Large Variations Research Articles

Large Variations in Phenylalanine Concentrations Associate Adverse Cardiac Remodelling in Adult Patients With Phenylketonuria-A Long-Term CMR Study.

Despite a phenylalanine (Phe) restrictive diet, most adult patients with 'classical' phenylketonuria (PKU) maintain life-long Phe concentrations above the normal range and receive tyrosine (Tyr) and protein-enriched diets to maintain acceptable concentrations and ensure normal development. While these interventions are highly successful in preventing adverse neuropsychiatric complications, their long- term consequences are incompletely explored. We observed early cardiomyopathic characteristics and associated hemodynamic changes in adult PKU patients and present here the results of a longitudinal evaluation of cardiac phenotype. Fifteen adult patients with PKU (age: 39.8 ± 8.1 years, 9 males and 6 females) underwent a comprehensive follow-up cardiac magnetic resonance (CMR) imaging assessment after a mean follow-up interval of 8.3 ± 0.3 years from the initial baseline visit. The CMR protocol included left (LV) and right (RV) ventricular and left atrial (LA) volumetric assessment, LV parametric mapping (precontrast and postcontrast T1 and T2 maps, extracellular volume [ECV]), multilayer LV myocardial strain, systolic and diastolic hemodynamic forces and RV and LA strain and aortic distensibility evaluation. Plasma concentrations of Phe, tyrosine (Tyr) and other biochemical markers of disease were retrospectively collected. For comparison, a group of 20 matched control subjects undergoing an identical CMR protocol was included. On average, the LV end-diastolic volume (EDV) (158 ± 29 vs. 143 ± 29 mL, p = 0.013) and end-systolic volume (ESV) (68 ± 18 vs. 62 ± 18 mL, p = 0.011) were lower at follow-up. In contrast, LV mass (LVM) (72 ± 25 vs. 82 ± 29 g, p < 0.001) and the ratio LVM/EDV (0.46 ± 0.12 vs. 0.58 ± 0.23 g/mL, p = 0.005) were increased, and T1 times were longer (940 ± 42 vs. 1010 ± 35 ms, p < 0.001). LV EF (57 ± 6 vs. 57 ± 7%, p = 0.90), longitudinal (GLS) and circumferential (GCS) systolic strain remained unchanged, but early diastolic hemodynamic (HD) forces were more markedly negative (-19.4 ± 7.0 vs. -26.5 ± 12.2%, p = 0.012), while LA strain 43.8 ± 11.3 vs. 37.3 ± 9.6%, p = 0.031) and aortic distensibility (6.38 ± 1.75 vs. 5.21 ± 1.17 10-3 mmHg-1, p = 0.008) decreased at follow-up. Compared with controls, PKU patients maintain reduced systolic function with lower LV EF and impaired GCS and have more markedly negative early diastolic HD pressures. A higher decrease in Phe concentration (ΔPhe) was associated with longer T1 times, ΔT1 (β = -0.78, p < 0.001), increased ECV, ΔECV (β = -0.61, p = 0.016) and a decrease in systolic function, ΔEF (β = 0.61, p = 0.017). In contrast, variations in Tyr concentrations did not affect the cardiac phenotype. At long-term follow-up, a marked drop in Phe plasma concentration was associated with detrimental cardiac remodelling consisting of decreased LV systolic function and increased diffuse fibrosis, in PKU patients. These new data prompt further investigation into the effects of large Phe variability over time and underline the usefulness of periodic cardiovascular assessment in adults with PKU.

Transcranial direct current stimulation alleviates the pain severity in people suffering from knee osteoarthritis: a systematic review and meta-analysis.

Considerable research has shown the benefits of transcranial direct current stimulation (tDCS) for the alleviation of pain associated with knee osteoarthritis (KOA). Still, a large variance in study protocols and observations across publications exists. We here thus completed a systematic review and meta-analysis to comprehensively and quantitatively characterize the effects of tDCS on KOA-related pain. A search strategy based on the Population, Intervention, Comparison, Outcome, and Study design (PICOS) principle was used to obtain the publications in 7 databases. Studies exploring the effects of tDCS on KOA-related pain were screened, and eligible studies were included. Ten studies of 518 participants using Visual Analogue Scale or Numeric Rating Scale to assess pain were included in the systematic review, and 9 of them were included in meta-analysis. The quality of these studies was good. Compared to control, tDCS induced significant short-term improvements in KOA-related pain with medium heterogeneity (standardized mean difference [SMD] = -0.91, 95% confidence interval [-1.24, -0.58], P < 0.001, I2 = 61%). Subgroup analyses showed that both home-based (SMD = -1.32, 95% CI [-1.65, -0.99], P < 0.001, I 2 = 0%) and laboratory-based intervention (SMD = -0.66, 95% CI [-0.99, -0.33], P < 0.001, I 2 = 40%) with at least 5 sessions per week (SMD = -1.02, 95% CI [-1.41, -0.64], P < 0.001, I 2 = 65%) and/or with a total number of at least 10 sessions (SMD = -1.12, 95% CI [-1.51, -0.74], P < 0.001, I 2 = 59%) can induce maximum benefits for the alleviation of KOA-related pain. The results here showed that tDCS is of great promise to alleviate KOA-related pain. Still, future studies with more rigorous design are needed to confirm the observations from this work, which can ultimately help the determination of appropriate intervention protocol that can maximize such benefits.

Differential prevalence of arsenic speciation in the kelps Laminaria digitata and L. hyperborea.

Large variability in highly toxic inorganic arsenic (iAs) has previously been reported for the kelp Laminaria digitata. This study aimed to compare iAs concentrations in two morphologically similar kelps species (L. digitata and L. hyperborea). Both species contained similarly high total arsenic concentrations. However, whilst L. hyperborea contained only trace levels of iAs (0.363±0.161mg/kg), iAs constituted the majority of arsenic species in L. digitata (61.6±18.7mg/kg). Since the identification of iAs relies on retention time of the arsenic species, co-elution of any other organoarsenicals was checked by determination of arsenosugars using HPLC-ICPMS and ESI-HR-MS. Additionally, hydride generation ICP-MS gave comparable results to HPLC-ICPMS analyses. Overall, given the previously observed variability in iAs within and across kelp biomass, and the possibility of commercial processing of mixed-species kelp biomass that may include L. digitata, it may be advisable to verify iAs concentration regularly in seaweed batches destined for any application that exposes humans or animals to risks associated with As toxicity.

The 2024 American Association for Thoracic Surgery expert consensus document: Current standards in donor lung procurement and preservation.

Donor lung procurement and preservation is critical for lung transplantationsuccess. Unfortunately, the large variability in techniques impacts organ utilization rates and transplantation outcomes. Compounding this variation, recent developments in cold static preservation and new technological advances with machine perfusion have increased the complexity of the procedure. The objective of the American Association for Thoracic Surgery (AATS) Clinical Practice Standards Committee (CPSC) expert panel was to make evidence-based recommendations for best practices in donor lung procurement and preservationbased on review of the existing literature. The AATS CPSC assembled an expert panel of 16 lung transplantation surgeons from 14 centers who developed a consensus document of recommendations. The panel was divided into 7 subgroups covering (1) intraoperative donor assessment, (2) surgical techniques, (3) ex situ static lung preservation methods, (4) hypothermic preservation, (5) normothermic exvivo lung perfusion (EVLP), (6) donation after circulatory death (DCD) and normothermic regional perfusion, and (7) donor management centers, organ assessment centers, and third-party procurementteams. Following a focused literature review, each subgroup formulated recommendation statements for each subtopic, which were reviewed and further refined using a Delphi process until a 75% consensus was achieved on each final statement by the voting group. The expert panel achieved consensus on 34 recommendations for current best practices in donor lung procurement and preservation both in brain-dead as well as DCD donation. The use of new methods of cold preservation, the role of EVLP, and DCD with and without concomitant heart donation are described in detail. Consistent and best practices in donor lung procurement and preservationare critical to improve both lung transplantation numbers as well as recipient outcomes. The recommendations described here provide guidance forprofessionals involved in the care of patients with end-stage lung disease considered for transplantation.

Path integral molecular dynamics approximations of quantum canonical observables

Mean-field molecular dynamics based on path integrals is used to approximate canonical quantum observables for particle systems consisting of nuclei and electrons. A computational bottleneck is the Monte Carlo sampling from the Gibbs density of the electron operator, which due to the fermion sign problem has a computational complexity that scales exponentially with the number of electrons. In this work, we construct an algorithm that approximates the mean-field Hamiltonian by path integrals for fermions. The algorithm is based on the determinant of a matrix with components based on Brownian bridges connecting permuted electron coordinates. The computational work for n electrons is O(n3), which reduces the computational complexity associated with the fermion sign problem. We analyze a bias resulting from this approximation and provide a rough computational error indicator. It remains to rigorously explain the surprisingly high accuracy for high temperatures. The method becomes infeasible at low temperatures due to a large sample variance.

Dynamic in vivo monitoring of granum structural changes of Ctenanthe setosa (Roscoe) Eichler during drought stress and subsequent recovery.

Investigating the effects of drought stress and subsequent recovery on the structure and function of chloroplasts is essential to understanding how plants adapt to environmental stressors. We investigated Ctenanthe setosa (Roscoe) Eichler, an ornamental plant that can tolerate prolonged drought periods (40 and 49 days of water withdrawal). Conventional biochemical, biophysical, physiological and (ultra)structural methods combined for the first time in a higher plant with in vivo small-angle neutron scattering (SANS) were used to characterize the alterations induced by drought stress and subsequent recovery. Upon drought stress, no significant changes occurred in the chloroplast ultrastructure, chlorophyll content, 77K fluorescence emission spectra and maximal quantum efficiency of PSII (Qy dark), but the actual quantum efficiency of PSII (Qy light) decreased, the amounts of PSI-LHCII complexes and PSII monomers declined, and that of PSII supercomplexes increased. Thickness of the leaf and of the adaxial hypodermis, chloroplast length and granum repeat distance (RD) values decreased upon drought stress, as shown by light microscopy and SANS, respectively. Because of the very slight (nm-range) changes in RD values, the large biological variability (significant differences in RD values among the leaves and studied leaf regions) and the invasive sampling required for this method, transmission electron microscopy (TEM) hardly showed significant differences. On the other side, in situ SANS analyses provided a unique insight in vivo into the fast structural recovery of the granum structure of drought-stressed leaves, which happened already 18 h after re-watering, while functional and biochemical recovery took place on a longer time scale.

Transformer-based neural speech decoding from surface and depth electrode signals

Objective.This study investigates speech decoding from neural signals captured by intracranial electrodes. Most prior works can only work with electrodes on a 2D grid (i.e. Electrocorticographic (ECoG) or ECoG array) and data from a single patient. We aim to design a deep-learning model architecture that can accommodate both surface ECoG and depth (stereotactic EEG or sEEG) electrodes. The architecture should allow training on data from multiple participants with large variability in electrode placements. The model should not have subject-specific layers and the trained model should perform well on participants unseen during training.Approach.We propose a novel transformer-based model architecture named SwinTW that can work with arbitrarily positioned electrodes by leveraging their 3D locations on the cortex rather than their positions on a 2D grid. We train subject-specific models using data from a single participant and multi-subject models exploiting data from multiple participants.Main results.The subject-specific models using only low-density 8 × 8 ECoG data achieved high decoding Pearson Correlation Coefficient with ground truth spectrogram (PCC = 0.817), overN= 43 participants, significantly outperforming our prior convolutional ResNet model and the 3D Swin transformer model. Incorporating additional strip, depth, and grid electrodes available in each participant (N= 39) led to further improvement (PCC = 0.838). For participants with only sEEG electrodes (N= 9), subject-specific models still enjoy comparable performance with an average PCC = 0.798. A single multi-subject model trained on ECoG data from 15 participants yielded comparable results (PCC = 0.837) as 15 models trained individually for these participants (PCC = 0.831). Furthermore, the multi-subject models achieved high performance on unseen participants, with an average PCC = 0.765 in leave-one-out cross-validation.Significance.The proposed SwinTW decoder enables future speech decoding approaches to utilize any electrode placement that is clinically optimal or feasible for a particular participant, including using only depth electrodes, which are more routinely implanted in chronic neurosurgical procedures. The success of the single multi-subject model when tested on participants within the training cohort demonstrates that the model architecture is capable of exploiting data from multiple participants with diverse electrode placements. The architecture's flexibility in training with both single-subject and multi-subject data, as well as grid and non-grid electrodes, ensures its broad applicability. Importantly, the generalizability of the multi-subject models in our study population suggests that a model trained using paired acoustic and neural data from multiple patients can potentially be applied to new patients with speech disability where acoustic-neural training data is not feasible.

Multi-spacecraft observations of the decay phase of solar energetic particle events

The parameters of solar energetic particle (SEP) event profiles such as the onset time and peak time have been researched extensively to obtain information on the acceleration and transport of SEPs. The corotation of particle-filled magnetic flux tubes with the Sun is generally thought to play a minor role in determining intensity profiles. However recent simulations have suggested that corotation affects the SEP decay phases and depends on the location of the observer with respect to the active region associated with the event. We aim to determine whether signatures of corotation are present in observations of the decay phases of SEP events, and we study the dependence of the parameters of the decay phase on the properties of the flares and coronal mass ejections associated with the events. We analysed multi-spacecraft observations of SEP intensity profiles from 11 events between 2020 and 2022 using data from Solar Orbiter, PSP, STEREO-A, and SOHO. We determined the decay-time constant, τ, in three energy channels; electrons ∼1 MeV, protons ∼25 MeV, and protons ∼60 MeV. We studied the dependence of τ on the longitudinal separation, Δ ϕ, between the source of the active region and the spacecraft magnetic footpoint on the Sun. Individual events show a tendency for the decay-time constant to decrease with increasing Δ ϕ. This agrees with test particle simulations. The magnitude of the event as measured through the intensity of the associated flare and SEP peak flux affects the measured τ values and likely is the cause of the observed large inter-event variability together with the varying solar wind and the conditions in the interplanetary magnetic field. We conclude that corotation affects decay phase of an SEP event and should be included in future simulations and interpretations of these events.

Seeing Into the Future: Adults' Accuracy Predicting the Vocabulary of Early Symbolic Communicators Who Use Augmentative and Alternative Communication.

Vocabulary access is important for individuals who use augmentative and alternative communication (AAC), especially for children in the early stages of language learning. This study sought to understand how accurate speech-language pathologists (SLPs), teachers, and parents are in predicting the vocabulary needed by early symbolic communicators who use AAC in three contexts. Ten groups, each with a child who used AAC as their primary mode of communication and who was classified as an early symbolic communicator and their parent, teacher, and SLP, participated. The parents, teachers, and SLPs predicted a vocabulary list of words children who use AAC needed to participate in a dinner, a math lesson, and a speech session using the blank page method and categorical inventories technique. Children were then recorded in 15-min videos participating in the three contexts. Words were recorded and compared to the words predicted. There was large variability in the accuracy of percentage of words the children used that were predicted by the adults out of all the words the children used. The adults were significantly more accurate predicting the vocabulary for the math lesson than the dinner. Parents, teachers, and SLPs predicted much of the vocabulary of early symbolic communicators who use AAC. Implications for early vocabulary selection and alternatives to predicting vocabulary are discussed.

ХАРАКТЕРИСТИКА ПРОЦЕССА ТЕПЛОВОЙ СТЕРИЛИЗАЦИИ ГЕТЕРОФАЗНОЙ ПИЩЕВОЙ СИСТЕМЫ НА ПРИМЕРЕ ЯБЛОЧНОГО СОКА С МЯКОТЬЮ

The paper presents the results of a study of the influence of thermostating regimes of a heterophase food system on cumulative lethality and rheological properties. Heterophase system FS – apple juice with pulp (RSV content – 11 %). The choice of FS is due to the maximum approximation of its properties to the properties of real FS from heterophase raw materials. To test the sterilization modes, FS was packed in glass jars with a capacity of 190 ml. The thermocouple was placed along the central axis of the jar at a geometric height of 18 mm. FS heating was carried out in a water thermostat of the WCH-16 type under isothermal conditions with a temperature stabilization error of no more than ±0.1 °C and subsequent cooling in water. Thermostat temperature range is 75, 80, 85, 90 and 95 °C. The processed experimental data of studies of heterophase FS are distinguished by a large variability in the nature of heating at the initial stage, which lasts about 10 minutes. The resulting character of the accumulation of lethality F(τ) for the entire temperature range tst 75–95 °C on the graphs is similar and differs in the obtained values. The average lethality of the F cycle was 10.3–223.72 minutes. High variability of heating dynamics FS from t0 to t ≈ tst largely depends on pomological varieties and the region where apples are grown, the ratio of puree and juice with pulp and processing equipment (crushers, mashers, homogenizers). The results of studies of the rheological properties of heterophase FS showed that within the heating range from 30 to 60 °C, it has the properties of a non-Newtonian fluid – a medium with a pronounced nonlinear change in dynamic viscosity with increasing shear rate

Accuracy and variability in clinical predictions of speech recognition outcomes for cochlear implant users

Objectives An improvement in speech perception is a major well-documented benefit of cochlear implantation (CI), which is commonly discussed with CI candidates to set expectations. However, a large variability exists in speech perception outcomes. We evaluated the accuracy of clinical predictions of post-CI speech perception scores. Design In an online survey, clinicians involved in CI care were asked to predict 6-month performance on AzBio sentences and CNC words for 15 anonymised CI patients based on demographic, medical, and audiological data, and preoperative speech recognition scores. Study sample Sixty-five participants (72% audiologists, 14% neurotologists, 14% speech-language pathologists, and CI researchers) provided predictions for two or more cases, and 43 provided predictions for all 15 CI cases. Results Clinical predictions had low accuracy and high variability (i.e. median interclass correlation coefficients [ICC] 0.11–0.13). No relationship was observed between clinicians’ confidence and prediction accuracy. Conclusions The present findings are consistent with previous research and indicate a concerning discrepancy between clinical predictions and actual speech perception outcomes for adult post-lingual CI users. Future research may explore incorporating predictions based on statistical models into speech outcome prognostication to reduce variance and improve counselling and expectations setting for individual CI candidates.

Examining the factors associated with disabilities among hypertensive patients in India

Hypertension is a major contributor to disability and mortality in India. The aim of this study was to examine the factors associated with activities of daily living (ADL) and instrumental activities of daily living (IADL) disabilities among patients with hypertension in India using secondary data from the longitudinal aging study in India (LASI) wave-1, encompassing a sample of 4,618 respondents. The disablement process model was adopted to categorize the variables into risk, intra-individual, and extra-individual factors. A zero-inflated negative binomial model was employed to identify factors associated with the absence of disabilities and those contributing to their progression. The results indicate that the risk and intra-individual factors had a larger variance in explaining disabilities than the extra-individual factor. Variables such as age, sex, depressive symptoms, psychosomatic symptoms, and physical activity were significantly associated with ADL and IADL disabilities. The findings highlight the need for targeted interventions addressing modifiable risk factors, promoting physical activity, managing depressive symptoms, and enhancing social support to reduce the disability burden in this population and improve the quality of life of hypertensive patients in India.

DDAVP response and its determinants in bleeding disorders: a systematic review and meta-analysis.

Desmopressin (DDAVP) can be used to prevent or stop bleeding. However, large inter-individual variability is observed in DDAVP response and determinants are largely unknown. In this systematic review and meta-analysis we aim to identify the response to DDAVP, and the factors that determine DDAVP response in patients. We included studies with patients with any bleeding disorder receiving DDAVP. First and second screening round and risk of bias assessment were performed by independent reviewers. The main outcome was proportion of patients with complete (factor level > 50 U/dL), or partial (30-50 U/dL) response to DDAVP. Determinants of response including disease type, age, sex, Von Willebrand factor (VWF) and factor VIII (FVIII) mutations, and baseline factor levels were investigated. In total, 591 articles were found and 103 were included. Of these, 71 articles (1772 patients) were suitable for the study's definition of response. Meta-analysis showed a pooled response proportion of 0·71 [0·64;0·78] and a significant difference in response between disease subtypes. For hemophilia A, baseline FVIII:C was a borderline significant determinant of response. In von Willebrand disease (VWD) type 1 patients, VWF:Ag, VWF:Act and FVIII:C were significant determinants. A large variation in response was observed for specific mutations in VWF and F8. Response to DDAVP varied between disease subtypes, and was largely determined by the baseline levels of FVIII:C for hemophilia A and VWF:Ag for VWD. Our findings highlight the significant differences in response and emphasize the need for a standardized response definition and further research into response mechanisms.

PET Quantification in Healthy Humans of Cyclooxygenase-2, a Potential Biomarker of Neuroinflammation.

Cyclooxygenase-2 (COX-2) is present in a healthy brain at low densities but can be markedly upregulated by excitatory input and by inflammogens. This study evaluated the sensitivity of the PET radioligand [11C]-6-methoxy-2-(4-(methylsulfonyl)phenyl)-N-(thiophen-2-ylmethyl)pyrimidin-4-amine ([11C]MC1) to detect COX-2 density in a healthy human brain. Methods: The specificity of [11C]MC1 was confirmed using lipopolysaccharide-injected rats and transgenic mice expressing the human COX-2 gene, with 120-min baseline and blocked scans using COX-1 and COX-2 selective agents. Twenty-seven healthy participants were injected with [11C]MC1. Ten of these participants received 2 PET scans: a baseline study followed by blockade with celecoxib (600 mg orally), a preferential COX-2 inhibitor. Seventeen participants underwent test-retest imaging. All scans included concurrent arterial sampling. The tissue-to-plasma ratio at equilibrium (i.e., total distribution volume) was determined using a 2-tissue compartment model (2TCM). Results: In humanized transgenic COX-2 mice, 70%-90% of [11C]MC1 brain uptake was blocked by nonradioactive MC1 and celecoxib (a COX-2 selective inhibitor) but not by PS13 (a COX-1 selective inhibitor), thereby confirming specific binding to human COX-2. Radioactivity in the human brain peaked at a concentration of about 4.0 SUV, indicating good passage through the blood-brain barrier. Values for the total distribution volume achieved stability after 80 min, indicating no radiometabolite contamination. Celecoxib reduced radioligand binding in neocortical areas by 25% but had little or no effect in subcortical regions and the cerebellum, which correlated with COX-2 messenger RNA expression levels. Binding site occupancy by celecoxib was virtually complete, as determined by the Lassen plots. Test-retest reliability was moderate (intraclass correlation coefficient, 0.65) but had relatively large variability (absolute retest variability, 20%). Reference tissue methods yielded results comparable to those of 2TCM but reduced retest variability by up to 75% and reduced intersubject variability (coefficient of variation) by about half. Thus, compared with 2TCM, which requires arterial blood, the reference tissue method is expected to significantly reduce the sample sizes required to detect statistically significant differences between groups. Conclusion: [11C]MC1 has adequate sensitivity to measure the low density of COX-2 in a healthy human brain, suggesting it can also quantify the COX-2 elevations expected in human disorders associated with neuroinflammation.

RET C611Y Germline Variant in Multiple Endocrine Neoplasia Type 2A in Denmark 1930–2021: A Nationwide Study

Background: Multiple endocrine neoplasia type 2A (MEN 2A) is a rare hereditary cancer syndrome caused by pathogenic variants in the rearranged during transfection (RET) gene and is characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO), primary hyperparathyroidism (PHPT), cutaneous lichen amyloidosis (CLA), and Hirschsprung’s disease. Phenotypic data on the RET C611Y variant remain sparse. Consequently, we aimed to establish a clinical risk profile. Methods: We conducted a nationwide study of all cases (n = 128) born after 1 January 1930 and recognized as carrying the RET C611Y variant in Denmark before 1 April 2021. Results: The median follow-up after birth was 47 years (range, 3–92). Age-related penetrance at age 70 years for MTC was 98% (CI, 91–100), for PHEO 24% (CI, 16–37), and for PHPT 10% (CI, 5–20). None had CLA or Hirschsprung’s disease. The age-related progression of MTC was significant (p &lt; 0.001). The median age at T0N0M0 was 11 years (2–62), at T1-4N0M0 was 37 years (12–65), at TxN1M0 was 47 years (16–79), and at TxNxM1 was 50 years (28–70). At the last follow-up, 56% of thyroidectomized cases (n = 103) were biochemically cured. Overall survival at 70 years was 74% (CI, 59–84). Conclusions: RET C611Y is associated with a very high penetrance of MTC and a low penetrance of PHEO and PHPT. CLA and Hirschsprung’s disease almost never occur. MTC seems moderately aggressive, but large variability can be seen. Overall survival may be comparable to that of the general population.

Quality of Psychiatric Care for Immigrants and People With a Non-English Language Preference: A Systematic Scoping Review.

Immigrants and persons with a non-English language preference (NELP) face unique challenges in the mental health care system. This systematic scoping review aimed to evaluate the literature for disparities in psychiatric care delivery, beyond access and utilization barriers, experienced by these two populations. The authors queried four databases: PubMed, PsycInfo, Web of Science, and CINAHL. Studies published between August 1993 and August 2023 were selected if they had a population that included immigrants to English-language countries or patients with a NELP and a mental illness, had a relevant comparison group, and included outcome measures focused on quality of psychiatric care delivery. Studies focusing solely on care access or utilization, studies without original data, case reports, and commentaries were excluded. The search identified 2,860 studies. Seventeen studies were included for full-text review (Cohen's κ=0.96). Large variability was found in the measures of quality used in the studies. Outcome variables were involuntary treatment rate, symptom management, unmet needs, medication use and monitoring, diagnosis, and psychiatric referral. Immigrants were more likely than nonimmigrants to receive involuntary treatments in all seven pertinent studies. An insufficient number of studies focused on other outcome measures, limiting analyses. Many studies highlighted differences in care, especially with regard to involuntary hospitalization. Outcome measures varied and deviated from established quality metrics. Insufficient data were available to determine whether the identified differences in care represent a care delivery gap. Studies that use standardized measures would assist in evaluating the quality of care received by immigrants and patients with a NELP.

Use of Machine Learning to Predict Individual Postprandial Glycemic Responses to Food Among Individuals With Type 2 Diabetes in India: Protocol for a Prospective Cohort Study.

Type 2 diabetes (T2D) is a leading cause of premature morbidity and mortality globally and affects more than 100 million people in the world's most populous country, India. Nutrition is a critical and evidence-based component of effective blood glucose control and most dietary advice emphasizes carbohydrate and calorie reduction. Emerging global evidence demonstrates marked interindividual differences in postprandial glucose response (PPGR) although no such data exists in India and previous studies have primarily evaluated PPGR variation in individuals without diabetes. This prospective cohort study seeks to characterize the PPGR variability among individuals with diabetes living in India and to identify factors associated with these differences. Adults with T2D and a hemoglobin A1c of ≥7 are being enrolled from 14 sites around India. Participants wear a continuous glucose monitor, eat a series of standardized meals, and record all free-living foods, activities, and medication use for a 14-day period. The study's primary outcome is PPGR, calculated as the incremental area under the curve 2 hours after each logged meal. Data collection commenced in May 2022, and the results will be ready for publication by September 2025. Results from our study will generate data to facilitate the creation of machine learning models to predict individual PPGR responses and to facilitate the prescription of personalized diets for individuals with T2D. This study will provide the first large scale examination variability in blood glucose responses to food in India and will be among the first to estimate PPGR variability for individuals with T2D in any jurisdiction. Clinical Trials Registry-India CTRI/2022/02/040619; https://tinyurl.com/mrywf6bf. DERR1-10.2196/59308.

Plug-and-play myoelectric control via a self-calibrating random forest common model.

Electromyographic (EMG) signals show large variabilities over time due to factors such as electrode shifting, user behaviour variations, etc., substantially degrading the performance of myoelectric control models in long-term use. Previously one-time model calibration was usually required each time before usage. However, the EMG characteristics could change even within a short period of time. Our objective is to develop a self-calibrating model, with an automatic and unsupervised self-calibration mechanism. We developed a computationally efficient random forest (RF) common model, which can (1) be pre-trained and easily adapt to a new user via one-shot calibration, and (2) keep calibrating itself once in a while by boosting the RF with new decision trees trained on pseudo-labels of testing samples in a data buffer. Our model has been validated in both offline and real-time, both open and closed-loop, both intra-day and long-term (up to 5 weeks) experiments. We tested this approach with data from 66 able-bodied participants. We also explored the effects of bidirectional user-model co-adaption in closed-loop experiments. We found that the self-calibrating model could gradually improve its performance in long-term use. With visual feedback, users will also adapt to the dynamic model meanwhile learn to perform hand gestures with significantly lower EMG amplitudes (less muscle effort). Our random forest-based approach provides a new alternative built on simple decision tree for myoelectric control applications, which is explainable, computationally efficient, and requires minimal data for model calibration.

P1075 Evaluation of characteristics of faecal urgency in patients with ulcerative colitis

Abstract Background Bowel urgency is one of the most bothersome symptoms of ulcerative colitis (UC). The Urgency Numerical Rating Scale (U-NRS) measures the degree of faecal urgency experienced over the past 24 hours by patients with UC on a scale of 0-10. We assumed that the scale has a large variance, as patients evaluate their own symptoms differently. The urge may be different quality for two patients with the same score. The score on the U-NRS may be influenced by the individual’s specific perception of symptoms (degree of pain, speed of urge). The objective of our study was to investigate the possible components of urgency using the U-NRS. Methods Patients with UC older than 18 years treated at our departments for at least 3 months and having complaints were enrolled in our study. The patients filled out our non-validated questionnaire with questions about fecal urgency (U-NRS), pain level, speed of urge, incontinence and lifestyle characteristics associated with incontinence. Statistical analysis was performed using SPSS program. Results 205 patients were enrolled, median age was 40 years, the mean of disease duration was 11.8±9.4 years. The mean U-NRS score was 3.2±3.2, 64 patients (31%) had 0 score and 8 (4%) had 10 score. 12% of the patients (n=24) felt most difficult to hold mucus, 38% (n=77) stool and 31% (n=63) other secretions. 9% (n=19) had urge with every stool in the last 24 hours, 35% (n=71) had less than half of defecations. Patient reported outcome (PRO2) had a significant but weak correlation with U-NRS (ͳb=0.348 p=0.000)(Figure 1). The speed of urge defined more the level of urgency than the pain level (R2=0.798, F(1, 203)=803.86 p&amp;lt;0.001, β=0.894 vs R2=0.805, F(2, 202)=417.98, p&amp;lt;0.001, β=0.117). The duration of faeces holding in the last 7 days had significant connection to U-NRS (R2=0.211, F(1, 203)=54.432, p&amp;lt;0.001, β=-0.46). Patients using public restroom at least once during the last week had significantly higher score on U-NRS than other patients (4.6±3.1 vs 2.4±3 p&amp;lt;0.0001). The usage of diapers was also significantly more often in patients with higher U-RNS score (5.2±3.2 vs 2.9±3.1,p&amp;lt;0.0001). Faecal leakage both during the day and night was significiantly higher with higher U-NRS score (p&amp;lt;0.0001 for both) Conclusion Urgency is more defined by the speed of urge than the pain. Using public restroom, usage of diapers and faecal leakage are associated with higher U-NRS. Bowel urgency greatly affects the daily life of UC patients, therefore, it has to be taken into count in therapy managing. Figure 1

DOP025 Subjects sharing bacterial amplicon sequence variants exhibit differences in their IgA and IgG coating of gut bacteria, with enrichment of IgG binding for bacteria typically found in the oral cavity

Abstract Background IgA is the predominant antibody in the gut, coating a larger proportion of intestinal bacteria. IgG is found in lower concentrations but tends to increase with gut inflammation. We aimed to characterize IgA- and IgG-coated gut microbial compositions in healthy controls and evaluate coating variations of shared bacteria across individuals. Methods We established a protocol for isolating IgA- and IgG-bound fecal bacteria, using magnetic streptavidin beads coated with biotin anti-human IgA or IgG (Fig. 1A). The initial stool, as well as the negative (unbound) and positive (IgG- or IgA-bound bacteria) fractions, were analyzed by 16S rRNA sequencing. For differential abundance, a non-parametric, permutation-based rank mean test was applied (dsFDR&amp;lt;0.25). Results Fecal samples from 13 healthy subjects (Mean age 40.6 years, 54% males) were simultaneously incubated with anti-human IgA- or IgG- coated beads. Within-sample variability was quantified using three different fecal aliquots per subject, and several controls were included throughout the process. Paired differential abundance between the positive and the negative IgA fractions identified 46 amplicon sequence variants (ASVs) bacteria significantly higher in the positive fraction (IgA bound) and 44 ASVs significantly higher in the negative fraction. To better characterize the bound and unbound ASVs, we calculated term enrichment f-scores using the dbBact knowledge base (PMID: 37326027). This indicated enrichment of bacteria consistently reported as IgA-bound in previous publications, implicating the validity of our separation of Ig-bound bacteria (Fig. 1B). Similar analysis for the IgG-bound bacteria, identified 58 and 49 differentially abundant ASVs in the positive and negative fractions, respectively, with significant enrichment of bacteria previously noted to show IgA-coating and of salivary/oral bacteria among IgG-bound bacteria (Fig. 1C). Using the Ig-coating index (ICI; PMID: 25171403) of each `shared` ASV (detected in more than two subjects), we noted large inter-individual variance among the controls, with 42.4% ASVs showing significant inter-individual variance in IgA-coating (FDR&amp;lt;0.1; Fig. 2A) and 30.3% ASVs with significant inter-individual variance in IgG-coating (FDR&amp;lt;0.1; Fig. 2B). Conclusion Healthy subjects show variations in the immunoglobulin coating of bacteria, even among shared ASVs, indicating a personalized immune-bacterial repertoire. However, it is still unclear if this variation contributes to the gut microbiome composition variations seen between subjects. In addition, we observed preferential enrichment for immunoglobulin coating of bacteria typically found in the oral cavity.