Frequent Events Research Articles

Screening for frailty and its association with activities of daily living, cognitive impairment, and falls among community-dwelling older adults in China

ObjectivesFrailty is a prevalent geriatric condition that significantly impacts the health of older adults. This study aimed to examine the prevalence of frailty among older Chinese adults aged ≥ 65 years and to assess its association with adverse geriatric outcomes.MethodThis study included 20,724 older adults aged ≥ 65 years in Jiangsu Province, China, utilizing a random, stratified, multistage cluster sampling approach. Frailty was assessed using the 5-item FRAIL scale. Geriatric outcomes, such as independence in activities of daily living (ADL), cognitive impairment, and frequent fall events (occurring four or more times in the preceding year), were evaluated. Logistic regression models were employed to evaluate the association between frailty and geriatric outcomes, with results presented as odds ratios (ORs) and 95% confidence intervals (CIs).ResultsThe mean age of the participants was 73.4 ± 6.4 years. The standardized prevalence of prefrailty and frailty was 35.2% and 10.3%, respectively. Individuals identified as prefrail or frail tended to live in rural areas, have lower educational levels, be widowed, have lower incomes, and engage in less physical activity. Prefrailty and frailty were associated with an increased risk of limitations in BADL (OR: 9.62, 95% CI: 7.43–12.46; and OR: 29.25, 95% CI: 22.42–38.17, respectively) and IADL (OR: 2.54, 95% CI 2.35–2.74; and OR: 5.19, 95% CI 4.66–5.78, respectively), positive cognitive impairment screening (OR: 1.23, 95% CI: 1.16–1.31; and OR: 1.72, 95% CI: 1.56–1.91, respectively), and frequent falls (occurring four or more times in the preceding year) (OR: 3.38, 95% CI: 2.50–4.56; and OR: 8.37, 95% CI: 6.01–11.65). The association between frailty and both limitations in BADL and falls was notably more pronounced among the younger age groups (p for interaction < 0.001).ConclusionsAccording to the 5-item FRAIL scale, frailty was associated with limitations in BADLs and IADLs, positive cognitive impairment screening, and recent falls among older adults living in the community. Screening for frailty in younger age groups has the potential to prevent declines in physical function and falls.

Climate Smart Agriculture: A Roadmap to Sustainable Food Security

Climate change (CC) and climate variability (CV) are causing irregular precipitation, rising sea levels, and frequent extreme weather events, which threaten global agricultural crop production through prolonged droughts, floods, and shifting agroclimatic zones. Addressing greenhouse gas emissions and ensuring food security are among the greatest challenges of this century. Climate Smart Agriculture (CSA) emerges as a global strategy to enhance food productivity amid these uncertainties. CSA aims to create climate-resilient agricultural systems that increase soil health, water, and nutrient efficiency, provide stable yields, and reduce greenhouse gas emissions. By improving farmers' incomes and resilience to climate impacts, CSA contributes to both climate change mitigation and adaptation. Future CSA development directions include leveraging advanced internet technology for secure agricultural information, optimizing cropping patterns and management, integrating "internet + weather" services, and implementing agricultural weather index-based insurance. These strategies offer new pathways for ecological protection, green agricultural development, and climate change mitigation.

Hand-foot syndrome in sorafenib and lenvatinib treatment for advanced thyroid cancer.

The aim of this study was to assess the clinical impact of hand-foot syndrome (HFS) during treatment with two multikinase inhibitors, sorafenib and lenvatinib, in a large group of patients with advanced thyroid cancer. Moreover, we looked for possible associations between HFS occurrence and clinical and pathological features. We retrospectively evaluated 239 patients with advanced thyroid cancer: 165 treated with lenvatinib and 74 with sorafenib. Statistical analyses were performed to verify which features could be correlated with HFS development. HFS was observed in 35/74 (47.4%) and in 43/165 (26.7%) patients treated with sorafenib or lenvatinib, respectively. The median latency from the drug beginning and HFS appearance was 27 days for sorafenib and 2.9 months for lenvatinib. G3/G4 toxicity was observed in 16/35 (45.7%) patients treated with sorafenib and only in 3/43 (7%) treated with lenvatinib. Drug dose reduction due to HFS was required in 19/74 (25.7%) and 3/165 (1.8%) patients treated with sorafenib and lenvatinib, respectively. HFS occurrence was significantly associated with a longer duration of therapy in both groups. HFS was a frequent adverse event during both lenvatinib and sorafenib therapy, with a higher frequency and toxicity grade during sorafenib treatment. HFS was the most frequent reason for drug reduction or discontinuation in patient treated with sorafenib. Early diagnosis of HFS is important to allow early intervention, possibly in a multidisciplinary setting, and to avoid treatment discontinuation, which is highly relevant to obtain the maximum effectiveness of systemic therapy.

Impact of global warming on labor productivity in the Chengdu-Chongqing economic circle, China

In recent years, the Chengdu-Chongqing Economic Circle (CCEC) has experienced frequent heat events, significantly impacting labor productivity. The CCEC is an important economic growth pole in western China. Therefore, an in-depth study of the impact of heat stress on labor productivity holds great significance for climate change adaptation and enhancing economic efficiency. Based on the relationship between the wet-bulb globe temperature (WBGT) and labor productivity of different industries, the labor productivity loss caused by heat in the CCEC was estimated using the observation data of the meteorological station and the projection results of the BCC-CSM2-MR model from the Coupled Model Intercomparison Project Phase 6 (CMIP6). The results showed that the impact of heat on the labor productivity of different industries in the CCEC mainly occurs from June to August, with the largest impact on agriculture, followed by industry, and the smallest impact on service sectors. Losses from heat stress to labor productivity in agriculture, industry, and services showed a significant increasing trend from 1980 to 2020 but a decreasing trend in comprehensive labor productivity loss. From 2020–2100, labor productivity losses in different industries due to heat stress show an increasing and then decreasing trend in the low emissions scenario, productivity losses in the medium emissions scenario are characterized by an increasing and then sustained change, and labor productivity losses in the high emissions scenario show a sustained increasing trend from 2020. By the end of the 21st century, the increase in labor productivity losses across different industries under the high emission scenario is approximately 15%–23%, and the large value center shifts slightly to the west. In most areas, the losses of agricultural, industrial, service, and comprehensive labor productivity exceed 45%, 32%, 20%, and 24%, respectively.

Ground Urban Heat Island: Strengthening the Connection Between Spaceborne Thermal Observations and Urban Heat Risk Management.

As urbanization progresses under a changing climate, urban populations face increasing threats from chronically higher heat exposures and more frequent extreme heat events. Understanding the complex urban thermal exposure patterns becomes crucial for effective heat risk management. The spatial advantage of satellite thermal observations positions surface urban heat islands (SUHI) as a primary measure for such applications at the city scale. However, satellite-inherent biases pose considerable uncertainties. To improve the representation of human-relevant heat exposure, this study proposes a simple but effective satellite-based measure- ground urban heat island (GUHI), focusing solely on radiant temperatures from urban ground elements. Leveraging ECOSTRESS land surface temperature product and radiation-based statistical downscaling, diurnally representative GUHIs were evaluated over NYC. The findings reveal that overall GUHI is consistently warmer than SUHI diurnally. However, GUHI exhibits complex spatial contrasts with SUHI, primarily influenced by vegetation coverage. Various indicators associated with urban structures and materials were examined, showing important but dissimilar roles in shaping the spatial dynamics of GUHI and SUHI. This study highlights the value of satellite thermal observations compared to air temperature while addressing uncertainties in widely adopted practices of using them. By improving the depiction of human-related urban heat patterns from Earth observations, this research offers valuable insight and more reliable measures to address the urgent requirements for urban heat risk management globally.

EUS-guided hepaticojejunostomy in patients with history of total gastrectomy: a multicenter retrospective feasibility study (with video)

EUS-guided hepaticogastrostomy (EUS-HGS) is an effective biliary drainage technique for patients with altered anatomy or duodenal strictures. EUS-guided hepaticojejunostomy (EUS-HJS) can be used to create a fistula between the left hepatic duct and the jejunum in patients with a history of total gastrectomy. No specific data on this technique have been published. The aim of this study was to assess the feasibility and safety of EUS-HJS in patients with a history of total gastrectomy. This retrospective multicenter study included all adult patients who underwent EUS-HJS at 3 tertiary French centers and 1 tertiary Swiss center between May 2011 and February 2023. The primary outcome was clinical success, which was defined as the disappearance of pruritus, jaundice, and/or cholangitis. An improvement in bilirubin >30% within the first week and/or bilirubin normalization within 1 month after the procedure were also considered indicators of clinical success. Secondary outcomes were technical success, rate of adverse events, need for endoscopic revision, possibility of resuming anticancer treatment, median survival, and technical differences compared with EUS-HGS. Twenty-one patients with history of complete gastrectomy who underwent EUS-HJS were included. Technical success was achieved in 100% of patients (95% confidence interval [CI], 85-100). Clinical success was achieved in 80% of patients (95% CI, 58-92). The incidence of recorded adverse events was 33% (95% CI, 17-55), with cholangitis being the most frequent adverse event. Seven patients (39%) were able to benefit from anticancertreatment after the procedure. Median survival time was 6 months (interquartile range, 1.5-12). EUS-HJS is an effective and feasible procedure for patients whose anatomy has been altered by total gastrectomy.

Phase II, Single-Arm Trial of Induction and Concurrent Vismodegib With Curative-Intent Radiation Therapy for Locally Advanced, Unresectable Basal Cell Carcinoma.

Locally advanced, unresectable basal cell carcinoma (LA BCC) can be treated with radiation therapy (RT), but locoregional control (LRC) rates are unsatisfactory. Vismodegib is a hedgehog pathway inhibitor (HPI) active in BCC that may radiosensitize BCC. We evaluated the combination of vismodegib and RT for patients with LA BCC. In this multicenter, single-arm, phase II study, patients with unresectable LA BCC received 12 weeks of induction vismodegib, followed by 7 weeks of concurrent vismodegib and RT. The primary end point was LRC rate at 1 year after the end of treatment. Secondary end points included objective response, progression-free survival (PFS), overall survival (OS), safety, and patient-reported quality of life (PRQOL). Twenty-four patients received vismodegib; five were unable to complete 12 weeks of induction therapy. LRC was achieved in 91% (95% CI, 68 to 98) of patients at 1 year. The response rate was 63% (95% CI, 38 to 84) after induction vismodegib and 83% (95% CI, 59 to 96) after concurrent vismodegib and RT. With a median follow-up of 5.7 years, 1-year PFS and OS rates were 100% and 96%, and at 5 years PFS and OS rates were 78% and 83%, respectively. Distant metastasis or BCC-related death has not been observed. The most frequent treatment-related adverse events (AEs) were dysgeusia, fatigue, and myalgias occurring in 83%, 75%, and 75% of patients. No grade 4 to 5 treatment-related AEs occurred. PRQOL demonstrated clinically meaningful improvements in all subscales, with emotions and functioning improvements persisting for a year after the end of treatment. In patients with unresectable LA BCC, the combination of vismodegib and RT yielded high rates of LRC and PFS and durable improvements in PRQOL.

Burden and Coping Strategies of Hypoglycemia in People with Diabetes.

Hypoglycemia is a limiting adverse effect of glucose-lowering medications and particularly insulin replacement therapy. This review provides insights into the burden of hypoglycemia in the management of diabetes and outlines strategies available to reduce the risk of hypoglycemia and improve patients' well-being. People with type 1 diabetes are primarily affected by hypoglycemic episodes which are associated with direct physical harms like injuries and cardiac events as well as indirect psychosocial consequences including constant anxiety, absenteeism, increased healthcare costs and overall poorer quality of life. These complications are more prominent amongst individuals with hypoglycemia unawareness or overnight hypoglycemia and could even extend to caregivers such as parents of children with diabetes. Patients experiencing frequent or severe hypoglycemic events might also develop a pathological fear of hypoglycemia and adopt aberrant behaviors intending to maintain higher blood glucose levels. Modern pharmaceutical options with a safer profile in terms of hypoglycemia are available including novel basal insulins with lower rates of nocturnal hypoglycemia along with ultra-rapid-acting insulin analogs with a shorter duration of action that might avert late post-meal hypoglycemia. Continuous glucose monitoring and sensor-augmented insulin pump therapy with low glucose suspend technology can also prevent hypoglycemia, although concerns about cost and patient satisfaction remain. Advancements in insulin therapy and technological modalities should be coupled with ongoing education and support for patients to become co-managers of their disease and reduce the risk of hypoglycemia.

Radiofrequency ablation of the hip: review.

Radiofrequency ablation (RFA) of the articular branches of the femoral and obturator nerves (the innervation of the anterior capsule of the hip) is an emerging treatment for chronic hip pain. Body mass index (BMI) greater than 30, older age, large acetabular/femoral head bone marrow lesions, chronic widespread pain, depression, and female sex increase the risk of developing hip pain. Chronic hip pain is a common condition with a wide range of etiologies, including hip osteoarthritis (OA), labral tears, osteonecrosis, post total hip arthroplasty (THA), post-operative dislocation/fracture, and cancer. The most common and well studied is hip OA. Management of chronic hip pain includes conservative measures (pharmacotherapy and exercise), surgery, and percutaneous procedures such as RFA. While surgery is effective, those whose medical comorbidities preclude surgery, those who do not wish to have surgery, and those whose pain persists after surgery (11-36% of patients) could benefit from RFA. Because of the aforementioned circumstances, hip RFA is often a palliative intervention. Hip RFA is an effective treatment, one recent retrospective study of 138 patients found 69% had >50% pain relief at 6 months. The most frequent adverse event reported for hip RFA is pain from needle placement. No serious bleeding events have been reported, despite the valid concern of the procedure's proximity to vasculature. This descriptive review details the pathophysiology of hip pain, its etiologies, its clinical presentation, conservative management, the anatomy/technique of hip RFA, hip RFA efficacy, and RFA adverse events.

Safety and tolerability of tirbanibulin ointment 1% treatment on 100 cm2 of the face or scalp in patients with actinic keratosis: A phase 3 study

Tirbanibulin is approved for actinic keratosis (AK) field treatment up to 25cm2. However, AK often affects larger areas; thus, AK treatments for larger fields are needed. Evaluate the safety and tolerability of tirbanibulin when applied to a field of approximately 100cm2. Phase 3, multicenter, open-label, single-arm study among adult patients having a treatment field on the face or balding scalp of approximately 100cm2 with 4-12 AKs. Patients received tirbanibulin to cover the treatment field once daily (5 consecutive days). Safety was assessed by evaluating treatment emergent adverse events and tolerability by composite score of 6 local tolerability signs (LTS). A total of 105 patients were included. The most common LTS were erythema (96.1%) and flaking/scaling (84.4%), being mostly mild-to-moderate severity, and resolved/returned to or close to baseline by Day 29. The only severe LTS were erythema (5.8%) and flaking/scaling (8.7%). Most frequent treatment emergent adverse events were application site pruritus (10.5%) and application site pain (8.6%). Mean total number of AKs decreased from 7.7 AKs at baseline to 1.8 AKs at Day 57. Mean percent of change (reduction) from baseline in lesion count was 77.8% at Day 57. No control group. No long-term follow-up. Safety and tolerability profiles in patients treated with tirbanibulin up to 100cm2 were consistent with those previously reported over smaller field. Tirbanibulin could be used on a larger field (>25cm2).

GIS and Remote Sensing as Decision Support Tools for Urban Flood Analysis and Recommendations: A Case Study of Vasana District in Ahmedabad

In recent years, urban flooding caused by heavy rainfall has become a pressing global issue, including in Indian cities that face challenges such as high population density, rapid development, and resulting encroachment on natural resources. The process of urbanization has significantly altered the natural characteristics of cities, such as green spaces, water bodies, and topography, replacing them with densely built areas and increasing the proportion of impermeable surfaces. This transformation has disrupted the natural drainage patterns and reduced the ability of the soil to absorb water. Consequently, urban areas with high imperviousness experience more frequent and severe flooding events, disrupting social life, ecological balance, and economic activities. The primary objective of this research paper is to explore the potential of Geographic Information Systems (GIS) and Remote Sensing as a tool for analysis and recommendations in Urban Flooding in Municipalities of fast-growing cities. The study focuses on the Vasna ward of Ahmedabad city, systematically investigating its current conditions using GIS and remote sensing, and proposing strategies to prevent future flood occurrences by incorporating sustainable urban drainage (SUDS) principles into the planning framework of the city.

Surgical Outcomes in Chiari 1 and Chiari 1.5 Malformation Treated by Posterior Fossa Reconstruction: A Comprehensive Analysis of 110 Pediatric Cases and Literature Review.

Background/Objectives: The management of Chiari malformations (CMs) remains a clinical challenge and a topic of great controversy. Results may vary between children and adults. The purpose of the current single-center study is to critically assess the one-year surgical outcomes of a cohort of 110 children with CM-1 or CM-1.5 who were treated using "posterior fossa reconstruction" (PFR), a surgical technique described in 1994 that has since been used in both adults and children. We also review the literature and discuss the possible causes of the drawbacks and pitfalls in children in whom PFR was ineffective in controlling the disease. Methods: The present cohort was selected from a prospective registry of adults and children with CMs collected since 2006. Patients included in this study were selected from a group of children with CMs who were operated on in our Pediatric Neurosurgical Unit between 1 January 2007 and 31 November 2023. Surgical outcome was defined based on clinical and neuroradiological results as very good, good, or bad. Results: The mean age of our child cohort was 9.9 ± 4.7 years, with 54 girls (49%) and 56 boys (51%). Sixty-six children had CM-1 (60%) while forty-four had CM-1.5 (40%). Following surgery, there was no neurological worsening or death among the children. Most children (70%) had an uneventful recovery and were discharged home on average one week after surgery. However, in 33 children (30%), we recorded at least one postoperative adverse event. Aseptic meningitis syndrome was the most frequent adverse event (n = 25, 22.7%). The final surgical outcome was evaluated one year after PFR by using both clinical and neuroradiological results. The one-year surgical outcome was excellent in 101 children (91.9%), good in 5 (4.5%), and bad in 4 (3.6%). Conclusions: PFR significantly enlarges the volume of the posterior fossa and recreates a CSF environment that generates buoyancy of the cerebellum, with a high percentage of excellent and good clinical results evaluated one year post-surgery.

Role of Pacific Ocean climate in regulating runoff in the source areas of water transfer projects on the Pacific Rim

Over the past two decades, more frequent and intense climate events have seriously threatened the operation of water transfer projects in the Pacific Rim region. However, the role of climatic change in driving runoff variations in the water source areas of these projects is unclear. We used tree-ring data to reconstruct changes in the runoff of the Hanjiang River since 1580 CE representing an important water source area for China’s south-north water transfer project. Comparisons with hydroclimatic reconstructions for the southwestern United States and central Chile indicated that the Pacific Rim region has experienced multiple coinciding droughts related to ENSO activity. Climate simulations indicate an increased likelihood of drought occurrence in the Pacific Rim region in the coming decades. The combination of warming-induced drought stresses with dynamic El Niño (warming ENSO) patterns is a thread to urban agglomerations and agricultural regions that rely on water transfer projects along the Pacific Rim.

Uncovering human behavioral heterogeneity in urban mobility under the impacts of disruptive weather events

Understanding the response of human mobility to disruptive weather events is beneficial for the development of urban risk mitigation and emergency response policies, thus enhancing urban resilience. Most human mobility studies relying on aggregate flow data inevitably neglect the heterogeneity of disaggregate travel patterns with distinctive spatiotemporal characteristics, causing the uncertainty problem for identifying meaningful travel behaviors. Moreover, there is a lack of robust methodological approaches to extracting stable and genuine travel patterns under normal or disruptive situations. To address these issues, this study proposes a data-driven approach to spatiotemporal flow decomposition based on non-negative matrix factorization. With sparseness factored in the decomposition, stable disaggregate travel patterns can be extracted from origin-destination mobility flows. By combining temporal, spatial, and urban functional perspectives, heterogeneous travel behaviors can be analyzed and inferred. With a case study of the Zhengzhou ‘7.20’ heavy rainfall in 2021, the most extreme rainfall ever recorded in China, this study validated the effectiveness of the proposed approach and managed to identify representative and interesting travel patterns and behaviors, facilitating a better understanding of human travel behaviors under external impacts. In practice, this study can provide valuable insights for coping strategies in the face of increasingly frequent disruptive events.

SPATIOTEMPORAL VARIABILITY OF DROUGHT IN ROMANIA DURING 1901-2021 USING THE STANDARDIZED PRECIPITATION EVAPOTRANSPIRATION INDEX (SPEI)

Drought represents one of the most frequent climatic events with impact on the environment, economy and society. In this study, we analyse the drought characteristics in Romania during the period 1901-2021, using a meteorological drought index: the Standardized Precipitation Evapotranspiration Index (SPEI). To provide a clear image over time, we have divided the data into four time periods: 1901 – 1930, 1931 – 1960, 1960 – 1990, and 1991-2021. The results indicate that the period between 1901 to 1930 is characterized by moderate droughts, in contrast to the period between 1991-2021 when extreme droughts prevailed. Also, the SPEI3's spatial analysis indicates that Romania's eastern and southeastern parts are becoming drier. This study provides a clear image of climate change and indicates that the extreme drought events affected Romania in the previous decade.

Alcoholic Etiology, Severity of Liver Disease, and Post-Transplant Adherence Are Correlated with Worse Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) in Liver Transplant Candidates.

Introduction: Psychosocial pre-transplant evaluation in patients undergoing liver transplantation (LT) could help identify those patients at higher risk of pharmacological non-adherence, organ rejection, and mortality. The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) is a validated tool for assessing LT candidates' psychosocial well-being. Data on the ability of the SIPAT evaluation to predict post-transplant outcomes are sparse. Material and Methods: clinical and psychosocial data from a sample of 134 candidates for LT were analyzed. Moreover, the association between pre-transplant psychosocial evaluation and post-transplant clinical outcomes, including organ rejection, mortality, and immunosuppressant drug adherence, was calculated. Results: At the pre-transplant evaluation, patients who showed high SIPAT scores (77, 57%) also had more liver disease assessed by model for end-stage liver disease (MELD; F = 5.04; p < 0.05), alcoholic etiology (F = 35.80; p < 0.001), encephalopathy (F = 5.02; p < 0.05), and portal hypertension (F = 7.45; p < 0.01). Of the 51 transplant patients, those who had a high pre-transplant SIPAT score showed lower post-transplant immunosuppressive adherence, linked to more frequent immunological events. Conclusions: Patients with an alcoholic etiology of liver disease and more severe liver dysfunction are likelier to not adhere to medical prescriptions following transplantation. Current data suggests that this specific group of patients could benefit from early psychological pre-habilitation before undergoing liver transplantation.

Floria: fast and accurate strain haplotyping in metagenomes.

Shotgun metagenomics allows for direct analysis of microbial community genetics, but scalable computational methods for the recovery of bacterial strain genomes from microbiomes remains a key challenge. We introduce Floria, a novel method designed for rapid and accurate recovery of strain haplotypes from short and long-read metagenome sequencing data, based on minimum error correction (MEC) read clustering and a strain-preserving network flow model. Floria can function as a standalone haplotyping method, outputting alleles and reads that co-occur on the same strain, as well as an end-to-end read-to-assembly pipeline (Floria-PL) for strain-level assembly. Benchmarking evaluations on synthetic metagenomes show that Floria is > 3× faster and recovers 21% more strain content than base-level assembly methods (Strainberry) while being over an order of magnitude faster when only phasing is required. Applying Floria to a set of 109 deeply sequenced nanopore metagenomes took <20 min on average per sample and identified several species that have consistent strain heterogeneity. Applying Floria's short-read haplotyping to a longitudinal gut metagenomics dataset revealed a dynamic multi-strain Anaerostipes hadrus community with frequent strain loss and emergence events over 636 days. With Floria, accurate haplotyping of metagenomic datasets takes mere minutes on standard workstations, paving the way for extensive strain-level metagenomic analyses. Floria is available at https://github.com/bluenote-1577/floria, and the Floria-PL pipeline is available at https://github.com/jsgounot/Floria_analysis_workflow along with code for reproducing the benchmarks.

A Phase I/II Study of Valemetostat (DS-3201b), an EZH1/2 Inhibitor, in Combination with Irinotecan in Patients with Recurrent Small-Cell Lung Cancer.

Recurrent small-cell lung cancer (SCLC) has few effective treatments. The EZH2-SLFN11 pathway is a driver of acquired chemoresistance that may be targeted. This phase I/II trial investigated valemetostat, an EZH1/2 inhibitor, with fixed-dose irinotecan in patients with recurrent SCLC. Phase I primary objectives were to assess safety, tolerability, and a recommended phase II dose (RP2D). The phase II primary objective was overall response rate (ORR), with secondary objectives of determining duration of response (DoR), progression-free survival (PFS), and overall survival (OS). Correlative analyses included immunohistochemistry of pretreatment and on-treatment tumor biopsies and pharmacokinetics analysis. Twenty-two patients were enrolled (phase I, n = 12; phase II, n = 10); one withdrew consent prior to treatment. Three dose-limiting toxicities (DLT) in dose-escalation resulted in valemetostat 100 mg orally daily selected as RP2D. Among 21 evaluable patients, the most frequent (≥20%) treatment-related adverse events were diarrhea, fatigue, nausea, and rash; three patients discontinued treatment for toxicity. Three of the first 10 patients in phase II experienced DLTs triggering a stopping rule. The ORR was 4/19 or 21% [95% confidence interval (CI), 6%-46%]. The median DoR, PFS, and OS were 4.6 months, 2.2 months (95% CI, 1.3-7.6 months), and 6.6 months (95% CI, 4.3 to not reached), respectively. SLFN11/EZH2 expression and SCLC subtyping markers did not correlate with response, but MHC-I expression did increase with treatment. Two responders demonstrated subtype switching on treatment. Combination valemetostat and irinotecan was not tolerated but demonstrated efficacy in recurrent SCLC. Valemetostat, combined with agents without overlapping toxicity, warrants further investigation in SCLC.

Large Pool Fires in the Process Industry. A Simple Model for Safety Distances Estimation

In recent years, the global production growth and the complexity of processes operation have increased safety concern, especially during the design project, considering potential accidental events as fires, explosions, and their related domino effects. Pool fire is one of the most frequent accidental events. Some procedures for safety distances estimation from pool fires were reported. However, there is a lack of adequate simple models to directly estimate safety distances covering a wide range of substances and pool diameters, considering a continuous interval of receptor vulnerabilities (from damage to people to domino effect prevention). In this paper, a simple model to estimate safety distances is proposed, suitable to be incorporated into complex models (e.g. safety management systems, layout optimization). A surrogate model is achieved by adopting a reference one. Methodologically, the main variables that play a key role modelling a pool fire were selected and their influence on the safety distance was analyzed to propose simple mathematical expressions. NLP optimization problems were solved to optimize the model parameters. A conservative, accurate and easy-to-use model was achieved with the aim of developing safer plants or for their safe operation by improving the optimal process design, or implementing safe management systems, considering risks.

Comprehensive Power Quality Assessment Based on a Data-Driven Determinant-Valued Extension Hierarchical Analysis Approach

The increasing demand for power quality in modern power supply facilities and the deepening changes in the power market have led to frequent power quality events, making the assessment of power quality a necessity. In view of the complexity of the model and the sensitivity of the parameters of the existing power quality assessment system, as well as the shortcomings of the traditional hierarchical analysis method, this paper proposes a data-driven power quality assessment system based on the improved determinant-valued extension hierarchical analysis, which makes the factors affecting power quality hierarchical, and enhances the conservatism of the matrix while reducing the human subjective factors, so as to analyze the main power quality problems in a clearer and more intuitive way. The evaluation system is validated and analyzed, and the corresponding evaluation result is “excellent”, which proves that the system effectively evaluates the power quality in real scenarios, and has a good prospect in power quality evaluation.