Statistical Mechanics of Horizontal Gene Transfer in Evolutionary Ecology

The biological world, especially its majority microbial component, is strongly interacting and may be dominated by collective effects. In this review, we provide a brief introduction for statistical physicists of the way in which living cells communicate genetically through transferred genes, as well as the ways in which they can reorganize their genomes in response to environmental pressure. We discuss how genome evolution can be thought of as related to the physical phenomenon of annealing, and describe the sense in which genomes can be said to exhibit an analogue of information entropy. As a direct application of these ideas, we analyze the variation with ocean depth of transposons in marine microbial genomes, predicting trends that are consistent with recent observations using metagenomic surveys.Comment: Accepted by Journal of Statistical Physic

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification. Funding: UK Research and Innovation and National Institute for Health Research

A randomised controlled trial to assess the relative benefits of large volume spacers and nebulisers to treat acute asthma in hospital

Objectives - To compare the clinical effectiveness, acceptability, and cost benefit of administering β2 agonists by means of a metered dose inhaler and large volume spacer with conventional nebulisers to children admitted to hospital with acute asthma. Methods - A randomised controlled trial was conducted over five months. Sixty one children older than 3 years admitted to a large teaching hospital and a district general hospital with acute asthma completed the study. Children received either 5 mg of salbutamol up to one hourly by jet nebuliser, or up to 10 puffs of salbutamol 100 μg by means of a metered dose inhaler and spacer up to one hourly. Results - Median hospital stay was 40 hours in the nebuliser group and 36.5 hours in the spacer group. Asthma disability scores at two weeks after discharge were significantly improved in the spacer group. Drug costs were £14.62 less for each patient in the spacer group. Conclusions - Large volume spacers are an acceptable, cost effective alternative to nebulisers in treating children admitted with acute asthma, provided that the children can use the mouthpiece, and symptoms are not severe. Their use facilitates effective home treatment by parents, with subsequent reduction in morbidity and re-admission rates.</p

Faecal elastase 1: A marker of exocrine pancreatic insufficiency in cystic fibrosis

Pancreatic elastase 1 (E1), a digestive protease, is synthesized by the acinar cells of the pancreas. Using an enzyme-linked immunosorbent assay, we evaluated stool E1 levels in the following groups of patients: (a) Specimens submitted for occult blood examination from 20 adults, over 3 consecutive days, to assess the inter-day variability in E1 excretion. There were no symptoms suggestive of pancreatic insufficiency in this group. The mean E1 concentration over all samples was 457 μg E1/g stool (range 124-1683). The intra-assay variation was 6.4% (n = 14) and the inter-assay variation was 8.8% (n = 12). The mean intra-patient variation was 17%. (b) Cystic fibrosis (CF) patients. Eight patients had E1 levels in the reference range (&gt; 200 μg E1/g stool). The remaining 25 patients had undetectable E1 levels. (c) A control group of children presenting with unexplained bronchiectasis and/or recurrent respiratory infections and no symptoms of pancreatic dysfunction. The mean E1 concentration in the group was 519 μg E1/g stool (range 139-1941). There was no significant difference in E1 concentrations between the two non-CF groups, nor between the pancreatic-sufficient CF patients when compared with both non-CF groups. There was a significant difference between the pancreatic-sufficient and insufficient CF groups (P &lt; 0.001 ) using the Mann-Whitney U test. All fifteen CF patients who were ΔF508 homozygotes had undetectable E1. It may be possible to relate CF genotype to the presence or absence of E1 and to the degree of pancreatic insufficiency. Measurement of faecal E1 in children with CF appears to differentiate them into a group of children with normal pancreatic function and a larger group with severe insufficiency.</p

Ciprofloxacin during upper respiratory tract infections to reduce Pseudomonas aeruginosa infection in paediatric cystic fibrosis: a pilot study

Objectives: Acute viral respiratory illnesses are associated with acquisition of Pseudomonas aeruginosa infection in cystic fibrosis (CF) patients. This study aimed to pilot a protocol for a randomized controlled trial to determine whether oral antipseudomonal antibiotics used at the onset of such episodes might delay onset of infection with this organism. Methods: A total of 41 children with CF aged 2–14 years, without chronic Pseudomonas infection, were randomized to receive ciprofloxacin (n = 28) or placebo (n = 13) at the onset of acute viral respiratory infections on an intention to treat basis, during a study period of up to 32 months. Results: There were no unexpected adverse events believed related to the use of the study medication. The rate of withdrawal from the study was low (approximately 7%) and did not differ between groups. Randomization was effective and acceptable to participants. Primary and secondary outcome measures all favoured active treatment, but there were no significant between group differences. The median rate of Pseudomonas isolates was 0/patient/year (interquartile range 0–0.38) in both the active and placebo groups. Kaplan–Meier survival curves showed no significant difference in time to first Pseudomonas isolate between groups. Conclusions: This study demonstrated the clinical feasibility of using oral ciprofloxacin in CF patients at times of viral infection. Within this sample size, no significant association was found between active treatment and decreased growth of Pseudomonas in follow-up microbiological samples. A definitive study would require at least 320 children to demonstrate significant differences in the rate of pseudomonal isolates. <br/