Hand hygiene techniques:Still a requirement for evidence for practice?

Introduction Two hand hygiene techniques are promoted internationally: the World Health Organisation’s 6 step and the Centre for Disease Control’s 3 step techniques; both of which may be considered to have suboptimum levels of empirical evidence for use with alcohol based hand rub (ABHR). Objectives The aim of the study was to compare the effectiveness of the two techniques in clinical practice. Methods A prospective parallel group randomised controlled trial (RCT) was conducted with 1:1 allocation of 6 step versus the 3 step ABHR hand hygiene technique in a clinical setting. The primary outcome was residual microbiological load. Secondary outcomes were hand surface coverage and duration. The participants were medical and nursing participants (n=120) in a large teaching hospital. Results The 6 step technique was statistically more effective at reducing the bacterial count 1900cfu/ml (95% CI 1300, 2400cfu/ml) to 380cfu/ml (95% CI 150, 860 cfu/ml) than the 3 step 1200cfu/ml (95% CI 940, 1850cfu/ml) to 750cfu/ml (95% CI 380, 1400cfu/ml) (p=0.016) but even with direct observation by two researchers and use of an instruction card demonstrating the technique, compliance with the 6 step technique was only 65%, compared to 100% compliance with 3 step technique. Further those participants with 100% compliance with 6 step technique had a significantly greater log reduction in bacterial load with no additional time or difference in coverage compared to those with 65% compliance with 6 step technique (p=0.01). Conclusion To our knowledge this is the first published RCT to demonstrate the 6 step technique is superior to the 3 step technique in reducing the residual bacterial load after hand hygiene using alcohol based hand rub in clinical practice. What remains unknown is whether the residual bacterial load after the 3 step technique is low enough to reduce risk of transmission from the hands and whether the 6 step technique can be adapted to enhance compliance in order to maximise reduction in residual bacterial load and reduce duration

A Pragmatic Randomized Controlled Trial of 6-Step vs 3-Step Hand Hygiene Technique in Acute Hospital Care in the United Kingdom.

OBJECTIVE To evaluate the microbiologic effectiveness of the World Health Organization's 6-step and the Centers for Disease Control and Prevention's 3-step hand hygiene techniques using alcohol-based handrub. DESIGN A parallel group randomized controlled trial. SETTING An acute care inner-city teaching hospital (Glasgow). PARTICIPANTS Doctors (n=42) and nurses (n=78) undertaking direct patient care. INTERVENTION Random 1:1 allocation of the 6-step (n=60) or the 3-step (n=60) technique. RESULTS The 6-step technique was microbiologically more effective at reducing the median log10 bacterial count. The 6-step technique reduced the count from 3.28 CFU/mL (95% CI, 3.11-3.38 CFU/mL) to 2.58 CFU/mL (2.08-2.93 CFU/mL), whereas the 3-step reduced it from 3.08 CFU/mL (2.977-3.27 CFU/mL) to 2.88 CFU/mL (-2.58 to 3.15 CFU/mL) (P=.02). However, the 6-step technique did not increase the total hand coverage area (98.8% vs 99.0%, P=.15) and required 15% (95% CI, 6%-24%) more time (42.50 seconds vs 35.0 seconds, P=.002). Total hand coverage was not related to the reduction in bacterial count. CONCLUSIONS Two techniques for hand hygiene using alcohol-based handrub are promoted in international guidance, the 6-step by the World Health Organization and 3-step by the Centers for Disease Control and Prevention. The study provides the first evidence in a randomized controlled trial that the 6-step technique is superior, thus these international guidance documents should consider this evidence, as should healthcare organizations using the 3-step technique in practice. Infect Control Hosp Epidemiol 2016;37:661-666

Harmonized gap-filled datasets from 20 urban flux tower sites

A total of 20 urban neighbourhood-scale eddy covariance flux tower datasets are made openly available after being harmonized to create a 50 site-year collection with broad diversity in climate and urban surface characteristics. Variables needed as inputs for land surface models (incoming radiation, temperature, humidity, air pressure, wind and precipitation) are quality controlled, gap-filled and prepended with 10 years of reanalysis-derived local data, enabling an extended spin up to equilibrate models with local climate conditions. For both gap filling and spin up, ERA5 reanalysis meteorological data are bias corrected using tower-based observations, accounting for diurnal, seasonal and local urban effects not modelled in ERA5. The bias correction methods developed perform well compared to methods used in other datasets (e.g. WFDE5 or FLUXNET2015). Other variables (turbulent and upwelling radiation fluxes) are harmonized and quality controlled without gap filling Site description metadata include local land cover fractions (buildings, roads, trees, grass etc.), building height and morphology, aerodynamic roughness estimates, population density and satellite imagery. This open collection can help extend our understanding of urban environmental processes through observational synthesis studies or in the evaluation of land surface environmental models in a wide range of urban settings. These data can be accessed from https://doi.org/10.5281/zenodo.7104984 (Lipson et al., 2022).Peer reviewe

Essential data variables for a minimum dataset for head and neck cancer trials and clinical research:HNCIG consensus recommendations and database

The Head and Neck Cancer International Group (HNCIG) has undertaken an international modified Delphi process to reach consensus on the essential data variables to be included in a minimum database for HNC research. Endorsed by 19 research organisations representing 34 countries, these recommendations provide the framework to facilitate and harmonise data collection and sharing for HNC research. These variables have also been incorporated into a ready to use downloadable HNCIG minimum database, available from the HNCIG website

Pilot Scale Production of Highly Efficacious and Stable Enterovirus 71 Vaccine Candidates

BACKGROUND: Enterovirus 71 (EV71) has caused several epidemics of hand, foot and mouth diseases (HFMD) in Asia and now is being recognized as an important neurotropic virus. Effective medications and prophylactic vaccine against EV71 infection are urgently needed. Based on the success of inactivated poliovirus vaccine, a prototype chemically inactivated EV71 vaccine candidate has been developed and currently in human phase 1 clinical trial. PRINCIPAL FINDING: In this report, we present the development of a serum-free cell-based EV71 vaccine. The optimization at each step of the manufacturing process was investigated, characterized and quantified. In the up-stream process development, different commercially available cell culture media either containing serum or serum-free was screened for cell growth and virus yield using the roller-bottle technology. VP-SFM serum-free medium was selected based on the Vero cell growth profile and EV71 virus production. After the up-stream processes (virus harvest, diafiltration and concentration), a combination of gel-filtration liquid chromatography and/or sucrose-gradient ultracentrifugation down-stream purification processes were investigated at a pilot scale of 40 liters each. Although the combination of chromatography and sucrose-gradient ultracentrifugation produced extremely pure EV71 infectious virus particles, the overall yield of vaccine was 7-10% as determined by a VP2-based quantitative ELISA. Using chromatography as the downstream purification, the virus yield was 30-43%. To retain the integrity of virus neutralization epitopes and the stability of the vaccine product, the best virus inactivation was found to be 0.025% formalin-treatment at 37 °C for 3 to 6 days. Furthermore, the formalin-inactivated virion vaccine candidate was found to be stable for >18 months at 4 °C and a microgram of viral proteins formulated with alum adjuvant could induce strong virus-neutralizing antibody responses in mice, rats, rabbits, and non-human primates. CONCLUSION: These results provide valuable information supporting the current cell-based serum-free EV71 vaccine candidate going into human Phase I clinical trials

Retention of Memory through Metamorphosis: Can a Moth Remember What It Learned As a Caterpillar?

Insects that undergo complete metamorphosis experience enormous changes in both morphology and lifestyle. The current study examines whether larval experience can persist through pupation into adulthood in Lepidoptera, and assesses two possible mechanisms that could underlie such behavior: exposure of emerging adults to chemicals from the larval environment, or associative learning transferred to adulthood via maintenance of intact synaptic connections. Fifth instar Manduca sexta caterpillars received an electrical shock associatively paired with a specific odor in order to create a conditioned odor aversion, and were assayed for learning in a Y choice apparatus as larvae and again as adult moths. We show that larvae learned to avoid the training odor, and that this aversion was still present in the adults. The adult aversion did not result from carryover of chemicals from the larval environment, as neither applying odorants to naïve pupae nor washing the pupae of trained caterpillars resulted in a change in behavior. In addition, we report that larvae trained at third instar still showed odor aversion after two molts, as fifth instars, but did not avoid the odor as adults, consistent with the idea that post-metamorphic recall involves regions of the brain that are not produced until later in larval development. The present study, the first to demonstrate conclusively that associative memory survives metamorphosis in Lepidoptera, provokes intriguing new questions about the organization and persistence of the central nervous system during metamorphosis. Our results have both ecological and evolutionary implications, as retention of memory through metamorphosis could influence host choice by polyphagous insects, shape habitat selection, and lead to eventual sympatric speciation

Road avoidance and its energetic consequences for reptiles

CITATION: Paterson, J. E., et al. 2019. Road avoidance and its energetic consequences for reptiles. Ecology and Evolution, 9(17):9794-9803, doi:10.1002/ece3.5515.The original publication is available at https://onlinelibrary.wiley.comRoads are one of the most widespread human-caused habitat modifications that can increase wildlife mortality rates and alter behavior. Roads can act as barriers with variable permeability to movement and can increase distances wildlife travel to access habitats. Movement is energetically costly, and avoidance of roads could therefore impact an animal's energy budget. We tested whether reptiles avoid roads or road crossings and explored whether the energetic consequences of road avoidance decreased individual fitness. Using telemetry data from Blanding's turtles (Emydoidea blandingii; 11,658 locations of 286 turtles from 15 sites) and eastern massasaugas (Sistrurus catenatus; 1,868 locations of 49 snakes from 3 sites), we compared frequency of observed road crossings and use of road-adjacent habitat by reptiles to expected frequencies based on simulated correlated random walks. Turtles and snakes did not avoid habitats near roads, but both species avoided road crossings. Compared with simulations, turtles made fewer crossings of paved roads with low speed limits and more crossings of paved roads with high speed limits. Snakes made fewer crossings of all road types than expected based on simulated paths. Turtles traveled longer daily distances when their home range contained roads, but the predicted energetic cost was negligible: substantially less than the cost of producing one egg. Snakes with roads in their home range did not travel further per day than snakes without roads in their home range. We found that turtles and snakes avoided crossing roads, but road avoidance is unlikely to impact fitness through energetic expenditures. Therefore, mortality from vehicle strikes remains the most significant impact of roads on reptile populations.https://onlinelibrary.wiley.com/doi/full/10.1002/ece3.5515Publisher's versio

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field