Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an environmental endocrine disruptor and model AhR agonist, is linked to skeletal abnormalities, cardiac edema, stunted growth rate, altered metabolism, and neurobehavioral deficits. We have previously reported transgenerational reproductive outcomes of developmental TCDD exposure in adult zebrafish (Danio rerio), an NIH-validated model for developmental and generational toxicology. Using the same paradigm of sublethal TCDD exposure (50 pg/ml) at both 3 and 7 weeks post fertilization (wpf), we investigated several novel endpoints, including longitudinal morphometrics and anxiety-linked behavior, in fish exposed as juveniles. We also assessed developmental abnormalities and neurobehavior in their F1 larval offspring. TCDD exposure induced timepoint-dependent decreases in several craniofacial and trunk morphometrics across juvenile development. In early adulthood, however, only exposed males underwent a transient period of compensatory growth, ending between 7 and 12 months post fertilization (mpf). At 12 mpf, exposed adult fish of both sexes displayed increased exploratory behaviors in a novel tank test. The F1 offspring of parents exposed at both 3 and 7 wpf were hyperactive, but neurobehavioral outcomes diverged depending on parental exposure window. F1 exposure-lineage larvae had increased rates of edema and skeletal abnormalities, but fewer unhatched larvae compared to controls. Parent- and timepoint-specific effects of exposure on abnormality rate were also evaluated; these outcomes were considerably less severe. Our novel behavioral findings expand current knowledge of the long-term and intergenerational consequences of early-life TCDD exposure in a zebrafish model, in addition to delineating minor longitudinal morphometric changes in exposed fish and abnormalities in larval offspring.

In Paper I, we presented an overview of the Southern-sky MWA Rapid Two-metre (SMART) survey, including the survey design and search pipeline. While the combination of MWA’s large field-of-view and the voltage capture system brings a survey speed of ${\sim} 450\, {\textrm{deg}}^{2}\,\textrm{h}^{-1}$, the progression of the survey relies on the availability of compact configuration of the Phase II array. Over the past few years, by taking advantage of multiple windows of opportunity when the compact configuration was available, we have advanced the survey to 75% of the planned sky coverage. To date, about 10% of the data collected thus far have been processed for a first-pass search, where 10 min of observation is processed for dispersion measures out to 250 ${\textrm{pc cm}}^{-3}$, to realise a shallow survey that is largely sensitive to long-period pulsars. The ongoing analysis has led to two new pulsar discoveries, as well as an independent discovery and a rediscovery of a previously incorrectly characterised pulsar, all from ${\sim} 3\% $ of the data for which candidate scrutiny is completed. In this sequel to Paper I, we describe the strategies for further detailed follow-up including improved sky localisation and convergence to timing solution, and illustrate them using example pulsar discoveries. The processing has also led to re-detection of 120 pulsars in the SMART observing band, bringing the total number of pulsars detected to date with the MWA to 180, and these are used to assess the search sensitivity of current processing pipelines. The planned second-pass (deep survey) processing is expected to yield a three-fold increase in sensitivity for long-period pulsars, and a substantial improvement to millisecond pulsars by adopting optimal de-dispersion plans. The SMART survey will complement the highly successful Parkes High Time Resolution Universe survey at 1.2–1.5 GHz, and inform future large survey efforts such as those planned with the low-frequency Square Kilometre Array (SKA-Low).

We present an overview of the Southern-sky MWA Rapid Two-metre (SMART) pulsar survey that exploits the Murchison Widefield Array’s large field of view and voltage-capture system to survey the sky south of 30$^{\circ}$ in declination for pulsars and fast transients in the 140–170 MHz band. The survey is enabled by the advent of the Phase II MWA’s compact configuration, which offers an enormous efficiency in beam-forming and processing costs, thereby making an all-sky survey of this magnitude tractable with the MWA. Even with the long dwell times employed for the survey (4800 s), data collection can be completed in $<$100 h of telescope time, while still retaining the ability to reach a limiting sensitivity of $\sim$2–3 mJy (at 150 MHz, near zenith), which is effectively 3–5 times deeper than the previous-generation low-frequency southern-sky pulsar survey, completed in the 1990s. Each observation is processed to generate $\sim$5000–8000 tied-array beams that tessellate the full $\sim 610\, {\textrm{deg}^{2}}$ field of view (at 155 MHz), which are then processed to search for pulsars. The voltage-capture recording of the survey also allows a multitude of post hoc processing options including the reprocessing of data for higher time resolution and even exploring image-based techniques for pulsar candidate identification. Due to the substantial computational cost in pulsar searches at low frequencies, the survey data processing is undertaken in multiple passes: in the first pass, a shallow survey is performed, where 10 min of each observation is processed, reaching about one-third of the full-search sensitivity. Here we present the system overview including details of ongoing processing and initial results. Further details including first pulsar discoveries and a census of low-frequency detections are presented in a companion paper. Future plans include deeper searches to reach the full sensitivity and acceleration searches to target binary and millisecond pulsars. Our simulation analysis forecasts $\sim$300 new pulsars upon the completion of full processing. The SMART survey will also generate a complete digital record of the low-frequency sky, which will serve as a valuable reference for future pulsar searches planned with the low-frequency Square Kilometre Array.

This article is a clinical guide which discusses the “state-of-the-art” usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion—this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy—while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward “bridging” methods that may be used to transition simply and safely from other antidepressants to MAOIs.

Over the last 25 years, radiowave detection of neutrino-generated signals, using cold polar ice as the neutrino target, has emerged as perhaps the most promising technique for detection of extragalactic ultra-high energy neutrinos (corresponding to neutrino energies in excess of 0.01 Joules, or 1017 electron volts). During the summer of 2021 and in tandem with the initial deployment of the Radio Neutrino Observatory in Greenland (RNO-G), we conducted radioglaciological measurements at Summit Station, Greenland to refine our understanding of the ice target. We report the result of one such measurement, the radio-frequency electric field attenuation length $L_\alpha$. We find an approximately linear dependence of $L_\alpha$ on frequency with the best fit of the average field attenuation for the upper 1500 m of ice: $\langle L_\alpha \rangle = ( ( 1154 \pm 121) - ( 0.81 \pm 0.14) \, ( \nu /{\rm MHz}) ) \,{\rm m}$ for frequencies ν ∈ [145 − 350] MHz.

Here we present stringent low-frequency (185 MHz) limits on coherent radio emission associated with a short-duration gamma-ray burst (SGRB). Our observations of the short gamma-ray burst (GRB) 180805A were taken with the upgraded Murchison Widefield Array (MWA) rapid-response system, which triggered within 20s of receiving the transient alert from the Swift Burst Alert Telescope, corresponding to 83.7 s post-burst. The SGRB was observed for a total of 30 min, resulting in a $3\sigma$ persistent flux density upper limit of 40.2 mJy beam–1. Transient searches were conducted at the Swift position of this GRB on 0.5 s, 5 s, 30 s and 2 min timescales, resulting in $3\sigma$ limits of 570–1 830, 270–630, 200–420, and 100–200 mJy beam–1, respectively. We also performed a dedispersion search for prompt signals at the position of the SGRB with a temporal and spectral resolution of 0.5 s and 1.28 MHz, respectively, resulting in a $6\sigma$ fluence upper-limit range from 570 Jy ms at DM $=3\,000$ pc cm–3 ( $z\sim 2.5$ ) to 1 750 Jy ms at DM $=200$ pc cm–3 ( $z\sim 0.1)$ , corresponding to the known redshift range of SGRBs. We compare the fluence prompt emission limit and the persistent upper limit to SGRB coherent emission models assuming the merger resulted in a stable magnetar remnant. Our observations were not sensitive enough to detect prompt emission associated with the alignment of magnetic fields of a binary neutron star just prior to the merger, from the interaction between the relativistic jet and the interstellar medium (ISM) or persistent pulsar-like emission from the spin-down of the magnetar. However, in the case of a more powerful SGRB (a gamma-ray fluence an order of magnitude higher than GRB 180805A and/or a brighter X-ray counterpart), our MWA observations may be sensitive enough to detect coherent radio emission from the jet-ISM interaction and/or the magnetar remnant. Finally, we demonstrate that of all current low- frequency radio telescopes, only the MWA has the sensitivity and response times capable of probing prompt emission models associated with the initial SGRB merger event.

Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.

A new high time resolution observing mode for the Murchison Widefield Array (MWA) is described, enabling full polarimetric observations with up to $30.72\,$ MHz of bandwidth and a time resolution of ${\sim}$ $0.8\,\upmu$ s. This mode makes use of a polyphase synthesis filter to ‘undo’ the polyphase analysis filter stage of the standard MWA’s Voltage Capture System observing mode. Sources of potential error in the reconstruction of the high time resolution data are identified and quantified, with the $S/N$ loss induced by the back-to-back system not exceeding $-0.65\,$ dB for typical noise-dominated samples. The system is further verified by observing three pulsars with known structure on microsecond timescales.

We describe system verification tests and early science results from the pulsar processor (PTUSE) developed for the newly commissioned 64-dish SARAO MeerKAT radio telescope in South Africa. MeerKAT is a high-gain ( ${\sim}2.8\,\mbox{K Jy}^{-1}$ ) low-system temperature ( ${\sim}18\,\mbox{K at }20\,\mbox{cm}$ ) radio array that currently operates at 580–1 670 MHz and can produce tied-array beams suitable for pulsar observations. This paper presents results from the MeerTime Large Survey Project and commissioning tests with PTUSE. Highlights include observations of the double pulsar $\mbox{J}0737{-}3039\mbox{A}$ , pulse profiles from 34 millisecond pulsars (MSPs) from a single 2.5-h observation of the Globular cluster Terzan 5, the rotation measure of Ter5O, a 420-sigma giant pulse from the Large Magellanic Cloud pulsar PSR $\mbox{J}0540{-}6919$ , and nulling identified in the slow pulsar PSR J0633–2015. One of the key design specifications for MeerKAT was absolute timing errors of less than 5 ns using their novel precise time system. Our timing of two bright MSPs confirm that MeerKAT delivers exceptional timing. PSR $\mbox{J}2241{-}5236$ exhibits a jitter limit of $<4\,\mbox{ns h}^{-1}$ whilst timing of PSR $\mbox{J}1909{-}3744$ over almost 11 months yields an rms residual of 66 ns with only 4 min integrations. Our results confirm that the MeerKAT is an exceptional pulsar telescope. The array can be split into four separate sub-arrays to time over 1 000 pulsars per day and the future deployment of S-band (1 750–3 500 MHz) receivers will further enhance its capabilities.

Introduction: Hyperkalemia is a common electrolyte disturbance associated with morbidity and mortality. Commonly used therapies for hyperkalemia include IV calcium, sodium bicarbonate, insulin, beta-adrenergic agents, ion-exchange resins, diuretics and hemodialysis. This study aims to evaluate which treatments are more commonly used to treat hyperkalemia and to examine factors which influence those clinical decisions. Methods: This is a retrospective chart review of all cases of hyperkalemia encountered in 2017 at a Canadian adult ED. Potassium values were classified as mild (5.5 - 6.5 mEq/L), moderate (>6.5 - 7.5 mEq/L) and severe (>7.5 mEq/L). Treatment choices were then recorded and matched to hemodynamic stability, degree of hyperkalemia and ECG findings. More statistical methods to test correlation between treatment and specific variables will be performed over the next 2 months, including logistic regression to highlight potential determinants of treatment and Chi-square tests to verify randomness and to construct 95% confidence intervals. Results: 1867 ED visits were identified, of which 479 met the inclusion criteria. 89.1% of hyperkalemia cases were mild, 8.2% were moderate, and 2.7% were severe. IV insulin was used in 22.1% of cases, followed by Kayexalate in 20.5%, sodium bicarbonate in 12.3%, IV calcium in 9.4%, frusemide in 7.3%, salbutamol in 2.7%, and dialysis in 1.9%. Moderate and severe hyperkalemia were associated with higher use of insulin (79.5% and 64.3% respectively), IV calcium (41% and 64.3% respectively), sodium bicarbonate (56.4% and 85.7% respectively). Bradycardia was associated with higher insulin and IV calcium use (46.7% and 33.3% respectively). Hypotension was associated with a similar increase in use of insulin and IV calcium (34.2% and 23.7% respectively). There were only 15 cases of cardiac arrest in which sodium bicarbonate and IV calcium were more frequently used (80% and 60% respectively). Conclusion: This study demonstrates variability in the ED management of hyperkalemia. We found that Insulin and Kayexalate were the 2 most common interventions, with degree of hyperkalemia, bradycardia and hypotension influencing rates of treatment. Overuse of kayexalate for emergent treatment of hyperkalemia is evident despite weak supporting evidence. Paradoxically, beta adrenergic agents were underutilized despite their rapid effect and safer profile. The development of a widely accepted guideline may help narrow the differences in practice and potentially improve outcomes.

The Murchison Widefield Array (MWA) is an open access telescope dedicated to studying the low-frequency (80–300 MHz) southern sky. Since beginning operations in mid-2013, the MWA has opened a new observational window in the southern hemisphere enabling many science areas. The driving science objectives of the original design were to observe 21 cm radiation from the Epoch of Reionisation (EoR), explore the radio time domain, perform Galactic and extragalactic surveys, and monitor solar, heliospheric, and ionospheric phenomena. All together $60+$ programs recorded 20 000 h producing 146 papers to date. In 2016, the telescope underwent a major upgrade resulting in alternating compact and extended configurations. Other upgrades, including digital back-ends and a rapid-response triggering system, have been developed since the original array was commissioned. In this paper, we review the major results from the prior operation of the MWA and then discuss the new science paths enabled by the improved capabilities. We group these science opportunities by the four original science themes but also include ideas for directions outside these categories.