Exploring factors that influence the efficacy of functional communication training.

Understanding factors that influence the efficacy of functional communication training has both practical and conceptual benefits. The current study extended research in this area by exploring data from 95 consecutive applications of functional communication training with extinction across two independent clinics. We selected candidate predictor variables based on conceptual analysis, conducted preliminary exploratory analyses, and then selectively applied quantitative methods that are used in precision medicine to examine their accuracy and predictive utility. Treatment outcomes were better when challenging behavior was maintained by a single function than they were when it was maintained by multiple functions; however, these differences were most apparent among cases with an escape function. We also analyzed within-session responding to explore the potential influence of unprogrammed establishing operations on decrements in treatment efficacy. Our within-session measure only distinguished responders from nonresponders when escape was one of the multiple functions. Additional research is needed to validate these findings with an independent sample and to address a number of clinical conceptual issues.

cometrics: A New Software Tool for Behavior-analytic Clinicians and Machine Learning Researchers.

Cometrics is a Microsoft Windows compatible clinical tool for the collection and recording of frequency- and duration-based target behaviors, physiological signals, and video data. This software package is designed to record in-vivo observational and physiological data. In addition, we have included features that allow observers to capture video from real-time camera feeds and import saved video for retroactive data collection. By using Microsoft Excel-based spreadsheets, also called keystroke files, assessment and treatment sessions are exported into a single document using the click of a button. Integrated interobserver agreement metrics allow comparisons across primary and reliability observers, with the output exported into a spreadsheet for easy reference. All file system interactions are handled by the user interface, so files and folders are created and managed without manual intervention. This software is available free-of-charge through the Microsoft Store for Windows 10 and 11 and the source code is publicly available on GitHub. Supplementary Information: The online version contains supplementary material available at 10.1007/s40617-023-00817-w.

Optofluidic Particle Manipulation: Optical Trapping in a Thin-Membrane Microchannel.

We demonstrate an optofluidic device which utilizes the optical scattering and gradient forces for particle trapping in microchannels featuring 300 nm thick membranes. On-chip waveguides are used to direct light into microfluidic trapping channels. Radiation pressure is used to push particles into a protrusion cavity, isolating the particles from liquid flow. Two different designs are presented: the first exclusively uses the optical scattering force for particle manipulation, and the second uses both scattering and gradient forces. Trapping performance is modeled for both cases. The first design, referred to as the orthogonal force design, is shown to have a 80% capture efficiency under typical operating conditions. The second design, referred to as the gradient force design, is shown to have 98% efficiency under the same conditions.

Optofluidic Particle Manipulation Platform with Nanomembrane.

We demonstrate a method for fabricating and utilizing an optofluidic particle manipulator on a silicon chip that features a 300 nm thick silicon dioxide membrane as part of a microfluidic channel. The fabrication method is based on etching silicon channels and converting the walls to silicon dioxide through thermal oxidation. Channels are encapsulated by a sacrificial polymer which fills the length of the fluid channel by way of spontaneous capillary action. The sacrificial material is then used as a mold for the formation of a nanoscale, solid-state, silicon dioxide membrane. The hollow channel is primarily used for fluid and particle transport but is capable of transmitting light over short distances and utilizes radiation pressure for particle trapping applications. The optofluidic platform features solid-core ridge waveguides which can direct light on and off of the silicon chip and intersect liquid channels. Optical loss values are characterized for liquid and solid-core structures and at interfaces. Estimates are provided for the optical power needed to trap particles of various sizes.

Generality of Findings From Single-Case Designs: It's Not All About the "N".

There is a common misconception in applied research that generalizations from a study to a specific client can only be made with a large sample size. In single-case design research, however, generalizations are made from a line of replication studies rather than from a single large-N study. In this brief tutorial, we summarize how generalizations are made from single-case design research, and provide a model elevator speech to assist behavior analysts in talking about single-case design research with others.

Increasing accuracy of rock-climbing techniques in novice athletes using expert modeling and video feedback.

Several studies have examined the efficacy of behavior analytic coaching strategies in sports to increase performance fluency. Rock climbing is a multifaceted sport requiring mastery of several complex behavior chains in order to successfully navigate climbing surfaces. To date, most investigations have focused on the physiological aspects of rock climbing, as opposed to training specific rock-climbing movements. In this replication and extension, researchers used a multiple baseline design across skills to examine an expert video modeling plus video and verbal feedback training package on foundational rock-climbing skills of novice adult climbers. Results demonstrated that all participants showed an increase in accurate performance for all three skills that were targeted in the intervention.

A phase 3 study of tezacaftor in combination with ivacaftor in children aged 6 through 11 years with cystic fibrosis.

BACKGROUND: Tezacaftor/ivacaftor is a new treatment option in many regions for patients aged ≥12 years who are homozygous (F/F) or heterozygous for the F508del-CFTR mutation and a residual function (F/RF) mutation. This Phase 3, 2-part, open-label study evaluated the pharmacokinetics (PK), safety, tolerability, and efficacy of tezacaftor/ivacaftor in children aged 6 through 11 years with these mutations. METHODS: Part A informed weight-based tezacaftor/ivacaftor dosages for part B. The primary objective of part B was to evaluate the safety and tolerability of tezacaftor/ivacaftor through 24 weeks; the secondary objective was to evaluate efficacy based on changes from baseline in percentage predicted forced expiratory volume in 1 s (ppFEV1), growth parameters, sweat chloride, and the Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score. RESULTS: After PK analysis in part A, 70 children received ≥1 dose of tezacaftor/ivacaftor in part B; 67 children completed treatment. Exposures in children aged 6 through 11 years were within the target range for those observed in patients aged ≥12 years. The safety profile of tezacaftor/ivacaftor was generally similar to prior studies in patients aged ≥12 years. One child discontinued treatment for a serious adverse event of constipation. Tezacaftor/ivacaftor treatment improved sweat chloride levels and CFQ-R respiratory domain scores, mean ppFEV1 remained stable in the normal range, and growth parameters remained stable over 24 weeks. CONCLUSIONS: Tezacaftor/ivacaftor was generally safe and well tolerated, and improved CFTR function in children aged 6 through 11 years with CF with F/F and F/RF genotypes, supporting tezacaftor/ivacaftor use in this age group. NCT02953314.

Vitamin D for the Immune System in Cystic Fibrosis (DISC): a double-blind, multicenter, randomized, placebo-controlled clinical trial.

BACKGROUND: Patients with cystic fibrosis (CF) have increased risk of vitamin D deficiency owing to fat malabsorption and other factors. Vitamin D deficiency has been associated with increased risk of pulmonary exacerbations of CF. OBJECTIVES: The primary objective of this study was to examine the impact of a single high-dose bolus of vitamin D3 followed by maintenance treatment given to adults with CF during an acute pulmonary exacerbation on future recurrence of pulmonary exacerbations. METHODS: This was a multicenter, double-blind, placebo-controlled, intent-to-treat clinical trial. Subjects with CF were randomly assigned to oral vitamin D3 given as a single dose of 250,000 International Units (IU) or to placebo within 72 h of hospital admission for an acute pulmonary exacerbation, followed by 50,000 IU of vitamin D3 or an identically matched placebo pill taken orally every other week starting at 3 mo after random assignment. The primary outcome was the composite endpoint of the time to next pulmonary exacerbation or death within 1 y. The secondary outcomes included circulating concentrations of the antimicrobial peptide cathelicidin and recovery of lung function as assessed by the percentage of predicted forced expiratory volume in 1 s (FEV1%). RESULTS: A total of 91 subjects were enrolled in the study. There were no differences between the vitamin D3 and placebo groups in time to next pulmonary exacerbation or death at 1 y. In addition, there were no differences in serial recovery of lung function after pulmonary exacerbation by FEV1% or in serial concentrations of plasma cathelicidin. CONCLUSIONS: Vitamin D3 initially given at the time of pulmonary exacerbation of CF did not alter the time to the next pulmonary exacerbation, 12-mo mortality, serial lung function, or serial plasma cathelicidin concentrations. This trial was registered at clinicaltrials.gov as NCT01426256.

The Vitamin D for Enhancing the Immune System in Cystic Fibrosis (DISC) trial: Rationale and design of a multi-center, double-blind, placebo-controlled trial of high dose bolus administration of vitamin D3 during acute pulmonary exacerbation of cystic fibrosis.

Vitamin D deficiency is highly prevalent in children and adults with cystic fibrosis (CF). Recent studies have found an association between vitamin D status and risk of pulmonary exacerbations in children and adults with CF. The ongoing Vitamin D for enhancing the Immune System in Cystic fibrosis (DISC) study is a multi-center, double-blind, randomized, placebo-controlled trial that will test the hypothesis of whether high dose vitamin D given as a single oral bolus of 250,000 IU to adults with CF during a pulmonary exacerbation followed by a maintenance dose of vitamin D will improve time to next pulmonary exacerbation and re-hospitalization, improve survival and lung function compared to placebo and reduce the rates of pulmonary exacerbation,. Subjects will be randomized 1:1 at each clinical site to vitamin D or placebo within 72 hours of hospital admission for pulmonary exacerbation. Clinical follow-up visits will occur at 1, 2, 3, and 7 days, and 1, 3, 6 and 12 months after randomization. Blood and sputum will be collected and determination of clinical outcomes will be assessed at each visit. The primary endpoint will be the time to next pulmonary exacerbation requiring antibiotics, re-hospitalization or death. The secondary endpoints will include lung function assessed by forced expiratory volume in 1 second (FEV1), blood markers of inflammatory cytokines, anti-microbial peptide expression by peripheral blood mononuclear cells and circulating concentrations in blood. Other exploratory endpoints will examine the phenotype of neutrophils and monocyte/macrophages in sputum. Nutritional status will be assessed by 3 day food records and food frequency questionnaire.

Patterns and Sequences: Interactive Exploration of Clickstreams to Understand Common Visitor Paths.

Modern web clickstream data consists of long, high-dimensional sequences of multivariate events, making it difficult to analyze. Following the overarching principle that the visual interface should provide information about the dataset at multiple levels of granularity and allow users to easily navigate across these levels, we identify four levels of granularity in clickstream analysis: patterns, segments, sequences and events. We present an analytic pipeline consisting of three stages: pattern mining, pattern pruning and coordinated exploration between patterns and sequences. Based on this approach, we discuss properties of maximal sequential patterns, propose methods to reduce the number of patterns and describe design considerations for visualizing the extracted sequential patterns and the corresponding raw sequences. We demonstrate the viability of our approach through an analysis scenario and discuss the strengths and limitations of the methods based on user feedback.

Contraceptive safety among women with cystic fibrosis: a systematic review.

BACKGROUND: With dramatic improvements in life expectancy for cystic fibrosis (CF) patients, contraception for women with CF has become an important issue. There are theoretical concerns that hormonal contraceptive use among women with CF may impact disease severity or risk for other adverse health outcomes, including thrombosis and poor bone health, as well as concerns that malabsorption or altered drug metabolism might impact contraceptive effectiveness. OBJECTIVE: To evaluate evidence on the safety and effectiveness of contraceptive methods among women with CF. SEARCH STRATEGY: We searched the PubMed database for all articles published from database inception through October 2015. SELECTION CRITERIA: We included studies that examined measures of disease severity, other health outcomes or indicators of contraceptive effectiveness among women with CF initiating or continuing a contraceptive method. RESULTS: Seven studies met our inclusion criteria. Three observational studies of fair to poor quality suggest that use of oral contraceptives (OCs) does not negatively impact CF disease severity, defined as changes in pulmonary function, number of exacerbations or need for intravenous antibiotics. Three small studies of poor quality reported on contraceptive failure among women with CF using combined hormonal contraceptives (combined OCs, patch or ring). One pregnancy was reported in a patch user out of 43 hormonal contraceptive users across all studies. One pharmacokinetic study reported that women with CF achieve steroid hormone plasma concentrations similar to healthy women after ingestion of combined OCs. CONCLUSIONS: Limited evidence suggests that hormonal contraceptive use does not negatively impact disease severity among women with CF and that hormonal contraceptive effectiveness is not impaired by CF. Studies were limited by small sample sizes and short duration of follow-up. No studies examined the effect of hormonal contraception on thrombosis or bone health among women with CF.

Evaluation of a Once/Day Tobramycin Regimen to Achieve Target Concentrations in Adult Patients with Cystic Fibrosis.

STUDY OBJECTIVE: To evaluate the success of an initial tobramycin dosing regimen to achieve target peak and trough concentrations in adult patients with pulmonary exacerbations of cystic fibrosis (CF). DESIGN: Retrospective single-center medical record review. SETTING: Large tertiary care academic medical center. PATIENTS: A total of 186 patient encounters where 112 patients with CF were treated for acute pulmonary exacerbations with 10 mg/kg/day of tobramycin between January 1, 2009, and December 5, 2014. MEASUREMENTS AND MAIN RESULTS: Baseline demographics, clinical characteristics, tobramycin data, and pharmacokinetic variables were collected. The primary outcome evaluated the success of the initial tobramycin dosing regimen in attaining the target peak concentration. Secondary end points were achievement of the target trough concentration, achievement of combined peak and trough targets, and incidence of nephrotoxicity. Bivariate and multivariate analyses were performed to evaluate factors associated with achieving target concentrations. Of the 186 patient encounters, 41% achieved the target peak with the first dosing regimen, 62% achieved a target trough, and 23% achieved the target peak and trough. Nephrotoxicity occurred in 10% of patient encounters. A body mass index (BMI) of 18.5-24.9 kg/m(2) was associated with higher odds of meeting the target peak compared with a BMI lower than 18.5 kg/m(2) (odds ratio [OR] 24.5; 95% confidence interval [CI] 5.2-117.2). Conversely, a BMI of 18.5-24.9 kg/m(2) was associated with lower odds of attaining the target trough compared with a BMI lower than 18.5 kg/m(2) (OR 0.16; 95% CI 0.05-0.56). Higher volume of distribution and elimination rate constants (Kel ) were associated with significantly lower odds of achieving the target peak. In addition, higher Kel values were associated with significantly higher odds of achieving the target trough. CONCLUSIONS: The current initial tobramycin regimen did not achieve target serum tobramycin concentrations reliably. Optimization of the initial CF tobramycin dosing regimen is warranted.

Higher mobility scores in patients with cystic fibrosis are associated with better lung function.

OBJECTIVE: The purpose of this study was to determine whether mobility and physical activity were associated with lung function in adults with cystic fibrosis (CF). DESIGN: This was a prospective cohort observational study in an urban, academic, specialized care center. Participants were ambulatory, nonhospitalized adults with CF. MAIN OUTCOME MEASURES: Mobility was assessed monthly by the Life-Space Assessment (LSA) questionnaire and quarterly by pedometer. Lung function was assessed by spirometry. RESULTS: Twenty-seven subjects participated. Subjects recorded mean pedometer steps of 20,213 ± 11,331 over three days and FEV1% predicted of 77.48% ± 22.60% over one year. The LSA score at enrollment was correlated with initial pedometer steps (r = 0.42 and P = 0.03), and mean LSA score over one year was correlated with mean number of steps (r = 0.51 and P = 0.007). LSA mobility and pedometer scores were correlated with FEV1% predicted at enrollment and throughout the study. CONCLUSIONS: Mobility and physical activity measured by LSA questionnaire and pedometer are positively associated with lung function in adults with CF. This study confirms the importance of mobility and physical activity and supports the utility of a simple office-based questionnaire as a measure of mobility in adults with CF.

Efficacy and safety of ivacaftor in patients with cystic fibrosis and a non-G551D gating mutation.

BACKGROUND: Ivacaftor is used to treat patients with CF and a G551D gating mutation; the KONNECTION study assessed the efficacy and safety of ivacaftor in patients with CF and a non-G551D gating mutation. METHODS: Patients with CF ≥6-years- old with non-G551D gating mutations received ivacaftor 150mg q12h or placebo for 8weeks in this 2-part, double-blind crossover study (Part 1) with a 16-week open-label extension (Part 2). The primary efficacy outcome was absolute change in FEV1 through 8 and 24weeks of ivacaftor treatment; secondary outcomes were changes in BMI, sweat chloride, and CFQ-R and safety through 8 and 24weeks of treatment. RESULTS: Eight weeks of ivacaftor resulted in significant improvements in percent predicted FEV1, BMI, sweat chloride, and CFQ-R scores that were maintained through 24weeks. Ivacaftor was generally well tolerated. CONCLUSIONS: Ivacaftor was efficacious in a group of patients with CF who had selected non-G551D gating mutations.