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Private landowners are key partners in chronic wasting disease (CWD) management, especially in landscapes where there is limited public ownership. In this study, we evaluated landowners' preferences for alternative hypothetical CWD management programs using a stated choice experiment. We were particularly interested in understanding preferences for the use of financial incentives to motivate white-tailed deer harvest and facilitate hunter access to private lands as potential CWD management tools. We used latent class analysis to characterize preference heterogeneity among landowners stemming from patterns of choice. We compared means and distributions of auxiliary variables related to landowners' perceived risks, trust, attitudes toward management, and sociodemographics across latent classes stemming from choice model results. The pooled model demonstrated that reducing deer population density, providing payments to landowners for CWD-positive deer taken from their property, the form of incentives for public access, and banning recreational deer feeding had a small positive effect on respondents' choice of CWD management program. However, providing financial payments to hunters for harvesting CWD-positive deer and the use of targeted culling had the opposite effect on choice. Latent class models revealed that a majority of respondents exhibited a pattern of preference where all forms of incentives exerted a negative effect on choice, but smaller subsets of landowners positively evaluate the use of some incentives. Post-hoc contrasts revealed relationships between patterns of preferences and trust, risk, and attitudes toward CWD management with small to medium effects. Results demonstrated limited support for the use of financial incentives as a tool to manage access and harvest in the southeast Minnesota CWD management zone.

The global nature of e-commerce is complicating privacy issues because perceptions of privacy, trust, risk, and fair information practices vary across cultures, and differences in national regulation create challenges for global information management strategies. Despite the spike in international regulatory attention devoted to privacy issues and the tensions associated with them, there has been very little research on the relationship between information privacy concerns and consumers' regulatory preferences, and even rarer is research that incorporates cultural values into a framework that includes privacy concerns and regulation. This study examines privacy concerns, a full complement of cultural values, trust, risk, and regulation at the individual level in a cohesive manner. Relying on a dataset of consumers gathered in the United States and India, the authors test a model that incorporates these constructs as well as trust and risk beliefs. The model explains 48% of the variance in consumers' regulatory preferences, and all but one of the hypotheses find statistical support.

This paper examines the determinants of financial industry actors’ regulatory preferences—examining why some financial industry actors prefer less stringent financial regulations while others prefer more stringent regulations. The determination of preferences, we argue, can be understood as mutually dependent. How an organization is connected to other organisations through network ties may help to explain its regulatory preferences. Our empirical point of focus is financial industry lobbying in the context of the European Union (EU). Using data from nearly nine hundred lobbying letters related to legislation on banking, insurance, and securities regulation, we map out a “socialization network” that models connections between financial industry firms, their associations, as well as a broad range of other organisations and actors that are auxiliary to this community of organizations. Using these data we find evidence that organizations’ preferences are informed by their location within this socialization network. Controlling for a range of other plausible factors, we find that 1) those connected via common associational ties, 2) those closer to one another in the network and 3) those more “embedded” in this network are all less likely to diverge in terms of their preferences from one another.

Do countries with high corporate social responsibility (CSR) performance support more stringent supranational regulation? Following this logic, existing scholarship claims that Nordic countries push for tougher regulations to sharpen their competitive advantage. On the basis of an examination of the negotiations over the EU Directive 2014/95/EU, a corporate transparency law that requires firms to report on their social, environmental, and human rights impacts, this paper argues that strong CSR performance does not necessarily entail strong support for regulation. Nordic companies perform well when it comes to sustainability, but except for Denmark, Nordic governments’ support for the Directive was lukewarm. To explain why, I examine the dynamics between CSR leaders, business associations, and party politics. I find that business associations are key for explaining this outcome. While some Nordic CSR leaders provided support, business associations, in which SMEs with lower CSR performance comprise the bulk of the members, were forceful opponents of regulation, unless domestic regulations are in place, in which case these associations support supranational regulations to level the playing field. I also stress the importance of partisan politics and extend the analysis to mandatory human rights due diligence. In sum, Nordic countries are much more heterogeneous than what the literature often suggests.

Background Patients have a unique role in deciding what treatments should be available for them and regulatory agencies should take their preferences into account when making treatment approval decisions. This is the first study designed to obtain quantitative patient-preference evidence to inform regulatory approval decisions by the Food and Drug Administration Center for Devices and Radiological Health. Methods Five-hundred and forty United States adults with body mass index (BMI) ≥30 kg/m 2 evaluated tradeoffs among effectiveness, safety, and other attributes of weight-loss devices in a scientific survey. Discrete-choice experiments were used to quantify the importance of safety, effectiveness, and other attributes of weight-loss devices to obese respondents. A tool based on these measures is being used to inform benefit-risk assessments for premarket approval of medical devices. Results Respondent choices yielded preference scores indicating their relative value for attributes of weight-loss devices in this study. We developed a tool to estimate the minimum weight loss acceptable by a patient to receive a device with a given risk profile and the maximum mortality risk tolerable in exchange for a given weight loss. For example, to accept a device with 0.01 % mortality risk, a risk tolerant patient will require about 10 % total body weight loss lasting 5 years. Conclusions Patient preference evidence was used make regulatory decision making more patient-centered. In addition, we captured the heterogeneity of patient preferences allowing market approval of effective devices for risk tolerant patients. CDRH is using the study tool to define minimum clinical effectiveness to evaluate new weight-loss devices. The methods presented can be applied to a wide variety of medical products. This study supports the ongoing development of a guidance document on incorporating patient preferences into medical-device premarket approval decisions.

The papain-like protease PLpro is an essential coronavirus enzyme that is required for processing viral polyproteins to generate a functional replicase complex and enable viral spread 1 , 2 . PLpro is also implicated in cleaving proteinaceous post-translational modifications on host proteins as an evasion mechanism against host antiviral immune responses 3 – 5 . Here we perform biochemical, structural and functional characterization of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PLpro (SCoV2-PLpro) and outline differences with SARS-CoV PLpro (SCoV-PLpro) in regulation of host interferon and NF-κB pathways. SCoV2-PLpro and SCoV-PLpro share 83% sequence identity but exhibit different host substrate preferences; SCoV2-PLpro preferentially cleaves the ubiquitin-like interferon-stimulated gene 15 protein (ISG15), whereas SCoV-PLpro predominantly targets ubiquitin chains. The crystal structure of SCoV2-PLpro in complex with ISG15 reveals distinctive interactions with the amino-terminal ubiquitin-like domain of ISG15, highlighting the high affinity and specificity of these interactions. Furthermore, upon infection, SCoV2-PLpro contributes to the cleavage of ISG15 from interferon responsive factor 3 (IRF3) and attenuates type I interferon responses. Notably, inhibition of SCoV2-PLpro with GRL-0617 impairs the virus-induced cytopathogenic effect, maintains the antiviral interferon pathway and reduces viral replication in infected cells. These results highlight a potential dual therapeutic strategy in which targeting of SCoV2-PLpro can suppress SARS-CoV-2 infection and promote antiviral immunity. Biochemical, structural and functional studies on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) papain-like protease PLpro reveal that it regulates host antiviral responses by preferentially cleaving the ubiquitin-like interferon-stimulated gene 15 protein (ISG15) and identify this protease as a potential therapeutic target for coronavirus disease 2019 (COVID-19).

Vaccinations are an effective choice to stop disease outbreaks, including COVID-19. There is little research on individuals' COVID-19 vaccination decision-making. We aimed to determine individual preferences for COVID-19 vaccinations in China, and to assess the factors influencing vaccination decision-making to facilitate vaccination coverage. A D-efficient discrete choice experiment was conducted across six Chinese provinces selected by the stratified random sampling method. Vaccine choice sets were constructed using seven attributes: vaccine effectiveness, side-effects, accessibility, number of doses, vaccination sites, duration of vaccine protection, and proportion of acquaintances vaccinated. Conditional logit and latent class models were used to identify preferences. Although all seven attributes were proved to significantly influence respondents’ vaccination decision, vaccine effectiveness, side-effects and proportion of acquaintances vaccinated were the most important. We also found a higher probability of vaccinating when the vaccine was more effective; risks of serious side effects were small; vaccinations were free and voluntary; the fewer the number of doses; the longer the protection duration; and the higher the proportion of acquaintances vaccinated. Higher local vaccine coverage created altruistic herd incentives to vaccinate rather than free-rider problems. The predicted vaccination uptake of the optimal vaccination scenario in our study was 84.77%. Preference heterogeneity was substantial. Individuals who were older, had a lower education level, lower income, higher trust in the vaccine and higher perceived risk of infection, displayed a higher probability to vaccinate. Preference heterogeneity among individuals should lead health authorities to address the diversity of expectations about COVID-19 vaccinations. To maximize COVID-19 vaccine uptake, health authorities should promote vaccine effectiveness; pro-actively communicate the absence or presence of vaccine side effects; and ensure rapid and wide media communication about local vaccine coverage.

Transcription factors (TFs) play key roles in both development and stress responses. By integrating into and rewiring original systems, novel TFs contribute significantly to the evolution of transcriptional regulatory networks. Here, we report a high-confidence transcriptional regulatory map covering 388 TFs from 47 families in Arabidopsis. Systematic analysis of this map revealed the architectural heterogeneity of developmental and stress response subnetworks and identified three types of novel network motifs that are absent from unicellular organisms and essential for multicellular development. Moreover, TFs of novel families that emerged during plant landing present higher binding specificities and are preferentially wired into developmental processes and these novel network motifs. Further unveiled connection between the binding specificity and wiring preference of TFs explains the wiring preferences of novel-family TFs. These results reveal distinct functional and evolutionary features of novel TFs, suggesting a plausible mechanism for their contribution to the evolution of multicellular organisms.

Patient preference studies could provide valuable insights to a National Institute for Health and Care Excellence committee into the preferences patients have for different treatment options, especially if the study sample is representative of the broader patient population. We identify three main uses of patient preference studies along a technology’s pathway from drug development to clinical use: in early clinical development to guide the selection of appropriate endpoints, to inform benefit-risk assessments carried out by regulators and to inform reimbursement decisions made by health technology assessment bodies. In the context of the National Institute for Health and Care Excellence’s methods and processes, we do not see a role for quantitative patient preference data to be directly incorporated into health economic modelling. Rather, we see a role for patient preference studies to be submitted alongside other types of evidence. Examples where patient preference studies might have added value in health technology assessments include cases where two distinctly different treatment options are being compared, when patients have to decide between multiple treatment options, when technologies have important non-health benefits or when a treatment is indicated for a heterogenous population.

When the DNA bases cytosine and guanine are next to each other, a methyl group is generally added to the pyrimidine, generating a mCpG dinucleotide. This modification alters DNA structure but can also affect function by inhibiting transcription factor (TF) binding. Yin et al. systematically analyzed the effect of CpG methylation on the binding of 542 human TFs (see the Perspective by Hughes and Lambert). In addition to inhibiting binding of some TFs, they found that mCpGs can promote binding of others, particularly TFs involved in development, such as homeodomain proteins. Science , this issue p. eaaj2239 ; see also p. 489 Genome-scale analysis reveals positive and negative binding of transcription factors to methylated CpG dinucleotides. The majority of CpG dinucleotides in the human genome are methylated at cytosine bases. However, active gene regulatory elements are generally hypomethylated relative to their flanking regions, and the binding of some transcription factors (TFs) is diminished by methylation of their target sequences. By analysis of 542 human TFs with methylation-sensitive SELEX (systematic evolution of ligands by exponential enrichment), we found that there are also many TFs that prefer CpG-methylated sequences. Most of these are in the extended homeodomain family. Structural analysis showed that homeodomain specificity for methylcytosine depends on direct hydrophobic interactions with the methylcytosine 5-methyl group. This study provides a systematic examination of the effect of an epigenetic DNA modification on human TF binding specificity and reveals that many developmentally important proteins display preference for mCpG-containing sequences.