This study investigated sex differences in iron status, and associations between iron status and endurance and musculoskeletal outcomes, in military training. 2,277 British Army trainees (581 women) participated. Iron markers and endurance performance (2.4 km run) were measured at the start (week 1) and end (week 13) of training. Whole-body areal body mineral density (aBMD) and markers of bone metabolism were measured at week 1. Injuries during training were recorded. Training decreased haemoglobin in men and women (mean change [95% CI], −0.1 [−0.2, −0.0] and −0.7 [−0.9, −0.6] g∙dL-1, both p < 0.001), but more so in women (p < 0.001). Ferritin decreased in men and women (−27 [−28, −23] and −5 [−8, −1] ug∙L, both p ≤ 0.001), but more so in men (p < 0.001). sTfR increased in men and women (2.9 [2.3, 3.6] and 3.8 [2.7, 4.9] nmol∙L, both p < 0.001), with no difference between sexes (p = 0.872). RDW increased in men (0.3 [0.2, 0.4]%, p < 0.001), but not women (0.1 [−0.1, 0.2]%, p = 0.956). MCV decreased in men (−1.5 [−1.8, −1.1] fL, p < 0.001), but not women (0.4 [−0.4, 1.3] fL, p = 0.087). Lower ferritin was associated with slower 2.4 km run time (p = 0.018), sustaining a lower limb overuse injury (p = 0.048), lower aBMD (p = 0.021), and higher βCTX and P1NP (both p < 0.001) controlling for sex. Improving iron stores before training may protect haemoglobin in women and improve endurance and protect against injury.

We present a comparison between the performance of a selection of source finders (SFs) using a new software tool called Hydra. The companion paper, Paper I, introduced the Hydra tool and demonstrated its performance using simulated data. Here we apply Hydra to assess the performance of different source finders by analysing real observational data taken from the Evolutionary Map of the Universe (EMU) Pilot Survey. EMU is a wide-field radio continuum survey whose primary goal is to make a deep ($20\mu$Jy/beam RMS noise), intermediate angular resolution ($15^{\prime\prime}$), 1 GHz survey of the entire sky south of $+30^{\circ}$ declination, and expecting to detect and catalogue up to 40 million sources. With the main EMU survey it is highly desirable to understand the performance of radio image SF software and to identify an approach that optimises source detection capabilities. Hydra has been developed to refine this process, as well as to deliver a range of metrics and source finding data products from multiple SFs. We present the performance of the five SFs tested here in terms of their completeness and reliability statistics, their flux density and source size measurements, and an exploration of case studies to highlight finder-specific limitations.

The latest generation of radio surveys are now producing sky survey images containing many millions of radio sources. In this context it is highly desirable to understand the performance of radio image source finder (SF) software and to identify an approach that optimises source detection capabilities. We have created Hydra to be an extensible multi-SF and cataloguing tool that can be used to compare and evaluate different SFs. Hydra, which currently includes the SFs Aegean, Caesar, ProFound, PyBDSF, and Selavy, provides for the addition of new SFs through containerisation and configuration files. The SF input RMS noise and island parameters are optimised to a 90% ‘percentage real detections’ threshold (calculated from the difference between detections in the real and inverted images), to enable comparison between SFs. Hydra provides completeness and reliability diagnostics through observed-deep ($\mathcal{D}$) and generated-shallow ($\mathcal{S}$) images, as well as other statistics. In addition, it has a visual inspection tool for comparing residual images through various selection filters, such as S/N bins in completeness or reliability. The tool allows the user to easily compare and evaluate different SFs in order to choose their desired SF, or a combination thereof. This paper is part one of a two part series. In this paper we introduce the Hydra software suite and validate its $\mathcal{D/S}$ metrics using simulated data. The companion paper demonstrates the utility of Hydra by comparing the performance of SFs using both simulated and real images.

Interim analyses in clinical trials can take on a multitude of forms. They are often used to guide Data and Safety Monitoring Board (DSMB) recommendations to study teams regarding recruitment targets for large, later-phase clinical trials. As collaborative biostatisticians working and teaching in multiple fields of research and across a broad array of trial phases, we note the large heterogeneity and confusion surrounding interim analyses in clinical trials. Thus, in this paper, we aim to provide a general overview and guidance on interim analyses for a nonstatistical audience. We explain each of the following types of interim analyses: efficacy, futility, safety, and sample size re-estimation, and we provide the reader with reasoning, examples, and implications for each. We emphasize that while the types of interim analyses employed may differ depending on the nature of the study, we would always recommend prespecification of the interim analytic plan to the extent possible with risk mitigation and trial integrity remaining a priority. Finally, we posit that interim analyses should be used as tools to help the DSMB make informed decisions in the context of the overarching study. They should generally not be deemed binding, and they should not be reviewed in isolation.

Dietary fibre modulates gastrointestinal (GI) health and function, providing laxation, shifting microbiota, and altering bile acid (BA) metabolism. Fruit juice production removes the polyphenol- and fibre-rich pomace fraction. The effects of orange and apple pomaces on GI outcomes were investigated in healthy, free-living adults. Healthy adults were enrolled in two double-blinded, crossover trials, being randomised by baseline bowel movement (BM) frequency. In the first trial, subjects (n 91) received orange juice (OJ, 0 g fibre/d) or OJ + orange pomace (OJ + P, 10 g fibre/d) for 4 weeks, separated by a 3-week washout. Similarly, in the second trial, subjects (n 90) received apple juice (AJ, 0 g fibre/d) or AJ + apple pomace (AJ + P, 10 g fibre/d). Bowel habit diaries, GI tolerance surveys and 3-d diet records were collected throughout. Fresh faecal samples were collected from a participant subset for microbiota and BA analyses in each study. Neither pomace interventions influenced BM frequency. At Week 4, OJ + P tended to increase (P = 0·066) GI symptom occurrence compared with OJ, while AJ + P tended (P = 0·089) to increase flatulence compared with AJ. Faecalibacterium (P = 0·038) and Negativibacillus (P = 0·043) were differentially abundant between pre- and post-interventions in the apple trial but were no longer significant after false discovery rate (FDR) correction. Baseline fibre intake was independently associated with several microbial genera in both trials. Orange or apple pomace supplementation was insufficient to elicit changes in bowel habits, microbiota diversity or BA of free-living adults with healthy baseline BM. Future studies should consider baseline BM frequency and habitual fibre intake.

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.

The National Institutes of Health Toolbox-Cognition Battery (NIHTB-CB) is a tablet-based cognitive assessment intended for individuals with neurological diseases of all ages. NIHTB-CB practice effects (PEs), however, need clarification if this measure is used to track longitudinal change. We explored the test–retest PEs on NIHTB-CB performance at 3 months in young healthy adults (n = 22). We examined corrected T-scores normalized for demographic factors and calculated PEs using Cohen’s d. There were significant PEs for all NIHTB-CB composite scores and on 4/7 subtests. This work suggests the need to further assess NIHTB-CB PEs as this may affect the interpretation of study results incorporating this battery.

A new specimen of Basilosaurus cetoides was discovered on the banks of the Flint River in Albany, Georgia, USA, in 2010. This fossil, which was the most complete specimen of the species from Georgia to date, consisted of five nearly complete and two partial post-thoracic vertebrae, tentatively identified as S4 through Ca6. During excavation, however, the site was looted and most of the specimen was lost to science. Nonetheless, we use this discovery as an opportunity to update the current state of knowledge on the stratigraphic, biogeographic, and environmental distribution of Basilosaurus in North America, as well as the position of the late Eocene shoreline in the southeastern United States. The results show that Basilosaurus was most abundant across the southeastern coastal plain during the early to middle Priabonian, coincident with the late Eocene maximum marine transgression. The decline in Basilosaurus localities is associated with the retreating shoreline of the terminal Eocene. The majority of Basilosaurus localities fall well south of the position of the late Eocene shoreline hypothesized in this study, suggesting the genus favored middle to outer neritic zones of the epicontinental sea. The comparatively low number of Priabonian specimens in the Atlantic Coastal Plain versus the Gulf Coastal Plain, then, suggests the presence of shallow zones in the Atlantic Coastal Plain that may have limited the distribution of Basilosaurus across the region. The hypothesized shoreline of this study ultimately differs from earlier reconstructions by extending the Mississippi embayment at the Bartonian/Priabonian boundary farther north than previously noted.

Researchers, clinicians and patients are increasingly using real-time monitoring methods to understand and predict suicidal thoughts and behaviours. These methods involve frequently assessing suicidal thoughts, but it is not known whether asking about suicide repeatedly is iatrogenic. We tested two questions about this approach: (a) does repeatedly assessing suicidal thinking over short periods of time increase suicidal thinking, and (b) is more frequent assessment of suicidal thinking associated with more severe suicidal thinking? In a real-time monitoring study (n = 101 participants, n = 12 793 surveys), we found no evidence to support the notion that repeated assessment of suicidal thoughts is iatrogenic.

Horseshoe crabs within Austrolimulidae represent the extreme limits to which the xiphosurid Bauplan could be modified. Recent interest in this group has uncovered an unprecedented diversity of these odd-ball xiphosurids and led to suggestions that Austrolimulidae arose during the Permian Period and had become extinct by the end of the Triassic Period. Here, we extend the temporal record of Austrolimulidae by documenting a new horseshoe crab from the Lower Jurassic (Hettangian) Bayreuth Formation, Franconiolimulus pochankei gen. et sp. nov. The novel specimen displays hypertrophied genal spines, a key feature indicative of Austrolimulidae, but does not show as prominent accentuation or reduction of other exoskeletal sections. In considering the interesting family, we explore the possible origins and explanations for the bizarre morphologies exhibited by the Austrolimulidae and present hypotheses regarding the extinction of the group. Further examination of horseshoe crab fossils with unique features will undoubtedly continue to increase the diversity and disparity of these curious xiphosurids.

Astrochemical models treat dust surfaces as ice covered. We investigate the effects of implementing increased bare dust binding energies of CO and S-bearing species on the chemistry in the outflows of asymptotic giant branch (AGB) stars. We demonstrate the potential for improving agreement with observations in the outflow of IK Tau.

Increasing the binding energies to measured and computationally derived values in high mass-loss AGB outflows increased the production of daughter species. Switching from a high binding energy on bare dust to weaker binding to ice, the gas phase abundance increased at a radius in agreement with observations of IK Tau, suggesting that displacement of bound species could contribute to this observational puzzle. Using a strong binding to bare dust, a gas phase increase was not observed, however parent species concentrations had to be increased by around a factor of four to explain observed concentrations.

Ice mélange has been postulated to impact glacier and fjord dynamics through a variety of mechanical and thermodynamic couplings. However, observations of these interactions are very limited. Here, we report on glaciological and oceanographic data that were collected from 2016 to 2017 at LeConte Glacier and Bay, Alaska, and serendipitously captured the formation, flow and break-up of ephemeral ice mélange. Sea ice formed overnight in mid-February. Over the subsequent week, the sea ice and icebergs were compacted by the advancing glacier terminus, after which the ice mélange flowed quasi-statically. The presence of ice mélange coincided with the lowest glacier velocities and frontal ablation rates in our record. In early April, increasing glacier runoff and the formation of a sub-ice-mélange plume began to melt and pull apart the ice mélange. The plume, outgoing tides and large calving events contributed to its break-up, which took place over a week and occurred in pulses. Unlike observations from elsewhere, the loss of ice mélange integrity did not coincide with the onset of seasonal glacier retreat. Our observations provide a challenge to ice mélange models aimed at quantifying the mechanical and thermodynamic couplings between ice mélange, glaciers and fjords.