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Frontiers in Neurology 2024Via mirror mechanism, motor training approaches based on the alternation of action observation and execution (i.e., Action Observation Training-AOT) promote the...
INTRODUCTION
Via mirror mechanism, motor training approaches based on the alternation of action observation and execution (i.e., Action Observation Training-AOT) promote the acquisition of motor abilities. Previous studies showed that both visual and auditory stimuli may elicit a common motor representation of music-related gestures; however, the potentialities of AOT for the acquisition of musical skills are still underexplored.
METHODS
Twenty-one music-naïve participants underwent two blocks of training: AOT and Key-light Observation Training (KOT). AOT consisted of the observation of a melodic sequence played on a keyboard with the right hand by an expert model, followed by participant's imitation. Observation and execution were repeated six consecutive times (T1-T6). KOT followed the same procedure, except for the visual content of the stimulus, depicting the sequential highlighting of the piano keys corresponding to the melody. The rate of correct notes (C), the trainee-model similarity of key-pressure strength (S), and the trainee-model consistency of note duration (R) were collected across T1-T6.
RESULTS
Both AOT and KOT improved musical performance. Noteworthy, AOT showed a higher learning magnitude relative to KOT in terms of C and S.
DISCUSSION
Action Observation Training promotes the acquisition of key elements of melodic sequences, encompassing not only the accurate sequencing of notes but also their expressive characteristics, such as key-pressure dynamics. The convergence of listening and observation of actions onto a shared motor representation not only explains several pedagogical approaches applied in all musical cultures worldwide, but also enhances the potential efficacy of current procedures for music training.
PubMed: 38872813
DOI: 10.3389/fneur.2024.1383053 -
BioRxiv : the Preprint Server For... Jun 2024Targeted mass spectrometry (MS) methods are powerful tools for selective and sensitive analysis of peptides identified by global discovery experiments. Selected reaction...
Targeted mass spectrometry (MS) methods are powerful tools for selective and sensitive analysis of peptides identified by global discovery experiments. Selected reaction monitoring (SRM) is currently the most widely accepted MS method in the clinic, due to its reliability and analytical performance. However, due to limited throughput and the difficulty in setting up and analyzing large scale assays, SRM and parallel reaction monitoring (PRM) are typically used only for very refined assays of on the order of 100 targets or less. Here we introduce a new MS platform with a quadrupole mass filter, collision cell, linear ion trap architecture that has increased acquisition rates compared to the analogous hardware found in the Orbitrap Tribrid series instruments. The platform can target more analytes than existing SRM and PRM instruments - in the range of 5000 to 8000 peptides per hour. This capability for high multiplexing is enabled by acquisition rates of 70-100 Hz for peptide applications, and the incorporation of real-time chromatogram alignment that adjusts for retention time drift and enables narrow time scheduled acquisition windows. Finally, we describe a Skyline external software tool that implements the building of targeted methods based on data independent acquisition chromatogram libraries or unscheduled analysis of heavy labeled standards. We show that the platform delivers ~10x lower LOQs than traditional SRM analysis for a highly multiplex assay and also demonstrate how analytical figures of merit change while varying method duration with a constant number of analytes, or by keeping a constant time duration while varying the number of analytes.
PubMed: 38854069
DOI: 10.1101/2024.05.31.596848 -
Epilepsia Open Jun 2024The main goal of presurgical evaluation in drug-resistant focal epilepsy is to identify a seizure onset zone (SOZ). Of the noninvasive, yet resource-intensive tests...
Determinants of successful ictal SPECT injection in phase 1 epilepsy presurgical evaluation: Findings from the pediatric epilepsy research consortium surgery database project.
OBJECTIVES
The main goal of presurgical evaluation in drug-resistant focal epilepsy is to identify a seizure onset zone (SOZ). Of the noninvasive, yet resource-intensive tests available, ictal single-photon emission computed tomography (SPECT) aids SOZ localization by measuring focal increases in blood flow within the SOZ via intravenous peri-ictal radionuclide administration. Recent studies indicate that geographic and center-specific factors impact utilization of these diagnostic procedures. Our study analyzed successful ictal SPECT acquisition (defined as peri-ictal injection during inpatient admission) using surgery-related data from the Pediatric Epilepsy Research Consortium (PERC) surgery database. We hypothesized that a high seizure burden, longer duration of video EEG monitoring (VEEG), and more center-specific hours of SPECT availability would increase the likelihood of successful ictal SPECT.
METHODS
We identified study participants (≤18 years of age) who underwent SPECT as part of their phase 1 VEEG from January 2018 to June 2022. We assessed association between ictal SPECT outcomes (success vs. failure) and variables including patient demographics, epilepsy history, and center-specific SPECT practices.
RESULTS
Phase 1 VEEG monitoring with ictal SPECT injection was planned in 297 participants and successful in 255 participants (85.86%). On multivariable analysis, the likelihood of a successful SPECT injection was higher in patients of non-Hispanic ethnicity (p = 0.040), shorter duration VEEG (p = 0.004), and higher hours of available SPECT services (p < 0.001). Higher seizure frequency (p = 0.033) was significant only in bivariate analysis. Patients treated at centers with more operational hours were more likely to experience pre-admission protocols prior to VEEG (p = 0.002).
SIGNIFICANCE
There is inter-center variability in protocols and SPECT acquisition capabilities. Shorter duration of EEG monitoring, non-Hispanic ethnicity (when on private insurance), extended operational hours of nuclear medicine as noted on multivariate analysis and higher seizure frequency in bivariate analysis are strongly associated with successful ictal SPECT injection.
PLAIN LANGUAGE SUMMARY
In pediatric patients with drug-resistant epilepsy, single-photon emission computed tomography (SPECT) scans can be helpful in localizing seizure onset zone. However, due to many logistical challenges described below, which include not only the half-life of the technetium isotope used to inject intravenously during a seizure (called the ictal SPECT scan) but also available nuclear scanner time in addition to the unpredictability of seizures, obtaining an ictal SPECT during a planned elective inpatient hospital stay is not guaranteed. Thus, as healthcare costs increase, planning a prolonged hospital stay during which an ictal SPECT scan is not feasible is not optimal. We leveraged our prospective surgery database to look at center-specific factors and patient-specific factors associated with an ictal SPECT injection in the first, pediatric-focussed, large-scale, multicenter, prospective, SPECT feasibility study. We found that longer availability of the scanner is the most important center-specific factor in assuring ictal SPECT injection. Although seizure frequency is an important patient-specific factor on bivariate analysis, this factor lost statistical significance when other factors like patient insurance status and video EEG duration were also considered in our multivariable logistical model.
PubMed: 38845472
DOI: 10.1002/epi4.12986 -
PharmacoEconomics - Open Jun 2024To perform a budget impact analysis (BIA) of introducing olaparib as maintenance therapy in women who have BRCA mutations (BRCAm) with platinum-sensitive recurrent...
OBJECTIVES
To perform a budget impact analysis (BIA) of introducing olaparib as maintenance therapy in women who have BRCA mutations (BRCAm) with platinum-sensitive recurrent ovarian cancer (PSROC) in combination with bevacizumab in Argentina.
METHODS
A BIA model was used to analyse over a 5-year time horizon the change in the health system's budget following the adoption of olaparib as maintenance therapy in BRCAm patients with PSROC. The BIA for each year was estimated by comparing the cost difference between the current scenario (treatment with bevacizumab) and the new scenario (the addition of olaparib) for a third-party payer. The BIA is estimated at the national health system level, and by healthcare sectors in Argentina (public sector, social security and private sector). International and national epidemiological data were used to determine the target patient population. Clinical efficacy, safety outcomes and duration of treatments were obtained from the pivotal clinical study report. Relevant direct medical costs were obtained from public data in Argentina and expert consultation. All the costs are reported in US dollars as of October 2022 ($1 = 152.59 Argentine pesos). A scenario analysis assessed the full coverage of the homologous recombination deficiency (HRD) test in Argentina. In addition, one-way sensitivity analysis was conducted to evaluate the model robustness.
RESULTS
For a third-party payer with a cohort of 1,000,000 women covered, the estimated target population was 2 individuals in year 1 and 6 individuals in year 5. The incorporation of olaparib, with a wholesale price per pack of $3176.32, was associated with a weighted average of the budget impact per member per month (PMPM) of $0.062 for the national health system, being above the estimated health system budget impact threshold ($0.0153). By healthcare sector, the results of budget impact PMPM for year 5 ranged between $0.08 (public sector) and $0.114 (private sector). For all perspectives, the variables that most influenced the budget impact was the incidence of ovarian cancer, the drug acquisition cost and the treatment duration.
CONCLUSIONS
The introduction of olaparib for the treatment of BRCAm women with PSROC has a high budget impact for all three health systems in Argentina.
PubMed: 38831188
DOI: 10.1007/s41669-024-00495-6 -
Applied Ergonomics Sep 2024Thresholds that guide diagnoses of probable and acceptable seasickness levels on board ships are scarcely reported in literature. Motion sickness incidence and motion...
Thresholds that guide diagnoses of probable and acceptable seasickness levels on board ships are scarcely reported in literature. Motion sickness incidence and motion sickness dose value thresholds exist, but are defined for specific environments, such as naval, or offered merely as optional criteria for ship performance metrics. The presented work communicates a novel means of developing seasickness diagnostic criteria during ship operation, based on observations from shipboard measurement systems and seafarers using an innovative platform. The innovative platform provides personalised seasickness criteria that are accessible during ship operation to estimate the probable level of seasickness on board. Results are compared to that from a traditional method of data acquisition and analyses, post operation, revealing a similar trend in diagnostic threshold magnitudes (13-85 m/s) that can be applicable to voyages with different durations (0.5-6 hr) considering desired levels of seasickness (10-50 %). The seasickness criteria are envisioned to be pertinent for the prediction of probable seasickness levels based on sea state forecasts and ship motion estimation.
Topics: Humans; Motion Sickness; Ships; Male; Adult; Naval Medicine
PubMed: 38810325
DOI: 10.1016/j.apergo.2024.104316 -
Interventional Cardiology (London,... 2024Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has evolved a great deal over recent years, with increased procedural success and lower...
BACKGROUND
Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has evolved a great deal over recent years, with increased procedural success and lower complication rates being reported. This study aims to evaluate the feasibility, safety and success of a dedicated CTO programme in a large UK PCI centre without on-site cardiothoracic surgery facilities.
METHODS
Clinical and procedural data were retrospectively collected for consecutive unselected patients undergoing CTO PCI between 2015 and 2019 from the local database and regional electronic patient records. In-hospital outcomes and long-term major adverse cardiovascular events (all-cause mortality, MI, stroke and target vessel revascularisation) were recorded.
RESULTS
A total of 170 patients underwent 191 CTO procedures during the study period. The mean age was 63 ± 10 years and 80.6% of patients were male (n=137). The clinical indications were: stable chronic coronary syndromes in 88.5% (n=169) of patients; staged procedures in the context of acute coronary syndromes in 1.6% (n=3); and presentation with acute coronary syndrome in 9.9% (n=19). The procedural success rate was 50.0% (n=25) for general interventional cardiologists and 90.1% (n=127) for dedicated CTO operators. In-hospital major adverse cardiovascular events occurred once (0.5%) and interhospital transfer for emergency salvage cardiac surgery was not required. Long-term follow-up data at a median duration of 3.8 years revealed 4 (2.4%) cardiac deaths, 14 (8.3%) spontaneous MI events and 10 (5.9%) target vessel revascularisations.
CONCLUSION
These data suggest CTO PCI using contemporary techniques is both safe and effective when undertaken in a high-volume non-surgical centre by experienced operators.
PubMed: 38808283
DOI: 10.15420/icr.2023.23 -
JMIR Diabetes May 2024Insurance benefit design influences whether individuals with diabetes who require a continuous glucose monitor (CGM) to provide real-time feedback on their blood glucose...
BACKGROUND
Insurance benefit design influences whether individuals with diabetes who require a continuous glucose monitor (CGM) to provide real-time feedback on their blood glucose levels can obtain the CGM device from either a pharmacy or a durable medical equipment supplier. The impact of the acquisition channel on device adherence and healthcare costs has not been systematically evaluated.
OBJECTIVE
Retrospective claims analysis compared the adherence rates for patients new to CGM therapy and the costs of care for individuals who obtained CGM devices from a pharmacy versus acquisition through a durable medical equipment supplier.
METHODS
Utilizing the Mariner Commercial Claims Database, individuals aged >18 years with documented diabetes and an initial CGM claim during the first quarter of 2021 (2021Q1, index date) were identified. Patients had to maintain uninterrupted enrollment for a duration of 15 months but file no CGM claim during the six months preceding the index date. Direct matching was employed to establish comparable Pharmacy and Durable Medical Equipment cohorts. Outcomes included quarterly adherence, reinitiation, and costs for the period from 2021Q1 to the third quarter of 2022 (2022Q3). Between-cohort differences in adherence rates and reinitiation rates were analyzed using z-tests, and cost differences were analyzed using t-tests.
RESULTS
Direct matching was employed to establish comparable Pharmacy and Durable Medical Equipment cohorts. A total of 2, 356 patients were identified, with 1,178 in the Pharmacy Cohort and 1,178 in the Durable Medical Equipment cohorts Cohort. Although adherence declined over time in both cohorts, the Durable Medical Equipment Cohort exhibited significantly superior adherence compared to the Pharmacy Cohort at 6 months (Pharmacy 52%; Durable Medical Equipment 65%; P<0.05), 9 months (Pharmacy 49%; Durable Medical Equipment cohorts 61%; P<0.05), and 12 months (Pharmacy 48%; Durable Medical Equipment 59%; P<0.05). Mean annual total medical costs for adherent patients in the Pharmacy Cohort were 53% higher than the Durable Medical Equipment Cohort (Pharmacy $10,635; Durable Medical Equipment $6,967; P<0.01). In non-adherent patients, the Durable Medical Equipment Cohort exhibited a significantly higher rate of therapy reinitiation during the period compared to the Pharmacy Cohort (Pharmacy 10%; Durable Medical Equipment 22%; P<0.05).
CONCLUSIONS
The results from this real-world claims analysis demonstrate that, in a matched set, individuals who received their CGM through a durable medical equipment supplier were more adherent to their device. For individuals who experienced a lapse in therapy, those whose supplies were provided through the durable medical equipment channel were more likely to resume use after an interruption than those who received their supplies from a pharmacy. In the matched cohort analysis, those who received their CGM equipment through a durable medical equipment supplier demonstrated a lower total cost of care.
PubMed: 38804821
DOI: 10.2196/58832 -
Archives of Disease in Childhood May 2024To resolve unsolved whole-genome sequencing (WGS) data in individuals with paediatric neurological disorders.
OBJECTIVE
To resolve unsolved whole-genome sequencing (WGS) data in individuals with paediatric neurological disorders.
DESIGN
A cohort study method using updated bioinformatic tools, new analysis targets, clinical information and literature databases was employed to reanalyse existing unsolved genome data.
PARTICIPANTS
From January 2016 to September 2023, a total of 615 individuals who aged under 18 years old, exhibited neurological disorders and received singleton WGS were recruited. 364 cases were unsolved during initial WGS analysis, in which 102 consented to reanalyse existing singleton WGS data.
RESULTS
Median duration for reanalysis after initial negative WGS results was 2 years and 4 months. The diagnostic yield was 29 of 102 individuals (28.4%) through reanalysis. New disease gene discovery and new target acquisitions contributed to 13 of 29 solved cases (44.8%). The reasons of non-detected causative variants during initial WGS analysis were variant reclassification in 9 individuals (31%), analytical issue in 9 (31%), new emerging disease-gene association in 8 (27.6%) and clinical update in 3 (10.3%). The 29 new diagnoses increased the cumulative diagnostic yield of clinical WGS in the entire study cohort to 45.5% after reanalysis.
CONCLUSIONS
Unsolved paediatric WGS individuals with neurological disorders could obtain molecular diagnoses through reanalysis within a timeframe of 2-2.5 years. New disease gene, structural variations and deep intronic splice variants make a significant contribution to diagnostic yield. This approach can provide precise genetic counselling to positive reanalysis results and end a diagnostic odyssey.
PubMed: 38789118
DOI: 10.1136/archdischild-2024-326985 -
Analytical Chemistry Jun 2024Here, we demonstrate the detection of nanoplastics (NPLs) in flow with stimulated Raman scattering (SRS) for the first time. NPLs (plastic particles <1000 nm) have...
Here, we demonstrate the detection of nanoplastics (NPLs) in flow with stimulated Raman scattering (SRS) for the first time. NPLs (plastic particles <1000 nm) have recently been detected in different environmental samples and personal care products. However, their characterization is still an analytical challenge. Multiple parameters, including size, chemical composition, and concentration (particle number and mass), need to be determined. In an earlier paper, online field flow fractionation (FFF)-Raman analysis with optical trapping was shown to be a promising tool for the detection of particles in this size range. SRS, which is based on the enhancement of a vibrational transition by the matching energy difference of two laser beams, would allow for much more sensitive detection and, hence, much shorter acquisition times compared to spontaneous Raman microspectroscopy (RM). Here, we show the applicability of SRS for the flow-based analysis of individual, untrapped NPLs. It was possible to detect polyethylene (PE), polystyrene (PS), and poly(methyl methacrylate) (PMMA) beads with diameters of 100-5000 nm. The high time resolution of 60.5 μs allows us to detect individual signals per particle and to correlate the number of detected particles to the injected mass concentration. Furthermore, due to the high time resolution, optically trapped beads could be distinguished from untrapped beads by their peak shapes. The SRS wavenumber settings add chemical selectivity to the measurement. Whereas optical trapping is necessary for the flow-based detection of particles by spontaneous RM, the current study demonstrates that SRS can detect particles in a flow without trapping. Additionally, the mean particle size could be estimated using the mean width (duration) and intensity of the SRS signals.
PubMed: 38771150
DOI: 10.1021/acs.analchem.3c05881 -
Heliyon May 2024To enhance the operability of the rat orthotopic left lung transplantation model, we implemented several improvements and meticulously detailed the procedure. One...
To enhance the operability of the rat orthotopic left lung transplantation model, we implemented several improvements and meticulously detailed the procedure. One hundred and thirty-one healthy male Sprague Dawley rats, weighing between 250 and 300 g, were utilized, with 64 serving as donors, 64 as recipients, and 3 as sham controls. We employed a modified three-cuff technique for the orthotopic left lung transplantation. Notably, our modified perfusion method could prevent donor lung edema, while waist-shaped cuffs minimized suture slippage during anastomosis. Additionally, positioning the recipient rat in a slightly left-elevated supine position during anastomosis reduced tension on the lung hilum, thus mitigating the risk of vascular laceration. The introduction of a unique two-person anastomosis technique significantly reduced operation time and substantially improved success rates. Furthermore, maximizing inflation of donor lungs both during preservation and surgery minimized the occurrence of postoperative atelectasis. Various other procedural refinements contributed to the enhanced operability of our model. Sixty-four rat orthotopic left lung transplantations were performed with only one surgical failure observed. The acquisition time for donor lungs averaged (19 ± 4) minutes, while (11 ± 1) minutes were allocated for donor lung hilum anatomy and cuff installation. Recipient thoracotomy and left lung hilar anatomy before anastomosis required (24 ± 8) minutes, with anastomosis itself taking (31 ± 6) minutes. Remarkably, the survival rate at the 4-h postoperative mark stood at 96.7 %. Even six months post-operation, transplanted left rat lungs continued to exhibit proper inflation and contraction rhythms, displaying signs of chronic pathological changes. In summary, our modified rat model of orthotopic left lung transplantation demonstrates robust operability, significantly reducing surgical duration, improving operation success rates, and enhancing postoperative survival rates. Furthermore, its long-term survival capacity enables the simulation of acute and chronic disease processes following lung transplantation.
PubMed: 38770296
DOI: 10.1016/j.heliyon.2024.e30728