COVID-19 and globalization

The world is experiencing a major pandemic caused by SARS-CoV-2, the Coronavirus causing COVID-19. This disease first entered the human population in Hubei province, China, in mid-November 2019 and manifested in Wuhan, the largest metropolitan area of Hubei, when a cluster of patients were admitted to hospital with a ‘severe pneumonia of unknown cause’ in early December. Although humanity has survived previous pandemics by infectious agents, the present one is unprecedented in its capacity to take advantage of modern globalization allowing for massive transborder spread at a surprising speed. When writing these lines, the pandemic affects 181 countries and territories, with around 1,084,000 infected subjects, more than 58,000 deaths and 225,000 recovered patients, according to the Johns Hopkins University

A review of ventilation opening area terminology

This is the author accepted manuscript. The final version is available from Elsevier via https://doi.org/10.1016/j.enbuild.2016.02.053The design of a natural ventilation strategy requires the establishment of the location and size of a series of purpose provided ventilation openings (PPOs). The success of the design is dependent on knowledge of the aerodynamic performance of the PPOs often described by their geometry (normally an area) and resistance to airflow. The incorrect interpretation of this information can lead inappropriate ventilation strategies and buildings that overheat and have an excessive energy demand. Many definitions of PPO area are used by standards, guidelines, text books, and software tools. Each can be assigned multiple terms and a single term can be assigned to different definitions. There is evidence that this leads to errors in practice. An effective area of a PPO, defined as the product of its discharge coefficient and its free area, is proposed as a standard description because it is unambiguous and its measurement is governed by recognised standards. It is hoped that PPO manufacturers will provide an effective area as standard and that its use will be recognised as best practice. It is intended that these steps will reduce design errors and lead to successful natural ventilation strategies and better building

Changing practice to support self-management and recovery in mental illness: application of an implementation model

Author Version made available in accordance with the publisher's policyHealth services introducing practice changes need effective implementation methods. Within the setting of a community mental health service offering recovery-oriented psychosocial support for people with mental illness, we aimed to (a) identify a well-founded implementation model and (b) assess its practical usefulness in introducing a new program for recovery-oriented self-management support. We reviewed the literature to identify implementation models applicable to community mental health, and having corresponding measurement tools. We used one of these models to inform organisational change strategies. The literature review showed few models with corresponding tools. The Promoting Action on Research Implementation in Health Services (PARIHS) model and the related Organizational Readiness to Change Assessment (ORCA) tool were used. PARIHS proposes prerequisites for health service change and the ORCA measures the extent to which these prerequisites are present. Application of the ORCA at two time points during implementation of the new program showed strategy-related gains for some prerequisites but not for others, reflecting observed implementation progress. Additional strategies to address target prerequisites could be drawn from the PARIHS model. The PARIHS model and ORCA tool have potential in designing and monitoring practice change strategies in community mental health. Further practical use and testing of implementation models appears justified in overcoming barriers to change

Measurement of ventilation effectiveness and indoor air quality in toilets at mass gathering events

Mass gathering events were closed in 2020 to reduce the spread of SARS-CoV-2. These events included music concerts, theatre shows, and sports matches. It is known, however, that the long-range aerosol transmission of pathogens, such as SARS-CoV-2, can be reduced with sufficient ventilation indoors. This paper examines the risk of reopening these mass gathering events by measuring the CO2 concentration, as a proxy for ventilation effectiveness, at 58 events, with a specific focus on small enclosed spaces with short occupancy. Toilets (sanitary accommodation) are spaces that are densely and continuously occupied for short durations throughout the events, such as during theatre intervals or half-time at sports events. The results showed that the average air quality in toilets was good at most events. There were, however, considerable peaks in CO2 concentration of up to 3431 ppm in toilets at times when occupancy was presumed high, indicating that the risk of exposure to exhaled breath, which may contain virus-laden aerosols, is higher in toilets than elsewhere in the venue (although occupancy duration will be much lower). Recommendations are provided to encourage building designers and operators to be mindful of the ventilation strategies used in toilets given their occupancy and size

Carcinogenic liver fluke secretes extracellular vesicles that promote cholangiocytes to adopt a tumorigenic phenotype

Background. Throughout Asia there is an unprecedented link between cholangiocarcinoma and infection with the liver fluke Opisthorchis viverrini. Multiple processes including chronic inflammation and secretion of parasite proteins into the biliary epithelium drive infection towards cancer. Until now, the mechanism and effects of parasite protein entry into cholangiocytes was unknown. Methods. Various microscopy techniques were used to identify O. viverrini extracellular vesicles (EVs) and their internalization by human cholangiocytes. Using mass spectrometry we characterised the EV proteome and associated changes in cholangiocytes after EV uptake, and detected EV proteins in bile of infected hamsters and humans. Cholangiocyte proliferation and IL-6 secretion was measured to assess the impact of EV internalization. Results. EVs were identified in fluke culture medium and bile of infected hosts. EVs internalized by cholangiocytes drove cell proliferation and IL-6 secretion and induced changes in protein expression associated with endocytosis, wound repair and cancer. Antibodies to an O. viverrinitetraspanin blocked EV uptake and IL-6 secretion by cholangiocytes. Conclusions. This is the first time that EVs from a multicellular pathogen have been identified in host tissues. Our findings imply a role for O. viverrini EVs in pathogenesis and highlight an approach to vaccine development for this infectious cancer

The utility of implantable loop recorders in patient management: an age- and indication-stratified study in the outpatient-implant era

INTRODUCTION: Implantable loop recorders (ILR) are now routinely implanted for long-term cardiac monitoring in the clinic setting. This study examined the real-world performance of these devices, focusing on the management decision changes made in response to ILR-recorded data. METHODS AND RESULTS: This was a single centre, prospective observational study of consecutive patients undergoing ILR implantation. All patients who underwent implantation of a Medtronic Reveal LINQ device from September 2017 to June 2019 at Barts Heart Centre were included.501 patients were included. 302 (60%) patients underwent ILR implantation for an indication of pre-syncope/syncope, 96 (19%) for palpitations, 72 (14%) for atrial fibrillation (AF) detection with a history of cryptogenic stroke and 31 (6%) for patients deemed to be high risk of serious cardiac arrhythmia.The primary outcome of this study was that an ILR-derived diagnosis altered management in 110 (22%) of patients. Secondary outcomes concerned sub-group analyses by indication: in patients who presented with syncope/presyncope, a change in management resulting from ILR data was positively associated with age (HR: 1.04 [95%CI 1.02-1.06]; p < 0.001) and negatively associated with a normal ECG at baseline (HR 0.54 [0.31-0.93]; p = 0.03). Few patients (1/57, 2%) aged < 40 years in this group underwent device implantation, compared to 19/62 patients (31%) aged 75 years and over (p = 0.0024). 22/183 (12%) of patients in the 40-74 age range had a device implanted.In patients who underwent ILR insertion following cryptogenic stroke, 13/72 patients (18%) had AF detected leading to a decision to commence anticoagulation. CONCLUSION: These results inform the utility of ILR in the clinical setting. Diagnoses provided by ILR that lead to changes in management are rare in patients under age 40, particularly following syncope, presyncope or palpitations. In older patients new diagnoses are frequently made and trigger important changes in treatment

Neonatal features of the Prader-Willi syndrome; the case for making the diagnosis during the first week of life

Early diagnosis is of proven benefit in Prader-Willi syndrome (PWS). We therefore examined key perinatal features to aid early recognition. Data were collected from case records of subjects attending a multi-disciplinary clinic and from a retrospective birth questionnaire. Ninety patients (54 male: 36 female) were seen between 1991-2015, most with paternal deletion (n=56) or maternal isodisomy (n=26). Features included cryptorchidism in 94% males, preterm birth (26%), birthweight &lt;2500g (24%), polyhydramnios (23%), breech presentation (23%) and need for nasogastric feeding (83%). Reduced fetal movements (FM) occurred in 82.5% patients compared with 4% healthy siblings. Of 35 children born since 1999, 23 were diagnosed clinically within 28 days while diagnosis in 12 was &gt; 28 days: 1-12 months in 7; and 3.75-10.5 years in 5. Typical PWS features in these 12 infants included hypotonia (100%), feeding difficulties (75%), cryptorchidism (83% males) and reduced FM (66%). Causes other than PWS including neuromuscular disease were considered in nine patients. Neonatal hypotonia, reduced FM, feeding difficulties and cryptorchidism should immediately suggest PWS, yet late diagnosis continues in some cases. Awareness of the typical features of PWS in newborn units is required to allow prompt detection even in the presence of confounding factors such as prematurity

A Case of Urogenital Human Schistosomiasis from a Non-endemic Area

© 2015 Calvo-Cano et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article

Metabolomics and lipidomics reveal perturbation of sphingolipid metabolism by a novel anti-trypanosomal 3-(oxazolo[4,5-b]pyridine-2-yl)anilide

Introduction: Trypanosoma brucei is the causative agent of human African trypanosomiasis, which is responsible for thousands of deaths every year. Current therapies are limited and there is an urgent need to develop new drugs. The anti-trypanosomal compound, 3-(oxazolo[4,5-b]pyridine-2-yl)anilide (OXPA), was initially identified in a phenotypic screen and subsequently optimized by structure–activity directed medicinal chemistry. It has been shown to be non-toxic and to be active against a number of trypanosomatid parasites. However, nothing is known about its mechanism of action. Objective: Here, we have utilized an untargeted metabolomics approach to investigate the biochemical effects and potential mode of action of this compound in T. brucei. Methods: Total metabolite extracts were analysed by HILIC-chromatography coupled to high resolution mass spectrometry. Results: Significant accumulation of ceramides was observed in OXPA-treated T. brucei. To further understand drug-induced changes in lipid metabolism, a lipidomics method was developed which enables the measurement of hundreds of lipids with high throughput and precision. The application of this LC–MS based approach to cultured bloodstream-form T. brucei putatively identified over 500 lipids in the parasite including glycerophospholipids, sphingolipids and fatty acyls, and confirmed the OXPA-induced accumulation of ceramides. Labelling with BODIPY-ceramide further confirmed the ceramide accumulation following drug treatment. Conclusion: These findings clearly demonstrate perturbation of ceramide metabolism by OXPA and indicate that the sphingolipid pathway is a promising drug target in T. brucei.No Full Tex

Tracing the mercury in the UK atmosphere – peaks and sources

During 2013 total gaseous mercury was monitored at the Auchencorth Moss and Harwell field sites, which are run by the UK’s Centre for Ecology & Hydrology and Ricardo-AEA respectively on behalf of the UK Department for the Environment, Food and Rural Affairs as part of the UK rural heavy metals monitoring network. The sites are the two UK EMEP supersites, part of the cooperative programme for monitoring and evaluation of long-range transmission of air pollutants in Europe. Auchencorth was first established in 1995, and is operated to EMEP level III. It is located about 20 km south-west of Edinburgh (55.450 N, 3.150 W). This is a rural, upland peat site with a large, uniform fetch. Harwell has had air monitoring since the 1970s, and is operated at EMEP level II, located about 26 km south of the city of Oxford (51.571 N, 1.325 W). This is a semi-rural site located near the Harwell Science and Innovation Campus. The Tekran mercury analyser (Model 2537A, Tekran Inc.), is used to measure TGM in air at both sites. It is run at a resolution of 5 minutes, using dual channels allowing for continuous monitoring. Observed concentrations of TGM is at the lower end of the northern hemispherical background level of 1.4-1.7 ng m-3 observed at other sites. The annual averages of TGM for 2013 for Auchencorth and Harwell respectively are: 1.33 and 1.45 ng m-3. Using measurements of other atmospheric species from colocated instruments, we have used the OpenAir Statistical Package for R, to analyse the influence of point sources on observations, specifically looking at the closure of coal fired power stations at Cockenzie and Didcot for Auchencorth and Harwell respectively, which were located within the local area. We also use air mass back trajectories and cluster analysis to assess the long range transport of mercury to the sites, investigating repeated episodic peak events of up to 2.8 ng m-3 observed at both sites during spring 2013