Sustainable Safety Research Articles

Safety and Potential Efficacy of Expanded Umbilical Cord-Derived Mesenchymal Stromal Cells in Luminal Ulcerative Colitis Patients.

Inflammatory bowel disease (IBD) is characterized by periods of flare-ups and remission. It is likely to be an autoimmune in origin, presenting persistent therapeutic challenges despite current therapies. This study aims to investigate the potential of umbilical cord mesenchymal stromal cells (UCMSCs) in treating ulcerative colitis (UC). This study is a prospective phase 1 pilot, open-label, single-arm, and single-center study. UCMSCs were cultured under current Good Manufacturing Practice (cGMP) conditions and intravenously administered to six patients with UC. Safety and efficacy were evaluated using the Mayo Score/Disease Activity Index. Among the six enrolled adult patients, five completed long-term follow-ups. All exhibited at diagnosis active UC confirmed through comprehensive assessment methods. Each patient received three injections intravenously 2 weeks apart with a dose of 100 million UCMSC each. No significant short-term or intermediate-term adverse events were detected post-UCMSC administration. Long-term follow-up at 12 and 24 months showed sustained safety and no adverse events. Notably, three out of five patients achieved a Mayo score of 0 for UC, maintained at both 12 and 24 months, indicating a highly significant response (P < 0.001). This study demonstrates the safety and potential efficacy of UCMSCs in active UC. However, larger trials are warranted to validate these preliminary findings and to establish the role of UCMSC therapy as an option for managing UC.

Introducing a systematic and sustainable patient safety oversight function in a U.K. arms-length healthcare body

Background The healthcare landscape is experiencing a profound period of change with accelerating developments in medical research, new treatments, care delivery and the use of innovative technology to meet the challenges of delivering care. These changes offer opportunities but as with all innovation, require careful management to reduce the likelihood of harm and error. Objective The National Institute for Health and Care Excellence (NICE) has set out to introduce an adaptable, sustainable and systematic patient safety oversight group to ensure that patient safety is embedded at an organisation level supporting the healthcare system to overcome challenges and deliver high quality care, safely implementing the latest innovations in a timely manner. Method The patient safety oversight group was established through a scoping exercise, led by the senior responsible officer and a small project team. The article sets out the methods used, including extensive internal engagement through structured interviews with senior leadership teams, purposive sampling, data synthesis and reporting. An overview of the group is given and considerations for promoting patient safety information flows and optimising the use of safety signal intelligence are made. Conclusion Through reflection on changing needs within and surrounding the organisation, along with patient safety and complexity literature, NICE has developed an adaptable, systematic and sustainable model for managing patient safety. In addition to generating learning within NICE, the process highlights opportunities for improvement within the patient safety system. Result NICE has developed an adaptable, systematic and sustainable model for managing patient safety.

OA10.03 Tarlatamab Sustained Clinical Benefit and Safety in Previously Treated SCLC: DeLLphi-301 Phase 2 Extended Follow-up

OA10.03 Tarlatamab Sustained Clinical Benefit and Safety in Previously Treated SCLC: DeLLphi-301 Phase 2 Extended Follow-up

Engineered nanomaterials reduce metal(loid) accumulation and enhance staple food production for sustainable agriculture.

Metal(loid) contaminants in food pose a global health concern. This study offers a global analysis of the impact of nanomaterials (NMs) on crop responses to metal(loid) stresses. Our findings reveal that NMs have a positive effect on the biomass production of staple crops (22.8%), while showing inhibitory effects on metal(loid) accumulation in plants (-38.3%) and oxidative damage (-21.6%) under metal(loid) stress conditions. These effects are influenced by various factors such as NM dose, exposure duration, size and composition. Here we introduce a method using interval-valued intuitionistic fuzzy values by integrating the technique for order preference by similarity to an ideal solution and entropy weights to compare the effectiveness of different NM application patterns. These results offer practical insights for the application of NMs in similar multi-criteria decision-making scenarios, contributing to sustainable agriculture and global food safety.

Efficacy and Safety of TransCon PTH in Adults with Hypoparathyroidism: 52-Week Results From the Phase 3 PaTHway Trial.

Conventional therapy for hypoparathyroidism aims to alleviate symptoms of hypocalcemia but does not address insufficient parathyroid hormone (PTH) levels. Assess the long-term efficacy and safety of TransCon PTH (palopegteriparatide) for hypoparathyroidism. Phase 3 trial with a 26-week double-blind, placebo-controlled period followed by a 156-week open-label extension (OLE). 21 sites across North America and Europe. 82 adults with hypoparathyroidism were randomized and received study drug and 78 completed week 52. All OLE participants received TransCon PTH administered once daily. Multi-component efficacy endpoint: proportion of participants at week 52 who achieved normal serum calcium (8.3-10.6 mg/dL) and independence from conventional therapy (≤600 mg/day of elemental calcium and no active vitamin D). Other efficacy endpoints included patient-reported outcomes (PROs) and bone mineral density (BMD). Safety was assessed by 24-hour urine calcium and treatment-emergent adverse events (TEAEs). At week 52, 81% (63/78) met the multi-component efficacy endpoint, 95% (74/78) achieved independence from conventional therapy, and none required active vitamin D. PROs showed sustained improvements in quality of life, physical functioning, and well-being. Mean BMD Z-scores decreased toward age- and sex-matched norms from baseline to week 52. Mean (SD) 24-hour urine calcium excretion decreased from 376 (168) mg/day at baseline to 195 (114) mg/day at week 52. Most TEAEs were mild or moderate and none led to trial discontinuation during the OLE. At week 52 of the PaTHway trial, TransCon PTH showed sustained efficacy, safety, and tolerability in adults with hypoparathyroidism.

Ground subsidence prediction with high precision: a novel spatiotemporal prediction model with Interferometric Synthetic Aperture Radar technology

ABSTRACT As the extraction of mineral resources intensifies, ground subsidence in mining areas has escalated, posing substantial challenges to sustainable development and operational safety. This subsidence, resulting directly from mining activities, significantly compromises the safety of nearby residents by damaging residential structures and infrastructure. Thus, developing precise and dependable methods for predicting ground subsidence is crucial. This study introduces an innovative Cabs-Unet model, which enhances the U-Net architecture by integrating a Convolutional Block Attention Module (CBAM) and Depthwise Separable Convolutions (DSC). This model aims to predict the spatiotemporal dynamics of the Interferometric Synthetic Aperture Radar (InSAR) time series. Employing Small Baseline Subset Interferometric Synthetic Aperture Radar (SBAS InSAR) technology, we gathered and validated data on ground subsidence at the Pengzhuang coal mine from May 2017 to November 2021, covering 130 scenes, with its accuracy corroborated by levelling survey results. An empirical evaluation of the Cabs-Unet model in two distinct subsidence zones demonstrated superior performance over conventional methods like Convolutional Long Short-Term Memory (ConvLSTM) and Predictive Recurrent Neural Network (PredRNN), with Root Mean Square Error (RMSE) values of 1.44 and 1.70, respectively. These findings highlight the model’s efficacy in accurately predicting spatiotemporal InSAR ground subsidence. Further predictive analysis using InSAR data indicated an expected increase in subsidence, projecting cumulative declines of −457 mm in Area A and −1278 mm in Area B by 17 July 2022. Our model proves effective in assessing subsidence, promptly detecting potential risks and facilitating the rapid implementation of risk mitigation strategies.

Short-term (24 weeks) treatment efficacy and safety of ruxolitinib cream in participants with vitiligo: a systematic review and meta-analysis

ImportanceVitiligo is a chronic skin disorder causing depigmentation. There is a lack of evidence-based medical evidence regarding ruxolitinib efficacy and safety for vitiligo.ObjectiveTo assess the efficacy and safety of ruxolitinib cream in the treatment of vitiligo.MethodsThe databases of PubMed, Embase, and Cochrane Library were searched. The literature screening was independently conducted by two reviewers.Data extraction and synthesisFor continuous variables, weighted mean difference (WMD) along with a 95% confidence interval (CI) was performed. For dichotomous outcomes, we calculated the odds ratios (ORs) or risk ratios (RRs), and their corresponding 95% CIs. The certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE).Main outcomes and measuresSymptoms, quality of life, and safety were evaluated using various measures, including the Facial Vitiligo Area Scoring Index (F-VASI), Total Vitiligo Area Scoring Index (T-VASI), Facial Body Surface Area (F-BAS), Total Body Surface Area (T-BAS) and Treatment-emergent Adverse Events (TEAEs).ResultsThree trials, involving a total of 830 participants from nine countries were included (female 388, 46.7%, male 442, 53.3%). The meta-analysis demonstrated a significant increase in the likelihood of participants achieving F-VASI75 (OR, 4.34 [95% CI 2.67–7.06]; high), F-VASI50 (OR 4.71 [95% CI 3.24–6.84]; high), T-VASI75 (OR 2.78 [95% CI 1.10–7.00]; moderate), and T-VASI50 (OR 4.47 [95% CI 2.52–7.92]; high) when compared ruxolitinib to vehicle. Ruxolitinib was associated with more lowered percentage change of F-VASI scores (MD − 32.79 [95% CI − 36.37 to − 29.21]; moderate), and T-VASI scores (MD − 20.22 [95% CI − 23.11 to − 17.33]; moderate) from baseline compared to vehicle. There may not be a significant difference in the occurrence of TEAEs between ruxolitinib and vehicle (RR 1.46 [95% CI 0.85–2.49]; high).ConclusionsThe findings suggest that ruxolitinib cream holds promise as a treatment option for vitiligo. Further long-term studies are needed to assess its sustained efficacy and safety profile.Systematic review registrationPROSPERO CRD42023431112.

S1200 Sustained Efficacy and Safety After 5 Years of Continuous Ozanimod Treatment Independent of Clinical Remission Status: An Interim Analysis of the True North Open-Label Extension Study

S1200 Sustained Efficacy and Safety After 5 Years of Continuous Ozanimod Treatment Independent of Clinical Remission Status: An Interim Analysis of the True North Open-Label Extension Study

The application of the Fuzzy Analytical Hierarchy Process (FAHP) as a multi-criteria analysis tool for road risk assessment: Algeria as a case study

In response to the escalating road safety challenges and the persistent increase in traffic accidents, it is imperative to adopt an integrated approach to address this multifaceted issue effectively. The main objective of this research is to classify or identify high-risk areas by studying the impact of the most significant factors contributing to road accidents. The methodology is based on a hierarchical model of three levels, including the essential factors that increase road risk. Subsequently, a fuzzy hierarchy process (FAHP) is conducted using a fuzzy scale to evaluate and analyse the most influential factors to determine the risk level for each road segment. This approach has been applied to the motorway in Algeria, specifically in the Mascara region, where the road was divided into 83 sections of 100 metres. The study's results revealed that factors related to infrastructure and those associated with drivers had the most significant impact, while environmental factors had less influence on road safety. The studied area exhibited risk levels ranging from moderate to low. The current state analysis of the roads (open to traffic) allows for the evaluation of factors that heighten road risks, this comprehensive evaluation is instrumental in formulating sustainable road safety strategies to mitigate future traffic accidents.

ТЕОРЕТИЧНИЙ АНАЛІЗ ПОНЯТТЯ РЕГУЛЯТОРНА ПОЛІТИКА У ПЛАНУВАННІ ТА ЗАБУДОВІ МІСТА: ОСНОВНІ ПІДХОДИ ТА СУЧАСНІ ТЕНДЕНЦІЇ

Regulatory policy in the field of urban planning and development is a key element of public administration aimed at ensuring economic stability, social welfare and sustainable development. In the conditions of globalization and intensive technological progress, effective regulation of urban planning processes is becoming more and more important for solving modern challenges. The purpose of this study is to carry out a theoretical analysis of the concept of regulatory policy in urban planning and development, to study the main approaches to its implementation, as well as to determine modern trends and opportunities for adapting international experience for Ukraine. In particular, the research aims to identify effective models of regulatory policy that can be integrated into national legislation and practice to improve the management of urban development. The research uses a comprehensive approach, which includes the analysis of scientific publications, comparative analysis of regulatory policies of different countries, methods of critical literature review and data synthesis. Special attention is paid to the experience of countries such as the USA, Germany and Singapore, where various approaches to the regulation of urban planning processes are used. The analysis showed that regulatory policy in urban planning and development is a multifaceted phenomenon, which includes such basic approaches as zoning, strategic spatial planning, energy efficiency, integration of transport infrastructure and active involvement of the public in the decision‒ making process. Modern trends in regulatory policy have been identified, including innovative approaches to planning, the use of digital technologies, an emphasis on sustainable development and environmental safety. A comparative analysis of the regulatory policies of the USA, Germany, and Singapore made it possible to identify effective models that can be adapted to the conditions of Ukraine. The study confirmed that an effective regulatory policy is an important prerequisite for sustainable economic development, social stability and protection of citizens' rights. Further research should focus on the integration of digital technologies into regulatory processes, improvement of control and monitoring mechanisms, which will contribute to the sustainable development of cities in Ukraine.

Emergency Response Competencies Strengthened by Sustainable Education: First Aid Training Program for Teachers

The primary aim of this study is to assess the knowledge, attitudes, and skills of primary school teachers regarding the management of musculoskeletal trauma through first aid interventions and to determine the effectiveness of a sustainable training program. The preparedness of 138 teachers who received first aid training for trauma intervention and the impact of these trainings on health practices were examined by pre- and post-tests. It was determined that 87% of the teachers participating in the study had not received emergency trauma training before. Pre-training test results showed that the participants had a low level of awareness. However, the increase in mean scores from 6 to 16 and the decrease in standard deviation after the training revealed a significant increase in teachers’ knowledge, attitudes, and skills. These results suggest that emergency trauma training programs significantly increase teachers’ ability to respond to emergencies and emphasize the importance of sustainable first aid training. Analyses based on gender and branch revealed that post-training test scores were similar and all teachers showed high performance. The findings emphasize the need for systematic and comprehensive emergency trauma training programs for all teachers and the importance of these programs for sustainable health and safety practices.

Community-Based Violence Intervention in the Aftermath of Homicide: Community Violence Prevention Specialists’ Proximity to and Perspectives on Community Safety and Healing

Communities impacted by homicide endure profound loss and trauma, yet the voices of those intimately acquainted with navigating its aftermath are often overlooked and undervalued. In this study, we center the perspectives of community violence prevention specialists (CVPS) to understand the role of community-based violence intervention (CVI) in the aftermath of homicide and identify essential needs for fostering holistic and sustainable safety and healing following homicide. Qualitative data collected from in-person, semi-structured focus groups and interviews between March 2022 and April 2023 with 45 CVPS in Baltimore, Milwaukee, and Sacramento were coded and thematically analyzed. We identified various intersecting ways in which CVPS have unique proximity to and perspective on homicide via personal histories and community relationships, crisis response, preventative peacemaking and community healing, understanding violence drivers, CVI implementation challenges, and policy advocacy. Their perspectives reveal nuanced insights into the dynamics of homicide and its prevention. CVI plays a critical role in the aftermath of homicide, and CVPS have invaluable expertise navigating its multi-tiered dynamics, positioning them as strategic responders to homicide and as experts in identifying community needs and solutions specific to violence recovery. Their voices, work, and wellbeing deserve investment and close attention.

Capacity building for road safety in LMICs: the need for a sustainable local knowledge and research infrastructure

Road crashes continue to be a major cause of death and serious injury for low- and middle-income countries (LMICs). At the global level, 90% of traffic fatalities occur in these countries with a dramatic daily amount of 3 260 road deaths, many of whom are children. The first UN Decade of Action for Road Safety 2011–2020 was designed to develop a massive movement towards a decrease of these numbers. This resulted in many initiatives to introduce the safe system approach in LMICs, i.e. to implement road safety management, make roads, road users, and vehicles safer, and improve post-crash health care. International organisations together with NGOs and universities prepared road safety guides and manuals, gave courses and webinars, introduced auditing and inspection systems, with the overall intention to build capacity in LMICs. Together these actions contributed to a variety of road safety developments in LMICs but the overall results were still modest. At the third Global Ministerial Conference on Road Safety in Stockholm, 2020, and in the Global Status report by the World Health Organization, 2023, the results of all efforts were presented and evaluated. Many countries made progress through road safety management and better legislation addressing risk factors such as speeding, drinking and driving, failing to use seatbelts, and poor infrastructure design. However, the reduction in road deaths strongly lagged behind the original goals. Continued implementation of programs and development of new approaches are needed to make a breakthrough, and to reach the goals of the 2nd Decade of Action, i.e. a 50% reduction in fatalities by 2030, and the same percentage reduction in injuries. The present position paper argues that despite the enormous amount of road safety information, which has been and is ‘sent’ to LMICs, and despite the quality and robustness of international organisations behind these programs, there is a shortfall in the scale of the knowledge and research infrastructure currently existing in LMICs, which is needed to ‘receive and transfer’ this knowledge. In order to develop evidence-based policy, LMICs need research programs that are able to transfer safe system principles to the local context and culture. Several literature overviews illustrate the lack of such research in LMICs, i.e. the limited number of programs at local universities and research institutes. Although recently initiatives have been taken in some countries, the implementation of such programs is urgently needed. Based on this observation we call on international organisations to establish a special program for the development of a sustainable road safety knowledge and research infrastructure in LMICs. Such structural local capacity is a prerequisite to translate international road safety knowledge into local guidelines and to develop an evidence-based road safety policy. Most importantly, this local infrastructure will give countries a national knowledge bank, thus providing them with an urgently needed sustainable road safety memory.

Magnetically targeted lidocaine sustained-release microspheres: optimization, pharmacokinetics, and pharmacodynamic radius of effect

ObjectiveThis study aimed to optimize the formulation of magnetically targeted lidocaine microspheres, reduce the microsphere particle size, and increase the drug loading and encapsulation rate of lidocaine. The optimized microspheres...

Microplastics originated from agricultural mulching films affect enchytraeid multigeneration reproduction and soil properties

Microplastics (MPs) are increasingly entering agricultural soils, often from the breakdown of agricultural plastics (e.g., mulching films). This study investigates the effects of realistic MPs from different mulching films: two conventional polyethylene (PE-1 and PE-2) and two biodegradable (starch-blended polybutylene adipate co-terephthalate; PBAT-BD-1 and PBAT-BD-2). MPs were mixed into Lufa 2.2 soil at a concentration range from 0.005 % to 5 % (w/w dry soil), wide enough to reflect both realistic environmental levels and “worst-case scenarios”. Effects on Enchytraeus crypticus reproduction over two generations and six important soil properties were studied. PBAT MPs notably reduced enchytraeid reproduction in the F0 generation, with a maximum decrease of 35.5 ± 9.6 % at 0.5 % concentration. F1 generation was unaffected by PBAT contamination. PE MPs had a more substantial reproductive impact, with up to a 55.3 ± 9.7 % decrease at 5 % PE-1 concentration compared to the control, showing a dose-related effect except for 1 %. Both MP types also significantly affected soil water holding capacity, pH, and total carbon. Other soil properties remained unaffected. Our results highlight the potential negative impacts of MPs originating from real agricultural plastics on soil health and raise concerns about the role of agricultural plastics in sustainable agriculture and food safety.

Nutrient strengthening and lead alleviation in Brassica Napus L. by foliar ZnO and TiO2-NPs modulating antioxidant system, improving photosynthetic efficiency and reducing lead uptake

With the anticipated foliar application of nanoparticles (NPs) as a potential strategy to improve crop production and ameliorate heavy metal toxicity, it is crucial to evaluate the role of NPs in improving the nutrient content of plants under Lead (Pb) stress for achieving higher agriculture productivity to ensure food security. Herein, Brassica napus L. grown under Pb contaminated soil (300 mg/kg) was sprayed with different rates (0, 25, 50, and 100 mg/L) of TiO2 and ZnO-NPs. The plants were evaluated for growth attributes, photosynthetic pigments, leaf exchange attributes, oxidant and antioxidant enzyme activities. The results revealed that 100 mg/L NPs foliar application significantly augmented plant growth, photosynthetic pigments, and leaf gas exchange attributes. Furthermore, 100 mg/L TiO2 and ZnO-NPs application showed a maximum increase in SPAD values (79.1%, 68.9%). NPs foliar application (100 mg/L TiO2 and ZnO-NPs) also substantially reduced malondialdehyde (44.3%, 38.3%), hydrogen peroxide (59.9%, 53.1%), electrolyte leakage (74.8%, 68.3%), and increased peroxidase (93.8%, 89.1%), catalase (91.3%, 84.1%), superoxide dismutase (81.8%, 73.5%) and ascorbate peroxidase (78.5%, 73.7%) thereby reducing Pb accumulation. NPs foliar application (100 mg/L) significantly reduced root Pb (45.7%, 42.3%) and shoot Pb (84.1%, 76.7%) concentration in TiO2 and ZnO-NPs respectively, as compared to control. Importantly, macro and micronutrient analysis showed that foliar application 100 mg/L TiO2 and ZnO-NPs increased shoot zinc (58.4%, 78.7%) iron (79.3%, 89.9%), manganese (62.8%, 68.6%), magnesium (72.1%, 93.7%), calcium (58.2%, 69.9%) and potassium (81.5%, 68.6%) when compared to control without NPs. The same trend was observed for root nutrient concentration. In conclusion, we found that the TiO2 and ZnO-NPs have the greatest efficiency at 100 mg/L concentration to alleviate Pb induced toxicity on growth, photosynthesis, and nutrient content of Brassica napus L. NPs foliar application is a promising strategy to ensure sustainable agriculture and food safety under metal contamination.

Optimizing Kernel Density Estimation Bandwidth for Road Traffic Accident Hazard Identification: A Case Study of the City of London

Road traffic accidents pose significant challenges to sustainable urban safety and intelligent transportation management. The effective hazard identification of crash hotspots is crucial in implementing targeted safety measures. A severity-weighted system was adopted to quantify crash hazard levels. Using 1059 valid crash records of the City of London, the spatial correlations of crash points were first examined via average nearest neighbor analysis. Then, the optimal KDE bandwidth was determined via ArcGIS’s automatic extraction method, multi-distance spatial cluster analysis, and incremental spatial autocorrelation (ISA) analysis. The predictive accuracy index (PAI) was used to evaluate the accuracy of KDE results at various bandwidths. The results revealed a clustered spatial distribution of crash points. The optimized KDE bandwidth obtained via ISA analysis was 134 m, and the yielded PAI was 4.381, indicating better predictive accuracies and balanced hotspot distributions and reflecting both local concentrations and the overall continuity of crash hazard hotspots. Applying this bandwidth to the validation data allowed the successful identification of most high-risk areas and potential crash hazard hotspots attributed to traffic environmental factors; this method exhibits reliability, accuracy, and robustness over medium to long time scales. This workflow can serve as an analytical template for assisting planners in improving the identification accuracy of hazard hotspots, thereby reducing crash occurrences, actively promoting sustainable traffic safety development, and providing valuable insights for targeted crash prevention and intelligent traffic safety management in urban areas.

Unintended food safety impacts of agricultural circular economies, with case studies in arsenic and mycotoxins

For millennia, food systems worldwide have employed practices befitting a circular economy: recycling of agricultural and food waste or byproducts, environmentally sustainable production methods, and food preservation to reduce waste. Many modern-day agricultural practices may also contribute to a circular economy through the reuse of waste products and/or reducing agricultural inputs. There are, however, food safety impacts. This paper describes two sustainable agricultural practices that have unintended positive and negative impacts on food safety: alternative rice cultivation practices and no-till agriculture. We highlight how alternative rice cultivation practices have intended benefits of water conservation and economic savings, yet also unintended effects on food safety by reducing foodborne arsenic levels while increasing cadmium levels. No-till agriculture reduces soil erosion and repurposes crop residues, but can lead to increased foodborne mycotoxin levels. Trade-offs, future research, and policy recommendations are discussed as we explore the duality of sustainable agricultural practices and food safety.

Blockchain-enabled transparent traffic enforcement for sustainable road safety in cities

With the progress of the times, cars have become an important means of transportation in our lives. However, with new cars of all kinds, road safety issues still cannot be effectively improved. While countries have responded by enforcing traffic laws and using electronic technology to enhance enforcement, challenges still need to be addressed, including blurred images and misjudgments by police agencies, and even exploiting loopholes in traffic enforcement frameworks to evade consequences through bribery or connections. exacerbating an accident and leaving victims and families in the lurch of the aftermath. To solve this problem, we proposed a data traceability law enforcement system based on blockchain and InterPlanetary File System (IPFS). The system ensures rapid traceability and protects law enforcement data from external attacks. The goal of leveraging blockchain’s decentralized nature and smart contracts is to instill accountability and fairness in road safety measures, mitigate the effects of corruption, and pave the way for a safer and more just transportation environment. Our experimental results show that under our stress test of 50 transactions per second, the throughput can be as high as 300 and the maximum delay can reach 2.01s, which is enough to experimentally prove that our system is feasible. Our approach is designed to solve the data corruption problem caused by the centralized server being paralyzed. It applies to all technology enforcement, with high flexibility and scalability for all participants to join or set privileges. we also provide an automated traffic law enforcement system in a smart city. To make the data storage more secure and fair, and not easily damaged by malicious people or tampered with by intentional attackers. This brings a breakthrough to the country’s program security.

Long-term efficacy and safety of continued complement C1s inhibition with sutimlimab in cold agglutinin disease: CADENZA study Part B

Cold agglutinin disease (CAD) is a rare autoimmune haemolytic anaemia mediated by the classical complement pathway (CP). Sutimlimab selectively targets complement C1s inhibiting classical CP activation. In CADENZA Part A (26-weeks), a placebo-controlled study in patients without recent transfusion history, sutimlimab reduced haemolysis, anaemia, and fatigue, and was generally well tolerated. The CADENZA study (NCT03347422) started in March 2018 (Part A) and completed in December 2021 (Part B). All patients in Part B were eligible to receive sutimlimab for up to 1 year after the last patient completed Part A. Efficacy and safety was assessed throughout Part B, until the last on-treatment visit with available assessment (LV), and after a 9-week washout. In total, 32/39 patients completed Part B; median treatment duration: 99 weeks. Similar sustained improvements in haemolysis, anaemia, and quality of life were observed in patients switching to sutimlimab and those continuing sutimlimab. Mean LV values for the combined group (ie, placebo-to-sutimlimab group and sutimlimab-to-sutimlimab group) improved from baseline for haemoglobin (≥11.0g/dL on-treatment vs 9.3g/dL at baseline), bilirubin (≤20.0μmol/L on-treatment vs 35.0μmol/L at baseline), and FACIT-Fatigue scores. Following a 9-week washout, inhibition of CP activity was reversed, and haemolytic markers approached baseline levels. Overall, sutimlimab was generally well tolerated throughout the study. No patients developed systemic lupus erythematosus or meningococcal infections. During the 9-week washout, most adverse events could be attributed to recurrence of underlying CAD. The CADENZA Part B results support the sustained efficacy and safety of sutimlimab for treatment of CAD; however, upon discontinuation disease activity reoccurs. Sanofi.