Central and Eastern United States (CEUS) earthquakes are less common than those in the tectonically active West Coast, but their significance is elevated due to higher population densities, less-attenuating bedrock geology, variable site-amplification effects, and a higher proportion of structures prone to damage from shaking. Associating CEUS earthquake focal mechanisms with causative crustal faults is challenging due to a lack of mapped faults. Aftershock productivity of CEUS earthquakes is difficult to predict because it is highly variable, displaying globally typical behavior in some regions (Wu et al., 2015; Wu and Chapman, 2017) and low decay rates (Stein and Liu, 2009; Calais et al., 2016; Toda and Stein, 2018) in others. Here, we study the aftershock sequence of an unusual Mw 4.24 CEUS earthquake that occurred below the Atlantic Coastal Plain east of Dover, Delaware, in late 2017. We analyze data from a temporary 14-station network and use template matching to search for aftershocks, which we locate using a custom 1D velocity model. We find aftershock locations favoring slip on a northwest–southeast-striking fault oblique to the presumed fault where the mainshock was located. We document an unusually low a value and large magnitude difference between the mainshock and the largest aftershock, as well as an average aftershock decay p value. Factors proposed to explain variations in aftershock productivity include fault alignment relative to the prevailing stress field (Hardebeck, 2010) and low productivity after a high stress drop (Wetzler et al., 2018). We test these hypotheses in relation to the 2017 Delaware earthquake aftershocks, showing the Delaware earthquake had a stress drop of 35 MPa, normal for an intraplate region (Boyd et al., 2017), and had favorable alignment for aftershock thrust faulting. We therefore propose a small fault of possible pre-Mesozoic origin, limiting the productivity observed.

In sustainable portfolio management, categorizing assets as “brown“ or “green“ based solely on ESG ratings can be misleading. A positive ESG score does not inherently indicate environmental responsibility unless it is evaluated relative to a meaningful benchmark. We propose a rescaled ESG rating system that measures each asset’s environmental standing relative to a threshold set by policymakers, reflecting the urgency of the current climate crisis. In this system, assets are assigned positive scores if they exceed the threshold (green) and negative scores if they fall below it (brown), enhancing the interpretability of sustainability metrics in portfolio construction. However, a challenge arises when aggregating these scores into an overall portfolio rating. Under sustainable portfolio optimization developed in [11], short positions in brown assets, otherwise effectively betting against polluting companies, can paradoxically improve the portfolio’s sustainability score. This creates a misleading incentive structure. To address this, we introduce a constraint that prohibits short positions in brown assets, ensuring that such investments do not positively impact the portfolio’s sustainability rating. While this restriction better aligns with environmental objectives, it also introduces complexity into the optimization process. To resolve this, we present an intuitive algorithm inspired by the active set method, which we refer to as Green Portfolio Optimization, capable of handling these constraints efficiently even in high-dimensional settings.

Rapid detection of antibiotic-resistant bacteria is a crucial tool in the global fight against antimicrobial resistance, helping to limit the spread of resistance and guide treatment decisions. Here, we report the design, synthesis, and electrochemical evaluation of β-lactam-based redox-activatable probes for detecting β-lactamase activity. The probes incorporate a β-lactam core linked to redox reporters through cleavable linkages, enabling signal generation upon enzymatic hydrolysis. High-performance liquid chromatography and differential pulse voltammetry analyses were used to assess time-dependent activation and concentration-dependent responses against commercial β-lactamase blends and metallo-β-lactamases. Selected probes, bearing cephalosporin recognition motifs and maltol redox reporters, were further evaluated against clinical isolates, demonstrating selective activation in carbapenemase-producing strains. To extend the platform toward solid-state biosensing, an azide-functionalized analog was clicked on alkyne-modified glassy carbon electrodes. Stepwise surface functionalization and immobilization were validated electrochemically using model redox reporters, confirming their activity. The immobilized probe retained responsiveness, demonstrating the feasibility of integrating this sensing strategy into solid-state diagnostic devices. By integrating stable cephalosporin scaffolds with redox-reporter signaling, this work introduces a novel probe system that unites chemical probe design with surface-based electrochemical sensing, providing a strong foundation for the development of portable, point-of-care diagnostics for β-lactamase-mediated antibiotic resistance.

Perfluorohexyloctane (F6H8) is a semifluorinated alkane increasingly used in medical applications. Emerging evidence, however, indicates that this compound can persist in biological systems and influence cellular processes. These observations suggest that the exceptional stability of F6H8, while beneficial for medical performance, may also have implications for long-term biological and health outcomes.

Fibroblast growth factor receptor 2 (FGFR2) alterations have emerged as an important targetable oncogenic driver in a biologically distinct subset of biliary tract cancers (BTCs), particularly intrahepatic cholangiocarcinoma (iCCA), alongside other actionable genomic events such as IDH1 mutations, BRAF V600E, HER2 amplification and MSI-H. FGFR2 fusions and mutations define a distinct molecular subgroup whose prevalence varies across geographic regions and etiologic backgrounds such as liver fluke-associated disease. Clinical studies of both reversible and irreversible FGFR inhibitors have demonstrated meaningful activity in FGFR2-rearranged iCCA, while also highlighting a characteristic toxicity profile dominated by on-target hyperphosphataemia. Parallel translational work using cfDNA-based liquid biopsy has mapped a spectrum of secondary kinase-domain mutations that underlie acquired resistance, informing the development of next-generation FGFR2-selective inhibitors (eg, lirafugratinib) and combination strategies with EGFR/ERBB blockade. Collectively, these data underscore the need for comprehensive molecular profiling and innovative umbrella trial designs to optimise targeted therapy in this rare, biologically heterogeneous malignancy.

BACKGROUND Fractional flow reserve (FFR)-negative coronary lesions are usually managed medically. Lesion-specific plaque characterization and FFR changes over time remain elusive. AIMS To assess disease progression in FFR-negative lesions over a two-year period using FFR derived from coronary CT angiography (CCTA) (FFRct) and to investigate whether FFR decline over a two-year period is associated with plaque characteristics. METHODS This single-center prospective study included patients undergoing coronary angiography with one or more invasive intermediate lesions (FFR 0.81-0.90) in non-stented, non-culprit coronary arteries. Two years after the index procedure, patients underwent CCTA with FFRct and quantitative plaque analysis. RESULTS We enrolled 131 patients (152 vessels). Two-year follow-up with FFRct and plaque analysis was available in 68 (52 ​%) patients (73 vessels). Compared to invasive FFR at baseline, FFRct at 2y follow-up was significantly lower (median difference -0.06) at vessel level analysis (p ​< ​0.001). FFR declined in 55 (75 ​%) lesions. The 35 study vessels with an FFRct≤0.80 ​at 2-year follow-up had higher total percent atheroma volume (PAV) (41 ​% vs. 23 ​%; p ​= ​0.002) and more high-risk plaque composition, including noncalcified PAV (30 ​% vs. 18 ​%; p ​= ​0.002), and low-attenuation PAV (1.1 ​% vs. 0.7 ​%; p ​= ​0.046) compared to vessels with an FFRct>0.80 (n ​= ​38). Rates of study vessel revascularization in the 131 patients were 6.9 ​% at 2 years and 15.1 ​% after 4.9 years of follow-up after index procedure. CONCLUSIONS Rates of coronary revascularization are substantial in patients with medically managed intermediate lesions. In this selected cohort, an FFRct ≤0.80 ​at two-year follow-up was associated with higher plaque burden and presence of high-risk plaque composition.

Introduction: Intracranial stenting during endovascular thrombectomy (EVT) is a common practice in the setting of failed reperfusion or severe stenosis. Immediate stent patency requires periprocedural antiplatelet therapy (APT). How APT intensity interacts with prior intravenous thrombolysis (IVT) to influence hemorrhagic risk remains uncertain. We aimed to assess whether the APT regimen modifies the association of IVT with early intracranial hemorrhage after intracranial stenting during EVT. Methods: This was a subanalysis of the RESISTANT registry, a multicenter, international, retrospective cohort (2016 to 2023) of adults with acute ischemic stroke who underwent intracranial stenting during EVT. APT regimens were categorized as conservative (intravenous or oral aspirin alone, or aspirin plus an oral P2Y12 inhibitor) and aggressive (any regimen including intravenous GPIIb/IIIa inhibitor or intravenous cangrelor). Four main groups were compared according to the APT regimen (conservative/aggressive) and the use of IVT (+/-). The primary outcome was a composite of sICH and parenchymal hematoma types 1 and 2 (sICH-PH2-PH1). Multivariable logistic regression models were used to evaluate the interaction between IVT and APT, adjusting for clinically relevant covariates. Results: Among the 823 included patients, 44 (5.3%) received conservative APT with IVT, 130 (15.8%) received conservative APT without IVT, 145 (17.6%) received aggressive APT with IVT, and 504 (61.2%) received aggressive APT without IVT. Among patients who received IVT, sICH-PH2-PH1 rates were 9.3% with conservative APT and 10.7% with aggressive APT; among those without IVT, rates were 3.2% and 9.9%, respectively. Administration of IVT (adjusted odds ratio [aOR] 5.84, 95%CI 1.07 to 43.92; p=0.05) and aggressive APT (aOR 4.81, 95% CI 1.41 to 30.22; p=0.03) were each associated with higher odds of hemorrhagic complications, with a significant IVT by APT interaction (P interaction =0.05; Figures 1 and 2 ). Within the aggressive APT plus IVT subgroup, sICH-PH2-PH1 occurred in 20% of patients treated with cangrelor and 6.1% treated with a glycoprotein IIb/IIIa inhibitor ( Figure 3 ). Conclusion: Among patients requiring intracranial stenting, aggressive periprocedural APT and prior IVT are each associated with higher hemorrhagic risk, with the combination showing the worst observed crude outcome. Prospective evaluation of protocolized APT pathways in the IVT setting is warranted.