Towards a New International Law of the Atmosphere?

Inclusion of the topic ‘protection of the atmosphere’ in the current work programme of the UN International Law Commission (ILC) reflects the long overdue recognition of the fact that the scope of contemporary international law for the Earth’s atmosphere extends far beyond the traditional discipline of ‘air law’ as a synonym for airspace and air navigation law. Instead, the atmospheric commons are regulated by a ‘regime complex’ comprising a multitude of economic uses including global communications, pollutant emissions and diffusion, in different geographical sectors and vertical zones, in the face of different categories of risks, and addressed by a wide range of different transnational institutions. Following several earlier attempts at identifying crosscutting legal rules and principles in this field (by, inter alia, the International Law Association, the UN Environment Programme, and the Institut de Droit International), the ILC has now embarked on a new codification/restatement project led by Special Rapporteur Shinya Murase – albeit hamstrung by a highly restrictive ‘understanding’ imposed by the Commission in 2013. This article assesses the prospects and limitations of the initial ILC reports and debates in 2014 and 2015, and potential avenues for progress in the years to come

The impact of acute surgical unit rostering on National Emergency Access Targets during the COVID-19 pandemic: a single hospital experience

Background: Surgical departments have been dramatically impacted by the novel coronavirus 19 (COVID-19) pandemic, with the cancellation of elective cases and changes to the provision of emergency surgical care. The aim of this study was to determine whether structural changes made within our facility's surgical department during COVID-19 altered National Emergency Access Target (NEAT) times and impacted on patient outcomes. Methods: Emergency surgical cases over a 4-month time period were retrospectively collected and statistically analysed, divided into pre- and mid-COVID-19 pandemic. Results: Baseline characteristics between the groups were comparable. There was a significant increase in consultant presence in theatre in the COVID group. There were also statistically significant reductions in NEAT times at each timepoint, although these did not meet national guidelines. There was no change in emergency surgical workload, complication rate or mortality rates within 30 days. Conclusion: Any significant change to services requires a coordinated hospital-wide approach, not just from a single department, and clinicians must continue to be wary of benchmarked times as the overall feasibility and safety of NEAT times has also been highlighted again

Improving gravitational-wave parameter estimation using Gaussian process regression

Folding uncertainty in theoretical models into Bayesian parameter estimation is necessary in order to make reliable inferences. A general means of achieving this is by marginalizing over model uncertainty using a prior distribution constructed using Gaussian process regression (GPR). As an example, we apply this technique to the measurement of chirp mass using (simulated) gravitational-wave signals from binary black holes that could be observed using advanced-era gravitational-wave detectors. Unless properly accounted for, uncertainty in the gravitational-wave templates could be the dominant source of error in studies of these systems. We explain our approach in detail and provide proofs of various features of the method, including the limiting behavior for high signal-to-noise, where systematic model uncertainties dominate over noise errors. We find that the marginalized likelihood constructed via GPR offers a significant improvement in parameter estimation over the standard, uncorrected likelihood both in our simple one-dimensional study, and theoretically in general. We also examine the dependence of the method on the size of training set used in the GPR; on the form of covariance function adopted for the GPR, and on changes to the detector noise power spectral density.Comment: 25 pages, 11 figures, Published March 201

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

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Paradox Research in Management Science: Looking Back to Move Forward

Paradox studies offer vital and timely insights into an array of organizational tensions. Yet this field stands at a critical juncture. Over the past 25 years, management scholars have drawn foundational insights from philosophy and psychology to apply a paradox lens to organizational phenomena. Yet extant studies selectively leverage ancient wisdom, adopting some key insights while abandoning others. Using a structured content analysis to review the burgeoning management literature, we surface six key themes, which represent the building blocks of a meta-theory of paradox. These six themes received varying attention in extant studies: paradox scholars emphasize types of paradoxes, collective approaches, and outcomes, but pay less attention to relationships within paradoxes, individual approaches, and dynamics. As this analysis suggests, management scholars have increasingly simplified the intricate, often messy phenomena of paradox. Greater simplicity renders phenomena understandable and testable, however, oversimplifying complex realities can foster reductionist and incomplete theories. We therefore propose a future research agenda targeted at enriching a meta-theory of paradox by reengaging these less developed themes. Doing so can sharpen the focus of this field, while revisiting its rich conceptual roots to capture the intricacies of paradox. This future research agenda leverages the potential of paradox across diverse streams of management science

Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012

OBJECTIVE: To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008. DESIGN: A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. METHODS: The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Recommendations were classified into three groups: (1) those directly targeting severe sepsis; (2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and (3) pediatric considerations. RESULTS: Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 h after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 h of the recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 h of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1B); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients (1C); fluid challenge technique continued as long as hemodynamic improvement is based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥65 mmHg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7-9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a PaO (2)/FiO (2) ratio of ≤100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 h) for patients with early ARDS and a PaO (2)/FI O (2) 180 mg/dL, targeting an upper blood glucose ≤180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 h after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 h of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5-10 min (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven "absolute"' adrenal insufficiency (2C). CONCLUSIONS: Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients