Colorectal cancer (CRC) is thought to arise when the cumulative mutational burden within colonic crypts exceeds a certain threshold that leads to clonal expansion and ultimately neoplastic transformation. Therefore, quantification of the fixation and subsequent expansion of somatic mutations in normal epithelium is key to understanding colorectal cancer initiation. The aim of the present study was to determine how advantaged expansions can be accommodated in the human colon. Immunohistochemistry was used to visualize loss of the cancer driver KDM6A in formalin-fixed paraffin-embedded (FFPE) normal human colonic epithelium. Combining microscopy with neural network-based image analysis, we determined the frequencies of KDM6A-mutant crypts and fission/fusion intermediates as well as the spatial distribution of clones. Mathematical modeling then defined the dynamics of their fixation and expansion. Interpretation of the age-related behavior of KDM6A-negative clones revealed significant competitive advantageps.Infection prevention strategies need to be identified and evaluated to reduce the risk associated with contaminated hospital sinks. This study used settle plates to compare the dispersal of Gram-negative bacteria from a conventional, rear-draining clinical handwash basin (CHWB) and a 'splash-reducing' CHWB with and/or without impaired drainage. Two scenarios were assessed dispersal from a contaminated basin and dispersal from a contaminated drain. The associated tap was operated for 1 min and, for all contamination scenarios, the 'splash-reducing' CHWB had significantly lower odds of spreading contamination than the conventional CHWB. The WHO's AWaRe classification categorizes antibiotics into three stewardship groups Access, Watch and Reserve. The Access group includes antibiotics with lower resistance potential than antibiotics in the other two groups. The UK five-year AMR strategy has set targets for reducing non-Access antibiotic use. The majority of penicillins are in the Access group and therefore patients with a penicillin allergy record are likely to receive more non-Access antibiotics. This study aimed to quantify the impact of penicillin allergy records on non-Access antibiotic prescribing and to estimate potential reductions in non-Access antibiotic use through penicillin allergy de-labelling. Inpatients of a 750-patient-bed UK district general hospital in England prescribed antibiotics between 1 April 2018 and 31 March 2019 were included. Variables included age, sex, co-morbidity, infection treated, antibiotic usage, hospital length of stay, penicillin allergy status. Multivariable logistic regression was used to explore the association between patient characteristics and their receipt of antibiotics in the Access and non-Access groups. A total of 67,059 antibiotic prescriptions for 23,356 inpatients were analysed. Penicillin allergy records were present in 14.3% of hospital admissions. Patients with a penicillin allergy record were around four times more likely (odds ratio= 4.7) to receive an antibiotic from the non-Access groups (i.e. Reserve and Watch groups). We estimate de-labelling 50% of hospital inpatients with a penicillin allergy record could reduce non-Access antibiotic use by 5.8% and total antibiotic use by 0.86%. Penicillin allergy records are associated with non-Access antibiotic prescribing. Penicillin allergy de-labelling has potential to reduce non-Access antibiotic use.Penicillin allergy records are associated with non-Access antibiotic prescribing. Penicillin allergy de-labelling has potential to reduce non-Access antibiotic use. The Neptune® surgical suction system (NSSS) and the Bair Hugger® (BH) forced-air warmer both discharge filtered exhaust or heated air into the operating room (OR), often in close proximity to a surgical site. To assess the effectiveness of this filtration, we examined the quantity and identity of microbial colonies emitted from their output ports compared with those obtained from circulating air entering the OR. Air samples were collected from each device using industry-standard sampling devices in which a measured volume of air is impacted on to a blood agar plate at a controlled flow rate. Twelve ORs were studied. Sample plates were incubated for one week per study protocol, then interpreted for colony counts and sent for species identification. The average colony count from the NSSS exhaust was not significantly different from that obtained from room air samples, however the average count from the BH output was significantly higher (P=0.0086) than room air. Genetic identification profiles revealed the presence of environmental or commensal organisms that differed depending on the source. High variability in colony counts from both devices suggests that certain NSSS and BH devices could be significant sources of OR air contamination. Our study showed that the BH patient warming device could be a source of airborne microbial contamination in the OR and that individual BH and NSSS units exhibit a higher output of microbial cfu than would be expected compared with incoming room air. We make simple suggestions on ways to mitigate these risks.Our study showed that the BH patient warming device could be a source of airborne microbial contamination in the OR and that individual BH and NSSS units exhibit a higher output of microbial cfu than would be expected compared with incoming room air. We make simple suggestions on ways to mitigate these risks.We have reported previously that retinal pigment epithelium (RPE) differentiated from induced pluripotent stem cells (iPSC) generated from fibroblasts of patients with age-related macular degeneration (AMD) exhibit a retinal degenerative disease phenotype and a distinct transcriptome compared to age-matched controls. Since the genetic composition of the iPSC and RPE are inherited from fibroblasts, we investigated whether differential behavior was present in the parental fibroblasts and iPSC prior to differentiation of the cell lines into RPE. Principal component analyses revealed significant overlap (essentially no differences) in the transcriptome of fibroblasts between AMD and controls. After reprogramming, there was no significant difference in the transcriptome of iPSC generated from AMD versus normal donors. GSK2656157 cell line In contrast, the transcriptome of RPE derived from iPSC segregated into two distinct clusters of AMD-derived cells versus controls. Interestingly, mitochondrial dysfunction in AMD-derived RPE was evident after approximately two months in culture.