Individual Events Research Articles

Trench investigation to quantify debris flow activity for landslide hazard mapping in populated areas: Lessons learned from Gol, southern Norway

AbstractWe here describe the results of stratigraphic and sedimentological examinations of debris flow deposits at Breidokk, Gol, southern Norway. The deposits are situated at the valley floor, below a steep slope with three large and several smaller debris flow channels incised into the thick till cover. The study area is populated and with abundant infrastructure such as roads, public and private buildings and other types of infrastructure, including underground water pipes and cables. Six, 10–15 m long and 1–3 m deep trenches were dug out with an excavator and examined. The sediments in the trenches consist of moraine‐, glaciofluvial/fluvial‐ and debris flow deposits. The latter consist of matrix supported, unsorted, massive beds from 1 cm to more than 1 m in thickness, with clasts up to 80 cm in diameter. A total of 16 post glacial debris flow beds are identified in five of the six trenches, representing a minimum of eight individual debris flow events. This is probably an underestimation of the debris flow activity through postglacial times as the location of the trenches was in large determined by infrastructure and were not optimally placed for mapping all debris flow deposits in the area. Also, correlation between trenches proved difficult. A total of 37 radiocarbon ages of buried soil and other organic material situated above and below debris flow deposits, together with the sedimentological and stratigraphical interpretation, show that debris flow activity has prevailed throughout the Holocene, also within the last 1000 years. A possible increase in activity within the last 3–4000 years BP has been noted. This is important knowledge to aid in the interpretation of the Quaternary history of the area but also to determine the hazard zones.

Abstract A001: HNRNPH1 regulates the alternative splicing of transcripts expressed by cancer-associated genes

Abstract The RNA binding protein HNRNPH1 is a critical regulator of alternative splicing (AS). We have previously demonstrated that HNRNPH1 mediates an exon exclusion event required for the expression of the mRNA encoding the fusion oncoprotein expressed in a subset (∼37%) of Ewing sarcomas. Furthermore, studies by others have shown that HNRNPH1 regulates a mutually exclusive exon (MXE) AS event (exon-18a versus exon-18b) that defines the expression of TCF3 transcript variants, which, when dysregulated, promotes tumorigenesis in Burkitt’s lymphoma. In this study, we have interrogated the transcriptome-wide effects of depleting HNRNPH1 by RNAi to further explore its regulation of transcripts expressed by cancer-associated genes. We performed whole transcriptome RNA sequencing (RNAseq; short-read, Illumina; long-read, PacBio IsoSeq) of two cell lines (HEK-293T and HT-1080) post 48-hour transfection with a control siRNA (siNeg) or an siRNA targeting HNRNPH1 (siHNRNPH1). We then assembled a workflow to quantify changes in individual AS events (percent-spliced-in, ΔPSI=±0.1) using rMATS and MAJIQ, and differential transcript expression (DTE) using RSEM (pValue≤0.05) and EBSeq (FDR≤0.05). RNAseq analyses were validated using PCR assays. The rMATS analysis revealed skipped exons (SE) as the most frequent event effected in HEK-293T and HT-1080 cells following HNRNPH1 silencing, with 1069 SE or MXE events from 607 genes common to both. Gene annotation (Metascape) of these 607 genes identified 49 as cancer-associated. Consistent with previous studies, we detected a significant change in the TCF3-exon-18a/18b MXE event using rMATS (decreased PSI for 18a) and MAJIQ (negative ΔPSI for 18a and positive ΔPSI for 18b) following HNRNPH1 silencing in both cell lines. Furthermore, DTE revealed a corresponding decrease in 18a-containing TCF3-transcripts and an increase in 18b-containing TCF3-transcripts, validating our analytical pipeline. Next, we extended our analysis to uncharacterized HNRNPH1-regulated AS events, beginning with examination of transcripts encoding the mitotic kinase AURKA. Previous studies have shown that AS of AURKA transcripts localizes to the untranslated regions (UTRs), particularly the 5’UTR. However, regulators of these AS events are unknown, and it is unclear how these UTR variants affect AURKA protein expression. Long-read RNAseq of AURKA mRNAs from both cell lines revealed extensive 5’UTR AS, and the rMATS and MAJIQ analyses showed decreased PSI and negative ΔPSI for a specific 5’UTR-exon following HNRNPH1 silencing. DTE revealed corresponding decreases in abundance of AURKA transcripts containing this exon (AURKA-203, -205, -209, and -213) upon HNRNPH1 depletion, which we confirmed with variant-specific RT-PCR. Furthermore, immunoblot analysis showed a decrease in AURKA protein expression following the silencing of HNRNPH1. Our assessment of AURKA AS suggests HNRNPH1 mediates the inclusion of a specific AURKA-5’UTR-exon, providing evidence for a previously uncharacterized post-transcriptional regulatory mechanism of AURKA expression. Citation Format: Tayvia Brownmiller, Patricio Pichling, Tamara L Jones, Ioannis Grammatikakis, Soumya Sundara Rajan, Erica C Pehrsson. HNRNPH1 regulates the alternative splicing of transcripts expressed by cancer-associated genes [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr A001.

Abstract 4138663: Peak nocturnal home blood pressure as an early and strong novel risk factor for stroke: the practitioner-based nationwide J-HOP Nocturnal BP study

Background: Clinical implications of high peak nighttime home blood pressure (BP) are currently unknown. This analysis investigated the association between peak nighttime home systolic BP (SBP) and cardiovascular events in individuals with ≥1 cardiovascular risk factor. Methods: In the Japan Morning Surge-Home Blood Pressure (J-HOP) study, nighttime home BP was automatically measured three times every night for 14 days at baseline using a nighttime home BP monitoring device (HEM-5001, Omron Healthcare). Peak nighttime home SBP was defined as average of the highest three values over the 14-night measurement period. Occurrence of cardiovascular events (stroke, coronary artery disease, heart failure, aortic dissection) was determined over a mean 7.1 years’ follow-up. Results: This analysis included 2545 individuals (mean age 63.3±10.3 years, 49% male). After adjustment for covariates (including age, sex, and average office, morning, evening, and nighttime home SBP), stroke risk was significantly higher in individuals with peak nighttime home SBP in the highest (Q5, ≥149.0 mmHg) versus lowest quintile (Q1, <119.3 mmHg) (hazard ratio [HR] 4.24, 95% confidence interval [CI] 1.07–16.77; p=0.039 overall and 8.92, 1.49–53.43; p=0.017 in the subgroup with ≥6 nighttime home SBP measurements). This increased stroke risk remained significant after controlling for day-by-day average real variability of nighttime BP. The average peak nighttime home SBP cut-off value for predicting an increased risk of incident stroke was 136 mmHg. Conclusions: We propose exaggerated peak nighttime home SBP determined from ≥6 measurements as a novel risk factor for stroke, independent of conventional office and home BP values.

Abstract 4137424: Circulating Levels of the Pro-Fibrotic Collagen Hormone Endotrophin are Associated with the Risk of Experiencing Major Adverse Cardiovascular Events in Individuals with Type 2 Diabetes – The Thousand&2 Study

Introduction: Cardiovascular disease (CVD) complications are the leading cause of mortality in individuals with type 2 diabetes (T2D). Abnormal extracellular matrix (ECM) remodelling leads to the release of ECM protein fragments into circulation, reflecting these complications. Endotrophin, a pro-fibrotic and -inflammatory hormone, released during collagen type 6 formation, has been linked to adverse outcomes in T2D, but not previously in a long-term perspective. Aim: To assess the 12-year prognostic value of circulating endotrophin levels, measured by PRO-C6, to predict the risk of major adverse cardiovascular events (MACE) in a large cohort of individuals with T2D. Methods: Endotrophin levels were measured with the NordicPRO-C6™ ELISA in 909 serum samples from the Thousand&2 study, which was initiated in 2011 and examined individuals with T2D, with and without known CVD. Clinical data were collected at baseline. Follow-up was 100% complete and performed on the 1 st of May 2024 with the registration of data on MACE from the Danish national registers. The primary outcome was MACE, defined as incident events of hospital admission for ischemic heart disease, heart failure, stroke, or all-cause mortality. PRO-C6 was split into tertiles and examined for survival probability by Kaplan-Meier analysis. Univariate Cox proportional hazard regression analysis was conducted to examine the association between PRO-C6 and the risk of MACE. A multivariable Cox model was additionally conducted, adjusted for age at baseline, sex, systolic blood pressure, duration of diabetes, HbA1c, estimated glomerular filtration rate, use of statins, albuminuria status, and current or prior smoking. Results: The baseline mean (±SD) age of the cohort was 64 (±10) years, 66% were males, mean (±SD) PRO-C6 was 11.9 (±7.01) ng/ml, the median follow-up time was 10.6 years, and number of MACE recorded was 472. The risk of experiencing MACE was significantly higher in the third tertile compared to the first and second tertile (Log-Rank p < 0.001). In the univariate Cox model, the estimated hazard ratio (HR), corresponding to a 2-fold increase of PRO-C6, was HR [95% Confidence Interval(CI)] = 2.1 [1.8-2.4], P <0.001. In the fully adjusted Cox model, PRO-C6 remained significantly associated with the risk of MACE (HR [95% CI] = 1.5 [1.2-1.8], P <0.001). Conclusion: Elevated circulating endotrophin is associated with MACE in T2D, independent of common risk factors.

Abstract 4134911: Coronary Artery Calcium Predicts Cardiovascular Events in Individuals with Controlled Atherosclerotic Risk Factors: A Multi-Cohort Study

Background: There is residual risk of atherosclerotic cardiovascular disease (ASCVD) that remains despite adequate risk factor (RF) control. Coronary artery calcium (CAC) has demonstrated value in ASCVD risk stratification. We evaluated the value of CAC in identifying residual risk of ASCVD events among those with traditional RF control. Methods: Participants without clinical ASCVD were pooled from the Multi-Ethnic Study of Atherosclerosis, Heinz Nixdorf Recall Study, Framingham Heart Study, and Jackson Heart Study. RF control was classified as “guideline-concordant” and “optimal” (Figure 1). Participants were stratified by the number of controlled RFs at baseline and CAC score (CAC = 0, 1-99, ≥100). Cox proportional hazards models examined the association between CAC and incident ASCVD events. Results: The study included 14,780 individuals (mean age 58 years (SD: 11), 54% female, 59% White, 27% Black, 50% CAC = 0). Over a median follow-up of 14.6 years, there were 1,441 incident ASCVD events. The distribution of CAC and ASCVD event incidence is shown in Panel A; 10% of those with 3 optimal RFs and 19% of those with 3 guideline-concordant RFs controlled had CAC > 100. The rate of ASCVD events decreased with more RFs controlled and increased with higher CAC. Overall, optimal RF control was associated with lower ASCVD event rates compared to guideline-concordant control. At every level of RF control, CAC > 100 was associated with increased HRs for incident ASCVD (Panel B). Those with CAC ≥ 100 and controlled RFs experienced ASCVD rates numerically comparable to or exceeding those with uncontrolled RFs but CAC = 0 (Panel A). Adjusted HR (95% CI) for ASCVD events with CAC > 100 compared to CAC = 0 was 5.0 (2.0, 12.9) in optimal RF control and 3.7 (2.6, 5.4) in guideline-concordant RF control. Conclusion: There is significant heterogeneity in residual ASCVD risk among those with optimal or guideline-concordant traditional RF control and CAC can help identify this risk. Irrespective of RF control, a higher CAC burden was associated with increased ASCVD risk. Future studies could use CAC testing to identify those with higher residual ASCVD risk despite effective traditional RF control to target for novel therapies.

Uncovering Below Cloud Rain‐Vapor Interactions During Tropical Rain Events Through Simultaneous and Continuous Real‐Time Monitoring of Rain and Vapor Isotopes

AbstractDue to limited water vapor measurements, vapor isotopes have been traditionally estimated under the assumption of isotopic equilibrium between rain and vapor below cloud base. However, recent advancements in analytical instruments allow more vapor isotopic measurements that have challenged this assumption. To enhance our understanding of rain‐vapor interactions below cloud base in tropical regions, we established an automated system to measure rain and vapor isotopes simultaneously and continuously in real time at minute intervals in Singapore. Among 324 rain events monitored from 2016 to 2019, 81% exhibited a substantial departure of rain and vapor isotopes from the expected equilibrium. This departure suggests that raindrop evaporation plays a larger role in determining their isotopes. The conclusion is supported by the generally lower slopes of the local meteoric water line. Seasonal variations in rain event characteristics indicate changing influences of rain‐vapor interactions: during monsoons, more frequent heavy rainfall maintains relatively high humidity below cloud base, favoring rain‐vapor isotopic equilibrium, whereas during inter‐monsoons, more light rain events lead to pronounced rain evaporation and larger isotopic differences. Furthermore, rain‐vapor interactions below cloud base significantly modulated their isotope evolution during individual events. As events progressed, reduced humidity favored evaporation, increasing rain isotope values and decreasing its d‐excess, whereas vapor isotope values decreased and its d‐excess increased. Our study introduces a new approach to capturing real‐time high‐resolution rain and vapor isotopes at minute intervals to understand the dynamics of rain‐vapor interactions below cloud base. Findings underscore the crucial role of these interactions in influencing rain and vapor isotopes during tropical rain events.

Abstract 4137804: Associations between falls and other serious adverse events and antihypertensive medication in individuals with dementia: An observational cohort study

Background: The balance of benefits and risks associated with lowering blood pressure levels in individuals with dementia remains controversial with a lack of evidence for possible harms associated with antihypertensive treatment (AHT). Objectives: We examined the association between AHT and serious adverse events (SAEs) in individuals with dementia compared to those without. Methods: This was a retrospective analysis using nationally representative, UK general practice population between 1998 and 2018, using data from electronic health records (Clinical Practice Research Datalink, GOLD). Individuals included were age ≥40 years and not previously prescribed AHT. Diagnosis of dementia was based on standardised clinical codes. The primary outcome was the first hospitalisation or death from a fall within 10 years of the follow-up period. Secondary outcomes were first hospitalisation or death from hypotension, syncope, and fracture. Cox regression analyses, adjusted for propensity score were used to assess the risk of SAEs. Results: In a population of 1,219,732 individuals, 23,510 had dementia. Antihypertensive medications were newly prescribed in 4,062/23,510 (17.3%) individuals with dementia and 142,385/1,196,222 (11.9%) individuals without dementia in the 12 months exposure period. In individuals with dementia, AHTs were associated with an increased risk of hospitalisation or death from falls (adjusted hazard ratio [aHR] 1.15, 95% confidence interval [CI] 1.08, 1.22), hypotension (aHR 1.51, 95%CI 1.29, 1.78), syncope (aHR 1.34, 95%CI 1.11, 1.61), but not fracture (aHR 1.05, 95%CI 0.96, 1.15). In individuals without dementia, the association between AHT and SAEs was similar, with an increased risk of hospitalisation or death from falls (aHR 1.07, 95%CI 1.05, 1.10). However, absolute risk of falls with AHT per 10,000 individuals per year was significantly higher in individuals with dementia (47, 95%CI 26, 70) compared to those without (14, 95%CI 10, 18). The absolute risks of hypotension and syncope with AHT were also higher in the individuals with dementia compared to those without. Conclusions: AHT was associated with increased risk of SAEs in individuals with and without dementia, however, the absolute risk of harm from falls was more than double in individuals with dementia. Clinicians, patients, and their carers should consider these risks before starting new antihypertensive medications, particularly in the context of dementia, although they remain small.

Engineering DNA Nanocube SAM Scaffolds for FRET-Based Biosensing: Interfacial Characterization and Sensor Demonstration.

Decorating a gold surface with molecular-level control over the positioning of DNA probes was demonstrated using a self-assembled monolayer (SAM) of wireframe DNA nanocube structures. The DNA nanocubes were specifically adsorbed and oriented using thiol-modified DNA on one face of the cube. The DNA nanocube SAM had a uniform coverage over the gold single crystal bead electrode with a separation of 20-30 nm measured by AFM. The face of the nanocube furthest from the gold surface was designed to hybridize with two different sequences of a 50 base single-stranded DNA probe that was modified with a fluorophore. The first 20 bases were hybridized with the DNA nanocube. One of a pair of FRET fluorophores was used for each probe strand. The dimensions of the nanocube controlled the relative spacing between these fluorophores. When the DNA probes were single-stranded, a FRET signal was observed. FRET decreased to background levels when a complementary DNA target was hybridized to either probe, resulting in a turn-off sensor with little cross-talk between the individual hybridization events. Hybridization isotherms for one target gave KA = 170 pM and a detection limit <50 pM. In addition, the DNA nanocube SAM was configured to be used as a turn-on NeutrAvidin sensor using biotinylated DNA targets hybridized to each probe resulting in an increase in FRET. We show that the wireframe DNA nanocube can be an effective scaffold for preparing biosensors with controlled separation between surface-bound probes facilitating precise sensor surface design and enabling a wide range of sensing modalities with more than one signal available for correlative confirmation of the target binding.

Spin-valley locked excited states spectroscoy in a one-particle bilayer graphene quantum dot

Current semiconductor qubits rely either on the spin or on the charge degree of freedom to encode quantum information. By contrast, in bilayer graphene the valley degree of freedom, stemming from the crystal lattice symmetry, is a robust quantum number that can therefore be harnessed for this purpose. The simplest implementation of a valley qubit would rely on two states with opposite valleys as in the case of a single-carrier bilayer graphene quantum dot immersed in a small perpendicular magnetic field (B⊥ ≲ 100 mT). However, the single-carrier quantum dot excited states spectrum has not been resolved to date in the relevant magnetic field range. Here, we fill this gap, by measuring the parallel and perpendicular magnetic field dependence of this spectrum with an unprecedented resolution of 4 μeV. We use a time-resolved charge detection technique that gives us access to individual tunnel events. Our results come as a direct verification of the predicted spectrum and establish a new upper-bound on inter-valley mixing, equal to our energy resolution. Our charge detection technique opens the door to measuring the relaxation time of a valley qubit in a single-carrier bilayer graphene quantum dot.

Re-processing Datawell Directional Waverider MkIII heave data affected by breaking waves

Observations of nearshore waves are essential for coastal management, planning and operations. However, shallow water deployments often encounter breaking waves, causing anomalous measurements that are rejected during quality control. A new methodology for re-processing wave data containing breaking waves has been developed, utilising data from the National Network of Regional Coastal Monitoring Programmes of England which operates 37 Datawell Directional Waverider MkIII buoys. Heave data affected by breaking waves is reviewed, anomalous heaves removed, and the remaining data re-processed. Validation through a two-stage process confirms that re-processed wave parameters closely match those derived from the established Datawell processing and ensures strong agreement between parameters derived from shorter re-processed records and full-length data. Applying this new approach to all measured storm wave data, 7.3% (928.5 hours) of storm wave data is recovered across the 37 sites. At some sites, the retention of additional storm wave data has considerable impacts on significant wave height (Hm0) return periods. At five sites, the 1 in 100 year return period increased by over one meter. The enhanced dataset now includes more individual storm events and more complete records of storm events, providing a more robust foundation for coastal management and planning.

Event-based high-resolution neutron image formation analysis using intensified CMOS cameras

We present a versatile optical setup for high-resolution neutron imaging with an adaptable field of view and magnification that can resolve individual neutron absorption events with an image intensifier and a CMOS camera. Its imaging performance is characterized by evaluating the resolution limits of the individual optical components and resulting design aspects are discussed. Neutron radiography measurements of a Siemens star pattern were performed in event mode acquisition comparing two common high-resolution neutron scintillators, crystalline Gadolinium Gallium Garnet (GGG) and powdered Gadolinium Oxysulfide (GOS). An analysis of the light signature caused by neutron absorption events is performed and some resulting issues for both GGG and GOS regarding optical system design are addressed. Both scintillators reach similar resolution (4–5 μ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\upmu }$$\\end{document}m) in event mode acquisition despite different light emission characteristics. The findings suggest that, in the case of GOS, the resolution is limited by the size of the light clusters which in turn originate from the photon scattering at the boundaries of the powder particles comprising it, while with GGG the lower light conversion efficiency makes it challenging to collect enough photons to trigger sufficient signal amplification in the image intensifier. Overall, the proposed event-based evaluation of scintillators allows for quantifying and optimizing various design parameters, which is much more complex than adopting conventional methods based on integrated images.

Development of a nomogram to assess thromboembolic risk in patients with liver abscesses

Thromboembolism, a serious complication in patients with liver abscesses, can lead to organ deterioration if left untreated. However, factors associated with thromboembolism in these patients remain poorly understood. We aimed to identify the factors associated with liver abscess complications, with a focus on thromboembolism and metastatic infection. Data from 325 patients diagnosed with liver abscesses between March 2019 and June 2023 were retrospectively collected. Baseline clinical and laboratory variables associated with thromboembolic events and metastatic infections were analyzed using logistic regression. A nomogram for predicting thromboembolism was constructed using significant predictors. Among the 325 patients, the median age was 68.0 years, and included 129 women. Fifty patients experienced thromboembolic events and 44 had metastatic infections. Significant predictors for thromboembolic events included white blood cell (WBC) ≥ 20,000/µL (odds ratio [OR] 3.401, p = 0.002), platelet count < 100,000/µL (OR 3.291, p = 0.004), and abscess septation (OR 2.704, p = 0.007). Age ≥ 65 years (OR 0.457, p = 0.040), WBC ≥ 20,000/µL (OR 3.340, p = 0.005), and abscess septation (OR 2.909, p = 0.008) were identified as factors associated with metastatic infections. A nomogram was constructed to predict thromboembolism using the following four variables: WBC ≥ 20,000/µL platelet count < 100,000/µL, albumin < 2.8 g/dL, and abscess septation, and demonstrated an AUROC of 0.755. Our study is the first to develop a reliable nomogram for thromboembolism prediction, utilizing easily accessible clinical parameters. This innovative model enables clinicians to efficiently identify high-risk patients, facilitating the implementation of additional studies to mitigate the risk of overlooked thromboembolic events in these at-risk individuals.

Coda-derived source properties estimated using local earthquakes in the Sea of Marmara, Türkiye

Abstract. Accurate estimates of the moment magnitude of earthquakes that physically measure the earthquake source energy are crucial for improving our understanding of seismic hazard in regions prone to tectonic activity. To address this demand, a method involving coda wave modelling was employed to estimate the moment magnitudes of earthquakes in the Sea of Marmara, northwestern Türkiye. This approach enabled us to model the source displacement spectrum of 303 local earthquakes efficiently recorded at 49 regional seismic stations between 2018 and 2020 in the region. The coda wave traces of individual events were inverted across 12 frequency ranges between 0.3 and 16 Hz. The resultant coda-derived moment magnitudes were found to be in good accordance with the conventional local magnitude estimates. However, the notable move-out between local magnitude and coda-derived moment magnitude estimates for smaller earthquakes less than a magnitude of 3.5 likely occurs due to potential biases arising from incorrect assumptions for anelastic attenuation and/or the finite sampling intervals of seismic recordings. Scaling relations between the total radiated energy and seismic moment imply a non-self-similar behaviour for the earthquakes in the Sea of Marmara. Our findings suggest that larger earthquakes in the study area exhibit distinct rupture dynamics compared to smaller ones, resulting in a more efficient release of seismic energy. Hence, we introduce an empirical relationship obtained from the scatter between local magnitude and coda-derived moment magnitude estimates.

One in Five Atherosclerotic Cardiovascular Disease Events in Individuals With Diabetes Attributed to Elevated Remnant Cholesterol

ABSTRACTAimsElevated remnant cholesterol (= the cholesterol carried in triglyceride‐rich lipoproteins) is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and is common in individuals with diabetes. We tested the hypothesis that ASCVD in individuals with diabetes can be partly attributed to elevated remnant cholesterol.Materials and MethodsWe included 3806 individuals with diabetes identified among 107,243 individuals from the Copenhagen General Population Study and used multivariable adjusted Poisson regression to estimate the fraction of ASCVD attributable to elevated remnant cholesterol. Elevated remnant cholesterol was defined as levels higher than those observed in individuals with non‐high‐density lipoprotein (non‐HDL) cholesterol &lt; 2.6 mmol/L (100 mg/dL), the European guideline goal. Results were replicated in the UK Biobank.ResultsDuring 15 years of follow‐up, 498 patients were diagnosed with ASCVD, 172 with peripheral artery disease, 185 with myocardial infarction and 195 with ischaemic stroke. In individuals with non‐HDL cholesterol &lt; 2.6 mmol/L (100 mg/dL) and in all individuals with diabetes, median remnant cholesterol levels were 0.5 mmol/L (20 mg/dL) and 0.8 mmol/L (31 mg/dL). The fraction of events attributable to elevated remnant cholesterol was 19% (95% confidence interval: 10%–28%) for ASCVD, 21% (5%–37%) for peripheral artery disease, 24% (10%–37%) for myocardial infarction and 17% (1%–31%) for ischaemic stroke; in the UK Biobank, corresponding values were 16% (9%–22%), 25% (12%–36%), 17% (8%–25%) and 7% (0%–19%), respectively.ConclusionsOne in five ASCVD events in individuals with diabetes can be attributed to elevated remnant cholesterol. It remains to be determined in clinical trials if remnant cholesterol‐lowering therapy may prevent ASCVD.

Long-term safety and efficacy of glucagon-like peptide-1 receptor agonists in individuals with obesity and without type 2 diabetes: A global retrospective cohort study.

We aimed to investigate the long-term impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on thyroid function, cardiovascular health, renal outcomes and adverse events in individuals with obesity and without type 2 diabetes (T2D). In this observational cohort study, we used propensity score matching to construct comparable cohorts of individuals with obesity and without T2D who were new to GLP-1 RA treatment and those who did not receive glucose-lowering medications. In total, 3,729,925 individuals with obesity were selected from the TriNetX Global Network, with an index event between 1 January 2016 and 31 March 2024. The primary outcomes were safety, cardiovascular, thyroid and clinical biochemical profile outcomes occurring within 5 years following the index event. After propensity score matching, the study included 12,123 individuals in each group. GLP-1 RA treatment was associated with a significantly lower risk of all-cause mortality (hazard ratio 0.23; 95% confidence interval 0.15-0.34) and several cardiovascular complications, including ischaemic heart disease, heart failure, arrhythmias, hypertension, stroke and atrial fibrillation (all p < 0.05). GLP-1 RAs were also associated with a lower risk of acute kidney injury and allergic reactions. These protective effects were consistent across various subgroups and regions. In this large observational study, GLP-1 RAs showed long-term protective effects on cardiovascular health, renal outcomes and adverse events in individuals with obesity and without T2D. Our findings suggest that GLP-1 RAs may offer a comprehensive approach to managing obesity and its related comorbidities, potentially improving overall health and survival in this population.

Comment on “Accelerometer-measured physical activity, sedentary behavior, and incidence of macrovascular and microvascular events in individuals with type 2 diabetes mellitus and prediabetes”

Comment on “Accelerometer-measured physical activity, sedentary behavior, and incidence of macrovascular and microvascular events in individuals with type 2 diabetes mellitus and prediabetes”

Dynamics of Barred Coast at Different Temporal Scales (by the Example of Vistula Spit in the Baltic Sea)

According to fundamental concepts, the morphodynamic system of an accumulative sandy coast with underwater bars exhibits cyclic behavior across various time scales. This raises the question: which factor is more significant for the dynamics of a given coast—individual storms or seasonal changes in wave activity? While observations and studies addressing this issue have primarily been conducted on oceanic coasts, there is a lack of comparable data for fetch-limited areas. Monitoring of the bottom topography along the west coast of Vistula Spit (Baltic Sea) revealed a cyclic behavior in morphology, transitioning from a straightened external bar to its connection with the shore. Analysis of field measurement results indicated that seasonal variations in wave intensity do not significantly impact coastal relief. Furthermore, it was found that the complete cycle of underwater bar evolution lasts approximately two years, during which the coast profile maintains a stable shape at the stage of the straightened external bar. The identification of the primary factor influencing coastal evolution can be characterized by the Dean number (Ω), which combines wave parameters (wave height and period) with sediment fall velocity. Utilizing ERA5 wave reanalysis data, we compared the variability of Ω values on both annual and monthly scales. The analysis revealed that for the section of the coast under consideration, there is no clearly dominant evolutionary factor; rather, the coast is influenced approximately equally by individual storm events and seasonal fluctuations in wave energy. Modeling storm-induced bed profile deformations using the CROSS-PB model demonstrated that the position of the external underwater bar remains nearly constant even during intense and prolonged storms. It is concluded that under specific conditions—determined by a combination of sediment size, coastal slope, and wave regime characteristics—the coast can remain stable, exhibiting minimal response to relatively strong storms and seasonal variations in wave energy. Such coasts are characterized by an absence of a dominant evolutionary factor as indicated by fluctuations in the Dean parameter, allowing their morphodynamic cycles to span several seasons. This type of morphodynamics in coastal accumulative relief appears to be typical for conditions found in fetch-limited areas, such as regional and semi-closed seas.

Bursty Star Formation in Dwarfs is Sensitive to Numerical Choices in Supernova Feedback Models

Simulations of galaxy formation are mostly unable to resolve the energy-conserving phase of individual supernova events, having to resort to subgrid models to distribute the energy and momentum resulting from stellar feedback. However, the properties of these simulated galaxies, including the morphology, stellar mass formed, and the burstiness of the star formation history, are highly sensitive to the numerical choices adopted in these subgrid models. Using the SMUGGLE stellar feedback model, we carry out idealized simulations of an M vir ∼ 1010 M ⊙ dwarf galaxy, a regime where most simulation codes predict significant burstiness in star formation, resulting in strong gas flows that lead to the formation of dark matter cores. We find that by varying only the directional distribution of momentum imparted from supernovae to the surrounding gas, while holding the total momentum per supernova constant, bursty star formation may be amplified or completely suppressed, and the total stellar mass formed can vary by as much as a factor of ∼3. In particular, when momentum is primarily directed perpendicular to the gas disk, less bursty and lower overall star formation rates result, yielding less gas turbulence, more disky morphologies, and a retention of cuspy dark matter density profiles. An improved understanding of the nonlinear coupling of stellar feedback into inhomogeneous gaseous media is thus needed to make robust predictions for stellar morphologies and dark matter core formation in dwarfs independent of uncertain numerical choices in the baryonic treatment.

Greenland Ice Sheet's Distinct Calving Styles Are Identified in Terminus Change Timeseries

AbstractAt least three primary iceberg calving styles have been identified in Greenland: serac collapse, which produces falling icebergs tens of meters in length; slab capsize, which produces rotating icebergs hundreds of meters in length; and tabular rifting, which produces kilometer‐scale icebergs. However, calving styles are mostly undocumented across Greenland. Here, we develop a method to disentangle the sizes of individual calving events and map the dominant calving style at glaciers, using the characteristic properties of step retreats in satellite‐derived terminus positions. At glaciers known to frequently produce calving teleseisms, step retreats greater than 200 m account for of net calved length since 2018. In contrast, at glaciers known to calve by serac failure, 200 m step retreats account of net calving. Thus, terminus change timeseries can offer promising insight into the dominant calving styles at marine‐terminating glaciers.

Analysis of Canopy Interception Characteristics and Influencing Factors in Typical Artificial Forest in the Loess Plateau Semi-Arid Region

Interception loss (IL) is an important process in the hydrological cycle within semi-arid forest ecosystems, directly affecting the amount of effective rainfall. However, the factors influencing IL during individual rainfall events remain to be quantified. This study collected rainfall, vegetation, and interception data during the 2022 and 2023 growing seasons in a typical black locust forest within the Zhifanggou watershed. It employed the Random Forest Regression (RFR) and back-propagation neural network (BPNN) methods to quantitatively evaluate the contribution rates of various factors to the IL and interception loss percentage (ILP). The IL among the 48 effective rainfall events was 172.05 mm, accounting for 19.54% of the rainfall amount. IL and ILP increased as the distance from the trunk decreased. During all rainfall events, both IL and ILP were significantly negatively correlated with the leaf area index (LAI) and canopy cover (CC); IL is significantly positively correlated with total rainfall (TR) and rainfall intensity (RI), while ILP is significantly negatively correlated with TR, RI, and rainfall duration (RD). The BPNN and RFR results indicated that rainfall, canopy, and tree characteristics contributed 43.06%, 44.79%, and 12.15% to IL, respectively, and 57.27%, 34.09%, and 8.63% to ILP, respectively. TR, CC, and LAI represented the primary influencing factors. Rainfall and canopy characteristics were the main factors affecting IL (ILP). As rainfall event magnitude increases, canopy contributions to IL and ILP decrease. In semi-arid areas, managing forest canopies to control IL helps address water imbalances in ecosystems.