Relative Ages Research Articles

Predicting systemic diseases in fundus images: systematic review of setting, reporting, bias, and models' clinical availability in deep learning studies.

Analyzing fundus images with deep learning techniques is promising for screening systematic diseases. However, the quality of the rapidly increasing number of studies was variable and lacked systematic evaluation. To systematically review all the articles that aimed to predict systemic parameters and conditions using fundus image and deep learning, assessing their performance, and providing suggestions that would enable translation into clinical practice. Two major electronic databases (MEDLINE and EMBASE) were searched until August 22, 2023, with keywords 'deep learning' and 'fundus'. Studies using deep learning and fundus images to predict systematic parameters were included, and assessed in four aspects: study characteristics, transparent reporting, risk of bias, and clinical availability. Transparent reporting was assessed by the TRIPOD statement, while the risk of bias was assessed by PROBAST. 4969 articles were identified through systematic research. Thirty-one articles were included in the review. A variety of vascular and non-vascular diseases can be predicted by fundus images, including diabetes and related diseases (19%), sex (22%) and age (19%). Most of the studies focused on developed countries. The models' reporting was insufficient in determining sample size and missing data treatment according to the TRIPOD. Full access to datasets and code was also under-reported. 1/31(3.2%) study was classified as having a low risk of bias overall, whereas 30/31(96.8%) were classified as having a high risk of bias according to the PROBAST. 5/31(16.1%) of studies used prospective external validation cohorts. Only two (6.4%) described the study's calibration. The number of publications by year increased significantly from 2018 to 2023. However, only two models (6.5%) were applied to the device, and no model has been applied in clinical. Deep learning fundus images have shown great potential in predicting systematic conditions in clinical situations. Further work needs to be done to improve the methodology and clinical application.

Geometry, kinematics, and mechanics of the interaction between strike-slip and normal faults in active rifts: An example from the Quaternary-active Kane Springs Wash fault zone, Nevada, USA

Abstract The interactions among dip-slip and strike-slip faults are critical features in rift segmentation, including strain and slip transfer between faults of different rift segments. Here, we focused on the influence of factors such as fault and fracture geometries, kinematics, and local stress fields on the interaction and linkage of synchronous strike-slip and normal faults. Well-exposed faults along the tectonically active boundary between the central and northern Basin and Range provided for both reliable geometric data and consideration of rift segment development. We documented relative ages and distributions of Quaternary deposits, scarps, and geometries of three ~20–65-km-long Quaternary faults: the N-striking, normal Coyote Spring fault; the ENE-striking, left-lateral Kane Springs Wash fault; and the N-striking, normal Wildcat Wash fault. The normal faults bend to accommodate slip-type differences across linkage zones, with the strike-slip fault and local processes influencing interactions. Influenced by the local stress field of the Kane Springs Wash fault, the Coyote Spring fault bends SE as it approaches and links to the Kane Springs Wash fault. Influenced by the off-fault or process-zone fractures of the Kane Springs Wash fault, the Wildcat Wash fault bends NE and links with the Kane Springs Wash fault. The Kane Springs Wash fault continues beyond the normal fault terminations, suggesting slip transfer between them via the Kane Springs Wash fault. These relations and the ages of offset units suggest that activity on the faults was approximately synchronous despite slip-type differences. Consequently, in slip transfer, the local strike-slip stress environment and off-fault fractures influenced the geometry of the normal fault terminations; the strike-slip fault formed a boundary to dip-slip fault propagation; and this boundary facilitated kinematic and geodetic segmentation, forming a Basin and Range rift segment boundary.

Spatial and temporal characterization of the rich fraction of plastid DNA present in the nuclear genome of Moringa oleifera reveals unanticipated complexity in NUPTs´ formation

BackgroundBeyond the massive amounts of DNA and genes transferred from the protoorganelle genome to the nucleus during the endosymbiotic event that gave rise to the plastids, stretches of plastid DNA of varying size are still being copied and relocated to the nuclear genome in a process that is ongoing and does not result in the concomitant shrinking of the plastid genome. As a result, plant nuclear genomes feature small, but variable, fraction of their genomes of plastid origin, the so-called nuclear plastid DNA sequences (NUPTs). However, the mechanisms underlying the origin and fixation of NUPTs are not yet fully elucidated and research on the topic has been mostly focused on a limited number of species and of plastid DNA.ResultsHere, we leveraged a chromosome-scale version of the genome of the orphan crop Moringa oleifera, which features the largest fraction of plastid DNA in any plant nuclear genome known so far, to gain insights into the mechanisms of origin of NUPTs. For this purpose, we examined the chromosomal distribution and arrangement of NUPTs, we explicitly modeled and tested the correlation between their age and size distribution, we characterized their sites of origin at the chloroplast genome and their sites of insertion at the nuclear one, as well as we investigated their arrangement in clusters. We found a bimodal distribution of NUPT relative ages, which implies NUPTs in moringa were formed through two separate events. Furthermore, NUPTs from every event showed markedly distinctive features, suggesting they originated through distinct mechanisms.ConclusionsOur results reveal an unanticipated complexity of the mechanisms at the origin of NUPTs and of the evolutionary forces behind their fixation and highlight moringa species as an exceptional model to assess the impact of plastid DNA in the evolution of the architecture and function of plant nuclear genomes.

Multimodal analysis of disease onset in Alzheimer’s disease using Connectome, Molecular, and genetics data

Alzheimer’s disease (AD) and its related age at onset (AAO) are highly heterogeneous, due to the inherent complexity of the disease. They are affected by multiple factors, such as neuroimaging and genetic predisposition. Multimodal integration of various data types is necessary; however, it has been nontrivial due to the high dimensionality of each modality. We aimed to identify multimodal biomarkers of AAO in AD using an extended version of sparse canonical correlation analysis, in which we integrated two imaging modalities, functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), and genetic data in the form of single-nucleotide polymorphisms (SNPs) obtained from the Alzheimer’s disease neuroimaging initiative database. These three modalities cover low-to-high-level complementary information and offer multiscale insights into the AAO. We identified multivariate markers of AAO in AD using fMRI, PET, and SNP. Furthermore, the markers identified were largely consistent with those reported in the existing literature. In particular, our serial mediation analysis suggests that genetic variants influence the AAO in AD by indirectly affecting brain connectivity by mediation of amyloid-beta protein accumulation, supporting a plausible path in existing research. Our approach provides comprehensive biomarkers related to AAO in AD and offers novel multimodal insights into AD.

Historical and genetic generalization of ideas of formation qualities of service leadership

The article reveals the genesis of the ideas of the formation of service leadership at various stages of the development of human civilization and analyzes the most modern works devoted to the training of leaders, both Ukrainian and foreign authors. It is emphasized that with the emergence of the states of the Ancient East, ancient thinkers emphasized that a true leader knows truth and falsehood, teaches his subjects and leads them from benevolent motives. In the days of Antiquity, it was believed that there will always be intelligent and knowledgeable people on the rowing waves, and happiness can be achieved if kings and lords begin to philosophize nobly and persistently. It is argued that in the context of the Roman pedagogical tradition, an important component of the content of training leaders was the formation of oratorical skills. It is emphasized that during the Middle Ages, attention was paid to the formation of spiritual qualities, moral skills, the leader's faith in God and his observance of God's Commandments. At the same time, it is emphasized that during the Renaissance there was a turn to the principles and ideals of the ancient cultural heritage, and in the New Age and the Age of Enlightenment, feudal relations, the church and absolutism were condemned, and the ideas of education and philanthropism were promoted in the education of leaders. It is noted that in modern times, thinkers searched for new approaches, concepts for the formation of service leadership qualities in line with reformist pedagogy, the movement of a new school, which was created by the elite to train industry managers. At the same time, it is noted that in Independent Ukraine, significant attention was paid to the formation of leadership qualities in the fields of pedagogy, psychology, leadership, management, history, and social psychology.

Influence of Relative Humidity and Aging on Morphology and Chemical Composition on Biomass Burning Particle

Influence of Relative Humidity and Aging on Morphology and Chemical Composition on Biomass Burning Particle

Preservation properties of some relative aging classes under $ (n-k+1) $-out-of-$ n $ systems

Preservation properties of some relative aging classes under $ (n-k+1) $-out-of-$ n $ systems

Acil servise kabul edilen travmalı hastaların yakınlarının yaşadıkları kaygı

Introduction: Emergency departments, which are the busiest and most complex units of hospitals, are areas where multidisciplinary teamwork is performed. Patients and their relatives admitted to emergency departments in an unprepared manner because of traumas face many uncertainties. Aim: The aim of the study was to determine the anxiety levels of relatives of patients admitted to emergency departments with trauma. Material and Methods: This descriptive study was conducted in the emergency department of a university hospital with the participation of a total of 97 patient relatives between December 2020 and April 2021. Data were collected using Information form and State Anxiety Inventory. Results: The mean age of the patient relatives was 35.1±8.4, and 54.6% of the patient relatives were men, and 55.7% were undergraduates. The mean State Anxiety Inventory score of patient relatives was found to be 37.3±6.3. It was also found that 63.9% had mild anxiety, and 36.1% had moderate anxiety levels. It was determined that the anxiety of the relatives of the patients varied according to the positive alcohol test results and the type of shift in which they were admitted (p < 0.05). Conclusion and suggestions: It was determined that the patient relatives admitted to the emergency department with traumas experienced mild anxiety during the first 24 hours after admission. Training should be continued to support the skills of emergency department staff in patient communication and psychosocial support, and patient relatives should be informed about the process.

Platinum and microspherule peaks as chronostratigraphic markers for onset of the Younger Dryas at Wakulla Springs, Florida

Anomalous peak abundances of platinum and Fe-rich microspherules with high-temperature minerals have previously been demonstrated to be a chronostratigraphic marker for the lower Younger Dryas Boundary (YDB) dating to 12.8 ka. This study used Bayesian analyses to test this hypothesis in multiple sequences (units) of sandy, weakly stratified sediments at Wakulla Springs, Florida. Our investigations included platinum geochemistry, granulometry, optically stimulated luminescence (OSL) dating, and culturally dated lithics. In addition, sediments were analyzed using scanning electron microscopy and energy dispersive x-ray spectroscopy to investigate dendritic, iron-rich microspherules previously identified elsewhere in peak abundances at the onset of the Younger Dryas (YD) cool climatic episode. Our work has revealed this abundance peak in platinum and dendritic spherules in five sediment sequences at Wakulla Springs. A YDB age of ~ 12.8 ka for the platinum and spherule chronostratigraphic datum in these Wakulla Springs sequences is consistent with the archaeological data and OSL dating. This study confirms the utility of this YDB datum layer for intersequence correlation and for assessing relative ages of Paleoamerican artifacts, including those of likely Clovis, pre-Clovis, and post-Clovis age and their possible responses to environmental changes known to have occurred during the Younger Dryas cool climatic episode.

Pharmacological Activities of Reishi (Ganoderma Lucidum): Potent Medicinal Mushroom

Medicinal mushroom, Ganoderma lucidum is a white rot mushroom used in medicinal properties and economic importance. It contains a wide variety of bioactive molecules, which have been proved to have several therapeutically properties to control various diseases and it has toxic effects on humans. However, broad spectrum of its pharmacological actions have been established which include immunomodulation, anticancer, ant diabetic, antioxidant, anti-inflammatory, antimicrobial properties and estrogenic activity. Therefore, in this review particular focus on assess the components of biologically active compounds, pharmacological activity, economical importance, and toxicity of Ganoderma lucidum medicinal mushroom. G. lucidum biological active compounds might be a valuable constituent for the treatment of sex-hormone related aging ailments such as osteoporosis. Various animal studies have been carried out on G. lucidum water and ethanol extracts and protective effects toward acute hepatitis in rat and mice have been reported. Immunomodulatory and anti-inflammatory activities of G. lucidum recommend potential application in the treatment of autoimmune disorder like rheumatoid arthritis Ganoderma lucidum has a significant result on the cardiovascular system, such as reduce blood cholesterol, triglyceride level and blood pressure. Benign prostatic hyperplasia (BPH) is one of the common widespread disease, symptoms are seen usually in older men age group. Ganoderma lucidum has a significant result on the cardiovascular system, such as reduce blood cholesterol, triglyceride level and blood pressure.

Magmatism at an ultra-slow spreading rift: high-resolution geomorphological studies of a Red Sea Rift segment in Hadarba Deep

The mid-ocean rift in the Red Sea is one of the youngest rifting systems on Earth. Only recently, state-of-the-art methods and modern deep-sea instruments have been used to explore this young and unique volcanic system. During the first autonomous underwater vehicle surveys of the Red Sea Rift in Spring 2022, we collected multibeam bathymetry, backscatter, sub-bottom profiler data, and water column data over a 9 km long ridge segment in the Hadarba Deep between 22.49°N and 22.56°N to investigate the volcano-tectonic processes of this ultra-slow spreading segment (12 mm/year spreading rate). The high-resolution hydroacoustic data was used to (1) delineate and quantify the geometry of tectonic structures and individual lava flows, (2) define lava flow morphology and eruption style, (3) estimate relative ages of flows and features, and (4) retrace the evolution of the volcanic activity. In addition, the geochemistry of several young lava flows provides information on the relation between the different magma that supply these eruptions. About 90 eruptive units with variable sedimentary cover have been identified within the 43 km2mapped region. The oldest lava flows are buried under 3 to 4.2 m of sediment, indicating ages of up to ~30 ka based on average sedimentation rate estimates (~14 cm/ka), while the youngest eruptions are covered by<10 cm of sediment, and are thus younger than 700 years. Three volcanic phases have been identified based on changes in flow morphology and distribution, and tectonic pattern. All three axial phases have an average eruptive frequency of ~100-250 years. The segment displays an overall low tectonic extension (<10% of the total extension) and low vertical offset. Our geomorphological maps, analyses, and statistics reveal a moderately faulted, ultra-slow spreading MOR segment in the Red Sea with a surprisingly large amount of magmatic extension, implying that the segment has been underlined by a large magma supply for at least 15 ka. All these observations provide valuable implications for the formation history of the Red Sea Rift and the formation of ultra-slow spreading crust.

Investigating Genetic and Environmental Substrates of the Relationship between Positive Mental Health and Biological Aging-A Study Protocol.

The Italian National Institute of Health (Istituto Superiore di Sanità) funded a 30-month project (July 2021-January 2024) to conduct a twin study of the relationships between Positive Mental Health (PMH) and cellular longevity. Only a few previous studies have focused on the biomarkers of aging in relation to psychological well-being, and none of them exploited the potential of the twin design. In this project, following the standard procedures of the Italian Twin Registry (ITR), we aim to recruit 200 adult twin pairs enrolled in the ITR. They are requested to complete a self-report questionnaire battery on PMH and to undergo a blood withdrawal for the assessment of aging biomarkers, i.e., telomere length and mitochondrial DNA functionality. The association between psychological and aging biomarker measures will be assessed, controlling for genetic and familial confounding effects using the twin study design. Biomarker assays are underway. Once data are available for the total study sample, statistical analyses will be performed. The project's results may shed light on new mechanisms underlying the mind-body connection and may prove helpful to promote psychological well-being in conjunction with biological functioning.

Ground-penetrating radar (GPR) survey and spatial analysis of the George and Addie Giddens Cemetery, Opelika, Alabama

ABSTRACT Interest in locating and preserving the cemeteries of enslaved African Americans has increased the need for new methodologies coupled with efficient, noninvasive geophysical techniques, such as ground-penetrating radar (GPR). The southeast United States, where many of such sites are located, provides many challenges to using GPR due to its humid climate and abundant vegetation, which deteriorates burial remains, disguises burial shafts, and forms physical obstacles to GPR surveys. These challenges make it difficult for GPR alone to locate caskets or burial shafts. To address these issues, this study uses GPR combined with an innovative spatial and observational methodology to locate burials in a humid climate and determine their burial conditions. These mixed methods led to the location of 129 potential graves. Knowing the spatial distribution of burial features provides a context for analyzing the relative burial ages and decay rates within the cemetery site.

Biostratigraphy of calcareous nannofossils and their distribution in Tonasa Formation, Mallasoro area Jeneponto, South Sulawesi

The age studies of the Tonasa Formation have been carried out from various relative ages, including using large foraminifera, small foraminifera, and nannofossil. Field and laboratory data were collected to observe the age and distribution of nannofossils in the study area. The results of observations from nannofossils in the Mallasoro section of the Jeneponto area are as many as 20 species were identified and examined in three markers of Sphenolithus pseudoradians (NP.22-NP.24), and the Last Occurrence of Dictyococcites scrippsae (NP.25-NN. 1). The age zonation of Tonasa Formation in this area is determined from the three datums is the Late Oligocene to Early Miocene (NP. 21 – NN.1) or correlated to CP.16c – CP.19a. The nannofossil abundances are distributed from bottom to top of the section is common to a few species, they are Cyclicargolithus floridanus, Sphenolithus moriformis, and Sphenolithus predistentus, respectively. Then followed by Zygrhabilithus bijugatus, Discoaster deflandrei, Dictyococcites scrippsae, and Coccolithus pelagicus in rare to present distributions and the others are present to single.

Assessing co-diversification in host-associated microbiomes.

When lineages of hosts and microbial symbionts engage in intimate interactions over evolutionary timescales, they can diversify in parallel (i.e., co-diversify), producing associations between the lineages' phylogenetic histories. Tests for co-diversification of individual microbial lineages and their hosts have been developed previously, and these have been applied to discover ancient symbioses in diverse branches of the tree of life. However, most host-microbe relationships are not binary but multipartite, in that a single host-associated microbiota can contain many microbial lineages, generating challenges for assessing co-diversification. Here, we review recent evidence for co-diversification in complex microbiota, highlight the limitations of prior studies, and outline a hypothesis testing approach designed to overcome some of these limitations. We advocate for the use of microbiota-wide scans for co-diversifying symbiont lineages and discuss tools developed for this purpose. Tests for co-diversification for simple host symbiont systems can be extended to entire phylogenies of microbial lineages (e.g., metagenome-assembled or isolate genomes, amplicon sequence variants) sampled from host clades, thereby providing a means for identifying co-diversifying symbionts present within complex microbiota. The relative ages of symbiont clades can corroborate co-diversification, and multi-level permutation tests can account for multiple comparisons and phylogenetic non-independence introduced by repeated sampling of host species. Discovering co-diversifying lineages will generate powerful opportunities for interrogating the molecular evolution and lineage turnover of ancestral, host-species specific symbionts within host-associated microbiota.

The Relationship between Telomere Length and Epigenetic Aging with Hematologic Diseases Risk: A Multivariable Mendelian Randomisation Study

Introduction: Aging is a complex phenomenon that involves multifaceted changes, including significant alterations in telomere length and epigenetic aging. When aging affects the hematopoietic system, it leads to a gradual increase in mutations in hematopoietic stem cells, making individuals more susceptible to the development of hematologic diseases. However, due to the limitations of observational studies, such as potential confounding factors and reverse causality, the precise causal direction and magnitude of the relationship between telomere length, epigenetic aging, and the incidence of hematologic diseases remain uncertain. Therefore, we conducted an investigation to determine the causal relevance of telomere length and epigenetic aging in relation to hematologic diseases using Mendelian randomization (MR). Methods: Firstly, we conducted a 2-sample single-variable Mendelian randomization (SVMR) study to examine the genetically predicted effects of telomere length and epigenetic age acceleration, as measured by HannumAge, Horvath Intrinsic Age, PhenoAge, GrimAge, and DNAm PAI-1 (DNA methylation-estimated plasminogen activator inhibitor-1) levels, on multiple hematologic diseases, including anemia, lymphoma, leukemia, myeloproliferative diseases, and hemostasis and coagulation diseases. Additionally, we used lasso regression to exclude multicollinearity in SNPs and subsequently performed multivariable MR using the screened SNPs to adjust for statistically significant risk factors, and MR Bayesian model averaging was performed to rank the significant risk factors based on their genetic evidence (Figure A). Results: Summary data were available for 19 malignant hematological neoplasms and 35 non-malignant hematological disorders, corresponding to 70,813 cases and 12,253,012 controls. Increased telomere length due to germline genetic variation was generally associated with increased risk for hematologic diseases. The strongest associations were observed for lymphoma, lymphoid leukaemia, Hodgkin lymphoma, chronic lymphocytic leukaemia, essential thrombocythaemia, unspecified types of non-Hodgkin lymphoma, multiple myeloma, Non-follicular lymphoma, unspecified iron deficiency, leukaemia, while higher levels of telomere length was associated with a reduced risk of pernicious anaemia (Figure B). Meta-analyzed IVW MR findings suggested that higher PhenoAge acceleration was associated with increased risks of myeloid leukemia, chronic lymphocytic leukemia, and lymphoid leukemia. Conversely, higher PhenoAge acceleration was linked to reduced risks of unspecified disorders of white blood cells and unspecified coagulation defects. Similarly, SVMR showed genetic predisposition for GrimAge acceleration to be associated with increased risks of amyloidosis, unspecified anemias, and myeloid leukemia. Conversely, genetically predicted GrimAge acceleration was associated with reduced risks of hemorrhagic anemia, hemolytic anemias, and idiopathic thrombocytopenic purpura. Furthermore, our findings suggested that elevated HannumAge acceleration increased the risks of lymphoma, leukemia, and lymphoid leukemia.Conversely, higher HannumAge acceleration was associated with a reduced risk of chronic myeloid leukemia. Additionally, higher levels of DNAm PAI-1 were found to be associated with an increased risk of chronic myeloid leukemia. However, there was no evidence of causality between genetically predicted Intrinsic epigenetic age acceleration and the 19 malignant hematological neoplasms and 35 non-malignant hematological disorders mentioned (Figure C). We utilized MVMR-LASSO to estimate the combined effects of telomere length and five epigenetic clocks on hematologic diseases. After adjusting for epigenetic aging, we observed a significant positive association between telomere length and various hematologic diseases, including leukemia, lymphoid leukemia, chronic lymphocytic leukemia, lymphomas, Hodgkin lymphoma, non-follicular lymphoma, unspecified types of non-Hodgkin lymphoma, essential thrombocythemia, and multiple myeloma (Figure D&E). Conclusion: Longer telomeres and epigenetic aging may increase the risk of developing most hematologic malignancies, while simultaneously raising or decreasing the risk of certain non-malignant hematologic diseases.

Who eats last? Intra-household gender inequality in food allocation among children in educationally backward areas of India

The practice of women eating after men is a common gender-inequitable food allocation mechanism among adults in Indian households and has been associated with poor health and nutritional outcomes for women. However, empirical evidence on whether a similar practice of girls eating after boys is prevalent among children is scarce. Using primary data from a household survey conducted in educationally backward areas of four Indian states, we provide new evidence of this practice among children. Almost 28 per cent of the sample households follow the mealtime custom of girls eating after boys. Scheduled Tribes and households with higher incomes are less likely to follow this practice. Other relevant factors include children’s relative ages by sex and an interplay between family size and children’s sex composition. While our findings may not be generalizable, they suggest an intersectionality between gender and other dimensions of inequality, namely social identity and economic class.

Longitudinal study of traumatic-stress related cellular and cognitive aging

Traumatic stress is associated with both accelerated epigenetic age and increased risk for dementia. Accelerated epigenetic age might link symptoms of traumatic stress to dementia-associated biomarkers, such as amyloid-beta (Aβ) proteins, neurofilament light (NFL), and inflammatory molecules. We tested this hypothesis using longitudinal data obtained from 214 trauma-exposed military veterans (85 % male, mean age at baseline: 53 years, 75 % White) who were assessed twice over the course of an average of 5.6 years. Cross-lagged panel mediation models evaluated measures of lifetime posttraumatic stress disorder and internalizing and externalizing comorbidity (assessed at Time 1; T1) in association with T1 epigenetic age (per the GrimAge algorithm) and T1 plasma markers of neuropathology along with bidirectional temporal paths between T1 and T2 epigenetic age and the plasma markers. Results revealed that a measure of externalizing comorbidity was associated with accelerated epigenetic age (β = 0.30, p <.01), which in turn, was associated with subsequent increases in Aβ-40 (β = 0.20, p <.001), Aβ-42 (β = 0.18, p <.001), and interleukin-6 (β = 0.18, p <.01). T1 advanced epigenetic age and the T1 neuropathology biomarkers NFL and glial fibrillary acidic protein predicted worse performance on T2 neurocognitive tasks assessing working memory, executive/attentional control, and/or verbal memory (ps = 0.03 to 0.009). Results suggest that advanced GrimAge is predictive of subsequent increases in neuropathology and inflammatory biomarkers as well as worse cognitive function, highlighting the clinical significance of this biomarker with respect to cognitive aging and brain health over time. The finding that advanced GrimAge mediated the association between psychiatric comorbidity and future neuropathology is important for understanding potential pathways to neurodegeneration and early identification of those at greatest risk.

Fluid diffusion related aging effect in a concrete dam modeled as a Timoshenko beam

Fluid diffusion related aging effect in a concrete dam modeled as a Timoshenko beam

Family screening in hypertrophic cardiomyopathy - clinical and genetic yield at baseline

Abstract Background Hypertrophic cardiomyopathy (HCM) is an inherited cardiac disorder, often with monogenic inheritance and accordingly, familial aggregation of HCM is common. International guidelines recommend family screening of relatives of patients with HCM to allow pre-symptomatic identification and early interventions. The clinical and genetic yield of implemented screening programs have been scarcely described and might improve by adjustments. We hypothesized that screening can be improved. Purpose To assess the yield of clinical and genetic family screening in HCM at first screening visit. Methods The study was a retrospective study of clinical and genetic cascade screening of adult relatives (age ≥18 years) of HCM probands, screened for familial occurrence of HCM from 2006 to 2022 at a regional assembly of clinics for inherited cardiac diseases (population 2.6 million). We collected demographic, clinical, symptomatic, and genetic characteristics from electronic health records, and a national pedigree database. Diagnostic work-up included a 12-lead ECG, and echocardiography. Relatives of probands carrying a likely pathogenic (LP) or pathogenic (P) variant were also offered cascade genetic testing. Patients and relatives were diagnosed according to the 2014 ESC guidelines. Results We included 603 adult relatives (55% female, mean age 44±15 years) (table 1). At baseline, 118 relatives (20%) fulfilled diagnostic criteria for HCM, and 135 (22%) were carriers of LP/P variants; 78 (13%) of these did not fulfill diagnostic criteria for HCM. Thus, the combined clinical and genetic yield of baseline screening was 33%. A total of 108 (18%) clinically unaffected relatives did not carry the family’s LP/P variant and were discharged from follow-up. This indicates that 50% of the relatives at baseline could be categorized as affected, genetically predisposed or clinically and genetically not at risk. Relatives fulfilling criteria for HCM at baseline were older (51 vs. 42 years, p&amp;lt;0.001), more likely to report cardiopulmonary symptoms (46% vs 16%, p&amp;lt;0.001), be male (59% vs 41%, p&amp;lt;0.001), and have abnormal ECG features (40% vs. 12%, p&amp;lt;0.001), compared to relatives not fulfilling criteria for HCM at baseline. On echocardiography, relatives fulfilling criteria for HCM had a mean maximal wall thickness of 17±4 mm and 14% had left ventricular outflow tract obstruction (gradient at rest/Valsalva≥30 mmHg). Conclusion At baseline screening, one in three relatives of HCM patients were diagnosed with HCM or found to be genetically predisposed to the disease. One in five clinically unaffected relatives not carrying the proband’s disease-causing variant could be discharged from screening. Considering the pattern of inheritance in HCM, the theoretical risk of developing HCM in the remaining 50% of the relatives is low. The non-diagnostic findings may be useful for identification of the remaining truly at-risk relatives.Table 1:Baseline characteristics