Prediction of far-field acoustic emissions from cavitation clouds during shock wave lithotripsy for development of a clinical device

This study presents the key simulation and decision stage of a multi-disciplinary project to develop a hospital device for monitoring the effectiveness of kidney stone fragmentation by shock wave lithotripsy (SWL). The device analyses, in real time, the pressure fields detected by sensors placed on the patient's torso, fields generated by the interaction of the incident shock wave, cavitation, kidney stone and soft tissue. Earlier free-Lagrange simulations of those interactions were restricted (by limited computational resources) to computational domains within a few centimetres of the stone. Later studies estimated the far-field pressures generated when those interactions involved only single bubbles. This study extends the free-Lagrange method to quantify the bubble–bubble interaction as a function of their separation. This, in turn, allowed identification of the validity of using a model of non-interacting bubbles to obtain estimations of the far-field pressures from 1000 bubbles distributed within the focus of the SWL field. Up to this point in the multi-disciplinary project, the design of the clinical device had been led by the simulations. This study records the decision point when the project's direction had to be led by far more costly clinical trials instead of the relatively inexpensive simulations. <br/

Gradient flux measurements of sea–air DMS transfer during the Surface Ocean Aerosol Production (SOAP) experiment

Direct measurements of marine dimethylsulfide (DMS) fluxes are sparse, particularly in the Southern Ocean. The Surface Ocean Aerosol Production (SOAP) voyage in February–March 2012 examined the distribution and flux of DMS in a biologically active frontal system in the southwest Pacific Ocean. Three distinct phytoplankton blooms were studied with oceanic DMS concentrations as high as 25 nmol L−1. Measurements of DMS fluxes were made using two independent methods: the eddy covariance (EC) technique using atmospheric pressure chemical ionization–mass spectrometry (API-CIMS) and the gradient flux (GF) technique from an autonomous catamaran platform. Catamaran flux measurements are relatively unaffected by airflow distortion and are made close to the water surface, where gas gradients are largest. Flux measurements were complemented by near-surface hydrographic measurements to elucidate physical factors influencing DMS emission. Individual DMS fluxes derived by EC showed significant scatter and, at times, consistent departures from the Coupled Ocean–Atmosphere Response Experiment gas transfer algorithm (COAREG). A direct comparison between the two flux methods was carried out to separate instrumental effects from environmental effects and showed good agreement with a regression slope of 0.96 (r2 = 0.89). A period of abnormal downward atmospheric heat flux enhanced near-surface ocean stratification and reduced turbulent exchange, during which GF and EC transfer velocities showed good agreement but modelled COAREG values were significantly higher. The transfer velocity derived from near-surface ocean turbulence measurements on a spar buoy compared well with the COAREG model in general but showed less variation. This first direct comparison between EC and GF fluxes of DMS provides confidence in compilation of flux estimates from both techniques, as well as in the stable periods when the observations are not well predicted by the COAREG model

Using eddy covariance to measure the dependence of air–sea CO2 exchange rate on friction velocity

Parameterisation of the air–sea gas transfer velocity of CO2 and other trace gases under open-ocean conditions has been a focus of air–sea interaction research and is required for accurately determining ocean carbon uptake. Ships are the most widely used platform for air–sea flux measurements but the quality of the data can be compromised by airflow distortion and sensor cross-sensitivity effects. Recent improvements in the understanding of these effects have led to enhanced corrections to the shipboard eddy covariance (EC) measurements. Here, we present a revised analysis of eddy covariance measurements of air–sea CO2 and momentum fluxes from the Southern Ocean Surface Ocean Aerosol Production (SOAP) study. We show that it is possible to significantly reduce the scatter in the EC data and achieve consistency between measurements taken on station and with the ship underway. The gas transfer velocities from the EC measurements correlate better with the EC friction velocity (u*) than with mean wind speeds derived from shipboard measurements corrected with an airflow distortion model. For the observed range of wind speeds (u10 N = 3–23 m s−1), the transfer velocities can be parameterised with a linear fit to u*. The SOAP data are compared to previous gas transfer parameterisations using u10 N computed from the EC friction velocity with the drag coefficient from the Coupled Ocean–Atmosphere Response Experiment (COARE) model version 3.5. The SOAP results are consistent with previous gas transfer studies, but at high wind speeds they do not support the sharp increase in gas transfer associated with bubble-mediated transfer predicted by physically based models

Horizontal gene transfer in bdelloid rotifers is ancient, ongoing and more frequent in species from desiccating habitats.

BACKGROUND: Although prevalent in prokaryotes, horizontal gene transfer (HGT) is rarer in multicellular eukaryotes. Bdelloid rotifers are microscopic animals that contain a higher proportion of horizontally transferred, non-metazoan genes in their genomes than typical of animals. It has been hypothesized that bdelloids incorporate foreign DNA when they repair their chromosomes following double-strand breaks caused by desiccation. HGT might thereby contribute to species divergence and adaptation, as in prokaryotes. If so, we expect that species should differ in their complement of foreign genes, rather than sharing the same set of foreign genes inherited from a common ancestor. Furthermore, there should be more foreign genes in species that desiccate more frequently. We tested these hypotheses by surveying HGT in four congeneric species of bdelloids from different habitats: two from permanent aquatic habitats and two from temporary aquatic habitats that desiccate regularly. RESULTS: Transcriptomes of all four species contain many genes with a closer match to non-metazoan genes than to metazoan genes. Whole genome sequencing of one species confirmed the presence of these foreign genes in the genome. Nearly half of foreign genes are shared between all four species and an outgroup from another family, but many hundreds are unique to particular species, which indicates that HGT is ongoing. Using a dated phylogeny, we estimate an average of 12.8 gains versus 2.0 losses of foreign genes per million years. Consistent with the desiccation hypothesis, the level of HGT is higher in the species that experience regular desiccation events than those that do not. However, HGT still contributed hundreds of foreign genes to the species from permanently aquatic habitats. Foreign genes were mainly enzymes with various annotated functions that include catabolism of complex polysaccharides and stress responses. We found evidence of differential loss of ancestral foreign genes previously associated with desiccation protection in the two non-desiccating species. CONCLUSIONS: Nearly half of foreign genes were acquired before the divergence of bdelloid families over 60 Mya. Nonetheless, HGT is ongoing in bdelloids and has contributed to putative functional differences among species. Variation among our study species is consistent with the hypothesis that desiccating habitats promote HGT

A lifecourse mendelian randomization study highlights the long-term influence of childhood body size on later life heart structure

Children with obesity typically have larger left ventricular heart dimensions during adulthood. However, whether this is due to a persistent effect of adiposity extending into adulthood is challenging to disentangle due to confounding factors throughout the lifecourse. We conducted a multivariable mendelian randomization (MR) study to separate the independent effects of childhood and adult body size on 4 magnetic resonance imaging (MRI) measures of heart structure and function in the UK Biobank (UKB) study. Strong evidence of a genetically predicted effect of childhood body size on all measures of adulthood heart structure was identified, which remained robust upon accounting for adult body size using a multivariable MR framework (e.g., left ventricular end-diastolic volume (LVEDV), Beta = 0.33, 95% confidence interval (CI) = 0.23 to 0.43, P = 4.6 × 10-10). Sensitivity analyses did not suggest that other lifecourse measures of body composition were responsible for these effects. Conversely, evidence of a genetically predicted effect of childhood body size on various other MRI-based measures, such as fat percentage in the liver (Beta = 0.14, 95% CI = 0.05 to 0.23, P = 0.002) and pancreas (Beta = 0.21, 95% CI = 0.10 to 0.33, P = 3.9 × 10-4), attenuated upon accounting for adult body size. Our findings suggest that childhood body size has a long-term (and potentially immutable) influence on heart structure in later life. In contrast, effects of childhood body size on other measures of adulthood organ size and fat percentage evaluated in this study are likely explained by the long-term consequence of remaining overweight throughout the lifecourse

A Genome-wide gene-expression analysis and database in transgenic mice during development of amyloid or tau pathology

We provide microarray data comparing genome-wide differential expression and pathology throughout life in four lines of "amyloid" transgenic mice (mutant human APP, PSEN1, or APP/PSEN1) and "TAU" transgenic mice (mutant human MAPT gene). Microarray data were validated by qPCR and by comparison to human studies, including genome-wide association study (GWAS) hits. Immune gene expression correlated tightly with plaques whereas synaptic genes correlated negatively with neurofibrillary tangles. Network analysis of immune gene modules revealed six hub genes in hippocampus of amyloid mice, four in common with cortex. The hippocampal network in TAU mice was similar except that Trem2 had hub status only in amyloid mice. The cortical network of TAU mice was entirely different with more hub genes and few in common with the other networks, suggesting reasons for specificity of cortical dysfunction in FTDP17. This Resource opens up many areas for investigation. All data are available and searchable at http://www.mouseac.org

The interaction between vaginal microbiota, cervical length and vaginal progesterone treatment for preterm birth risk

Background: Preterm birth is the primary cause of infant death worldwide. A short cervix in the second trimester of pregnancy is a risk factor for preterm birth. In specific patient cohorts, vaginal progesterone reduces this risk. Using 16S rRNA gene sequencing we undertook a prospective study in women at risk of preterm birth (n=161) to assess 1) the relationship between vaginal microbiota and cervical length in the second trimester and preterm birth-risk, and 2) the impact of vaginal progesterone on vaginal bacterial communities in women with a short cervix. Results: Lactobacillus iners dominance at 16 weeks gestation was significantly associated with both a short cervix <25mm (n=15, P<0.05), and preterm birth <34+0 weeks (n=18, 38P<0.01; 69% PPV). In contrast, L. crispatus dominance was highly predictive of term birth (n=127, 98% PPV). Cervical shortening and preterm birth were not associated with vaginal dysbiosis. A longitudinal characterization of vaginal microbiota (<18, 22, 28 and 34 weeks) was then undertaken in women receiving vaginal progesterone (400mg/OD, n=25) versus controls (n=42). Progesterone did not alter vaginal bacterial community structure nor reduce L. iners-associated preterm birth (<34 weeks). Conclusions: L. iners dominance of the vaginal microbiota at 16 weeks gestation is a risk factor for preterm birth, whereas L. crispatus dominance is protective against preterm birth. Vaginal progesterone does not appear to impact the pregnancy vaginal microbiota. Patients and clinicians who may be concerned about ‘infection risk’ associated with use of a vaginal pessary during high-risk pregnancy can be reassured

Reducing outcome measures in mental health: a systematic review of the methods

Economic and Social Research Council (ESRC) Grant number ES/J500057/1 and South London and Maudsley NHS Trust

A novel membrane inlet-infrared gas analysis (MI-IRGA) system for monitoring of seawater carbonate system

Increased atmospheric CO 2 concentrations are driving changes in ocean chemistry at unprecedented rates resulting in ocean acidification, which is predicted to impact the functioning of marine biota, in particular of marine calcifiers. However, the precise understanding of such impacts relies on an analytical system that determines the mechanisms and impact of elevated pCO 2 on the physiology of organisms at scales from species to entire communities. Recent work has highlighted the need within experiments to control all aspects of the carbonate system to resolve the role of different inorganic carbon species on the physiological responses observed across taxa in real-time. Presently however, there are limited options available for continuous quantification of physiological responses, coupled with real-time calculation of the seawater carbonate chemistry system within microcosm environments. Here, we describe and characterise the performance of a novel pCO 2 membrane equilibrium system (the Membrane Inlet Infra-Red Gas Analyser, MI-IRGA) integrated with a continuous pH and oxygen monitoring platform. The system can detect changes in the seawater carbonate chemistry and determine organism physiological responses, while providing the user with real-time control over the microcosm system. We evaluate the systems control, response time and associated error, and demonstrate the flexibility of the system to operate under field conditions and within a laboratory. We use the system to measure physiological parameters (photosynthesis and respiration) for the corals Pocillipora damicornis and Porites cylindrica; in doing so we present a novel dataset examining the interactive role of temperature, light and pCO 2 on the physiology of P. cylindrica