A multi-mode sonar transmitter

This project was initiated to evaluate appropriate microprocessor and digital logic techniques that could increase the flexibility and effectiveness of a sonar transmitter. The study led to a multi-channel signal synthesis concept designed to exploit 'phased array' steering techniques. Two versions of the equipment have now been built and evaluated. Mk.I is a relatively low power 15 channel system with 2 kilowatts total electrical power using a 40 kHz 15 λ x 1 line array. This system proved the practicability of the basic concept and its success led to the 16 kilowatt Mk2 high power version which drives a 16λ x 16 λ wideband transducer array. The study included: The design and construction of a multi-channel signal generator. The writing of control and signal synthesis software. The design, evaluation and commissioning of suitable linear power amplifiers . Investigations into suitable transducers and phased array design, leading to the manufacture of suitable matched wide band multi-channel 'staved' transducer arrays. Finally, a series of trials were made in a variety of open water conditions to evaluate the systems performance and investigate the multiple modes of operation that have been developed. The system has successfully demonstrated that transmitter beam steering is both practical and flexible. The techniques implemented permit sector interrogation by 'within-pulse' type sweeps, by 'Ripple-fire' and by transmitting steered 'Pings' sequentially on prededermined bearings. Each mode allows considerable flexibility in the generated waveform shape and frequency. The 'Multi-Mode' capability of this approach was conceived primarily as a research tool but many of the modes can be isolated and exploited in dedicated applications

Enhanced X-ray variability from V1647 Ori, the young star in outburst illuminating McNeil's Nebula

We report a ~38 ks X-ray observation of McNeil's Nebula obtained with XMM on 2004 April 4. V1647 Ori, the young star in outburst illuminating McNeil's Nebula, is detected with XMM and appears variable in X-rays. We investigate the hardness ratio variability and time variations of the event energy distribution with quantile analysis, and show that the large increase of the count rate from V1647 Ori observed during the second half of the observation is not associated with any large plasma temperature variations as for typical X-ray flares from young low-mass stars. X-ray spectral fitting shows that the bulk (~75%) of the intrinsic X-ray emission in the 0.5-8 keV energy band comes from a soft plasma component (0.9 keV) reminiscent of the X-ray spectrum of the classical T Tauri star TW Hya, for which X-ray emission is believed to be generated by an accretion shock onto the photosphere of a low-mass star. The hard plasma component (4.2 keV) contributes ~25% of the total X-ray emission, and can be understood only in the framework of plasma heating sustained by magnetic reconnection events. We find a hydrogen column density of NH=4.1E22 cm-2, which points out a significant excess of hydrogen column density compared to the value derived from optical/IR observations, consistent with the picture of the rise of a wind/jet unveiled from ground optical spectroscopy. The X-ray flux observed with XMM ranges from roughly the flux observed by Chandra on 2004 March 22 (~10 times greater than the pre-outburst X-ray flux) to a value two times greater than that caught by Chandra on 2004 March 7 (~200 times greater than the pre-outburst X-ray flux). We have investigated the possibility that V1647 Ori displays a periodic variation in X-ray brightness as suggested by the combined Chandra+XMM data set (abridged).Comment: 11 pages and 8 Figures. Accepted for publication by Astronomy & Astrophysic

Disk Formation by AGB Winds in Dipole Magnetic Fields

We present a simple, robust mechanism by which an isolated star can produce an equatorial disk. The mechanism requires that the star have a simple dipole magnetic field on the surface and an isotropic wind acceleration mechanism. The wind couples to the field, stretching it until the field lines become mostly radial and oppositely directed above and below the magnetic equator, as occurs in the solar wind. The interaction between the wind plasma and magnetic field near the star produces a steady outflow in which magnetic forces direct plasma toward the equator, constructing a disk. In the context of a slow (10 km/s) outflow (10^{-5} M_sun/yr) from an AGB star, MHD simulations demonstrate that a dense equatorial disk will be produced for dipole field strengths of only a few Gauss on the surface of the star. A disk formed by this model can be dynamically important for the shaping of Planetary Nebulae.Comment: 14 pages, 8 figures, 1 table, accepted by Ap

Simulation-Based Investigation of a Model for the Interaction Between Stellar Magnetospheres and Circumstellar Accretion Disks

We examine, parametrically, the interaction between the magnetosphere of a rotating, young stellar object (YSO) and a circumstellar accretion disk using 2.5-D (cylindrically symmetric) numerical magnetoydrodynamic simulations. The interaction drives a collimated outflow, and we find that the jet formation mechanism is robust. For variations in initial disk density of a factor of 16, variations of stellar dipole strength of a factor of 4, and for various initial conditions with respect to the disk truncation radius and the existence of a disk field, outflows with similar morphologies were consistently produced. Secondly, the system is self-regulating, where the outflow properties depend relatively weakly on the parameters above. The large scale magnetic field structure rapidly evolves to a configuration that removes angular momentum from the disk at a rate that depends most strongly on the field and weakly on the rotation rate of the foot-points of the field in the disk and the mass outflow rate. Third, the simulated jets are episodic, with the timescale of jet outbursts identical to the timescale of magnetically induced oscillations of the inner edge of the disk. To better understand the physics controlling these disk oscillations, we present a semi-analytical model and confirm that the oscillation period is set by the spin down rate of the disk inner edge. Finally, our simulations offer strong evidence that it is indeed the interaction of the stellar magnetosphere with the disk, rather than some primordial field in the disk itself, that is responsible for the formation of jets from these systems.Comment: Accepted by ApJ; 34 pages, including 12 figures and 3 table

Low-field thermal mixing in [1-13C] pyruvic acid for brute-force hyperpolarization

We detail the process of low-field thermal mixing (LFTM) between 1H and 13C nuclei in neat [1-13C] pyruvic acid at cryogenic temperatures (4–15 K). Using fast-field-cycling NMR, 1H nuclei in the molecule were polarized at modest high field (2 T) and then equilibrated with 13C nuclei by fast cycling (∼300–400 ms) to a low field (0–300 G) that activates thermal mixing. The 13C NMR spectrum was recorded after fast cycling back to 2 T. The 13C signal derives from 1H polarization via LFTM, in which the polarized (‘cold’) proton bath contacts the unpolarised (‘hot’) 13C bath at a field so low that Zeeman and dipolar interactions are similar-sized and fluctuations in the latter drive 1H–13C equilibration. By varying mixing time (tmix) and field (Bmix), we determined field-dependent rates of polarization transfer (1/τ) and decay (1/T1m) during mixing. This defines conditions for effective mixing, as utilized in ‘brute-force’ hyperpolarization of low-γ nuclei like 13C using Boltzmann polarization from nearby protons. For neat pyruvic acid, near-optimum mixing occurs for tmix ∼ 100–300 ms and Bmix ∼ 30–60 G. Three forms of frozen neat pyruvic acid were tested: two glassy samples, (one well-deoxygenated, the other O2-exposed) and one sample pre-treated by annealing (also well-deoxygenated). Both annealing and the presence of O2 are known to dramatically alter high-field longitudinal relaxation (T1) of 1H and 13C (up to 102–103-fold effects). Here, we found smaller, but still critical factors of ∼(2–5)× on both τ and T1m. Annealed, well-deoxygenated samples exhibit the longest time constants, e.g., τ ∼ 30–70 ms and T1m ∼ 1–20 s, each growing vs. Bmix. Mixing ‘turns off’ for Bmix > ∼100 G. That T1m ≫ τ is consistent with earlier success with polarization transfer from 1H to 13C by LFTM

An X-ray Outburst from the Rapidly Accreting Young Star That Illuminates McNeil's Nebula

Young, low-mass stars are luminous X-ray sources whose powerful X-ray flares may exert a profound influence over the process of planet formation. The origin of such emission is uncertain. Although many or perhaps most recently formed, low-mass stars emit X-rays as a consequence of solar-like coronal activity, it has also been suggested that X-ray emission may be a direct result of mass accretion onto the forming star. Here we report X-ray imaging spectroscopy observations which reveal a factor ~50 increase in the X-ray flux from a young star that is presently undergoing a spectacular optical/IR outburst. The outburst is thought to be due to the sudden onset of a phase of rapid accretion. The coincidence of a surge in X-ray brightness with the optical/IR eruption demonstrates that strongly enhanced high-energy emission from young stars can occur as a consequence of high accretion rates. We suggest that such accretion- enhanced X-ray emission from erupting young stars may be short-lived, because intense star-disk magnetospheric interactions are quenched rapidly by the subsequent accretion flood.Comment: 15 pages, 3 figures; published in Natur

Study protocol for a phase 1/2, single-centre, double-blind, double-dummy, randomized, active-controlled, age de-escalation trial to assess the safety, tolerability and immunogenicity of a measles and rubella vaccine delivered by a microneedle patch in healthy adults (18 to 40 years), measles and rubella vaccine-primed toddlers (15 to 18 months) and measles and rubella vaccine-naïve infants (9 to 10 months) in The Gambia [Measles and Rubella Vaccine Microneedle Patch Phase 1/2 Age De-escalation Trial].

BACKGROUND: New strategies to increase measles and rubella vaccine coverage, particularly in low- and middle-income countries, are needed if elimination goals are to be achieved. With this regard, measles and rubella vaccine microneedle patches (MRV-MNP), in which the vaccine is embedded in dissolving microneedles, offer several potential advantages over subcutaneous delivery. These include ease of administration, increased thermostability, an absence of sharps waste, reduced overall costs and pain-free administration. This trial will provide the first clinical trial data on MRV-MNP use and the first clinical vaccine trial of MNP technology in children and infants. METHODS: This is a phase 1/2, randomized, active-controlled, double-blind, double-dummy, age de-escalation trial. Based on the defined eligibility criteria for the trial, including screening laboratory investigations, 45 adults [18-40 years] followed by 120 toddlers [15-18 months] and 120 infants [9-10 months] will be enrolled in series. To allow double-blinding, participants will receive either the MRV-MNP and a placebo (0.9% sodium chloride) subcutaneous (SC) injection or a placebo MNP and the MRV by SC injection (MRV-SC). Local and systemic adverse event data will be collected for 14 days following study product administration. Safety laboratories will be repeated on day 7 and, in the adult cohort alone, on day 14. Unsolicited adverse events including serious adverse events will be collected until the final study visit for each participant on day 180. Measles and rubella serum neutralizing antibodies will be measured at baseline, on day 42 and on day 180. Cohort progression will be dependent on review of the unblinded safety data by an independent data monitoring committee. DISCUSSION: This trial will provide the first clinical data on the use of a MNP to deliver the MRV and the first data on the use of MNPs in a paediatric population. It will guide future product development decisions for what may be a key technology for future measles and rubella elimination. TRIAL REGISTRATION: Pan-African Clinical Trials Registry 202008836432905 . CLINICALTRIALS: gov NCT04394689

A measles and rubella vaccine microneedle patch in The Gambia: a phase 1/2, double-blind, double-dummy, randomised, active-controlled, age de-escalation trial.

BACKGROUND: Microneedle patches (MNPs) have been ranked as the highest global priority innovation for overcoming immunisation barriers in low-income and middle-income countries. This trial aimed to provide the first data on the tolerability, safety, and immunogenicity of a measles and rubella vaccine (MRV)-MNP in children. METHODS: This single-centre, phase 1/2, double-blind, double-dummy, randomised, active-controlled, age de-escalation trial was conducted in The Gambia. To be eligible, all participants had to be healthy according to prespecified criteria, aged 18-40 years for the adult cohort, 15-18 months for toddlers, or 9-10 months for infants, and to be available for visits throughout the follow-up period. The three age cohorts were randomly assigned in a 2:1 ratio (adults) or 1:1 ratio (toddlers and infants) to receive either an MRV-MNP (Micron Biomedical, Atlanta, GA, USA) and a placebo (0·9% sodium chloride) subcutaneous injection, or a placebo-MNP and an MRV subcutaneous injection (MRV-SC; Serum Institute of India, Pune, India). Unmasked staff ransomly assigned the participants using an online application, and they prepared visually identical preparations of the MRV-MNP or placebo-MNP and MRV-SC or placebo-SC, but were not involved in collecting endpoint data. Staff administering the study interventions, participants, parents, and study staff assessing trial endpoints were masked to treatment allocation. The safety population consists of all vaccinated participants, and analysis was conducted according to route of MRV administration, irrespective of subsequent protocol deviations. The immunogenicity population consisted of all vaccinated participants who had a baseline and day 42 visit result available, and who had no protocol deviations considered to substantially affect the immunogenicity endpoints. Solicited local and systemic adverse events were collected for 14 days following vaccination. Unsolicited adverse events were collected to day 180. Age de-escalation between cohorts was based on the review of the safety data to day 14 by an independent data monitoring committee. Serum neutralising antibodies to measles and rubella were measured at baseline, day 42, and day 180. Analysis was descriptive and included safety events, seroprotection and seroconversion rates, and geometric mean antibody concentrations. The trial was registered with the Pan African Clinical Trials Registry PACTR202008836432905, and is complete. FINDINGS: Recruitment took place between May 18, 2021, and May 27, 2022. 45 adults, 120 toddlers, and 120 infants were randomly allocated and vaccinated. There were no safety concerns in the first 14 days following vaccination in either adults or toddlers, and age de-escalation proceeded accordingly. In infants, 93% (52/56; 95% CI 83·0-97·2) seroconverted to measles and 100% (58/58; 93·8-100) seroconverted to rubella following MRV-MNP administration, while 90% (52/58; 79·2-95·2) and 100% (59/59; 93·9-100) seroconverted to measles and rubella respectively, following MRV-SC. Induration at the MRV-MNP application site was the most frequent local reaction occurring in 46 (77%) of 60 toddlers and 39 (65%) of 60 infants. Related unsolicited adverse events, most commonly discolouration at the application site, were reported in 35 (58%) of 60 toddlers and 57 (95%) of 60 infants that had received the MRV-MNP. All local reactions were mild. There were no related severe or serious adverse events. INTERPRETATION: The safety and immunogenicity data support the accelerated development of the MRV-MNP. FUNDING: Bill & Melinda Gates Foundation

The Australasian Resuscitation In Sepsis Evaluation : fluids or vasopressors in emergency department sepsis (ARISE FLUIDS), a multi-centre observational study describing current practice in Australia and New Zealand

Objectives: To describe haemodynamic resuscitation practices in ED patients with suspected sepsis and hypotension. Methods: This was a prospective, multicentre, observational study conducted in 70 hospitals in Australia and New Zealand between September 2018 and January 2019. Consecutive adults presenting to the ED during a 30-day period at each site, with suspected sepsis and hypotension (systolic blood pressure <100 mmHg) despite at least 1000 mL fluid resuscitation, were eligible. Data included baseline demographics, clinical and laboratory variables and intravenous fluid volume administered, vasopressor administration at baseline and 6- and 24-h post-enrolment, time to antimicrobial administration, intensive care admission, organ support and in-hospital mortality. Results: A total of 4477 patients were screened and 591 were included with a mean (standard deviation) age of 62 (19) years, Acute Physiology and Chronic Health Evaluation II score 15.2 (6.6) and a median (interquartile range) systolic blood pressure of 94 mmHg (87–100). Median time to first intravenous antimicrobials was 77 min (42–148). A vasopressor infusion was commenced within 24 h in 177 (30.2%) patients, with noradrenaline the most frequently used (n = 138, 78%). A median of 2000 mL (1500–3000) of intravenous fluids was administered prior to commencing vasopressors. The total volume of fluid administered from pre-enrolment to 24 h was 4200 mL (3000–5661), with a range from 1000 to 12 200 mL. Two hundred and eighteen patients (37.1%) were admitted to an intensive care unit. Overall in-hospital mortality was 6.2% (95% confidence interval 4.4–8.5%). Conclusion: Current resuscitation practice in patients with sepsis and hypotension varies widely and occupies the spectrum between a restricted volume/earlier vasopressor and liberal fluid/later vasopressor strategy