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Influence of surrounding topography on earthquake ground motions in intermontane basin settings: Insights from the Kathmandu basin
No full textIntermontane basins in active orogenic regions face significant seismic hazard due to their proximity to sustained tectonic activity. While the sediments deposited in these basins create a relatively flat topography suitable for urban and infrastructure developments, their unconsolidated sedimentary fill locally amplifies earthquake-induced ground motions, thereby increasing the seismic hazard and risk. Documented observations suggest that ground motion estimates in these basins are often poorly constrained due to oversight of surrounding surface topography and insufficient sub-surface information about deeper basin layering, leading to inaccurate hazard assessments. In this study, we systematically evaluate the implications of these two factors on ground motion characteristics up to 4.4 Hz, which is crucial for earthquake engineering practices. We conducted 3D simulations around the Kathmandu catchment area (Nepal) using hypothetical thrust-faulting moment tensor sources at various depths and locations. The results show a significant reduction, by an order of magnitude, in the peak ground velocities (PGV) at the catchment area due to surface topography. However, this effect is prominent only for very shallow earthquakes producing predominant surface waves; for deeper sources, the de-amplification may be negligible or even result in amplification due to scattered body waves converted into surface waves. To incorporate basin-specific material properties, we performed the analysis in a computationally-feasible 2D domain, which shows that the existence of topography can reduce the energy entering the basin, hence resulting in a reduced basin amplification. The deeper layers of the Kathmandu basin play a critical role in controlling the spatial variability of the observed amplification, with significant differences within the basin compared to scenarios that exclude these deeper layers. We conclude that neglecting topography in ground motion predictions may lead to an overestimation of ground motion amplification in the basin. Pronounced topographic features in the surrounding of intermontane basins can result in further scattering of the received energy content from earthquakes occurring outside of the basin, especially for the high-frequency motions. In addition, in order to provide site-specific measures of ground motion in intermontane basins, high spatial resolution of the underlying geological structure is deemed imperative
Modelling tree survival for investigating climate change effects
No full textUsing German forest health monitoring data we investigate the main drivers leading to tree mortality and the association between defoliation and mortality; in particular (a) whether defoliation is a proxy for other covariates (climate, soil, water budget); (b) whether defoliation is a tree response that mitigates the effects of climate change and (c) whether there is a threshold of defoliation which could be used as an early warning sign for irreversible damage. Results show that environmental drivers leading to tree mortality differ by species, but some are always required in the model. The defoliation effect on mortality differs by species but it is always strong and monotonic. There is some evidence that a defoliation threshold exists for spruce, fir, and beech. We model tree survival with a smooth additive Cox model allowing for random effects taking care of dependence between neighboring trees and nonlinear functions of spatial time varying and functional predictors on defoliation, climate, soil and hydrology characteristics. Due to the large sample size and large number of parameters, we use parallel computing combined with marginal discretization of covariates. We propose a “boost forward penalize backward” scheme based on combining component-wise gradient boosting with integrated backward selection. Supplementary materials for this article are available online, including a standardized description of the materials available for reproducing the work.</p
A protocol for a pilot randomised controlled trial of a Tailored Intervention for people with moderate-to-severe Chronic Obstructive Pulmonary Disease and Co-morbidities delivered by Pharmacists and Consultant respiratory Physicians (TICC-PCP) in Scotland
No full textBackgroundSymptomatic chronic obstructive pulmonary disease (COPD) is a global health problem associated with a number of co-morbidities, disproportionately affecting people who are poor. Sub-optimal management of symptomatic COPD and co-morbidities negatively impacts quality of life, ability to work and survival. Previous trials of healthcare professional-led complex interventions have targeted COPD management, but not also simultaneously targeted the treatment of co-morbidities. Recommendations for complex intervention testing include feasibility studies followed by pilot randomised controlled trials (RCTs), including economic and parallel process evaluations. Following a feasibility study, a Tailored, home-based Intervention for people with COPD and Co-morbidities by generalist prescribing Pharmacists collaborating with Consultant respiratory Physicians (TICC PCP) is undergoing pilot testing. The pilot study aims to recruit at least 70% of invited participants within 4 months; deliver TICC PCP to at least 70% of participants in the intervention arm; retain at least 80% of participants (excluding those who died or developed incapacity before the end of the study) until 21-month data collection; and collect at least 90% of in person data at each study time point. In addition, findings from the economic and process evaluations along with information obtained on the proposed quantitative efficacy outcomes inform on the sample size required for a subsequent definitive RCT will help inform on future research.MethodsWe describe methods for a multicentre pilot RCT, with parallel economic and qualitative process evaluations of TICC PCP. Set in Glasgow and Edinburgh (Scotland), we plan to recruit 100 people with symptomatic COPD and conduct home-based assessments at baseline and at subsequent three monthly follow up visits over a period of 21 months. Independent researchers will collect extensive health and social care data at recruitment (baseline) before participants are randomised (stratified by site and number of respiratory hospitalisations in the past 12 months), to TICC PCP in addition to usual care (UC), or UC alone. Collected data will include objective and subjective measures of health, healthcare utilisation (including prescribing), home circumstances, health related quality of life, healthcare resource use and intervention costs. Follow up data will be collected three monthly for 21 months. The intervention, delivered by NHS Pharmacists visiting participants at home monthly for 6 months, then every 2 months for the next 6 months, involves clinical assessment and intervention at home including prescribing for COPD and co-morbidities. Pharmacists will also assess and help participants to address wider health needs, e.g. appointment attendance and home equipment. Pharmacists will collaborate mainly with consultant respiratory physicians, and General Practitioners.DiscussionA holistic, 1 year long, individualised home-based intervention for people with symptomatic COPD and co-morbidities may help address unmet health needs. We will utilise the information obtained from this pilot study, including: the recruitment and retention rates; the sample size required to detect a minimal clinically important difference in the proposed efficacy outcomes of interest; the economic analyses; and process evaluation, to determine whether we should progress to a definitive RCT with parallel process and economic evaluation.Trial registrationThe trial is registered with the UK Clinical Trials Registry (ISRCTN 43508703)
The efficient tail hypothesis: an extreme value perspective on market efficiency
No full textIn econometrics, the Efficient Market Hypothesis posits that asset prices reflect all available information in the market. Several empirical investigations show that market efficiency drops when it undergoes extreme events. Many models for multivariate extremes focus on positive dependence, making them unsuitable for studying extremal dependence in financial markets where data often exhibit both positive and negative extremal dependence. To this end, we construct regular variation models on the entirety of R and develop a bivariate measure for asymmetry in the strength of extremal dependence between adjacent orthants. Our directional tail dependence (DTD) measure allows us to define the Efficient Tail Hypothesis (ETH) -- an analogue of the Efficient Market Hypothesis -- for the extremal behaviour of the market. Asymptotic results for estimators of DTD are described, and we discuss testing of the ETH via permutation-based methods and present novel tools for visualization. Empirical study of China's futures market leads to a rejection of the ETH and we identify potential profitable investment opportunities. To promote the research of microstructure in China's derivatives market, we open-source our high-frequency data, which are being collected continuously from multiple derivative exchanges
Targeting Cis-regulatory elements for CRISPR-mediated transcriptional activation of the human MIR503HG locus
No full textAdvances in genome annotation have revealed a striking increase in the number and complexity of non-coding RNA (ncRNA) genes, particularly multi-transcript loci that harbor long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) within the same genomic region. These loci can often function as coordinated regulatory units, with their transcription modulated by shared cis-acting regulatory elements (CREs). Traditional gene manipulation approaches, which typically target individual transcripts, are insufficient to capture the full regulatory and therapeutic potential of these complex loci. Here, we present “cis-ON” a single-vector lentiviral delivery system based on CRISPR activation (CRISPRa), designed to simultaneously upregulate multiple noncoding RNA transcripts by targeting a single CRE.We focused on the evolutionarily conserved MIR503HG locus, which encodes seven lncRNA isoforms and hosts the miR-424/503 cluster, both implicated in various cellular processes, including proliferation, angiogenesis, and endothelial-to-mesenchymal transition. Using integrative analysis of histone marks (H3K27Ac, H3K4Me3), DNase hypersensitivity, and CAGE-seq data, we identified the primary promoter of the MIR503HG locus. A dual fluorescent reporter screen selected optimal single guide RNAs (sgRNAs) for targeting this region. We then engineered cis-ON, a novel lentiviral system combining dCas9-VPR and sgRNA to enable a streamlined single-vector delivery approach. Transduction of primary human endothelial cells with this system robustly activated the entire locus including the MIR503HG isoforms and co-embedded miRNAs miR-424 and miR-503, demonstrating coordinated transcriptional regulation. Additionally, the neighboring LINC00629 lncRNA locus remained unaffected, highlighting regulatory specificity.This approach demonstrates the feasibility of modulating complex ncRNA loci across a ∼ 10 kb genomic region by targeting a single CRE, bypassing limitations of transcriptspecific strategies. By enabling simultaneous upregulation of lncRNAs and miRNAs, the cis-ON platform provides a streamlined strategy for restoring regulatory networks disrupted in disease
Trust, but verify:Managerial ability and conditional accounting conservatism
No full textHigh-ability managers’ performance track records and “integrity” culture foster capital providers’ trust and reduce career risks, allowing them to set the firm’s financial reporting policies. Employing this discretion, high-ability managers are likely to report less conditionally conservative earnings. Data from S&P 1500 U.S. firms between 1996 and 2017 support this conjecture. Additional analysis continues to suggest that high-ability managers lower conditional accounting conservatism under limited boundary conditions. We also document that some high-ability managers misuse their financial reporting discretion opportunistically. Despite this, using a two-stage method, we show that our proposed theoretical mechanism—firms with a stronger corporate integrity culture, which promotes trust—enables high-ability managers to report less conditionally conservatively. This study contributes to the research on accounting conservatism and managerial behavior, cautioning capital providers against placing excessive trust in high-ability managers, as in some cases, that trust has been found to be misplaced
The Secrets of the Extreme Durability of Odonata Wings
No full textEssential properties considered in the design, fabrication, and application of contemporary bio/nanomaterials have been modeled on adaptations of biological systems, one of which is the robustness of insect wings. Proto-odonate wing development in Meganeuridae began during the Carboniferous period; over 350 million years of wing evolution has selected for agility and long-distance flight capacity in dragonflies and damselflies, making them suitable model taxa for bio-inspired design related to flight. Dragonfly species vary in flight behavior, reflected by variation in wing stiffness and flexibility due to differential venation patterns, wing biochemistry, and wing shape and size. We analyzed 8 distinct characteristics of dragonfly wings that are related to wing durability and could serve as bio-designs for novel technical innovations: venation, nano-architectural surface, pterostigma, antiwetting properties, antimicrobial properties, antifatigue features, antiaging features, and sensory structures. Specifically, we examined a tropical African species of Libellulidae dragonfly, Aethriamanta rezia, using scanning electron microscopy and cuticular profiling, which revealed the presence of hydrocarbons responsible for these functions. Furthermore, we investigated the optical response of the wings within the UV-vis-NIR region. We discuss these wing features in the context of durability and environmental stresses
Anthropogenic Noise Exposure Suppresses the Immune Response in Mytilus spp. Following Vibrio splendidus Challenge
No full textINTRODUCTION: Anthropogenic noise is a growing environmental stressor in marine ecosystems, yet its effects on immune function in bivalves remain poorly understood.METHODS: This study examined the transcriptional response of blue mussels, Mytilus spp., following exposure to ship noise for seven days, followed by a low-dose Vibrio splendidus bath challenge. RESULTS: Transcriptomic analysis at multiple time points postnoise exposure revealed only subtle changes in expression signatures which appeared to resolve at later time points. However, compared with the controls, mussels exposed to ship noise showed a reduced number of differentially expressed genes in their gill tissue following bacterial challenge. This indicated a suppressed immune response, as indicated by reduced expression of immunerelated genes compared to controls. While bacterial burden and mortality did not significantly differ between noise-exposed and control groups, the proportion of GFP-tagged Vibrio splendidus colonies was higher in noise-exposed mussels. CONCLUSIONS: These findings contribute to a growing body of evidence that anthropogenic noise may impair immune function in bivalves, with implications for aquaculture and marine ecosystem health.</p
Evaluation of benzimidazole resistance in equine cyathostomins in the Kermanshah province of Iran using coprological analysis and allele-specific PCR
No full textBackground: Resistance to benzimidazole (BZ) by cyathostomin nematodes has become a major threat to equine health around the world. We aimed to evaluate the efficacy of BZ drugs against small strongyle nematodes in horses of western Iran using coprological and molecular examination. Methods: Faecal egg count reduction tests were performed on 398 horses kept in 16 stables in western Iran (Kermanshah Province), to detect benzimidazole resistance in small strongyle nematodes. Allele-specific PCR was used to identify the F200Y (TAC/TTC) SNP in the beta-tubulin gene codon in cyathostomin larvae. Results: There was a 96.1% - 98.3% (90% CI) reduction in faecal egg counts following mebendazole treatment and a 96.6% - 98.7% (90% CI) reduction in faecal egg counts following fenbendazole treatment. The allele-specific PCR showed BZ-susceptible homozygote genotypes in all examined samples (Two pools of 10 to 50 L3 of cyathostomin nematodes from each of the 18 selected horses). Conclusion: Benzimidazole resistance in equine small strongyles has been reported globally, and the results of the present study were unexpected. The probable reasons for the slow development of BZ-resistance are climatic conditions in the country that have significant negative effects on the ability of free stages of the resistant strongyle nematode to survive and develop.</p
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