Genome editing in context

Genome editing has created a new continuum between what might occur in nature and what can only occur in the laboratory. Remarkable though it is that we have developed the capacity to predictably and finely alter genetic codes it is perhaps as remarkable that a new technology enabling this has appeared, spread widely and become easily affordable and accessible within such a short timescale. The speed at which the CRISPR/Cas9 technology use has grown almost defies comparison. A factor contributing to this, and also to the complexity of the surrounding debates, is the sheer breadth of possible applications of the technology, in terms of target organisms and genetic constructs, and in terms of the processes it could be used to influence. These combined characteristics, while opening a world of possibilities for science and society, also present a pressing and complex set of questions about governance and regulation; it is difficult to have appropriately informed discussion let alone for regulation to keep pace.

Understanding decisions about antibiotic prescribing in ICU: an application of the Necessity Concerns Framework

Background: Antibiotics are extensively prescribed in intensive care units (ICUs), yet little is known about how antibiotic-related decisions are made in this setting. We explored how beliefs, perceptions and contextual factors influenced ICU clinicians' antibiotic prescribing. Methods: We conducted 4 focus groups and 34 semistructured interviews with clinicians involved in antibiotic prescribing in four English ICUs. Focus groups explored factors influencing prescribing, whereas interviews examined decision-making processes using two clinical vignettes. Data were analysed using thematic analysis, applying the Necessity Concerns Framework. Results: Clinicians' antibiotic decisions were influenced by their judgement of the necessity for prescribing/not prescribing, relative to their concerns about potential adverse consequences. Antibiotic necessity perceptions were strongly influenced by beliefs that antibiotics would protect patients from deterioration and themselves from the ethical and legal consequences of undertreatment. Clinicians also reported concerns about prescribing antibiotics. These generally centred on antimicrobial resistance; however, protecting the individual patient was prioritised over these societal concerns. Few participants identified antibiotic toxicity concerns as a key influencer. Clinical uncertainty often complicated balancing antibiotic necessity against concerns. Decisions to start or continue antibiotics often represented € erring on the side of caution' as a protective response in uncertainty. This approach was reinforced by previous experiences of negative consequences ( € being burnt') which motivated prescribing € just in case' of an infection. Prescribing decisions were also context-dependent, exemplified by a lower perceived threshold to prescribe antibiotics out-of-hours, input from external team members and local prescribing norms. Conclusion: Efforts to improve antibiotic stewardship should consider clinicians' desire to protect with a prescription. Rapid molecular microbiology, with appropriate communication, may diminish clinicians' fears of not prescribing or of using narrower-spectrum antibiotics

LegalBench: A Collaboratively Built Benchmark for Measuring Legal Reasoning in Large Language Models

The advent of large language models (LLMs) and their adoption by the legal community has given rise to the question: what types of legal reasoning can LLMs perform? To enable greater study of this question, we present LegalBench: a collaboratively constructed legal reasoning benchmark consisting of 162 tasks covering six different types of legal reasoning. LegalBench was built through an interdisciplinary process, in which we collected tasks designed and hand-crafted by legal professionals. Because these subject matter experts took a leading role in construction, tasks either measure legal reasoning capabilities that are practically useful, or measure reasoning skills that lawyers find interesting. To enable cross-disciplinary conversations about LLMs in the law, we additionally show how popular legal frameworks for describing legal reasoning -- which distinguish between its many forms -- correspond to LegalBench tasks, thus giving lawyers and LLM developers a common vocabulary. This paper describes LegalBench, presents an empirical evaluation of 20 open-source and commercial LLMs, and illustrates the types of research explorations LegalBench enables.Comment: 143 pages, 79 tables, 4 figure

LegalBench: A Collaboratively Built Benchmark for Measuring Legal Reasoning in Large Language Models

The advent of large language models (LLMs) and their adoption by the legal community has given rise to the question: what types of legal reasoning can LLMs perform? To enable greater study of this question, we present LegalBench: a collaboratively constructed legal reasoning benchmark consisting of 162 tasks covering six different types of legal reasoning. LegalBench was built through an interdisciplinary process, in which we collected tasks designed and hand-crafted by legal professionals. Because these subject matter experts took a leading role in construction, tasks either measure legal reasoning capabilities that are practically useful, or measure reasoning skills that lawyers find interesting. To enable cross-disciplinary conversations about LLMs in the law, we additionally show how popular legal frameworks for describing legal reasoning—which distinguish between its many forms—correspond to LegalBench tasks, thus giving lawyers and LLM developers a common vocabulary. This paper describes LegalBench, presents an empirical evaluation of 20 open-source and commercial LLMs, and illustrates the types of research explorations LegalBench enables

Intensivists’ beliefs about rapid multiplex molecular diagnostic testing and its potential role in improving prescribing decisions and antimicrobial stewardship: a qualitative study

Background Rapid molecular diagnostic tests to investigate the microbial aetiology of pneumonias may improve treatment and antimicrobial stewardship in intensive care units (ICUs). Clinicians’ endorsement and uptake of these tests is crucial to maximise engagement; however, adoption may be impeded if users harbour unaddressed concerns or if device usage is incompatible with local practice. Accordingly, we strove to identify ICU clinicians’ beliefs about molecular diagnostic tests for pneumonias before implementation at the point-of-care. Methods We conducted semi-structured interviews with 35 critical care doctors working in four ICUs in the United Kingdom. A clinical vignette depicting a fictitious patient with signs of pneumonia was used to explore clinicians’ beliefs about the importance of molecular diagnostics and their concerns. Data were analysed thematically. Results Clinicians’ beliefs about molecular tests could be grouped into two categories: perceived potential of molecular diagnostics to improve antibiotic prescribing (Molecular Diagnostic Necessity) and concerns about how the test results could be implemented into practice (Molecular Diagnostic Concerns). Molecular Diagnostic Necessity stemmed from beliefs that positive results would facilitate targeted antimicrobial therapy; that negative results would signal the absence of a pathogen, and consequently that having the molecular diagnostic results would bolster clinicians’ prescribing confidence. Molecular Diagnostic Concerns included unfamiliarity with the device’s capabilities, worry that it would detect non-pathogenic bacteria, uncertainty whether it would fail to detect pathogens, and discomfort with withholding antibiotics until receiving molecular test results. Conclusions Clinicians believed rapid molecular diagnostics for pneumonias were potentially important and were open to using them; however, they harboured concerns about the tests’ capabilities and integration into clinical practice. Implementation strategies should bolster users’ necessity beliefs while reducing their concerns; this can be accomplished by publicising the tests’ purpose and benefits, identifying and addressing clinicians’ misconceptions, establishing a trial period for first-hand familiarisation, and emphasising that, with a swift (e.g., 60–90 min) test, antibiotics can be started and refined after molecular diagnostic results become available