Implementation and evaluation of a SARI surveillance system in a tertiary hospital in Scotland in 2021/2022.

OBJECTIVE: To set up and evaluate a new surveillance system for severe acute respiratory infection (SARI) in Scotland. STUDY DESIGN: Cross-sectional study and evaluation of surveillance system. METHODS: The SARI case definition comprised patients aged 16 years or over with an acute respiratory illness presentation requiring testing for influenza and SARS-CoV-2 and hospital admission. Data were collected from SARI cases by research nurses in one tertiary teaching hospital using a bespoke data collection tool from November 2021 to May 2022. Descriptive analyses of SARI cases were carried out. The following attributes of the surveillance system were evaluated according to Centers for Disease Control and Prevention (CDC) guidelines: stability, data quality, timeliness, positive predictive value, representativeness, simplicity, acceptability and flexibility. RESULTS: The final surveillance dataset comprised 1163 records, with cases peaking in ISO week 50 (week ending 19/12/2021). The system produced a stable stream of surveillance data, with the proportion of SARI records with sufficient information for effective surveillance increasing from 65.4% during the first month to 87.0% over time. Similarly, the proportion where data collection was completed promptly was low initially, but increased to 50%-65% during later periods. CONCLUSION: SARI surveillance was successfully established in one hospital, but for a national system, additional sentinel hospital sites across Scotland, with flexibility to ensure consistently high data completeness and timeliness are needed. Data collection should be automated where possible, and demands on clinicians minimised. SARI surveillance should be embedded and resourced as part of a national respiratory surveillance strategy.

Multi-gigaelectronvolt acceleration of positrons in a self-loaded plasma wakefield.

Electrical breakdown sets a limit on the kinetic energy that particles in a conventional radio-frequency accelerator can reach. New accelerator concepts must be developed to achieve higher energies and to make future particle colliders more compact and affordable. The plasma wakefield accelerator (PWFA) embodies one such concept, in which the electric field of a plasma wake excited by a bunch of charged particles (such as electrons) is used to accelerate a trailing bunch of particles. To apply plasma acceleration to electron-positron colliders, it is imperative that both the electrons and their antimatter counterpart, the positrons, are efficiently accelerated at high fields using plasmas. Although substantial progress has recently been reported on high-field, high-efficiency acceleration of electrons in a PWFA powered by an electron bunch, such an electron-driven wake is unsuitable for the acceleration and focusing of a positron bunch. Here we demonstrate a new regime of PWFAs where particles in the front of a single positron bunch transfer their energy to a substantial number of those in the rear of the same bunch by exciting a wakefield in the plasma. In the process, the accelerating field is altered--'self-loaded'--so that about a billion positrons gain five gigaelectronvolts of energy with a narrow energy spread over a distance of just 1.3 metres. They extract about 30 per cent of the wake's energy and form a spectrally distinct bunch with a root-mean-square energy spread as low as 1.8 per cent. This ability to transfer energy efficiently from the front to the rear within a single positron bunch makes the PWFA scheme very attractive as an energy booster to an electron-positron collider.

High-efficiency acceleration of an electron beam in a plasma wakefield accelerator.

High-efficiency acceleration of charged particle beams at high gradients of energy gain per unit length is necessary to achieve an affordable and compact high-energy collider. The plasma wakefield accelerator is one concept being developed for this purpose. In plasma wakefield acceleration, a charge-density wake with high accelerating fields is driven by the passage of an ultra-relativistic bunch of charged particles (the drive bunch) through a plasma. If a second bunch of relativistic electrons (the trailing bunch) with sufficient charge follows in the wake of the drive bunch at an appropriate distance, it can be efficiently accelerated to high energy. Previous experiments using just a single 42-gigaelectronvolt drive bunch have accelerated electrons with a continuous energy spectrum and a maximum energy of up to 85 gigaelectronvolts from the tail of the same bunch in less than a metre of plasma. However, the total charge of these accelerated electrons was insufficient to extract a substantial amount of energy from the wake. Here we report high-efficiency acceleration of a discrete trailing bunch of electrons that contains sufficient charge to extract a substantial amount of energy from the high-gradient, nonlinear plasma wakefield accelerator. Specifically, we show the acceleration of about 74 picocoulombs of charge contained in the core of the trailing bunch in an accelerating gradient of about 4.4 gigavolts per metre. These core particles gain about 1.6 gigaelectronvolts of energy per particle, with a final energy spread as low as 0.7 per cent (2.0 per cent on average), and an energy-transfer efficiency from the wake to the bunch that can exceed 30 per cent (17.7 per cent on average). This acceleration of a distinct bunch of electrons containing a substantial charge and having a small energy spread with both a high accelerating gradient and a high energy-transfer efficiency represents a milestone in the development of plasma wakefield acceleration into a compact and affordable accelerator technology.

Producing multi-coloured bunches through beam-induced ionization injection in plasma wakefield accelerator.

This paper discusses the properties of electron beams formed in plasma wakefield accelerators through ionization injection. In particular, the potential for generating a beam composed of co-located multi-colour beamlets is demonstrated in the case where the ionization is initiated by the evolving charge field of the drive beam itself. The physics of the processes of ionization and injection are explored through OSIRIS simulations. Experimental evidence showing similar features are presented from the data obtained in the E217 experiment at the FACET facility of the SLAC National Laboratory. This article is part of the Theo Murphy meeting issue 'Directions in particle beam-driven plasma wakefield acceleration'.

Betatron radiation and emittance growth in plasma wakefield accelerators.

Beam-driven plasma wakefield acceleration (PWFA) has demonstrated significant progress during the past two decades of research. The new Facility for Advanced Accelerator Experimental Tests (FACET) II, currently under construction, will provide 10 GeV electron beams with unprecedented parameters for the next generation of PWFA experiments. In the context of the FACET II facility, we present simulation results on expected betatron radiation and its potential application to diagnose emittance preservation and hosing instability in the upcoming PWFA experiments. This article is part of the Theo Murphy meeting issue 'Directions in particle beam-driven plasma wakefield acceleration'.

Genetic Diversity and Protective Efficacy of the RTS,S/AS01 Malaria Vaccine.

BACKGROUND: The RTS,S/AS01 vaccine targets the circumsporozoite protein of Plasmodium falciparum and has partial protective efficacy against clinical and severe malaria disease in infants and children. We investigated whether the vaccine efficacy was specific to certain parasite genotypes at the circumsporozoite protein locus. METHODS: We used polymerase chain reaction-based next-generation sequencing of DNA extracted from samples from 4985 participants to survey circumsporozoite protein polymorphisms. We evaluated the effect that polymorphic positions and haplotypic regions within the circumsporozoite protein had on vaccine efficacy against first episodes of clinical malaria within 1 year after vaccination. RESULTS: In the per-protocol group of 4577 RTS,S/AS01-vaccinated participants and 2335 control-vaccinated participants who were 5 to 17 months of age, the 1-year cumulative vaccine efficacy was 50.3% (95% confidence interval [CI], 34.6 to 62.3) against clinical malaria in which parasites matched the vaccine in the entire circumsporozoite protein C-terminal (139 infections), as compared with 33.4% (95% CI, 29.3 to 37.2) against mismatched malaria (1951 infections) (P=0.04 for differential vaccine efficacy). The vaccine efficacy based on the hazard ratio was 62.7% (95% CI, 51.6 to 71.3) against matched infections versus 54.2% (95% CI, 49.9 to 58.1) against mismatched infections (P=0.06). In the group of infants 6 to 12 weeks of age, there was no evidence of differential allele-specific vaccine efficacy. CONCLUSIONS: These results suggest that among children 5 to 17 months of age, the RTS,S vaccine has greater activity against malaria parasites with the matched circumsporozoite protein allele than against mismatched malaria. The overall vaccine efficacy in this age category will depend on the proportion of matched alleles in the local parasite population; in this trial, less than 10% of parasites had matched alleles. (Funded by the National Institutes of Health and others.).

Measurement of Transverse Wakefields Induced by a Misaligned Positron Bunch in a Hollow Channel Plasma Accelerator.

Hollow channel plasma wakefield acceleration is a proposed method to provide high acceleration gradients for electrons and positrons alike: a key to future lepton colliders. However, beams which are misaligned from the channel axis induce strong transverse wakefields, deflecting beams and reducing the collider luminosity. This undesirable consequence sets a tight constraint on the alignment accuracy of the beam propagating through the channel. Direct measurements of beam misalignment-induced transverse wakefields are therefore essential for designing mitigation strategies. We present the first quantitative measurements of transverse wakefields in a hollow plasma channel, induced by an off-axis 20 GeV positron bunch, and measured with another 20 GeV lower charge trailing positron probe bunch. The measurements are largely consistent with theory.

Role of Direct Laser Acceleration of Electrons in a Laser Wakefield Accelerator with Ionization Injection.

We show the first experimental demonstration that electrons being accelerated in a laser wakefield accelerator operating in the forced or blowout regimes gain significant energy from both the direct laser acceleration (DLA) and the laser wakefield acceleration mechanisms. Supporting full-scale 3D particle-in-cell simulations elucidate the role of the DLA of electrons in a laser wakefield accelerator when ionization injection of electrons is employed. An explanation is given for how electrons can maintain the DLA resonance condition in a laser wakefield accelerator despite the evolving properties of both the drive laser and the electrons. The produced electron beams exhibit characteristic features that are indicative of DLA as an additional acceleration mechanism.

Observation of Betatron X-Ray Radiation in a Self-Modulated Laser Wakefield Accelerator Driven with Picosecond Laser Pulses.

We investigate a new regime for betatron x-ray emission that utilizes kilojoule-class picosecond lasers to drive wakes in plasmas. When such laser pulses with intensities of ∼5×10^{18} W/cm^{2} are focused into plasmas with electron densities of ∼1×10^{19} cm^{-3}, they undergo self-modulation and channeling, which accelerates electrons up to 200 MeV energies and causes those electrons to emit x rays. The measured x-ray spectra are fit with a synchrotron spectrum with a critical energy of 10-20 keV, and 2D particle-in-cell simulations were used to model the acceleration and radiation of the electrons in our experimental conditions.

Moving towards a reliable HIV incidence test - current status, resources available, future directions and challenges ahead.

In 2011 the Incidence Assay Critical Path Working Group reviewed the current state of HIV incidence assays and helped to determine a critical path to the introduction of an HIV incidence assay. At that time the Consortium for Evaluation and Performance of HIV Incidence Assays (CEPHIA) was formed to spur progress and raise standards among assay developers, scientists and laboratories involved in HIV incidence measurement and to structure and conduct a direct independent comparative evaluation of the performance of 10 existing HIV incidence assays, to be considered singly and in combinations as recent infection test algorithms. In this paper we report on a new framework for HIV incidence assay evaluation that has emerged from this effort over the past 5 years, which includes a preliminary target product profile for an incidence assay, a consensus around key performance metrics along with analytical tools and deployment of a standardized approach for incidence assay evaluation. The specimen panels for this evaluation have been collected in large volumes, characterized using a novel approach for infection dating rules and assembled into panels designed to assess the impact of important sources of measurement error with incidence assays such as viral subtype, elite host control of viraemia and antiretroviral treatment. We present the specific rationale for several of these innovations, and discuss important resources for assay developers and researchers that have recently become available. Finally, we summarize the key remaining steps on the path to development and implementation of reliable assays for monitoring HIV incidence at a population level.

Formation of Ultrarelativistic Electron Rings from a Laser-Wakefield Accelerator.

Ultrarelativistic-energy electron ring structures have been observed from laser-wakefield acceleration experiments in the blowout regime. These electron rings had 170-280 MeV energies with 5%-25% energy spread and ∼10 pC of charge and were observed over a range of plasma densities and compositions. Three-dimensional particle-in-cell simulations show that laser intensity enhancement in the wake leads to sheath splitting and the formation of a hollow toroidal pocket in the electron density around the wake behind the first wake period. If the laser propagates over a distance greater than the ideal dephasing length, some of the dephasing electrons in the second period can become trapped within the pocket and form an ultrarelativistic electron ring that propagates in free space over a meter-scale distance upon exiting the plasma. Such a structure acts as a relativistic potential well, which has applications for accelerating positively charged particles such as positrons.

Interactions of microorganisms with polymer nanocomposite surfaces containing oxidized carbon nanotubes.

In many environmental scenarios, the fate and impact of polymer nanocomposites (PNCs) that contain carbon nanotubes (CNT/PNCs) will be influenced by their interactions with microorganisms, with implications for antimicrobial properties and the long-term persistence of PNCs. Using oxidized single-wall (O-SWCNTs) and multi-wall CNTs (O-MWCNTs), we explored the influence that CNT loading (mass fraction≤0.1%-10%) and type have on the initial interactions of Pseudomonas aeruginosa with O-CNT/poly(vinyl alcohol) (PVOH) nanocomposites containing well-dispersed O-CNTs. LIVE/DEAD staining revealed that, despite oxidation, the inclusion of O-SWCNTs or O-MWCNTs caused PNC surfaces to exhibit antimicrobial properties. The fraction of living cells deposited on both O-SWCNT and O-MWCNT/PNC surfaces decreased exponentially with increasing CNT loading, with O-SWCNTs being approximately three times more cytotoxic on a % w/w basis. Although not every contact event between attached microorganisms and CNTs led to cell death, the cytotoxicity of the CNT/PNC surfaces scaled with the total contact area that existed between the microorganisms and CNTs. However, because the antimicrobial properties of CNT/PNC surfaces require direct CNT-microbe contact, dead cells were able to shield living cells from the cytotoxic effects of CNTs, allowing biofilm formation to occur on CNT/PNCs exposed to Pseudomonas aeruginosa for longer time periods.

Beam loading by distributed injection of electrons in a plasma wakefield accelerator.

We show through experiments and supporting simulations that propagation of a highly relativistic and dense electron bunch through a plasma can lead to distributed injection of electrons, which depletes the accelerating field, i.e., beam loads the wake. The source of the injected electrons is ionization of the second electron of rubidium (Rb II) within the wake. This injection of excess charge is large enough to severely beam load the wake, and thereby reduce the transformer ratio T. The reduction of the average T with increasing beam loading is quantified for the first time by measuring the ratio of peak energy gain and loss of electrons while changing the beam emittance. Simulations show that beam loading by Rb II electrons contributes to the reduction of the peak accelerating field from its weakly loaded value of 43 GV/m to a strongly loaded value of 26 GV/m.

Distribution and risk factors of Trichomonas vaginalis infection in England: an epidemiological study using electronic health records from sexually transmitted infection clinics, 2009-2011.

We used data from the Genitourinary Medicine Clinic Activity Dataset (GUMCAD) over a 3-year period (2009-2011) to investigate the distribution and risk factors of Trichomonas vaginalis infection in England. Socio-demographic and clinical risk factors associated with a diagnosis of T. vaginalis were explored using multivariable logistic regression. Rates of T. vaginalis infection were highest in London and the West Midlands. For men and women, T. vaginalis infection was significantly associated with: older age compared to those aged 20-24 years, non-white ethnicity (in particular black Caribbean and black 'other' ethnic groups), and birth in the Caribbean vs. birth in the UK. Current gonorrhoea or chlamydia infection was associated with a diagnosis of T. vaginalis in women. Further research is required to assess the public health impact and cost-effectiveness of introducing targeted screening for women at high risk of infection in areas of higher prevalence.

Angular dependence of betatron x-ray spectra from a laser-wakefield accelerator.

We present the first measurements of the angular dependence of the betatron x-ray spectrum produced by electrons inside the cavity of a laser-wakefield accelerator. Electrons accelerated up to 300 MeV energies produce a beam of broadband, forward-directed betatron x-ray radiation extending up to 80 keV. The angular resolved spectrum from an image plate-based spectrometer with differential filtering provides data in a single laser shot. The simultaneous spectral and spatial x-ray analysis allows for a three-dimensional reconstruction of electron trajectories with micrometer resolution, and we find that the angular dependence of the x-ray spectrum is showing strong evidence of anisotropic electron trajectories.

Prioritizing investments in public health: a multi-criteria decision analysis.

BACKGROUND: The evidence on public health interventions has traditionally focussed on a limited number of costs and benefits, adopted inconsistent methods and is not always relevant to the UK context. This paper develops a multi-criteria decision analysis (MCDA) approach to overcome these challenges. METHODS: A document review and stakeholder consultation was used to identify interventions and the criteria against which they should be assessed. The interventions were measured against these criteria using literature reviews and decision models. Criteria weights were generated using a discrete choice experiment. RESULTS: Fourteen interventions were included in the final ranking. Taxation was ranked as the highest priority. Mass-media campaigns and brief interventions ranked in the top half of interventions. School-based educational interventions, statins and interventions to address mental health problems ranked in the bottom half of interventions. CONCLUSIONS: This paper demonstrates that it is possible to incorporate criteria other than cost-effectiveness in the prioritization of public health investment using an MCDA approach. There are numerous approaches available that adopt the MCDA framework. Further research is required to determine the most appropriate approach in different settings.

A polymorphism that affects OCT-1 binding to the TNF promoter region is associated with severe malaria.

Genetic variation in cytokine promoter regions is postulated to influence susceptibility to infection, but the molecular mechanisms by which such polymorphisms might affect gene regulation are unknown. Through systematic DNA footprinting of the TNF (encoding tumour necrosis factor, TNF) promoter region, we have identified a single nucleotide polymorphism (SNP) that causes the helix-turn-helix transcription factor OCT-1 to bind to a novel region of complex protein-DNA interactions and alters gene expression in human monocytes. The OCT-1-binding genotype, found in approximately 5% of Africans, is associated with fourfold increased susceptibility to cerebral malaria in large case-control studies of West African and East African populations, after correction for other known TNF polymorphisms and linked HLA alleles.

Rapid increase in gonorrhoea and syphilis diagnoses in England in 2011.

There has been a rapid rise in the number of gonorrhoea and syphilis diagnoses in England during 2011, an increase of 25% and 10% respectively. Large increases of both gonorrhoea (61%) and syphilis (28%) were observed among men who have sex with men. Although these rises can partly be attributed to increased testing, ongoing high-levels of unsafe sexual behaviour probably contributed to the rise. The rise in gonorrhoea rates is worrying in an era of decreased susceptibility to treatments.

Demonstration of a narrow energy spread, ∼0.5 GeV electron beam from a two-stage laser wakefield accelerator.

Laser wakefield acceleration of electrons holds great promise for producing ultracompact stages of GeV scale, high-quality electron beams for applications such as x-ray free electron lasers and high-energy colliders. Ultrahigh intensity laser pulses can be self-guided by relativistic plasma waves (the wake) over tens of vacuum diffraction lengths, to give >1 GeV energy in centimeter-scale low density plasmas using ionization-induced injection to inject charge into the wake even at low densities. By restricting electron injection to a distinct short region, the injector stage, energetic electron beams (of the order of 100 MeV) with a relatively large energy spread are generated. Some of these electrons are then further accelerated by a second, longer accelerator stage, which increases their energy to ∼0.5 GeV while reducing the relative energy spread to <5% FWHM.

Immunity to non-cerebral severe malaria is acquired after one or two infections.

In areas of stable transmission, clinical immunity to mild malaria is acquired slowly, so it is not usually effective until early adolescence. Life-threatening disease is, however, restricted to a much younger age group, indicating that resistance to the severe clinical consequences of infection is acquired more quickly. Understanding how rapidly immunity develops to severe malaria is essential, as severe malaria should be the primary target of intervention strategies, and predicting the result of interventions that reduce host exposure will require consideration of these dynamics. Severe disease in childhood is less frequent in areas where transmission is the greatest. One explanation for this is that infants experience increased exposure to infection while they are protected from disease, possibly by maternal antibody. They therefore emerge from this period of clinical protection with considerably more immunity than those who experience lower transmission intensities. Here we use this data, assuming a period of clinical protection, to estimate the number of prior infections needed to reduce the risk of severe disease to negligible levels. Contrary to expectations, one or two successful infective bites seem to be all that is necessary across a broad range of transmission intensities.