion unit has tripled in the last 7 years leading to long delays in treatment initiation. Switching patients from intravenous (IV) to subcutaneous (SC) infliximab reduces the demand on infusion units and offers patients more flexibility. We aim to compare the real-life direct (drug price and administration costs) and indirect costs (travel costs and time lost to work for patients) associated with switching patients from IV to SC CT-P13, an infliximab biosimilar, in a tertiary UK IBD centre. Methods We analysed data from all adult IBD patients at Leeds Teaching Hospitals Trust who had been identified as eligible to switch from IV to SC CT-P13. All patients were on a standard dosing regimen (5mg/kg 8 weekly) and were invited to switch via a letter from the IBD lead clinician. Patients were classified as IV or SC based on their decision to switch within 3 months. Figure one demonstrates how direct and indirect costs were calculated. We then compared the calculated annual costs by intention-to-treat (i.e. if all patients had switched from IV to SC) and as-treated (comparing all on IV pre-switch to some on IV and some SC post switch). Results 169 patients were identified as eligible to switch to SC CT-P13, 98 (58%) switched within 3 months. One patient was excluded as they had subsequently moved out of area. Prior to switching, total annual IV cost for 168 patients was calculated as £689,507.04 (direct = £653,671.20, indirect = £35,835.84). In the as-treated analysis after the switch, IV cost for 70 patients was £285,490.02 (direct = £272,363, indirect = £13,127.02) and SC cost for 98 patients was £389,432.81 (direct = £382,200, indirect = £7,232.81) giving a total annual cost for 168 patients of £674,922.83. In this analysis, after a proportion of patients switched to SC CT-P13, annual direct costs to the health service were £891.80 more per year, however indirect costs or cost to the patient were lower resulting in a lower total spend. See figure 2 for a breakdown of direct and indirect costs. Conclusion Our real-world analysis demonstrates that a switch from IV to SC CT-P13 is broadly cost neutral to the health service. Whilst the SC option has higher drug costs, a switch to SC allows for more efficient running of IV induction therapies by reducing demand on the infusion unit and reduces costs to the patient in terms of travel, parking and potential loss of working hours.