Individual Frequency Research Articles

Prognostic Value of Red Cell Distribution Width in Outcome of Acute Ischemic Stroke

Background: Red cell distribution width (RDW) is a haematological parameter that indicates the range of sizes of red blood cells. It is now widely acknowledged as a prognostic indicator for ischaemic stroke. Aim and Objective: To Study theprognostic value of red cell distribution width (RDW) in outcome of acute ischemic stroke. Materials and Method: The cross-sectional study was undertaken at Aarupadi Veedu Medical College in Puducherry. It included 61 patients, aged 18-80 years, who were diagnosed with acute ischemic stroke within 48 hours. Clinical assessment of patient by NIHSS Score and measuring the outcome by modified Rankin scale. The study took place in both the Outpatient and Inpatient in Department of General Medicine. Results: The study indicates a notable proportion of male more than female ,older participants (64.0% aged 56 years and above), There is a significant occurrence of hypertension (62.3%) and diabetes mellitus (63.9%) a substantial frequency of individuals who do not smoke (63.9%), and a majority of participants who do not use alcohol (77.0%). Levels of RDW exhibited significant positive relationships with stroke severity. Conclusion: The study highlights the potential of Red Cell Distribution Width (RDW) as a helpful predictive indicator in outcome of ischemic stroke. Increased RDW levels were observed to have a substantial correlate with more severe stroke and disability, as indicated by strong associations with NIHSS and mRS scores. The study emphasizes the usefulness of RDW in assessing the severity of ischaemic stroke and emphasizes the need for additional research to improve its clinical use.

The influence of the general vibration on the quality of the assessment of the pilot's physiological indicators

The article considers flight safety issues related to continuous monitoring of the pilot's functional state by using means of monitoring physiological health indicators, which is due to the complexity of flight work, accompanied by a whole range of unfavorable factors that reduce the efficiency of professional activity. The article studies the influence of the general vibration factor on the quality (accuracy) of the assessment of the pilot's physiological indicators recorded by non-invasive diagnostic devices in transmitted light. Such indicators include heart rate, fractional blood saturation level, and respiratory rate. A mathematical model of quasi-deterministic general vibration, which is the resultant of individual frequency components of corrected vibration acceleration directed along three axes of the Cartesian coordinate system, has been developed. Mathematical modeling of the effect of general vibration on the information photoplethysmographic signal has been performed and it has been shown that the effect changes the frequency-time structure of the signal and relative errors of the estimated physiological parameters appear – the level of fractional blood saturation (4.16 %), heart rate (4.78 %) and respiration (3.75 %). As a result of a practical experiment to analyze the effect of general vibration on the quality of assessment of the specified physiological parameters, it was found that, compared to the declared error of a pulse oximeter of ±2 %, the errors in determining the heart rate, fractional blood saturation and respiration rate increased by 3.221 %; 2.483 % and 1.906 %, respectively. The results of theoretical and practical studies have a strong pair correlation according to Pearson, the pair correlation coefficients were 0.72, 0.83, 0.76 for the results of measurements of heart rate, fractional blood saturation level and respiratory rate, respectively, which indicates the validity of the adopted simplifi ations in the development of the mathematical model. The obtained results can be used to develop devices for non-invasive diagnostics of the pilot's physiological indicators, functioning directly during the flight.

The GDF15 3′ UTR Polymorphism rs1054564 Is Associated with Diabetes and Subclinical Atherosclerosis

Growth differentiation factor 15 (GDF15) is a stress-response cytokine related to a wide variety of metabolic diseases. However, the impact of GDF15-specific genetic variants on the abovementioned conditions is poorly known. The aim of this study was to assess the impact of selected GDF15 single-nucleotide polymorphisms (SNPs) on metabolic disturbances and subclinical atherosclerosis. A cross-sectional study involving 153 participants of a metabolic patient-based cohort was performed. Three selected SNPs (rs888663, rs1054564 and rs1059369) in a locus on chromosome 19 including the GDF15 gene were genotyped by Polymerase Chain Reaction (PCR), and its relationship with the serum GDF15 levels, health status and clinical variables were analyzed. Of the three SNPs analyzed, only rs1054564 showed different distributions between the healthy volunteers and patients suffering lipid alterations and associated disorders. Accordingly, just the rs1054564 variant carriers showed a significant increase in GDF15 serum levels compared to the wild-type carriers. The group of variant carriers showed a higher frequency of individuals with diabetes, compared to the wild-type carrier group, without showing differences in other metabolic conditions. Additionally, the frequency of individuals with atherosclerotic carotid plaque was higher in the rs1054564 variant carriers than in the wild-type carriers. Logistic regression models identified that the presence of the rs1054564 variant carriers increase the likelihood for both diabetes and carotid plaque independently of confounding factors. Overall, the findings of this study identify the rs1054564 variant as a potential indicator for the likelihood of diabetes and subclinical atherosclerosis.

Novel bias-reduced coherence measure for EEG-based speech tracking in listeners with hearing impairment

In the literature, auditory attention is explored through neural speech tracking, primarily entailing modeling and analyzing electroencephalography (EEG) responses to natural speech via linear filtering. Our study takes a novel approach, introducing an enhanced coherence estimation technique to assess the strength of neural speech tracking. This enables effective discrimination between attended and ignored speech. To mitigate the impact of colored noise in EEG, we address two biases–overall coherence-level bias and spectral peak-shifting bias. In a listening study involving 32 participants with hearing impairment, tasked with attending to competing talkers in background noise, our coherence-based method effectively discerns EEG representations of attended and ignored speech. We comprehensively analyze frequency bands, individual frequencies, and EEG channels. Frequency bands of importance are shown to be delta, theta and alpha, and the important EEG channels are the central. Lastly, we showcase coherence differences across different noise reduction settings implemented in hearing aids (HAs), underscoring our method's potential to objectively assess auditory attention and enhance HA efficacy.

Searching for similarities in the accretion flow of Seyfert 1 galaxies and cataclysmic variables based on the flare profiles of IRAS 13224-3809, 1H 0707-495, Mrk 766, and MV Lyr

We studied the fast variability of three selected active galactic nuclei (AGNs), IRAS\,13224-3809, 1H\,0707-495, and Mrk\,766, and the cataclysmic variable MV\,Lyr, which were observed by the and spacecrafts, respectively. Our goal is to search for the common origin of the variability and to test the so-called sandwich model, in which a geometrically thick corona surrounds a geometrically thin disc. We studied the substructures of the averaged flare profiles. The flare profile method identifies individual flares in the light curve, and averages them. The direct fitting of the profile substructures identified individual characteristic frequencies that are seen in standard power density spectra (PDS) as a break frequency or quasi-periodic oscillation. The credibility of the flare profile substructures is demonstrated by comparison with the autocorrelation function. We found that the flare profiles of AGNs are similar to those of a cataclysmic variable in the low state. We explain this as a consequence of a truncated inner disc in a sandwich model. The same scenario is also able to explain the characteristic break frequencies in X-ray PDS, which are not seen in the optical. We also searched for substructures in the flare profile of IRAS\,13224-3809. In addition to a permanently present main flare, we found that a transient side-lobe appears before the main flare and is only seen in a high-flux period. The complex flare profile of this AGN suggests that an additional source of X-rays appears during the high-flux period. We propose a scenario in which an accretion flow fluctuation enters the sandwich corona and propagates further to some very central part of the accretion disc.

Frequency dependence of reflections on radar landmarks

Purpose. Reducing the dispersion of radar reflections from local objects, with multi-frequency sensing, to solve the problem of orientation by radar reflections from objects. Methodology. Reflections from local objects in the entire frequency range of the radar station (RS) at the same radio engineering position were measured by three independent radars of the same type on different days and at different antenna elevations. The deviation of the radar stations in the position did not exceed 500 meters. Coordinates (azimuth, range) of reflections of several separate local objects were allocated for each radar. The average values of reflections from local objects and their dispersion in the frequency range were calculated. Using various algorithms, individual frequencies were sampled and the reflected signals were averaged at these frequencies. The decrease in the dispersion of the reflected signal from the number of frequencies at which reflections were measured and from the algorithm for selecting these frequencies was investigated. Findings. Averaging the values of reflections from local objects for several frequencies leads to a decrease in dispersion and, as a result, to a more accurate correspondence of the reflected signal level to the geometric size of the local object. The variance decreases most rapidly for a small number of frequencies selected for averaging when selecting frequencies located in an interval of at least 1% relative to each other. Originality. To solve the problem of orientation based on radar reflections from local objects, it is necessary to identify the landmarks selected on a digital terrain model. Due to the fact that local objects (hills) are a collection of many reflectors falling into the allowed volume of the radar, with different levels of reflections and random phases, there may not be radar reflection from a local object at a certain frequency, or it may be very small. In order to unambiguously identify all landmarks, measurements must be carried out at several frequencies. The work has established how many frequencies measurements should be performed at and on what principle these frequencies should be selected. Practical value. The advent of digital terrain models made it possible to solve the problem of terrain orientation by comparing radar reflections from local objects with reflection models based on digital terrain maps. Radar reflection models use mathematical expectations of reflection values, unlike real reflections, which have random deviations in signal levels depending on the operating frequency. Reducing the variance of these deviations increases the accuracy of identifying characteristic local objects (landmarks) used to orient the radar in the absence of data from satellite navigation systems.

Predictors of Successful Weight Loss in Extremely Obese Individuals Undergoing Roux-en-Y Gastric Bypass Surgery.

Roux-en-Y gastric bypass (RYGB) is a standard treatment for severe obesity, but some patients do not achieve the expected success in weight loss. The aim of this study was to evaluate possible predictors of weight loss after RYGB. Sixty-three patients were included. Pre- and postoperative data were collected from medical records, including comorbidities, anthropometry, energy/macronutrient intake, and physical activity level (PAL). Variants in the brain-derived neurotrophic factor (BDNF; rs6265) and lysophospholipase like 1 (LYPLAL1; rs4846567) genes were investigated. Excess weight loss (EWL) >50% was considered to be successful weight loss (SWL). Logistic regression models were used to verify predictor variables. Participants' median preoperative body mass index (BMI) was 53 kg/m2 (interquartile range, 46 to 58). At 12 and 24 months after surgery, EWL was 63% and 67%, and the failure rate was 19% and 16%, respectively. The individuals with insufficient weight loss (IWL) after 12 months had higher preoperative weight, BMI, and overweight. At 24 months, lowest frequency of individuals with SWL in the first year was found in the IWL group. No significant differences were found between the groups in dietary intake and PAL. In the logistic regression, high initial BMI was a predictor of the worst response in both periods, and high initial total weight loss was a predictor of a better response at 24 months. The polymorphism analysis did not show differences between groups in either gene. Lower preoperative BMI and greater weight loss at 12 months were predictors of SWL after RYGB.

The glow of axion quark nugget dark matter

Context. The existence of axion quark nuggets is a potential consequence of the axion field, which provides a possible solution to the charge-conjugation parity violation in quantum chromodynamics. In addition to explaining the cosmological discrepancy of matter-antimatter asymmetry and a visible-to-dark-matter ratio of Ωdark/Ωvisible ≃ 5, these composite compact objects are expected to represent a potentially ubiquitous electromagnetic background radiation by interacting with ordinary baryonic matter. We conducted an in-depth analysis of axion quark nugget-baryonic matter interactions in the environment of the intracluster medium in the constrained cosmological Simulation of the LOcal Web (SLOW). Aims. Here, we aim to provide upper limit predictions on electromagnetic counterparts of axion quark nuggets in the environment of galaxy clusters by inferring their thermal and non-thermal emission spectrum originating from axion quark nugget-cluster gas interactions. Methods. We analyzed the emission of axion quark nuggets in a large sample of 161 simulated galaxy clusters using the SLOW simulation. These clusters are divided into a sub-sample of 150 galaxy clusters, ordered in five mass bins ranging from 0.8 to 31.7 × 1014 M⊙, along with 11 cross-identified galaxy clusters from observations. We investigated dark matter-baryonic matter interactions in galaxy clusters in their present stage at the redshift of z = 0 by assuming all dark matter consists of axion quark nuggets. The resulting electromagnetic signatures were compared to thermal Bremsstrahlung and non-thermal cosmic ray (CR) synchrotron emission in each galaxy cluster. We further investigated individual frequency bands imitating the observable range of the WMAP, Planck, Euclid, and XRISM telescopes for the most promising cross-identified galaxy clusters hosting detectable signatures of axion quark nugget emission. Results. We observed a positive excess in the low- and high-energy frequency windows, where thermal and non-thermal axion quark nugget emission can significantly contribute to (or even outshine) the emission of the intracluster medium (ICM) in frequencies up to νT ≲ 3842.19 GHz and νT ϵ [3.97, 10.99] × 1010GHz, respectively. Emission signatures of axion quark nuggets are found to be observable if CR synchrotron emission of individual clusters is sufficiently low. The degeneracy in the parameters contributing to an emission excess makes it challenging to offer predictions with respect to pinpointing specific regions of a positive axion quark nugget excess; however, a general increase in the total galaxy cluster emission is expected based on this dark matter model. Axion quark nuggets constitute an increment of 4.80% of the total galaxy cluster emission in the low-energy regime of νT ≲ 3842.19 GHz for a selection of cross-identified galaxy clusters. We propose that the Fornax and Virgo clusters represent the most promising candidates in the search for axion quark nugget emission signatures. Conclusions. The results from our simulations point towards the possibility of detecting an axion quark nugget excess in galaxy clusters in observations if their signatures can be sufficiently disentangled from the ICM radiation. While this model proposes a promising explanation for the composition of dark matter, with the potential to have this outcome verified by observations, we propose further changes that are aimed at refining our methods. Our ultimate goal is to identify the extracted electromagnetic counterparts of axion quark nuggets with even greater precision in the near future.

Stellar Models are Reliable at Low Metallicity: An Asteroseismic Age for the Ancient Very Metal-poor Star KIC 8144907

Very-metal-poor stars ([Fe/H] < −2) are important laboratories for testing stellar models and reconstructing the formation history of our galaxy. Asteroseismology is a powerful tool to probe stellar interiors and measure ages, but few asteroseismic detections are known in very-metal-poor stars and none have allowed detailed modeling of oscillation frequencies. We report the discovery of a low-luminosity Kepler red giant (KIC 8144907) with high signal-to-noise ratio oscillations, [Fe/H] = −2.66 ± 0.08 and [α/Fe] = 0.38 ± 0.06, making it by far the most metal-poor star to date for which detailed asteroseismic modeling is possible. By combining the oscillation spectrum from Kepler with high-resolution spectroscopy, we measure an asteroseismic mass and age of 0.79 ± 0.02(ran) ± 0.01(sys) M ⊙ and 12.0 ± 0.6(ran) ± 0.4(sys) Gyr, with remarkable agreement across different codes and input physics, demonstrating that stellar models and asteroseismology are reliable for very-metal-poor stars when individual frequencies are used. The results also provide a direct age anchor for the early formation of the Milky Way, implying that substantial star formation did not commence until redshift z ≈ 3 (if the star formed in situ) or that the Milky Way has undergone merger events for at least ≈12 Gyr (if the star was accreted by a dwarf satellite merger such as Gaia-Enceladus).

Evaluating the accuracy of a self-administered smartphone hearing test application in a geriatric population.

As the global population ages, hearing loss becomes increasingly prevalent, and is associated with neurocognitive and psychiatric comorbidities, impacting quality of life. Early screening and timely intervention might prevent or delay cognitive decline, a gap in care that can potentially be addressed by self-administered smartphone hearing tests. This study aims to evaluate the accuracy of Mimi™ (Berlin, Germany), a commercially available self-administered smartphone hearing test compared to pure tone audiogram (PTA) in terms of both hearing levels and hearing thresholds in our local geriatric population > 65 years-old. Fifty-two participants above 65 years of age requiring conventional audiograms were recruited from a National Referral University Hospital Otolaryngology clinic from March to June 2022. All participants were administered the conventional PTA tests in a sound-proof booth conducted by audiology technicians followed by Mimi™ Hearing Test in a quiet clinic room. Comparisons between the hearing levels of both tests were analyzed using Spearman's rank correlation coefficient, Bland-Altman plots and Gwet's Kappa which looked at concordance. Hearing thresholds were then analysed using the Wilcoxon signed rank (SR) test. Mimi™ showed strong to very strong correlation with good agreement compared to readings obtained from formal PTA. Concordance in determining hearing loss also showed substantial to almost perfect agreement at each individual frequency, with values of kappa falling between 0.735-0.857. In terms of thresholds, there were no significant differences in thresholds given by both tests except for 2.0 kHz, HFPTA and 4FPTA (p < 0.05). Mimi™ serves as a good screening tool for detection of moderate hearing loss for early pickup and treatment except at higher frequencies. The smartphone hearing test is also less accurate in determining the extent of hearing loss and formal PTA after hearing loss is detected on screening should still be standard of care.

Melatonin receptor 1A variants as genetic cause of idiopathic osteoporosis.

Idiopathic osteoporosis (IOP) is a rare form of early-onset osteoporosis diagnosed in patients with no known metabolic or hormonal cause of bone loss and unknown pathogenesis. Patients with IOP commonly report both childhood fractures and family history of osteoporosis, raising the possibility of genetic etiologies of IOP. Whole-exome sequencing analyses of different IOP cohorts identified multiple variants in melatonin receptor 1A (MTNR1A) with a potential pathogenic outcome. A rare MTNR1A variant (rs374152717) was found in members of an Ashkenazi Jewish family with IOP, and an MTNR1A variant (rs28383653) was found in a nonrelated female IOP cohort (4%). Both variants occur at a substantially higher frequency in Ashkenazi Jewish individuals than in the general population. We investigated consequences of the heterozygous (rs374152717) variant [MTNR1Ac.184+1G>T (MTNR1Ac.184+1G>T)] on bone physiology. A mouse model of the human rs374152717 variant reproduced the low bone mass (BM) phenotype of young-adult patients with IOP. Low BM occurred because of induction of senescence in mutant osteoblasts followed by compromised differentiation and function. In human cells, introduction of rs374152717 led to translation of a nonfunctional protein and subsequent dysregulation of melatonin signaling. These studies provide evidence that MTNR1A mutations entail a genetic etiology of IOP and establish the rs374152717 variant as a loss-of-function allele that impairs bone turnover by inducing senescence in osteoblasts. The higher prevalence of the MTNR1A variants identified in IOP cohorts versus the general population indicates a greater risk of IOP in those carrying these variants, especially Ashkenazi Jewish individuals bearing the rs374152717 variant.

Development of a Quality Control System Using Modal Analysis to Evaluate a Multi-Point Projection Welding Process.

The article presents the results of the development and research regarding the application of modal analysis to the evaluation of a multi-point projection welding process. The quality control system is based on the information provided by modal analysis for the entire welding station after the previously completed welding process. The research is carried out due to the lack of an effective method for assessing the course of the multi-spot projection welding process in the case of a single current circuit passing through many points at the same time. A study of the applicability of modal analysis in investigating the quality of a multipoint joint was conducted for four DIN 928 nuts welded to a steel profile. The aim of the study was to determine the influence of weld defects on the displacement of resonant frequencies. To realize the objective, the dynamic properties of the entire welding station, including the sample in the frequency domain, were investigated. In the first stage of the study, a finite element method was used to perform modal analysis and examine the form of vibrations for the individual natural frequencies of the welding fixture including the sample. Then, quality verification using the dynamic resistance method was performed, which was compared later with the modal approach. The last stage of the study was to conduct modal analysis in the frequency domain to verify the numerical studies.

The Prevalence of Various Stages of Heart Failure in Individuals Over 40 Years Old: The Findings from Yazd Health Study

identification and prevention of HF. Therefore, this study aims to evaluate the prevalence of various stages of HF in individuals over 40 years old within a large population of Iranian adults. Methods: In this descriptive cross-sectional study, a random sub sample of Yazd Health Study (YaHS) participants aged 40-70 years was evaluated. History and clinical examination of the patients was conducted by a cardiologist and then, the participants underwent echocardiography to determine the stages of heart failure. Results: Among 410 Yazd population -the representative sample with mean age 58.0±9.2 years, 183 patients (44.6%) were in stage 0, 121 (29.5%) in stage A, 77(18.8%) in stage B, and 29 (7.1%) in stage C heart failure. No individuals were in stage D. There was a significant difference between the frequency of individuals with different stages of HF in terms of diabetes, hypertension, obesity, and history of ischemic heart disease (p&lt;0.05). In addition, the frequency of HF increased in the age group &gt;60 years and the obesity group (p&lt;0.05). Conclusion: According to these, about half of the patients with HF were in stage A and B. Therefore, appropriate measures are needed to identify these groups of patients, especially individuals with risk factors of diabetes, hypertension, obesity and those over 60 years to prevent the progression of the disease to higher stages which lead to poorer outcome.

Early selection for rust resistance in eucalypt progenies and implications for other traits of interest in tree breeding

Planting of resistant clones is the main control strategy for rust caused by Austropuccinia psidii on eucalypts in Brazil. Phenotyping for resistance to rust is performed at the last stage of the breeding programme on genetic material preselected for growth and industrial traits, which therefore may include susceptible genotypes. An alternative way to increase the frequency of resistant individuals in the breeding population is to perform resistance phenotyping during the initial stages of the programme. However, the impact of this approach on other characteristics considered as priority in the selection of genetic material should be assessed. In this study, we evaluated whether early selection for resistance to rust influenced total diameter at breast height (DBH), height (TH), average annual increment (IMA) and basic wood density (BWD), which are important selection criteria in eucalypt breeding. For this, a total of 6 703 plants from 70 full-sib progenies of Eucalyptus grandis, E. urophylla and hybrids of these species were phenotyped for rust resistance before transplanting, under controlled conditions, and again at seven months after transplanting, under field conditions and natural infection. Subsequently, the breeding population was evaluated for BWD indirectly through pilodyn penetration at 24 months after planting, and for DBH, TH and MAI at 37 months. Considering the final phenotype, 25.3% individuals were classified as resistant and 74.7% were susceptible to rust. Comparative genetic analyses between resistant and susceptible individuals showed that selection for resistance, performed early, did not influence DBH, TH, MAI or BWD traits. Thus, the early selection of resistant genotypes speeds up the exclusion of susceptible genotypes, saving time and resources in the development of new commercial clones without interfering with other important traits for tree breeding.

6846 Rare Variants in SEMA3A in Individuals with Constitutional Delay of Puberty (CDP)

Abstract Disclosure: W. He: None. E.C. Schafer: None. R. Brauner: None. A. Delaney: None. L. Dunkel: None. R. Grinspon: None. J.E. Hall: None. J.N. Hirschhorn: None. S. Howard: None. A. Latronico: None. A.A. Jorge: None. K. McElreavey: None. V. Mericq: None. P.M. Merino: None. M.R. Palmert: None. R.A. Rey: None. R.C. Rezende: None. S.B. Seminara: None. N. Shaw: None. T. Delayed Puberty Genetics Consortium: None. Y. Chan: None. Background: Constitutional delay of puberty (CDP), also known as self-limited delayed puberty, refers to late onset of puberty with relatively normal progression afterward. In contrast, idiopathic hypogonadotropic hypogonadism (IHH) results in a long-lasting defect in reproductive endocrine activity. Both CDP and IHH are highly heritable and are sometimes observed in different family members in the same pedigree. Previous work by our group and others has suggested genetic overlap between the two conditions. In this study, we aimed to identify specific IHH-related genes that are also genetic causes of CDP. Methods: The Delayed Puberty Consortium assembled exome data for 233 individuals of diverse ancestries with CDP, with onset of puberty between 12 and 18 y in girls and between 13.5 and 18 y in boys. For control data, we used exome sequencing data from gnomAD v2.1.1 (n=125,748). After data harmonization and quality control, we used a modification of the “TRAPD” method to perform gene-based burden testing for 63 genes associated with IHH. We analyzed rare variants (minor allele frequency &amp;lt; 0.01) with high impact (premature stop, frameshift, start-lost, stop-lost) in all individuals across ancestries (n=233), as allele frequencies for high-impact variants are unlikely to vary widely across populations. We also analyzed rare variants with moderate impact (missense, inframe insertions/deletions) predicted to be deleterious by the Primate AI algorithm (score &amp;gt;0.6) in non-Finnish European (NFE) individuals with CDP (n=99), then meta-analyzed the results for high- and moderate-impact variants. We considered p-values &amp;lt; 7.9 x 10-4 (0.05 with Bonferroni adjustment for 63 genes) significant. Results: Of the 63 genes analyzed, SEMA3A (which encodes semaphorin-3A) exhibited significant enrichment for moderate-impact variants in the NFE CDP cohort compared to controls (variant frequency in CDP vs control: 0.064 vs 0.0076, p = 1.3 x 10-4) and in the meta-analysis of both high- and moderate-impact variants (p = 3.5 x 10-6). Novel SEMA3A variants identified exclusively in CDP individuals but not in controls were a frameshift variant, p.F546fsX2, and a missense variant, I252R. Also, three missense variants in SEMA3A were observed at a higher frequency in NFE CDP individuals compared with controls: p.R66T, p.V461A, and p.T717I. No other IHH genes showed significant enrichment of rare variants in the CDP cohort. Conclusion: Rare variants in SEMA3A contribute to both CDP and IHH. While functional studies are required to assess the effects of these specific variants on protein function, previous in vitro studies of similar SEMA3A variants demonstrated defects in secretion or signaling activity. Subsequent studies employing individual-level ancestry-matched controls and larger CDP cohorts are planned to identify additional genes that contribute to CDP. Presentation: 6/1/2024

12330 Rare Variants in SEMA3A in Individuals with Constitutional Delay of Puberty (CDP)

Abstract Disclosure: W. He: None. E.C. Schafer: None. R. Brauner: None. A. Delaney: None. L. Dunkel: None. R. Grinspon: None. J.E. Hall: None. J.N. Hirschhorn: None. S. Howard: None. A. Latronico: None. A.A. Jorge: None. K. McElreavey: None. V. Mericq: None. P.M. Merino: None. M.R. Palmert: None. R.A. Rey: None. R.C. Rezende: None. S.B. Seminara: None. N. Shaw: None. T. Delayed Puberty Genetics Consortium: None. Y. Chan: None. Background: Constitutional delay of puberty (CDP), also known as self-limited delayed puberty, refers to late onset of puberty with relatively normal progression afterward. In contrast, idiopathic hypogonadotropic hypogonadism (IHH) results in a long-lasting defect in reproductive endocrine activity. Both CDP and IHH are highly heritable and are sometimes observed in different family members in the same pedigree. Previous work by our group and others has suggested genetic overlap between the two conditions. In this study, we aimed to identify specific IHH-related genes that are also genetic causes of CDP. Methods: The Delayed Puberty Consortium assembled exome data for 233 individuals of diverse ancestries with CDP, with onset of puberty between 12 and 18 y in girls and between 13.5 and 18 y in boys. For control data, we used exome sequencing data from gnomAD v2.1.1 (n=125,748). After data harmonization and quality control, we used a modification of the “TRAPD” method to perform gene-based burden testing for 63 genes associated with IHH. We analyzed rare variants (minor allele frequency &amp;lt; 0.01) with high impact (premature stop, frameshift, start-lost, stop-lost) in all individuals across ancestries (n=233), as allele frequencies for high-impact variants are unlikely to vary widely across populations. We also analyzed rare variants with moderate impact (missense, inframe insertions/deletions) predicted to be deleterious by the Primate AI algorithm (score &amp;gt;0.6) in non-Finnish European (NFE) individuals with CDP (n=99), then meta-analyzed the results for high- and moderate-impact variants. We considered p-values &amp;lt; 7.9 x 10-4 (0.05 with Bonferroni adjustment for 63 genes) significant. Results: Of the 63 genes analyzed, SEMA3A (which encodes semaphorin-3A) exhibited significant enrichment for moderate-impact variants in the NFE CDP cohort compared to controls (variant frequency in CDP vs control: 0.064 vs 0.0076, p = 1.3 x 10-4) and in the meta-analysis of both high- and moderate-impact variants (p = 3.5 x 10-6). Novel SEMA3A variants identified exclusively in CDP individuals but not in controls were a frameshift variant, p.F546fsX2, and a missense variant, I252R. Also, three missense variants in SEMA3A were observed at a higher frequency in NFE CDP individuals compared with controls: p.R66T, p.V461A, and p.T717I. No other IHH genes showed significant enrichment of rare variants in the CDP cohort. Conclusion: Rare variants in SEMA3A contribute to both CDP and IHH. While functional studies are required to assess the effects of these specific variants on protein function, previous in vitro studies of similar SEMA3A variants demonstrated defects in secretion or signaling activity. Subsequent studies employing individual-level ancestry-matched controls and larger CDP cohorts are planned to identify additional genes that contribute to CDP. Presentation: 6/1/2024

Realistic Uncertainties for Fundamental Properties of Asteroseismic Red Giants and the Interplay between Mixing Length, Metallicity, and νmax

Asteroseismic modeling is a powerful way to derive stellar properties. However, the derived quantities are limited by built-in assumptions used in stellar models. This work presents a detailed characterization of stellar model uncertainties in asteroseismic red giants, focusing on the mixing-length parameter α MLT, the initial helium fraction Y init, the solar abundance scale, and the overshoot parameters. First, we estimate error floors due to model uncertainties to be ≈0.4% in mass, ≈0.2% in radius, and ≈17% in age, primarily due to the uncertain state of α MLT and Y init. The systematic uncertainties in age exceed typical statistical uncertainties, suggesting the importance of their evaluation in asteroseismic applications. Second, we demonstrate that the uncertainties from α MLT can be entirely mitigated by direct radius measurements or partially through νmax . Utilizing radii from Kepler eclipsing binaries, we determined the α MLT values and calibrated the α MLT–[M/H] relation. The correlation observed between the two variables is positive, consistent with previous studies using 1D stellar models, but in contrast with outcomes from 3D simulations. Third, we explore the implications of using asteroseismic modeling to test the νmax scaling relation. We found that a perceived dependency of νmax on [M/H] from individual frequency modeling can be largely removed by incorporating the calibrated α MLT–[M/H] relation. Variations in Y init can also affect νmax predictions. These findings suggest that νmax conveys information not fully captured by individual frequencies, and that it should be carefully considered as an important observable for asteroseismic modeling.

Intraspecific body size variation across distributional moments reveals trait filtering processes.

Natural populations are composed of individuals that vary in their morphological traits, timing and interactions. The distribution of a trait can be described by several dimensions, or mathematical moments-mean, variance, skew and kurtosis. Shifts in the distribution of a trait across these moments in response to environmental variation can help to reveal which trait values are gained or lost, and consequently how trait filtering processes are altering populations. To examine the role and drivers of intraspecific variation within a trait filtering framework, we investigate variation in body size among five wild bumblebee species in the Colorado Rocky Mountains. First, we examine the relationships between environmental factors (climate and floral food resources) and body size distributions across bumblebee social castes to identify demographic responses to environmental variation. Next, we examine changes in the moments of trait distributions to reveal potential mechanisms behind intraspecific shifts in body size. Finally, we examine how intraspecific body size variation is related to diet breadth and phenology. We found that climate conditions have a strong effect on observed body size variation across all distributional moments, but the filtering mechanism varies by social caste. For example, with earlier spring snowmelt queens declined in mean size and became negatively skewed and more kurtotic. This suggests a skewed filter admitting a greater frequency of small individuals. With greater availability of floral food resources, queens increased in mean size, but workers and males decreased in size. Observed shifts in body size variation also correspond with variation in diet breadth and phenology. Populations with larger average body size were associated with more generalized foraging in workers of short-tongued species and increased specialization in longer-tongued workers. Altered phenological timing was associated with species- and caste-specific shifts in skew. Across an assemblage of wild bumblebees, we find complex patterns of trait variation that may not have been captured if we had simply considered mean and variance. The four-moment approach we employ here provides holistic insight into intraspecific trait variation, which may otherwise be overlooked and reveals potential underlying filtering processes driving such variation within populations.

Resting-state EEG spectral and fractal features in dementia with Lewy bodies with and without visual hallucinations

ObjectiveComplex visual hallucinations (VH) are a core feature of dementia with Lewy bodies (DLB), though they may not occur in all patients. Power spectral density (PSD) analysis of resting-state EEG (rs-EEG) shows associations between some frequency bands (e.g., θ), individual alpha frequency (IAF) and VH. However, new tools that improve early differential diagnosis and symptom-based stratification with higher sensitivity and specificity, even within the DLB population, are desirable. We aimed to assess differences in rs-EEG data between DLB patients with VH (DLB-VH+) and without VH (DLB-VH-), comparing innovative non-linear approaches with more traditional linear ones. MethodsWe retrospectively analyzed rs-EEG recordings of DLB-VH+, DLB-VH-, Alzheimer’s disease patients and age-matched healthy controls. EEG was analyzed using the nonlinear Higuchi’s Fractal Dimension (FD) measure, and the results were compared with those of entropy and standard linear methods based on PSD and IAF. ResultsOnly the FD measure could discriminate between DLB-VH+ and DLB-VH-. ConclusionsIn conclusion, rs-EEG differences between DLB-VH+ and DLB-VH- are better characterized by FD analysis than by a more traditional power spectrum approach. SignificanceThis suggests that the presence of complex VH is associated with less complex brain dynamics at rest, as reflected by the FD measure.

Investigating the synergistic neuromodulation effect of bilateral rTMS and VR brain-computer interfaces training in chronic stroke patients

Objective.Stroke is a major cause of adult disability worldwide, resulting in motor impairments. To regain motor function, patients undergo rehabilitation, typically involving repetitive movement training. For those who lack volitional movement, novel technology-based approaches have emerged that directly involve the central nervous system, through neuromodulation techniques such as transcranial magnetic stimulation (TMS), and closed-loop neurofeedback like brain-computer interfaces (BCIs). This, can be augmented through proprioceptive feedback delivered many times by embodied virtual reality (VR). Nonetheless, despite a growing body of research demonstrating the individual efficacy of each technique, there is limited information on their combined effects.Approach.In this study, we analyzed the Electroencephalographic (EEG) signals acquired from 10 patients with more than 4 months since stroke during a longitudinal intervention with repetitive TMS followed by VR-BCI training. From the EEG, the event related desynchronization (ERD) and individual alpha frequency (IAF) were extracted, evaluated over time and correlated with clinical outcome.Main results.Every patient's clinical outcome improved after treatment, and ERD magnitude increased during simultaneous rTMS and VR-BCI. Additionally, IAF values showed a significant correlation with clinical outcome, nonetheless, no relationship was found between differences in ERD pre- post- intervention with the clinical improvement.Significance.This study furnishes empirical evidence supporting the efficacy of the joint action of rTMS and VR-BCI in enhancing patient recovery. It also suggests a relationship between IAF and rehabilitation outcomes, that could potentially serve as a retrievable biomarker for stroke recovery.