Water surface response to turbulent flow over a backward-facing step

The water surface response to subcritical turbulent flow over a backward-facing step (BFS) is studied via high-resolution large-eddy simulation (LES). The LES method is validated first using data of previously reported experiments. The LES-predicted water surface is decomposed into different types of gravity waves as well as turbulence-driven forced waves. Analysis of the LES data reveals the interplay between low-frequency large-scale turbulence structures, which are the result of flow separation from the step and reattachment behind the step, and the dynamics of the water surface. The water surface deformation is mainly the result of freely propagating gravity waves and forced waves, owing to turbulence in the form of rollers and/or hairpin vortices. Gravity waves with zero group velocity define the characteristic spatial and temporal scales of the surface deformations at higher frequencies, while large eddies determine their low-frequency modulation. These deformations are mainly confined in lateral bands that propagate downstream following the advection of the near-surface streamwise vortices (rollers) that are shed from the step. Steeper surface waves are observed in regions of negative perturbation velocity gradient and down-welling, downstream of the larger rollers, and are associated with thin isolated regions of high vorticity near the surface. The investigation of such a complex flow has shown that the decomposition of the water surface fluctuations into its different physical components may be used to identify the dynamics of the underlying flow structure

Frequencies and patterns of microbiology test requests from primary care in Oxfordshire, UK, 2008-2018: a retrospective cohort study of electronic health records to inform point of care testing

Objectives: To inform point-of-care test (POCT) development, we quantified the primary care demand for laboratory microbiology tests by describing their frequencies overall, frequencies of positives, most common organisms identified, temporal trends in testing and patterns of cotesting on the same and subsequent dates. Design: Retrospective cohort study. Setting: Primary care practices in Oxfordshire. Participants :393 905 patients (65% female; 49% aged 18–49). Primary and secondary outcome measures The frequencies of all microbiology tests requested between 2008 and 2018 were quantified. Patterns of cotesting were investigated with heat maps. All analyses were done overall, by sex and age categories. Results: 1 596 752 microbiology tests were requested. Urine culture±microscopy was the most common of all tests (n=673 612, 42%), was mainly requested without other tests and was the most common test requested in follow-up within 7 and 14 days. Of all urine cultures, 180 047 (27%) were positive and 172 651 (26%) showed mixed growth, and Escherichia coli was the most prevalent organism (132 277, 73% of positive urine cultures). Antenatal urine cultures and blood tests in pregnancy (hepatitis B, HIV and syphilis) formed a common test combination, consistent with their use in antenatal screening. Conclusions: The greatest burden of microbiology testing in primary care is attributable to urine culture ± microscopy; genital and routine antenatal urine and blood testing are also significant contributors. Further research should focus on the feasibility and impact of POCTs for these specimen types

Water surface response to turbulent flow over a backward-facing step

The water surface response to subcritical turbulent flow over a backward-facing step (BFS) is studied via high-resolution large-eddy simulation (LES). The LES method is validated first using data of previously reported experiments. The LES-predicted water surface is decomposed into different types of gravity waves as well as turbulence-driven forced waves. Analysis of the LES data reveals the interplay between low-frequency large-scale turbulence structures, which are the result of flow separation from the step and reattachment behind the step, and the dynamics of the water surface. The water surface deformation is mainly the result of freely propagating gravity waves and forced waves, owing to turbulence in the form of rollers and/or hairpin vortices. Gravity waves with zero group velocity define the characteristic spatial and temporal scales of the surface deformations at higher frequencies, while large eddies determine their low-frequency modulation. These deformations are mainly confined in lateral bands that propagate downstream following the advection of the near-surface streamwise vortices (rollers) that are shed from the step. Steeper surface waves are observed in regions of negative perturbation velocity gradient and down-welling, downstream of the larger rollers, and are associated with thin isolated regions of high vorticity near the surface. The investigation of such a complex flow has shown that the decomposition of the water surface fluctuations into its different physical components may be used to identify the dynamics of the underlying flow structure

Supporting surveillance capacity for antimicrobial resistance: Laboratory capacity strengthening for drug resistant infections in low and middle income countries.

Development of antimicrobial resistance (AMR) threatens our ability to treat common and life threatening infections. Identifying the emergence of AMR requires strengthening of surveillance for AMR, particularly in low and middle-income countries (LMICs) where the burden of infection is highest and health systems are least able to respond. This work aimed, through a combination of desk-based investigation, discussion with colleagues worldwide, and visits to three contrasting countries (Ethiopia, Malawi and Vietnam), to map and compare existing models and surveillance systems for AMR, to examine what worked and what did not work. Current capacity for AMR surveillance varies in LMICs, but and systems in development are focussed on laboratory surveillance. This approach limits understanding of AMR and the extent to which laboratory results can inform local, national and international public health policy. An integrated model, combining clinical, laboratory and demographic surveillance in sentinel sites is more informative and costs for clinical and demographic surveillance are proportionally much lower. The speed and extent to which AMR surveillance can be strengthened depends on the functioning of the health system, and the resources available. Where there is existing laboratory capacity, it may be possible to develop 5-20 sentinel sites with a long term view of establishing comprehensive surveillance; but where health systems are weaker and laboratory infrastructure less developed, available expertise and resources may limit this to 1-2 sentinel sites. Prioritising core functions, such as automated blood cultures, reduces investment at each site. Expertise to support AMR surveillance in LMICs may come from a variety of international, or national, institutions. It is important that these organisations collaborate to support the health systems on which AMR surveillance is built, as well as improving technical capacity specifically relating to AMR surveillance. Strong collaborations, and leadership, drive successful AMR surveillance systems across countries and contexts

Covert dissemination of carbapenemase-producing Klebsiella pneumoniae (KPC) in a successfully controlled outbreak: long and short-read whole-genome sequencing demonstrate multiple genetic modes of transmission

Background: Carbapenemase-producing Enterobacteriaceae (CPE), including KPC-producing Klebsiella pneumoniae (KPC-Kpn), are an increasing threat to patient safety. Objectives: To use WGS to investigate the extent and complexity of carbapenemase gene dissemination in a controlled KPC outbreak. Materials and methods: Enterobacteriaceae with reduced ertapenem susceptibility recovered from rectal screening swabs/clinical samples, during a 3 month KPC outbreak (2013–14), were investigated for carbapenemase production, antimicrobial susceptibility, variable-number-tandem-repeat profile and WGS [short-read (Illumina), long-read (MinION)]. Short-read sequences were used for MLST and plasmid/Tn4401 fingerprinting, and long-read sequence assemblies for plasmid identification. Phylogenetic analysis used IQTree followed by ClonalFrameML, and outbreak transmission dynamics were inferred using SCOTTI. Results: Twenty patients harboured KPC-positive isolates (6 infected, 14 colonized), and 23 distinct KPC-producing Enterobacteriaceae were identified. Four distinct KPC plasmids were characterized but of 20 KPC-Kpn (from six STs), 17 isolates shared a single pKpQIL-D2 KPC plasmid. All isolates had an identical transposon (Tn4401a), except one KPC-Kpn (ST661) with a single nucleotide variant. A sporadic case of KPC-Kpn (ST491) with Tn4401a-carrying pKpQILD2 plasmid was identified 10 months before the outbreak. This plasmid was later seen in two other species and other KPC-Kpn (ST14,ST661) including clonal spread of KPC-Kpn (ST661) from a symptomatic case to nine ward contacts. Conclusions: WGS of outbreak KPC isolates demonstrated blaKPC dissemination via horizontal transposition (Tn4401a), plasmid spread (pKpQIL-D2) and clonal spread (K. pneumoniae ST661). Despite rapid outbreak control, considerable dissemination of blaKPC still occurred among K. pneumoniae and other Enterobacteriaceae, emphasizing its high transmission potential and the need for enhanced control efforts

GPCRDB: information system for G protein-coupled receptors

The GPCRDB is a Molecular Class-Specific Information System (MCSIS) that collects, combines, validates and disseminates large amounts of heterogeneous data on G protein-coupled receptors (GPCRs). The GPCRDB contains experimental data on sequences, ligand-binding constants, mutations and oligomers, as well as many different types of computationally derived data such as multiple sequence alignments and homology models. The GPCRDB provides access to the data via a number of different access methods. It offers visualization and analysis tools, and a number of query systems. The data is updated automatically on a monthly basis. The GPCRDB can be found online at http://www.gpcr.org/7tm/

Instantaneous transport of a passive scalar in a turbulent separated flow

The results of large-eddy simulations of flow and transient solute transport over a backward facing step and through a 180° bend are presented. The simulations are validated successfully in terms of hydrodynamics and tracer transport with experimental velocity data and measured residence time distribution curves confirming the accuracy of the method. The hydrodynamics are characterised by flow separation and subsequent recirculation in vertical and horizontal directions and the solute dispersion process is a direct response to the significant unsteadiness and turbulence in the flow. The turbulence in the system is analysed and quantified in terms of power density spectra and covariance of velocity fluctuations. The injection of an instantaneous passive tracer and its dispersion through the system is simulated. Large-eddy simulations enable the resolution of the instantaneous flow field and it is demonstrated that the instabilities of intermittent large-scale structures play a distinguished role in the solute transport. The advection and diffusion of the scalar is governed by the severe unsteadiness of the flow and this is visualised and quantified. The analysis of the scalar mass transport budget quantifies the mechanisms controlling the turbulent mixing and reveals that the mass flux is dominated by advection

GPCRDB: information system for G protein-coupled receptors

The GPCRDB is a Molecular Class-Specific Information System (MCSIS) that collects, combines, validates and disseminates large amounts of heterogeneous data on G protein-coupled receptors (GPCRs). The GPCRDB contains experimental data on sequences, ligand-binding constants, mutations and oligomers, as well as many different types of computationally derived data such as multiple sequence alignments and homology models. The GPCRDB provides access to the data via a number of different access methods. It offers visualization and analysis tools, and a number of query systems. The data is updated automatically on a monthly basis. The GPCRDB can be found online at http://www.gpcr.org/7tm/

The duration, dynamics and determinants of SARS-CoV-2 antibody responses in individual healthcare workers

BACKGROUND: SARS-CoV-2 IgG antibody measurements can be used to estimate the proportion of a population exposed or infected and may be informative about the risk of future infection. Previous estimates of the duration of antibody responses vary. METHODS: We present 6 months of data from a longitudinal seroprevalence study of 3276 UK healthcare workers (HCWs). Serial measurements of SARS-CoV-2 anti-nucleocapsid and anti-spike IgG were obtained. Interval censored survival analysis was used to investigate the duration of detectable responses. Additionally, Bayesian mixed linear models were used to investigate anti-nucleocapsid waning. RESULTS: Anti-spike IgG levels remained stably detected after a positive result, e.g., in 94% (95% credibility interval, CrI, 91-96%) of HCWs at 180 days. Anti-nucleocapsid IgG levels rose to a peak at 24 (95% credibility interval, CrI 19-31) days post first PCR-positive test, before beginning to fall. Considering 452 anti-nucleocapsid seropositive HCWs over a median of 121 days from their maximum positive IgG titre, the mean estimated antibody half-life was 85 (95%CrI, 81-90) days. Higher maximum observed anti-nucleocapsid titres were associated with longer estimated antibody half-lives. Increasing age, Asian ethnicity and prior self-reported symptoms were independently associated with higher maximum anti-nucleocapsid levels and increasing age and a positive PCR test undertaken for symptoms with longer anti-nucleocapsid half-lives. CONCLUSION: SARS-CoV-2 anti-nucleocapsid antibodies wane within months, and faster in younger adults and those without symptoms. However, anti-spike IgG remains stably detected. Ongoing longitudinal studies are required to track the long-term duration of antibody levels and their association with immunity to SARS-CoV-2 reinfection