Project description:BackgroundMusic performance anxiety is a common experience among elite and professional musicians and impedes performers from achieving flow state, or a state of focused, sustained engagement that promotes optimal performance.ObjectiveThe aim of this study was to use heart rate variability (HRV) to determine the psychophysiological underpinnings of optimal music performance.MethodsWe assessed HRV to study how autonomic-cardiac modulation was associated with flow during piano performance. Twenty-two pianists (15-22 years) with at least a Grade 8 Royal Conservatory of Music certification prepared two standardized pieces and a self-selected piece. Performer heart rate data were measured with a Polar 800 watch in 5-min periods immediately before performances, during performances and post-performance. HRV was employed to assess autonomic modulation of cardiac intervals. HRV indices of sympathetic and parasympathetic modulation of the heart were analyzed in 2.5-min segments to monitor short-term autonomic adjustments using the Kubios HRV Software. Flow state was measured using the 36-item Flow State Scale (FSS). Relationships were analyzed using zero-order correlations and multiple linear regressions.ResultsOur sample consisted of 22 RCM Grade 8 certified pianists. Participants achieved the highest level of flow during performance of the Bach piece. Decreased HRV was observed during performance, as indicated by a significant drop in total power. Flow state was positively associated with High Frequency (HF) power during the pre-performance phase, and inversely associated with Low Frequency (LF) power during performance.ConclusionInverse association of flow with LF-HRV during performance affirms the importance of vagal-HR modulation for achievement of flow state. Increased HF-HRV and reduced LF-HRV immediately prior to performance suggests that flow state may be shaped as much by physiological preparation during pre-performance as it is by physiologic responses during performance. Further research is required to validate the correlation between autonomic modulation of the heart and flow state. Evidence of this correlation between autonomic modulation of the heart and achievement of flow state may pave the way for further research on enhancing musical performance and targeting MPA through HRV-based interventions.
Project description:BackgroundAt the start of the COVID-19 pandemic, guidance was needed more than ever to direct frontline healthcare and national containment strategies. Rigorous guidance based on robust research was compromised by the emergence of the pandemic and the urgency of need for guidance. Rather than aiming to "get guidance right", guidance developers needed to "get guidance right now".AimTo examine how guidance developers have responded to the need for credible guidance at the start of the COVID-19 pandemic.MethodsAn exploratory mixed-methods study was conducted among guidance developers. A web-based survey and follow-up interviews were used to examine the most pertinent challenges in developing COVID-19 guidance, strategies used to address these, and perspectives on the implications of the COVID-19 pandemic on future guidance development.ResultsThe survey was completed by 46 guidance developers. Survey findings showed that conventional methods of guidance development were largely unsuited for COVID-19 guidance, with 80% (n = 37) of respondents resorting to other methods. From the survey and five follow-up interviews, two themes were identified to bolster the credibility of guidance in a setting of extreme uncertainty: (1) strengthening end-user involvement and (2) conjoining evidence review and recommendation formulation. 70% (n = 32) of survey respondents foresaw possible changes in future guidance production, most notably shortening development time, by reconsidering how to balance between rigour and speed for different types of questions.Conclusion"Getting guidance right" and "getting guidance right now" are not opposites, rather uncertainties are always part of guidance development and require guidance developers to balance scientific robustness with usability, acceptability, adequacy and contingency. This crisis points to the need to acknowledge uncertainties of scientific evidence more explicitly and points to mechanisms to live with such uncertainty, thus extending guidance development methods and processes more widely.
Project description:Replication is vital for increasing precision and accuracy of scientific claims. However, when replications "succeed" or "fail," they could have reputational consequences for the claim's originators. Surveys of United States adults (N = 4,786), undergraduates (N = 428), and researchers (N = 313) showed that reputational assessments of scientists were based more on how they pursue knowledge and respond to replication evidence, not whether the initial results were true. When comparing one scientist that produced boring but certain results with another that produced exciting but uncertain results, opinion favored the former despite researchers' belief in more rewards for the latter. Considering idealized views of scientific practices offers an opportunity to address incentives to reward both innovation and verification.
Project description:(1) Background: The oncology field has drastically changed with the advent of precision medicine, led by the discovery of druggable genes or immune targets assessed through next-generation sequencing. Biomarker-based treatments are increasingly emerging, and currently, six tissue-agnostic therapies are FDA-approved. (2) Methods: We performed a review of the literature and reported the trials that led to the approval of tissue-agnostic treatments and ongoing clinical trials currently investigating novel biomarker-based approaches. (3) Results: We discussed the approval of agnostic treatments: pembrolizumab and dostarlimab for MMRd/MSI-H, pembrolizumab for TMB-H, larotrectinib and entrectinib for NTRK-fusions, dabrafenib plus trametinib for BRAF V600E mutation, and selpercatinib for RET fusions. In addition, we reported novel clinical trials of biomarker-based approaches, including ALK, HER2, FGFR, and NRG1. (4) Conclusions: Precision medicine is constantly evolving, and with the improvement of diagnostic tools that allow a wider genomic definition of the tumor, tissue-agnostic targeted therapies are a promising treatment strategy tailored to the specific tumor genomic profile, leading to improved survival outcomes.
Project description:BackgroundAdequate pain management for preterm born neonates suffering from the extremely painful disease necrotizing enterocolitis (NEC) is essential, since neonatal exposure to pain is related to negative short-term and long-term consequences. The aim of this study was to describe the current pain management and its effectiveness in NEC patients.MethodsIn this single-center, retrospective study, neonates (gestational age < 32 weeks and/or birth weight < 1500 g) with NEC Bell's stage II or III were included. Information on pain (based on COMFORTneo and NRS scores) and analgesic therapy was collected and analyzed for the acute disease period.ResultsOf 79 patients included, 74 (94%) received intravenous analgesic therapy: most commonly morphine, fentanyl, and acetaminophen. The median COMFORTneo score was 11 (IQR 10-11), however, 49 patients had at least one COMFORTneo score ≥ 14 indicating pain. Nineteen patients had persistent high pain scores ≥ 14 with a median duration of 7.2 h (IQR 2.8-14.0).ConclusionsThis study showed that despite analgesic therapy, most NEC patients showed signs of pain, and in some, pain persisted for several hours. It suggests that current analgesic therapy frequently failed to prevent pain and existing pain was often insufficiently treated. This supports the urgent need for individualized pain management guidelines for NEC patients.ImpactThis study is unique in reporting on pain management in neonates suffering from necrotizing enterocolitis (NEC) during the full acute disease period. Despite analgesic therapy, the majority of NEC patients experience pain, and in some patients, pain persists for several hours. These findings highlight the need for improvement of neonatal pain management in NEC patients, including better pain monitoring and guidelines for individualized analgesic therapy. Improved pain management guidelines may help to prevent short-term and long-term consequences of neonatal exposure to pain, as well as excessive exposure to opioids.
Project description:IntroductionCommonly used scoring systems rely on blood counts, histological and cytological examination of bone marrow and peripheral blood as well as cytogenetic assessments to estimate prognosis of patients with myelodysplastic syndromes (MDS) and guide therapy decisions. Next-generation sequencing (NGS) has identified recurrent genetic abnormalities in up to 90% of patients with MDS and may provide important information regarding the pathogenesis of the disease, diagnostic and prognostic evaluation, and therapy selection. Areas covered: Herein, the authors review the role of NGS in diagnosis, treatment, and prognosis of MDS at various disease stages, and discuss advantages and caveats of incorporating molecular genetics in routine management of MDS. While a vast majority of patients harbor recurrent mutations implicated in MDS pathogenesis, similar mutations can be detected in otherwise healthy individuals with other hematologic malignancies. Besides establishing a diagnosis, NGS may be used to monitor minimal residual disease following treatment. Expert opinion: As more targeted therapies become available, assessment of genetic mutations will become central to individualized therapy selection and may improve diagnostic accuracy and further guide management for each patient. However, multiple challenges remain before NGS can be incorporated into routine clinical practice.
Project description:The insertion of exogenous genetic cargo into insects using transposable elements is a powerful research tool with potential applications in meeting food security and public health challenges facing humanity. piggyBac is the transposable element most commonly utilized for insect germline transformation. The described efficiency of this process is variable in the published literature, and a comprehensive review of transformation efficiency in insects is lacking. This study compared and contrasted all available published data with a comprehensive data set provided by a biotechnology group specializing in insect transformation. Based on analysis of these data, with particular focus on the more complete observational data from the biotechnology group, we designed a decision tool to aid researchers' decision-making when using piggyBac to transform insects by microinjection. A combination of statistical techniques was used to define appropriate summary statistics of piggyBac transformation efficiency by species and insect order. Publication bias was assessed by comparing the data sets. The bias was assessed using strategies co-opted from the medical literature. The work culminated in building the Goldilocks decision tool, a Markov-Chain Monte-Carlo simulation operated via a graphical interface and providing guidance on best practice for those seeking to transform insects using piggyBac.