Preparation of carbon molecular sieve membranes from an optimized ionic liquid-regenerated cellulose precursor

Novel carbon molecular sieve membranes with high separation performance and stability in the presence of humidified streams were prepared from an optimized ionic liquid-regenerated cellulose precursor, in a single carbonization step. Membranes prepared at two different carbonization end temperatures (550 degrees C and 600 degrees C) were analyzed through scanning electron microscopy, thermogravimetric analysis, Fourier transform infrared spectroscopy, carbon dioxide adsorption and permeation experiments. The prepared membranes exhibited uniform thickness of approximately 20 mu m and a well-developed microporous structure. The permeation performance of these carbon molecular sieve membranes was above the Robeson upper bound curve for polymeric membranes. In particular, the membrane prepared at 550 degrees C end temperature exhibited permeability to oxygen of 5.16 barrer and O-2/N-2 ideal selectivity of 32.3 and permeability to helium of 126 barrer and He/N-2 ideal selectivity of 788; besides, permeation experiments performed in the presence of ca. 80% relative humidity showed that humidity does not originate pore blockage. These results open the door for the preparation of tailor made precursors that originate carbon molecular sieve membranes with extraordinary separation performances, mechanical resistance and stability

Compendium of TCDD-mediated transcriptomic response datasets in mammalian model systems

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most potent congener of the dioxin class of environmental contaminants. Exposure to TCDD causes a wide range of toxic outcomes, ranging from chloracne to acute lethality. The severity of toxicity is highly dependent on the aryl hydrocarbon receptor (AHR). Binding of TCDD to the AHR leads to changes in transcription of numerous genes. Studies evaluating the transcriptional changes brought on by TCDD may provide valuable insight into the role of the AHR in human health and disease. We therefore compiled a collection of transcriptomic datasets that can be used to aid the scientific community in better understanding the transcriptional effects of ligand-activated AHR.Peer reviewe

Thiopurine monotherapy is effective in ulcerative colitis but significantly less so in Crohn’s disease: long-term outcomes for 11 928 patients in the UK inflammatory bowel disease bioresource

Objective: Thiopurines are widely used as maintenance therapy in inflammatory bowel disease (IBD) but the evidence base for their use is sparse and their role increasingly questioned. Using the largest series reported to date, we assessed the long-term effectiveness of thiopurines in ulcerative colitis (UC) and Crohn’s disease (CD), including their impact on need for surgery. Design: Outcomes were assessed in 11 928 patients (4968 UC, 6960 CD) in the UK IBD BioResource initiated on thiopurine monotherapy with the intention of maintaining medically induced remission. Effectiveness was assessed retrospectively using patient-level data and a definition that required avoidance of escalation to biological therapy or surgery while on thiopurines. Analyses included overall effectiveness, time-to-event analysis for treatment escalation and comparison of surgery rates in patients tolerant or intolerant of thiopurines. Results: Using 68 132 patient-years of exposure, thiopurine monotherapy appeared effective for the duration of treatment in 2617/4968 (52.7%) patients with UC compared with 2378/6960 (34.2%) patients with CD (p<0.0001). This difference was corroborated in a multivariable analysis: after adjusting for variables including treatment era, thiopurine monotherapy was less effective in CD than UC (OR 0.47, 95% CI 0.43 to 0.51, p<0.0001). Thiopurine intolerance was associated with increased risk of surgery in UC (HR 2.44, p<0.0001); with a more modest impact on need for surgery in CD (HR=1.23, p=0.0015). Conclusion: Thiopurine monotherapy is an effective long-term treatment for UC but significantly less effective in CD

Evaluation of Musical Creativity and Musical Metacreation Systems

The field of computational creativity, including musical metacreation, strives to develop artificial systems that are capable of demonstrating creative behavior or producing creative artefacts. But the claim of creativity is often assessed, subjectively only on the part of the researcher and not objectively at all. This article provides theoretical motivation for more systematic evaluation of musical metacreation and computationally creative systems and presents an overview of current methods used to assess human and machine creativity that may be adapted for this purpose. In order to highlight the need for a varied set of evaluation tools, a distinction is drawn among three types of creative systems: those that are purely generative, those that contain internal or external feedback, and those that are capable of reflection and self-reflection. To address the evaluation of each of these aspects, concrete examples of methods and techniques are suggested to help researchers (1) evaluate their systems' creative process and generated artefacts, and test their impact on the perceptual, cognitive, and affective states of the audience, and (2) build mechanisms for reflection into the creative system, including models of human perception and cognition, to endow creative systems with internal evaluative mechanisms to drive self-reflective processes. The first type of evaluation can be considered external to the creative system and may be employed by the researcher to both better understand the efficacy of their system and its impact and to incorporate feedback into the system. Here we take the stance that understanding human creativity can lend insight to computational approaches, and knowledge of how humans perceive creative systems and their output can be incorporated into artificial agents as feedback to provide a sense of how a creation will impact the audience. The second type centers around internal evaluation, in which the system is able to reason about its own behavior and generated output. We argue that creative behavior cannot occur without feedback and reflection by the creative/metacreative system itself. More rigorous empirical testing will allow computational and metacreative systems to become more creative by definition and can be used to demonstrate the impact and novelty of particular approaches

Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial

Background Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19. Methods In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days. Patients were randomly assigned via a central web-based randomisation system (TruST). Randomisation was stratified by site and age (65 years or ≥65 years), and within each stratum, blocks were of random sizes of two, four, or six patients. Participants in both groups continued to receive other therapies required to manage their condition. Participants, study staff, and investigators were masked to the study assignment. The primary outcome was the 7-point WHO ordinal scale for clinical status at day 29 after random assignment. The intention-to-treat population included all patients who were randomly assigned and met the enrolment criteria. The safety population included all participants who received at least one dose of study medication. This study was registered with the ISRCTN registry, ISRCTN30564012. Findings Between June 5, 2020, and Jan 25, 2021, 406 patients were randomly assigned to brensocatib or placebo; 192 (47·3%) to the brensocatib group and 214 (52·7%) to the placebo group. Two participants were excluded after being randomly assigned in the brensocatib group (214 patients included in the placebo group and 190 included in the brensocatib group in the intention-to-treat population). Primary outcome data was unavailable for six patients (three in the brensocatib group and three in the placebo group). Patients in the brensocatib group had worse clinical status at day 29 after being randomly assigned than those in the placebo group (adjusted odds ratio 0·72 [95% CI 0·57–0·92]). Prespecified subgroup analyses of the primary outcome supported the primary results. 185 participants reported at least one adverse event; 99 (46%) in the placebo group and 86 (45%) in the brensocatib group. The most common adverse events were gastrointestinal disorders and infections. One death in the placebo group was judged as possibly related to study drug. Interpretation Brensocatib treatment did not improve clinical status at day 29 in patients hospitalised with COVID-19