England SimSmoke: the impact of nicotine vaping on smoking prevalence and smoking‐attributable deaths in England

BACKGROUND AND AIMS: While the use of nicotine vaping products (NVPs) is widespread, their impact on smoking prevalence is controversial. This study considered the potential impact of NVPs on smoking prevalence in England. DESIGN: Indirect simulation model. The England SimSmoke model is validated through 2012, before NVP use became more widely used by smokers. Because information on NVP-related transitions is limited, an indirect method is used; the difference in observed smoking prevalence (reflecting NVPs) is compared with a 2012-2019 counterfactual No-NVP scenario (without NVPs) to estimate the impact of NVPs on smoking and smoking-attributable deaths. SETTING: England, 2000-2019. PARTICIPANTS: Nationally representative sample of population. MEASUREMENTS: England's population, mortality rates, and smoking prevalence estimates from three national surveys and tobacco control policies. FINDINGS: Between 2000 and 2012, SimSmoke projected a decline in age 18+ smoking prevalence of 23.5% in men and 27.0% in women. These projections, as well as those by specific age groups, were generally consistent with findings from the three national surveys. Comparing 2012-2019 relative reduction in age 18+ prevalence from the Annual Population Survey (males 27.5%) with the model-predicted No-NVP reduction (males 7.3%), the implied NVP-attributable relative reduction in adult smoking prevalence was 20.2% (95% CI, 18.8%-22.0%) for males and 20.4% (18.7%-22.2%) for females. The NVP-attributable reduction was 27.2% (22.8%-31.6%) for males and 31.7% (27.4%-36.5%) for females ages 18-24 and 18.6% (15.2%-21.8%) for males and 15.0% (11.1%-18.8%) for females ages 25-34, with similar reductions for ages 35 and above. The implied reduction in smoking prevalence between 2012 and 2019 equates to 165,660 (132,453-199,501) averted deaths by 2052. Other surveys yielded smaller, but relatively consistent results. CONCLUSIONS: An indirect method of simulation modeling indicates that substantial reductions in smoking prevalence occurred in England from 2012 to 2019 coinciding with the growth in nicotine vaping product use

Atmospheric pollution, soil nutrients and climate effects on Mucoromycota arbuscular mycorrhizal fungi

Fine root endophyte mycorrhizal fungi in the Endogonales (Mucoromycota arbuscular mycorrhizal fungi, M-AMF) are now recognized as at least as important globally as Glomeromycota AMF (G-AMF), yet little is known about the environmental factors which influence M-AMF diversity and colonization, partly because they typically only co-colonize plants with G-AMF. Wild populations of Lycopodiella inundata predominantly form mycorrhizas with M-AMF and therefore allow focussed study of M-AMF environmental drivers. Using microscopic examination and DNA sequencing we measured M-AMF colonization and diversity over three consecutive seasons and modelled interactions between these response variables and environmental data. Significant relationships were found between M-AMF colonization and soil S, P, C:N ratio, electrical conductivity, and the previously overlooked micronutrient Mn. Estimated N deposition was negatively related to M-AMF colonization. Thirty-nine Endogonales Operational Taxonomic Units (OTUs) were identified in L. inundata roots, a greater diversity than previously recognized in this plant. Endogonales OTU richness correlated negatively with soil C:N while community composition was mostly influenced by soil P. This study provides first evidence that M-AMF have distinct ecological preferences in response to edaphic variables also related to air pollution. Future studies require site-level atmospheric pollution monitoring to guide critical load policy for mycorrhizal fungi in heathlands and grasslands

"The Mystery of the Raddlesham Mumps": A case study for combined storytelling in a theatre play and Virtual Reality

“The Mystery of the Raddlesham Mumps” is a poem by Murray Lachlan Young, aimed at both children and adults. This poem has been adapted as a theatre play with a short prequel as a Virtual Reality (VR)/tablet app. We used this unique combination to explore the potential interaction between these different media elements for the level of “presence” and “immersion” in the story (i.e. the level to which one can imagine oneself within the story at the expense of the sense of physical time and space). The theatre audience had the opportunity to play the VR/tablet app in the foyer before the performance started. After the performance, a questionnaire measured participants’ level of immersion and presence in the theatre play and their enjoyment of both play and app. The results showed that people of all ages interacted with and liked the app. Ratings for the play were also high and did not depend on prior engagement with the app. However, the play was liked more by adults than children, and the reverse was true for the app, suggesting a potential generation shift in multimedia story telling

Capsular profiling of the Cronobacter genus and the association of specific Cronobacter sakazakii and C. malonaticus capsule types with neonatal meningitis and necrotizing enterocolitis

Background: Cronobacter sakazakii and C. malonaticus can cause serious diseases especially in infants where they are associated with rare but fatal neonatal infections such as meningitis and necrotising enterocolitis. Methods: This study used 104 whole genome sequenced strains, covering all seven species in the genus, to analyse capsule associated clusters of genes involved in the biosynthesis of the O-antigen, colanic acid, bacterial cellulose, enterobacterial common antigen (ECA), and a previously uncharacterised K-antigen. Results: Phylogeny of the gnd and galF genes flanking the O-antigen region enabled the defining of 38 subgroups which are potential serotypes. Two variants of the colanic acid synthesis gene cluster (CA1 and CA2) were found which differed with the absence of galE in CA2. Cellulose (bcs genes) were present in all species, but were absent in C. sakazakii sequence type (ST) 13 and clonal complex (CC) 100 strains. The ECA locus was found in all strains. The K-antigen capsular polysaccharide Region 1 (kpsEDCS) and Region 3 (kpsMT) genes were found in all Cronobacter strains. The highly variable Region 2 genes were assigned to 2 homology groups (K1 and K2). C. sakazakii and C. malonaticus isolates with capsular type [K2:CA2:Cell+] were associated with neonatal meningitis and necrotizing enterocolitis. Other capsular types were less associated with clinical infections. Conclusion: This study proposes a new capsular typing scheme which identifies a possible important virulence trait associated with severe neonatal infections. The various capsular polysaccharide structures warrant further investigation as they could be relevant to macrophage survival, desiccation resistance, environmental survival, and biofilm formation in the hospital environment, including neonatal enteral feeding tubes

The impact of local and national restrictions in response to COVID-19 on social contacts in England: a longitudinal natural experiment.

BACKGROUND: England's COVID-19 response transitioned from a national lockdown to localised interventions. In response to rising cases, these were supplemented by national restrictions on contacts (the Rule of Six), then 10 pm closing for bars and restaurants, and encouragement to work from home. These were quickly followed by a 3-tier system applying different restrictions in different localities. As cases continued to rise, a second national lockdown was declared. We used a national survey to quantify the impact of these restrictions on epidemiologically relevant contacts. METHODS: We compared paired measures on setting-specific contacts before and after each restriction started and tested for differences using paired permutation tests on the mean change in contacts and the proportion of individuals decreasing their contacts. RESULTS: Following the imposition of each measure, individuals tended to report fewer contacts than they had before. However, the magnitude of the changes was relatively small and variable. For instance, although early closure of bars and restaurants appeared to have no measurable effect on contacts, the work from home directive reduced mean daily work contacts by 0.99 (95% confidence interval CI] 0.03-1.94), and the Rule of Six reduced non-work and school contacts by a mean of 0.25 (0.01-0.5) per day. Whilst Tier 3 appeared to also reduce non-work and school contacts, the evidence for an effect of the lesser restrictions (Tiers 1 and 2) was much weaker. There may also have been some evidence of saturation of effects, with those who were in Tier 1 (least restrictive) reducing their contacts markedly when they entered lockdown, which was not reflected in similar changes in those who were already under tighter restrictions (Tiers 2 and 3). CONCLUSIONS: The imposition of various local and national measures in England during the summer and autumn of 2020 has gradually reduced contacts. However, these changes are smaller than the initial lockdown in March. This may partly be because many individuals were already starting from a lower number of contacts

UBR5 is a Novel E3 Ubiquitin Ligase involved in Skeletal Muscle Hypertrophy and Recovery from Atrophy

We have recently identified that a HECT domain E3 ubiquitin ligase, named UBR5, was epigenetically altered (via DNA methylation) after human skeletal muscle hypertrophy, where its gene expression was positively correlated with increased lean leg mass in humans [1]. This was counterintuitive given the well-defined role of other E3 ligase family members, MuRF1 and MAFbx in muscle atrophy. Therefore, in the present study we aimed to investigate this relatively uncharacterised E3 ubiquitin ligase using multiple in-vivo and in-vitro models of skeletal muscle atrophy, injury, recovery from atrophy as well as anabolism and hypertrophy. We report for the first time, that during atrophy evoked by tetrodotoxin (TTX) nerve silencing in rats, the UBR5 promoter was significantly hypomethylated with a concomitant increase in gene expression early (3 & 7 days) after the induction of atrophy. However, at these timepoints larger increases in MuRF1/MAFbx were observed, and UBR5 expression had returned to baseline levels during later atrophy (14 days) where muscle mass loss was greatest. We confirmed an alternate gene expression profile for UBR5 versus MuRF1/MAFbx in a secondary model of atrophy induced by 7 days continuous low frequency electrical stimulation, where UBR5 demonstrated no significant increase, whereas MuRF1/MAFbx were elevated. Further, after partial (52%) recovery of muscle mass following 7 days TTX-cessation, UBR5 was hypomethylated and increased at the gene expression level, while alternately, reductions in gene expression of MuRF1 and MAFbx were observed. To substantiate these gene expression findings, we observed a significant increase in UBR5 protein abundance after full recovery (14 days) of muscle mass from hindlimb unloading (HU) in rats. Aged rats also demonstrated a similar temporal increase in UBR5 protein abundance after recovery from HU. Further, we confirmed significant increases in UBR5 protein during recovery from nerve crush injury in mice at 28 and 45 days, that related to a full recovery of muscle mass between 45-60 days. During anabolism and hypertrophy, UBR5 gene expression increased following an acute bout of mechanical loading in three-dimensional bioengineered mouse muscle in-vitro, and after chronic electrical stimulation-induced hypertrophy in rats in-vivo, without increases in MuRF1/MAFbx. Additionally, increased UBR5 protein abundance was identified following synergist ablation/functional overload (FO)-induced hypertrophy of the plantaris muscle in mice in-vivo, and finally over a 7-day time-course of regeneration in primary human muscle cells in-vitro. Finally, genetic association studies (> 700,000 SNPs) in human cohorts identified that the A alleles of rs10505025 and rs4734621 SNPs were strongly associated with larger cross-sectional area of fast-twitch muscle fibres and favoured strength/power versus endurance/untrained phenotypes. Overall, we suggest that UBR5 is a novel E3 ubiquitin ligase that is alternatively regulated compared to MuRF1/MAFbx, and is elevated during early atrophy (but not later atrophy), recovery, anabolism and hypertrophy in animals in-vivo as well as during human muscle cell regeneration in-vitro. In humans, genetic variations of the UBR5 gene are strongly associated with larger fast-twitch muscle fibres and strength/power performance

Current realities versus theoretical optima: quantifying efficiency and sociospatial equity of travel time to hospitals in low-income and middle-income countries.

BACKGROUND: Having hospitals located in urban areas where people, resources and wealth concentrate is efficient, but leaves long travel times for the rural and often poorer population and goes against the equity objective. We aimed to assess the current efficiency (mean travel time in the whole population) and equity (difference in travel time between the poorest and least poor deciles) of hospital care provision in four sub-Saharan African countries, and to compare them against their theoretical optima. METHODS: We overlaid the locations of 480, 115, 3787 and 256 hospitals in Kenya, Malawi, Nigeria and Tanzania, respectively, with high-resolution maps of travel time, population and wealth to estimate current efficiency and equity. To identify the potential optima, we simulated 7500 sets of hospitals locations based on various population and wealth weightings and percentage reallocations for each country. RESULTS: The average travel time ranged from 38 to 79 min across countries, and the respective optima were mildly shorter (<15%). The observed equity gaps were wider than their optima. Compared with the best case scenarios, differences in the equity gaps varied from 7% in Tanzania to 77% in Nigeria. In Kenya, Malawi and Tanzania, narrower equity gaps without increasing average travel time were seen from simulations that held 75%-90% of hospitals at their current locations. INTERPRETATIONS: Current hospital distribution in the four sub-Saharan African countries could be considered efficient. Simultaneous gains in efficiency and equity do not necessarily require a fundamental redesign of the healthcare system. Our analytical approach is readily extendible to aid decision support in adding and upgrading existing hospitals

Daily antibiotic cost of nosocomial infections in a Turkish university hospital

BACKGROUND: Many studies associated nosocomial infections with increased hospital costs due to extra days in hospital, staff time, extra investigations and drug treatment. The cost of antibiotic treatment for these infections represents a significant part of hospital expenditure. This prospective observational study was designed to determine the daily antibiotic cost of nosocomial infections per infected adult patient in Akdeniz University Hospital. METHODS: All adult patients admitted to the ICUs between January 1, 2000, and June 30, 2003 who had only one nosocomial infection during their stay were included in the study. Infection sites and pathogens, antimicrobial treatment of patient and it's cost were recorded. Daily antibiotic costs were calculated per infected patient. RESULTS: Among the 8460 study patients, 817 (16.6%) developed 1407 episodes of nosocomial infection. Two hundred thirty three (2.7%) presented with only one nosocomial infection. Mean daily antibiotic cost was $89.64. Daily antibiotic cost was$99.02 for pneumonia, $94.32 for bloodstream infection,$94.31 for surgical site infection, $52.37 for urinary tract infection, and$162.35 for the other infections per patient. The treatment of Pseudomonas aeruginosa infections was the most expensive infection treated. Piperacillin-tazobactam and amikacin were the most prescribed antibiotics, and meropenem was the most expensive drug for treatment of the nosocomial infections in the ICU. CONCLUSIONS: Daily antibiotic cost of nosocomial infections is an important part of extra costs that should be reduced providing rational antibiotic usage in hospitals