Comparing Treatment Efficacy of Upper Airway Stimulation to CPAP for Obstructive Sleep Apnea

Introduction Upper airway stimulation (UAS) is newer treatment option for the management of Obstructive Sleep Apnea (OSA) and presents an alternative to the traditional Continuous Positive Airway Pressure (CPAP). Previously published data has shown good control of disease severity utilizing UAS with high patient tolerance and compliance. We aim to compare a cohort of patients treated with UAS and CPAP and evaluate therapy usage and disease control through use of the mean disease alleviation concept. Methods We evaluated demographic, pre and post-treatment sleep study, and therapy utilization data of cohorts of patients with OSA treated with CPAP and UAS. We compared the two groups and used the mean disease alleviation (MDA) concept to assess overall control of disease. Results We included 101 patients undergoing UAS therapy and postoperative PSG. We compared this group to a cohort of 149 patients diagnosed with moderate-severe OSA and treated with CPAP who were undergoing sleep study in our lab. We found the UAS group to be significantly older, with more severe disease, and a lower BMI. Utilizing the MDA concept, we found the UAS group to have a significantly higher utilization of therapy and disease alleviation with lower residual Apnea-Hypopnea Index (AHI) Conclusion UAS is an alternative treatment option to CPAP which is well tolerated by patients and offers good disease control

Structure-Based Optimization of Covalent, Small-Molecule Stabilizers of the 14-3-3σ/ERα Protein-Protein Interaction from Nonselective Fragments

The stabilization of protein-protein interactions (PPIs) has emerged as a promising strategy in chemical biology and drug discovery. The identification of suitable starting points for stabilizing native PPIs and their subsequent elaboration into selective and potent molecular glues lacks structure-guided optimization strategies. We have previously identified a disulfide fragment that stabilized the hub protein 14-3-3σ bound to several of its clients, including ERα and C-RAF. Here, we show the structure-based optimization of the nonselective fragment toward selective and highly potent small-molecule stabilizers of the 14-3-3σ/ERα complex. The more elaborated molecular glues, for example, show no stabilization of 14-3-3σ/C-RAF up to 150 μM compound. Orthogonal biophysical assays, including mass spectrometry and fluorescence anisotropy, were used to establish structure-activity relationships. The binding modes of 37 compounds were elucidated with X-ray crystallography, which further assisted the concomitant structure-guided optimization. By targeting specific amino acids in the 14-3-3σ/ERα interface and locking the conformation with a spirocycle, the optimized covalent stabilizer 181 achieved potency, cooperativity, and selectivity similar to the natural product Fusicoccin-A. This case study showcases the value of addressing the structure, kinetics, and cooperativity for molecular glue development. </p

Economic Evaluations of Occupational Health Interventions from a Company’s Perspective: A Systematic Review of Methods to Estimate the Cost of Health-Related Productivity Loss

Objectives: To investigate the methods used to estimate the indirect costs of health-related productivity in economic evaluations from a company’s perspective. Methods: The primary literature search was conducted in Medline and Embase. Supplemental searches were conducted in the Cochrane NHS Economic Evaluation Database, the National Institute for Occupational Safety and Health database, the Ryerson International Labour, Occupational Safety and Health Index database, scans of reference lists and researcher’s own literature database. Article selection was conducted independently by two researchers based on title, keywords, and abstract, and if needed, full text. Differences were resolved by a consensus procedure. Articles were selected based on seven criteria addressing study population, type of intervention, comparative intervention, outcome, costs, language and perspective, respectively. Characteristics of the measurement and valuation of health-related productivity were extracted and analyzed descriptively. Results: A total of 34 studies were included. Costs of health-related productivity were estimated using (a combination of) data related to sick leave, compensated sick leave, light or modified duty or work presenteeism. Data were collected from different sources (e.g. administrative databases, worker self-report, supervisors) and by different methods (e.g. questionnaires, interviews). Valuation varied in terms of reported time units, composition and source of the corresponding price weights, and whether additional elements, such as replacement costs, were included. Conclusions: Methods for measuring and valuing health-related productivity vary widely, hindering comparability of results and decision-making. We provide suggestions for improvement

A consensus guide to capturing the ability to inhibit actions and impulsive behaviors in the stop-signal task.

Response inhibition is essential for navigating everyday life. Its derailment is considered integral to numerous neurological and psychiatric disorders, and more generally, to a wide range of behavioral and health problems. Response-inhibition efficiency furthermore correlates with treatment outcome in some of these conditions. The stop-signal task is an essential tool to determine how quickly response inhibition is implemented. Despite its apparent simplicity, there are many features (ranging from task design to data analysis) that vary across studies in ways that can easily compromise the validity of the obtained results. Our goal is to facilitate a more accurate use of the stop-signal task. To this end, we provide 12 easy-to-implement consensus recommendations and point out the problems that can arise when they are not followed. Furthermore, we provide user-friendly open-source resources intended to inform statistical-power considerations, facilitate the correct implementation of the task, and assist in proper data analysis

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

The impact of salient action effects on 6-, 7-, and 11-month-olds' goal-predictive gaze shifts for a human grasping action.

When infants observe a human grasping action, experience-based accounts predict that all infants familiar with grasping actions should be able to predict the goal regardless of additional agency cues such as an action effect. Cue-based accounts, however, suggest that infants use agency cues to identify and predict action goals when the action or the agent is not familiar. From these accounts, we hypothesized that younger infants would need additional agency cues such as a salient action effect to predict the goal of a human grasping action, whereas older infants should be able to predict the goal regardless of agency cues. In three experiments, we presented 6-, 7-, and 11-month-olds with videos of a manual grasping action presented either with or without an additional salient action effect (Exp. 1 and 2), or we presented 7-month-olds with videos of a mechanical claw performing a grasping action presented with a salient action effect (Exp. 3). The 6-month-olds showed tracking gaze behavior, and the 11-month-olds showed predictive gaze behavior, regardless of the action effect. However, the 7-month-olds showed predictive gaze behavior in the action-effect condition, but tracking gaze behavior in the no-action-effect condition and in the action-effect condition with a mechanical claw. The results therefore support the idea that salient action effects are especially important for infants' goal predictions from 7 months on, and that this facilitating influence of action effects is selective for the observation of human hands

Time perception during human-computer interactions: Subjectively experienced time as part of the user experience

Recent studies have shown that the user experience (UX) is associated with the subjective experience of time during human-computer interactions. In this paper, we investigate this relationship more thoroughly. We exposed $n=33$ participants to four different websites with varying degrees of objective usability, attractiveness, and content. Participants rated both their subjectively experienced time (SXT) and various UX components as defined by the CUE-model. The results showed that SXT correlates highly with subjective usability as part of the perception of instrumental qualities, even though both measures were rated at different points in time to avoid a common-method bias. Moreover, SXT showed weak correlations with visual attractiveness (perception of non-instrumental qualities) and was closely linked to the user's emotional state. The results imply that SXT is part of the perception of instrumental qualities of an interaction. The study underlines the importance of considering the subjective experience of time rather than objective temporal measures when measuring UX

Do preferences for words and actions influence word-object and action-object learning in early childhood?

Children live in a multimodal world: For example, communication with young children not only includes information from the auditory linguistic modality in the form of speech but also from the visual modality in the form of actions that caregivers use in the interaction with children. Dynamic systems approaches suggest that multimodal input can help children to learn from the environment while also allowing the child to shape their own learning experience through selective attention. This selective attention might be influenced by the child's preferences, which, in turn, might shape the child's learning behaviour. In this study, we investigated how children's selective attention to information from the linguistic or the action modality influence learning in both domains. Two- to 3-year-old children and adults participated in a novel gaze-contingent paradigm that allowed them to choose between being provided with the labels for or the actions that one can do with novel and familiar objects. At test, participants saw the two novel objects and either heard one of the labels or saw one of the actions that had been performed on one of the objects. Following label and action presentation, we investigated whether children fixated the target object, i.e., the object whose respective action/label had been presented, as an index of word and action learning. Children learned word but not action-object associations, and their target looking in the word-object condition was influenced by their selective attention to words in the earlier phase. Adults learned word-object associations and action-object associations, and their target looking in the action-object condition was influenced by their selective attention to actions in the earlier phase. Gaze-contingent eye-tracking paradigms provide us a unique method to analyse children's active learning preferences, which will help us better understand children's learning behaviour in a complex world. In particular, we show that in multimodal environments, children's preferences might help to structure the complex input into chunks that are compatible with the child's cognitive capacities in the moment

Semantic consistency of actions and word learning

This study investigates the influence of semantic consistency of actions on word learning. Is it easier to learn a word for an object, if the object always moves in the same way? Or is it easier when the object moves in different ways