Target Safety Research Articles

Applications of novel processing technologies to enhance the safety and bioactivity of milk.

Bioactive compounds in food can have high impacts on human health, such as antioxidant, antithrombotic, antitumor, and anti-inflammatory activities. However, many of them are sensitive to thermal treatments incurred during processing, which can reduce their availability and activity. Milk, including ovine, caprine, bovine, and human is a rich source of bioactive compounds, including immunoglobulins, vitamins, and amino acids. However, processing by various novel thermal and non-thermal technologies has different levels of impacts on these compounds, according to the studies reported in the literature, predominantly in the last 10 years. The reported effect of these technologies either covers microbial inactivation or the bioactive composition; however, there is a lack of comprehensive compilation of studies that compare the effect of these technologies on bioactive compounds in milk (especially, caprine and ovine) to microbial inactivation at similar settings. This research gap makes it challenging to conclude on the specific processing parameters that could be optimized to achieve targets of microbial safety and nutritional quality at the same time. This review covers the effect of a wide range of thermal and non-thermal processing technologies including high-pressure processing, pressure-assisted thermal sterilization, pulsed-electric field treatment, cold plasma, microwave-assisted thermal sterilization, ultra-high-pressure homogenization, ultrasonication, irradiation on the bioactive compounds as well as on microbial inactivation in milk. Although a combination of more than one technology could improve the reduction of bacterial contaminants to meet the required food safety standards and retain bioactive compounds, there is still scope for research on these hurdle approaches to simultaneously achieve food safety and bioactivity targets.

Potential Crash Rate Benchmarks for Automated Vehicles

Most automobile manufacturers and several technology companies are testing automated vehicles (AVs) on public roads. While automation of the driving task is expected to reduce crashes, there is no consensus as to how safe an AV must be before it can be deployed. An AV should be at least as safe as the average driver, but national crash rates include drunk and distracted driving, meaning that an AV that crashes at the average rate is somewhere between drunk and sober. In this paper, safety benchmarks for AVs are explored from three perspectives. First, crash rates from naturalistic driving studies are used to determine the crash risk of the model (i.e., sober, rested, attentive, cautious) driver. Second, stated preference surveys in the literature are reviewed to estimate the AV risk acceptable to the public. Third, crash, injury, and fatality rates from other transportation modes are compared as baseline safety levels. A range of potential safety targets is presented as a guide for policymakers, regulators, and AV developers to assist in evaluating the safety of automated driving technologies for public use.

Implementation of six patient safety goals at a public health centre with in-patient services in Bali, Indonesia: A qualitative case study

Background and purpose: The Indonesian government requires all health care facilities including public health centres (PHCs) to implement a patient safety program as part of the accreditation standard process. The implementation of patient safety in PHCs have faced various problems, including human resources and infrastructure issues. This study aims to explore the implementation of patient safety target procedures in an accredited inpatient PHC in Tabanan District, Bali, Indonesia.Methods: We conducted a qualitative case study that adopts four main domains in patient safety, consisting of executive officers, community or patient who received services, systems in service delivery and methods, and elements in each domain. The research location was at Penebel I PHC, an inpatient PHC with the accreditation status of “utama”. Data collection was carried out from March to April 2020. It includes observation of the patient safety implementation, review on tracking patient safety documents and in-depth interviews with 11 informants who are PHC staff, patients’ safety task force and the family of patients. The data were analysed using thematic analysis by creating a grid of themes, sub-themes and data reduction to narrative presentation.Results: The patient safety procedure in Penebel I PHC has been carried out through the standard and procedure according to the Ministry of Health (MoH) regulation which consist of patient identification; communication between staff and patients; maintain the safety of High Alert and Look Alike Sound Alike (LASA) medications. However, there is a need to improve the capacity of implementing officers to increase their communication competencies as well as to enhance cooperation between officers in health services to avoid patient safety incidents.Conclusion: The implementation of six patient safety goals in-corporate through four main domains of health care services has been running according to the MoH’s standard. There is a need to improve the competence of officers, cooperation between officers in carrying out patient safety management and improve communication between officers and patients so that the information conveyed by officers is truly understood by patients.

Extending the Heston model to forecast motor vehicle collision rates

We present an alternative approach to the forecasting of motor vehicle collision rates. We adopt an oft-used tool in mathematical finance, the Heston Stochastic Volatility model, to forecast the short-term and long-term evolution of motor vehicle collision rates. We incorporate a number of extensions to the Heston model to make it fit for modelling motor vehicle collision rates. We incorporate the temporally-unstable and non-deterministic nature of collision rate fluctuations, and introduce a parameter to account for periods of accelerated safety. We also adjust estimates to account for the seasonality of collision patterns. Using these parameters, we perform a short-term forecast of collision rates and explore a number of plausible scenarios using long-term forecasts. The short-term forecast shows a close affinity with realised rates (over 95% accuracy), and outperforms forecasting models currently used in road safety research (Vasicek, SARIMA, SARIMA-GARCH). The long-term scenarios suggest that modest targets to reduce collision rates (1.83% annually) and targets to reduce the fluctuations of month-to-month collision rates (by half) could have significant benefits for road safety. The median forecast in this scenario suggests a 50% fall in collision rates, with 75% of simulations suggesting that an effective change in collision rates is observed before 2044. The main benefit the model provides is eschewing the necessity for setting unreasonable safety targets that are often missed. Instead, the model presents the effects that modest and achievable targets can have on road safety over the long run, while incorporating random variability. Examining the parameters that underlie expected collision rates will aid policymakers in determining the effectiveness of implemented policies.

Road Traffic Crash Data Management in ASEAN: 3-5-2 Perspective


 
 
 Every year approximately 1.3 million people are killed on roads around the world. Without new and effective actions, deaths in low to middle-income countries are forecasted to rise steeply, as the level of motorization is increasing. The availability of road safety data is fundamental to improving road safety outcomes, tracking progress, and achieving the road safety targets set by each country. With consistent and standardize collection and management, these data will provide beneficial and accurate insights for trends monitoring, future and time series prediction, and ultimately a reliable review of currently implemented programs. However, managing the data is a challenging aspect especially when it involves multiple agencies with different focuses and requirements and countless bureaucracy. By continued adoption of the "3-5-2" concept from football strategies, this paper will review the status-quo conditions of road crash data collection and management in the middle-income tier ASEAN countries. These shall be one of the core values for effective road safety management and improvement stipulated under the Decade of Action for Road Safety.
 
 

Modulation of steroidogenesis by Actaea racemosa and vitamin C combination, in letrozole induced polycystic ovarian syndrome rat model: promising activity without the risk of hepatic adverse effect

BackgroundComplementary remedies such as the Chinese herb ‘Sheng Ma’ (Black cohosh; Actaea racemosa ‘AR’) are being sought to overcome the shortcomings of conventional hormonal and surgical therapies developed for the treatment of polycystic ovary syndrome (PCOS). However, AR-induced hepatotoxicity necessitates a cautionary warning to be labeled on its products as recommended by the United States Pharmacopeia, where four out of seven hepatotoxic cases in Sweden were possibly associated with black cohosh products.MethodsWe investigated the effects, safety, and molecular targets of black cohosh ethanolic extract and/or vitamin C on ovarian functionality and oxidative response in hyperandrogenism-induced PCOS rats. A well-established rat model using oral letrozole, daily, for 21 days was employed. The rats then received the AR extract with and without vitamin C for 28 days. The hormonal evaluation, antioxidant status, histopathological examination, immunohistochemical analysis, cell proliferation, and the expression ratio of the aromatase (Cyp19α1) gene were evaluated. Additionally, holistic profiling of the AR arsenal of secondary metabolites was performed using ultra-high-performance liquid chromatography (UHPLC) coupled with quadrupole high-resolution time of flight mass spectrometry (QTOF-MS).ResultsBeneficial effects were exerted by AR in PCOS rats as antioxidant status, hormonal profile, lipid profile, glucose level, liver functions, and the induced Ki-67 expression in the granulosa, theca cell layers and interstitial stromal cells were all improved. Notably, the combination of AR with vitamin C was not only more effective in reversing the dysregulated levels of testosterone, luteinizing hormone, and mRNA level of Cyp19α1 gene in the PCOS rat, but also safer. The combination regulated both ovarian and hepatic malondialdehyde (MDA) and glutathione (GSH) levels with histological improvement observed in the liver and ovaries. In addition, the untargeted metabolomic profiling enabled the identification of 61 metabolites allocated in five major chemical classes.ConclusionThis study demonstrated the benefit of the combinatorial effects of AR and vitamin C in mitigating the reproductive and metabolic disorders associated with PCOS with the elimination of AR hepatotoxic risk.

Joint ESH excellence centers' national meeting on renal sympathetic denervation: A Greek experts’ survey

ObjectiveThe efficacy of renal sympathetic denervation (RDN) has been affirmed by a number of recent clinical studies, despite controversies in this field over the last five years. Therefore, it is of paramount importance that hypertension experts debate the merits of RDN by revealing and expressing their personal beliefs and perspectives regarding this procedure. MethodsA cross-sectional survey was conducted among Greek leaders of the Hypertension Excellence Centers with the use of a closed-type questionnaire specifically designed to elicit information and evaluate the respondent's views and perspectives about RDN efficacy, safety and ideal target patient population. ResultsA total of 36 participants completed the survey. Based on the results, RDN was considered efficient (91.7%) and safe (94.5%), while the overwhelming majority of the participants felt confident in the long-term efficacy (88.9%) of the intervention and that it lacks reliable predictors of blood pressure response (94.5%). Patients with resistant (91.7%), ultra-resistant (94.4%), and uncontrolled hypertension (80.6%) were suggested as ideal candidates for RDN. Establishing a close co-operation between interventionalists and hypertension experts was considered essential to ensure the efficacy (97.2%) as well as the safety (97.3%) of the procedure. ConclusionThe vast majority of Greek hypertension experts surveyed were convinced of the efficacy and safety of RDN based on the preponderance of available scientific and clinical data. Identification of the ideal patient group remains controversial. Respondents generally agreed on the necessity of building close collaborative relationships between interventionalists and hypertension experts in order to improve RDN clinical outcome.

Synthesis and Characterization of the Novel Rodent-Active and CNS-Penetrant P2X7 Receptor Antagonist Lu AF27139.

There remains an insufficient number of P2X7 receptor antagonists with adequate rodent potency, CNS permeability, and pharmacokinetic properties from which to evaluate CNS disease hypotheses preclinically. Herein, we describe the molecular pharmacology, safety, pharmacokinetics, and functional CNS target engagement of Lu AF27139, a novel rodent-active and CNS-penetrant P2X7 receptor antagonist. Lu AF27139 is highly selective and potent against rat, mouse, and human forms of the receptors. The rat pharmacokinetic profile is favorable with high oral bioavailability, modest clearance (0.79 L/(h kg)), and good CNS permeability. In vivo mouse CNS microdialysis studies of lipopolysaccharide (LPS)-primed and 2'(3')-O-(benzoylbenzoyl)adenosine-5'-triphosphate (BzATP)-induced IL-1β release demonstrate functional CNS target engagement. Importantly, Lu AF27139 was without effect in standard in vitro and in vivo toxicity studies. Based on these properties, we believe Lu AF27139 will be a valuable tool for probing the role of the P2X7 receptor in rodent models of CNS diseases.

Target reliability index optimization framework for multiple building classes based on community-level objectives

The impact of a disaster is spread over a region and thus the corresponding risks can be managed effectively by carefully considering the community impact. Since structural design codes regulate the safety levels of structures, it is appropriate to consider a community-level objective in the determination of the safety levels stipulated in the structural design codes. However, evaluating community disaster impact requires consideration of loss interdependency among different buildings, which could be a complex task. Furthermore, implementing a community-level objective to design safety level determination requires the establishment of feasible methods to calculate it in a reasonable time. This paper develops a simple and viable framework for community-level objective-based design safety target optimization for multiple building classes subjected to seismic hazard. To reduce the computation cost, the framework employs an efficient procedure of using an artificial neural network to approximate the seismic response of buildings with common characteristics (occupancy use, and type and size of lateral resisting system). The methodology is illustrated for optimizing the target reliability indices of office and hospital building classes exposed to seismic hazard, with minimizing regional economic cost as objective. Simple loss and interdependency models are used for this illustration due to lack of available complex models, which can be replaced by more recent and complex models to improve accuracy of the analysis once they become available.

RELATIONSHIP OF KNOWLEDGE AND WORK MOTIVATION OF NURSES WITH ATTITUDES TO SUPPORT THE APPLICATION OF PATIENT SAFETY INPATIENT ROOM OF WONOSARI YOGYAKARTA GENERAL HOSPITAL

The application of patient safety goals is a mandatory system that must be implemented by nurses in hospitals so that patient safety is guaranteed. Increasing the level of knowledge and work motivation of nurses is expected to support the expectations of patient safety goals and efforts to minimize unexpected events. The high incidence of patient safety in the hospital illustrates that nurses still lack understanding of the importance of patient safety. Knowing the relationship between the level of knowledge and work motivation of nurses with the attitude of supporting the implementation of patient safety goals in the inpatient room of RSUD Wonosari YogyakartaThis research is a quantitative analytic descriptive correlation study with a cross sectional approach. The population sample in this study were 60 nurses at Wonosari Yogyakarta Hospital. The sampling technique used stratified random sampling, and data analysis used the Spearman Rank. The results of the spearman rank correlation test stated that there was no relationship between the level of knowledge and attitudes to support the implementation of patient safety targets by nurses in the inpatient room of RSUD Wonosari Yogyakarta with a p value of 0.323> 0.05. There is a relationship between the work motivation of nurses and the attitude of supporting the implementation of patient safety goals in the inpatient room of RSUD Wonosari Yogyakarta with a p value of 0.049 <0.05. There is no relationship between the level of knowledge and attitudes to support the implementation of patient safety goals by nurses in the inpatient room of RSUD Wonosari Yogyakarta. There is a relationship between the work motivation of nurses and the attitude of supporting the implementation of patient safety goals in the inpatient room of Wonosari Yogyakarta Hospital
 Keywords: Patient Safety; Knowledge; Motivation; Nurses

Associating ridesourcing with road safety outcomes: Insights from Austin, Texas.

Improving road safety and setting targets for reducing traffic-related crashes and deaths are highlighted as part of the United Nations sustainable development goals and worldwide vision zero efforts. The advent of transportation network companies and ridesourcing expands mobility options in cities and may impact road safety outcomes. We analyze the effects of ridesourcing use on road crashes, injuries, fatalities, and driving while intoxicated (DWI) offenses in Travis County, Texas. Our approach leverages real-time ridesourcing volume to explain variation in road safety outcomes. Spatial panel data models with fixed-effects are deployed to examine whether the use of ridesourcing is significantly associated with road crashes and other safety metrics. Our results suggest that for a 10% increase in ridesourcing trips, we expect a 0.12% decrease in road crashes, a 0.25% decrease in road injuries, and a 0.36% decrease in DWI offenses in Travis County. On the other hand, ridesourcing use is not significantly associated with road fatalities. This study augments existing work because it moves beyond binary indicators of ridesourcing availability and analyzes crash and ridesourcing trips patterns within an urbanized area rather than their metropolitan-level variation. Contributions include developing a data-rich approach for assessing the impacts of ridesourcing use on the transportation system’s safety, which may serve as a template for future analyses for other cities. Our findings provide feedback to policymakers by clarifying associations between ridesourcing use and traffic safety and uncover the potential to achieve safer mobility systems with transportation network companies.

Investigating the effectiveness of simplified labels for safe use communication: The case of household detergents

AbstractThis study assessed the effectiveness of safety communication on the back labels of hazardous products (with regulatory and safety information as dictated by regulatory requirements), with household detergents as a test case. The potential of simplification to increase label effectiveness was evaluated by comparing the currently used labelling approach with two simplified alternatives. The labels mainly differed in terms of the amount of information and the prominence of pictograms. The generalisability of theoretical insights on the effectiveness of pictograms in safety messages to a more real‐life context was tested by (a) realistic labels containing several other information elements besides the safety information and (b) target users who are knowledgeable about the product type. One thousand eight hundred (1,800) respondents participated in an online experiment and were randomly exposed to one of the labels. The positive cognitive and behavioural effects commonly attributed to pictorials could not be confirmed, but positive affective effects did emerge. Specifically, even though participants were asked to carefully read the label, they did not spend enough time to process all the content except for the most simplified label. The results did not show meaningful differences between the three labels in terms of information recall (which was poor for all executions), hazard perceptions and behavioural intentions when confronted with an accident. In contrast to this lack of differentiation in cognitive and behavioural intention effects, we did find a clear difference in the affective measure. A majority of the respondents preferred the simplified safety labels. As such, avoiding information overload, and conveying the information in an easier way by means of more prominent use of pictograms, appeared to be appreciated by consumers of household products, while it did not negatively impact label effectiveness.

Factors Affecting the Failure of Patient Safety Target Indicators in the Regional Hospital of the Datu Beru Takengon Central Aceh

Work stress is caused by many factors from workplace, family, home, or environment. Excessive work stress will make someone anxious until developing excessive fatigue. Fatigue will decrease performance and increase work error rate that cause fatal workaccident.This study aimed to analyze influence of working stressors against nurses fatigue in patien room in haji hospital Medan. This study was quantitative method with a cross-sectional design, with a sample of 53 respondents. This study used questioners of the NIOSH Generic Job Stress Questionaire and Industrial Fatigue Research Committee which has been translated into Indonesian and has cheeked for validity and reliability. The results of the study regarding the influence work fatigue and work stress (P-value 0,000, r : 1,000), the influence workload and work fatigue (P-value 0,000, r : 1,000), the influence interpersonal conflict and work fatigue (P-value 0,000, r : 1,000), the influence job satisfaction and work fatigue (P-value 0,000, r : -0,588), the influence social support and work fatigue (P-value 0,000, r : -0,892), and based on the logistic regression test workload were variables the most influential, with an odds ratio of 94,5. The conclusion shows that workload is a variable that has strong influence on fatigue. Nurses with heavy workload are 94,5 times more likely to experience fatigue. So that the hospital needs to monitor and evaluate the performances of the nurses so the workload can be fixed and adjusted with the right capacity and ability of the nurses in providing services

Metformin doses to ensure efficacy and safety in patients with reduced kidney function.

We aimed to develop a metformin dosing strategy to optimise efficacy and safety in patients with reduced kidney function. Metformin data from two studies stratified by kidney function were analysed. The relationship between metformin clearance and kidney function estimates was explored using a regression analysis. The maintenance dose range was predicted at different bands of kidney function to achieve an efficacy target of 1 mg/L for steady-state plasma concentrations. The dosing strategy was evaluated using simulations from a published metformin pharmacokinetic model to determine the probability of concentrations exceeding those associated with lactic acidosis risk, i.e. a steady-state average concentration of 3 mg/L and a maximum (peak) concentration of 5 mg/L. A strong relationship between metformin clearance and estimated kidney function using the Cockcroft and Gault (r2 = 0.699), MDRD (r2 = 0.717) and CKD-Epi (r2 = 0.735) equations was found. The probability of exceeding the safety targets for plasma metformin concentration was <5% for most doses and kidney function levels. The lower dose of 500 mg daily was required to maintain concentrations below the safety limits for patients with an eGFR of 15–29 mL/min. Our analysis suggests that a maximum daily dose of 2250, 1700, 1250, 1000, and 500 in patients with normal kidney function, CKD stage 2, 3a, 3b and 4, respectively, will provide a reasonable probability of achieving efficacy and safety. Our results support the cautious of use metformin at appropriate doses in patients with impaired kidney function.

Sensors on the Move: Onboard Camera-Based Real-Time Traffic Alerts Paving the Way for Cooperative Roads.

European road safety has improved greatly in recent decades. However, the current numbers are still far away to reach the European Commission’s road safety targets. In this context, Cooperative Intelligent Transport Systems (C-ITS) are expected to significantly improve road safety, traffic efficiency and comfort of driving, by helping the driver to make better decisions and adapt to the traffic situation. This paper puts forward two vision-based applications for traffic sign recognition (TSR) and real-time weather alerts, such as for fog-banks. These modules will support operators in road infrastructure maintenance tasks as well as drivers, giving them valuable information via C-ITS messages. Different state-of-the-art methods are analysed using both publicly available datasets (GTSB) as well as our own image databases (Ceit-TSR and Ceit-Foggy). The selected models for TSR implementation are based on Aggregated Chanel Features (ACF) and Convolutional Neural Networks (CNN) that reach more than 90% accuracy in real time. Regarding fog detection, an image feature extraction method on different colour spaces is proposed to differentiate sunny, cloudy and foggy scenes, as well as its visibility level. Both applications are already running in an onboard probe vehicle system.

Lateral collision risk assessment of parallel routes in ocean area based on space-based ADS-B

In order to ensure the safe operation of parallel routes in the ocean area, it is necessary to assess the risk of lateral collision of routes. The data used in the assessment often come from the real flights, while the traditional land-based ADS-B equipment has limited coverage and cannot be used for research. The space-based ADS-B system can receive and send the flight position of the aircraft over the ocean area. In this paper, the ocean tracks in space-based ADS-B data are first extracted. According to the different route structures, the data of fixed route and flexible route are preprocessed by segmented Kalman filter and cubic polynomial fitting method respectively. Then the processed track position error is calculated, and Q-Q (Quantile-Quantile) median method is used to test the normal distribution of the error, and k-means clustering is used to obtain the clustering center and occurrence frequency of positioning error and flight error. Finally, a collision risk model based on Bayesian network is established, and the error distribution parameters and occurrence frequency are brought into the model to evaluate the collision risk of parallel routes in the ocean area. The results show that the lateral collision risk based on space-based ADS-B ocean flight data is lower than 0.5 × 10−8 times/hour specified by ICAO when the fixed route separation is 14n miles and the flexible route separation is 49n miles. And the actual lateral interval of the Pacific flexible route is 50n miles (Jiang, 2010), which meets the safety target level.

Cardiac hERG K+ Channel as Safety and Pharmacological Target.

The human ether-á-go-go related gene (hERG, KCNH2) encodes the pore-forming subunit of the potassium channel responsible for a fast component of the cardiac delayed rectifier potassium current (IKr). Outward IKr is an important determinant of cardiac action potential (AP) repolarization and effectively controls the duration of the QT interval in humans. Dysfunction of hERG channel can cause severe ventricular arrhythmias and thus modulators of the channel, including hERG inhibitors and activators, continue to attract intense pharmacological interest. Certain inhibitors of hERG channel prolong the action potential duration (APD) and effective refractory period (ERP) to suppress premature ventricular contraction and are used as class III antiarrhythmic agents. However, a reduction of the hERG/IKr current has been recognized as a predominant mechanism responsible for the drug-induced delayed repolarization known as acquired long QT syndromes (LQTS), which is linked to an increased risk for "torsades de pointes" (TdP) ventricular arrhythmias and sudden cardiac death. Many drugs of different classes and structures have been identified to carry TdP risk. Hence, assessing hERG/IKr blockade of new drug candidates is mandatory in the drug development process according to the regulatory agencies. In contrast, several hERG channel activators have been shown to enhance IKr and shorten the APD and thus might have potential antiarrhythmic effects against pathological LQTS. However, these activators may also be proarrhythmic due to excessive shortening of APD and the ERP.

A N-(4-chlorophenyl)-γ-amino acid derivatives exerts in vitro anticancer activity on non-small cell lung carcinoma cells and enhances citosine arabinoside (AraC)-induced cell death via mitochondria-targeted pathway

A Non-Small Cell Lung Cancer (NSCLC) is among the leading cause of cancer-associated morbidity and mortality worldwide. Novel treatment and drug repurposing strategies are needed. Cytosine arabinoside (AraC) is an S-phase inhibitor historically used for the treatment of leukemia. Previously AraC was not investigated as a therapeutic option for NSCLC. We explored a novel adjuvant therapy concept in vitro targeting S-phase and mitochondrial pathways. A synthetic pathway to generate novel mitochondria damaging N-(4-chlorophenyl)-γ-amino acid derivatives bearing an azole, diazole and triazole moieties was described. The resulting compounds were evaluated for their anticancer activity on well described A549 cells. Five compounds demonstrated convincing anticancer activity comparable to cytosine arabinoside (AraC). The most promising compound 7g (IC50 = 38.38 µM) bearing 3,4-dichlorophenyl moiety was able to induce the mitochondrial injury, leading to significant (p < 0.05) ROS production and inhibition of ATP synthesis. 7g synergized with AraC and significantly decreased A549 viability in comparison to AraC and 7g monotherapy or UC. The cytotoxic effect on A549 viability after AraC combination with 7g was similar to doxorubicin monotherapy. These results suggest that 7g could be potentially explored adjuvant enhancing the activity of standard chemotherapeutic agents. Further studies are needed to better understand the safety, efficacy, and precise cellular targets of of N-(4-chlorophenyl)-γ-amino acids.

From Slow Food to Slow Meat: Slowing Line Speeds to Improve Worker Health and Animal Welfare in Canadian Abattoirs

This paper examines the regulation of production line speeds in Canadian meat and poultry processing facilities to better understand their impact on worker safety and animal welfare. The paper begins with an overview of the regulatory framework that sets line speed conditions in federally licensed facilities. It notes how recent shifts in food safety governance facilitate increased speeds that endanger workers and animals on the kill floor. First, it highlights tensions between regulatory objectives in the Safe Food for Canadians Regulations that focus on food safety targets and humane handling guidelines respectively. It then turns to the occupational health and safety risks associated with working at meat and poultry processing facilities. Particular emphasis is placed on the way that COVID-19 outbreaks in Canadian slaughterhouses drew attention to this grueling work that had previously been ignored. The paper concludes by noting that the pandemic has created a unique policy window to slow down production speeds; a policy window that should be seized.

Systematic Analysis of Protein Targets Associated with Adverse Events of Drugs from Clinical Trials and Postmarketing Reports.

Adverse drug reactions (ADRs) are undesired effects of medicines that can harm patients and are a significant source of attrition in drug development. ADRs are anticipated by routinely screening drugs against secondary pharmacology protein panels. However, there is still a lack of quantitative information on the links between these off-target proteins and the reporting of ADRs in humans. Here, we present a systematic analysis of associations between measured and predicted in vitro bioactivities of drugs and adverse events (AEs) in humans from two sources of data: the Side Effect Resource, derived from clinical trials, and the Food and Drug Administration Adverse Event Reporting System, derived from postmarketing surveillance. The ratio of a drug's therapeutic unbound plasma concentration over the drug's in vitro potency against a given protein was used to select proteins most likely to be relevant to in vivo effects. In examining individual target bioactivities as predictors of AEs, we found a trade-off between the positive predictive value and the fraction of drugs with AEs that can be detected. However, considering sets of multiple targets for the same AE can help identify a greater fraction of AE-associated drugs. Of the 45 targets with statistically significant associations to AEs, 30 are included on existing safety target panels. The remaining 15 targets include 9 carbonic anhydrases, of which CA5B is significantly associated with cholestatic jaundice. We include the full quantitative data on associations between measured and predicted in vitro bioactivities and AEs in humans in this work, which can be used to make a more informed selection of safety profiling targets.