Charge disproportionation and the pressure-induced insulator-metal transition in cubic perovskite PbCrO3.

The perovskite PbCrO3 is an antiferromagnetic insulator. However, the fundamental interactions leading to the insulating state in this single-valent perovskite are unclear. Moreover, the origin of the unprecedented volume drop observed at a modest pressure of P = 1.6 GPa remains an outstanding problem. We report a variety of in situ pressure measurements including electron transport properties, X-ray absorption spectrum, and crystal structure study by X-ray and neutron diffraction. These studies reveal key information leading to the elucidation of the physics behind the insulating state and the pressure-induced transition. We argue that a charge disproportionation 3Cr(4+) → 2Cr(3+) + Cr(6+) in association with the 6s-p hybridization on the Pb(2+) is responsible for the insulating ground state of PbCrO3 at ambient pressure and the charge disproportionation phase is suppressed under pressure to give rise to a metallic phase at high pressure. The model is well supported by density function theory plus the correlation energy U (DFT+U) calculations.

How reliable are test results from 17 laboratories on the basis of EN 1500 for a hand rub based on 80% (w/w)?

INTRODUCTION: A ring trial organized by the Association of Applied Hygiene (VAH) on the bactericidal efficacy of an ethanol-based hand rub was carried out in 17 laboratories according to EN 1500 with the aim of describing the variability of test results and fulfilment of the methodological acceptance criteria. METHOD: As a test product, a hand rub based on 80% ethanol (w/w) was tested in comparison with the reference alcohol (60% iso-propanol, v/v) in a crossover design. After pre-washing and contamination following the norm, hands were treated either with the reference alcohol (2 × 3 mL for 2 × 30 s) or the test product (3 mL in 30 s). Post-decontamination values were determined immediately after the rub-in period. Validated neutralizers were used. The arithmetic means of all individual log10 pre-values, post-values and reduction values were calculated per laboratory. Non-inferiority was assumed when the Hodges-Lehmann 97.5% confidence limit was <0.6 in comparison with the reference. A z-score was calculated to determine the laboratory performance. RESULTS: Two laboratories did not meet the acceptance criteria and were excluded from the analysis. The bactericidal efficacy of the test product was non-inferior to the reference product in four laboratories and not non-inferior in 11 laboratories. The z-score for the Hodges-Lehmann 97.5% confidence limit indicated a satisfactory performance in all laboratories. CONCLUSION: We consider the EN 1500 test method to be robust in terms of the variability of test results. For products of borderline efficacy, the evaluation should be based on more than one test.

In-vivo efficacy of alcohol-based hand rubs against noroviruses: a novel standardized European test method simulating practical conditions.

BACKGROUND: Non-enveloped viruses are particularly resistant to disinfectants, so it is necessary to use disinfectants with proven virucidal activity in order to prevent and control the spread of viral infections. However, a test such as EN 1500, which uses an internal standard as the reference treatment for determining the bactericidal efficacy of hand rubs, is still lacking. This study aimed to establish a European standard for testing the in-vivo efficacy of hand rubs against non-enveloped viruses. METHODS: The concentration and mode of application of ethanol as the reference were determined, and compared with the efficacies of two commonly used hand rubs. The hands of volunteers were contaminated with murine norovirus strain S99. RESULTS: 70% wt/wt ethanol (2 x 3 mL in 2 x 30 s) was used as the internal reference treatment. The commercial ethanol-based hand rub was able to reduce the titre of murine norovirus significantly in 30 s, whereas a hand rub based on ethanol and propan-2-ol was significantly less effective compared with the reference. CONCLUSION: This study established a possible standard for testing the in-vivo efficacy of hand rubs against non-enveloped viruses using murine norovirus, a low contamination volume technique and ethanol as the internal reference. These findings need to be confirmed in European ring trials.

Failure of sodium hypochlorite to meet the EN 1500 efficacy requirement for hygienic hand disinfection.

This study evaluated the bactericidal efficacy of two alternative hand antiseptics, based on sodium hypochlorite or sodium hypochlorite and hypochlorous acid, compared with isopropanol on the hands of volunteers artificially contaminated with Escherichia coli using EN 1500. The reference alcohol was applied according to the norm, and the study formulations were used as in common practice (3 mL for 30 s). The products showed mean log10 reductions of 1.63 and 1.89, both of which were inferior to the reference treatment (4.78). Due to the failure to achieve sufficient bactericidal efficacy within 30 s, sodium hypochlorite (0.05-0.06%) should not be considered for hand disinfection.

Evolving the EN 1500 test method for alcohol-based hand rub closer to clinical reality by reducing the organic load on hands and enabling product to be applied to dry hands.

BACKGROUND: The methods currently used in Europe and North America to evaluate the bactericidal efficacy of hand hygiene products have some limitations (e.g. selection of test organism, method of contamination), and none of the methods allow prediction of actual clinical efficacy. Therefore, the World Health Organization has proposed the development of methods that better reflect typical clinical reality. METHODS: In Experiment 1, two contamination methods (immersion method according to EN 1500 and low-volume method according to ASTM E2755) were tested with the EN 1500 test organism Escherichia coli using 60% v/v iso-propanol. Experiment 2 compared the two contamination methods with Enterococcus faecalis. Experiment 3 compared the two test organisms using the low-volume contamination method. Data within each experiment were compared using the Wilcoxon test for paired samples, and data from all experiments were combined and fit to linear mixed-effects models. RESULTS: Mixed-effects analysis confirmed that both the test organism and the contamination method impacted the pre-values, and all three factors influenced log10 reductions. Higher pre-values resulted in significantly higher log10 reductions, immersion contributed to significantly higher log10 reductions, and E. coli showed significantly lower log10 reductions. CONCLUSION: An efficacy evaluation against E. faecalis with a low-volume contamination method could be considered as an alternative to the EN 1500 standard. This could help to improve the clinical relevance of the test method by including a Gram-positive organism and reducing the soil load, allowing product application closer to reality.

Bactericidal efficacy of two modified WHO-recommended alcohol-based hand rubs using two types of rub-in techniques for 15 s.

We evaluated the bactericidal efficacy of two modified WHO-recommended alcohol-based hand rubs (3 mL) after a 15-s rubbing period using two different rub-in techniques (three vs six steps). The formulation based on 80% w/w ethanol and 0.5% v/v glycerol (modified WHO I) showed a mean log10-reduction of 3.63 ± 0.87 (six steps) and 3.80 ± 0.71 (three steps) which was inferior to the reference treatment (4.27 ± 0.98; six steps). The efficacy of the formulation based on 75% w/w isopropanol and 0.5% v/v glycerol (modified WHO II) was not inferior to the reference treatment for either rub-in technique.

Efficacies of the original and modified World Health Organization-recommended hand-rub formulations.

The World Health Organization (WHO) hand-rub formulations have been in use around the world for at least the past 10 years. The advent of coronavirus disease 2019 (COVID-19) has further enhanced their use. We reviewed published efficacy data for the original and modified formulations. Only efficacy data according to the European Norms (EN) were found. The bactericidal efficacy of the original formulations was, under practical conditions, partly insufficient (EN 1500, only effective in 60 s; EN 12791, efficacy too low in 5 min). The first modification with higher alcohol concentrations improves their efficacy as hygienic hand rub (effective in 30 s). The second (0.725% glycerol) and third (0.5% glycerol) modification improves their efficacy for surgical hand preparation (effective in 5 and 3 min). The original and second modified formulations were tested and demonstrate activity against enveloped viruses including severe acute resiratory syndrome coronavirus 2 (SARS-CoV-2) in 30 s. The ethanol-based formulation is also active against some non-enveloped test viruses in 60 s (suspension tests, EN 14476). In-vivo data on the formulations would provide a more reliable result on the virucidal efficacy on contaminated hands but are currently not available. Nevertheless, the most recent modifications should be adopted for use in healthcare.

COVID-19-associated shortage of alcohol-based hand rubs, face masks, medical gloves, and gowns: proposal for a risk-adapted approach to ensure patient and healthcare worker safety.

The coronavirus disease 2019 (COVID-19) pandemic has caused a huge demand for alcohol-based hand rubs, medical gloves, face masks, and gowns in healthcare and from the public. More and more hospitals face a serious shortage of these articles. We propose a risk-adapted approach to ensure adequate patient and healthcare worker safety for as long as possible.

Prion disease and recommended procedures for flexible endoscope reprocessing - a review of policies worldwide and proposal for a simplified approach.

Several guidelines recommend specific treatments for endoscopes, procedures of quarantine for endoscopes, or additional treatments for the endoscope washer disinfector (EWD) in suspected or confirmed cases of Creutzfeldt-Jakob disease (CJD) or variant CJD (vCJD) but vary in many details. This study therefore reviewed guidelines on reprocessing flexible endoscopes after use in patients with suspected or confirmed prion disease. In addition, a literature search was performed in Medline on prion, CJD, vCJD, chemical inactivation, transmission healthcare, epidemiology healthcare, concentration tissue human and endoscope. Thus far, no case of CJD or vCJD transmitted by flexible endoscope has been reported. In animals it has been shown that oral uptake of 0.1-5 g of bovine spongiform encephalopathy (BSE)-infected brain homogenate is necessary for transmission. The maximum prion concentration in other tissues (e.g., terminal ileum) is at least 100-fold lower. Automated cleaning of endoscopes alone results in very low total residual protein ≤5.6 mg per duodenoscopes. Recommendations vary between countries, sometimes with additional cleaning, use of alkaline cleaners, no use of cleaners with fixative properties, use of disinfectants without fixative properties or single-use disinfectants. Sodium hydroxide (1 M) and sodium hypochlorite (10,000 and 25,000 mg/L) are very effective in preventing transmission via contaminated wires implanted into animal brains, but their relevance for endoscopes is questionable. Based on circumstantial evidence, it is proposed to consider validated reprocessing as appropriate in the case of delayed suspected prion disease when immediate bedside cleaning, routine use of alkaline cleaners, no fixative agents anywhere prior to disinfection and single use brushes and cleaning solutions can be assured.

Do pneumatic tube transport systems transmit potential pathogens? A hygienic risk assessment in a university hospital.

BACKGROUND: Prompted by an outbreak of vancomycin-resistant enterococci (VRE) in a medical facility, this study examined a pneumatic tube transport system (PTS) as a potential transmission channel. METHOD: Samples from the receiving station and entry racks were gathered via smear technique. Sponges used for PTS decontamination were soaked with 0.89% NaCl and transported through the channel. Micro-organisms were recovered from the tubes and cleaning sponges using a wash-away technique. Air sampling was performed at the receiving station in order to detect any airborne contamination. Tubes were artificially inoculated with Escherichia coli K12 NCTC 10538 and Staphylococcus epidermidis DSM 20044 and sent through the PTS to investigate channel contamination. RESULTS: No pathogens were detected in effluent air from the PTS or in tubes during routine operation. Entry racks for the test tubes were contaminated with coagulase-negative staphylococci (CNS), aerobic bacilli, moulds and vancomycin-susceptible Enterococcus faecium. E. coli proved to be unsuitable for detecting bacterial transmission by the PTS due to low persistence, but S. epidermidis was more resilient. After sending contaminated test tubes through the PTS, levels of S. epidermidis only decreased marginally. Subsequently, sponges soaked with disinfectant solution were put through the system and these eliminated S. epidermidis completely from the first attempt. DISCUSSION: Routine hygienic maintenance of the PTS makes pathogen transmission highly unlikely, although entry racks should be disinfected regularly. Any involvement of the PTS in the VRE outbreak at the study institution was unlikely.

Hand antisepsis without decreasing efficacy by shortening the rub-in time of alcohol-based handrubs to 15 seconds.

BACKGROUND: A previous study among neonatal intensive care unit (NICU) nurses showed that the antibacterial efficacy of alcohol-based handrubs (ABHR) can be achieved in 15 s instead of 30 s with a significant increase in the frequency of hand antisepsis. This study aimed to examine 15-s vs 30-s antisepsis performance by measuring microbial load on fingertips and compliance among nurses in a low-risk gynaecological ward. METHODS: An independent trained observer monitored the frequency and compliance with hand antisepsis during shifts in a crossover design. Fingertips including thumbs were rinsed in soy broth before hand rubbing at the beginning of a shift and then hourly to determine the bacterial load. Performance activity was assigned to the contamination class of the Fulkerson scale. Immediately before the lunch break, volunteers cleaned their hands for a randomly determined application time of 15 or 30 s. RESULTS: Examination of bacterial load on fingertips revealed no difference between 15 vs 30 s application time. Controlled hand antisepsis before the lunch break also showed no difference in efficacy for either test series. Participants rubbing for 15 s were more likely to perform hand antisepsis compared with those rubbing for 30 s (P=0.2). The compliance increased from 54.7% to 69.5% in the 15-s trial. DISCUSSION: Shortening the duration for hand antisepsis did not decrease efficacy. Shortening the application time to 15 s should be considered within the critical components of a successful multimodal intervention strategy to improve hand-hygiene compliance in clinical practice.

Surgical hand disinfection using alcohol: the effects of alcohol type, mode and duration of application.

Due to their strong antimicrobial activity, rapid action, good dermal tolerance and ease of application, alcohol-based hand rubs are recommended for pre-operative preparation of the surgical team's hands. Using the EN 12791 protocol, three commercial products containing either mixtures of propan-1-ol and propan-2-ol or ethanol at total alcohol concentrations (w/w) between 73% (propanols) and 78.2% (ethanol), as the main active agents, were tested with a shortened application of 1.5 min rather than the usual 3 min. Preparation A containing 30% propan-1-ol and 45% propan-2-ol not only passed the test at this short application but even exceeded, though not significantly, the efficacy of the reference disinfection procedure in EN 12791 when applied for 3 min. Preparation B containing 45% propan-1-ol and 28% propan-2-ol fulfilled the required standard whereas the ethanol (78.2%)-based product C did not (P<0.1). This demonstrates that some, but not all, alcohol-based hand rubs pass the test even within 1.5 min, emphasising the importance of validation before a product is introduced into clinical practice. In another series with both preparation A and 60% v/v propan-1-ol, it was demonstrated that the additional inclusion of the forearms into the disinfection procedure, not required by EN 12791 but normal practice in surgical hand disinfection, does not significantly interfere with the antimicrobial efficacy of either hand rub. Therefore, the mode of test procedure in EN 12791 does not need specific adaptation for hand disinfection by surgical teams.

Enterococcus hirae, Enterococcus faecium and Enterococcus faecalis show different sensitivities to typical biocidal agents used for disinfection.

BACKGROUND: Enterococcus faecium and E. faecalis are known nosocomial pathogens. The bactericidal activity of biocidal agents used for disinfection, however, is determined with E. hirae. AIM: To find out whether E. hirae is a suitable species to evaluate the efficacy of biocidal agents against the clinically relevant species E. faecalis and E. faecium. METHODS: The bactericidal activity was determined in suspension tests according to EN 13727 using E. faecium ATCC 6057, E. faecalis ATCC 47077 and E. hirae ATCC 10541. Glutaraldehyde, ethanol, benzalkonium chloride, peracetic acid and sodium hypochlorite were used with three exposure times per biocide. When major differences in the sensitivity of the three enterococcal species to the respective substance was found, two more replicates were performed. The number of colony-forming units (cfu) was transformed into decimal logarithms. Results from replicate experiments were described with means and standard deviations. FINDINGS: At a 5-min exposure time, E. hirae was found to be more tolerant to 0.2% glutaraldehyde and 0.0125% peracetic acid compared to E. faecium and E. faecalis, whereas it was more susceptible to 40% ethanol and 3% sodium hypochlorite. Only with 0.00125% benzalkoniumchloride (15 min) was the susceptibility of E. hirae between that of E. faecium and E. faecalis. CONCLUSIONS: E. hirae is a suitable species when a bactericidal activity should be determined against enterococci with glutaraldehyde and peracetic acid. E. hirae may not be a suitable species for ethanol or sodium hypochlorite if the bactericidal activity should include the clinical pathogens E. faecium and E. faecalis.

Lack of sustained efficacy for alcohol-based surgical hand rubs containing 'residual active ingredients' according to EN 12791.

The World Health Organization recommends the use of hand rubs with 'sustained activity' for surgical hand preparation. This review aims to verify whether any of the alcohol-based hand rubs containing non-volatile 'active ingredients' such as chlorhexidine digluconate (CHG), mecetronium ethylsulphate (MES), or ortho-phenylphenol (OPP) provides such sustained efficacy for surgical hand disinfection. Literature was searched to find studies according to EN 12791. Published data sets were analysed to verify whether any of the formulations has a superior efficacy (P<0.01) after 3h in comparison to the reference procedure. Formulations with 0.5 and 1% CHG in 70% iso-propanol or 61% ethanol were not superior after 3h. Formulations with 0.2% MES in 45% iso-propanol and 30% n-propanol were also not superior when applied for 1min (one data set), 1.5min as currently recommended for use (14 data sets), and 2min (one data set). When applied for 3min the formulations were superior in three out of seven data sets. The hand rub with 0.1% OPP in 78.2% ethanol was also not superior to the reference treatment when applied as recommended for 1.5min. It appears reasonable and responsible to limit the dermal exposure and environmental input to biocidal agents with a clear benefit such as the alcohols. In analogy to avoiding dyes and fragrances in hand rubs, formulations containing 'active' substances without a clear benefit but with potential risks should be avoided when alternative formulations with the same level of antimicrobial activity, dermal tolerance, and user acceptability are available.

Glycerol significantly decreases the three hour efficacy of alcohol-based surgical hand rubs.

BACKGROUND: Glycerol in alcohol-based hand rubs has positive effects on skin condition and user acceptability, but, to the authors' knowledge, its effect on the bactericidal effect of alcohol-based pre-operative hand rubs has not been reported. AIM: To investigate the impact of glycerol on the reduction of resident hand flora by ethanol 80% (w/w), isopropanol 75% (w/w) and n-propanol 60% (V/V). METHODS: In three series of in-vivo laboratory tests on volunteers hands, the efficacy of each of three alcohol-based formulations was tested concurrently with and without added glycerol 1.45% (V/V) according to European Norm EN 12791 for testing pre-operative hand rubs. Formulations were allotted at random to 24 volunteers to rub on to their hands for 3 min. Viable counts from fingertip samples were compared with the respective pretreatment counts immediately after treatment and 3 h later. FINDINGS: The 3-h bactericidal effects of the three pure alcoholic formulations were significantly greater than those of formulations containing glycerol (P < 0.01). With ethanol, this was also true for the immediate effect. CONCLUSION: Glycerol 1.45% (V/V) inhibits the bactericidal efficacy of alcohol-based surgical hand rubs, especially sustained efficacy.

Molecular arrangement in water: random but not quite.

Water defines life on Earth from the cellular to the terrestrial level. Yet the molecular level arrangement in water is not well understood, posing problems in comprehending its very special chemical, physical and biological properties. Here we present high-resolution x-ray diffraction data for water clearly showing that its molecular arrangement exhibits specific correlations that are consistent with the presence of rings of H(2)O molecules linked together by hydrogen bonds into tetrahedral-like units from a continuous network. This level of molecular arrangement complexity is beyond what a simple 'two-state' model of water (Bernal and Fowler 1933 J. Chem. Phys.1 515-48) could explain. It may not be explained by the recently put forward 'chains-clusters of completely uncorrelated molecules' model (Wernet et al 2004 Science 304 995-9) either. Rather it indicates that water is homogeneous down to the molecular level where different water molecules form tetrahedral units of different perfection and/or participate in rings of different sizes, thus experiencing different local environments. The local diversity of this tetrahedral network coupled to the flexibility of the hydrogen bonds that hold it together may explain well the rich phase diagram of water and why it responds non-uniformly to external stimuli such as, for example, temperature and pressure.

Ethanol in pre-surgical hand rubs: concentration and duration of application for achieving European Norm EN 12791.

In Europe, ethanol is a common active agent in hand rub formulations and nowadays it is also recommended in guidelines for hand hygiene published by the Centers for Disease Control and Prevention and by the World Health Organization. However, data on the range of concentrations and durations of application providing a basis for passing the efficacy test of the European norm EN 12791 are still lacking. Therefore, the bactericidal efficacy of rubbing clean hands with pure ethanol in volume concentrations of 95%, 85% or 75% during 3 min was compared with that of the reference procedure of EN 12791 employing n-propanol 60% v/v for 3 min, immediately and 3h after disinfection. Ethanol 85% was also tested at a 5 min application. A Latin-square design was used with 20 randomly allotted volunteers. Whereas the mean immediate bacterial reductions caused by ethanol at concentrations of 75% (log RF 1.68) and 95% (log RF 2.70) were significantly less efficacious compared to that of the reference (log RF 3.27), at 85% they were not significantly less active with both applications, 3 and 5 min (log RFs 2.90 and 3.12, respectively). Three hours after antisepsis, the bacterial reduction on the gloved hand was only significantly less efficacious than that of the reference when 75% ethanol was used. It is concluded that ethanol-based hand rubs have a good chance of meeting the EN 12791 requirements if their ethanol concentration is >75% v/v but <95% v/v and if they are applied for at least 3 min.

Testing of the World Health Organization-recommended formulations for surgical hand preparation and proposals for increased efficacy.

The 2009 World Health Organization (WHO) Guidelines on hand hygiene in health care recommend alcohol-based hand rubs for both hygienic and pre-surgical hand treatment. Two formulations based on ethanol 80% v/v and 2-propanol 75% v/v are proposed for local preparation in healthcare settings where commercial products are not available or too expensive. Both formulations and our suggested modifications (using mass rather than volume percent concentrations) were evaluated for their conformity with the efficacy requirements of the forthcoming amendment of the European Norm (EN) 12791, i.e. non-inferiority of a product when compared with a reference procedure (1-propanol 60% v/v for 3 min) immediately and 3 h after antisepsis. In this study, the WHO-recommended formulations were tested for 3 min and 5 min. Neither formulation met the efficacy requirements of EN 12791 with 3 min application. Increasing the respective concentrations to 80 w/w (85% v/v) and 75 w/w (80% v/v), together with a prolonged application of 5 min, rendered the immediate effect of both formulations non-inferior to the reference antisepsis procedure. This was not the case with the 3h effect, which remained significantly inferior to the reference. Although the original formulations do not meet the efficacy requirements of EN 12791, the clinical significance of this finding deserves further clinical trials. To comply with the requirement of EN 12791, an amendment to the formulations is possible by increasing the alcohol concentrations through changing volume into mass percent and prolonging the duration of application from 3 min to 5 min.