The management of tetanus in adults in an intensive care unit in Southern Vietnam

Background: Tetanus remains common in many low- and middle-income countries (LMICs) yet the evidence base guiding management of this disease is extremely limited, particularly with respect to contemporary management options. Sharing knowledge about practice may facilitate improvement in outcomes elsewhere. Methods: We describe clinical interventions and outcomes of 180 adult patients ≥16 years-old with tetanus enrolled in prospective observational studies at a specialist infectious diseases hospital in Southern Vietnam. Patients were treated according to a holistic management protocol encompassing wound-care, antitoxin, antibiotics, symptom control, airway management, nutrition and de-escalation criteria. Results: Mortality rate in our cohort was 2.8%, with 90 (50%) patients requiring mechanical ventilation for a median 16 [IQR 12-24] days. Median [IQR] duration of ICU stay was 15 [8-23] days. Autonomic nervous system dysfunction occurred in 45 (25%) patients. Hospital acquired infections occurred in 77 (43%) of patients. Conclusion: We report favourable outcomes for patients with tetanus in a single centre LMIC ICU, treated according to a holistic protocol. Nevertheless, many patients required prolonged intensive care support and hospital acquired infections were common

Screening fungi isolated from historic Discovery Hut on Ross Island, Antarctica for cellulose degradation

To survive in Antarctica, early explorers of Antarctica's Heroic Age erected wooden buildings and brought in large quantities of supplies. The introduction of wood and other organic materials may have provided new nutrient sources for fungi that were indigenous to Antarctica or were brought in with the materials. From 30 samples taken from Discovery Hut, 156 filamentous fungi were isolated on selective media. Of these, 108 were screened for hydrolytic activity on carboxymethyl cellulose, of which 29 demonstrated activities. Endo-1, 4-β-glucanase activity was confirmed in the extracellular supernatant from seven isolates when grown at 4°C, and also when they were grown at 15°C. Cladosporium oxysporum and Geomyces sp. were shown to grow on a variety of synthetic cellulose substrates and to use cellulose as a nutrient source at temperate and cold temperatures. The research findings from the present study demonstrate that Antarctic filamentous fungi isolated from a variety of substrates (wood, straw, and food stuffs) are capable of cellulose degradation and can grow well at low temperatures

Excess direct hospital cost of treating adult patients with ventilator associated respiratory infection (VARI) in Vietnam

INTRODUCTION: Ventilator associated respiratory infections (VARIs) are the most common hospital acquired infections in critical care worldwide. This work aims to estimate the total annual direct hospital cost of treating VARI throughout Vietnam. METHODS: A costing model was constructed to evaluate the excess cost of diagnostics and treatment of VARI in Vietnam. Model inputs included costs for extra lengths of stay, diagnostics, VARI incidence, utilisation of ventilators and antibiotic therapy. RESULTS: With the current VARI incidence rate of 21.7 episodes per 1000 ventilation-days, we estimated 34,428 VARI episodes in the 577 critical care units in Vietnam per year. The extra cost per VARI episode was $1,174.90 and the total annual excess cost was US$40.4 million. A 1% absolute reduction in VARI incidence density would save US$1.86 million annually. For each episode of VARI, the share of excess cost components was 45.1$117 per capita, VARI represents a substantial cost to the health service in Vietnam. Enhanced infection prevention and control and antimicrobial stewardship programmes should be implemented to reduce this

Excavations and the afterlife of a professional football stadium, Peel Park, Accrington, Lancashire: towards an archaeology of football

Association football is now a multi-billion dollar global industry whose emergence spans the post-medieval to the modern world. With its professional roots in late 19th-century industrial Lancashire, stadiums built for the professionalization of football first appear in frequency in the North of England. While many historians of sport focus on consumerism and ‘topophilia’ (attachment to place) regarding these local football grounds, archaeological research that has been conducted on the spectator experience suggests status differentiation within them. Our excavations at Peel Park confirm this impression while also showing a significant afterlife to this stadium, particularly through children’s play

Modelling upper respiratory viral load dynamics of SARS-CoV-2

Relationships between viral load, severity of illness, and transmissibility of virus, are fundamental to understanding pathogenesis and devising better therapeutic and prevention strategies for COVID-19. Here we present within-host modelling of viral load dynamics observed in the upper respiratory tract (URT), drawing upon 2172 serial measurements from 605 subjects, collected from 17 different studies. We developed a mechanistic model to describe viral load dynamics and host response, and contrast this with simpler mixed-effects regression analysis of peak viral load and its subsequent decline. We observed wide variation in URT viral load between individuals, over 5 orders of magnitude, at any given point in time since symptom onset. This variation was not explained by age, sex, or severity of illness, and these variables were not associated with the modelled early or late phases of immune-mediated control of viral load. We explored the application of the mechanistic model to identify measured immune responses associated with control of viral load. Neutralizing antibody correlated strongly with modelled immune-mediated control of viral load amongst subjects who produced neutralizing antibody. Our models can be used to identify host and viral factors which control URT viral load dynamics, informing future treatment and transmission blocking interventions

Empagliflozin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background Empagliflozin has been proposed as a treatment for COVID-19 on the basis of its anti-inflammatory, metabolic, and haemodynamic effects. The RECOVERY trial aimed to assess its safety and efficacy in patients admitted to hospital with COVID-19. Methods In the randomised, controlled, open-label RECOVERY trial, several possible treatments are compared with usual care in patients hospitalised with COVID-19. In this analysis, we assess eligible and consenting adults who were randomly allocated in a 1:1 ratio to either usual standard of care alone or usual standard of care plus oral empagliflozin 10 mg once daily for 28 days or until discharge (whichever came first) using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28-day mortality; secondary outcomes were duration of hospitalisation and (among participants not on invasive mechanical ventilation at baseline) the composite of invasive mechanical ventilation or death. On March 3, 2023 the independent data monitoring committee recommended that the investigators review the data and recruitment was consequently stopped on March 7, 2023. The ongoing RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings Between July 28, 2021 and March 6, 2023, 4271 patients were randomly allocated to receive either empagliflozin (2113 patients) or usual care alone (2158 patients). Primary and secondary outcome data were known for greater than 99% of randomly assigned patients. Overall, 289 (14%) of 2113 patients allocated to empagliflozin and 307 (14%) of 2158 patients allocated to usual care died within 28 days (rate ratio 0·96 [95% CI 0·82–1·13]; p=0·64). There was no evidence of significant differences in duration of hospitalisation (median 8 days for both groups) or the proportion of patients discharged from hospital alive within 28 days (1678 [79%] in the empagliflozin group vs 1677 [78%] in the usual care group; rate ratio 1·03 [95% CI 0·96–1·10]; p=0·44). Among those not on invasive mechanical ventilation at baseline, there was no evidence of a significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (338 [16%] of 2084 vs 371 [17%] of 2143; risk ratio 0·95 [95% CI 0·84–1·08]; p=0·44). Two serious adverse events believed to be related to empagliflozin were reported: both were ketosis without acidosis. Interpretation In adults hospitalised with COVID-19, empagliflozin was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death so is not indicated for the treatment of such patients unless there is an established indication due to a different condition such as diabetes. Funding UK Research and Innovation (Medical Research Council) and National Institute of Health Research (MC_PC_19056), and Wellcome Trust (222406/Z/20/Z)

Geospatial analysis and living urban geometry

This essay outlines how to incorporate morphological rules within the exigencies of our technological age. We propose using the current evolution of GIS (Geographical Information Systems) technologies beyond their original representational domain, towards predictive and dynamic spatial models that help in constructing the new discipline of "urban seeding". We condemn the high-rise tower block as an unsuitable typology for a living city, and propose to re-establish human-scale urban fabric that resembles the traditional city. Pedestrian presence, density, and movement all reveal that open space between modernist buildings is not urban at all, but neither is the open space found in today's sprawling suburbs. True urban space contains and encourages pedestrian interactions, and has to be designed and built according to specific rules. The opposition between traditional self-organized versus modernist planned cities challenges the very core of the urban planning discipline. Planning has to be re-framed from being a tool creating a fixed future to become a visionary adaptive tool of dynamic states in evolution

MOOC for AR VR training: obstacles, challenges and Usability

This paper provides a case study of massive open online course (MOOC) for augmented reality (AR) and virtual reality (VR). The research studies the obstacles, challenges and usability issues entailed in the management of a novel MOOC for AR and VR training. The electronic learning form of MOOC has been adapted and made available for a number of universities and organizations. It brings learning opportunities for university students and industrial professionals to go through online-based courses on their own pace, and some MOOCs provide certifications for specialized subjects. However, the nature of working on AR and VR requires specialized equipment such as mobile tablets with high computing capability, workstation with fast graphic processing units (GPU) and head-mount-devices (HMD). This case study investigation outlines an overview of the potential obstacles and issues with the intention of how MOOC addresses best practices and the fundamental requirements of AR and VR training

SLC6A14, a Pivotal Actor on Cancer Stage: When Function Meets Structure

SLC6A14 (ATB0,+) is a sodium- and chloride-dependent neutral and dibasic amino acid transporter that regulates the distribution of amino acids across cell membranes. The transporter is overexpressed in many human cancers characterized by an increased demand for amino acids; as such, it was recently acknowledged as a novel target for cancer therapy. The knowledge on the molecular mechanism of SLC6A14 transport is still limited, but some elegant studies on related transporters report the involvement of the 12 transmembrane \u3b1-helices in the transport mechanism, and describe structural rearrangements mediated by electrostatic interactions with some pivotal gating residues. In the present work, we constructed a SLC6A14 model in outward-facing conformation via homology modeling and used molecular dynamics simulations to predict amino acid residues critical for substrate recognition and translocation. We docked the proteinogenic amino acids and other known substrates in the SLC6A14 binding site to study both gating regions and the exposed residues involved in transport. Interestingly, some of these residues correspond to those previously identified in other LeuT-fold transporters; however, we could also identify a novel relevant residue with such function. For the first time, by combined approaches of molecular docking and molecular dynamics simulations, we highlight the potential role of these residues in neutral amino acid transport. This novel information unravels new aspects of the human SLC6A14 structure-function relationship and may have important outcomes for cancer treatment through the design of novel inhibitors of SLC6A14-mediated transport