Severe Wind Research Articles

Incidence and prevalence of traumatic and non-traumatic wounds and burns and access to wound care in Sierra Leone; data from a nationwide household survey (PRESSCO) 2020

ObjectivesThis wound section of the PREvalence Study on Surgical COnditions (PRESSCO) determines the incidence and prevalence of wounds and burns in Sierra Leone. It further describes access to wound care and wound-related healthcare-seeking behaviour. MethodsBetween October 2019 and March 2020, a nationwide cross-sectional household survey was performed. The survey was based on Surgeons OverSeas Assessment of Surgical Need (SOSAS). Additional questions relating to wounds and burns were added. Following randomization, 25 households in 75 clusters were sampled. Severe wounds were clinically examined. ResultsOf the 3600 individuals included, 143 had developed 151 wounds, including burns (15.2%) during the year preceding the interview (incidence 4.2%). A total of 77 people had 83 wounds and burns at the time of the survey (prevalence 2.3%), of which 23 were severe (prevalence 0.6%). Burn incidence and prevalence were 0.6% and 0.1%, respectively. Most wounds were on extremities (73.5%), often resulting from cuts (32.8%), falls (22.4%), or road traffic accidents (RTA; 16.4%). Risk factors for developing a wound were male sex (p=0.004), older age (p=0.037) and smoking (p=0.001). Severe wounds had a median duration of 18 months. For 70.2% of wounds, care at a health facility was sought. Only 49.9% of households reported financial capacity to visit a secondary health facility. For 56 (37.1%) of wounds, the desired care was not obtainable. An estimated 44,000 (95% CI 29,760 – 67,410) people in Sierra Leone suffer from a severe wound. An estimated 11,000 (95% CI 6,416 – 18,268) annual deaths occur due to wounds, predominantly due to RTA’s (66.7%) and accidental injuries (20.0%). ConclusionsWounds and burns account for an extensive burden on the health and economics of the individual, the household, and the Sierra Leonean society. For over one-third of wounds, the desired surgical care was not obtainable.

The impact of diabetes mellitus on the outcomes of revascularization for chronic limb-threatening ischemia in the BEST-CLI trial

ObjectiveSeveral observational studies have demonstrated an association between diabetes mellitus (DM) and above-ankle amputation after lower extremity revascularization (LER). However, data from prospective randomized trials is lacking. This analysis compares the outcomes of patients with and without DM enrolled in the Best Endovascular vs Best Surgical Therapy in patients with Chronic Limb-Threatening Ischemia (BEST-CLI) trial. MethodsBaseline characteristics were compared between patients with and without DM in the BEST-CLI trial. Cox regression was used to determine the association between DM and major outcomes of major adverse limb events (MALE), reintervention, above-ankle amputation, and all-cause death. ResultsAmong 1777 patients who underwent LER, 69.2% had DM. Compared with patients without DM, those with DM were significantly younger, less likely to be White, and more likely to be Hispanic. Patients with DM were more likely to have hypertension, hyperlipidemia, coronary artery disease, congestive heart failure, and renal disease and be on optimal medical therapy (antiplatelets and statins), whereas patients without DM were significantly more likely to be smokers and have chronic obstructive pulmonary disease. Patients with DM were significantly more likely to present with late Wound Ischemia foot Infection (WIfI) stages (3-4) (73.7% vs 45.9%; P < .001) that were driven predominantly by differences in wound and infection grade. Conversely, patients without DM had significantly lower ankle pressures and toe pressures and were significantly more likely to have WIfI ischemia grade 3 compared with patients with DM (60% vs 52.5%; P = .016). At 3 years, patients with DM exhibited higher rates of above-ankle amputation and all-cause death compared with patients without DM. Kaplan-Meier analysis demonstrated significantly higher MALE or all-cause death compared with patients without DM (3-year estimate: 53.5% vs 46.4%; P < .001). After adjusting for potential confounders, regression analysis demonstrated that DM was independently associated with increased above-ankle amputation (1.75 [1.22-2.51]), all-cause death (1.63 [1.31-2.03]), and MALE or all-cause death (1.24 [1.04-1.47]). ConclusionsPatients with DM undergoing LER for chronic limb-threatening ischemia experienced a greater incidence of MALE or all-cause death compared with patients without DM. The impact of DM seems to be mediated by more severe wounds and infections at the time of presentation, and a higher prevalence of cardiac and renal disease.

Spreadable thermosensitive nanocomposite hydrogel dressing with ultrasound-responsive bactericidal/repair-promoting regulation and cascade antioxidantion for infected burn wound repair

Treating severe burn wounds poses significant challenges, including considerable cell loss, excessive inflammation, and a high susceptibility to bacterial infections. Ideal burn dressings should exhibit excellent antibacterial properties, anti-inflammatory effects, and promote cell proliferation. Additionally, they need facilitate painless dressing changes and be user-friendly. Herein, we synthesized a thermosensitive hydrogel by crosslinking poly (N-isopropylacrylamide-co-allyloxybenzaldehyde) (PNA) and amino-terminated Pluronic F127 (APF) through a Schiff base reaction. It exhibited reversible gel-sol transition and spreadability. By incorporating piezoelectric gold nanoparticle-modified barium titanate (Au@BaTiO3) and cascade antioxidant MOF-818, a nanocomposite hydrogel dressing with diverse bioactive functionalities was developed. Results demonstrated that the nanocomposite hydrogel possessed gel-sol transition properties, maintained a stable gel state within a broad temperature range, and desirable self-healing property. Au@BaTiO3 exhibited good piezoelectric properties and ROS generation upon ultrasound stimulation, while MOF-818 displayed highly efficient cascade nanozyme activity. The combination of Au@BaTiO3 and MOF-818 promoted fibroblast proliferation and migration, reduced intracellular ROS levels, and induced anti-inflammatory polarization of macrophages under ultrasound stimulation. In vitro and in vivo antibacterial results disclosed that the nanocomposite hydrogel had excellent antibacterial activity under high-intensity ultrasound stimulation. When applied to infected burn wounds, the nanocomposite hydrogel can rapidly sterilize the wound upon initial high-intensity ultrasound, and then reduce inflammation and promote M2 macrophage polarization by the following low-intensity ultrasound stimulation, and thus accelerating the healing by improving granulation tissue formation, angiogenesis, and collagen deposition.

H-Bonds Enhanced Natural Polyphenols Bined Polysaccharide/Gelatin Composites with Controlled Photothermal Stimulation Phase Transition for Wound Care.

Severe open wounds should be closed immediately and regularly undergo re-examination and debridement. Therefore, dressings should effectively cover the wound, creating a moist environment for healing while meeting mechanical requirements for daily movement and adaptability. Herein, a low-cost and easy-to-prepare plant polysaccharide hydrogel was reported. The Mesona chinensis Benth polysaccharide strengthened the hydrogel network by hydrogen bonding and changed the phase transition temperature, but retained the thermal response characteristics of the hydrogel. By adjusting the polysaccharide concentration, MepGel(1) can be prepared to remain stable as a semisolid at body temperature and transform into a shear-thinning semifluid state when appropriately heated. The composite hydrogel could be easily shaped, effectively closing wounds of different shapes, while maintaining excellent mechanical properties. Importantly, this composite hydrogel had a near-infrared photothermal effect resulting in excellent antibacterial effect and collided with its own thermal response producing functions conducive to wound care, like accelerating the self-healing of the dressing, achieving re-adhesion, and further covering the wound. Furthermore, the hydrogel had excellent biocompatibility, enhancing immunity and promoting healing of bacterial-infected wounds. The low cost and rich functionality demonstrated by MepGel had the potential to face the enormous challenges and economic burden of clinical wound healing.

Absorbable and biodegradable enzyme-crosslinked gelatin/alginate semi-IPN hydrogel wound dressings containing curcumin

Effective wound management presents a substantial financial and time-related obstacle for healthcare institutions. Enhancing healthcare involves implementing innovative wound treatment methods to minimize healing time and expenses. This study is centered on the development of a non-toxic wound dressing using only two natural polymers and an enzyme. By adding 10 % wt microbial transglutaminase, the mechanical properties of the dressing were improved. This formulation increased the swelling rate by 70 %, deswelling rate by 15 %, conversion rate by 9 %, and networking rate by 20 %. Additionally, the non-toxic dressing showed a cell viability rate of 106 %. In drug delivery tests, explosive release behavior was observed, which is advantageous for open wounds. Cell staining experiments were also carried out to evaluate wound behavior in terms of collagen formation, granulation, and inflammation. The results suggest that the optimized hydrogel has great potential as a wound dressing. Its excellent absorption, antioxidant, and biocompatibility characteristics enhance tissue granulation rate and reduce wound treatment time by half compared to conventional methods, while also minimizing scarring risk. This innovative treatment, which eliminates the need for frequent changes, is beneficial for both secondary intentions and severe open wounds requiring bottom-up healing.

Lower Extremity Traumatic Wound Management: Relative Significance of Negative Pressure Wound Therapy in the Orthopedic Setting.

Significance: Lower extremity traumatic wounds are associated with numerous perioperative challenges. Their etiologies determine the characteristics and extent of the injury. The timing of subsequent surgical intervention and wound healing optimization after lower extremity trauma are integral to successful perioperative lower extremity wound management. Recent Advances: Managing trauma to the lower extremities uses a multidisciplinary surgical approach. The objective of this review is to summarize lower limb trauma assessment, advancements in lower extremity trauma management, and the clinical applications of advanced wound care in lower limb traumatic wounds. The advent of lower limb reconstruction and the development of advanced wound care modalities have helped to improve the management of these complex injuries. Critical Issues: The extensive involvement of bone, soft tissues, nerves, and blood vessels of severe lower extremity trauma wounds presents a challenge for clinicians in both the acute care setting and during patient rehabilitation. If not properly managed, these injuries may be subject to a decline in limb function and may possibly result in limb loss. To reveal developing limb-threatening conditions, serial examinations should be performed. Future Directions: The majority of lower limb traumatic wound will benefit from the perioperative administration of an appropriate negative pressure wound therapy (NPWT)-based system, which can help to promote granulation tissue and remove wound exudate before definitive closure and/or reconstruction. NPWT should be included as an important adjunct in the surgical management of lower limb traumatic wounds.

Exploration of the fala house construction system in Alor Regency

The fala house is one of the traditional houses of the Abui tribe in Alor which is also known as a warehouse house. This building is ± 16 m high and consists of 4 floors with functions as a residence, barn, and storage area for heirlooms. This building's design and dimensions are also tailored to withstand the frequent high winds and earthquakes in the Alor region. To provide the Alor community as a whole with literature and a reference for creating disaster-resistant dwellings, this study intends to investigate the fala house construction system. An ethnographic design in conjunction with an exploratory description is the methodology employed to examine the Fala House's construction system. One of Takpala Village's thirteen fala homes serves as the research item. Purposive sampling was used to identify the home of the village chief, who served as the resource person, to choose this item. While secondary data was gathered through a review of the literature, primary data was acquired through close inspection and recording of the artifacts as well as technical information on workmanship and local names of fala house construction through interviews. According to research, the Fala house is built using a traditional method in which the main pillar is buried directly in the ground. The attic pillars that rest on the main beam are braced and connected to the building using a tie system. Because fala houses are built with a building method that can withstand shocks from earthquakes and severe winds, they have withstood a lengthy time of disaster adaptation and are still standing today.

Initiation, organizational modes and environmental conditions of severe convective wind events during the warm season over North China

Initiation, organizational modes and environmental conditions of severe convective wind events during the warm season over North China

Quasi-Linear Convective Systems and Derechos across Europe: Climatology, Accompanying Hazards, and Societal Impacts

Abstract In this work, we use 8 years (2014–21) of Operational Programme for the Exchange of Weather Radar Information (OPERA) radar data, ESWD severe weather reports, and arrival time difference (ATD) lightning detection network (ATDnet) data to create a climatology of quasi-linear convective systems (QLCSs) across Europe. In the first step, 15-min radar scans were used to identify 1475 QLCS polygons. Severe weather reports, lightning data, and morphological properties were used to classify QLCSs according to their intensity into 1151 marginal (78.0%), 272 moderate (18.5%), and 52 derecho (3.5%) events. The manual evaluation led to the recognition of QLCS morphological and precipitation archetypes, areal extent, duration, speed, forward motion, width, length, accompanying hazards, injuries, and fatalities. Results indicate that QLCSs are the most frequent during summer in central Europe, while in southern Europe, their occurrence is extended to late autumn. A bow echo feature occurred in around 29% of QLCS cases, while a mesoscale convective vortex occurred in almost 9%. Among precipitation modes, trailing and embedded stratiform types accounted for around 50% of QLCSs. The most frequent hazard accompanying QLCSs was lightning (taking up on average 94.4% of the area impacted by QLCS), followed by severe wind gusts (7.9%), excessive precipitation (6.1%), large hail (2.9%), and tornadoes (0.5%). Derechos had the largest coverage of severe wind reports (49.8%), while back-building QLCSs were the most prone to excessive precipitation events (13.5%). QLCSs caused 104 fatalities and 886 injuries. Severe wind gusts were responsible for 87.6% of fatalities and 73.6% of injuries. Nearly half of all fatalities and injuries were associated with only the 10 most impactful QLCS events, mostly warm-season derechos.

Approaches to scarless burn wound healing: application of 3D printed skin substitutes with dual properties of anti-infection and balancing wound hydration levels

Severe burn wounds face two primary challenges: dysregulated cellular impairment functions following infection and an unbalanced wound hydration microenvironment leading to excessive inflammation and collagen deposition. These results in hypertrophic scar contraction, causing significant deformity and disability in survivors. A three-dimensional (3D) printed double-layer hydrogel (DLH) was designed and fabricated to address the problem of scar formation after burn injury. DLH was developed using methacrylated silk fibroin (SFMA) and gelatin methacryloyl (GelMA) for the upper layer, and GelMA and hyaluronic acid methacryloyl (HAMA) for the lower layer. To combat infection, copper-epigallocatechin gallate (Cu-EGCG) was incorporated into the lower layer bioink, collectively referred to as DLS. To balance wound hydration levels, HaCaT cells were additionally encapsulated in the upper layer, designed as DLS/c. DLH demonstrated suitable porosity, appropriate mechanical properties, and excellent biocompatibility. DLS exhibited potent antimicrobial properties, exerted anti-inflammatory effects by regulating macrophage polarisation, and may enhance angiogenesis through the HIF-1α/VEGF pathway. In the DLS/c group, animal studies showed significant improvements in epidermal formation, barrier function, and epidermal hydration, accompanied by reduced inflammation. In addition, Masson's trichrome and Sirius red staining revealed that the structure and ratio of dermal collagen in DLS/c resembled that of normal skin, indicating considerable potential for scarless wound healing. This biomimetic matrix shows promise in addressing the challenges of burn wounds and aiming for scarless repair, with benefits such as anti-infection, epidermal hydration, biological induction, and optimised topological properties. Shown in Acknowledgements.

Natural Polymer-Based Hydrogel Dressings for Wound Healing.

Significance: Acute wounds such as severe burns and chronic wounds like diabetic ulcers present a significant threat to human health. Wound dressings made from natural polymers offer inherent properties that effectively enhance wound healing outcomes and reduce healing time. Recent Advances: Numerous innovative hydrogels are being developed and translated to the clinic to successfully treat various wound types. This underscores the substantial potential of hydrogels in the future wound care market. Economically, annual sales of wound care products are projected to reach $15-22 billion by 2024. Critical Issues: While chitosan-, cellulose-, and collagen-based hydrogel dressings are currently commercially available, scaling-up and manufacturing hydrogels for commercial products remain a challenging process. In addition, ensuring the sterility and stability of the chemical or biological components comprising the hydrogel is a critical consideration. Future Directions: In light of the persistent increase in wound fatalities and the resulting economic and social impacts, as well as the importance of educating the public about dietary health and disease, there should be increased investment in new wound care dressings, particularly hydrogels derived from natural products. With numerous researchers dedicated to advancing preclinical hydrogels, the future holds promise for more innovative and more personalized hydrogel wound dressings.

Non-stationary modeling and simulation of strong winds

Wind velocity is usually assumed to obey a stationary stochastic process in wind engineering, and this may cause significant bias in describing extremely severe strong wind such as typhoons and thunderstorms. To take into account the non-stationary characteristics of extreme wind, a novel evolutionary power spectral density (EPSD) model is proposed, and the spectral representation method (SRM) is introduced to simulate the whole process of strong winds. Firstly, the wavelet transform (WT) method is adopted to capture the three-dimensional time-varying properties of the low-frequency mean winds, and the associated turbulence features, including turbulent intensity, gust factor, probability density function, and power spectrum, are analyzed in depth. Secondly, the measured horizontal EPSD of strong winds are estimated. Thirdly, the performance of the proposed EPSD model is validated. Finally, the whole process of non-stationary strong winds are simulated and discussed. The results show that the proposed EPSD models are in good agreement with the measured EPSD, and the time-frequency features of the power spectrum of the simulated winds are well reproduced, which provides a powerful tool for large eddy simulation and wind engineering studies under non-stationary extreme wind climate.

Optimized Depilation Method and Comparative Analysis of Hair Growth Cycle in Mouse Strains.

In mice, hair growth follows a mosaic or wavy patterning. Therefore, synchronization of the hair growth cycle is required to adequately evaluate any trichogenic interventions pre-clinically. Depilation is the established method for synchronizing the growth phase of mouse hair follicles. When attempting to reproduce procedures reported in the literature, C57BL/6J mice developed severe wounds. This led us not only to optimize the procedure, but also to test the procedure in other strains, namely Sv129 and the F1 generation from C57BL/6J crossed with Sv129 (B6129F1 mixed background), for which the hair growth cycle has not been ascertained yet. Here, we describe an optimized depilation procedure, using cold wax and an extra step to protect the animal skin that minimizes injury, improving experimental conditions and animal welfare in all strains. Moreover, our results show that, although hair cycle kinetics are similar in all the analyzed strains, Sv129 and B6129F1 skins are morphologically different from C57BL/6J skin, presenting an increased number and size of hair follicles in anagen, consistent to the higher hair density observed macroscopically. Altogether, the results disclose an optimized mouse depilation method that excludes the detrimental and confounding effects of skin injury in hair growth studies and reveals the hair cycle features of other mouse strains, supporting their use in hair growth pre-clinical studies.

Investigating the Near-Surface Wind Fields of Downbursts Using a Series of High-Resolution Idealized Simulations

Abstract Short-lived and poorly organized convective cells, often called weakly forced thunderstorms (WFTs), are a common phenomenon during the warm season across the eastern and southeastern United States. While typically benign, wet downbursts emanating from such convection can have substantial societal impacts, including tree, power line, and property damage from strong outflow winds. Observational studies have documented the occurrence of severe (25.7 m s−1 or higher) wind speeds from wet downbursts, but the frequency of severe downbursts, including the spatial extent and temporal duration of severe winds, remains unclear. The ability for modern observing networks to reliably observe such events is also unknown; however, answering these questions is important for improving forecast skill and verifying convective warnings accurately. This study attempts to answer these questions by drawing statistical inferences from 97 high-resolution idealized simulations of single-cell downburst events. It was found that while 35% of the simulations featured severe winds, the spatial and temporal extent of such winds is limited—O(10) km2 or less and persisting for around 5 min on average. Furthermore, through a series of simulated network experiments, it is postulated that the probability that a modern mesonet observes a severe wind gust given a severe downburst is around 1%. From these results, a statistical argument is made that most tree impacts associated with pulse convection are likely caused by subsevere winds. Several implications for forecasting, warning, and verifying WFT events fall out from these discussions.

Exploring the Usefulness of Machine Learning Severe Weather Guidance in the Warn-on-Forecast System: Results from the 2022 NOAA Hazardous Weather Testbed Spring Forecasting Experiment

Abstract Artificial intelligence (AI) is gaining popularity for severe weather forecasting. Recently, the authors developed an AI system using machine learning (ML) to produce probabilistic guidance for severe weather hazards, including tornadoes, large hail, and severe winds, using the National Severe Storms Laboratory’s (NSSL) Warn-on-Forecast System (WoFS) as input. Known as WoFS-ML-Severe, it performed well in retrospective cases, but its operational usefulness had yet to be determined. To examine the potential usefulness of the ML guidance, we conducted a control and treatment (experimental) group experiment during the 2022 NOAA Hazardous Weather Testbed Spring Forecasting Experiment (HWT-SFE). The control group had full access to WoFS, while the experimental group had access to WoFS and ML products. Explainability graphics were also integrated into the WoFS web viewer. Both groups issued 1-h convective outlooks for each hazard. After issuing their forecasts, we surveyed participants on their confidence, the number of products viewed, and the usefulness of the ML guidance. We found the ML-based outlooks outperformed non-ML-based outlooks for multiple verification metrics for all three hazards and were rated subjectively higher by the participants. However, the difference in confidence between the two groups was not significant, and the experimental group self-reported viewing more products than the control group. Participants had mixed sentiments toward explainability products as it improved their understanding of the input/output relationships, but viewing them added to their workload. Although the experiment demonstrated the usefulness of ML guidance for severe weather forecasting, there are avenues to improve upon the ML guidance, and more training and exposure are needed to exploit its benefits fully. Significance Statement We developed an artificial intelligence (AI) system to predict tornadoes, large hail, and damaging straight-line winds. The AI system was leveraged in real time during the 2022 NOAA Hazardous Weather Testbed Spring Forecasting Experiment. This study reveals that forecasters using AI guidance produced more reliable and spatially accurate outlooks than those without. While AI and complementary explainability products did not reduce forecaster workload, both demonstrated great potential for improving severe weather forecasting. This research also highlights the importance of user feedback in refining AI tools for severe weather forecasting.

Plerixafor for pathogen-agnostic treatment in murine thigh infection and zebrafish sepsis.

Plerixafor is a CXCR4 antagonist approved in 2008 by the FDA for hematopoietic stem cell collection. Subsequently, plerixafor has shown promise as a potential pathogen-agnostic immunomodulator in a variety of preclinical animal models. Additionally, investigator-led studies demonstrated plerixafor prevents viral and bacterial infections in patients with WHIM syndrome, a rare immunodeficiency with aberrant CXCR4 signaling. Here, we investigated whether plerixafor could be repurposed to treat sepsis or severe wound infections, either alone or as an adjunct therapy. In a Pseudomonas aeruginosa lipopolysaccharide (LPS)-induced zebrafish sepsis model, plerixafor reduced sepsis mortality and morbidity assessed by tail edema. There was a U-shaped response curve with the greatest effect seen at 0.1 μM concentration. We used Acinetobacter baumannii infection in a neutropenic murine thigh infection model. Plerixafor did not show reduced bacterial growth at 24 h in the mouse thigh model, nor did it amplify the effects of a rifampin antibiotic therapy, in varying regimens. While plerixafor did not mitigate or treat bacterial wound infections in mice, it did reduce sepsis mortality in zebra fish. The observed mortality reduction in our LPS model of zebrafish was consistent with prior research demonstrating a mortality benefit in a murine model of sepsis. However, based on our results, plerixafor is unlikely to be successful as an adjunct therapy for wound infections. Further research is needed to better define the scope of plerixafor as a pathogen-agnostic therapy. Future directions may include the use of longer acting CXCR4 antagonists, biased CXCR4 signaling, and optimization of animal models.

Anomaly-Based Variable Models: Examples of Unusual Track and Extreme Precipitation of Tropical Cyclones

Tropical cyclones (TCs) can cause severe wind and rain hazards. Unusual TC tracks and their extreme precipitation forecasts have become two difficult problems faced by conventional models of primitive equations. The case study in this paper finds that the numerical computation of the climatological component in conventional models restricts the prediction of unusual TC tracks. The climatological component should be a forcing quantity, not a predictor in the numerical integration of all models. Anomaly-based variable models can overcome the bottleneck of forecast time length or the one-week forecasting barrier, which is limited to less than one week for conventional models. The challenge in extreme precipitation forecasting is how to physically get the vertical velocity. The anomalous moisture stress modulus (AMSM), as an indicator of heavy rainfall presented in this paper, considers the two conditions associated with vertical velocity and anomalous specific humidity in the lower troposphere. Vertical velocity is produced by the orthogonal collision of horizontal anomalous airflows.

Inter‐day energy storage expansion framework against extreme wind droughts based on extreme value theory and deep generation models

AbstractThe worldwide occurrence of wind droughts challenges the balance of power systems between energy production and consumption. Expanding inter‐day energy storage serves as a strategic solution, yet optimizing its capacity depends on accurately modeling future renewable energy uncertainties to avoid over‐ or under‐investment. Existing approaches that use the historical extreme scenario set (HESS) to represent future conditions are contentious due to potential inadequacies in forecasting future extreme scenarios (ESs), including those on a decadal or centennial scale. This study addresses the issue by proposing an advanced energy storage expansion framework that leverages Extreme Value Theory (EVT) and a novel Deep Generative Model, namely the Diffusion Model. To model the extremes in a principled way, this work leverages EVT to establish a severity‐probability mapping for wind droughts, guiding the training process of the Diffusion Model. This model excels in generating ESs that accurately reflect the distribution of real‐world extremes, thereby significantly enhancing the predictive capacity of HESS. Case studies on a real‐world power system confirm the method's capacity to generate high‐quality ESs, encompassing the most severe historical wind droughts not included in the training dataset, thereby facilitating resilient energy storage expansion against unforeseen extremes.

A content analysis of legal policy responses to xylazine in the illicit drug supply in the United States

BackgroundXylazine is a veterinary sedative that is quickly spreading in the U.S. illicit drug supply and is increasingly associated with fatal overdoses and severe wounds. In response, xylazine has been deemed an emerging public health threat and several policy initiatives have been introduced to combat its spread and negative broad health impact. We aimed to synthesize trends in all-time U.S. policy responses to xylazine in the drug supply. MethodsIn April 2024, we systematically identified and categorized proposed and enacted policy initiatives that related to human xylazine consumption by searching LexisNexis and Thomas Reuters Westlaw legal databases. ResultsOf 58 unique policy initiatives, most were introduced in 2023 (n = 37/58, 64 %) and concentrated in Northeastern states. Penalties for xylazine possession, often tied to state drug scheduling changes, were the most common provision (n = 34/58; 59 %) and Schedule III was the most frequently proposed scheduling level (n = 17/30; 57 %). Other provisions included proposals to enhance: test strip access (n = 11/58; 19 %), public awareness and education (n = 3/58; 5 %), xylazine-specific research (n = 4/58; 7 %), and surveillance (n = 8/58; 14 %). ConclusionU.S. state and federal policy responses to xylazine grew rapidly in 2023, were most concentrated in states affected most by xylazine, and scheduling was the most commonly proposed policy approach. Research measuring policy effects should be prioritized as policies are implemented.

Extracellular Vesicles Derived from Type 2 Diabetic Mesenchymal Stem Cells Induce Endothelial Mesenchymal Transition under High Glucose Conditions Through the TGFβ/Smad3 Signaling Pathway.

Type 2 diabetes mellitus (T2DM) is associated with endothelial dysfunction, which results in delayed wound healing. Mesenchymal stem cells (MSCs) play a vital role in supporting endothelial cells (ECs) and promoting wound healing by paracrine effects through their secretome-containing extracellular vesicles. We previously reported the impaired wound healing ability of adipose tissue-derived MSC from T2DM donors; however, whether extracellular vesicles isolated from T2DM adipose tissue-derived MSCs (dEVs) exhibit altered functions in comparison to those derived from healthy donors (nEVs) is still unclear. In this study, we found that nEVs induced EC survival and angiogenesis, whereas dEVs lost these abilities. In addition, under high glucose conditions, nEV protected ECs from endothelial-mesenchymal transition (EndMT), whereas dEV significantly induced EndMT by activating the transforming growth factor-β/Smad3 signaling pathway, which impaired the tube formation and invivo wound healing abilities of ECs. Interestingly, the treatment of dEV-internalized ECs with nEVs rescued the induced EndMT effects. Of note, the internalization of nEV into T2DM adipose tissue-derived MSC resulted in the production of an altered n-dEV, which inhibited EndMT and supported the survival of T2DM db/db mice from severe wounds. Taken together, our findings suggest the role of dEV in endothelial dysfunction and delayed wound healing in T2DM by the promotion of EndMT. Moreover, nEV treatment can be considered a promising candidate for cell-free therapy to protect ECs in T2DM.