Early Versus Late Tracheostomy for Patients with High and Low Cervical Spinal Cord Injuries

Objectives: This study aimed to evaluate the effects of early versus late tracheostomies among patients with cervical spinal cord injuries (CSCIs). Methods: This retrospective study included 69 adult CSCI patients who underwent bedside percutaneous tracheostomies at the Intensive Care Unit of Khoula Hospital, Muscat, Oman, between January 2011 and October 2015. The tracheostomy was considered early if the procedure took place within one week of the CSCI. The impact of an early tracheostomy on patient outcomes was analysed in terms of duration of mechanical ventilation and intensive care unit (ICU) stay among patients with high (C1–C2 vertebrae) and low (C3–C7 vertebrae) CSCIs. Ventilator dependence, bradycardia episodes and surgical intervention outcomes were also examined. Results: Patients with a high CSCI who underwent an early tracheostomy spent significantly fewer days on mechanical ventilation compared to those who underwent a late tracheostomy (9.3 ± 7.2 days versus 13.7 ± 3.2 days; P = 0.041). Low CSCI patients who received an early tracheostomy also experienced significantly fewer days on mechanical ventilation compared to those undergoing a late tracheostomy (12.1 ± 10.4 days versus 25.2 ± 17.7 days; P = 0.035). Moreover, ICU mortality was significantly lower for high CSCI patients who underwent an early tracheostomy (P = 0.015). However, there was no association between length of ICU stay and either type of CSCI or timing of the tracheostomy procedure. Conclusion: An early tracheostomy is beneficial in reducing the duration of mechanical ventilation among patients with CSCIs, irrespective of the level of injury

Proteorhodopsin Phototrophy Promotes Survival of Marine Bacteria during Starvation

Mutational analysis provides direct evidence for the link between proteorhodopsin light-harvesting and enhanced survival of marine bacteria

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

A Prospective Study on Diabetic Retinopathy Detection Based on Modify Convolutional Neural Network Using Fundus Images at Sindh Institute of Ophthalmology & Visual Sciences

Diabetic Retinopathy (DR) is the most common complication that arises due to diabetes, and it affects the retina. It is the leading cause of blindness globally, and early detection can protect patients from losing sight. However, the early detection of Diabetic Retinopathy is an difficult task that needs clinical experts’ interpretation of fundus images. In this study, a deep learning model was trained and validated on a private dataset and tested in real time at the Sindh Institute of Ophthalmology & Visual Sciences (SIOVS). The intelligent model evaluated the quality of the test images. The implemented model classified the test images into DR-Positive and DR-Negative ones. Furthermore, the results were reviewed by clinical experts to assess the model’s performance. A total number of 398 patients, including 232 male and 166 female patients, were screened for five weeks. The model achieves 93.72% accuracy, 97.30% sensitivity, and 92.90% specificity on the test data as labelled by clinical experts on Diabetic Retinopathy

Regulation of proteorhodopsin phototrophy in the flavobacterium Dokdonia sp. MED134

17th Ocean Sciences Meeting, 23-28 February 2014, Honolulu, Hawaii USARecent advances reveal the benefit of proteorhodopsin (PR) phototrophy for promoting growth and survival in marine bacteria. Still, the metabolic pathways actually mediating these light responses remain unknown. We therefore investigated metabolic activities and gene expression patterns in Dokdonia sp. MED134 growing in seawater with low concentrations of complex (yeast extract and peptone) or simple (alanine) dissolved organic carbon (DOC). Remarkably, anaplerotic CO2 fixation supplied 30% of the carbon demand in these carbon-limited cultures, with much stronger light responses in alanine. Expression analysis of 11 key genes in bicarbonate uptake, anaplerotic CO2 fixation and TCA cycle pathways showed the PR gene was up-regulated 40-fold in the light, independently of DOC source. Strikingly, the two genes in the glyoxylate shunt (icl and ms) were up-regulated 40- to 100-fold in the light – but only in seawater with alanine. This implies the glyoxylate shunt, which is widespread in marine bacteria, efficiently allows house holding with carbon when PR phototrophy provides ATP. Thus, regulatory interactions between DOC quality and central metabolic pathways critically determine the fitness of surface ocean bacteria engaging in PR phototrophyPeer Reviewe

Synthesis and characterization of nanohybrid materials based on block copolymers and clays

Η ανάμειξη ανόργανων υλικών με πολυμερή οδηγεί στην παρασκευή σύνθετων υλικών τα οποία παρουσιάζουν βελτιωμένες ιδιότητες σε σχέση με τα αρχικά συστατικά. Μια σημαντική κατηγορία τέτοιων σύνθετων υλικών αποτελούν τα νανοσύνθετα υλικά στα οποία το ανόργανο πρόσθετο έχει τουλάχιστον μια διάσταση της τάξης του νανομέτρου. Σε αυτήν την κατηγορία ανήκουν τα υβρίδια που προκύπτουν από την ανάμειξη πολυμερών με πολυστρωματικούς πυριτιούχους πηλούς. Τα υλικά αυτά εμφανίζουν ανάλογα με τη δομή του σύνθετου υλικού υψηλότερη θερμική αντοχή και καλύτερες μηχανικές ιδιότητες ενώ συγχρόνως διατηρούν πλεονεκτήματα των αρχικών πολυμερών, όπως η διαφάνεια ή η ευκολία στην κατεργασία . Αντικείμενο της παρούσας εργασίας είναι η σύνθεση και η μελέτη των αλληλεπιδράσεων και των ιδιοτήτων νανοσύνθετων υλικών που αποτελούνται από πολυστρωματικούς πυριτιούχους πηλούς και δισυσταδικά συμπολυμερή πολυαιθυλενοξειδίου-πολυστυρενίου (PEO-b-PS). Ο πηλός που χρησιμοποιήθηκε ήταν ο φυσικός υδρόφιλος μοντμοριλλονίτης νατρίου (Na+) ενώ τα συμπολυμερή συντέθηκαν στο εργαστήριο με τη χρήση ελεγχόμενου ριζικού πολυμερισμού. Από την βιβλιογραφία είναι γνωστό ότι το ομοπολυμερές του PEO έχει την δυνατότητα παρεμβολής ανάμεσα στα στρώματα του μοντμοριλλονίτη Νa+καθώς είναι υδρόφιλο μόριο και επομένως οι αλληλεπιδράσεις του με την επιφάνεια του πηλού είναι ευνοϊκές. Αντίθετα το ομοπολυμερές του PS είναι υδρόφοβο με αποτέλεσμα οι αλληλεπιδράσεις του με τον πηλό να είναι μη ευνοϊκές και επομένως δεν δίνει δομές παρεμβολής αλλά φασικά διαχωρισμένες δομές. Σκοπός της εργασίας αυτής είναι να μελετήσει τι συμβαίνει στην περίπτωση των αμφίφιλων συμπολυμερών PEO-b-PS. Ποιες είναι οι συνολικές αλληλεπιδράσεις των συμπολυμερών με τον φυσικό υδρόφιλο μοντμοριλλονίτη και ποια η δομή των νανοσύνθετων υλικών που προκύπτουν. Ειδικότερα εξετάστηκε η επίδραση του μοριακού βάρους και της σύστασης των συμπολυμερών στην τελική δομή των νανοσύνθετων υλικών. Για τον σκοπό αυτό αρχικά συντέθηκαν επτά συμπολυμερή PEO-b-PS με ελεγχόμενο ριζικό πολυμερισμό μεταφοράς ατόμου (Atom Transfer Radical Polymerization, ATRP) και στην συνέχεια τα πολυμερή χαρακτηρίσθηκαν ως προς το μοριακό βάρος, την κατανομή μοριακών βαρών και την σύστασή τους. Μελετήθηκαν επίσης οι θερμικές ιδιότητες των πολυμερών και η θερμοδυναμική τους κατάσταση. Για την παρασκευή των νανοσύνθετων υλικών χρησιμοποιήθηκε η μέθοδος παρεμβολής τήγματος πολυμερούς. Στην συνέχεια χρησιμοποιήθηκε περίθλαση ακτίνων Χ για την μελέτη της δομής τους και για την εύρεση της διαστρωματικής τους απόστασης. Βρέθηκε ότι η δομή που εμφανίζουν τα νανοϋβρίδια είναι δομή παρεμβολής με διαστρωματικές αποστάσεις που μοιάζουν με αυτές που εμφανίζει το ομοπολυμερές PEO όταν αναμειγνύεται με το ίδιο ανόργανο υλικό και φαίνεται ότι ο λόγος που καθορίζει την τελική δομή σε όλες τις περιπτώσεις είναι η σύσταση PEO ως προς Na+. Για να ερευνηθεί ο ρόλος που παίζει η συστάδα του PS σε όλη την διαδικασία μελετήθηκαν οι αλληλεπιδράσεις που αναπτύσσονται ανάμεσα στις συστάδες του συμπολυμερούς και της ανόργανης επιφάνειας με την βοήθεια φασματοσκοπίας υπερύθρου. Τέλος, μελετήθηκε ο φθορισμός της συστάδας του πολυστυρενίου και η επίδραση που έχει σε αυτόν η θέση του πολυστυρενίου στο σύστημα. Η τεχνική που χρησιμοποιήθηκε για τον σκοπό αυτό είναι η φθορισμομετρία η οποία έδειξε ότι ο εγγενής φθορισμός του πολυστυρενίου χάνεται όταν αυτό βρίσκεται περιορισμένο μεταξύ των στρωμάτων του ανόργανου υλικού. Στην περίπτωση των νανοσύνθετων υλικών Na+/PEO-b-PS ο φθορισμός του PS είναι μετρήσιμος, γεγονός που αποδεικνύει ότι η συστάδα του PS βρίσκεται έξω από τις γαλαρίες.Mixing polymers with inorganic materials leads to the synthesis of composites, which have improved properties with respect to the original materials. An important category among them, are the nanohybrids in which the inorganic component has at least one dimension at the nanometer scale. This category includes hybrids that are formed by mixing polymers with layered silicate clays. Such materials exhibit (depending on their structure) high thermal resistance and improved mechanical properties, whereas they retain the advantages of the initial polymers, such as the transparency or the easy processability. The purpose of the present project is the synthesis and the study of the interactions and the properties of nanocomposite materials which consist of layered silicate clays and poly(ethylene oxide)-b-poly(styrene) (PEO-b-PS) diblock copolymers. The clay used is a natural hydrophilic sodium montmorillonite (Na+) whereas the copolymers were synthesized in the lab, in the framework of this work, utilizing controlled radical polymerization. It is well known from the literature that the PEO homopolymer has the ability to intercalate between the layers of the clay, as it is hydrophilic molecule, therefore has favorable interactions with the surface of the clay. On the other hand, the PS homopolymer is hydrophobic molecule and has unfavorable interactions with the clay, leading to phase separated structures. This study is focalized in the case of PEO-b-PS amphiphilic copolymers. The total interactions of the copolymers with the natural montmorillonite as well as the structure of the resulted nanocomposite materials are investigated. Especially, the influence of the molecular weight and the concentration of the copolymers to the final structure of the nanocomposite materials is examined in detail. Seven PEO-b-PS copolymers with varying molecular weight and composition were synthesized utilizing controlled Atom Transfer Radical Polymerization (ATRP). Their molecular weight and their polydispersity were evaluated with Size Exclusion Chromatography (SEC) whereas their composition was measured with 1H Nuclear Magnetic Resonance (1H NMR). The thermal properties and the thermodynamic condition of the polymers were also studied with Differential Scanning Calorimetry (DSC) and Small Angle X-ray Scattering (SAXS) respectively. For the preparation of the nanocomposite materials, the polymer melt intercalation method was used and hybrids with composition that varied from pure polymer to pure clay were synthesized. Following the synthesis, X-ray diffraction (XRD) was utilized to study the structure and to determine the interlayer distance. It was found that all nanohybrids have intercalated structure with interlayer distances that are similar to the ones that correspond to the respective of PEO homopolymer when it is mixed with the same inorganic material. There is, thus, a strong indication that in every case the final structure is determined by just the Na+/PEO ratio in the copolymer hybrids. In order to investigate the role of the PS block in the system, the interactions between the blocks of the copolymer and the inorganic surface were studied by infrared spectroscopy (FTIR). Finally, the fluorescence of the PS block as well as the way it is affected by whether the polystyrene is intercalated or not was studied. It was proved that the intrinsic fluorescence of PS is vanished when it is intercalated between the inorganic layers. In the case of the Na+/PEO-b-PS nanocomposites the PS fluorescence is measurable, evidencing that the PS block is outside of the inorganic galleries and only the PEO block of the copolymer intercalates

Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial

We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19. In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978. Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50–72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74–1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67–1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74–1·58]; BRII-196 plus BRII-198 1·00 [0·68–1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91–1·37]) and 155 (88%) in the BRII-196 plus BRII-198 group (1·08 [0·88–1·32]). The composite safety outcome up to day 90 was met by 48 (27%) patients in the placebo group, 42 (23%) in the sotrovimab group, and 45 (26%) in the BRII-196 plus BRII-198 group. 13 (7%) patients in the placebo group, 14 (8%) in the sotrovimab group, and 15 (9%) in the BRII-196 plus BRII-198 group died up to day 90. Neither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19. US National Institutes of Health and Operation Warp Spee