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.

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.

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.

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.

The Murchison Widefield Array (MWA) is an electronically steered low-frequency (<300 MHz) radio interferometer, with a ‘slew’ time less than 8 s. Low-frequency (∼100 MHz) radio telescopes are ideally suited for rapid response follow-up of transients due to their large field of view, the inverted spectrum of coherent emission, and the fact that the dispersion delay between a 1 GHz and 100 MHz pulse is on the order of 1–10 min for dispersion measures of 100–2000 pc/cm3. The MWA has previously been used to provide fast follow-up for transient events including gamma-ray bursts (GRBs), fast radio bursts (FRBs), and gravitational waves, using systems that respond to gamma-ray coordinates network packet-based notifications. We describe a system for automatically triggering MWA observations of such events, based on Virtual Observatory Event standard triggers, which is more flexible, capable, and accurate than previous systems. The system can respond to external multi-messenger triggers, which makes it well-suited to searching for prompt coherent radio emission from GRBs, the study of FRBs and gravitational waves, single pulse studies of pulsars, and rapid follow-up of high-energy superflares from flare stars. The new triggering system has the capability to trigger observations in both the regular correlator mode (limited to ≥0.5 s integrations) and using the Voltage Capture System (VCS, 0.1 ms integration) of the MWA and represents a new mode of operation for the MWA. The upgraded standard correlator triggering capability has been in use since MWA observing semester 2018B (July–Dec 2018), and the VCS and buffered mode triggers will become available for observing in a future semester.

Transmission of acute respiratory infections (ARI) and acute gastroenteritis (AGE) often occurs in households. The aim of this study was to assess which proportion of ARI and AGE is introduced and transmitted by children in German households with children attending child care. We recruited families with children aged 0–6 years in Braunschweig (Germany), for a 4 months prospective cohort study in the winter period 2014/2015. Every household member was included in a health diary and used nasal swabs for pathogen identification in case of ARI. We defined a transmission if two persons had overlapping periods with symptoms and used additional definitions for sensitivity analyses. In total, 77 households participated with 282 persons. We observed 277 transmission events for ARI and 23 for AGE. In most cases, the first infected person in a household was a child (ARI: 63%, AGE: 53%), and the risk of within-household transmission was two times higher when the index case was a child. In 26 ARI-transmission events, pathogens were detected for both cases; hereof in 35% (95% confidence interval (17–56%)) the pathogens were different. Thus, symptomatic infections in household members, apparently linked in time, were in 2/3 associated with the same pathogens.

Herbicide content in honey mesquite (Prosopis juliflora (Swartz) DC. var. glandulosa (Torr.) Cockerell) phloem 48 hr after treatment was higher in stems within 20 cm of the foliage than in those near the soil line. Similar levels of (2,4,5-trichlorophenoxy)acetic acid (2,4,5-T) occurred from applications of either 0.56 or 1.12 kg/ha, whereas three times as much 4-amino-3,5,6-trichloropicolinic acid (picloram) occurred in plants sprayed with the high rate than in those sprayed with the low rate. Herbicide concentration was highest in June and lowest in August.

Pumice layers of set S from Mount St. Helens can be correlated with certain ash beds associated with young flood deposits of the channeled scabland. The correlation points to an age of about 13,000 14C yr B.P. for the last major flood to have crossed the scabland. Until recently, the last major episode of flooding was thought to be closer to 20,000 yr B.P., an age inferred chiefly from the relation of the flood to glacial events of the northern Rocky Mountains. Several investigations within the last few years have suggested that the last major flood occurred well after 20,000 yr B.P. Tentative correlations of ash beds of the scabland with set S pumice layers, the relations of flood and glacial events along the northwestern margin of the Columbia Plateau, and a radiocarbon date from the Snake River drainage southeast of the plateau all indicate an age much younger than 20,000 yr. The postulated age of about 13,000 yr B.P. is further supported by a radiocarbon date in the Columbia River valley downstream from the scabland tract. Basal peat from a bog on the Portland delta of Bretz, which is a downvalley deposit of the last major scabland flood, has been dated as 13,080 ± 300 yr B.P. (W-3404).

Valine (Val) is considered to be the fifth-limiting amino acid in a maize–soyabean meal diet for pigs. Excess leucine (Leu) levels often occur in commercial diets, which may attenuate the effect of Val deficiency because of an increased oxidation of Val. The objective of the present experiment was to determine the effect of increasing concentrations of Leu on the response of young piglets to dietary Val. In all, 75 Large White×Landrace entire male pigs, 44 days of age and with a mean starting weight of 13.5 kg, were used. Three of these were sacrificed at the start to determine their mean initial chemical composition. A summit feed first limiting in Val was serially diluted with a non-protein diluent to produce a series of five digestible Val concentrations of 11.9, 10.1, 8.3, 6.6 and 4.8 g/kg, with a sixth treatment being added to test that the feeds were limiting in Val. Three identical Val series, each with six levels of Val, were supplemented with increasing amounts of Leu (23, 45 and 67 g/kg), thus 18 treatments in total. All pigs were killed at the end of the trial after 18 days for analysis of water, protein, lipid and ash in the carcass. The levels of Val and Leu and their interaction significantly influenced all the measurements taken in the trial. Daily gain in liveweight, water and protein, and feed conversion efficiency all increased with dietary Val content, whereas feed intake decreased as both Val and Leu contents increased. The deleterious effect of increased Leu on feed intake and growth was more marked at lower levels of Val. Supplementing the feed with the lowest Val content with additional Val largely overcame the effect of excess Leu. The efficiency of utilisation of Val for protein growth was unaffected by the level of Leu in the feed, the primary response to excess Leu being a reduction in feed intake. An intake of around 9 g Val/day yielded maximal protein growth during the period from 44 to 62 days of age in pigs of the genotype used in this trial.

Primiparous ewes (n=32) were assigned to dietary treatments in a 2×2 factorial arrangement to determine effects of nutrient restriction and melatonin supplementation on maternal and fetal pancreatic weight, digestive enzyme activity, concentration of insulin-containing clusters and plasma insulin concentrations. Treatments consisted of nutrient intake with 60% (RES) or 100% (ADQ) of requirements and melatonin supplementation at 0 (CON) or 5 mg/day (MEL). Treatments began on day 50 of gestation and continued until day 130. On day 130, blood was collected under general anesthesia from the uterine artery, uterine vein, umbilical artery and umbilical vein for plasma insulin analysis. Ewes were then euthanized and the pancreas removed from the ewe and fetus, trimmed of mesentery and fat, weighed and snap-frozen until enzyme analysis. In addition, samples of pancreatic tissue were fixed in 10% formalin solution for histological examination including quantitative characterization of size and distribution of insulin-containing cell clusters. Nutrient restriction decreased (P⩽0.001) maternal pancreatic mass (g) and α-amylase activity (U/g, kU/pancreas, U/kg BW). Ewes supplemented with melatonin had increased pancreatic mass (P=0.03) and α-amylase content (kU/pancreas and U/kg BW). Melatonin supplementation decreased (P=0.002) maternal pancreatic insulin-positive tissue area (relative to section of tissue), and size of the largest insulin-containing cell cluster (P=0.04). Nutrient restriction decreased pancreatic insulin-positive tissue area (P=0.03) and percent of large (32 001 to 512 000 µm2) and giant (⩾512 001 µm2) insulin-containing cell clusters (P=0.04) in the fetus. Insulin concentrations in plasma from the uterine vein, umbilical artery and umbilical vein were greater (P⩽0.01) in animals receiving 100% requirements. When comparing ewes to fetuses, ewes had a greater percentage of medium insulin-containing cell clusters (2001 to 32 000 µm2) while fetuses had more (P<0.001) pancreatic insulin-positive area (relative to section of tissue) and a greater percent of small, large and giant insulin-containing cell clusters (P⩽0.02). Larger insulin-containing clusters were observed in fetuses (P<0.001) compared with ewes. In summary, the maternal pancreas responded to nutrient restriction by decreasing pancreatic weight and activity of digestive enzymes while melatonin supplementation increased α-amylase content. Nutrient restriction decreased the number of pancreatic insulin-containing clusters in fetuses while melatonin supplementation did not influence insulin concentration. This indicated using melatonin as a therapeutic agent to mitigate reduced pancreatic function in the fetus due to maternal nutrient restriction may not be beneficial.