Developing activity theory in information studies (DATIS)

Over the last two decades the use of Activity Theory has grown within the field of information studies. However, while there is a budding community, the use and development of Activity Theory in information studies remains underdeveloped and fragmented. This community building workshop provides an opportunity to: (1) introduce information scholars to the basic conceptual premises of Activity Theory focusing on the use, development and contribution of Activity Theory; (2) provide a forum to extend the development of Activity Theory; and (3) It will also provide a networking opportunity for scholars already utilizing activity theory and an opportunity to discuss the contributions iSchool scholars can make to the wider Activity Theory community. The aim of the afternoon session is to both stimulate discourse and advance the use of the theory. A 500-word position paper is due 4th of March

Systematic approach to outcome assessment from coded electronic healthcare records in the DaRe2THINK NHS-embedded randomized trial

Aims Improving the efficiency of clinical trials is key to their continued importance in directing evidence-based patient care. Digital innovations, in particular the use of electronic healthcare records (EHRs), allow for large-scale screening and follow up of participants. However, it is critical these developments are accompanied by robust and transparent methods that can support high-quality and high clinical value research. Methods and results The DaRe2THINK trial includes a series of novel processes, including nationwide pseudonymized pre screening of the primary-care EHR across England, digital enrolment, remote e-consent, and ‘no-visit’ follow up by linking all primary- and secondary-care health data with patient-reported outcomes. DaRe2THINK is a pragmatic, healthcare-embedded randomized trial testing whether earlier use of direct oral anticoagulants in patients with prior or current atrial fibrillation can prevent thromboembolic events and cognitive decline (www.birmingham.ac.uk/dare2think). This study outlines the systematic approach and methodology employed to define patient information and outcome events. This includes transparency on all medical code lists and phenotypes used in the trial across a variety of national data sources, including Clinical Practice Research Datalink Aurum (primary care), Hospital Episode Statistics (secondary care), and the Office for National Statistics (mortality). Conclusion Co-designed by a patient and public involvement team, DaRe2THINK presents an opportunity to transform the approach to randomized trials in the setting of routine healthcare, providing high-quality evidence generation in populations representative of the community at risk

Atmospheric fates of Criegee intermediates in the ozonolysis of isoprene

We use a large laboratory, modeling, and field dataset to investigate the isoprene + O_3 reaction, with the goal of better understanding the fates of the C_1 and C_4 Criegee intermediates in the atmosphere. Although ozonolysis can produce several distinct Criegee intermediates, the C_1 stabilized Criegee (CH_2OO, 61 ± 9%) is the only one observed to react bimolecularly. We suggest that the C_4 Criegees have a low stabilization fraction and propose pathways for their decomposition. Both prompt and non-prompt reactions are important in the production of OH (28% ± 5%) and formaldehyde (81% ± 16%). The yields of unimolecular products (OH, formaldehyde, methacrolein (42 ± 6%) and methyl vinyl ketone (18 ± 6%)) are fairly insensitive to water, i.e., changes in yields in response to water vapor (≤4% absolute) are within the error of the analysis. We propose a comprehensive reaction mechanism that can be incorporated into atmospheric models, which reproduces laboratory data over a wide range of relative humidities. The mechanism proposes that CH_2OO + H_2O (k_((H_2O)) ∼ 1 × 10^(−15) cm^3 molec^(−1) s^(−1)) yields 73% hydroxymethyl hydroperoxide (HMHP), 6% formaldehyde + H_2O_2, and 21% formic acid + H_2O; and CH_2OO + (H_2O)_2 (k_((H_2O)_2) ∼ 1 × 10^(−12) cm^3 molec^(−1) s^(−1)) yields 40% HMHP, 6% formaldehyde + H_2O_2, and 54% formic acid + H_2O. Competitive rate determinations (k_(SO_2/k(H_2O)n=1,2) ∼ 2.2 (±0.3) × 10^4) and field observations suggest that water vapor is a sink for greater than 98% of CH2OO in a Southeastern US forest, even during pollution episodes ([SO_2] ∼ 10 ppb). The importance of the CH_2OO + (H_2O)n reaction is demonstrated by high HMHP mixing ratios observed over the forest canopy. We find that CH_2OO does not substantially affect the lifetime of SO_2 or HCOOH in the Southeast US, e.g., CH_2OO + SO_2 reaction is a minor contribution (<6%) to sulfate formation. Extrapolating, these results imply that sulfate production by stabilized Criegees is likely unimportant in regions dominated by the reactivity of ozone with isoprene. In contrast, hydroperoxide, organic acid, and formaldehyde formation from isoprene ozonolysis in those areas may be significant

H-ATLAS/GAMA: quantifying the morphological evolution of the galaxy population using cosmic calorimetry

Using results from the Herschel Astrophysical Terrahertz Large-Area Survey (H-ATLAS) and the Galaxy and Mass Assembly (GAMA) project, we show that, for galaxy masses above ≃ 108 M⊙, 51 per cent of the stellar mass-density in the local Universe is in early-type galaxies (ETGs; Sérsic n > 2.5) while 89 per cent of the rate of production of stellar mass-density is occurring in late-type galaxies (LTGs; Sérsic n < 2.5). From this zero-redshift benchmark, we have used a calorimetric technique to quantify the importance of the morphological transformation of galaxies over the history of the Universe. The extragalactic background radiation contains all the energy generated by nuclear fusion in stars since the big bang. By resolving this background radiation into individual galaxies using the deepest far-infrared survey with the Herschel Space Observatory and a deep near-infrared/optical survey with the Hubble Space Telescope (HST), and using measurements of the Sérsic index of these galaxies derived from the HST images, we estimate that ≃83 per cent of the stellar mass-density formed over the history of the Universe occurred in LTGs. The difference between this value and the fraction of the stellar mass-density that is in LTGs today implies there must have been a major transformation of LTGs into ETGs after the formation of most of the stars

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead