Correction to: Heparin resistance in COVID­19 patients in the intensive care unit.

In the original publication of this article, one of the co-author name "D. de Monteverde-Robb" was inadvertently mentioned as "R. de Monteverde-Robb". The correct author name is "D. de Monteverde-Robb". This error has been corrected with this erratum.

Heparin resistance in COVID-19 patients in the intensive care unit.

Patients with COVID-19 have a coagulopathy and high thrombotic risk. In a cohort of 69 intensive care unit (ICU) patients we investigated for evidence of heparin resistance in those that have received therapeutic anticoagulation. 15 of the patients have received therapeutic anticoagulation with either unfractionated heparin (UFH) or low molecular weight heparin (LMWH), of which full information was available on 14 patients. Heparin resistance to UFH was documented in 8/10 (80%) patients and sub-optimal peak anti-Xa following therapeutic LMWH in 5/5 (100%) patients where this was measured (some patients received both anticoagulants sequentially). Spiking plasma from 12 COVID-19 ICU patient samples demonstrated decreased in-vitro recovery of anti-Xa compared to normal pooled plasma. In conclusion, we have found evidence of heparin resistance in critically unwell COVID-19 patients. Further studies investigating this are required to determine the optimal thromboprophylaxis in COVID-19 and management of thrombotic episodes.

Altered chemical evolution in landfill leachate post implementation of biodegradable waste diversion.

Within the UK implementation of the European Union Landfill Directive (1999) has led to the diversion of biodegradable waste (BW) from municipal solid wastes away from landfills. It has been widely anticipated, but thus far not verified, that the diversion of BW and consequent reduction in BW reaching landfill would lead to a change in the degradation processes occurring within landfills and that this would be reflected in an altered evolution in leachate chemistry compared to pre-Directive landfills. This paper provides evidence based on leachate chemistry from two operational landfills together with calculations of the reduced BW content, that demonstrate the acetogenic phase that characterised pre-Directive landfill leachates is missing and is now more typical of methanogenic phase leachate. The paper demonstrates how data from national datasets and detailed landfill records can be used to constrain likely and upper estimates of the amount of BW going into post-Directive landfills, and the observed change in the evolution of leachate chemistry which has resulted from a decrease in BW content from typical values of BW (pre-Landfill Directive) of 22% to an inferred 12% in the case-study landfills. Data provided here add to the growing literature that estimates the amount of BW in recent post-Directive landfills which importantly allow the quantitative linkage between a decrease in landfilled BW and observed changes in leachate chemistry to be established such that future landfill operators can increase confidence in the effect of Directive implementation on landfill operational parameters.

Delignification and enhanced gas release from soil containing lignocellulose by treatment with bacterial lignin degraders.

AIMS: The aim of the study was to isolate bacterial lignin-degrading bacteria from municipal solid waste (MSW) soil, and to investigate whether they could be used to delignify lignocellulose-containing soil, and enhance methane release. METHODS AND RESULTS: A set of 20 bacterial lignin degraders, including 11 new isolates from MSW soil, were tested for delignification and phenol release in soil containing 1% pine lignocellulose. A group of seven strains were then tested for enhancement of gas release from soil containing 1% lignocellulose in small-scale column tests. Using an aerobic pretreatment, aerobic strains such as Pseudomonas putida showed enhanced gas release from the treated sample, but four bacterial isolates showed 5-10-fold enhancement in gas release in an in situ experiment under microanaerobic conditions: Agrobacterium sp., Lysinibacillus sphaericus, Comamonas testosteroni and Enterobacter sp. CONCLUSIONS: The results show that facultative anaerobic bacterial lignin degraders found in landfill soil can be used for in situ delignification and enhanced gas release in soil containing lignocellulose. SIGNIFICANCE AND IMPACT OF THE STUDY: The study demonstrates the feasibility of using an in situ bacterial treatment to enhance gas release and resource recovery from landfill soil containing lignocellulosic waste.

Sizing criteria for a low footprint passive mine water treatment system.

The objective of this paper is to present data from a novel vertical flow mine water treatment system, demonstrate how these data can be used to generate sizing formulae for this technology, and present a comparison between the size of system based on these formulae and those of conventionally designed passive systems. The paper focuses on passive treatment of circum-neutral ferruginous mine waters bearing up to 50 mgl(-1) of iron in either ferrous or ferric form. The Vertical Flow Reactor (VFR) operates by passing mine water down through an accreting bed of ochre, the ochre bed being responsible for the intensification of iron removal by self-filtration and/or autocatalytic iron oxidation and precipitation. Key to the design and operation of the VFR system is the decrease in permeability in this ochre bed over time. The paper demonstrates that the VFR system can remove iron at many times the 10 g/m2/day removal rate - an often employed figure for the sizing of aerobic settling ponds and wetlands. The paper demonstrates that VFRs are viable and novel passive treatment system for mine waters with a smaller footprint than conventional systems.

Towards "Precision Mining" of wastewater: Selective recovery of Cu from acid mine drainage onto diatomite supported nanoscale zerovalent iron particles.

This paper introduces the concept of 'Precision Mining' of metals which can be defined as a process for the selective in situ uptake of a metal from a material or media, with subsequent retrieval and recovery of the target metal. In order to demonstrate this concept nanoscale zerovalent iron (nZVI) was loaded onto diatomaceous earth (DE) and tested for the selective uptake of Cu from acid mine drainage (AMD) and subsequent release. Batch experiments were conducted using the AMD and nZVI-DE at 4.0-16.0 g/L. Results demonstrate nZVI-DE as highly selective for Cu removal with >99% uptake recorded after 0.25 h when using nZVI-DE concentrations ≥12.0 g/L, despite appreciable concentrations of numerous other metals in the AMD, namely: Co, Ni, Mn and Zn. Cu uptake was maintained in excess of 4 and 24 h when using nZVI-DE concentrations of 12.0 and 16.0 g/L respectively. Near-total Cu release from the nZVI-DE was then recorded and attributed to the depletion of the nZVI component and the subsequent Eh, DO and pH recovery. This novel Cu uptake and release mechanism, once appropriately engineered, holds great promise as a novel 'Precision Mining' process for the rapid and selective Cu recovery from acidic wastewater, process effluents and leach liquors.

Selective formation of copper nanoparticles from acid mine drainage using nanoscale zerovalent iron particles.

Nanoscale zerovalent iron (nZVI) has been investigated for the selective formation of Cu nanoparticles from acid mine drainage (AMD) taken from a legacy mine site in the UK. Batch experiments were conducted containing unbuffered (pH 2.67 at t = 0) and pH buffered (pH < 3.1) AMD which were exposed to nZVI at 0.1-2.0 g/L. Results demonstrate that nZVI is selective for Cu, Cd and Al removal (>99.9% removal of all metals within 1 h when nZVI ≥ 1.0 g/L) from unbuffered AMD despite the coexistent of numerous other metals in the AMD, namely: Na, Ca, Mg, K, Mn and Zn. An acidic pH buffer enabled similarly high Cu removal but maximum removal of only <1.5% and <0.5% Cd and Al respectively. HRTEM-EDS confirmed the formation of discrete spherical nanoparticles comprised of up to 68% wt. Cu, with a relatively narrow size distribution (typically 20-100 nm diameter). XPS confirmed such nanoparticles as containing Cu°, with the Cu removal mechanism therefore likely via cementation with Fe°. Overall the results demonstrate nZVI as effective for the one-pot and selective formation of Cu°-bearing nanoparticles from acidic wastewater, with the technique therefore potentially highly useful for the selective upcycling of dissolved Cu in wastewater into high value nanomaterials.

Iron-mineral accretion from acid mine drainage and its application in passive treatment.

This study demonstrates substantial removal of iron (Fe) from acid mine drainage (pH ≈3) in a passive vertical flow reactor (VFR) with an equivalent footprint of 154 m(2) per L/s mine water and residence times of >23 h. Average Fe removal rate was 67% with a high of 85% over the 10-month trial. The fraction of Fe passing a 0.22 µm filter (referred to here as Fe-filt) was seen to be removed in the VFR even when Fe(II) was absent, indicating that the contribution of microbial Fe(II) oxidation and precipitation was not the dominant removal mechanism in the VFR. Removal rates of Fe-filt in the VFR were up to 70% in residence times as low as 8 h compared with laboratory experiments where much smaller changes in Fe-filt were observed over 60 h. Centrifugation indicated that 80-90% of the influent Fe had particle sizes <35 nm. Together with analyses and geochemical modelling, this suggests that the Fe-filt fraction exists as either truly aqueous (but oversaturated) Fe(III) or nanoparticulate Fe(III) and that this metastability persists. When the water was contacted with VFR sludge, the Fe-filt fraction was destabilized, leading to an appreciably higher removal of this fraction. Heterogeneous precipitation and/or aggregation of nanoparticulate Fe(III) precipitates are considered predominant removal mechanisms. Microbial analyses of the mine water revealed the abundance of extracellular polymeric substance-generating Fe-oxidizing bacterium 'Ferrovum myxofaciens', which may aid the removal of iron and explain the unusual appearance and physical properties of the sludge.

Intravenous sedation for handicapped dental patients: a clinical trial of midazolam and propofol.

A double blind, cross-over study to compare intravenous sedation using continuous infusions of midazolam and propofol was carried out in 18 handicapped patients, aged between 5 and 26 years. Using a syringe pump (Ohmeda 9000) midazolam was delivered at 0.4 mg/kg/h with a bolus dose of 0.02 mg/kg and propofol was infused at 4.0 mg/kg/h with a bolus dose of 0.2 mg/kg. Sequential analysis showed that induction and recovery times were shorter with propofol (P < 0.05 and P < 0.01 respectively) and more work was performed over unit time (P < 0.05), with 15.7 units of work being completed per hour on patients under propofol sedation compared to 11.0 units under midazolam. The quality of sedation was assessed as better in patients receiving propofol; eight cases were abandoned under midazolam infusion due to failure of induction, uncontrolled movement and/or emotional outbursts compared with none under propofol. All parents/patients preferred propofol sedation, because recovery was faster and smoother.

New perspectives on the passive treatment of ferruginous circumneutral mine waters in the UK.

This paper examines major physico-chemical processes during the passive treatment of ferruginous circumneutral drainage from abandoned coal mines in the UK. Data collected over several years of studies on mine water treatment systems shed new light on the relative importance of hydraulics, settling velocity, Fe(II) oxidation rates and cascade aeration, which, in turn, informs the design of future systems. This paper demonstrates that (1) the complex settling behaviour of Fe(III) precipitates may be described by a first-order volumetric process and that settling rate is different for different mine waters; (2) the hydraulic efficiency (ratio of time to peak tracer concentration to nominal residence time) of the settling ponds studied was widely variable at low flow rates in comparison to constructed wetlands; (3) aeration cascades contribute dissolved oxygen and lead to a rise in pH due to CO2 degassing, which are very important in reducing the required time for iron oxidation and removal; (4) for at least 10 of the 30 sites examined, modelling of the rates of Fe(II) oxidation and particulate settling reveals that removal of iron is primarily dependent on settling rate; and (5) that substantial increases in pH can be brought about by forced aeration of mine water over several hours. Findings of this study apply to the majority of coal mine water treatment sites in the UK and may have broader application to other ferruginous waters with circumneutral pH or after treatment to increase pH.

Prolonged neuromuscular blockade following suxamethonium in a patient with a normal genotype.

A patient is described who developed prolonged apnoea following a single normal dose of suxamethonium which was shown by nerve stimulation to be due to persistent neuromuscular blockade. The plasma cholinesterase profile demonstrated a normal genotype.

The PIO2 vs. SpO2 diagram: a non-invasive measure of pulmonary oxygen exchange.

A non-invasive method for measuring pulmonary oxygen exchange is described using a plot of inspired oxygen partial pressure (PIO2) vs. oxygen saturation (SpO2). This method was assessed using nine normal subjects and 35 patients undergoing major surgery, including five thoracotomies. In each patient PIO2 was varied to produce a range of values of SpO2 between 85% and 99%. A model based on the inspired to arterial oxygen difference involving the shunt equation, solved by simultaneous numerical methods, was used to show how the PIO2 vs. SaO2 relationship could be used to derive two parameters of oxygen exchange, the PIO2-Pco2 difference and the Virtual Shunt. The model allows the inspired to arterial difference in PO2 to be divided into (a) an inspired to 'ideal' alveolar difference attributable to the balance between alveolar ventilation and oxygen uptake; (b) an 'ideal' alveolar to end-capillary difference attributable to inhomogeneity in ventilation/perfusion ratios; and (c) end-capillary to arterial difference attributable to true shunt, which was termed 'virtual shunt' because of the uncertainties of assuming fixed values for haemoglobin concentration and arteriovenous oxygen content difference. The coefficient of determination showed that there was a good fit of the model to the data. Because the method is model-based it enables extrapolation to different PIO2 values as well as the study of the evolution of changes in gas exchange under varying conditions.

A study to compare the effectiveness of temazepam and a chloral hydrate/hydroxyzine combination in sedating paediatric dental patients.

The study compared the effectiveness of temazepam and a mixture of chloral hydrate and hydroxyzine in sedating 20 young children aged 20 to 60 months (mean age 38.7 months). All the children exhibited negative behaviour during a screening visit and required at least two visits for restorative treatment with the use of sedation. The children were assigned randomly to receive either 50 mg/kg of chloral hydrate with 25 mg of hydroxyzine or 0.3 mg/kg of temazepam for the first visit, and the alternate regimen for the second visit, in a double-blind manner. Pulse rate and blood oxygen saturation levels were monitored before, during and after the operative procedures. All the treatment sessions were video-recorded and evaluated independently by three paediatric dentists for the degree of crying, movement, sleep and overall behaviour during specific procedures and at specific time intervals. The results showed no statistically significant differences between the two pharmacologic regimens with regard to crying, movement, sleep and overall behaviour. No significant difference in behaviour was found related to either the order of administration of the drugs or to the sex of the patients. It was concluded that 0.3 mg/kg temazepam and a mixture of 50 mg/kg chloral hydrate with 25 mg hydroxyzine had similar sedative effects on the children receiving dental treatment.

A method for producing the coherent frequency: a steady-state auditory evoked response in the electroencephalogram.

Transient and steady-state auditory evoked responses in the electroencephalogram are used to study the effect on the brain of graded changes in the concentration of general anesthetics. A method is described using modern signal processing techniques to improve the analysis of steady-state auditory evoked responses (SSAER). The SSAER was obtained using headphones to give 100-200 auditory click stimuli from 6.5 Hz.to 50.5Hz in 1-Hz steps. The resulting electroencephalogram signals were filtered and subject to Fourier analysis, after which a series of coherence indexes were derived based on waves with significant power in the fundamental but with minimal harmonic content. These were plotted against the range of stimuli and fitted with a third-order polynomial. The frequency at which the maximum coherence index was achieved (highest possible value = 1) was derived from polynomial interpolation. The repeatability of the method was examined in 10 awake subjects using runs of ascending then descending stimulating frequencies. The mean maximum coherence index was at 38 Hz, with the 95% confidence interval of 37.3 Hz-38.9 Hz. There was no difference between ascending and descending sweeps. The method provides an automatic analysis of the SSAER that obviates the need to make subjective decisions about which is the dominant wave, a major problem in the analysis of the transient auditory evoked responses.

Postoperative hypoxaemia: mechanisms and time course.

Postoperative hypoxaemia results predominantly from two mechanisms. Gas exchange is impaired during anaesthesia as a result of reduced tone in the muscles of the chest wall and probably alterations in bronchomotor and vascular tone, and the resulting changes persist into the postoperative period. In addition, there is an abnormality of control of breathing, which results in episodic obstructive apnoea. These episodes continue for several days after operation and are related to sleep pattern and analgesic administration, although the precise effects of different analgesic regimens have not been evaluated. Oxygen administration is effect in reducing the degree of hypoxaemia.

A measure of consciousness and memory during isoflurane administration: the coherent frequency.

The coherent frequency (CF) of the auditory evoked response (AER) is derived using auditory clicks presented at frequencies in the range 5-47 Hz. CF and psychological performance were measured while seven subjects breathed isoflurane in doses increasing from 0% to 0.2%, 0.4% and 0.8% end-tidal concentration and then decreasing to 0%. With increasing doses of isoflurane, CF decreased and there was a decrease in within-list recognition (WLR) and category recognition (CR) scores. There was a correlation between changes in CF and WLR (P < 0.05) and between CF and category recognition (CR) (P < 0.05). A painful stimulus given in conjunction with 0.4% isoflurane caused an increase in CF, WLR and CR in some subjects. This did not reach statistical significance for the group as a whole, apart from the short word interval scores in the WLR which indicated an increase in attention (P < 0.01). Subjects did not respond with 0.8% isoflurane, either before or after painful stimulation. Reduction of end-tidal isoflurane from 0.8% to 0% caused an increase in the CF and improved performance on the psychological tests. A category generation task on recovery showed no evidence of implicit learning of words presented in conjunction with 0.8% isoflurane.(ABSTRACT TRUNCATED AT 250 WORDS)

Nitrous oxide sedation causes post-hyperventilation apnoea.

We have studied, in six normal subjects, the effect of nitrous oxide sedation on the ventilatory pattern and oxygen saturation using pulse oximetry (SpO2) after hyperventilation to an end-tidal carbon dioxide partial pressure (PE'CO2) of 3 kPa. This value of PE'CO2 was shown to be less than the apnoeic threshold of all these subjects when their ventilation vs PE'CO2 response curves were plotted. All subjects became apnoeic when told to relax following hyperventilation while breathing 75% nitrous oxide for 90 s. Apnoea was defined as cessation of breathing for 20 s or more. The mean duration of apnoea was 78 s (range 29-130 s). All subjects demonstrated arterial desaturation (mean SpO2 75%, range 44-87%). In contrast, following hyperventilation with air, no apnoea was seen in any subject, although there was some evidence of desaturation (mean SpO2 92.5%, range 88-98%). It was concluded that subjects who are sedated with nitrous oxide behave similarly to those who are anaesthetized rather than to those who were fully conscious, in that they become apnoeic below the apnoeic threshold point. The reduction in SpO2 after hyperventilation was explained almost entirely by apnoea and may explain abnormalities of respiratory control and hypoxaemia in patients recovering from general anaesthesia or sedation accompanied by hypocapnia. This mechanism may be of importance in obstetric patients after breathing Entonox, when apnoea and hypoxaemia may reduce oxygen delivery to the fetus.

Continuous measurements of oxygen saturation during haemodialysis.

A new technique for recording and analysing continuous measurements of oxygen saturation (SpO2) by pulse oximeter during haemodialysis was used to compare changes in SpO2 in eight patients during two 4 h periods of dialysis using a cuprophane membrane, once using an acetate dialysate, and once using bicarbonate. The computer-derived patterns of SpO2 show whether hypoxaemia was caused mainly by extrapulmonary abnormalities (ventilatory control) or intrapulmonary abnormalities (V/Q distribution). The patterns of oxygen saturation were analysed for (i) stability, (ii) the lower median 20th centile of SpO2, and (iii) time below a SpO2 of 90%. Not all patients had reduced oxygenation during acetate dialysis. Three of eight patients had a stable pattern with acetate dialysis and six of eight were stable with bicarbonate. Five of eight patients had a lower SpO2 with acetate but one patient had a lower SpO2 with bicarbonate. Four patients had prolonged, clinically significant periods of oxygen desaturation with SpO2 less than 90%; two of these had particularly prolonged periods during acetate (62 min and 12 min), but one patient showed a longer period during bicarbonate than acetate dialysis (7 min). In two patients the SpO2 declined to less than 84%. The patterns of SpO2 suggested that the decrease in oxygen saturation was due more to extrapulmonary abnormalities causing an instability in ventilatory control rather than to venous admixture. It is recommended that pulse oximetry is used to identify patients at risk of hypoxaemia, to monitor these patients during haemodialysis, and to administer oxygen to those whose SpO2 falls below 90%, particularly if they have anaemia or cardiovascular disease.