Avalon Pharma (United States)

Strong-motion flat-files form the backbone of ground-motion modelling and seismic hazard assessment, yet India has long lacked a uniformly processed, comprehensive strong-motion database aligned with international standards. The study addresses this critical gap by developing a systematically processed ground-motion flat-file for earthquakes recorded across the Indian subcontinent, particularly for the Himalayan region where seismic hazard remains high and strong-motion data are sparse. The compiled flat-file includes 778 manually processed accelerograms from 195 earthquakes spanning the time period 1986-2018. These events, with moment magnitudes Mw ≥ 2.0 and epicentral distances Repi < 600 km, were recorded at 254 seismic stations. The diversity of source-to-site configurations captured in this dataset enhances its applicability for developing regionally representative GMMs and for examining spatial variations in ground-motion characteristics. The waveform processing followed a consistent step-by-step protocol involving baseline correction, tapering, filtering, windowing and signal-to-noise ratio. The resulting flat-file contains a comprehensive suite of Intensity Measures (IMs) including Peak Ground measures (PGA, PGV, PGD), Spectral Acceleration (SA), Fourier Amplitude Spectrum (FAS), Effective Amplitude Spectrum (EAS), Arias intensity (AI), Cumulative absolute velocity (CAV), Significant Duration (SD), Acceleration Spectrum Intensity (ASI), Velocity Spectrum Intensity (VSI), and Characteristic Intensity (Ic). The reliability of the processed IMs was validated through residual analysis of FAS against an empirical model. As the first uniformly processed strong-motion flat-file for India that includes both horizontal and vertical components, this dataset provides a much-needed foundation for advancing ground-motion modelling and seismic hazard assessment in the region. Overall, this flat-file significantly strengthens the database, evaluates attenuation behaviour, conducting parametric and near-field ground-motion studies, and supporting site-specific seismic hazard assessments across the Indian region.

Abstract Toll-like receptor 9 (TLR9) is an innate DNA sensor that activates pro-inflammatory pathways and contributes to the maturation of antigen presenting cells. TLR9 deficiency has been implicated in impaired tumor immunosurveillance and attenuated responsiveness to immune checkpoint blockade. We developed an adeno-associated virus (AAV) vector encoding TLR9 to restore receptor expression in individuals with TLR9 deficiency and augment antitumor immunity. We first evaluated transgene biodistribution in mice 21 days after intraperitoneal administration of 1x10 11 vector genomes (vg) of AAV6.2FF-TLR9 using RNA in-situ hybridization. TLR9 was detected in liver, spleen, pancreas, ovary, heart, and lymph node, indicating systemic transduction and transcription following intraperitoneal delivery. To assess safety, mice and hamsters received low (1.5x10 13 vg/kg) or high (4.5x10 13 vg/kg) dose of AAV6.2FF-TLR9 intraperitoneally and were evaluated at 7, 28, and 56 days post-administration. Across both species and dosages, no adverse vector-related changes were observed in leukocyte counts, plasma biomarkers of hepatic or renal function, pro-inflammatory cytokines, or upon histopathological examination. The broad tissue expression and favorable safety profile of intraperitoneally delivered AAV6.2FF-TLR9 support progression of this vector toward clinical development as a gene replacement strategy to potentially enhance to efficacy of checkpoint blockade in patients with metastatic malignancies and impaired TLR9 signaling.

The Taupō Volcanic Zone (TVZ) in New Zealand is a region of highly productive Quaternary volcanism and high hydrothermal heat flux. We investigate the mid-crustal seismic velocity structure of a region within the central, rhyolitic part of the TVZ encompassing high-temperature geothermal systems (e.g. Wairakei, Rotokawa). Using double-difference tomographic inversion of local earthquake data we derive 3-D models of P-wave velocity ( Vp ) and Vp/Vs for the subsurface. Both high ( > 6.0 km/s) and low ( < 5.5 km/s) Vp heterogeneities are seen in the mid-crust between 5 and 11 km depth. Regions with high Vp are interpreted to indicate the presence of solidified, more mafic, material within an otherwise quartzo-feldspathic crust, while regions with low Vp values are inferred to represent bodies of crystal-rich magma with a low melt fraction. Using the new 3-D velocity model we then relocated ∼ 9100 earthquakes recorded between 2009 and 2022. The relocated seismicity is strongly clustered, including in the vicinity of some of the geothermal systems (e.g. Rotokawa) where fluid is currently being extracted for electric-power production. Mid-crustal seismicity is also observed west of the Wairakei geothermal field, as well as along the south-eastern margin of the Ngakuru graben and on the western margin of the Whakamaru caldera. The depth distribution of the highest-quality hypocentres shows that 90% of the seismicity at Rotokawa geothermal field occurs at depths shallower than 5.1 km, consistent with a shallow brittle–ductile transition and the presence of a cooling pluton beneath Rotokawa seen in magnetotelluric data. • A 3-D image of P -wave velocity ( Vp ) illuminates the mid-crustal structure beneath collapse calderas and geothermal systems. • Vp in the mid-crust is spatially heterogeneous, with anomalies ± 20 % . • Low Vp anomalies at 7-11 km depth are interpreted to be crystal-rich low-melt fraction magma. • Relocated seismicity is clustered within the geothermal systems and in an area near the Taupō Rift axis. • The top of the brittle–ductile transition inferred from the seismicity is as shallow as 5 . 1 ± 0 . 3 km in places.

Myocardial bridging is a congenital coronary anomaly in which a segment of a coronary artery travels intramyocardially instead of on the epicardial surface. While often asymptomatic, myocardial bridging can occasionally result in ischemia or arrhythmias. We present the case of a 37-year-old woman with recurrent exertional chest pain and exercise-induced hypotension. Stress testing revealed mild anterior ischemia, and coronary angiography demonstrated a mid-left anterior descending myocardial bridge. Intravascular ultrasound confirmed extensive systolic compression with increased plaque burden at the bridged site. Medical therapy with vasodilators and beta-blockers was not tolerated due to adverse effects, and symptoms persisted. The patient underwent surgical unroofing of the bridged segment, which resulted in complete resolution of chest pain and improved exercise tolerance. This case highlights the role of advanced imaging in the diagnosis of MB and the importance of individualized management when medical therapy fails.

Penelitian ini menyajikan analisis triangulatif terhadap lanskap inklusi keuangan digital Indonesia, dengan membandingkannya terhadap negara-negara tetangga di ASEAN. Dengan memanfaatkan basis data Global Findex 2025 dari Bank Dunia yang baru dirilis—yang mencakup indikator-indikator baru terkait konektivitas dan keamanan digital—penelitian ini memetakan posisi Indonesia dalam hal adopsi pembayaran digital dan kesenjangan gender. Temuan dari survei sisi permintaan (demand-side) ini kemudian dianalisis secara kontekstual dengan kerangka kebijakan regional ASEAN, seperti inisiatif Konektivitas Pembayaran Regional (Regional Payment Connectivity) dan toolkit kebijakan untuk UMKM digital. Sebagai pilar ketiga triangulasi, data survei global ini disandingkan dengan data pasar dan regulasi domestik sisi penawaran (supply-side) pasca-2024 dari Otoritas Jasa Keuangan (OJK) Indonesia, yang mencakup pertumbuhan layanan keuangan digital seperti Buy Now, Pay Later (BNPL) dan penguatan kerangka perlindungan konsumen. Hasil analisis menunjukkan bahwa meskipun Indonesia menunjukkan kemajuan pesat dalam adopsi pembayaran digital yang didorong oleh kebijakan, keberhasilan ini menutupi tantangan mendasar dalam hal ketahanan keuangan dan kesenjangan gender yang lebih bernuansa. Kesenjangan ini menjadi lebih jelas ketika data persepsi dari survei global dikontraskan dengan realitas transaksional pasar domestik. Artikel ini berargumen bahwa metode triangulasi ini menawarkan model yang lebih kokoh untuk analisis kebijakan, mengungkap area-area kritis untuk intervensi yang tidak akan terlihat dari analisis sumber tunggal, dan menggarisbawahi pergeseran penting dari sekadar mengukur akses keuangan menuju evaluasi kualitas dan keberlanjutan inklusi.

Introduction: Coronary artery calcification (CAC), a hallmark of advanced atherosclerosis, is driven by inflammatory cytokines like TNF-α, IL-6, and ICAM-1, worsening outcomes Post-Per Cutaneous Coronary Intervention (PCI). Drug-coated balloons (DCBs) offer a stent-free alternative to drug-eluting stents (DES) in CAC, but their anti-inflammatory mechanisms remain unclear. This study evaluates DCB-induced TNF-α suppression and its link to clinical and angiographic outcomes. Hypothesis: DCBs reduce inflammation-driven calcification via TNF-α modulation, improving procedural success and lowering major adverse cardiac events (MACE). Methods: A systematic review (2020–2025) of PubMed, EMBASE, and Cochrane Library identified studies evaluating DCB use in CAC. Inclusion criteria required reporting pre- and post-procedural inflammatory markers (TNF-α, IL-6, ICAM-1) or MACE (cardiac death, myocardial infarction, target lesion revascularization). Three studies (n=1,218) were analyzed using random-effects models and mixed regression. Results: DCBs significantly reduced TNF-α in calcified lesions (41.78±6.21 vs. 37.91±5.89 pg/mL; p =0.018), with greater reductions in severe calcification (Δ=−6.3 vs. −2.1 pg/mL; p =0.03). No changes in IL-6 (2.55±1.02 vs. 3.11±1.34 pg/mL; p =0.18) or ICAM-1 (14.11±3.45 vs. 13.91±3.12 ng/mL; p =0.62) were observed. MACE rates in calcified lesions (11.3%; 95% CI:8.2–14.4%) matched non-calcified lesions (9.8%; p =0.24). Angiographic success was 92%, with lower stent deformation vs. DES (4% vs. 12%; p =0.01). DCBs showed non-inferior late lumen loss to DES (0.24±0.18 vs. 0.27±0.21 mm; p =0.15). Subgroup analysis linked baseline TNF-α &gt;50 pg/mL to higher 12-month TLR (18.7% vs. 8.9%; p =0.004). Conclusions: DCBs selectively suppress TNF-α in CAC, correlating with reduced restenosis and high procedural success. While IL-6/ICAM-1 remained unaffected, TNF-α modulation positions DCBs as viable DES alternatives in complex CAC. Limitations include short follow-up and protocol heterogeneity. Future studies should standardize lesion preparation and extend cytokine monitoring.

Human pressures and climate change are transforming coral reef ecosystems, threatening both the biodiversity and the services they provide. These disturbances can reshape the functional composition of reef fish communities, weakening the ecological processes that support reef stability and resilience. Understanding these changes is essential for informing effective management and conservation. Here, we present findings from an expedition that surveyed 64 Cuban reefs along a 2000 nautical-mile route, examining variation in enforcement and fishing intensity. We hypothesized reef fish functional diversity declines where enforcement is weak and fishing pressure is high, predicting strong associations between diversity indices, enforcement strength, and fishing intensity. We quantified species biomass, defined functional traits using ten ordinal and nominal variables, and calculated functional alpha- and beta-diversity indices at each site. To analyze patterns in alpha and beta-diversity, we used linear models and multivariate statistics, respectively, with enforcement and fishing intensity as covariates. All alpha diversity indices, except functional evenness, increased with stronger enforcement and decreased with higher fishing intensity, indicating local fish communities responded strongly to management. Beta diversity analyses revealed significant differences in community composition across sites, also following gradients of stronger enforcement but, conversely, lower fishing intensity. Our results highlight clear trends: (1) unprotected sites showed predator depletion, while (2) well-protected sites supported higher biomass and larger mobile predators due to fishing exclusion. Together, these findings demonstrate the critical role of effective enforcement in maintaining reef fish functional diversity and protecting the ecological processes that support coral reef resilience.

This study assessed COVID-19 preventive practices among 200 young adults in Tangail town, Bangladesh, focusing on the influence of socio- demographic factors such as sex and education level. Data collected through a pre-tested, semi-structured questionnaire revealed that 79% visited crowded places, 89% wore masks, 94.5% disinfected hands with soap, and 92% obeyed government restrictions. Significant gender differences were observed, with females showing higher compliance in mask-wearing and hand hygiene practices. Education level was also linked to better adherence, with those having higher education showing greater adherence to preventive practices. These findings highlight the need for targeted public health strategies and improved communication to address gaps in preventive behaviors and enhance preparedness for future pandemics.

ObjectivesThe use of cost-effectiveness methods to support policy decisions has become well established, but difficulties can arise when evaluating a new treatment that is indicated to be used in combination with an established backbone treatment. If the latter has been priced close to the decision maker’s willingness-to-pay threshold, this may mean that there is no headroom for the new treatment to demonstrate value, at any price, even if the combination is clinically effective. Without a mechanism for attributing value to component treatments within a combination therapy, the health system risks generating negative funding decisions for combinations of proven clinical benefit to patients. The aim of this work was to define a value attribution methodology, which could be used to allocate value between the components of any combination treatment. MethodsThe framework is grounded in the standard decision rules of cost-effectiveness analysis and provides solutions according to key features of the problem: perfect/imperfect information about component treatment monotherapy effects and balanced/unbalanced market power between their manufacturers. ResultsThe share of incremental value varies depending on whether there is perfect/imperfect information and balance/imbalance of market power, with some scenarios requiring the manufacturers to negotiate a share of the incremental value within a range defined by the framework. ConclusionsIt is possible to define a framework that is independent of price and focuses on benefits expressed as quality-adjusted life-year gains (and/or quality-adjusted life-year equivalents for cost savings), a standard metric used by many health technology assessment agencies to evaluate novel treatments.