A pharmacist-driven protocol for methicillin-resistant Staphylococcus aureus nares screening and empiric vancomycin discontinuation was instituted in a community healthcare system utilizing a tele-antimicrobial stewardship program to reduce inappropriate use of vancomycin. The protocol and associated intervention resulted in a significant decrease in both vancomycin utilization and the rate of acute kidney injury.

The personalised oncology paradigm remains challenging to deliver despite technological advances in genomics-based identification of actionable variants combined with the increasing focus of drug development on these specific targets. To ensure we continue to build concerted momentum to improve outcomes across all cancer types, financial, technological and operational barriers need to be addressed. For example, complete integration and certification of the ‘molecular tumour board’ into ‘standard of care’ ensures a unified clinical decision pathway that both counteracts fragmentation and is the cornerstone of evidence-based delivery inside and outside of a research setting. Generally, integrated delivery has been restricted to specific (common) cancer types either within major cancer centres or small regional networks. Here, we focus on solutions in real-world integration of genomics, pathology, surgery, oncological treatments, data from clinical source systems and analysis of whole-body imaging as digital data that can facilitate cost-effectiveness analysis, clinical trial recruitment, and outcome assessment. This urgent imperative for cancer also extends across the early diagnosis and adjuvant treatment interventions, individualised cancer vaccines, immune cell therapies, personalised synthetic lethal therapeutics and cancer screening and prevention. Oncology care systems worldwide require proactive step-changes in solutions that include inter-operative digital working that can solve patient centred challenges to ensure inclusive, quality, sustainable, fair and cost-effective adoption and efficient delivery. Here we highlight workforce, technical, clinical, regulatory and economic challenges that prevent the implementation of precision oncology at scale, and offer a systematic roadmap of integrated solutions for standard of care based on minimal essential digital tools. These include unified decision support tools, quality control, data flows within an ethical and legal data framework, training and certification, monitoring and feedback. Bridging the technical, operational, regulatory and economic gaps demands the joint actions from public and industry stakeholders across national and global boundaries.

Despite the Supreme Court’s lack of direct electoral accountability, voters may factor its outputs into their voting decisions because elected representatives can affect the Court’s powers and composition. In this paper, we uncover an ironic predicament that faces candidates running on reforming this institution. Citizens who possess higher levels of diffuse support for the Court are more likely to rank it as an important factor in their voting logic. But because this diffuse support has sorted along partisan lines, candidate messaging about reform may not motivate partisans who have lost support for the Court because they view it as less important than other pressing issues. Thus, although Democrats are sympathetic to reform, Democratic candidates may have weak incentives to promote reform given low levels of diffuse support among their constituents. This dynamic mitigates against the possibility of a public or congressional backlash against the Court, preserving the status quo.

This collectively authored article argues for a regional turn in the historical study of transnational activism. By considering not only pan-regional movements but also examples of borderland contexts, transregional connections and diasporic understandings of ‘region’, our discussion identifies fresh possibilities for investigating the evolution and functioning of transnational activism. Based on a Royal Historical Society-funded workshop held at and supported by Northumbria University, the article brings together insights from diverse locations and arenas of contestation. The first part considers literatures on three macro-regional settings – South Asia, Western Europe and Latin America – to illustrate the importance of distinctive regional contexts and constructs in shaping transnational activism and its goals. The second part turns to case studies of transnational activism in and beyond Eastern Europe, West Africa, the Caribbean and East Asia. In doing so, it explores very different notions of the regional to identify how transnational activism has both shaped and been shaped by these ideas. Taken together, the two parts highlight the role of regional identities and projects in challenging inequalities and external domination. Our analysis and examples indicate the possibilities of a regionally rooted approach for writing histories of transnational activism.

Area-based conservation is a widely used approach for maintaining biodiversity, and there are ongoing discussions over what is an appropriate global conservation area coverage target. To inform such debates, it is necessary to know the extent and ecological representativeness of the current conservation area network, but this is hampered by gaps in existing global datasets. In particular, although data on privately and community-governed protected areas and other effective area-based conservation measures are often available at the national level, it can take many years to incorporate these into official datasets. This suggests a complementary approach is needed based on selecting a sample of countries and using their national-scale datasets to produce more accurate metrics. However, every country added to the sample increases the costs of data collection, collation and analysis. To address this, here we present a data collection framework underpinned by a spatial prioritization algorithm, which identifies a minimum set of countries that are also representative of 10 factors that influence conservation area establishment and biodiversity patterns. We then illustrate this approach by identifying a representative set of sampling units that cover 10% of the terrestrial realm, which included areas in only 25 countries. In contrast, selecting 10% of the terrestrial realm at random included areas across a mean of 162 countries. These sampling units could be the focus of future data collation on different types of conservation area. Analysing these data could produce more rapid and accurate estimates of global conservation area coverage and ecological representativeness, complementing existing international reporting systems.

Behavioural science has made significant contributions to public policy over the last decade from tax compliance to pensions and energy use. However, behavioural insights (BI) have not yet been able to claim significant policy shifts in the area of crime, despite increasing interest and experimentation. This paper offers a critical reflection on the state of BI and crime from the perspective of those who have been at the forefront of this work since the inception of the world's first behavioural science team in government. We outline how existing theories of crime have already laid foundations for the successful application of BI but identify opportunities to build on these with tools from behavioural science. We conclude by examining how continued cross-pollination of ideas between BI and disciplines such as applied criminology points to promising directions for future research.

This paper uses the Current Population Survey to study older workers' transitions out of employment and into retirement during the first year of the pandemic. We find that, among workers ages 55 to 79, the likelihood of leaving employment over the course of a year rose by 6.7 percentage points, a 43-percent increase over baseline. Workers without a college degree, Asian–Americans, those whose jobs were not amenable to social distancing, and part-time workers saw disproportionate impacts. In contrast, the likelihood of retiring increased by 1 percentage point, and there was no immediate retirement boom for full-time workers under 70.

We detected no correlation between standardized antimicrobial administration ratios (SAARs) and healthcare facility-onset Clostridioides difficile infection (HO-CDI) rates in 102 acute-care Veterans Affairs medical centers over 16 months. SAARs may be useful for investigating trends in local antimicrobial use, but no ratio threshold demarcated HO-CDI risk.

Sealings recovered from the Omo M10 temple, a provincial center of the Andean Tiwanaku state (AD 500–1100), and from the Muru Ut Pata neighborhood of the Tiwanaku capital, as well as a signet ring from the Akapana East complex of Tiwanaku's highland capital, shed light on the hitherto undocumented use of seals and sealings in Central Andean complex society. The identification of Tiwanaku sealings related to the signet ring seal has implications for understanding the transmission of identity, authority, and authenticity over time and distance in early Andean states.

The business and human rights agenda is gaining momentum internationally, perhaps best evidenced through recent legislative responses to tackling modern slavery. Using a reflexive law lens, we analyse three recent laws – the UK Modern Slavery Act 2015, the French ‘duty of vigilance’ law of 2017, and the Australian Modern Slavery Act 2018 (Cth). The three laws, or their accompanying guidance, share characteristics in terms of reporting requirements: the supply chain; risk mapping/assessment and management; analysis of subsidiary and supply chain risk; and effectiveness. The French Act has a broader scope as it is a due diligence, rather than a reporting law and includes obligations with regard to human rights and fundamental freedoms, health and safety, and the environment. It is the only Act of the three with substantive penalty provisions. All reporting requirements in the French and Australian Acts are mandatory, but the UK Act has limited mandatory reporting requirements. We find that only 22 companies globally will be required to report under all three laws. Using a subset of this dataset, we analysed 59 French vigilance plans and UK modern slavery statements published by nine manufacturing companies. This provided some preliminary analysis of how businesses have reported under the French Droit de Vigilance and the UK Modern Slavery Act (reports under the Australian Modern Slavery Act for these companies were not published at time of writing). Overall, businesses are using less demanding measures such as introducing policies and delivering training more commonly than the somewhat more resource-intensive activities such as audits. The more onerous requirements of the French law were reflected in the content and level of detail in the vigilance plans, compared with the UK modern slavery statements. However, for some companies, there were strong similarities between the UK and French publications, indicating ‘creep’ from the French Act into UK reports or a ‘race to the top’.

The Subglacial Antarctic Lakes Scientific Access (SALSA) Project accessed Mercer Subglacial Lake using environmentally clean hot-water drilling to examine interactions among ice, water, sediment, rock, microbes and carbon reservoirs within the lake water column and underlying sediments. A ~0.4 m diameter borehole was melted through 1087 m of ice and maintained over ~10 days, allowing observation of ice properties and collection of water and sediment with various tools. Over this period, SALSA collected: 60 L of lake water and 10 L of deep borehole water; microbes >0.2 μm in diameter from in situ filtration of ~100 L of lake water; 10 multicores 0.32–0.49 m long; 1.0 and 1.76 m long gravity cores; three conductivity–temperature–depth profiles of borehole and lake water; five discrete depth current meter measurements in the lake and images of ice, the lake water–ice interface and lake sediments. Temperature and conductivity data showed the hydrodynamic character of water mixing between the borehole and lake after entry. Models simulating melting of the ~6 m thick basal accreted ice layer imply that debris fall-out through the ~15 m water column to the lake sediments from borehole melting had little effect on the stratigraphy of surficial sediment cores.

Healthcare personnel with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection were interviewed to describe activities and practices in and outside the workplace. Among 2,625 healthcare personnel, workplace-related factors that may increase infection risk were more common among nursing-home personnel than hospital personnel, whereas selected factors outside the workplace were more common among hospital personnel.

ABSTRACT IMPACT: Our data reveal a histone modifying enzyme involved in regulating inflammation that may be a novel target for treating non-healing diabetic wounds. OBJECTIVES/GOALS: We investigate molecular mechanisms that regulate the inflammatory phenotype of macrophages in normal and diabetic wound healing. Our goal is to identify novel pathways that may be used to better treat diabetic patients with non-healing wounds. METHODS/STUDY POPULATION: We utilize normal and transgenic murine models on standard chow or high-diet to identify chromatin modifying enzymes involved in regulating macrophage function during wound healing. We validate our murine studies with human blood monocytes or wound macrophages from diabetic patients undergoing limb amputation surgery. RESULTS/ANTICIPATED RESULTS: We have identified the histone methyltransferase SETDB2 as a regulator inflammation in normal and diabetic wound macrophages. We found that SETDB2 was dependent on IFNβ singaling and that both IFNβ and Setdb2 expression were impaired in diabetic wound macrophages. Further, we show that SETDB2 regulates inflammatory response and immune cell trafficking pathways. We also show that SETDB2 genomic localization is dependent on *NFκΒ deposition of the promoter. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our results indicate that SETDB2 is a regulator of macrophage plasticity and that SETDB2 expression is impaired in diabetic wound macrophages leading to hyper-inflammatory response and delayed wound healing. These data provide a novel potential therapeutic pathway for treating non-healing diabetic wounds.