Evaluation of seasonal influences on adrenocorticotropic hormone response to the thyrotropin-releasing hormone stimulation test and its accuracy for diagnosis of pituitary pars intermedia dysfunction.

Pituitary pars intermedia dysfunction (PPID) is an age-related neurodegenerative disorder, affecting >20 % of older horses. There is a need for improved endocrine tests for early disease detection, and the thyrotropin-releasing hormone (TRH) stimulation test has been recommended for diagnosis of early or mild cases. However, it is currently not recommended for year-round use due to marked seasonal variability. The aims of this cohort study were to evaluate effects of month and season on adrenocorticotropic hormone (ACTH) responses to TRH stimulation and to derive monthly cut-offs for PPID diagnosis. Sixty-three horses were assigned to control (n = 17), subclinical PPID (n = 21) and clinical PPID (n = 25) groups, based on a composite reference standard that combined clinical history and examination findings with endocrine test results. TRH stimulation tests were performed monthly for a 12-month period. Circannual changes were evaluated with one- and two-way repeated-measures analysis of variance and receiver operating characteristic curve analysis was used to derive cut-off values for basal and TRH-stimulated ACTH. TRH-stimulated ACTH concentrations were lowest in February-May and highest in August-October. Specificity of both basal and 30 min post-TRH ACTH was generally higher than sensitivity, and TRH stimulation had improved diagnostic accuracy compared to basal ACTH, although its sensitivity was not significantly greater year-round. TRH stimulation tests yielded considerably more positive results than basal ACTH in the subclinical group, but few additional positive results in clinical PPID cases. There were large differences between cut-offs that maximised sensitivity or specificity for TRH-stimulated ACTH, highlighting the importance of considering clinical presentation alongside test results in diagnostic decision-making.

The weather determines the number of cases of tick paralysis in dogs and cats in eastern Australia, caused by Ixodes holocyclus, the eastern paralysis tick.

We studied over 222,000 cases of emergency veterinary consultations in four regions along the eastern coast of Australia. We found that cases of tick paralysis (TP) caused by the eastern paralysis tick, Ixodes holocyclus, accounted for 7.5% of these cases: >16,000 cases. The season of TP and the number (prevalence) of TP cases varied among regions and over the years. Our study of the association between weather and (i) the start of the season of TP, and (ii) the number of TP cases revealed much about the intricate relationship between the weather and I. holocyclus. We studied the effect of the hypothetical availability of isoxazoline-containing tick-preventative medicines and found that an increase in the availability of these medicines had significantly contributed to the decrease in TP cases. We found that the weather in winter accounted for the time of the year the season of TP starts whereas the weather in summer accounted for the number of TP cases in the TP season. Last, through a study of the effects of shifts in the climate under four hypothetical scenarios (warmer/cooler and drier/wetter than average), we propose that the start of the season of TP depends on how soon the weather in winter becomes suitable for the activity (e.g. host-seeking) and the development of I. holocyclus nymphs, and that the number of TP cases during the TP season depends on how many engorged female ticks and their eggs survive during summer.

FORWARDS-1: an adaptive, single-blind, placebo-controlled ascending dose study of acute baclofen on safety parameters in opioid dependence during methadone-maintenance treatment-a pharmacokinetic-pharmacodynamic study.

BACKGROUND: Treatment of opiate addiction with opiate substitution treatment (e.g. methadone) is beneficial. However, some individuals desire or would benefit from abstinence but there are limited options to attenuate problems with opiate withdrawal. Preclinical and preliminary clinical evidence suggests that the GABA-B agonist, baclofen, has the desired properties to facilitate opiate detoxification and prevent relapse. This study aims to understand whether there are any safety issues in administering baclofen to opioid-dependent individuals receiving methadone. METHODS: Opiate-dependent individuals (DSM-5 severe opioid use disorder) maintained on methadone will be recruited from addiction services in northwest London (NHS and third sector providers). Participants will be medically healthy with no severe chronic obstructive pulmonary disease or type 2 respiratory failure, no current dependence on other substances (excluding nicotine), no current severe DSM-5 psychiatric disorders, and no contraindications for baclofen or 4800 IU vitamin D (placebo). Eligible participants will be randomised in a 3:1 ratio to receive baclofen or placebo in an adaptive, single-blind, ascending dose design. A Bayesian dose-escalation model will inform the baclofen dose (10, 30, 60, or 90 mg) based on the incidence of 'dose-limiting toxicity' (DLT) events and participant-specific methadone dose. A range of respiratory, cardiovascular, and sedative measures including the National Early Warning Score (NEWS2) and Glasgow Coma Scale will determine DLT. On the experimental day, participants will consume their usual daily dose of methadone followed by an acute dose of baclofen or placebo (vitamin D3) ~ 1 h later. Measures including oxygen saturation, transcutaneous CO2, respiratory rate, QTc interval, subjective effects (sedation, drug liking, craving), plasma levels (baclofen, methadone), and adverse events will be obtained using validated questionnaires and examinations periodically for 5 h after dosing. DISCUSSION: Study outcomes will determine what dose of baclofen is safe to prescribe to those receiving methadone, to inform a subsequent proof-of-concept trial of the efficacy baclofen to facilitate opiate detoxification. To proceed, the minimum acceptable dose is 30 mg of baclofen in patients receiving ≤ 60 mg/day methadone based on the clinical experience of baclofen's use in alcoholism and guidelines for the management of opiate dependence. TRIAL REGISTRATION: Clinicaltrials.gov NCT05161351. Registered on 16 December 2021.

Λ-enhanced gray molasses in a tetrahedral laser beam geometry.

We report the observation of sub-Doppler cooling of lithium using an irregular-tetrahedral laser beam arrangement, which is produced by a nanofabricated diffraction grating. We are able to capture 11(2)% of the lithium atoms from a grating magneto-optical trap into Λ-enhanced D1 gray molasses. The molasses cools the captured atoms to a radial temperature of 60(9) µK and an axial temperature of 23(3) µK. In contrast to results from conventional counterpropagating beam configurations, we do not observe cooling when our optical fields are detuned from Raman resonance. An optical Bloch equation simulation of the cooling dynamics agrees with our data. Our results show that grating magneto-optical traps can serve as a robust source of cold atoms for tweezer-array and atom-chip experiments, even when the atomic species is not amenable to sub-Doppler cooling in bright optical molasses.

A constant pressure flowmeter for extreme-high vacuum.

We demonstrate operation of a constant-pressure flowmeter capable of generating and accurately measuring flows as low as 2 × 10-13 mol/s. Generation of such small flows is accomplished by using a small conductance element with C ≈ 50 nL/s. Accurate measurement then requires both low outgassing materials (< 1 × 10-15 mol/s) and small volume changes (≈ 70 µL). We outline the present flowmeter's construction, detail its operation, and quantify its uncertainty. The type-B uncertainty is < 0.2 % (k = 1) over the entire operating range. In particular, we present an analysis of its hydraulic system, and quantify the shift and uncertainty due to the slightly compressible oil. Finally, we compare our flowmeter against a NIST standard flowmeter, and find agreement to within 0.5 % (k = 2).

Point Absorber Limits to Future Gravitational-Wave Detectors.

High-quality optical resonant cavities require low optical loss, typically on the scale of parts per million. However, unintended micron-scale contaminants on the resonator mirrors that absorb the light circulating in the cavity can deform the surface thermoelastically and thus increase losses by scattering light out of the resonant mode. The point absorber effect is a limiting factor in some high-power cavity experiments, for example, the Advanced LIGO gravitational-wave detector. In this Letter, we present a general approach to the point absorber effect from first principles and simulate its contribution to the increased scattering. The achievable circulating power in current and future gravitational-wave detectors is calculated statistically given different point absorber configurations. Our formulation is further confirmed experimentally in comparison with the scattered power in the arm cavity of Advanced LIGO measured by in situ photodiodes. The understanding presented here provides an important tool in the global effort to design future gravitational-wave detectors that support high optical power and thus reduce quantum noise.

Summary of Utah Project on Exfoliation Syndrome (UPEXS): using a large database to identify systemic comorbidities.

The purpose of the Utah Project on Exfoliation Syndrome (UPEXS) is to identify associations between exfoliation syndrome (XFS) and other diseases that share the commonality of abnormalities in elastin and Lysyl Oxidase-Like 1 gene regulation. The UPEXS is unique because it uses the Utah Population Database, which is linked to the Utah genealogy, that contains a compilation of large pedigrees of most families in the state of Utah that go back multiple generations (3 to ≥11). The health and medical records of these family members are linked to vital records and can be used effectively in studies focused on genetic disorders like XFS, where familial clustering of a disorder is a trend. There is increasing evidence that patients with XFS have a higher risk of certain systemic disorders that reflect the systemic tissue abnormalities of XFS. Epidemiological studies focused on patients with XFS have shown that there is an increased risk of these individuals developing other pathologies that have abnormalities in extracellular matrix metabolism and repair. UPEXS has focused on suspected comorbidities that involve abnormalities in elastin maintenance, a protein that plays a role in the makeup of the extracellular matrix. In this paper, the results from the analysis of chronic obstructive pulmonary disease, inguinal hernias, pelvic organ prolapse, obstructive sleep apnoea and atrial fibrillation are summarised along with the utility of using such a large dataset.

Cosmic Ray Background Removal With Deep Neural Networks in SBND.

In liquid argon time projection chambers exposed to neutrino beams and running on or near surface levels, cosmic muons, and other cosmic particles are incident on the detectors while a single neutrino-induced event is being recorded. In practice, this means that data from surface liquid argon time projection chambers will be dominated by cosmic particles, both as a source of event triggers and as the majority of the particle count in true neutrino-triggered events. In this work, we demonstrate a novel application of deep learning techniques to remove these background particles by applying deep learning on full detector images from the SBND detector, the near detector in the Fermilab Short-Baseline Neutrino Program. We use this technique to identify, on a pixel-by-pixel level, whether recorded activity originated from cosmic particles or neutrino interactions.

Constraints on Lightly Ionizing Particles from CDMSlite.

The Cryogenic Dark Matter Search low ionization threshold experiment (CDMSlite) achieved efficient detection of very small recoil energies in its germanium target, resulting in sensitivity to lightly ionizing particles (LIPs) in a previously unexplored region of charge, mass, and velocity parameter space. We report first direct-detection limits calculated using the optimum interval method on the vertical intensity of cosmogenically produced LIPs with an electric charge smaller than e/(3×10^{5}), as well as the strongest limits for charge ≤e/160, with a minimum vertical intensity of 1.36×10^{-7} cm^{-2} s^{-1} sr^{-1} at charge e/160. These results apply over a wide range of LIP masses (5 MeV/c^{2} to 100 TeV/c^{2}) and cover a wide range of ßγ values (0.1-10^{6}), thus excluding nonrelativistic LIPs with ßγ as small as 0.1 for the first time.

Light Dark Matter Search with a High-Resolution Athermal Phonon Detector Operated above Ground.

We present limits on spin-independent dark matter-nucleon interactions using a 10.6 g Si athermal phonon detector with a baseline energy resolution of σ_{E}=3.86±0.04(stat)_{-0.00}^{+0.19}(syst) eV. This exclusion analysis sets the most stringent dark matter-nucleon scattering cross-section limits achieved by a cryogenic detector for dark matter particle masses from 93 to 140 MeV/c^{2}, with a raw exposure of 9.9 g d acquired at an above-ground facility. This work illustrates the scientific potential of detectors with athermal phonon sensors with eV-scale energy resolution for future dark matter searches.

Understanding the effects of neutron scattering for neutron-yield-isotropy measurements at the NIF.

Neutron-yield diagnostics at the NIF have been upgraded to include 48 detectors placed around the NIF target chamber to assess the DT-neutron-yield isotropy for inertial confinement fusion experiments. Real-time neutron-activation detectors are used to understand yield asymmetries due to Doppler shifts in the neutron energy attributed to hotspot motion, variations in the fuel and ablator areal densities, and other physics effects. In order to isolate target physics effects, we must understand the contribution due to neutron scattering associated with the different hardware configurations used for each experiment. We present results from several calibration experiments that demonstrate the ability to achieve our goal of 1% or better precision in determining the yield isotropy.

Approaching the motional ground state of a 10-kg object.

The motion of a mechanical object, even a human-sized object, should be governed by the rules of quantum mechanics. Coaxing them into a quantum state is, however, difficult because the thermal environment masks any quantum signature of the object's motion. The thermal environment also masks the effects of proposed modifications of quantum mechanics at large mass scales. We prepared the center-of-mass motion of a 10-kilogram mechanical oscillator in a state with an average phonon occupation of 10.8. The reduction in temperature, from room temperature to 77 nanokelvin, is commensurate with an 11 orders-of-magnitude suppression of quantum back-action by feedback and a 13 orders-of-magnitude increase in the mass of an object prepared close to its motional ground state. Our approach will enable the possibility of probing gravity on massive quantum systems.

A Bitter-type electromagnet for complex atomic trapping and manipulation.

We create a pair of symmetric Bitter-type electromagnet assemblies capable of producing multiple field configurations including uniform magnetic fields, spherical quadruple traps, or Ioffe-Pritchard magnetic bottles. Unlike other designs, our coil allows both radial and azimuthal cooling water flows by incorporating an innovative 3D-printed water distribution manifold. Combined with a double-coil geometry, such orthogonal flows permit stacking of non-concentric Bitter coils. We achieve a low thermal resistance of 4.2(1) °C kW-1 and high water flow rate of 10.0(3) l min-1 at a pressure of 190(10) kPa.

The five line-of-sight neutron time-of-flight (nToF) suite on the National Ignition Facility (NIF).

Measurement of the neutron spectrum from inertial confinement fusion implosions is one of the primary diagnostics of implosion performance. Analysis of the spectrum gives access to quantities such as neutron yield, hot-spot velocity, apparent ion temperature, and compressed fuel ρr through measurement of the down-scatter ratio. On the National Ignition Facility, the neutron time-of-flight suite has been upgraded to include five independent, collimated lines of sight, each comprising a high dynamic range bibenzyl/diphenylacetylene-stilbene scintillator [R. Hatarik et al., Plasma Fusion Res. 9, 4404104 (2014)] and high-speed fused silica Cherenkov detectors [A. S. Moore et al., Rev. Sci. Instrum. 89, 10I120 (2018)].

Machine learning approach to muon spectroscopy analysis.

In recent years, artificial intelligence techniques have proved to be very successful when applied to problems in physical sciences. Here we apply an unsupervised machine learning (ML) algorithm called principal component analysis (PCA) as a tool to analyse the data from muon spectroscopy experiments. Specifically, we apply the ML technique to detect phase transitions in various materials. The measured quantity in muon spectroscopy is an asymmetry function, which may hold information about the distribution of the intrinsic magnetic field in combination with the dynamics of the sample. Sharp changes of shape of asymmetry functions-measured at different temperatures-might indicate a phase transition. Existing methods of processing the muon spectroscopy data are based on regression analysis, but choosing the right fitting function requires knowledge about the underlying physics of the probed material. Conversely, PCA focuses on small differences in the asymmetry curves and works without any prior assumptions about the studied samples. We discovered that the PCA method works well in detecting phase transitions in muon spectroscopy experiments and can serve as an alternative to current analysis, especially if the physics of the studied material are not entirely known. Additionally, we found out that our ML technique seems to work best with large numbers of measurements, regardless of whether the algorithm takes data only for a single material or whether the analysis is performed simultaneously for many materials with different physical properties.

Anaesthetic management for robotic-assisted laparoscopic prostatectomy: the first UK national survey of current practice.

Robotic-assisted laparoscopic prostatectomy (RALP) is the most common robotic surgical procedure, but there are little published data to inform anaesthetic practice. We aimed to characterise the range of anaesthetic practice for RALP in the United Kingdom through a national survey. We conducted an online national survey to determine current anaesthetic practice for RALP. The survey was distributed to all NHS hospitals within the UK that perform RALP. Thirty-four (79%) of 43 hospitals responded to the survey. Fourteen (41%) centres routinely provide spinal anaesthesia and 79% of these use diamorphine as their intrathecal opioid of choice. Thirty-one (91%) centres administer intravenous strong opioids intraoperatively, and a wide range of non-opioid analgesic agents are also administered. Five (15%) centres reported that they discharge a minority of patients on the day of surgery. High-volume centres are more likely to have a formalised enhanced recovery after surgery (ERAS) pathway and to provide ambulatory surgery for selected patients. This represents the first UK national survey of anaesthetic practice for RALP. The results of the survey revealed significant variation in anaesthetic practice implying a lack of consensus on best perioperative management.

Confinement of an alkaline-earth element in a grating magneto-optical trap.

We demonstrate a compact magneto-optical trap (MOT) of alkaline-earth atoms using a nanofabricated diffraction grating chip. A single input laser beam, resonant with the broad 1S0 → 1P1 transition of strontium, forms the MOT in combination with three diffracted beams from the grating chip and a magnetic field produced by permanent magnets. A differential pumping tube limits the effect of the heated, effusive source on the background pressure in the trapping region. The system has a total volume of around 2.4 l. With our setup, we have trapped up to 5 × 106 88Sr atoms at a temperature of ∼6 mK, and with a trap lifetime of ∼1 s. Our results will aid the effort to miniaturize quantum technologies based on alkaline-earth atoms.

A radiofrequency voltage-controlled current source for quantum spin manipulation.

We present a wide-bandwidth, voltage-controlled current source that is easily integrated with radiofrequency magnetic field coils. Our design uses current feedback to compensate for the frequency-dependent impedance of a radiofrequency antenna. We are able to deliver peak currents greater than 100 mA over a 300 kHz to 54 MHz frequency span. The radiofrequency current source fits onto a printed circuit board smaller than 4 cm2 and consumes less than 1.3 W of power. It is suitable for use in deployable quantum sensors and nuclear magnetic resonance systems.

"Ask me what I need": A call for shifting responsibility upwards and creating inclusive learning environments in clinical placement.

BACKGROUND: Ontario's human-rights legislation and institutions' support for students with disabilities have influenced these students' increased enrolment in the postsecondary environment. Yet more attention is paid to in-classroom than to out-of-classroom experiences. Students with disabilities enrolled in nursing are least likely to be accommodated. This has significant implications for access and equity upon graduation, as clinical placements are a bridge between school and employment. OBJECTIVES: To explore clinical instructors' and students who identify with disabilities' perspectives on nursing clinical placements. METHOD: A descriptive case-report was used: interactive take-home diaries were completed and semi-structured interviews were conducted with clinical instructors (n-14) and nursing students with disabilities (n-14) in Ontario. An iterative inductive analysis was undertaken. RESULTS: Three overarching themes were identified: (a) an immovable clinical environment in relation to technology and time, (b) a perceived conflict between nursing and disability identity, and (c) a need to shift responsibility upwards while listening to lived experience. The clinical environment is a highly contested space; different identity groups have distinct roles and differing degrees of power within it. CONCLUSION: Our research calls for a shift in the nursing landscape to be led by education and medical institutions that can build supportive networks, develop clear policies and listen to nursing students with disabilities.

Survey of cases of tick-paralysis and the presence of the eastern paralysis tick, Ixodes holocyclus, and the southern paralysis tick, Ixodes cornuatus, in the Greater Melbourne Area.

OBJECTIVE: The objective of this study was to test the hypothesis that the paralysis ticks, Ixodes holocyclus and Ixodes cornuatus, are epizootic and/or enzootic in the Greater Melbourne Area (GMA). METHODS: We examined the ticks in the museum collections of Australia, wrote to, phoned and visited veterinarians and other colleagues in the GMA to gather information about the cases of tick paralysis and to request the ticks for identification. RESULTS: We present evidence of I. holocyclus at 24 postcodes and I. cornuatus at 28 postcodes in the GMA. CONCLUSIONS: We found evidence that I. holocyclus is epizootic at four postcodes in the GMA: at East Melbourne, Williamstown, Moonee Ponds and Hoppers Crossing. We did not find evidence that I. holocyclus is enzootic in the GMA. I. cornuatus is apparently enzootic in the GMA at Bullengarook, Kinglake, Chum Creek and Healesville. Our hypothesis is that I. cornuatus is also enzootic at Mt Macedon, Gisborne and at other bushy postcodes in the GMA. Since this tick is apparently enzootic in the GMA, it may also be epizootic at postcodes adjacent to busy postcodes such as Bullengarook, Kinglake, Chum Creek and Healesville. The concept of hitch-hiker larvae, nymphs and adult female ticks may explain many of the cases of tick paralysis due to I. holocyclus in the GMA. The accurate assessment of the risk of tick paralysis in dogs and cats in the GMA requires a more detailed map of the distribution of I. holocyclus and I. cornuatus in Victoria.