78 research outputs found
Law Schools as Knowledge Centers in the Digital Age
This article explores what it would mean for law schools to be âknowledge centersâ in the digital age, and to have this as a central mission. It describes the activities of legal knowledge centers as: (1) focusing on solving real legal problems in society outside of the academy; (2) evaluating the problem-solving effectiveness of the legal knowledge being developed; (3) re-conceptualizing the structures used to represent legal knowledge, the processes through which legal knowledge is created, and the methods used to apply that knowledge; and (4) disseminating legal knowledge in ways that assist its implementation. The Article uses as extended examples of knowledge centers in the digital age the research laboratories in the sciences, and in particular research laboratories in linguistics and information science. It uses numerous examples to suggest how law schools might implement the concept of a knowledge center
Law Schools as Knowledge Centers in the Digital Age
This article explores what it would mean for law schools to be âknowledge centersâ in the digital age, and to have this as a central mission. It describes the activities of legal knowledge centers as: (1) focusing on solving real legal problems in society outside of the academy; (2) evaluating the problem-solving effectiveness of the legal knowledge being developed; (3) re-conceptualizing the structures used to represent legal knowledge, the processes through which legal knowledge is created, and the methods used to apply that knowledge; and (4) disseminating legal knowledge in ways that assist its implementation. The Article uses as extended examples of knowledge centers in the digital age the research laboratories in the sciences, and in particular research laboratories in linguistics and information science. It uses numerous examples to suggest how law schools might implement the concept of a knowledge center
A Symmetric Approach to Compilation and Decompilation
Just as specializing a source interpreter can achieve compilation from a source language to a target language, we observe that specializing a target interpreter can achieve compilation from the target language to the source language. In both cases, the key issue is the choice of whether to perform an evaluation or to emit code that represents this evaluation. We substantiate this observation by specializing two source interpreters and two target interpreters. We first consider a source language of arithmetic expressions and a target language for a stack machine, and then the lambda-calculus and the SECD-machine language. In each case, we prove that the target-to-source compiler is a left inverse of the source-to-target compiler, i.e., it is a decompiler. In the context of partial evaluation, compilation by source-interpreter specialization is classically referred to as a Futamura projection. By symmetry, it seems logical to refer to decompilation by target-interpreter specialization as a Futamura embedding
Towards a New Paradigm for Intuitive Theatrical Lighting Control
A simplified model of a lighting process applied in theatrical productions is one that involves two key players. The first is that of the lighting designer, to produce a set of intentions and plans for the scenes that define the show. The second, the lighting technician, has the job of translating these designs into practice using control equipment, luminaires, and other technical instruments. The lighting design often becomes a âworking documentâ subject to change and adaptation as the physical reality of the design becomes apparent, and the input of other stakeholders is considered. This process can be a valuable creative tool, and also a difficult technical hurdle to overcome, depending on a varied number of factors. A common frustration with this process is that either the complexity of the task, or difficulty in communication can make it difficult for the final creative vision to be effectively realised. Strains may also arise in the case of small, often touring, theatre companies where the lighting designer and technician may be the same person, and frequently one of the performers as well. Considering the design aspect, there can be challenges in ensuring efficacy of lighting plans between venues in touring productions, with 2D lighting sketches or even 3D computer simulations confined to the paper or screen. From a technical perspective, the role of the lighting technician in theatres and performance situations has included the operation of lighting control equipment during shows. The equipment has evolved over time but has, until recently, been grounded upon the basis of faders and the mixing desk. It is argued that this paradigm has failed to keep pace with the change in other interactive technologies. The on-going research described in this paper explores existing and upcoming technologies in the field, whilst also seeking to understand the roles and communication workflows of those involved in theatrical lighting to find the best areas to seek improvement, adopting principles of user-centred design. The intention of this research is to develop a new paradigm, and manifestation of it, using a control method for lighting or projection that allows a more intuitive form of operation in theatre productions, which will be scalable and flexible
Unfractionated heparin inhibits live wild type SARS-CoV-2 cell infectivity at therapeutically relevant concentrations.
BACKGROUND AND PURPOSE: Currently, there are no licensed vaccines and limited antivirals for the treatment of COVID-19. Heparin (delivered systemically) is currently used to treat anticoagulant anomalies in COVID-19 patients. Additionally, in the United Kingdom, Brazil and Australia, nebulised unfractionated heparin (UFH) is being trialled in COVID-19 patients as a potential treatment. A systematic comparison of the potential antiviral effect of various heparin preparations on live wild type SARS-CoV-2, in vitro, is needed. EXPERIMENTAL APPROACH: Seven different heparin preparations including UFH and low MW heparins (LMWH) of porcine or bovine origin were screened for antiviral activity against live SARS-CoV-2 (Australia/VIC01/2020) using a plaque inhibition assay with Vero E6 cells. Interaction of heparin with spike protein RBD was studied using differential scanning fluorimetry and the inhibition of RBD binding to human ACE2 protein using elisa assays was examined. KEY RESULTS: All the UFH preparations had potent antiviral effects, with IC50 values ranging between 25 and 41 Όg·ml-1 , whereas LMWHs were less inhibitory by ~150-fold (IC50 range 3.4-7.8 mg·ml-1 ). Mechanistically, we observed that heparin binds and destabilizes the RBD protein and furthermore, we show heparin directly inhibits the binding of RBD to the human ACE2 protein receptor. CONCLUSION AND IMPLICATIONS: This comparison of clinically relevant heparins shows that UFH has significantly stronger SARS-CoV-2 antiviral activity compared to LMWHs. UFH acts to directly inhibit binding of spike protein to the human ACE2 protein receptor. Overall, the data strongly support further clinical investigation of UFH as a potential treatment for patients with COVID-19
Correction to: Using CPAP in COVID-19 patients outside of the intensive care setting: a comparison of survival and outcomes between dialysis and non-dialysis dependent patients
Abstract: Background: SARS-CoV-2 (COVID-19) is a novel coronavirus associated with high mortality rates. The use of Continuous Positive Airway Pressure (CPAP) has been recognised as a management option for severe COVID-19 (NHS, Specialty guides for patient management during the coronavirus pandemic Guidance for the role and use of non-invasive respiratory support in adult patients with coronavirus (confirmed or suspected), https://www.nice.org.uk/guidance/ng159). We offered ward-based CPAP to COVID-19, dialysis patients not suitable for escalation to ICU. The aim of the study was to evaluate the use of CPAP for COVID-19 dialysis patients compared to non-dialysis COVID-19 patients outside of the intensive care setting. We further aimed to investigate factors associated with improved outcomes. Methods: Data was collected from a single centre (Royal Preston Hospital, UK), from March to June 2020. Treatment outcomes were compared for dialysis and non-dialysis dependent patients who received CPAP with limitations on their escalation and resuscitation status. Kaplan-Meier survival curves and Cox regression models were used to compare outcomes. The primary study outcome was 30 day mortality. Confounders including length of admission, systemic anticoagulation and ultrafiltration volumes on dialysis were also analysed. Results: Over the study period, 40 dialysis patients tested positive for COVID-19, with 30 requiring hospital admission. 93% (n = 28) required supplementary oxygen and 12% (n = 9) required CPAP on the ward. These patients were compared to a serial selection of 14 non-dialysis patients treated with CPAP during the same period. Results showed a significant difference in 30 day survival rates between the two groups: 88.9% in the dialysis group vs. 21.4% in the non-dialysis group. Statistical modelling showed that anticoagulation was also an important factor and correlated with better outcomes. Conclusion: This is to the best of our knowledge, the largest series of COVID-19 dialysis patients treated with CPAP in a ward-based setting. In general, dialysis dependent patients have multiple co-morbidities including cardiovascular disease and diabetes mellitus making them vulnerable to COVID-19 and not always suitable for treatment in ICU. We showed a significantly lower 30 day mortality rate with the use of CPAP in the dialysis group (11.1%) compared to the non-dialysis group (78.6%). Despite a small sample size, we believe this study provides impetus for further work clarifying the role of CPAP in treating COVID-19 dialysis dependent patients
Long-Term Outcomes with Subcutaneous C1-Inhibitor Replacement Therapy for Prevention of Hereditary Angioedema Attacks
Background
For the prevention of attacks of hereditary angioedema (HAE), the efficacy and safety of subcutaneous human C1-esterase inhibitor (C1-INH[SC]; HAEGARDA, CSL Behring) was established in the 16-week Clinical Study for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy (COMPACT).
Objective
To assess the long-term safety, occurrence of angioedema attacks, and use of rescue medication with C1-INH(SC).
Methods
Open-label, randomized, parallel-arm extension of COMPACT across 11 countries. Patients with frequent angioedema attacks, either study treatment-naive or who had completed COMPACT, were randomly assigned (1:1) to 40 IU/kg or 60 IU/kg C1-INH(SC) twice per week, with conditional uptitration to optimize prophylaxis (ClinicalTrials.gov registration no. NCT02316353).
Results
A total of 126 patients with a monthly attack rate of 4.3 in 3 months before entry in COMPACT were enrolled and treated for a mean of 1.5 years; 44 patients (34.9%) had more than 2 years of exposure. Mean steady-state C1-INH functional activity increased to 66.6% with 60 IU/kg. Incidence of adverse events was low and similar in both dose groups (11.3 and 8.5 events per patient-year for 40 IU/kg and 60 IU/kg, respectively). For 40 IU/kg and 60 IU/kg, median annualized attack rates were 1.3 and 1.0, respectively, and median rescue medication use was 0.2 and 0.0 times per year, respectively. Of 23 patients receiving 60 IU/kg for more than 2 years, 19 (83%) were attack-free during months 25 to 30 of treatment.
Conclusions
In patients with frequent HAE attacks, long-term replacement therapy with C1-INH(SC) is safe and exhibits a substantial and sustained prophylactic effect, with the vast majority of patients becoming free from debilitating disease symptoms
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