Impact of Fruit and Vegetable Enzyme Supplementation on Aerobic Performance and Lactate Response in Older Adults Following High-Intensity Interval Exercise Through Exergaming: Randomized Experimental Matched-Pair Study.

Background: Exercise offers substantial health benefits but can induce oxidative stress and inflammation, especially in high-intensity formats such as high-intensity interval exercise (HIIE). Exergaming has become an effective, enjoyable fitness tool for all ages, particularly older adults. Enzyme supplements may enhance exercise performance by improving lactate metabolism and reducing oxidative stress. Objective: This study investigates the efficacy of fruit and vegetable enzyme supplementation in modulating fatigue and enhancing aerobic capacity in older adults following HIIE through exergaming. Methods: The study recruited 16 older adult female participants and allocated them into 2 distinct groups (enzyme and placebo) based on their pretest lactate levels. This division used pairwise grouping to guarantee comparability between the groups, ensuring the integrity of the results. They engaged in HIIE using Nintendo Switch Ring Fit Adventure, performing 8 sets of 20 seconds of maximum effort exercise interspersed with 30 seconds of rest, totaling 370 seconds of exercise. Key metrics assessed included blood lactate levels, heart rate, rating of perceived exertion, and training impulse. Participants in the enzyme group were administered a fruit and vegetable enzyme supplement at a dosage of 30 mL twice daily over a period of 14 days. Results: The enzyme group showed significantly lower blood lactate levels compared to the placebo group, notably after the fourth (mean 4.29, SD 0.67 vs mean 6.34, SD 1.17 mmol/L; P=.001) and eighth (mean 5.84, SD 0.63 vs mean 8.20, SD 1.15 mmol/L; P<.001) exercise sessions. This trend continued at 5 minutes (mean 6.85, SD 0.82 vs mean 8.60, SD 1.13 mmol/L; P=.003) and 10 minutes (mean 5.91, SD 1.16 vs mean 8.21, SD 1.27 mmol/L; P=.002) after exercise. Although both groups exceeded 85% of their estimated maximum heart rate during the exercise, enzyme supplementation did not markedly affect the perceived intensity or effort. Conclusions: The study indicates that fruit and vegetable enzyme supplementation can significantly reduce blood lactate levels in older adults following HIIE through exergaming. This suggests a potential role for these enzymes in modulating lactate production or clearance during and after high-intensity exercise. These findings have implications for developing targeted interventions to enhance exercise tolerance and recovery in older adults.

Faecal immunochemical tests can improve colonoscopy triage in patients with iron deficiency: A systematic review and meta-analysis.

BACKGROUND: Use of the faecal immunochemical test (FIT) to triage patients with iron deficiency (ID) for colonoscopy due to suspected colorectal cancer (CRC) may improve distribution of colonoscopic resources. We reviewed the diagnostic performance of FIT for detecting advanced colorectal neoplasia, including CRC and advanced pre-cancerous neoplasia (APCN), in patients with ID, with or without anaemia. METHODS: We performed a systematic review of three databases for studies comprising of patients with ID, with or without anaemia, completing a quantitative FIT within six months prior to colonoscopy, where test performance was compared against the reference standard colonoscopy. Random effects meta-analyses determined the diagnostic performance of FIT for advanced colorectal neoplasia. RESULTS: Nine studies were included on a total of n=1761 patients with ID, reporting FIT positivity thresholds between 4-150 µg haemoglobin/g faeces. Only one study included a non-anaemic ID (NAID) cohort. FIT detected CRC and APCN in ID patients with 90.7 % and 49.3 % sensitivity, and 81.0 % and 82.4 % specificity, respectively. FIT was 88.0 % sensitive and 83.4 % specific for CRC in patients with ID anaemia at a FIT positivity threshold of 10 µg haemoglobin/g faeces. CONCLUSIONS: FIT shows high sensitivity for advanced colorectal neoplasia and may be used to triage those with ID anaemia where colonoscopic resources are limited, enabling those at higher risk of CRC to be prioritised for colonoscopy. There is a need for further research investigating the diagnostic performance of FIT in NAID patients.

Chapter 4: Introduction and Getting Ready for Real-Ear Probe Microphone Measures.

Probe microphone measurements are an essential step in an individualized hearing aid fitting. These measurements allow audiologists to account for the individual's hearing and ear canal acoustics when programming hearing aids. An evidence-based hearing aid fitting includes matching the measured output of the hearing aids to targets for each input level and frequency. This allows the audiologist to confidently counsel the patient that the acoustic fitting is accurate, and the next step is for the individual to use the amplification during all waking hours to adapt to the newly amplified sounds. This also avoids mistakes such as overamplification or insufficient gain, which can endanger the patient and/or lead to a compromised fitting.

A generalized Hosmer-Lemeshow goodness-of-fit test for a family of generalized linear models.

Generalized linear models (GLMs) are very widely used, but formal goodness-of-fit (GOF) tests for the overall fit of the model seem to be in wide use only for certain classes of GLMs. We develop and apply a new goodness-of-fit test, similar to the well-known and commonly used Hosmer-Lemeshow (HL) test, that can be used with a wide variety of GLMs. The test statistic is a variant of the HL statistic, but we rigorously derive an asymptotically correct sampling distribution using methods of Stute and Zhu (Scand J Stat 29(3):535-545, 2002) and demonstrate its consistency. We compare the performance of our new test with other GOF tests for GLMs, including a naive direct application of the HL test to the Poisson problem. Our test provides competitive or comparable power in various simulation settings and we identify a situation where a naive version of the test fails to hold its size. Our generalized HL test is straightforward to implement and interpret and an R package is publicly available. Supplementary Information: The online version contains supplementary material available at 10.1007/s11749-023-00912-8.

Faecal Immunochemical Test (FIT) Sensitivity; A Five Year Audit.

Introduction: Colorectal cancer has a high prevalence and mortality rate in the United Kingdom. Cancerous colorectal lesions often bleed into the gastrointestinal lumen. The faecal immunochemical test (FIT) detects haemoglobin (Hb) in the faeces of patients and is used as a first line test in the diagnosis of colorectal cancer. Materials and Methods: A retrospective audit of all FIT performed and all colorectal cancers diagnosed in the Hull and East Riding of Yorkshire counties of the United Kingdom (population approximately 609,300) between 2018 and 2022 was conducted. FIT were performed using a HM-JACKarc analyser from Kyowa medical. The predominant symptom suggestive of colorectal cancer which prompted the FIT was recorded. Colorectal cancer was diagnosed using the gold standard of histological biopsy following colonoscopy. Results: Between 2018 and 2022, 56,202 FIT were performed on symptomatic patients. Follow on testing identified 1,511 with colorectal cancer. Of these people, only 450 people with a confirmed colorectal cancer had a FIT within the 12 months preceding their diagnosis. Of these 450 FIT results, 36 had a concentration of <10 µg/g and may be considered to be a false negative. The sensitivity of FIT in the patients identified was 92.00%. The most common reason stated by the clinician for a FIT being performed in patients with colorectal cancer was a change in bowel habits, followed by iron deficient anaemia. The number of patients diagnosed with colorectal cancer decreased in 2020, but increased significantly in 2021. Discussion: This study shows that 8.00% of people diagnosed with colorectal cancer in the Hull and East Riding of Yorkshire regions had a negative FIT. This study also shows that the SARS-CoV-2 pandemic affected the number of people diagnosed with colorectal cancer, and therefore skews the prevalence and pre-test probability of a positive test. There are many reasons why a FIT could produce a false negative result, the most likely being biological factors affecting the stability of haemoglobin within the gastrointestinal tract, or pre-analytical factors influencing faecal sampling preventing the detection of haemoglobin. Some colorectal lesions do not protrude into the gastrointestinal lumen and are less likely to bleed. Conclusion: This is the first study showing data from outside of a structured clinical trial and provides the largest study to date showing the sensitivity of FIT in a routine clinical setting. This study also provides evidence for the impact COVID-19 had on the rate of colorectal cancer diagnosis.

A hybrid IA-LC-MS/MS method for adrenocorticotropic hormone(1-24) to support interpretation of low-dose cosyntropin-stimulation test.

Adrenocorticotropic hormone 1-24 (ACTH[1-24]) has a similar effect as endogenous ACTH(1-39) to generate cortisol by targeting the MC2R receptor on the adrenal gland. A new investigational ACTH receptor antagonist drug is being developed to treat diseases of ACTH excess (e.g., Cushing's disease) by binding to the MC2R receptor. Administration of ACTH(1-24) was used in a Phase I clinical study to assess the ability of this drug candidate to suppress the cortisol response to ACTH stimulation. A hybrid immunoaffinity-LCMS assay measuring ACTH(1-24) with a concentration range of 10 to 400 pg/ml was developed to support the study. Consistent and acceptable A&P results were achieved. The assay development and qualification will be discussed.

[Box: see text].

Risk Factors for Suboptimal Colon Cancer Diagnosis and Management at a Safety-Net Hospital System.

INTRODUCTION: Colon cancer (CC) is the second leading cause of cancer-related deaths in the United States. Quality measures have been introduced by the American Gastroenterological Association and Commission on Cancer for optimal management of CC. In this study, we sought to identify factors that may hinder the timely diagnosis and treatment of CC at a safety-net hospital system. METHODS: Retrospective chart review was performed for patients aged ≥18 y diagnosed with CC from 2018 to 2021. Primary outcomes were time from positive fecal immunochemical test to colonoscopy, time from diagnosis to surgery, and time from diagnosis to adjuvant chemotherapy. Secondary end points were demographic characteristics associated with suboptimal outcomes in any of the above measures. RESULTS: One hundred ninety patients were diagnosed with nonmetastatic CC. The majority were Hispanic and non-English-speaking. 74.1% of patients with a positive fecal immunochemical test received a colonoscopy within 180 d. 59.6% of nonemergent cases received surgery within 60 d of diagnosis. 77% of those eligible received adjuvant chemotherapy within 120 d of diagnosis. No clinically significant demographic factor was associated with delay in colonoscopy, surgery, or adjuvant chemotherapy. Most frequent cause of delay in surgery (38.0%) was optimization of comorbidities. Most frequent cause of delay in adjuvant chemotherapy (71.4%) was delay in surgery itself. CONCLUSIONS: No clinically significant demographic factor was associated with experiencing delays in diagnostic colonoscopy, surgery, or adjuvant chemotherapy.

Optimizing Ultraviolet Illumination for Detecting Fluorescent Orthodontic Adhesive Residues during Debonding Procedures.

BACKGROUND: Fluorescence-aided identification technique (FIT) studies for orthodontic resins are relatively new, using an arbitrary selection of resins, lights, and work parameters. In order to provide FIT guidelines for optimal visualization, the objectives of this study were to describe the electromagnetic characteristics of fluorescent orthodontic resins, determine appropriate light specification, and describe light and work parameter effects on resin fluorescence. METHODS: This in vitro study assessed five fluorescent orthodontic resins and a non-fluorescent control resin using spectrophotometry, a scaled image analysis of 25 µm thick resins to compare intensities, and a visual assessment. Light sources varied by flashlight lens (narrow [N], average [X], and magnified [Z]) and UV intensity (X and X High). Work parameters included distance (20-300 mm) and angulation (15-70°). Visual scores were assigned to determine discernibility. RESULTS: The average excitation maxima was 384 nm. Fluorescence increased with more direct UV light exposure. The highest intensity was recorded with Light X High at 50 mm and 70°. Visual assessment followed image analysis trends, and fluorescence was clinically discernable for all 25 µm thick samples. CONCLUSIONS: Excitation wavelength range of 395-405 nm is appropriate for FIT illumination. All resins were anisotropic and showed greater fluorescence with greater angle, higher UV intensity, and closer proximity.

A Bayesian Measure of Model Accuracy.

Ensuring that the proposed probabilistic model accurately represents the problem is a critical step in statistical modeling, as choosing a poorly fitting model can have significant repercussions on the decision-making process. The primary objective of statistical modeling often revolves around predicting new observations, highlighting the importance of assessing the model's accuracy. However, current methods for evaluating predictive ability typically involve model comparison, which may not guarantee a good model selection. This work presents an accuracy measure designed for evaluating a model's predictive capability. This measure, which is straightforward and easy to understand, includes a decision criterion for model rejection. The development of this proposal adopts a Bayesian perspective of inference, elucidating the underlying concepts and outlining the necessary procedures for application. To illustrate its utility, the proposed methodology was applied to real-world data, facilitating an assessment of its practicality in real-world scenarios.

Detecting the FLJ22447 lncRNA in Ovarian Cancer with Cyclopentane-Modified FIT-PNAs (cpFIT-PNAs).

Ovarian cancer (OC) is one of the most lethal gynecologic cancers that is typically diagnosed at the very late stage of disease progression. Thus, there is an unmet need to develop diagnostic probes for early detection of OC. One approach may rely on RNA as a molecular biomarker. In this regard, FLJ22447 lncRNA is an RNA biomarker that is over-expressed in ovarian cancer (OC) and in cancer-associated fibroblasts (CAFs). CAFs appear early on in OC as they provide a metastatic niche for OC progression. FIT-PNAs (forced intercalation-peptide nucleic acids) are DNA analogs that are designed to fluoresce upon hybridization to their complementary RNA target sequence. In recent studies, we have shown that the introduction of cyclopentane PNAs into FIT-PNAs (cpFIT-PNA) results in superior RNA sensors. Herein, we report the design and synthesis of cpFIT-PNAs for the detection of this RNA biomarker in living OC cells (OVCAR8) and in CAFs. cpFIT-PNA was compared to FIT-PNA and the cell-penetrating peptide (CPP) of choice was either a simple one (four L-lysines) or a CPP with enhanced cellular uptake (CLIP6). The combination of CLIP6 with cpFIT-PNA resulted in a superior sensing of FLJ22447 lncRNA in OVCAR8 cells as well as in CAFs. Moreover, incubation of CLIP6-cpFIT-PNA in OVCAR8 cells leads to a significant decrease (ca. 60%) in FLJ22447 lncRNA levels and in cell viability, highlighting the potential theranostic use of such molecules.

Novel Chemoresistive Sensors for Indoor CO2 Monitoring: Validation in an Operational Environment.

Health and safety considerations of indoor occupants in enclosed spaces are crucial for building management which involves the strict control and monitoring of carbon dioxide levels to maintain acceptable air quality standards. For this study, we developed a wireless, noninvasive, and portable platform for the continuous monitoring of carbon dioxide concentration in enclosed environments, i.e., academic rooms. The system aimed to monitor and detect carbon dioxide using novel low-cost metal oxide-based chemoresistive sensors, achieving sensing performance comparable to those of commercially available detectors based on optical working principle, e.g., nondispersive infrared sensors. In particular, a predictive study of carbon dioxide levels was performed by exploiting random forest and curve fitting algorithms on chemoresistive sensor data collected in an academic room, then comparing the results with lab-based measurements. The performance of the models was evaluated with real environment conditions during 7 weeks. The field measurements were conducted to validate and support the development of the system for real-time monitoring and alerting in the presence of relevant concentrations (above 1,000 ppm). Therefore, the study highlighted that the curve fitting model obtained was able to recognize with an F1-score of 0.77 the presence of poor air quality, defined as concentration above 1,000 ppm of carbon dioxide as reported by the Occupational Safety and Health Administration.

National Identity Development Among Minority Youth: Longitudinal Relations with National Fit Perceptions and School Belonging.

Across Western Europe, immigrant-origin minority youth often struggle to belong socially and to develop national self-identification. Yet, almost no research to-date has asked how these youth perceive the cultural contents of the national identity in their residence country-or rather, to what extent they perceive youth like them to (mis)fit the national identity. The present study addressed this research gap by centering schools as developmental contexts of evolving belonging and national self-identification and newly inquiring into minority youth's perceptions of national (mis)fit as critical levers of their national identity development. Drawing on data from two annual waves of the Leuven-Children of Immigrants Longitudinal Study (Leuven-CILS), a sample of 942 Moroccan- and Turkish-origin youth (Mage-T1 = 14.98, SD = 1.22; 52% female) in 62 Belgian schools was used. Cross-lagged analysis combined repeated measures of school belonging and national self-identification with vignette measures of the perceived national fit of (imagined) culturally different peers. While school belonging and national self-identification were unrelated over time, earlier perceived national fit uniquely enabled more national self-identification one year later, over and above evolving school belonging. These findings suggest that experiencing belonging in school does not suffice for minority youth to develop national self-identification. Schools may, however, promote national identity development through redefining national identities to include cultural diversity-thereby signaling to minority youth that they can fit the national identity.

Stereomicroscope-Based in Vitro Study Evaluating the Marginal and Internal Fit of PEEK and PEKK Crowns.

Purpose: The aim of the in vitro study was to compare the internal merge and marginal perfection of polyetheretherketone (PEEK) and polyetherketoneketone (PEKK) crowns under a stereomicroscope. Methods: All-ceramic preparation is done on the maxillary first premolar which is mounted on the wax block which was scanned using 3Shape scanner and duplicated into 30 acrylic CAD/CAM dies (n = 15) for the placement of PEEK and PEKK crowns. The YENADENT milling system was used to fabricate 15 samples from Group A PEEK crowns and to fabricate 15 samples from Group B PEKK crowns. According to the manufacturer's instructions, an equal amount of the dual-cure resin luting agent (Rely X U200 Self-Adhesive resin, 3M, Germany) was dispensed on the mixing pad before being mixed with cement and painted on the internal surfaces of the copings with the finger pressure crowns which were luted. The values were then analyzed using one-way ANOVA (post hoc) followed by Dunnett's t-test. Results: Among those two groups, PEEK group materials showed the lowest mean value of (28.73.3 ± 4.01) for marginal fit and (26.72 ± 2.53) for internal gap, whereas PEKK group showed a mean value of (32.85 ± 4.63) and (33.06 ± 4.14), respectively. Conclusion: Among these two groups, comparatively less marginal fit and internal adaptation is seen in PEKK when compared to the PEEK crowns. While the marginal fit and internal adaptation of both PEEK and PEKK copings were in acceptable clinical range.

Evaluation of the Impact of Digital Dentistry on the Precision of Implant Placement and Prosthesis Fabrication: An In-Vitro Study.

BACKGROUND: Digital dentistry has revolutionized the field of implant dentistry, offering enhanced accuracy and precision in implant placement and prosthesis fabrication. This study aims to evaluate the effect of digital dentistry on the accuracy of implant placement and prosthesis fit through a comprehensive in-vitro assessment. METHODS: In this in-vitro study, a Digital Dentistry Group and a Conventional Group were compared regarding implant placement accuracy and prosthesis fit. Measurements of coronal deviation, apical deviation, global deviation, angulation deviation, and depth deviation were obtained for implant placement accuracy, while marginal fit and internal fit were assessed for prosthesis fit. Statistical analysis was performed to determine significant differences between the two groups. RESULTS: The Digital Dentistry Group demonstrated significantly lower values of coronal deviation, apical deviation, global deviation, angulation deviation, and depth deviation compared to the Conventional Group (p < 0.001). Similarly, the Digital Dentistry Group exhibited superior marginal fit and internal fit (p < 0.001) when compared to the Conventional Group. CONCLUSION: This in-vitro study provides evidence supporting the superior accuracy of implant placement and improved prosthesis fit achieved through digital dentistry techniques. The use of intraoral scanners, computer-aided design/computer-aided manufacturing (CAD/CAM) systems, and three-dimensional (3D) imaging enables precise digital impressions, virtual planning, and custom-made prostheses with superior fit and esthetics. Incorporating digital dentistry into clinical practice can enhance treatment outcomes and patient satisfaction in implant dentistry.

Evaluation of periodontal parameters on abutment teeth rehabilitated with single-unit crowns: A 12-month follow-up.

Purpose: This prospective study evaluated the effects of the metal-free crowns on the periodontal tissues of abutment teeth during a 12-month follow-up. Materials and Methods: A sample of 24 patients (N = 32 abutment teeth) who needed a single-tooth restoration were enrolled to receive either a metal-ceramic (n = 21) or lithium disilicate (n = 11). The single-unit crowns were evaluated at baseline, 3-and 12-month follow-up. The periodontal parameters were evaluated: plaque index (PI), gingival bleeding index (GBI), bleeding on probing (BOP), probing depth (PD), clinical attachment loss (CAL), radiographically and clinical crown fitting, bone resorption, and marginal finish lines. Statistical analyses were performed using the Exact Fisher and Mann-Whitney tests, and the Wilcoxon signed-rank test as a post hoc test for Friedman (95 % confidence interval). Results: The marginal finish line showed a statistical difference with a biomaterial type (p =.004). After a 12-months, a significant increase was observed in PI and mean PD for abutment teeth of metal-ceramic crowns. The metal-free crowns presented higher values for GBI and CAL (p2 < 0.05). Only distal cervical evaluation and dental biofilm formation in the abutment teeth showed a statistical difference between the groups at the 12-month follow-up. The supragingival margin metal-ceramic group revealed higher PI values (p2 = 0.005) between the period and the subgingival margin of both biomaterials showed greater GBI scores (p2 < 0.05). Conclusions: Metal-free crowns showed better periodontal outcomes compared to metal-ceramic crowns. Single-unit crown marginal location affects the periodontal tissue condition of the abutment teeth. The marginal fit was not changed regarding the biomaterial type.

Modelling the impact of bias in fecal immunochemical testing on long-term outcomes of colorectal cancer screening.

BACKGROUND: As the impact of unmanaged bias (i.e. systematic source of inaccuracy) in fecal immunochemical test (FIT) analytical performance on long-term colorectal cancer (CRC) outcomes is unknown, we assessed the impact bias in FIT performance in an ongoing FIT-based CRC screening program. METHODS: This study consisted of two parts: cross-sectional observational data analysis to estimate change in short-term outcomes and microsimulation modelling to estimate change in long-term outcomes assuming different levels of bias by assuming 15 % lower up to 15 % higher Hemoglobin detected in the stool compared to observed. Two scenarios were considered: bias occurring 1) one-time only, due to the occasional bias associated with the FIT kits used in 2020 and 2) consistently due to a constant bias associated with the FIT kits used from 2020 onwards. RESULTS: With a hypothetical bias of -15 % to +15 %, we observed a positivity rate ranging from 6.7 % to 7.8 %, and a detection rate for CRC between 0.65 % and 0.68 %. Single biases in FIT performance resulted in less than 0.1 % change in long-term CRC screening outcomes, while consistent biases resulted in a much larger change (up to 1.4 % in CRC cases and CRC-related deaths and up to 2.07 % in total costs). Detecting lower Hemoglobin concentrations resulted in a relatively larger change on long-term CRC outcomes in comparison to positive bias. CONCLUSIONS: Because of the substantial impact of consistent FIT bias, it is important to set evidence-based acceptance criteria of bias on long-term CRC screening outcomes and in particular, the introduction of an asymmetrical or upward shifted tolerance interval for FIT bias.

The InterModel Vigorish as a Lens for Understanding (and Quantifying) the Value of Item Response Models for Dichotomously Coded Items.

The deployment of statistical models-such as those used in item response theory-necessitates the use of indices that are informative about the degree to which a given model is appropriate for a specific data context. We introduce the InterModel Vigorish (IMV) as an index that can be used to quantify accuracy for models of dichotomous item responses based on the improvement across two sets of predictions (i.e., predictions from two item response models or predictions from a single such model relative to prediction based on the mean). This index has a range of desirable features: It can be used for the comparison of non-nested models and its values are highly portable and generalizable. We use this fact to compare predictive performance across a variety of simulated data contexts and also demonstrate qualitative differences in behavior between the IMV and other common indices (e.g., the AIC and RMSEA). We also illustrate the utility of the IMV in empirical applications with data from 89 dichotomous item response datasets. These empirical applications help illustrate how the IMV can be used in practice and substantiate our claims regarding various aspects of model performance. These findings indicate that the IMV may be a useful indicator in psychometrics, especially as it allows for easy comparison of predictions across a variety of contexts.

An empirical study on the relationship between rider recreational specialization, individual-environment fit, and heart flow experience.

The aim of the study is to create and validate a model of the relationship between specialization in leisure activities, the individual's adaptation to the environment and the heart flow experience. In order to clarify the role of the individual's adaptation to the environment in the relationship between specialization in leisure activities and the heart flow experience. The study utilized purposive sampling, cluster sampling, and random sampling. Using questionnaires and interviews to survey 525 cycling enthusiasts. Descriptive analysis, model construction and testing of the constructed path relationships were conducted using SPSS 20.0 and Amos 20.0. The results indicate that the model of the relationship between recovery specialization, individual-environment fit and heart flow experience has a good overall fit. The model shows good reliability and validity. Cyclists' recreational specialization has a statistically significant effect on individual-environment fit (ß = 0.38, P < 0.001). The fit between individual and environment has a statistically significant influence on the heart flow experience (ß = 0.39, P < 0.001). The fit between individual and environment serves as a mediating variable between recreational specialization and the heart flow experience, with the path showing statistical significance (ß = 0.15, P < 0.001). Recreational specialization has a statistically significant effect on the heart flow experience (ß = 0.30, P < 0.001). And the overall path of the effects of recreational specialization of cyclists on the fit between individual and environment is (ß = 0.45, P < 0.001), with the path showing statistical significance. Conclusion: The stronger the recreational specialization of cyclists and the greater the fit between individual and environment, the stronger their heart flow experience. The fit between individual and environment plays a partially mediating role.

Patient-advocate-led global coalition adapting fit-for-purpose outcomes measures to assure meaningful inclusion of DEEs in clinical trials.

Existing clinical tools that measure non-seizure outcomes lack the range and granularity needed to capture skills in developmental and epileptic encephalopathy (DEE)-affected individuals who also fall in the severe to profound range of intellectual disability. This effectively excludes those with severe impairments from clinical trials, impeding the ability of sponsors to evaluate disease-modifying therapies (DMTs). The Inchstone Project, an international, patient advocate-led collaboration, brings together leading researchers, clinicians, pharmaceutical companies, and advocates to develop an adapted, validated assessment battery within 5 years. The goal is to support trials of DMTs for the DEEs by providing sufficiently sensitive measurement tools to demonstrate therapeutic efficacy. An initial pilot study administered 7 established assessments to 10 individuals affected by SCN2A-DEE, identifying specific limitations of existing measures and areas for improvement. It was clear that most tools do not account for challenges throughout the DEE population, including vision impairments, significant motor impairments and profound intellectual disability, which need to be accounted for in creating a 'fit-for-purpose' battery for the DEE population. Several novel assessments, including two measures of responsivity developed for use in monitoring recovery after acquired brain injury as well as individualized Goal Attainment Scaling, showed promise in this group. The team also completed a DEE-wide survey with over 270 caregivers documenting their children's abilities and priorities for their improvement from new treatments. The Inchstone team is using this information to evaluate how existing tools might be updated to better capture what is most important to families and measure their child's small but important improvements over time. These efforts are building a coherent picture across multiple DEEs of what domains, or concepts of interest, have the greatest impact on most patients and families. The Inchstone team is on course to adapt non-seizure outcome measures that are (1) sufficiently sensitive to measure small increments of meaningful change ('Inchstones') and (2) applicable to multiple DEE conditions.

DEE-P Connection's Inchstone project is adapting assessment tools to measure the smallest developmental changes in those affected by developmental and epileptic encephalopathies (DEEs) - severe epilepsy and related developmental disorders. More sensitive measures will allow profoundly impacted individuals to be effectively included in clinical trials and result in better DEE treatments. Caregivers of children with DEEs understand firsthand that clinical tools intended to measure non-seizure outcomes, like communication and motor skills, were not designed for and don't work for their children. More sensitive tools are needed to measure the small changes that occur in DEEs. The limitations of existing measurement tools for DEEs have significant consequences: - Non-seizure responses to new therapies cannot be measured without tools designed specifically for individuals with severe to profound intellectual disability.- If a response cannot be measured in a trial, a potentially beneficial impact will be missed and a therapy, having failed to demonstrate an effect, may not gain regulatory approval.- DEE-affected individuals are less likely to benefit from the wave of new disease-modifying therapies providing hope for many other rare genetic diseases. DEE-P Connections, a patient advocacy organization supporting families caring for those severely affected by DEEs, launched The Inchstone Project to address this problem. This team science research collaborative unites researchers, pharmaceutical companies, advocates and others around a shared vision of adapting existing tools to reliably capture the small but important changes in skills in those severely affected by DEEs. To better understand these gaps, the Inchstone team conducted a pilot study with 10 children with SCN2A DEE. The team administered multiple assessments to explore how to adapt the tools to better capture the abilities and growth of this population. The team also completed a comprehensive DEE-wide survey with over 270 caregivers documenting their children's abilities and priorities for their improvement from new treatments, helping to document how existing tools may be updated to better capture what's most important to families and measure their children's small but important improvements over time. The Inchstone Project is on course to assure those profoundly impacted by DEEs are meaningfully included in clinical trials by establishing trusted and reliable non-seizure measurement tools.