Direct imaging of changes in aerosol particle viscosity upon hydration and chemical aging

Organic aerosol particles (OA) play major roles in atmospheric chemistry, climate, and public health. Aerosol particle viscosity is highly important since it can determine the ability of chemical species such as oxidants, organics or water to diffuse into the particle bulk. Recent measurements indicate that OA may be present in highly viscous states, however, diffusion rates of small molecules such as water are not limited by these high viscosities. Direct observational evidence of kinetic barriers caused by high viscosity and low diffusivity in aerosol particles were not available until recently; and techniques that are able to dynamically quantify and track viscosity changes during atmospherically relevant processes are still unavailable for atmospheric aerosols. Here we report quantitative, real-time, online observations of microscopic viscosity changes in aerosol particles of atmospherically relevant composition, using fluorescence lifetime imaging (FLIM) of viscosity. We show that microviscosity in ozonated oleic acid droplets and secondary organic aerosol (SOA) particles formed by ozonolysis of myrcene increases substantially with decreasing humidity and atmospheric oxidative aging processes. Furthermore, we found unexpected heterogeneities of microviscosity inside individual aerosol particles. The results of this study enhance our understanding of organic aerosol processes on microscopic scales and may have important implications for the modeling of atmospheric aerosol growth, composition and interactions with trace gases and clouds.Engineering and Physical Sciences Research Council (Career Acceleration Fellowship (Grant ID: EP/I003983/1), Prize studentship), Natural Environment Research Council (Studentship NE/J500070/1), European Research Council (Grant ID: 279405), Max Planck Society, European Union project PEGASOS (Grant ID: 265148

Supporting the consumption and co-authoring of locative media experiences for a rural village community: design and field trial evaluation of the SHARC2.0 framework

Locative Media Experiences (LMEs) have significant potential in enabling visitors to engage with the places that they visit through an appreciation of local history. For example, a visitor to Berlin that is exploring remnants of the Berlin Wall may be encouraged to appreciate (or in part experience) the falling of the Berlin wall by consuming multimedia directly related to her current location such as listening to audio recordings of the assembled crowds on 10th November 1989. However, despite the growing popularity of enabling technologies (such as GPS-equipped smart phones and tablets), the availability of tools that support the authoring of LMEs is limited. In addition, mobile apps that support the consumption of LMEs typically adopt an approach that precludes users from being able to respond with their own multimedia contributions. In this article we describe the design and evaluation of the SHARC2.0 framework that has been developed as part of our long-term and participatory engagement with the rural village of Wray in the north of England. Wray has very limited cellular data coverage which has placed a requirement on the framework and associated tools to operate without reliance on network connectivity. A field study is presented which featured a LME relating to Wray’s local history and which contained multimedia content contributed by members of the community including historic photos (taken from an existing ‘Digital Noticeboard’ system), audio-clips (from a local historian and village residents) and video (contributed during a design workshop). The novelty of our approach relates to the ability of multiple authors to contribute to a LME in-situ, and the utilisation of personal cloud storage for storing the contents associated with a multi-authored LME

Current status and future development of solvent-based carbon capture

Solvent-based carbon capture is the most commercially-ready technology for economically and sustainably reaching carbon emission reduction targets in the power sector. Globally, the technology has been deployed to deal with flue gases from large scale power plants and different carbon-intensive industries. The success of the technology is due to significant R&D activities on the process development and decades of industrial experience on acid gas removal processes from gaseous mixtures. In this paper, current status of PCC based on chemical absorption—commercial deployment and demonstration projects, analysis of different solvents and process configurations—is reviewed. Although some successes have been recorded in developing this technology, its commercialization has been generally slow as evidenced in the cancellation of high profile projects across the world. This is partly due to the huge cost burden of the technology and unpredictable government policies. Different research directions, namely new process development involving process intensification, new solvent development and a combination of both, are discussed in this paper as possible pathways for reducing the huge cost of the technology

Restrained Th17 response and myeloid cell infiltration into the central nervous system by human decidua-derived mesenchymal stem cells during experimental autoimmune encephalomyelitis

Background: Multiple sclerosis is a widespread inflammatory demyelinating disease. Several immunomodulatory therapies are available, including interferon-β, glatiramer acetate, natalizumab, fingolimod, and mitoxantrone. Although useful to delay disease progression, they do not provide a definitive cure and are associated with some undesirable side-effects. Accordingly, the search for new therapeutic methods constitutes an active investigation field. The use of mesenchymal stem cells (MSCs) to modify the disease course is currently the subject of intense interest. Decidua-derived MSCs (DMSCs) are a cell population obtained from human placental extraembryonic membranes able to differentiate into the three germ layers. This study explores the therapeutic potential of DMSCs. Methods: We used the experimental autoimmune encephalomyelitis (EAE) animal model to evaluate the effect of DMSCs on clinical signs of the disease and on the presence of inflammatory infiltrates in the central nervous system. We also compared the inflammatory profile of spleen T cells from DMSC-treated mice with that of EAE control animals, and the influence of DMSCs on the in vitro definition of the Th17 phenotype. Furthermore, we analyzed the effects on the presence of some critical cell types in central nervous system infiltrates. Results: Preventive intraperitoneal injection of DMSCs resulted in a significant delay of external signs of EAE. In addition, treatment of animals already presenting with moderate symptoms resulted in mild EAE with reduced disease scores. Besides decreased inflammatory infiltration, diminished percentages of CD4+IL17+, CD11b+Ly6G+ and CD11b+Ly6C+ cells were found in infiltrates of treated animals. Early immune response was mitigated, with spleen cells of DMSC-treated mice displaying low proliferative response to antigen, decreased production of interleukin (IL)-17, and increased production of the anti-inflammatory cytokines IL-4 and IL-10. Moreover, lower RORγT and higher GATA-3 expression levels were detected in DMSC-treated mice. DMSCs also showed a detrimental influence on the in vitro definition of the Th17 phenotype. Conclusions: DMSCs modulated the clinical course of EAE, modified the frequency and cell composition of the central nervous system infiltrates during the disease, and mediated an impairment of Th17 phenotype establishment in favor of the Th2 subtype. These results suggest that DMSCs might provide a new cell-based therapy for the control of multiple sclerosis.This work was sponsored by grants from Acción Estratégica en Salud (PI13/00297 and PI11/00581), the Neurosciences and Aging Foundation, the Francisco Soria Melguizo Foundation, Octopharma, and Parkinson Madrid (PI2012/0032).S

Antimicrobial consumption and resistance in adult hospital inpatients in 53 countries:results of an internet-based global point prevalence survey

Summary: Background: The Global Point Prevalence Survey (Global-PPS) established an international network of hospitals to measure antimicrobial prescribing and resistance worldwide. We aimed to assess antimicrobial prescribing and resistance in hospital inpatients. Methods: We used a standardised surveillance method to collect detailed data about antimicrobial prescribing and resistance from hospitals worldwide, which were grouped by UN region. The internet-based survey included all inpatients (adults, children, and neonates) receiving an antimicrobial who were on the ward at 0800 h on one specific day between January and September, 2015. Hospitals were classified as primary, secondary, tertiary (including infectious diseases hospitals), and paediatric hospitals. Five main ward types were defined: medical wards, surgical wards, intensive-care units, haematology oncology wards, and medical transplantation (bone marrow or solid transplants) wards. Data recorded included patient characteristics, antimicrobials received, diagnosis, therapeutic indication according to predefined lists, and markers of prescribing quality (eg, whether a stop or review date were recorded, and whether local prescribing guidelines existed and were adhered to). We report findings for adult inpatients. Findings: The Global-PPS for 2015 included adult data from 303 hospitals in 53 countries, including eight lower-middle-income and 17 upper-middle-income countries. 86 776 inpatients were admitted to 3315 adult wards, of whom 29 891 (34·4%) received at least one antimicrobial. 41 213 antimicrobial prescriptions were issued, of which 36 792 (89·3%) were antibacterial agents for systemic use. The top three antibiotics prescribed worldwide were penicillins with β-lactamase inhibitors, third-generation cephalosporins, and fluoroquinolones. Carbapenems were most frequently prescribed in Latin America and west and central Asia. Of patients who received at least one antimicrobial, 5926 (19·8%) received a targeted antibacterial treatment for systemic use, and 1769 (5·9%) received a treatment targeting at least one multidrug-resistant organism. The frequency of health-care-associated infections was highest in Latin America (1518 [11·9%]) and east and south Asia (5363 [10·1%]). Overall, the reason for treatment was recorded in 31 694 (76·9%) of antimicrobial prescriptions, and a stop or review date in 15 778 (38·3%). Local antibiotic guidelines were missing for 7050 (19·2%) of the 36 792 antibiotic prescriptions, and guideline compliance was 77·4%. Interpretation: The Global-PPS showed that worldwide surveillance can be accomplished with voluntary participation. It provided quantifiable measures to assess and compare the quantity and quality of antibiotic prescribing and resistance in hospital patients worldwide. These data will help to improve the quality of antibiotic prescribing through education and practice changes, particularly in low-income and middle-income countries that have no tools to monitor antibiotic prescribing in hospitals. Funding: bioMérieux

The ACTIVE cognitive training trial and predicted medical expenditures

<p>Abstract</p> <p>Background</p> <p>Health care expenditures for older adults are disproportionately high and increasing at both the individual and population levels. We evaluated the effects of the three cognitive training interventions (memory, reasoning, or speed of processing) in the ACTIVE study on changes in predicted medical care expenditures.</p> <p>Methods</p> <p>ACTIVE was a multisite randomized controlled trial of older adults (≥ 65). Five-year follow-up data were available for 1,804 of the 2,802 participants. Propensity score weighting was used to adjust for potential attrition bias. Changes in predicted annual<b/>medical expenditures were calculated at the first and fifth annual follow-up assessments using a new method for translating functional status scores. Multiple linear regression methods were used in this cost-offset analysis.</p> <p>Results</p> <p>At one and five years post-training, annual predicted expenditures declined<b/>by $223 (p = .024) and$128 (p = .309), respectively, in the speed of processing treatment group, but there were no statistically significant changes in the memory or reasoning treatment groups compared to the no-contact control group at either period. Statistical adjustment for age, race, education, MMSE scores, ADL and IADL performance scores, EPT scores, chronic condition counts, and the SF-36 PCS and MCS scores at baseline did not alter the one-year ($244; p = .012) or five-year ($143; p = .250) expenditure declines in the speed of processing treatment group.</p> <p>Conclusion</p> <p>The speed of processing intervention significantly reduced subsequent annual predicted medical care expenditures at the one-year post-baseline comparison, but annual savings were no longer statistically significant at the five-year post-baseline comparison.</p

The interaction of bacterial pathogens with platelets.

In recent years, the frequency of serious cardiovascular infections such as endocarditis has increased, particularly in association with nosocomially acquired antibiotic-resistant pathogens. Growing evidence suggests a crucial role for the interaction of bacteria with human platelets in the pathogenesis of cardiovascular infections. Here, we review the nature of the interactions between platelets and bacteria, and the role of these interactions in the pathogenesis of endocarditis and other cardiovascular diseases

Measurement of the tt¯ production cross-section as a function of jet multiplicity and jet transverse momentum in 7 TeV proton-proton collisions with the ATLAS detector

The tt¯ production cross-section dependence on jet multiplicity and jet transverse momentum is reported for proton-proton collisions at a centre-of-mass energy of 7 TeV in the single-lepton channel. The data were collected with the ATLAS detector at the CERN Large Hadron Collider and comprise the full 2011 data sample corresponding to an integrated luminosity of 4.6 fb−1. Differential cross-sections are presented as a function of the jet multiplicity for up to eight jets using jet transverse momentum thresholds of 25, 40, 60, and 80 GeV, and as a function of jet transverse momentum up to the fifth jet. The results are shown after background subtraction and corrections for all known detector effects, within a kinematic range closely matched to the experimental acceptance. Several QCD-based Monte Carlo models are compared with the results. Sensitivity to the parton shower modelling is found at the higher jet multiplicities, at high transverse momentum of the leading jet and in the transverse momentum spectrum of the fifth leading jet. The MC@NLO+HERWIG MC is found to predict too few events at higher jet multiplicities

Ivermectin for COVID-19 in adults in the community (PRINCIPLE): an open, randomised, controlled, adaptive platform trial of short- and longer-term outcomes

Background The evidence for whether ivermectin impacts recovery, hospital admissions, and longer-term outcomes in COVID-19 is contested. The WHO recommends its use only in the context of clinical trials. Methods In this multicentre, open-label, multi-arm, adaptive platform randomised controlled trial, we included participants aged ≥18 years in the community, with a positive SARS-CoV-2 test, and symptoms lasting ≤14 days. Participants were randomised to usual care, usual care plus ivermectin tablets (target 300-400 μg/kg per dose, once daily for 3 days), or usual care plus other interventions. Co-primary endpoints were time to first self-reported recovery, and COVID-19 related hospitalisation/death within 28 days, analysed using Bayesian models. Recovery at 6 months was the primary, longer term outcome. Trial registration: ISRCTN86534580. Findings The primary analysis included 8811 SARS-CoV-2 positive participants (median symptom duration 5 days), randomised to ivermectin (n=2157), usual care (n=3256), and other treatments (n=3398) from June 23, 2021 to July 1, 2022. Time to self-reported recovery was shorter in the ivermectin group compared with usual care (hazard ratio 1·15 [95% Bayesian credible interval, 1·07 to 1·23], median decrease 2.06 days [1·00 to 3·06]), probability of meaningful effect (pre-specified hazard ratio ≥1.2) 0·192). COVID-19-related hospitalisations/deaths (odds ratio 1·02 [0·63 to 1·62]; estimated percentage difference 0% [-1% to 0·6%]), serious adverse events (three and five respectively), and the proportion feeling fully recovered were similar in both groups at 6 months (74·3% and 71·2% respectively (RR = 1·05, [1·02 to 1·08]) and also at 3 and 12 months.,. Interpretation Ivermectin for COVID-19 is unlikely to provide clinically meaningful improvement in recovery, hospital admissions, or longer-term outcomes. Further trials of ivermectin for SARS-Cov-2 infection in vaccinated community populations appear unwarranted. Funding UKRI / National Institute of Health Research (MC_PC_19079)

Patient-specific cancer genes contribute to recurrently perturbed pathways and establish therapeutic vulnerabilities in esophageal adenocarcinoma

The identification of cancer-promoting genetic alterations is challenging particularly in highly unstable and heterogeneous cancers, such as esophageal adenocarcinoma (EAC). Here we describe a machine learning algorithm to identify cancer genes in individual patients considering all types of damaging alterations simultaneously. Analysing 261 EACs from the OCCAMS Consortium, we discover helper genes that, alongside well-known drivers, promote cancer. We confirm the robustness of our approach in 107 additional EACs. Unlike recurrent alterations of known drivers, these cancer helper genes are rare or patient-specific. However, they converge towards perturbations of well-known cancer processes. Recurrence of the same process perturbations, rather than individual genes, divides EACs into six clusters differing in their molecular and clinical features. Experimentally mimicking the alterations of predicted helper genes in cancer and pre-cancer cells validates their contribution to disease progression, while reverting their alterations reveals EAC acquired dependencies that can be exploited in therapy