Phenothiazinium photosensitisers XI. Improved toluidine blue photoantimicrobials.

The phenothiazinium derivative toluidine blue O (TBO) is widely employed as a photoantimicrobial agent in clinical trialling, particularly in dentistry. However, its activity against a range of pathogenic microbial species is not significantly different to that of the standard photoantimicrobial methylene blue. In the current study, derivatives of TBO with varying hydrocarbon substitution in chromophore position 2 were synthesised via the established anilinethiosulphonic route, using the mild oxidant silver(II) carbonate to allow substituent preservation. The resulting series of analogues demonstrated the expected increases in visible absorption wavelength and lipophilicity with increasing hydrocarbon content, as well as decreased aggregation for derivatives with bulkier substituents, and all produced singlet oxygen on illumination in vitro. Screening against a range of bacterial and fungal pathogens relevant to infection control showed remarkable increases in activity relative to the parent compound, particularly against the clinically important Gram-negative bacterium Pseudomonas aeruginosa. In addition, in order to demonstrate clinical relevance, the photoactivities of the new derivatives against microbial targets were compared to conventional antibacterial and antifungal drugs, as well as biocides commonly used for local disinfection. Activity here was also generally greater than that of the conventional agents used for comparison, considerably so relative to the local disinfectant agents

Observations and dynamical implications of active normal faulting in South Peru

SUMMARY Orogenic plateaus can exist in a delicate balance in which the buoyancy forces due to gravity acting on the high topography and thick crust of the plateau interior are balanced by the compressional forces acting across their forelands. Any shortening or extension within a plateau can indicate a perturbation to this force balance. In this study, we present new observations of the kinematics, morphology and slip rates of active normal faults in the South Peruvian Altiplano obtained from field studies, high-resolution DEMs, Quaternary dating and remote sensing. We then investigate the implications of this faulting for the forces acting on the Andes. We find that the mountains are extending ∼NNE–SSW to ∼NE–SW along a normal fault system that cuts obliquely across the Altiplano plateau, which in many places reactivates Miocene-age reverse faults. Radiocarbon dating of offset late Quaternary moraines and alluvial fan surfaces indicates horizontal extension rates across the fault system of between 1 and 4 mm yr–1—equivalent to an extensional strain rate in the range of 0.5–2 × 10−8 1 yr–1 averaged across the plateau. We suggest the rate and pattern of extension implies there has been a change in the forces exerted between the foreland and the Andes mountains. A reduction in the average shear stresses on the sub-Andean foreland detachment of ≲4 MPa (20–25 per cent of the total force) can account for the rate of extension. These results show that, within a mountain belt, the pattern of faulting is sensitive to small spatial and temporal variations in the strength of faults along their margins.Denman Baynes Senior Studentship, Clare College Cambridge Arup Santander Mobility Grant (University of Cambridge

Impact of COVID-19 on Obesity Management Services in the United Kingdom (The COMS-UK study)

Coronavirus Disease-2019 (COVID-19) has had a severe impact on all aspects of global healthcare delivery. This study aimed to investigate the nationwide impact of the pandemic on obesity management services in the UK in a questionnaire-based survey conducted of professionals involved in the delivery. A total of 168 clinicians took the survey; the majority of which maintained their usual clinical roles and were not redeployed except physicians and nurse specialists. Nearly all (97.8%) elective bariatric surgery was cancelled, 67.3% of units cancelled all multidisciplinary meeting activity, and the majority reduced clinics (69.6%). Most respondents anticipated that the services would recommence within 1–3 months. This study found that the COVID-19 pandemic has had a severe impact on the services involved in the management of patients suffering from severe, complex obesity in the UK

Reducing mortality and morbidity in patients with severe COVID-19 disease by advancing ongoing trials of Mesenchymal Stromal (stem) Cell (MSC) therapy - Achieving global consensus and visibility for cellular host-directed therapies

As of May 17th 2020, the novel coronavirus disease 2019 (COVID-19) pandemic has caused 307,395 deaths worldwide, out of 3,917,366 cases reported to the World Health Organization. No specific treatments for reducing mortality or morbidity are yet available. Deaths from COVID-19 will continue to rise globally until effective and appropriate treatments and/or vaccines are found. In search of effective treatments, the global medical, scientific, pharma and funding communities have rapidly initiated over 500 COVID-19 clinical trials on a range of antiviral drug regimens and repurposed drugs in various combinations. A paradigm shift is underway from the current focus of drug development targeting the pathogen, to advancing cellular Host-Directed Therapies (HDTs) for tackling the aberrant host immune and inflammatory responses which underlie the pathogenesis of SARS-CoV-2 and high COVID-19 mortality rates. We focus this editorial specifically on the background to, and the rationale for, the use and evaluation of mesenchymal stromal (Stem) cells (MSCs) in treatment trials of patients with severe COVID-19 disease. Currently, the ClinicalTrials.gov and the WHO Clinical Trials Registry Platform (WHO ICTRP) report a combined 28 trials exploring the potential of MSCs or their products for treatment of COVID-19. MSCs should also be trialed for treatment of other circulating WHO priority Blueprint pathogens such as MERS-CoV which causes upto 34% mortality rates. It's about time funding agencies invested more into development MSCs per se, and also for a range of other HDTs, in combination with other therapeutic interventions. MSC therapy could turn out to be an important contribution to bringing an end to the high COVID-19 death rates and preventing long-term functional disability in those who survive disease

Effect of a magnetosphere compression on Jovian radio emissions: in situ case study using Juno data

During its 53-day polar orbit around Jupiter, Juno often crosses the boundaries of the Jovian magnetosphere (namely the magnetopause and bow shock). From the boundary locations, the upstream solar wind dynamic pressure can be inferred, which in turn illustrates the state of compression or relaxation of the system. The aim of this study is to examine Jovian radio emissions during magnetospheric compressions, in order to determine the relationship between the solar wind and Jovian radio emissions. In this paper, we give a complete list of bow shock and magnetopause crossings (from June 2016 to August 2022), along with some extra informations (e.g. solar wind dynamic pressure and position of the standoff distances inferred from Joy et al. (2002)). We then select two compression events that occur in succession (inferred from magnetopause crossings) and we present a case study of the response of the Jovian radio emissions. We demonstrate that magnetospheric compressions lead to the activation of new radio sources. Newly activated broadband kilometric emissions are observed almost simultaneously to compression of the magnetosphere, with sources covering a large range of longitudes. Decametric emission sources are seen to be activated more than one rotation later only at specific longitudes and dusk local times. Finally, the activation of narrowband kilometric radiation is not observed during the compression phase, but when the magnetosphere is in its expansion phase

Young children's research: children aged 4-8 years finding solutions at home and at school

Children's research capacities have become increasingly recognised by adults, yet children remain excluded from the academy, with reports of their research participation generally located in adults' agenda. Such practice restricts children's freedom to make choices in matters affecting them, underestimates children’s capabilities and denies children particular rights. The present paper reports on one aspect of a small-scale critical ethnographic study adopting a constructivist grounded approach to conceptualise ways in which children's naturalistic behaviours may be perceived as research. The study builds on multi-disciplinary theoretical perspectives, embracing 'new' sociology, psychology, economics, philosophy and early childhood education and care (ECEC). Research questions include: 'What is the nature of ECEC research?' and 'Do children’s enquiries count as research?' Initially, data were collected from the academy: professional researchers (n=14) confirmed 'finding solutions' as a research behaviour and indicated children aged 4-8 years, their practitioners and primary carers as 'theoretical sampling'. Consequently, multi-modal case studies were constructed with children (n=138) and their practitioners (n=17) in three ‘good’ schools, with selected children and their primary carers also participating at home. This paper reports on data emerging from children aged 4-8 years at school (n=17) and at home (n=5). Outcomes indicate that participating children found diverse solutions to diverse problems, some of which they set themselves. Some solutions engaged children in high order thinking, whilst others did not; selecting resources and trialing activities engaged children in 'finding solutions'. Conversely, when children's time, provocations and activities were directed by adults, the quality of their solutions was limited, they focused on pleasing adults and their motivation to propose solutions decreased. In this study, professional researchers recognised 'finding solutions' as research behaviour and children aged 4-8 years naturalistically presented with capacities for finding solutions; however, the children's encounters with adults affected the solutions they found

Lithium-ion battery fast charging: A review

In the recent years, lithium-ion batteries have become the battery technology of choice for portable devices, electric vehicles and grid storage. While increasing numbers of car manufacturers are introducing electrified models into their offering, range anxiety and the length of time required to recharge the batteries are still a common concern. The high currents needed to accelerate the charging process have been known to reduce energy efficiency and cause accelerated capacity and power fade. Fast charging is a multiscale problem, therefore insights from atomic to system level are required to understand and improve fast charging performance. The present paper reviews the literature on the physical phenomena that limit battery charging speeds, the degradation mechanisms that commonly result from charging at high currents, and the approaches that have been proposed to address these issues. Special attention is paid to low temperature charging. Alternative fast charging protocols are presented and critically assessed. Safety implications are explored, including the potential influence of fast charging on thermal runaway characteristics. Finally, knowledge gaps are identified and recommendations are made for the direction of future research. The need to develop reliable in operando methods to detect lithium plating and mechanical degradation is highlighted. Robust model-based charging optimisation strategies are identified as key to enabling fast charging in all conditions. Thermal management strategies to both cool batteries during charging and preheat them in cold weather are acknowledged as critical, with a particular focus on techniques capable of achieving high speeds and good temperature homogeneities

A modified AUGIS/BOMSS Delphi process to establish research priorities in bariatric and metabolic surgery

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordBackground: Delphi methodology may be utilised to develop consensus opinion amongst a group of experts. The aim of our study was to use a modified Delphi process to determine the future research priorities amongbariatric and metabolic healthcare professionalsin the United Kingdom. Methods: Members of the Association of Upper Gastrointestinal Surgeons and the British Obesity and Metabolic Surgery Society (BOMSS) were invited to submit individual research questions viaan online survey (phase I). Two rounds of prioritisation by multidisciplinary expert healthcare professionals (phase II and III) were completed to determine a final list of high priority research questions. Results: Fifty-one bariatric and metabolic surgery-focused questions were identified in phase I. 35questions were taken forward for prioritisation in phase II. Eleven high priority questions were identified in phase III. The final list of high priority questions had an emphasis on the pathophysiology and long-term sequelae of bariatric and metabolic surgery.ConclusionA modified Delphi process has produced a list of 11 high priority research questions in bariatric and metabolic surgery. Future studies and awards from funding bodies should reflect this consensus list of prioritised questions in the interest of improving patient care and encouraging collaborative research across multiple centres