Individual Events Research Articles

Scintillation event imaging with a single photon avalanche diode camera

Position and time measurements of scintillation events encode information about the radiation source. Single photon avalanche diode (SPAD) arrays offer multiple-megapixel spatial resolution and tens of picoseconds temporal resolution for detecting single photons. Current lensless designs for measuring scintillation events use sensors that are lower in spatial resolution. Camera-based designs use sensors that are lower in temporal resolution or readout rate and cannot image individual interactions. Here we propose to image scintillation events in a thick, monolithic scintillator using a high-resolution SPAD camera. We demonstrate that a commercial SPAD camera is able to gather sufficient signal to image individual scintillation events and observe 3D shifts in their spatial distribution. Simulations show that a SPAD camera can localize individual scintillation events in 3D. We report direct imaging of gamma-ray interactions in a scintillator with a SPAD camera. The proposed design may allow to measure complex signatures of individual particles interacting in the scintillator.

The Biodiversity and Climate Variability Experiment (BioCliVE): Quantifying the role of biodiversity in buffering ecosystems against climatic variability

Extreme climate events such as floods and droughts are becoming increasingly frequent and intense across the world. Future climate scenarios predict both an increase in individual extreme events, as well as chronic changes in climatic seasonality. Yet, the combined and relative effects of these pressures on ecosystems remain unknown. Concurrently, human-induced ecological disruption is accelerating species extinction rates, which are estimated to be 100 to 1000 times greater than pre-human levels. This is alarming as greater biological diversity is thought to buffer ecosystem functioning against extreme climate events, thereby safeguarding the provisioning of essential ecological services that contribute to human well-being. However, how and to what extent biodiversity buffers ecosystems against climate variability remains unclear. We recently constructed experimental grassland communities in a mesocosm-based field design representing a realistic gradient of plant diversity. Both extreme events (drought and flood) and a change in seasonality of precipitation are manipulated in a full factorial design to quantify the effects of future seasonal shifts and extremes in precipitation. We will: 1) determine to what extent higher biological diversity ensures that grasslands can continue to provide multiple ecosystem services even in the context of climate change and 2) unravel the fundamental mechanisms by which this is achieved including species asynchrony and positive species interactions. Results of our experimental approach will advance our understanding of the buffering potential of plant diversity and contribute to the development of strategies for sustainable service provisioning of our ecosystems in the face of climate change.

Effectiveness and risk of ARB and ACEi among different ethnic groups in England: A reference trial (ONTARGET) emulation analysis using UK Clinical Practice Research Datalink Aurum-linked data.

Guidelines by the National Institute for Health and Care Excellence recommend an angiotensin receptor blocker (ARB) rather than an angiotensin-converting enzyme inhibitor (ACEi) for the treatment of hypertension for people of African and Caribbean descent, due to an increased risk of angioedema associated with ACEi use observed in US trials. However, the effectiveness and risk of these drugs in Black populations in UK routine care is unknown. We applied a reference trial emulation approach to UK Clinical Practice Research Datalink Aurum data (linked with data from Hospital Episode Statistics and Office for National Statistics) to study the comparative effectiveness of ARB and ACEi in ethnic minority groups in England, after benchmarking results against the ONTARGET trial. Approximately 17,593 Black, 30,805 South Asian, and 524,623 White patients receiving a prescription for ARB/ACEi between 1 January 2001 and 31 July 2019 were included with a median follow-up of 5.2 years. The primary composite outcome was cardiovascular-related death, myocardial infarction, stroke, or hospitalisation for heart failure with individual components studied as secondary outcomes. Angioedema was a safety endpoint. We assessed outcomes using an inverse-probability-weighted Cox proportional hazards model for ARB versus ACEi with heterogeneity by ethnicity assessed on the relative and absolute scale. For the primary outcome, 27,327 (18.0%) events were recorded in the ARB group (event rate: 25% per 5.5 person-years) and 80,624 (19.1%) events (event rate: 26% per 5.5 person-years) in the ACEi group. We benchmarked results against ONTARGET and observed hazard ratio (HR) 0.96 (95% CI: 0.95, 0.98) for the primary outcome, with an absolute incidence rate difference (IRD)% of -1.01 (95% CI: -1.42, -0.60) per 5.5 person-years. We found no evidence of treatment effect heterogeneity by ethnicity for the primary outcome on the multiplicative (Pint = 0.422) or additive scale (Pint = 0.287). Results were consistent for most secondary outcomes. However, for cardiovascular-related death, which occurred in 37,554 (6.6%) people, there was strong evidence of heterogeneity on the multiplicative (Pint = 0.002) and additive scale (Pint < 0.001). Compared to ACEi, ARB were associated with more events in Black individuals (HR 1.20 (95% CI: 1.02, 1.40); IRD% 1.07 (95% CI: 0.10, 2.04); number-needed-to-harm (NNH): 93) and associated with fewer events in White individuals (HR 0.91 (95% CI: 0.88, 0.93); IRD% -0.87 (95% CI: -1.10, -0.63); number-needed-to-treat (NNT): 115), and no differences in South Asian individuals (HR 0.97 (95% CI: 0.86, 1.09); IRD% -0.17 (95% CI: -0.87, 0.53)). For angioedema, HR 0.56 (95% CI: 0.46, 0.67) with no heterogeneity for ARB versus ACEi on the multiplicative scale (Pint = 0.306). However, there was heterogeneity on the additive scale (Pint = 0.023). Absolute risks were higher in Black individuals (IRD% -0.49 (95% CI: -0.79, -0.18); NNT: 204) compared with White individuals (IRD% -0.06 (95% CI: -0.09, -0.03); NNT: 1667) and no difference among South Asian individuals (IRD% -0.05 (95% CI: -0.15, 0.05) for ARB versus ACEi. These results demonstrate variation in drug effects of ACEi and ARB for some outcomes by ethnicity and suggest the potential for adverse consequences from current UK guideline recommendations for ARB in preference to ACEi for Black individuals.

Practice Reshapes the Geometry and Dynamics of Task-tailored Representations.

Extensive practice makes task performance more efficient and precise, leading to automaticity. However, theories of automaticity differ on which levels of task representations (e.g., low-level features, stimulus-response mappings, or high-level conjunctive memories of individual events) change with practice, despite predicting the same pattern of improvement (e.g., power law of practice). To resolve this controversy, we built on recent theoretical advances in understanding computations through neural population dynamics. Specifically, we hypothesized that practice optimizes the neural representational geometry of task representations to minimally separate the highest-level task contingencies needed for successful performance. This involves efficiently reaching conjunctive neural states that integrate task-critical features nonlinearly while abstracting over non-critical dimensions. To test this hypothesis, human participants (n = 40) engaged in extensive practice of a simple, context-dependent action selection task over 3 days while recording EEG. During initial rapid improvement in task performance, representations of the highest-level, context-specific conjunctions of task-features were enhanced as a function of the number of successful episodes. Crucially, only enhancement of these conjunctive representations, and not lower-order representations, predicted the power-law improvement in performance. Simultaneously, over sessions, these conjunctive neural states became more stable earlier in time and more aligned, abstracting over redundant task features, which correlated with offline performance gain in reducing switch costs. Thus, practice optimizes the dynamic representational geometry as task-tailored neural states that minimally tesselate the task space, taming their high-dimensionality.

Prognostic significance of the estimated pulse wave velocity in critically ill patients with coronary heart disease: analysis from the MIMIC‑IV database.

There are currently no specialized risk-scoring systems for critically ill patients with coronary heart disease (CHD). Arterial stiffness, as measured by estimated pulse wave velocity (ePWV), has emerged as a potential indicator of mortality or adverse cardiovascular events in individuals with CHD. This study aimed to evaluate the association between ePWV and all-cause mortality among critically ill patients with CHD beyond traditional risk scores. This study included 11 001 participants with CHD from the Medical Information Mart for Intensive Care IV, with a one-year follow-up. The primary endpoint was one-year all-cause mortality, and the secondary endpoint was in-hospital mortality. Elevated ePWV was significantly associated with higher risks of in-hospital (OR 1.15, 95% CI 1.12-1.17, p<0.001) and one-year (HR 1.21, 95% CI 1.20-1.23, p<0.001) mortality. These associations remained consistent when adjusted for traditional risk scores and potential confounders. When ePWV was integrated into traditional risk scoring models (OASIS, SOFA score, APSIII, SIRS score, SAPS II, and LODS score), the predictive accuracy (area under the curve: 64.55 to 70.56, 64.32 to 72.51, 72.35 to 75.80, 55.58 to 67.68, 71.27 to 73.53, 67.24 to 73.40, p<0.001) and reclassification (net reclassification index: 0.230, 0.268, 0.257, 0.255, 0.221, 0.254; integrated discrimination improvement: 0.049, 0.072, 0.054, 0.068, 0.037, 0.061, p<0.001) of these models significantly improved for one-year mortality. Similar results were also found for in-hospital mortality. ePWV is a strong independent predictor of both short- and long-term mortality in critically ill patients with CHD. Importantly, integrating ePWV into traditional risk scores significantly boosts the predictive accuracy for one-year and in-hospital all-cause mortality.

Vesicle docking and fusion pore modulation by the neuronal calcium sensor Synaptotagmin-1.

Synaptotagmin-1 (Syt1) is a major calcium sensor for rapid neurotransmitter release in neurons and hormone release in many neuroendocrine cells. It possesses two tandem cytosolic C2 domains that bind calcium, negatively charged phospholipids, and the neuronal SNARE complex. Calcium binding to Syt1 triggers exocytosis, but how this occurs is not well understood. Syt1 has additional roles in docking dense core vesicles (DCV) and synaptic vesicles (SV) to the plasma membrane (PM) and in regulating fusion pore dynamics. Thus, Syt1 perturbations could affect release through vesicle docking, fusion triggering, fusion pore regulation, or a combination of these. Here, using a human neuroendocrine cell line, we show that neutralization of highly conserved polybasic patches in either C2 domain of Syt1 impairs both DCV docking and efficient release of serotonin from DCVs. Interestingly, the same mutations resulted in larger fusion pores and faster release of serotonin during individual fusion events. Thus, Syt1's roles in vesicle docking, fusion triggering, and fusion pore control may be functionally related.

A study on the grey relation analysis between the overall performance and individual event scores of international elite trampolinists.

This study applied grey relational analysis to assess the relationship between individual trampoline event scores and overall performance of top male and female athletes in the 2020 Tokyo Olympics. Analyzing execution, horizontal, difficulty, timing of flight, and total scores, results showed males excelled significantly in difficulty, timing, and overall performance, while execution and horizontal scores were comparable. For males, timing of flight (excluding outliers) had the greatest influence on total score, followed by difficulty and execution. In females, difficulty dominated, followed by timing and horizontal, with execution least impactful. The study highlighted the primary roles of timing and difficulty scores in overall trampoline performance, with gender variations in score contributions. The findings illuminated the interplay of score components, offering a theoretical framework for targeted trampoline training. For international athletes, key considerations included boosting height index for a robust trampoline foundation; tailoring difficulty levels to athletes' abilities while adhering to scoring rules, without sacrificing technical prowess; and sustaining training to refine quality and stability of routines.

On Canopy Rainfall Interception Modeling in a Eucalyptus Plantation

The interaction between the forest canopy and precipitation is a fundamental process for understanding the hydrological cycle in forests. Physical models have been applied to estimate canopy water interception, and their efficiency has been tested based on metrics used to assess hydrological models. For eucalyptus plantations in Brazil, more studies are needed on the canopy rainfall interception model. Thus, we calibrated the Gash model using two complete hydrological years of observation in a eucalyptus plantation in southeastern Brazil. The model’s parametrization was conducted using 17 trees individually in different planting spacings (3 m × 2 m, 3 m × 3 m, and 3 m × 5 m). The average values of the model’s parameters were taken to represent the forest, and the average parameters for each planting spacing were used to assess the model’s performance according to the planting spacings. We used NSE, KGE, and Pbias statistical metrics to assess the model’s performance. For individual trees and rainfall events, the model showed an average NSE and Pbias of 0.59 and 18.2%, respectively, meaning a “satisfactory” performance for eight trees and “poor” performance for nine trees. When the model was averaged for the entire forest and individual rainfall events were considered, the metrics were improved, being 0.643 for NSE and 8.2% for Pbias, indicating a “good” model performance, which was strengthened by an average KGE of 0.746. Regarding the model for the planting spacings, the best results were found for the 3.0 m × 2.0 m spacing (“a good performance”). For the other spacings, Pbias was higher than 15%, leading to inferior performance, but with the NSE and KGE compatible with “good” performance. The practical implications of our findings are significant, as they can be used to enhance the accuracy of models for a better understanding of the hydrological cycle in eucalyptus forests in Brazil, thereby contributing to more effective forest management and conservation.

Comparison of Biliary Complications Between Living and Deceased Donor Liver Transplantations: A Systematic Review and Meta-analysis.

To understand if the risk of biliary complications is higher with living donor liver transplantation (LDLT) compared to deceased donor liver transplantation (DDLT), the present meta-analysis was conducted to analyze the differences between these two types of liver transplantations.Three databases were searched from inception to September 2023 for comparative studies reporting biliary complications with LDLT and DDLT. Odds ratios (OR) with 95% confidence intervals were calculated for all the dichotomous outcomes.Twenty-eight studies were included in the final analysis. LDLT was associated with a significantly higher incidence of biliary complications than DDLT (OR 1.96, 95% CI: 1.56-2.47). However, on subgroup analysis, only studies published in or before 2014 reported a higher incidence of biliary complications with LDLT, but not with studies published after 2014. An analysis of individual adverse events showed that LDLT was associated with a higher incidence of both bile leak (OR 3.38, 95% CI: 2.52-4.53) and biliary stricture (OR 1.75, 95% CI: 1.20-2.55).LDLT was associated with a higher incidence of overall biliary complications, including bile leak and biliary stricture. With advances in surgical techniques, there has been a reduction in the risk of biliary complications.

Electronic detection of apoptotic cells on a microchip

Robust and rapid detection of apoptosis in cells is crucially needed for diagnostics, drug discovery, studying pathogenic mechanisms and tracking patient response to medical interventions and treatments. Traditionally, the methods employed to detect apoptosis rely on complex instrumentation like flow cytometers and fluorescence microscopes, which are both expensive and complex-to-operate except in centralized laboratories with trained labor. In this work, we introduce a microfluidic device that can screen cells in a suspension for apoptosis markers and report the assays results as electronic data. Specifically, our device identifies apoptotic cells by detecting externalized phosphatidylserine on a cell membrane – a well-established biomarker that is also targeted by fluorophore-based labeling in conventional assays. In our device, apoptotic cells are discriminated from others through biochemical capture followed by transduction of individual capture events into electrical signals via integrated electrical sensors. The developed technology was tested on simulated samples containing controlled amounts of cells with artificially-induced apoptosis and validated by benchmarking against conventional flow cytometry. Combining sample manipulation and electronic detection on a disposable microfluidic chip, our cell apoptosis assay is amenable to be implemented in a variety of settings and therefore has the potential to create new opportunities for cell-based diagnostics and therapeutics and contribute to improved healthcare outcomes on a large scale.

The Polarity of IMF By Strongly Modulates Particle Precipitation During High‐Speed Streams

AbstractRecent studies have suggested that the interplanetary magnetic field (IMF) component modulates particle precipitation during solstices, or periods of high dipole tilt . So far this explicit IMF ‐effect has only been shown in statistical studies. Here we analyzed a sequence of high‐speed stream (HSS) driven events of auroral ( keV) and medium energy ( keV and keV) particle precipitation. We show that when HSSs are comparable in terms of IMF and solar wind parameters, they can lead to systematically stronger particle precipitation in individual events when the signs of and are opposite. We also perform a superposed epoch analysis of 485 HSSs giving further evidence that the ‐effect is especially significant during HSSs. This is likely due to the persistent IMF polarity during HSSs. We show evidence that the dependence in particle precipitation is caused by a similar dependence in substorm occurrence.

A Meta-Analysis of Randomized Controlled Trials Comparing the Efficacy and Safety of Hydrophilic Versus Lipophilic Statins in Acute Coronary Syndrome Patients.

Statins differ in their solubility. Some previous studies suggested a difference in clinical efficacy and adverse events between hydrophilic and lipophilic statins. The purpose of this study is to compare the efficacy and safety of hydrophilic and lipophilic statins in patients with acute coronary syndrome. The databases of MEDLINE/PubMed, Cochrane Library, the Web of Science, and Scopus were systemically searched for articles published from inception until the 18th of July 2024. The primary outcome included major adverse cardiac events (MACE), while the secondary outcomes included myocardial infarction (MI), unstable angina (UA), revascularization, stroke, all-cause mortality, cardiovascular deaths, and adverse events. The results were pooled as risk ratio (RR) along with their 95% confidence intervals (CI). Nine studies were included. Hydrophilic statins showed a significantly higher risk of MACE and UA compared to lipophilic statins (RR 1.11 [95% CI 1.02, 1.21] and 1.30 [95% CI 1.04, 1.62]), but subgroup analysis showed a lack of significant difference between statins of similar intensity (1.01 [95% CI 0.86, 1.18] and 0.98 [0.67, 1.45], respectively). Both statins showed comparable results regarding the occurrence of MI (1.18 [95% CI 0.98, 1.40]), revascularization (1.09 [95% CI 0.99, 1.20]), stroke (1.16 [95% CI 0.80, 1.66]), all-cause mortality (1.13 [95% CI 0.92, 1.38]), cardiovascular deaths (1.14 [95% CI 0.76, 1.72]), adverse events leading to discontinuation (1.03 [95% CI 0.56,1.90]), increased alanine aminotransferase (0.61 [95% CI 0.32, 1.16]), increased creatine kinase (0.90 [95% CI 0.30, 2.72]), and increased serum creatinine (1.03 [95% CI 0.49, 2.19]). The efficacy and safety of hydrophilic and lipophilic statins are comparable when the cholesterol-lowering intensity of statins is similar. This suggests that intensity, rather than the lipophilicity of the statin, plays a more important role in the secondary prevention of MACE and individual adverse events.

P129 ASSESS THE ACCURACY OF FOUR RISK ASSESSMENT MODELS (RISKFRS, RISKWHO, RISKACC/AHA, AND RISKJBS) IN PREDICTING 10-YEAR CARDIOVASCULAR EVENT RISK IN INDIAN ACUTE MYOCARDIAL INFARCTION PATIENTS

Background: Despite numerous risk assessment models available for estimating the 10-year risk of cardiovascular (CV) events in individuals requiring primary prevention of CV disease, their applicability and accuracy in the Indian population remain inadequately studied. Objective of the study is to Assess and compare the predictive accuracy of four cardiovascular risk assessment models—RiskFRS, RiskWHO, RiskACC/AHA, and RiskJBS—in determining the 10-year cardiovascular event risk among Indian acute MI patients. Methods: In this study, 250 participants (mean age 59.4 ± 10.6 years; 205 males) without prior cardiovascular disease who experienced acute myocardial infarction (MI) were assessed using four established risk assessment models: Framingham Risk Score (RiskFRS), World Health Organization risk prediction charts (RiskWHO), American College of Cardiology/American Heart Association pooled cohort equations (RiskACC/AHA), and the 3rd Joint British Societies’ risk calculator (RiskJBS). These models estimated the participants’ predicted 10-year risk of cardiovascular events if assessed before the acute MI. Results: RiskWHO provided the lowest risk estimates, with 86.6% of patients estimated to have less than 20% 10-year risk. Conversely, RiskFRS and RiskACC/AHA yielded higher risk estimates (61.7% and 69.8% with less than 20% risk, respectively; p values &lt;0.001 compared to RiskWHO). However, RiskJBS identified the highest proportion of patients as high-risk (only 44.1% at less than 20% risk, p values &lt; 0.01 compared to all other three risk scores). Conclusions: In Indian patients experiencing acute MI, RiskJBS identifies a larger proportion of patients as ’high-risk’ compared to RiskWHO, RiskFRS, and RiskACC/AHA. However, further validation through large-scale prospective studies is necessary. These findings underscore the importance of tailoring risk assessment models to the unique characteristics of the Indian population and highlight the need for additional research to optimize cardiovascular risk prediction and management strategies in this demographic.

Coherence of Compressional Pc3‐4 Pulsation Driven by Upstream Waves in Topside Ionosphere Observed by the Swarm Constellation

AbstractIn this study, we presented a detailed analysis of ultralow frequency compressional waves with frequencies ranging from 16 to 100 mHz by using magnetic measurements of Swarm A and B, when the two spacecraft were flying in a counter‐rotating configuration. These waves are assumed to be driven by processes in the fore‐shock region and subsequently termed as upstream waves (UWs). An automatic detection algorithm for identifying UW events has been developed and applied to the Swarm magnetic measurements. Different to previous studies we take advantage of the counter‐rotating Swarm constellation to investigate the large‐scale homogeneous wavefield. Only B‐field oscillations from both Swarm A and B satellites satisfy the following criteria are accepted for UWs analysis: (a) highly correlated with normalized correlation coefficient (Cc) larger than 0.9; (b) shifted by less than 3 s between observations; (c) separated up to 90° in latitude and/or longitude. By this procedure we have identified from the years 2018–2023 in total 577 orbits containing UWs in the magnetic recordings of both spacecraft. In the first step, we checked phase shifts between UW detections at large latitudinal separation. The two counter‐rotating spacecraft allowed to make use of the Doppler effect to check the possible propagation of UWs at ionospheric altitude. Although individual events show signs of north‐south wave propagation, on average no systematic motion could be found. Similarly, possible wave motions toward or away from noon hours have been checked. By analyzing the simultaneous observations at larger longitudinal separation, also hardly any phase differences are identified in the east‐west direction. Further by evaluating the statistical results, a mean tiny local time effect seems to emerge, indicating on average an earlier arrival of the waves in the morning and later in the evening hours.

Pluralism and the Design of Autonomous Vehicles

This paper advocates for an ethical analysis of autonomous vehicle systems (AVSs) based on a moral epistemic pluralism. This paper contends that approaching the design of intricate social technologies, such as AVSs, is most effective when acknowledging a diverse range of values. Additionally, a comprehensive ethical framework for autonomous vehicles should be applied across two interconnected layers. The first layer centers on the individual level, where each autonomous vehicle becomes a unit of moral consideration. The second layer focuses on the system level, directing moral attention toward the intricate autonomous vehicle system as a whole. Distinguishing the approach from metaphysical pluralism, the paper responds to counterarguments from a moral relativist and value monist perspectives. It concludes by emphasizing the necessity of embracing epistemic pluralism to navigate the complex ethical landscape of AVSs, urging a holistic understanding that transcends individual events and integrates system-level considerations.

On the Association of Substorm Identification Methods

AbstractSubstorms are a rapid release of energy that is redistributed throughout the magnetosphere‐ionosphere system, resulting in many observable signals, such as enhancements in the aurora, energetic particle injections, and ground magnetic field perturbations. Numerous substorm identification techniques and onset lists based on each of these signals have been provided in the literature, but often with no cross‐calibration. Since the signals produced are not necessarily unique to substorms and may not be sufficiently similar to be identified for each and every substorm, individual event lists may miss or misidentify substorms, hindering our understanding and the development and validation of substorm models. To gauge the scale of this problem, we use metrics derived from contingency tables to quantify the association between lists of substorms derived from SuperMAG SML/SMU indices, midlatitude magnetometer data, particle injections, and auroral enhancements. Overall, although some degree of pairwise association is found between the lists, even lists generated by applying conceptually similar gradient‐based identification to ground magnetometer data achieve an association with less than 50% event coincidence. We discuss possible explanations of the levels of association seen from our results, as well as their implications for substorm analyses.

The prognostic role of remnant cholesterol in Asian menopausal women received percutaneous coronary intervention with acute coronary syndrome

BackgroundRemnant cholesterol (RC) exert a significant influence on atherosclerotic cardiovascular disease development. However, the prognostic implications of RC in menopausal women received percutaneous coronary intervention (PCI) who experiencing acute coronary syndrome (ACS) remain uncertain.MethodsRC was derived by subtracting the sum of high-density lipoprotein cholesterol and low-density lipoprotein cholesterol from the total cholesterol. Kaplan-Meier survival and Cox regression analysis were employed for assessing the correlation between continuous RC levels and composite and individual adverse events in Q1-Q4 quartiles. Receiver operator characteristic (ROC) curves, derived from Cox regression, were employed for analyzing the relationship between RC and both composite and individual adverse events.Results1505 consecutive menopausal women who underwent PCI and diagnosed with ACS were included. Kaplan-Meier survival analysis demonstrated a progressive reduction in composite adverse event survival rates across the four groups, observed in both the general population and among diabetic individuals, as RC values increased (Log-rank P < 0.001). The analysis of multivariate Cox regression indicated RC remained independently associated with both composite and individual adverse events. ROC analysis showed that RC enhanced the area under the curve both in total and diabetic populations for composite adverse events.ConclusionAmong menopausal women diagnosed with ACS who underwent PCI, heightened levels of RC were found to be independently correlated with an increased occurrence of adverse events.

The Hydrological Impact of Historical and Modern Earthquakes in Central-Southern Italy: Data Analysis and Seismotectonic Insights

Abstract We present the results of research conducted on the hydrological effects induced by historical and modern earthquakes in the central-southern Apennines of Italy. We investigated thirty-nine seismic events of magnitude between M 4.1 and 7.1 that occurred between 1688 and 2020. We collected 526 observations of coseismic and postseismic hydrological effects such as increase or decrease in streamflow, variations in the water levels in wells, formation and/or disappearance of springs and changes in their discharge, and changes in the chemical and physical characteristics of waters. More than half of the observations were new data unpublished to date in the scientific literature. We find that the ease of finding data of interest is strongly influenced by the historical period in which the seismic event occurred. We summarize the methodology of data retrieval and its classification and present examples and maps of coseismic hydrological changes associated with individual seismic events. Most of our novel data derive from seismic postcards, macroseismic questionnaires, and hydrographic annals. However, a nonnegligible set of data comes from a careful rereading of sources—both historical and modern—that were at first considered fruitless. The majority of data concerns an excess flow in streams and springs, and physical–chemical variations such as turbidity, an increase in temperature, and gas emission. We also find that the maximum distance to which seismically induced streamflow responses have been reported can be related to the earthquake magnitude and use this distance to derive an alternative magnitude for some of the strongest earthquakes of our dataset. Finally, we show a potential application of this type of research because the distribution of coseismic hydrological changes can provide constraints in discriminating between the causative faults of strong historical seismic events for which the instrumental data are scarce or not available.

Immune-related events in individuals with solid tumors on immunotherapy associate with Th17 and Th2 signatures.

BACKGROUNDImmune-related adverse events (irAEs) and their associated morbidity/mortality are a key concern for patients receiving immune checkpoint inhibitors (ICIs). Prospective evaluation of the drivers of irAEs in a diverse pan-tumor cohort is needed to identify patients at greatest risk and to develop rational treatment and interception strategies.METHODSIn an observational study, we prospectively collected blood samples and performed regular clinical evaluations for irAEs in patients receiving ICI therapy as standard of care for solid tumors. We performed in-parallel analysis of cytokines by Luminex immunoassay and circulating immune cells by cytometry by time-of-flight (CyTOF) at baseline and on treatment to investigate mechanisms of irAEs.RESULTSWe enrolled 111 patients, of whom 40.5% developed a symptomatic irAE (grade ≥ 2). Development of a grade ≥ 2 irAE was positively associated with the use of combination ICI and a history of an autoimmune disorder. Early changes in T helper 17 (Th17) (IL-6, IL-17f), type 2 (IL-5, IL-13, IL-25), and type 1 (TNF-α) cytokine signatures and congruent on-treatment expansions of Th17 and Th2 effector memory (Th2EM) T cell populations in peripheral blood were positively associated with the development of grade ≥2 irAEs. IL-6 levels were also associated with inferior cancer-specific survival and overall survival.CONCLUSIONSIn a diverse, prospective pan-tumor cohort, Th17 and Th2 skewing during early ICI treatment was associated with the development of clinically relevant irAEs but not antitumor responses, providing possible targets for monitoring and therapeutic interventions.FUNDINGJohns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy, the NCI SPORE in Gastrointestinal Cancers (P50 CA062924), NCI grant (R50CA243627 to LD), the NIH Center Core Grant (P30 CA006973), Swim Across America (to MY), NIAMS (K23AR075872 to LC), and imCORE-Genentech grant 137515 (to Johns Hopkins Medicine on behalf of MY).

Single-Molecule Identification and Quantification of Steviol Glycosides with a Deep Learning-Powered Nanopore Sensor.

Steviol glycosides (SGs) are a class of high-potency noncalorie natural sweeteners made up of a common diterpenoid core and varying glycans. Thus, the diversity of glycans in composition, linkage, and isomerism results in the tremendous structural complexity of the SG family, which poses challenges for the precise identification and leads to the fact that SGs are frequently used in mixtures and their variances in biological activity remain largely unexplored. Here we show that a wild-type aerolysin nanopore can detect and discriminate diverse SG species through the modulable electro-osmotic flow effect at varied applied voltages. At low voltages, the neutral SG molecule was drawn and stuck in the pore entrance due to an energy barrier around R220 sites. The ensuing binding events enable the identification of the majority of SG species. Increasing the voltage can break the barrier and cause translocation events, allowing for the unambiguous identification of several pairs of SGs differing by only one hydroxyl group through recognition accumulation from multiple sensing regions and sites. Based on nanopore data of 15 SGs, a deep learning-based artificial intelligence (AI) model was created to process the individual blockage events, achieving the rapid, automated, and precise single-molecule identification and quantification of SGs in real samples. This work highlights the value of nanopore sensing for precise structural analysis of complex glycans-containing glycosides, as well as the potential for sensitive and rapid quality assurance analysis of glycoside products with the use of AI.