Levels Of Stringency Research Articles

Procedural inclusiveness can mitigate trust challenges in environmental policymaking

ABSTRACT Decreasing political trust poses severe challenges, particularly in policy domains where solutions to societal problems are urgently needed. The reason is that low trust decreases citizens' support for policy interventions. Since trust is difficult to increase in the short to medium term, this study explores how negative trust effects on policy support could be mitigated through policymaking procedures. We connect literature on policy design processes and trust to argue that involving broader actor coalitions when designing a policy is likely to mitigate the negative trust effect on public policy support. We test this argument with an empirical focus on environmental policy, based on data from a survey experiment in Switzerland (N = 6116). Our study design combines a choice experiment with treatment conditions for procedural inclusiveness and various levels of policy stringency with a novel approach to measuring trust. The main finding is that greater inclusiveness in terms of engaging a broader actor coalition in the policy design process reduces otherwise negative effects of low trust on policy support. The main policy implication is that political trust challenges are not a predicament for failure in addressing urgent societal problems but can be offset by including broad actor coalitions in policy design processes.

Changes in physical activity among Canadian adults more than 6 months into the COVID-19 pandemic: a secondary analysis of the INTERACT cohort study

ObjectiveTo estimate the effect of (a) the COVID-19 pandemic and (b) COVID-19 restriction stringency on daily minutes of device-measured moderate-to-vigorous physical activity (MVPA).DesignPhysical activity data were collected from the INTerventions,...

The impact of COVID-19 stringency measures on emerging stock market stability: Does economic resilience matter?

PurposeThe current research aims to investigate the impact of coronavirus 2019 (COVID-19) evolution, government stringency measures and economic resilience on stock market volatility in the Middle East and North African (MENA) emerging markets. Other macroeconomic factors were also taken into account.Design/methodology/approachBased on financial data from 10 selected MENA countries, we tested an integrated framework that has not yet been explored in prior research. The exponential generalized autoregressive conditional heteroskedasticity (E-GARCH) was adopted to analyze data from March 2020 to February 2022.FindingsOur research illustrates the direct and indirect effects of the virus outbreak on stock market stability and reports that economic resilience could alleviate the volatility shock. This finding is robust across the various proxies of economic resilience used in this study. We also argue that the negative impact of the pandemic on equity market variation gets more pronounced in countries with higher level of stringency scores.Practical implicationsPolicymakers ought to strengthen their economic structures and reinforce the economic governance at the national level to gain existing and potential investors’ trust and ensure lower stock market volatilities in times of crisis. Our study also recommends some key economic factors to consider while establishing efficient policies to tackle unexpected shocks and prevent financial meltdowns.Originality/valueOur findings add to the evolving literature on the reaction of economic and financial markets to the sanitary crisis, particularly in developing countries where research is still scarce. This study is the first of its kind to investigate the stock market reaction to stringency measures in the understudied MENA region.

The heterogeneous effects of COVID-19 lockdowns on crime across the world

There is a vast literature evaluating the empirical association between stay-at-home policies and crime during the COVID-19 pandemic. However, these academic efforts have primarily focused on the effects within specific cities or regions rather than adopting a cross-national comparative approach. Moreover, this body of literature not only generally lacks causal estimates but also has overlooked possible heterogeneities across different levels of stringency in mobility restrictions. This paper exploits the spatial and temporal variation of government responses to the pandemic in 45 cities across five continents to identify the causal impact of strict lockdown policies on the number of offenses reported to local police. We find that cities that implemented strict lockdowns experienced larger declines in some crime types (robbery, burglary, vehicle theft) but not others (assault, theft, homicide). This decline in crime rates attributed to more stringent policy responses represents only a small proportion of the effects documented in the literature.

Resident marine sportfishing effort in the United States varied non-monotonically with COVID policy stringency

Governments responded to the Covid-19 pandemic with different policies to curtail the spread of the virus. We show how sportfishing levels are related to the stringency of Covid-19 policies. Specifically, we relate the total number of resident sportfishing trips taken each month in each of 16 U.S. states to a state-level index of COVID policy stringency. We model the number of recreational fishing trips taken in each state-month using a fixed effect Poisson regression model with state-specific seasonality and time trends. We estimate separate models for different fishing modes, and find that for fishing trips taken on private boats the number of trips may have increased by approximately 20% at moderate levels of stringency, while at high levels of stringency like those experienced in many states in March and April of 2020, trips may have stayed constant or declined by 10–20%. Similar inverse-U shaped relationships between trips and stringency are found for fishing trips from the shore and from charter boats.

Intimate partner violence and its correlates in middle-aged and older adults during the COVID-19 pandemic: A multi-country secondary analysis.

Intimate partner violence (IPV) may have been exacerbated during the COVID-19 pandemic. Middle-aged and older adults, ages 45 years or older, are at higher risk of COVID-19 mortality and social isolation. However, most studies on IPV during the pandemic do not focus on this important subpopulation. Informed by the social-ecological theory, this study examines individual, household, community, and country-level correlates of IPV among middle-aged and older adults in multiple countries using a cross-sectional online survey. Data from 2867 participants aged 45 or older in the International Sexual Health and Reproductive Health (I-SHARE) survey from July 2020 to February 2021 were described using univariate analysis. IPV was defined using four validated WHO measures. Individual characteristics included self-isolation and food security. At the country-level, we examined social distancing stringency. Logistic regression models with a random intercept for country were conducted to explore IPV correlates among 1730 eligible individuals from 20 countries with complete data. Most participants were heterosexual (2469/2867), cisgender (2531/2867) females (1589/2867) between the ages of 45-54 (1539/2867). 12.1% (346/2867) of participants experienced IPV during social distancing measures. After adjustment, participants who self-isolated experienced 1.4 (95% CI 1.0, 2.0, p = 0.04) times the odds of IPV compared to those who had not isolated. Those who reported an increase in food insecurity compared to pre-pandemic experienced 2.2 times the odds (95% CI 1.6, 3.0, p<0.0001) of IPV compared to those who did not report increased food insecurity. People in countries with more stringent social distancing policies were less likely to experience IPV compared to people in countries with lower levels of stringency (aOR = 0.6, 95% CI 0.4, 0.9, p = 0.04). IPV was common among middle-aged and older adults during the COVID-19 pandemic. Our data suggest the need for further crisis management and social protection measures for middle-aged and older adults who have intersecting vulnerabilities to IPV to mitigate COVID-19 impact.

Enforcement actions against European banks in the years 2005–2022. Do financial penalties imposed on European banks follow any patterns?

AbstractThis study aims to identify, by year and over the entire period under study (2005–2022), the countries with the most restrictive bank sanctioning policies in terms of amounts and numbers of penalties to point out the most active institutions in terms of imposing penalties, and to determine the regularities governing the process of imposing these burdens. Using linear ordering methods, groups of countries with similar levels of supervisory stringency identified with one of the supervisory actions, which are financial penalties, are distinguished. A total of 53 banks (the 50 largest European banks and an additional three banks designated as G-SIIs by the EBA) are identified from a constructed database of more than 300 European banks with penalties imposed between 2005 and 2022. The study’s conclusions indicate that the frequency of penalties cannot be clearly equated with the restrictiveness of supervisory institutions, as evidenced by the example of Hungary (multiplication of small penalties). The positioning of countries regarding the number of penalties, their value and grouping using linear ordering allows the conclusion that highly developed countries are characterized by relatively high restrictiveness. The results also show the difference between the Anglo-Saxon and continental models. The analysis in this article is the first comprehensive study of penalties imposed on banks by different types of institutions in 36 jurisdictions from the pre-GFC period up to the year in which the COVID-19 pandemic expired. The multi-faceted approach also provides a basis for formulating practical regulatory implications by redirecting sanctioning policy towards banks to their management and reducing the frequency of penalties while increasing their severity.

Clear as a bell? Policy stringency and elderly health during Covid-19

This paper investigates how restriction policies have impacted elderly self-assessed health (SAH) in Europe during the pandemic, and how the Covid-19 infection interacts with policy stringency to modulate the SAH deterioration. Using the Survey of Health, Aging and Retirement in Europe (SHARE) between October 2019 and August 2021, including 9,034 adults aged 50 years and above, alongside with a stringency index from the Oxford's Coronavirus Government Response Tracker (OxCGRT), we design both an adjusted probit model and a recursive bivariate probit model to test for endogeneity of Covid-19 infection. Estimations results show a bell curve between stringency and SAH degradation: a deleterious effect of restrictions at low levels of stringency up to a tipping point after which more stringent policies become protective. Covid-19 infection moderates this association. Depending on individuals' initial health, the effect of restrictions is uneven: highly stringent policies become damaging for individuals most likely to enter a vulnerabilization path, for whom the bell curve is thus inverted. Overall, this study shows clear patterns of association between policy stringency and perceived health among older Europeans, and highlights the potential trade-off between targeting as many people as possible, those in poor health or those on the edge of vulnerability.

A New Measure of Climate Transition Risk Based on Distance to a Global Emission Factor Frontier

Targeted financing of transition to a "net zero" global economy entails climate transition risk. We propose a measure of transition risk at the country-sector dyad level composed of five tiers of transition risk based on two factors: i) the gap between a dyad's existing emission factor (EF) – a measure of the greenhouse gas intensity of output – and the global 'frontier' sectoral EF, and ii) a dyad's recent convergence towards the frontier EF. Dyads that are either close to the frontier or converging towards the frontier carry lower transition risk. Our measure, using 45 sectors across 66 countries, accounts for both direct greenhouse gas emissions as well as those that enter into production through complex supply chains as captured by intercountry, input-output tables, and can be applied at different levels of stringency to high-, middle-, and low-income economies. Our measure thus accounts for, and sheds light on, EF reductions through investment in lower emissions production techniques in own facilities as well as sourcing intermediate inputs with lower embodied emissions.

Quantifying the Asymmetric Effects of Policy Stringency on Tourism: The Case of COVID-19 Pandemic

ABSTRACT Despite the growing body of literature on policies and their effects, few studies have examined the asymmetric effect of public policies at varying levels of stringency on the tourism industry. Using policy response to the COVID-19 pandemic as a case, this study quantifies the non-linear and asymmetric effects of public policies by examining the impacts of various levels of containment policy stringency on tourism recovery among 115 countries/regions internationally. Our findings show that containment policies impeded global tourism recovery, as expected. However, the negative impact appeared disproportionately larger when the policy measures were more stringent. The results contribute to the tourism policy literature and complements previous studies by providing a more comprehensive understanding of the effects of public policies on tourism.

The imperative of building and fostering a strong compliance culture in the evolving cross-border payments space

It is a period of substantial change for the ever-growing cross-border payments space, with numerous new trends emerging, along with new technologies, new market entrants and participants, and unprecedented regulatory collaboration around the G20 Roadmap for Enhancing Cross-border Payments. This paper discusses the drivers for the changes underway, explains the continued context of elevated compliance risks in the cross-border payments space, and calls for the entire ecosystem, including banks, service providers, new entrants and regulators, to focus on building and fostering a strong culture of compliance. This imperative is even more critical for new entrants who may not be subject to the same level of stringency within their current applicable regulatory regime and who may believe that this gives them more flexibility than other service providers. Building and fostering such a culture of compliance will have numerous benefits, including the reduction of crime. This paper argues that the universal commitment to such a culture of compliance among all parties involved in the ecosystem must begin with the adoption of an inquisitive compliance mindset, that is, a mindset that acknowledges the critical importance of compliance requirements, the rationale for their adoption and a willingness to ask questions and get detailed responses on an ongoing basis. Such a dynamic understanding would facilitate any future changes required by evolving regulations.

A Tumor-Bearing Murine Xenograft Model As a Bioassay for Assessing CAR-T Product Potency Shows Positive Predictive Value for Clinical Performance

Potency assays are required for cellular and gene therapy (CGT) final product (FP) lot release, stability testing, and manufacturing updates, as per the FDA draft guidance on Potency Tests for CGT Products (2011), and Manufacturing Changes and Comparability for Human CGT Products (2023). These assays by definition measure the ability of a product to effect a desired result, and the FDA allows for “considerable flexibility” in determining the appropriate potency assay. However, standard in vitro potency assays are limited in their capacity to meaningfully assess manufacturing comparability and consistency, or product quality to provide predictive value for clinical performance. For chimeric antigen receptor (CAR)-T cell products, certificates of analysis typically report key FP attributes such as CAR expression, cell concentration and viability, impurities and target-specific in vitro potency, among others. However, clinical effectiveness of CAR-T is dependent on complex pharmacokinetics (PK)/ pharmacodynamics (PD) including in vivo engraftment, trafficking, drug exposure kinetics, tumor antigen-driven T cell expansion in tumor microenvironment, survival and persistence, and other factors that are not easily recapitulated in short-term in vitro assays. We developed a bioassay for assessing CAR-T FP potency using a tumor-bearing murine NSG xenograft model to evaluate in vivo performance of GMP-manufactured autologous (Auto) or allogeneic (Allo) CAR-T FPs. We hypothesized that this complex in vivo system may better model PK/PD and provide a more meaningful way to assess CAR-T FP potency. Preclinical dose-finding data from both RUO and GMP anti-BCMA CAR-T lots were used to establish a potency specification for RPMI-8226 tumor control at a “stress dose” of 5e6 CAR-T cells at &amp;lt;60% of the tumor volume compared to the untreated control group at 21 days after CAR-T cell infusion. Using these specifications, we evaluated the in vivo potency performance of GMP-manufactured Auto FP samples (P-BCMA-101; NCT03288493) generated from multiple myeloma (MM) patients and administered in the clinic with known responses ranging from poor (no response or stable disease) to significant (very good partial response [VGPR] or stringent complete response [sCR]). In addition, GMP-manufactured Allo FP samples generated from healthy donors (P-BMCA-ALLO1; NCT04960579) were also tested. We report that half of the P-BCMA-101 products (50%) previously demonstrating favorable clinical outcomes in MM patients were also able to control RPMI-8226 tumor in vivo, while none of the P-BCMA-101 products (0%) that resulted in poor clinical responses were capable of tumor control. These data show translational relevance considering the known clinical outcomes in MM patients, albeit at a high level of stringency at current specifications. Interestingly, all the Allo products (100%) performed at least as well as or better than the Auto products capable of controlling tumor, demonstrating a greater potency of Allo CAR-T cells manufactured from healthy donors. There is great demand for potency assays that can reliably assess manufacturing consistency and product quality, and that might provide some level of predictive value for clinical performance, especially considering the current limitations of standard in vitro potency assays. In vivo potency bioassays have been proposed or utilized for other products with complex biological mechanisms of action including vaccines, gene therapies, and other cell therapy products. The potency bioassay described herein demonstrated a level of positive predictive value for clinical performance using Auto FPs of known clinical outcome in MM patients. In the Auto CAR-T setting, this assay could be utilized for correlative studies including possible biomarker identification. In the Allo CAR-T setting, this potency bioassay may inform FP manufacturing consistency and quality for lot release to ensure patients receive only the highest quality products.

A duplex droplet digital PCR assay for absolute quantification and characterization of long self-amplifying RNA

Self-amplifying messenger ribonucleic acid (saRNA) provides extended expression of genes of interest by encoding an alphavirus-derived RNA replicase and thus is 2–3 times larger than conventional messenger RNA. However, quality assessment of long RNA transcripts is challenging using standard techniques. Here, we utilized a multiplex droplet digital polymerase chain reaction (ddPCR) assay to assess the quality of saRNA produced from an in vitro transcription reaction and the replication kinetics in human cell lines. Using the one-step reverse transcription ddPCR, we show that an in vitro transcription generates 50–60% full-length saRNA transcripts. However, we note that the two-step reverse transcription ddPCR assay results in a 20% decrease from results obtained using the one-step and confirmed using capillary gel electrophoresis. Additionally, we provided three formulas that differ in the level of stringency and assumptions made to calculate the fraction of intact saRNA. Using ddPCR, we also showed that subgenomic transcripts of saRNA were 19-to-108-fold higher than genomic transcripts at different hours post-transfection of mammalian cells in copies. Therefore, we demonstrate that multiplex ddPCR is well suited for quality assessment of long RNA and replication kinetics of saRNA based on absolute quantification.

Association between major histocompatibility complex haplotypes and susceptibility of unvaccinated and vaccinated cattle to paratuberculosis

Bovine Johne’s disease (BJD) or paratuberculosis is caused by Mycobacterium avium spp. paratuberculosis (MAP) and is a worldwide problem among domestic and wild ruminants. While vaccines are available, natural differences in background immunity between breeds within species and between individuals within herds suggest that genetic differences may be able to be exploited in marker-assisted selection as an aid to disease control. The major histocompatibility complex (MHC) is an important component in immune recognition with considerable genetic variability. In this study, associations between the MHC and resistance to BJD were explored in dairy cattle across two herds in which some of the cattle had been vaccinated with Silirum® (n = 540 cows). A BJD susceptible animal was exposed to MAP and became infected, while a resistant animal was exposed but did not become infected. There are different ways to define both exposure and infection, with different levels of stringency, therefore many classifications of the same set of animals are possible and were included in the analysis. The polymorphic regions of major histocompatibility complex class I (MHC I) and class II (MHC II) genes were amplified from the genomic DNA by PCR and sequenced, targeting exons 2 and 3 of the classical and non-classical MHC I genes and exon 2 from the DRB3, DQA1, DQA2 + 3 and DQB MHC II genes. The frequencies of MHC I and MHC II haplotypes and alleles were determined in susceptible and resistant populations. In unvaccinated animals, seven MHC I haplotypes and seven MHC II haplotypes were associated with susceptibility while two MHC I and six MHC II haplotypes were associated with resistance (P < 0.05). In vaccinated animals, two MHC I and three MHC II haplotypes were associated with susceptibility, while one MHC I and two MHC II haplotypes were associated with resistance (P < 0.05). The alleles in significant haplotypes were also identified. Case definitions with higher stringency resulted in fewer animals being included in the analyses, but the power to detect an association was not reduced and there was an increase in strength and consistency of associations. Consistent use of stringent case definitions is likely to improve agreement in future association studies.

Learning to live with COVID-19 in Norway: Moving from a pandemic to an endemic state

ObjectivesTo analyze the relationship between the stringency of policies that focus on containment, mitigation and elimination and practices to change behavior implemented during the COVID-19 pandemic and apparent impacts in the Norwegian population and society. In particular, to consider how the escalation and de-escalation of policy stringency relates to both health and non-health societal factors. MethodsObservational analysis of publicly available statistics, government documents and media sources. ResultsThe stringency of policies relating to social containment, mitigation and elimination and practices to change behaviour were linked to infection rates and pressures on the health system until the endemic phase of COVID-19. In the endemic phase all restrictions were removed despite high levels of infection justified on the basis of the success of the vaccination programme. ConclusionsIn the Norwegian context containment policies were highly effective in limiting both infections and deaths from COVID-19 and more so than reliance on vaccinations alone despite high levels of public participation. In part this is due to the significant trust in the state apparent in Norway that leads to compliance with even highly restrictive policies. Therefore compliance may be more important than the level of stringency in explaining the consequence of public policies on pandemic outcomes.

The value of reducing the Green Premium: cost-saving innovation, emissions abatement, and climate goals

Carbon-emitting technologies often cost less than carbon-emission-free alternatives; this difference in cost is known as the Green Premium. Innovations that decrease the Green Premium contribute to achieving climate goals, but a conceptual framework to quantify that contribution has been lacking. Here, we devise a framework to translate reductions in the Green Premium into equivalent reductions in carbon emissions. We introduce a new integrated assessment model designed for teaching and communication, the Climate Optimized INvestment model, to facilitate transparent investigation of cost-saving innovation. We look at consequences of introducing a new technology with potential for learning and improvement for scenarios with three levels of stringency of carbon constraint: an Unlimited budget scenario in which carbon emissions abatement is determined only by balancing marginal costs; a Large budget scenario with a maximum budget for future cumulative emissions equivalent to 50 times the initial-year emissions; and a Small budget scenario with a maximum budget for future cumulative emissions equivalent to 15 times the initial-year emissions. At all of these stringency levels, we find the least-cost solutions involve investing in a learning subsidy to bring the cost of the new technology down the learning curve. Reducing the Green Premium can lead to enhanced carbon abatement, lower abatement costs even after reaching net-zero emissions, less climate damage, and increased net-present-value of consumption. We find both the value of Green Premium reductions and the value of carbon dioxide removal are greater under more stringent mitigation targets. Our study suggests a crucial role for both public and private sectors in promoting and developing innovations that can contribute to achieving zero emissions goals.

How the Stringency of the COVID-19 Restrictions Influences Motivation for Adherence and Well-Being: The Critical Role of Proportionality.

The stringency of the measures taken by governments to combat the COVID-19 pandemic varied considerably across countries and time. In the present study, we examined how the proportionality to the epidemiological situation is related to citizens'behavior, motivation and mental health. Across 421 days between March 2020 and March 2022, 273,722 Belgian participants (Mage = 49.47; 63.9% female; 33% single) completed an online questionnaire. Multiple linear mixed regression modeling was used to examine the interaction between the epidemiological situation, as indicated by the actual hospitalization numbers, and the stringency index to predict day-to-day variation in the variables of interest. Systematic evidence emerged showing that disproportional situations, as opposed to proportional situations, were associated with a clear pattern of maladaptive outcomes. Specifically, when either strict or lenient measures were disproportional in relation to the epidemiological situation, people reported lower autonomous motivation, more controlled motivation and amotivation, less adherence to sanitary rules, higher perceived risk of infection, lower need satisfaction, and higher anxiety and depressive symptoms. Perceived risk severity especially covaried with the stringency of the measures. At the absolute level, citizens reported the highest need satisfaction and mental health during days with proportional lenient measures. Stringent measures are not per se demotivating or compromising of people's well-being, nor are lenient measures as such motivating or enhancing well-being. Only proportional measures, that is, measures with a level of stringency that is aligned with the actual epidemiological situation, are associated with the greatest motivational, behavioral, and mental health benefits.

Quantifying COVID-19 policy impacts on subjective well-being during the early phase of the pandemic: A cross-sectional analysis of United States survey data from March to August 2020.

To stop the spread of COVID-19, a number of public health policies and restrictions were implemented during the pre-vaccination phase of the pandemic. This study provides a quantitative assessment of how these policies impacted subjective well-being (SWB) in the United States over a 6-month period spanning March to August 2020. We study two specific research objectives. First, we aim to quantify the impacts of COVID-19 public health policies at different levels of stringency on SWB. Second, we train and implement a conditional inference tree model for predicting individual SWB based both on socio-demographic characteristics and policies then in place. Our results indicate that policies such as enforcing strict stay-at-home requirements and closing workplaces were negatively associated with SWB, and that an individual's socio-demographic characteristics, including income status, job, and gender, conditionally interact with policies such as workplace closure in a predictive model of SWB. Therefore, although such policies may have positive health implications, they also have secondary environmental and social implications that need to be taken into account in any cost-benefit analysis of such policies for future pandemic preparedness. Our proposed methodology suggests a way to quantify such impacts through the lens of SWB, and to further advance the science of pandemic preparedness from a public health perspective.

P07.11.B A NOVEL CRISPR/CAS9 KNOCKOUT LIBRARY UNCOVERS PAN-ESSENTIAL MIRNAS IN HUMAN CANCER CELL LINES

Abstract BACKGROUND MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression that play an important role during cancer initiation and progression. Genome-wide functional screening using the CRISPR/Cas9 system is a powerful tool to uncover genetic dependencies for distinct tumor entities, and has revealed novel insights into pan-cancer fitness genes. Current libraries are focused on single guide RNAs (sgRNAs) targeting protein-coding genes, thereby limiting functional genomics-based investigations of miRNA function. MATERIAL AND METHODS We here designed a novel CRISPR/Cas9 knockout library of 8,107 distinct sgRNAs targeting a total of 1,769 human miRNAs. Using a total of 45 human cancer cell lines, representing 16 different tumor entities, we performed negative selection screens to identify miRNA fitness genes. Screen hits per cell line were scored on the basis of a combination of a supervised Bayesian gene essentiality analysis (BAGEL2) and an unsupervised gene ranking algorithm (MAGeCK). miRNA genes that scored across all cell lines, i.e. potentially pan-essential miRNAs, were identified using a combination of the Adaptive Daisy Model (ADaM) algorithm and the Fitness Percentile (FiPer) method. RESULTS In silico analyses revealed that our library has significantly lower off-target activity for protein-coding genes as compared to previously described miRNA-targeting sgRNA libraries, while providing a higher coverage of miRNAs present in the human genome. In total, only 13% (n=230) of all targeted miRNAs induced a fitness effect on one or more cell lines, and the majority (83%) of these genes induced a dependency in less than 50% of the tested cell lines. Pan-cancer fitness gene detection by ADaM or FiPer differed solely on the level of stringency. As such, ADaM and FiPer identified 34 core fitness or 54 common essential miRNAs, respectively, and almost all core fitness genes (97%) were identified as common essential. Preliminary network analyses revealed that protein-coding genes that are regulated by core fitness miRNAs are significantly enriched for cell cycle and p53 signaling networks, providing a first rationale for their dependency profiles in human cancer cell lines. CONCLUSION We here established a novel method for functional investigation of miRNAs by means of genome-wide CRISPR/Cas9 knockout screens. Our sgRNA library outperforms previously established libraries in terms of specificity and overall miRNA coverage, making it a novel tool to investigate miRNA function in a genome-wide fashion. We here use this library to define a first-of-its-kind genome-wide functional annotation of miRNAs, revealing a subset of pan-cancer fitness miRNAs that might regulate essential cellular processes such as cell cycle progression. Our data highlight the wide potential of this library in investigating miRNA function in diverse biological settings.

Assessment of the impact of government response measures on the spread of COVID-19: panel data evidence for 50 countries

This article investigates the impact of Government’s response measures to new COVID-19 cases. This is proxied by a stringency index of 50 countries from April 2020 to March 2022. Our World in Data COVID-19 dataset was utilised employing several panel econometrics methods. This article fills a gap in empirical research by employing a range of econometric methods over an extended period and countries. The article provides the basis for the formulation and implementation of government response measures or policies to other major public health events that may occur in the future. The research found a positive association between Government’s response measures and new cases initially and in the long term and a significant short-term error correction component. This indicates an incremental and repeatable implementation approach, proposing a cyclical or lagged relationship where response measures reach a level of stringency after some time, then induce a decline in new cases. The timing, speed, and stringency of implementation of the government policy response measures are crucial in our understanding of the relationship or link between the government policy response measures and new COVID-19 cases.