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Seismic fragility and vulnerability assessment is an essential step in the evaluation of probabilistic seismic risk. Ideally, models developed and calibrated for the building portfolio of interest would be readily available. However, the lack of damage data and insufficient analytical studies lead to a paucity of fragility and vulnerability models, in particular in the developing world. This study describes the development of an analytical fragility and vulnerability model covering the most common building classes at the global scale. Nearly five hundred functions were developed to cover the majority of combinations of construction material, height, lateral load resisting system and seismic design level. The fragility and vulnerability were derived using nonlinear time-history analyses on equivalent single-degree-of-freedom oscillators and a large set of ground motion records representing several tectonic environments. The resulting fragility and vulnerability functions were validated through a series of tests which include the calculation of the average annual loss ratio for a number of locations, the comparison of probabilities of collapse across all building classes, and the repetition of past seismic events. The set of vulnerability functions was used for the assessment of economic losses due to earthquakes as part of the global seismic risk model supported by the Global Earthquake Model Foundation.

Purpose FDA investigational device exemption (IDE) studies are considered a gold standard of assessing safety and efficacy of novel devices through RCTs. The fragility index (FI) has emerged as a means to assess robustness of statistically significant study results and inversely, the reverse fragility index (RFI) for non-significant differences. Previous authors have defined results as fragile if loss to follow up is greater than the FI or RFI. The aim of this study was to assess the FI, RFI, and robustness of data supplied by IDE studies in spinal surgery. Methods This was a systematic review of the literature. Inclusion criteria included randomized controlled trials with dichotomous outcome measures conducted under IDE guidelines between 2000 and 2023. FI and RFI were calculated through successively changing events to non-events until the outcome changed to non-significance or significance, respectively. The fragility quotient (FQ) and reverse fragility quotient (RFQ) were calculated by dividing the FI and RFI, respectively, by the sample size. Results Thirty-two studies met inclusion criteria with a total of 40 unique outcome measures; 240 outcomes were analyzed. Twenty-six studies reported 96 statistically significant results. The median FI was 6 (IQR: 3-9.25), and patients lost to follow up was greater than the FI in 99.0% (95/96) of results. The average FQ was 0.027. Thirty studies reported 144 statistically insignificant results and a median RFI of 6 (IQR: 4-8). The average RFQ extrapolated was 0.021, and loss to follow up was greater than the RFI in 98.6% (142/144) of results. Conclusions IDE studies in spine surgery are surprisingly fragile given their reputations, large sample sizes, and intent to establish safety in investigational devices. This study found a median FI and RFI of 6. The number of patients lost to follow-up was greater than FIand RFI in 98.8% (237/240) of reported outcomes. FQ and RFQ tell us that changes of two to three patients per hundred can flip the significance of reported outcomes. This is an important reminder of the limitations of RCTs. Analysis of fragility in future studies may help clarify the strength of the relationship between reported data and their conclusions.

Fragility curves are fundamental tools in seismic risk assessments, providing insights into the vulnerability of structures to earthquake-induced damages. These curves, which plot the probability of a structure reaching or exceeding various damage states against earthquake intensity, are critical for developing effective modification strategies. This review aims to present the characteristics between building- and site-specific fragility curves, which incorporate detailed local characteristics, and generic fragility curves that apply broader, more generalized parameters. We utilize the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) methodology to systematically review the literature to address key research questions about the methodological differences, applications, and implications of these curve types in assessing seismic risks. The methods involved a comprehensive search and combination of existing studies on the topic, focusing on how these curves are developed and applied in real-world scenarios. The results from this review show that building- and site-specific curves, while more precise, require extensive data and are therefore more complex and costly to develop. In contrast, generic curves, though less accurate, offer a cost-effective solution for preliminary risk assessments over large areas. The conclusions drawn from this review suggest that while each type has its merits, the choice between building- and site-specific and generic fragility curves should be guided by the specific requirements of the seismic risk assessment task, including available resources and the need for precision in the vulnerability estimations.

The origins of fragility Some chromosomal locations, known as common fragile sites, are predisposed to breakage. These sites have pathological relevance because they are often associated with chromosomal translocations. An analysis of the replication dynamics along a 1.6-Mb region of FRA3B , a common fragile site in human lymphocytes that hosts the FHIT tumour suppressor gene, shows that, rather than breakage being due to replication stalling, FRA3B site fragility results from an unusually low density of replication origins. Surprisingly, fragility is cell-type-specific, which may have implications for current models of translocations and tumorigenesis. Some chromosomal locations, known as common fragile sites, are predisposed to breakage. These sites have pathogenic relevance as they are frequently associated with chromosomal translocations. Here, it is found that rather than breakage being due to replication stalling, the fragility of site FRA3B results from an unusually low density of replication origins in this region. Unexpectedly, fragility is found to be cell-type-specific, which may have implications for current models of translocations. Common fragile sites have long been identified by cytogeneticists as chromosomal regions prone to breakage upon replication stress 1 . They are increasingly recognized to be preferential targets for oncogene-induced DNA damage in pre-neoplastic lesions 2 and hotspots for chromosomal rearrangements in various cancers 3 . Common fragile site instability was attributed to the fact that they contain sequences prone to form secondary structures that may impair replication fork movement, possibly leading to fork collapse resulting in DNA breaks 4 . Here we show, in contrast to this view, that the fragility of FRA3B —the most active common fragile site in human lymphocytes—does not rely on fork slowing or stalling but on a paucity of initiation events. Indeed, in lymphoblastoid cells, but not in fibroblasts, initiation events are excluded from a FRA3B core extending approximately 700 kilobases, which forces forks coming from flanking regions to cover long distances in order to complete replication. We also show that origins of the flanking regions fire in mid-S phase, leaving the site incompletely replicated upon fork slowing. Notably, FRA3B instability is specific to cells showing this particular initiation pattern. The fact that both origin setting 5 , 6 and replication timing are highly plastic 7 , 8 in mammalian cells explains the tissue specificity of common fragile site instability we observed. Thus, we propose that common fragile sites correspond to the latest initiation-poor regions to complete replication in a given cell type. For historical reasons, common fragile sites have been essentially mapped in lymphocytes 1 . Therefore, common fragile site contribution to chromosomal rearrangements in tumours should be reassessed after mapping fragile sites in the cell type from which each tumour originates.

This study investigates the effects of ground-motion sequences on fragility and vulnerability of reinforced concrete (RC) moment-resisting frames (MRFs). Two four-storey, four-bay RC MRFs are selected as case studies. These structures, which share the same geometry, are representative of distinct vulnerability classes in the Mediterranean region and are characterized by different material properties, cross-section dimensions, and detailing. The first case study is a ductile MRF designed according to Eurocode 8 (i.e., a special-code frame), while the second is a non-ductile MRF designed to sustain only gravity loads (i.e., a pre-code frame). The influence of masonry infills on their seismic performance is also investigated. Advanced numerical models are developed to perform cloud-based sequential nonlinear time history analyses using ground-motion sequences assembled by randomly pairing two real records via Latin hypercube sampling. Different structure-specific damage states are considered to derive fragility curves for the undamaged structures, when subjected to a single ground-motion record, and state-dependent fragility curves by considering the additional damage induced by a second ground-motion record within the sequence. Damage-to-loss models are then used to derive mean vulnerability relationships. Results of the analysis show the importance of considering the effect of damage accumulation in the pre-code frames. Moreover, the presence of infills shows an overall positive contribution to the seismic performance of both frame types. Vector-valued vulnerability relationships accounting for the damaging effect of two ground-motion records are finally presented in the form of mean vulnerability surfaces.

Field surveys and data on the earthquake reveal that RC (reinforced concrete) bridges and buildings have been widely found in engineering structures, with abundant samples at disposal. By taking actual seismically damaged samples in the Wenchuan Earthquake happened in 2008 as examples, the paper established probability models for fragility matrix within Intensity VH-X/XI for the said two engineering structures based on EMS-98, MSK-81 and CSIS-08, and analyzed the comparative models for failure ratio and exceedance probability curves defined by these three scales. The paper, according to these analytical findings, proposed relevant measures and methods for improving the earthquake resistance of RC bridges.

Background: Considering the limited and conflicting data regarding prevalence and risk factors of osteoporosis (OP) in systemic sclerosis (SSc), we aimed at evaluating a large population of patients at several Italian institutions. Enrollment started in October 2024 and will end in October 2025.   Materials and Methods: We are investigating the presence of OP in randomly selected subjects fulfilling the 2013 ACR/EULAR SSc classification criteria using a partially retrospective design. Exclusion criteria include ongoing pregnancy, cancer, metabolic bone diseases other than OP, and therapies interfering with bone health; exceptions are chronic kidney disease, anti-osteoporotic drugs, glucocorticoids (GC), and proton pump inhibitors. OP was defined as history of fragility fractures (FX) and/or of bone mineral density (BMD) values with T-scores < -2.5 or Z-scores < -2.0. BMD is evaluated using DXA scans within 12 months before enrollment or performed at enrollment. Demographic and anthropometric data, menopausal status, dietary calcium intake, Charlson Comorbidity Index (CCI), and concurrent medications are assessed. Sarcopenia, when detected with the SARC-F+EBM questionnaire, is evaluated with functional tests such as hand grip strength, chair stand test, and gait speed. A characterization of SSc is performed, including age at diagnosis, disease duration, and organ involvement. The cumulative SSc-related damage is expressed with the Scleroderma Clinical Trials Consortium Damage Index (SCTC-DI). We provide the results of the pre-planned interim analysis performed in April 2025; the final analysis is planned in October 2025.   Results: The interim analysis focused on 315 patients, with a mean age at enrollment of 63.2±11.3 years. They were diagnosed with SSc at a mean age of 51.2±12.4 years and had been affected for a median time of 10 years (interquartile range - IQR 12). Females made up the majority (n = 292; 92.7%) of the cohort, with 266 (91.1%) having been postmenopausal for a mean time of 17.3±10.1 years. The mean BMI was 24.3±4.4 kg/m², and 16.8% of patients were sarcopenic. Dietary calcium intake was insufficient (<700 mg) in 70.4% of cases, and optimal (>1000 mg) only in 3.9%. Approximately 30% of patients were taking GCs. The mean CCI score was 3.7±1.6, suggesting a 10-year mortality risk of approximately 40%. The median SCTC-DI score was 3 (IQR 3). Our main finding was that OP affected 136 (43.2%) subjects: 84 (61.8%) had reduced BMD values only, and 52 (38.2%) had a history of FX.   Conclusions: Our interim analysis showed that 43.2% of patients were affected by OP, suggesting a potentially high burden in SSc. To identify any predictive factors of OP in SSc, the final analysis will include correlations with SSc organ involvement, biochemical markers, densitometric values, sarcopenia, body composition parameters, and FX risk calculations with the DeFRA algorithm.

Convolutional neural networks (CNNs) have achieved impressive results on imbalanced image data, but they still have difficulty generalizing to minority classes and their decisions are difficult to interpret. These problems are related because the method by which CNNs generalize to minority classes, which requires improvement, is wrapped in a black-box. To demystify CNN decisions on imbalanced data, we focus on their latent features. Although CNNs embed the pattern knowledge learned from a training set in model parameters, the effect of this knowledge is contained in feature and classification embeddings (FE and CE). These embeddings can be extracted from a trained model and their global, class properties (e.g., frequency, magnitude and identity) can be analyzed. We find that important information regarding the ability of a neural network to generalize to minority classes resides in the class top-K CE and FE. We show that a CNN learns a limited number of class top-K CE per category, and that their magnitudes vary based on whether the same class is balanced or imbalanced. We hypothesize that latent class diversity is as important as the number of class examples, which has important implications for re-sampling and cost-sensitive methods. These methods generally focus on rebalancing model weights, class numbers and margins; instead of diversifying class latent features. We also demonstrate that a CNN has difficulty generalizing to test data if the magnitude of its top-K latent features do not match the training set. We use three popular image datasets and two cost-sensitive algorithms commonly employed in imbalanced learning for our experiments.

Background: Randomized controlled trial (RCT) outcomes reaching statistical significance, frequently determined by P <.05, are often used to guide decision making. Noted lack of reproducibility of some RCTs has brought special attention to the limitations of this approach. In this meta-analysis, we assessed the robustness of RCTs evaluating platelet-rich plasma (PRP) for the treatment of chronic noninsertional Achilles tendinopathy (AT) by using fragility indices. Methods: The present study was a systematic review and meta-analysis of RCTs comparing outcomes after PRP injection vs alternative treatment in patients with AT. Representative data sets were generated for each reported continuous outcome event using summary statistics. Fragility indices refer to the minimal number of patients whose status would have to change from a nonevent to an event to turn a statistically significant result into a nonsignificant result, or vice versa. The fragility index (FI) and continuous FI (CFI) were determined for dichotomous and continuous outcomes, respectively, by manipulating each data set until reversal of significance (a=0.05) was achieved. The corresponding fragility quotient (FQ) and continuous FQ (CFQ) were calculated by dividing FI/CFI by sample size. Results: Of 432 studies screened, 8 studies (52 outcome events) were included in this analysis. The 12 dichotomous outcomes had a median FI of 4.5 (FQ: 0.111), and the 40 continuous outcomes had a median CFI of 5 (CFQ: 0.154). All 52 outcome events included lost-to-follow-up data, and 12 (23.1%) indicated a greater number of patients lost to follow-up than the FI or CFI. Conclusion: Our findings suggest that RCTs evaluating PRP for AT therapy lack statistical robustness, because changing only a small number of events may alter outcome significance. Level of Evidence: Level II, therapeutic study.