Targets For Safety Research Articles

Nanopore Detection of Small Molecules Based on Replacement and Complexation Chemical Interactions.

Small molecules play important roles in a variety of biological processes such as metabolism, cell signaling and enzyme regulation, and can serve as valuable biomarkers for human diseases. Moreover, they are essential to drug discovery and development, and are important targets for environmental monitoring and food safety. Due to the size incompatibility, small molecule transport is difficult to be monitored with a nanopore. A popular strategy for nanopore detection of small molecules is to introduce a molecular probe as a ligand (or recognition element) and rely on their effect on the ligand transport. One limitation for this sensing strategy is that the probe molecule needs to have a slightly smaller size than the nanopore constriction or can be easily unfolded or unzipped through the pore. Herein, by taking advantage of replacement and complexation chemical interactions, a generic approach is reported for detection of small molecules by using large biomolecules with well-defined stable 3D structures such as aptamers as recognition elements. Given the versatile use of aptamers as capture agents for a wide variety of species, the developed nanopore sensing strategy should find applications in many fields.

Oxidized TMB mediated dual-optical sensing-based paper analytical device for high-throughput visual monitoring of 2,4-dichlorophenoxyacetic acid

High-throughput and accurate monitoring of pesticide residues is extremely crucial, but remains challenging. Herein, oxidized 3,3′,5,5′-tetramethylbenzidine (oxTMB) mediated dual-optical sensing-based paper analytical device (PAD) was unveiled for on-site visual detection of 2,4-dichlorophenoxyacetic acid (2,4-D) in real samples. Colorimetric blue oxTMB (652 nm) can be reduced to colorless TMB by ascorbic acid (AA). Meanwhile, oxTMB was demonstrated for the first time to switch oxidation and condensation reactions between o-phenylenediamine and AA to produce yellow-emission (564 nm) and blue-emission (429 nm) probes. Thus, colorimetric and ratiometric fluorescent dual-mode detection system was developed for 2,4-D detection by combining with alkaline phosphatase (ALP) initiating AA generation (ascorbic acid-2-phosphate as the substrate). Notably, the developed method can correct itself to improve the accuracy due to the dual-response signals. Using the principle, ALP-loaded PAD (array 3 × 10) was designed for efficient and high-performance detection of 2,4-D in turnip and cauliflower with good sensitivity (0.09 μg/mL for colorimetry, 0.06 μg/mL for fluorometry), satisfactory recovery (98.0 %–107.2 %), and high consistency (relative error ≤ 3.1 %). This work demonstrated a promising strategy for high-throughput visual detection of 2,4-D, which may provide a new pathway for the further development of dual-mode sensing platforms to efficiently detect other targets for food safety.

Issue of VHF Continuous Emission Radars Coordinate Measurement Discrepancy

The research delves into the significance of continuous emission radars of very high frequency (VHF) range in detecting small unmanned aircraft and marine targets for navigation safety. Recognising the need for improved radars and reduced coordinate measurement errors, the study aims to analyse discrepancies in azimuth and range determination in radars with fixed-phased antenna arrays. By developing effective tools with low computational complexity for target azimuth determination, the research seeks to enhance radar performance. Employing analytical, classification, functional, and statistical methods, the study comprehensively examines the peculiarities and differences of radars. It meticulously analyses coordinate measurement errors and investigates their causes. The impact of these discrepancies on radar performance and their relevance in various applications, particularly maritime navigation, is carefully evaluated. The findings emphasise the critical role of continuous emission radars in ensuring shipping safety and economic efficiency. The recommendations derived from the study offer valuable insights for improving radar effectiveness, addressing operational limitations, and enhancing overall functionality. By tackling coordinate measurement errors and providing accurate azimuth determination tools, this research contributes to advancing continuous emission radar technology and its practical applications. Through its findings and recommendations, the study aims to optimise radar performance, enhance navigation safety, and improve economic efficiency in diverse sectors.

Recommendations of Gentamicin Dose Based on Different Pharmacokinetic/Pharmacodynamic Targets for Intensive Care Adult Patients: A Redefining Approach.

In addition to the maximum plasma concentration (Cmax) to the minimum inhibitory concentration (MIC) ratio, the 24-hour area under the concentration-time curve (AUC24h) to MIC has recently been suggested as pharmacokinetic/pharmacodynamic (PK/PD) targets for efficacy and safety in once-daily dosing of gentamicin (ODDG) in critically ill patients. This study aimed to predict the optimal effective dose and risk of nephrotoxicity for gentamicin in critically ill patients for two different PK/PD targets within the first 3 days of infection. The gathered pharmacokinetic and demographic data in critically ill patients from 21 previously published studies were used to build a one-compartment pharmacokinetic model. The Monte Carlo Simulation (MCS) method was conducted with the use of gentamicin once-daily dosing ranging from 5-10 mg/kg. The percentage target attainment (PTA) for efficacy, Cmax/MIC ~8-10 and AUC24h/MIC ≥110 targets, were studied. The AUC24h >700 mg⋅h/L and Cmin >2 mg/L were used to predict the risk of nephrotoxicity. Gentamicin 7 mg/kg/day could achieve both efficacy targets for more than 90% when the MIC was <0.5 mg/L. When the MIC increased to 1 mg/L, gentamicin 8 mg/kg/day could reach the PK/PD and safety targets. However, for pathogens with MIC ≥2 mg/L, no studied gentamicin doses were sufficient to reach the efficacy target. The risk of nephrotoxicity using AUC24h >700 mg⋅h/L was small, but the risk was greater when applying a Cmin target >2 mg/L. Considering both targets of Cmax/MIC ~8-10 and AUC24h/MIC ≥110, an initial gentamicin dose of 8 mg/kg/day should be recommended in critically ill patients for pathogens with MIC of ≤1 mg/L. Clinical validation of our results is essential.

What is the right gentamicin dose for multiple trauma patients? A Monte Carlo simulation exploration study.

The appropriate dose of gentamicin is important to prevent and treat infections. The study aimed to determine the optimal dose of gentamicin to achieve the probability of pharmacokinetic/pharmacodynamic (PK) targets for efficacy and safety in multiple trauma patients. PK parameters of gentamicin in multiple trauma patients were gathered to develop a one-compartment PK model for prediction. The Monte Carlo simulation method was performed. The 24-h area under the concentration time curve to the minimum inhibitory concentration ratio (AUC24h/MIC) ≥50 was defined for the infection prevention target. AUC24h/MIC ≥110 or the maximum serum concentration to MIC ratio ≥8-10 was for the treatment of serious Gram-negative infection target. The risk of nephrotoxicity was the minimum serum concentration ≥2 mg/L. The optimal dose of gentamicin was determined when the efficacy target was >90% and the risk of nephrotoxicity was lowest. The optimal gentamicin dose to prevent infection when the MIC was <1 mg/L was 6-7 mg/kg/day. A higher dose of gentamicin up to 10 mg/kg/day could not reach the target for treating serious Gram-negative infection when the expected MIC was ≥1 mg/L. The probability of nephrotoxicity was minimal at 0.2-4% with gentamicin doses of 5-10 mg/kg/day for 3 days. Once daily gentamicin doses of 6-7 mg/kg are recommended to prevent infections in patients with multiple trauma. Gentamicin monotherapy could not be recommended for serious infections. Further clinical studies are required to confirm our results.

Caring for a "Blue" Population: Addressing Priorities of the Officer Safety and Wellness Group in Nurse Practitioner Practice.

Increased public concern over policing and the psychological impact of trauma-associated events by first responders have highlighted a critical need to improve the availability of mental health and wellness resources for law enforcement officers. The national Officer Safety and Wellness Group prioritized mental health, alcohol use, fatigue, and body weight/poor nutrition as targets for safety and wellness initiatives. Departmental culture will need to change from silence and fear-driven hesitancy to a culture of openness and support. Increased education, openness, and support for mental health will likely reduce stigma and improve access to care. Psychiatric-mental health nurse practitioners and other advanced practice nurses who wish to work with law enforcement officers should be aware of the specific health risks and standards of care that are summarized in this article. [Journal of Psychosocial Nursing and Mental Health Services, 61(10), 13-18.].

Coastal high-frequency radars in the Mediterranean – Part 2: Applications in support of science priorities and societal needs

Abstract. The Mediterranean Sea is a prominent climate-change hot spot, with many socioeconomically vital coastal areas being the most vulnerable targets for maritime safety, diverse met-ocean hazards and marine pollution. Providing an unprecedented spatial and temporal resolution at wide coastal areas, high-frequency radars (HFRs) have been steadily gaining recognition as an effective land-based remote sensing technology for continuous monitoring of the surface circulation, increasingly waves and occasionally winds. HFR measurements have boosted the thorough scientific knowledge of coastal processes, also fostering a broad range of applications, which has promoted their integration in coastal ocean observing systems worldwide, with more than half of the European sites located in the Mediterranean coastal areas. In this work, we present a review of existing HFR data multidisciplinary science-based applications in the Mediterranean Sea, primarily focused on meeting end-user and science-driven requirements, addressing regional challenges in three main topics: (i) maritime safety, (ii) extreme hazards and (iii) environmental transport process. Additionally, the HFR observing and monitoring regional capabilities in the Mediterranean coastal areas required to underpin the underlying science and the further development of applications are also analyzed. The outcome of this assessment has allowed us to provide a set of recommendations for future improvement prospects to maximize the contribution to extending science-based HFR products into societally relevant downstream services to support blue growth in the Mediterranean coastal areas, helping to meet the UN's Decade of Ocean Science for Sustainable Development and the EU's Green Deal goals.

Evidence-based chlorination targets for household water safety in humanitarian settings: Recommendations from a multi-site study in refugee camps in South Sudan, Jordan, and Rwanda

The current Sphere guideline for water chlorination in humanitarian emergencies fails to reliably ensure household water safety in refugee camps. We investigated post-distribution chlorine decay and household water safety in refugee camps in South Sudan, Jordan, and Rwanda between 2013-2015 with the goal of demonstrating an approach for generating site-specific and evidence-based chlorination targets that better ensure household water safety than the status quo Sphere guideline. In each of four field studies we conducted, we observed how water quality changed between distribution and point of consumption. We implemented a nonlinear optimization approach for the novel technical challenge of modelling post-distribution chlorine decay in order to generate estimates on what free residual chlorine (FRC) levels must be at water distribution points, in order to provide adequate FRC protection up to the point of consumption in households many hours later at each site. The site-specific FRC targets developed through this modelling approach improved the proportion of households having sufficient chlorine residual (i.e., ≥0.2 mg/L FRC) at the point of consumption in three out of four field studies (South Sudan 2013, Jordan 2014, and Rwanda 2015). These sites tended to be hotter (i.e., average mid-afternoon air temperatures >30°C) and/or had poorer water, sanitation, and hygiene (WASH) conditions, contributing to considerable chlorine decay between distribution and consumption. Our modelling approach did not work as well where chlorine decay was small in absolute terms (Jordan 2015). In such settings, which were cooler (20 to 30°C) and had better WASH conditions, we found that the upper range of the current Sphere chlorination guideline (i.e., 0.5 mg/L FRC) provided sufficient residual chlorine for ensuring household water safety up to 24 hours post-distribution. Site-specific and evidence-based chlorination targets generated from post-distribution chlorine decay modelling could help improve household water safety and public health outcomes in refugee camp settings where the current Sphere chlorination guideline does not provide adequate residual protection. Water quality monitoring in refugee/IDP camps should shift focus from distribution points to household points of consumption in order to monitor if the intended public health goal of safe water at the point of consumption is being achieved.

PROTOCOL: Effectiveness of road safety interventions: An evidence and gap map.

The Decade of Action for Road Safety 2011-2020, officially proclaimed by the UN General Assembly in March 2010, sought to reduce morbidity and mortality due to road traffic injuries (RTI) significantly. While there is reasonable agreement internationally on safer designs of motor vehicles (except locally produced vehicles like three-wheeled scooter taxis, tuk-tuks, jeepneys, etc.), there is a lack of evidence based interventions in road and infrastructure design, police enforcement and post-crash care. Researchers in the field of traffic safety have been aware of the existence of counterintuitive results in their area of work for more than four decades. The fact that many interventions do not result in reductions in RTI is mainly because a large number of studies only measure intermediate outcomes like change in behaviour or knowledge and not the actual results in the field. The scope of this evidence and gap map (EGM) is to cover relevant studies in road safety sector from all countries and present the effectiveness of interventions in terms of mainly traffic crash injuries as its outcome. The interventions adopted in this EGM are classified into five broad categories: Human factors, vehicle factors and protective devices, road design, infrastructure and traffic control, post-crash pre-hospital care and legal and institutional framework. In order to come closer to accomplishing targets for road safety, it is important to allocate resources to promote interventions that are effective in achieving outcomes in the context of road safety. A mapping will provide a comprehensive overview of existing knowledge in the area of road safety and its effectiveness across the world. The map will guide programme managers to high quality evidence and inform targeted commissioning of future research.

A tandem GGDEF-EAL domain protein-regulated c-di-GMP signal contributes to spoilage-related activities of Shewanella baltica OS155.

Cyclic diguanylate (c-di-GMP) is a second messenger involved in the regulation of various physiological processes in bacteria. However, its function in spoilage bacteria has not yet been addressed. Here, we studied the function of a tandem GGDEF-EAL domain protein, Sbal_3235, in the spoilage bacterium Shewanella baltica OS155. The deletion of sbal_3235 significantly reduced the c-di-GMP level, biofilm formation, and exopolysaccharide, trimethylamine (TMA), and putrescine production; sbal_3235 deletion also downregulated the expression of the torS and speF genes and affected membrane fatty acid composition. Site-directed mutagenesis in conserved GGDEF and EAL motifs abolished diguanylate cyclase (DGC) and phosphodiesterase (PDE) activity, respectively. These data indicate that Sbal_3235 is an essential contributor to the c-di-GMP pool with bifunctional DGC and PDE activity, which is involved in the biofilm formation and spoilage activity of S. baltica OS155. Our findings expand the biochemical role of c-di-GMP and uncover its link to spoilage activities, providing novel targets for food quality and safety controlling.

Vancomycin Population Pharmacokinetics in Critically Ill Adults During Sustained Low-Efficiency Dialysis

Sustained low-efficiency dialysis (SLED) is a hybrid form of dialysis that is increasingly used in critically ill patients with kidney injury and hemodynamic instability. Antimicrobial dosing for patients receiving SLED is informed by pharmacokinetic studies that describe the drug clearance. Studies available to assist in the dosing of vancomycin in the context of SLED are lacking. The objective of this prospective observational study was to describe the population pharmacokinetics of vancomycin in critically ill patients receiving SLED, and use simulation studies to propose dosing strategies. Serial serum samples were obtained from 31 critically ill patients prescribed vancomycin while receiving SLED. Vancomycin concentrations were quantified in plasma using a validated liquid chromatography mass spectrometry/mass spectrometry method. A population pharmacokinetic model was developed, and Monte Carlo simulation was used to determine the probability of target attainment at different doses. From a total of 335 serum samples from 31 patients receiving 52 sessions of SLED therapy, a two-compartment linear model with zero-order input was developed. The mean (standard deviation) clearance of vancomycin on and off SLED was 5.97 (4.04) and 2.40 (1.46)L/h, respectively. Using pharmacodynamic targets for efficacy (area under the concentration-time curve from time zero to 24h [AUC24]/minimum inhibitory concentration [MIC] ≥ 400) and safety (AUC24 ≥ 700), a loading dose of 2400mg followed by daily doses of 1600mg is recommended. Subsequent dosing should be informed by therapeutic drug monitoring of vancomycin levels. In critically ill patients receiving SLED, vancomycin clearance is highly variable with a narrow therapeutic window. Empiric dosing is proposed but subsequent dosing should be guided by drug levels.

Linezolid pharmacokinetics in MDR-TB: a systematic review, meta-analysis and Monte Carlo simulation.

ObjectivesThe oxazolidinone linezolid is an effective component of drug-resistant TB treatment, but its use is limited by toxicity and the optimum dose is uncertain. Current strategies are not informed by clinical pharmacokinetic (PK)/pharmacodynamic (PD) data; we aimed to address this gap.MethodsWe defined linezolid PK/PD targets for efficacy (fAUC0–24:MIC >119 mg/L/h) and safety (fCmin <1.38 mg/L). We extracted individual-level linezolid PK data from existing studies on TB patients and performed meta-analysis, producing summary estimates of fAUC0–24 and fCmin for published doses. Combining these with a published MIC distribution, we performed Monte Carlo simulations of target attainment.ResultsThe efficacy target was attained in all simulated individuals at 300 mg q12h and 600 mg q12h, but only 20.7% missed the safety target at 300 mg q12h versus 98.5% at 600 mg q12h. Although suggesting 300 mg q12h should be used preferentially, these data were reliant on a single centre. Efficacy and safety targets were missed by 41.0% and 24.2%, respectively, at 300 mg q24h and by 44.6% and 27.5%, respectively, at 600 mg q24h. However, the confounding effect of between-study heterogeneity on target attainment for q24h regimens was considerable.ConclusionsLinezolid dosing at 300 mg q12h may retain the efficacy of the 600 mg q12h licensed dosing with improved safety. Data to evaluate commonly used 300 mg q24h and 600 mg q24h doses are limited. Comprehensive, prospectively obtained PK/PD data for linezolid doses in drug-resistant TB treatment are required.

Examining the influence of urban definition when assessing relative safety of drinking-water in Nigeria

Reducing inequalities is a priority from a human rights perspective and in water and public health initiatives. There are periodic calls for differential national and global standards for rural and urban areas, often justified by the suggestion that, for a given water source type, safety is worse in urban areas. For instance, initially proposed post-2015 water targets included classifying urban but not rural protected dug wells as unimproved. The objectives of this study were to: (i) examine the influence of urban extent definition on water safety in Nigeria, (ii) compare the frequency of thermotolerant coliform (TTC) contamination and prevalence of sanitary risks between rural and urban water sources of a given type and (iii) investigate differences in exposure to contaminated drinking-water in rural and urban areas. We use spatially referenced data from a Nigerian national randomized sample survey of five improved water source types to assess the extent of any disparities in urban–rural safety. We combined the survey data on TTC and sanitary risk with map layers depicting urban versus rural areas according to eight urban definitions. When examining water safety separately for each improved source type, we found no significant urban–rural differences in TTC contamination and sanitary risk for groundwater sources (boreholes and protected dug wells) and inconclusive findings for piped water and stored water. However, when improved and unimproved source types were combined, TTC contamination was 1.6 to 2.3 times more likely in rural compared to urban water sources depending on the urban definition. Our results suggest that different targets for urban and rural water safety are not justified and that rural dwellers are more exposed to unsafe water than urban dwellers. Additionally, urban–rural analyses should assess multiple definitions or indicators of urban to assess robustness of findings and to characterize a gradient that disaggregates the urban–rural dichotomy.

Results of a pilot intervention to improve health and safety for health care workers.

To test the feasibility of a multicomponent pilot intervention to improve worker safety and wellness in two Boston hospitals. A 3-month intervention was conducted on seven hospital units. Pre- (374 workers) and postsurveys (303 workers) assessed changes in safety/ergonomic behaviors and practices, and social support. Wellness outcomes included self-reported pain/aching in specific body areas (musculoskeletal disorders or MSDs) and physical activity (PA). Pain was reported frequently (81%), and PA averaged 4 hours per week. There was a postintervention increase in safe patient handling (P < 0.0001), safety practices (P = 0.0004), ergonomics (P = 0.009), and supervisor support (P = 0.01), but no changes in MSDs or PA. Safe patient handling, ergonomics, and safety practices are good targets for worker safety and wellness interventions; longer intervention periods may reduce the risk of MSDs.

Safety Design Requirements for Safety Systems and Components of JSFR

Safety design requirements for JSFR were summarized taking the development targets of the FaCT project and design feature of JSFR into account. The related safety principle and requirements for Monju, CRBRP, PRISM, SPX, LWRs, IAEA standards, goals of GIF, basic principle of INPRO etc. were also taken into account so that the safety design requirements can be a next-generation global standard. The development targets for safety and reliability are set based on those of FaCT, namely, ensuring safety and reliability equal to future LWR and related fuel cycle facilities. In order to achieve these targets, the defence-in-depth concept is used as the basic safety design principle. General features of the safety design requirements are 1) Achievement of higher reliability, 2) Achievement of higher inspectability and maintainability, 3) Introduction of passive safety features, 4) Reduction of operator action needs, 5) Design consideration against Beyond Design Basis Events, 6) In-Vessel Retention of degraded core materials, 7) Prevention and mitigation against sodium chemical reactions, and 8) Design against external events. The current specific requirements for each system and component are summarized taking the basic design concept of JSFR into account, which is an advanced loop-type large-output power plant with a mixed-oxide-fuelled core.

Safety Design Requirements for Safety Systems and Components of JSFR

Safety design requirements for JSFR were summarized taking the development targets of the FaCT project and design feature of JSFR into account. The related safety principle and requirements for Monju, CRBRP, PRISM, SPX, LWRs, IAEA standards, goals of GIF, basic principle of INPRO etc. were also taken into account so that the safety design requirements can be a next-generation global standard. The development targets for safety and reliability are set based on those of FaCT, namely, ensuring safety and reliability equal to future LWR and related fuel cycle facilities. In order to achieve these targets, the defence-in-depth concept is used as the basic safety design principle. General features of the safety design requirements are 1) Achievement of higher reliability, 2) Achievement of higher inspectability and maintainability, 3) Introduction of passive safety features, 4) Reduction of operator action needs, 5) Design consideration against Beyond Design Basis Events, 6) In-Vessel Retention of degraded core materials, 7) Prevention and mitigation against sodium chemical reactions, and 8) Design against external events. The current specific requirements for each system and component are summarized taking the basic design concept of JSFR into account, which is an advanced loop-type large-output power plant with a mixed-oxide-fuelled core.

Optimal TARGETs for cardiovascular safety and benefit in ESRD

Optimal TARGETs for cardiovascular safety and benefit in ESRD

What next targets for anaesthesia safety?

What next targets for anaesthesia safety?

Setting vehicle side impact safety design targets using a regression-based approach

This paper presents a methodology for setting design variable targets for vehicle side impact safety using a statistical data-based approach. It is assumed that vehicles are to be designed for a high star rating in the Lateral Impact New Car Assessment Programme (LINCAP) conducted by the National Highway Traffic Safety Administration (NHTSA). Accordingly, the Thoracic Trauma Index (TTI) is the relevant injury parameter, which is expressed as a function of design variables in the form of a multilinear regression relation. The expression for TTI (front), which has been derived in an earlier work, has been complemented here with a new regression-based relationship for TTI (rear) through extensive statistical analysis of publicdomain LINCAP test data posted by NHTSA. Using 'best subset' regression analysis, significant variables affecting TTI (rear) have been identified and the latter has been expressed as a function of these variables yielding a high degree of correlation with test data. Using a simple computer-based tool, it is shown how numerical targets for design variables can be arrived at within predefined ranges for a given value of TTI (front or rear).

Exploring the beliefs underpinning drivers’ intentions to comply with speed limits

Using the theory of planned behaviour (TPB; [Ajzen, I. (1985). From intentions to actions: A theory of planned behavior. In J. Kuhl, J. Beckmann (Eds.), Action control: From cognition to behavior (pp. 11–39). Berlin: Springer-Verlag.]) as a theoretical framework, the present study was designed to: (a) identify the beliefs underpinning drivers’ intentions to comply with speed limits, and (b) test the expectancy-value theory held to underpin those beliefs. A sample of drivers ( N = 598) completed questionnaires designed to measure TPB variables with respect to compliance with speed limits. The results of hierarchical multiple regression analyses provided support for the expectancy-value theory held to underpin each behavioural beliefs (outcome beliefs X outcome evaluations), normative beliefs (referent beliefs X motivation to comply), and control beliefs (control frequency beliefs X control power beliefs). Belief targets for road safety countermeasures that aim persuade drivers to comply with speed limits were also identified by selecting those beliefs that were the statistically significant predictors of direct TPB measures (attitudes, subjective norm, perceived control) and intention. Theoretical and practical implications of the results are discussed.