Retrospective application of a validated algorithm for estimation of adrenal gland volume after computed tomography on 46 dogs undergoing adrenalectomy.

Canine adrenal gland volume can be predicted based on body weight and computed tomography (CT) measurements using a validated algorithm. Use of this algorithm to detect adrenal pathology, including hyperplasia, hypoplasia and neoplasia, in clinical cases has not been described. The objective of this study was to illustrate application of the algorithm by estimating subject-specific adrenal gland volume in a historical cohort of dogs with known adrenal disease. Forty-six dogs that underwent CT and subsequent adrenalectomy were included. Clinical records and CT images from dogs that underwent adrenalectomy and histologic examination of the excised adrenal gland(s) were reviewed. Normal adrenal gland volumes for each dog were estimated using the algorithm, and compared with measured volumes of the affected glands. Linear measurement of the largest lesion diameter was also recorded. Fifty-eight adrenal glands were removed from 46 dogs, with pathology confirmed in all glands. Pathology included 28 adenomas, 13 carcinomas, 11 pheochromocytomas and 6 other benign pathologies. The volume of all removed adrenal glands was measured to be larger than the expected normal volume estimated by the algorithm, ranging from 1.1 to 212.9 times larger than estimated. Adrenal glands with malignant and benign pathology showed variable volumes with overlapping ranges recorded. Assessment of the dimensions of any focal lesion against a cut-off of 20 mm failed to discriminate malignancy. This study illustrates and supports the application of a validated volumetric algorithm for estimation of subject-specific adrenal gland volume to identify the presence of pathology and as a tool to assist clinical decision-making.

Tissue informative cell-free DNA methylation sites in amyotrophic lateral sclerosis.

Cell-free DNA (cfDNA) is increasingly recognized as a promising biomarker candidate for disease monitoring. However, its utility in neurodegenerative diseases, like amyotrophic lateral sclerosis (ALS), remains underexplored. Existing biomarker discovery approaches are tailored to a specific disease context or are too expensive to be clinically practical. Here, we address these challenges through a new approach combining advances in molecular and computational technologies. First, we develop statistical tools to select tissue-informative DNA methylation sites relevant to a disease process of interest. We then employ a capture protocol to select these sites and perform targeted methylation sequencing. Multi-modal information about the DNA methylation patterns are then utilized in machine learning algorithms trained to predict disease status and disease progression. We applied our method to two independent cohorts of ALS patients and controls (n=192). Overall, we found that the targeted sites accurately predicted ALS status and replicated between cohorts. Additionally, we identified epigenetic features associated with ALS phenotypes, including disease severity. These findings highlight the potential of cfDNA as a non-invasive biomarker for ALS.

Assessing the frequency and types of errors involved in the use of a modified intravenous N-acetylcysteine protocol for acetaminophen overdose.

BACKGROUND: Acetaminophen overdose is a leading cause of acute liver failure in developing countries. N-acetylcysteine (NAC) is a highly effective antidote for acetaminophen hepatotoxicity, typically initiated in the emergency department. Due to a known high rate of errors with the standard three-bag IV NAC protocol, in 2019, the Ontario Poison Center changed to a modified 3% IV NAC one-bag protocol. This study was undertaken to determine the frequency and types of errors associated with the use of this protocol. METHODS: Data were gathered via chart review of Ontario Poison Centre electronic medical record cases identified as receiving IV NAC for acetaminophen overdose between August 1 and September 30, 2022. 218 total charts were identified, and 188 were deemed eligible based on inclusion and exclusion criteria. RESULTS: Errors were identified in 25% of charts, consisting of dosing errors in 11.7%, stopping errors in 9.0%, initiation errors in 3.7%, and interruptions in therapy in 3.2%. Dosing errors were the most common type of error (44.4%), with overdoses occurring three times more than underdoses. Errors were identified at 39% of geographic locations in the charts reviewed, with similar frequency in Ontario, Manitoba, and Nunavut. Clinical outcomes were similar in charts with and without errors. INTERPRETATION: The rate of errors identified with this 3% IV NAC one-bag protocol is lower than reported for the standard three-bag protocol, but remains high due to dosing errors. Previously reported issues with prolonged interruptions in therapy with the standard three-bag protocol were low with the current 3% one-bag protocol. Although severe outcomes are rare, IV NAC overdose can be fatal. Identifying local factors in emergency departments that can contribute to administration errors (i.e., dose calculation, pump programming issues) can enhance the safety of this important antidote.

RéSUMé: CONTEXTE: La surdose d'acétaminophène est l'une des principales causes d'insuffisance hépatique aiguë dans les pays en développement. La N-acétylcystéine (NAC) est un antidote très efficace contre l'hépatotoxicité de l'acétaminophène, généralement initiée au service des urgences. En raison d'un taux élevé connu d'erreurs avec le protocole NAC standard à 3 sacs IV, en 2019, le Centre antipoison de l'Ontario a adopté un protocole NAC à 1 sac IV modifié à 3 %. Cette étude a été entreprise pour déterminer la fréquence et les types d'erreurs associées à l'utilisation de ce protocole. MéTHODES: Les données ont été recueillies au moyen d'un examen des dossiers médicaux électroniques du Centre antipoison de l'Ontario qui ont reçu une dose IV de NAC pour une surdose d'acétaminophène entre le 1 août et le 30 septembre 2022. 218 cartes au total ont été identifiées, et 188 ont été jugées admissibles en fonction de critères d'inclusion et d'exclusion. RéSULTATS: Des erreurs ont été relevées dans 25 % des dossiers, soit des erreurs de dosage dans 11,7 %, des erreurs d'arrêt dans 9,0 %, des erreurs d'initiation dans 3,7 % et des interruptions du traitement dans 3,2 %. Les erreurs de dosage étaient le type d'erreur le plus courant (44,4 %), les surdoses étant trois fois plus fréquentes que les sous-doses. Des erreurs ont été relevées à 39 % des emplacements géographiques dans les cartes examinées, avec une fréquence similaire en Ontario, au Manitoba et au Nunavut. Les résultats cliniques étaient similaires dans les tableaux avec et sans erreurs. INTERPRéTATION: Le taux d'erreurs identifiées avec ce protocole à un sac NAC IV à 3 % est inférieur à celui du protocole standard à 3 sacs, mais reste élevé en raison d'erreurs de dosage. Les problèmes précédemment rapportés avec les interruptions prolongées du traitement avec le protocole standard à 3 sacs étaient faibles avec le protocole actuel à 3% à un sac. Bien que les résultats graves soient rares, une surdose de NAC IV peut être fatale. L'identification de facteurs locaux dans les services d'urgence qui peuvent contribuer aux erreurs d'administration (c.-à-d. le calcul de la dose, les problèmes de programmation de la pompe) peut améliorer l'innocuité de cet antidote important.

Is Hypertension Diagnostic Testing and Diagnosis Associated With Psychological Distress?

BACKGROUND: Psychological impacts of hypertension diagnostic testing and new hypertension diagnoses are unclear. METHODS: BP-CHECK was a randomized diagnostic study conducted in 2017-2019 in an integrated healthcare system. Participants with no hypertension diagnosis or medications and elevated blood pressure (BP) were randomized to one of three diagnostic regimens: (i) Clinic, (ii) Home, or (iii) Kiosk. Participants completed questionnaires at baseline, after completion of the diagnostic regimens, and at 6 months. Outcomes included changes from baseline in health-related quality of life (HRQOL), BP-related worry, and thoughts about having a stroke or heart attack. RESULTS: Participants (n = 482) were mostly over age 50 (77.0%), and White race (80.3%). HRQOL did not significantly change from baseline to 3 weeks or 6 months. Among all participants, BP-related worry and concerns about having a heart attack or stroke increased significantly from baseline to 3 weeks, with heart attack and stroke concerns significantly higher in the Kiosk compared Clinic and Home groups. At 6 months, thoughts about having a heart attack or stroke returned to baseline overall and in the Kiosk group, however BP-related worry was significantly higher among those with, compared to those without, a new hypertension diagnosis. CONCLUSIONS: The hypertension diagnostic process did not lead to short-term or intermediate-term changes in self-reported HRQOL. However, BP-related worry increased short-term and persisted at 6 months among individuals with a new hypertension diagnosis. Results warrant validation in more representative populations and additional exploration of the impacts of this worry on psychological well-being and hypertension control. CLINICALTRIALS.GOV IDENTIFIER: NCT03130257.

Biomechanical Gait Effects of a Single Intervention with Wearable Closed Loop Control FES System in Chronic Stroke Patients. A Proof-of-Concept Pilot Study.

Foot drop is a gait disturbance characterized by difficulty in performing ankle dorsiflexion during the swing phase of the gait cycle. Current available evidence shows that functional electrical stimulation (FES) on the musculature responsible for dorsal ankle flexion during gait can have positive effects on walking ability. This study aims to present a proof of concept for a novel easy-to-use FES system and evaluates the biomechanical effects during gait in stroke patients, compared to unassisted walking. Gait was quantitatively evaluated in a movement analysis laboratory for five subjects with chronic stroke, in basal condition without assistance and in gait assisted with FES. Improvements were found in all temporospatial parameters during FES-assisted gait, evidenced by statistically significant differences only in gait speed (p=0.02). Joint kinematics showed positive changes in hip abduction and ankle dorsiflexion variables during the swing phase of the gait cycle. No significant differences were found in the Gait Deviation Index. In conclusion, the present pilot study demonstrates that the use of this FES system in the tibialis anterior muscle can cause gait functional improvements in subjects with foot drop due to chronic stroke.

Thermal Transport in Nanoelectronic Devices Cooled by On-Chip Magnetic Refrigeration.

On-chip demagnetization refrigeration has recently emerged as a powerful tool for reaching microkelvin electron temperatures in nanoscale structures. The relative importance of cooling on-chip and off-chip components and the thermal subsystem dynamics are yet to be analyzed. We study a Coulomb blockade thermometer with on-chip copper refrigerant both experimentally and numerically, showing that dynamics in this device are captured by a first-principles model. Our work shows how to simulate thermal dynamics in devices down to microkelvin temperatures, and outlines a recipe for a low-investment platform for quantum technologies and fundamental nanoscience in this novel temperature range.

Considering inelasticity in the real-time monitoring of particle size for twin-screw granulation via acoustic emissions.

A recently developed process analytical technology (PAT) using artificial intelligence to form the framework of its model, combining frequency-domain acoustic emissions (AE) and elastic impact mechanics to accurately predict complex particle size distributions (PSD) in real-time. This model was modified in this study to give more accurate predictions for the more highly cohesive granules typical of pharmaceutical solid oral dosage formulations. AE spectra were collected from the granulated impacts of various formulations with ranging characteristics from largely elastic to highly inelastic collision responses. A viscoelastic (Hertzian spring-dashpot) and elastoplastic (Walton-Braun) contact force model were compared to understand how these different micro-mechanical approaches would affect the prediction accuracy of particle sizes relevant to granulation. Retraining the artificial intelligence model with the Walton-Braun transformation and a more comprehensive dataset of AE spectra spanning a broad range of granulated formulations showed the prediction error drop to as low as 2% compared to the original elastic version showing errors as large as 18.6% with representative formulations of the industry. The improved PAT shows good applicability to monitoring bimodal PSD that are typical of continuous twin-screw granulation.

Assessment of a compounded synthetic adrenocorticotropic hormone product in 17 healthy dogs.

OBJECTIVES: Synthetic adrenocorticotropic hormone or tetracosactide is routinely used in the diagnosis of hypoadrenocorticism and frequently in the diagnosis and treatment of hyperadrenocorticism. There have been repeated shortages of tetracosactide in recent years in Australia. This study investigated the agreement of serum cortisol after a compounded tetracosactide (Bova Aus), compared to commercial tetracosactide (Synacthen®) in healthy dogs. METHODS: Prospective crossover study using 20 dogs. Ten dogs received 5 µg/kg Synacthen® on day 1 and 5 µg/kg compounded tetracosactide on Day 2. The other 10 dogs received the reverse order. Cortisol concentrations in each dog 1 h after injection were compared for agreement, which was defined as the limits of agreement of the Bland-Altman ratio to be within a range of 0.8-1.25. Passing-Bablok regression analysis examined for constant and proportional biases. RESULTS: Three dogs were excluded with post-stimulation serum cortisol concentrations markedly outside reference interval. For the remaining 17 dogs, Bland-Altman ratio analysis of cortisol concentration (tetracosactide/Synacthen®) at 1 h found virtually no constant bias (mean of ratios 1.01;95% CI 0.97-1.05) and 95% limits of agreement were 0.88 (95% CI 0.78-0.90) and 1.17 (95% CI 1.13-1.25). This met our criteria for agreement between cortisol concentrations. Bias of the Bland-Altman difference was 2.8 nmol/L (95% CI -7.2 to 12.8); 95% limits of agreement -35.2 nmol/L (95% CI -57.0 to -26.1) and 40.8 nmol/L (95% CI 31.7-62.6). Passing-Bablok regression analysis did not identify bias. CONCLUSION: In healthy dogs, cortisol concentrations were in agreement after compounded tetracosactide compared to commercial tetracosactide, Synacthen®.

Trophic and spatial patterns of contaminants in fishes from the Republic of the Marshall Islands in the equatorial Pacific.

The Republic of the Marshall Islands (RMI) has been affected by marine pollution from militarization and urbanization. To address concerns raised by the Marshall Islands Marine Resources Authority, this study examined concentrations of dissolved contaminants in reef and pelagic fishes in the RMI and assessed potential associated risks. Metals, organochlorine pesticides, polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs) were examined in reef and pelagic fishes from six atolls: Kwajalein, Majuro, Jaluit, Utirik, Rongelap, and Wotje. Clear trophic patterns emerged for metals. Total arsenic was highest in higher trophic level reef fishes, particularly in the camouflage grouper (Epinephelus polyphekadion) (>100 µg g-1 total As), but inorganic arsenic was negligible in higher trophic levels and showed an inverse trend with the highest percentages present in parrotfishes and herbivores. Copper and mercury were elevated in higher trophic level reef and pelagic fishes, respectively, and the maximum mercury concentrations (6.45 µg g-1 in Gymnosarda unicolor) were among the highest reported in the Pacific. Conversely, cadmium and lead were highest in lower trophic levels, like surgeonfishes and parrotfishes. PCBs were more clearly linked to locations and were highest at two atolls with military history (Kwajalein and Jaluit) (>U.S. EPA Screening Value of 2.5 ppb). PAHs were ubiquitous across taxa (detected in 97% of samples), but the highest concentrations were in lower trophic levels. Organochlorine pesticides were detected at very low concentrations that do not likely pose a risk. We compare concentrations to established thresholds for human health and find that - for specific locations and species - contaminant concentrations may pose a risk to fish and other marine taxa, as well as human consumers. This study provides baseline information that aids the development of marine conservation and public health recommendations and addresses a data gap that persists for marine pollution throughout the Pacific Islands.

Seahorse brood pouch morphology and control of male parturition in Hippocampus abdominalis.

INTRODUCTION: Syngnathids (seahorses, pipefishes and seadragons) are among the few vertebrates that display male pregnancy. During seahorse pregnancy, males incubate developing embryos embedded in a placenta within a fleshy brood pouch, before expelling fully developed neonates at parturition. The mechanisms underpinning seahorse parturition are poorly understood. METHODS: We examined the morphology of the brood pouch using microcomputed tomography and histological techniques, in combination with physiological assays, to examine how male pot-bellied seahorses (Hippocampus abdominalis) control labour. In female-pregnant vertebrates, nonapeptide hormones (such as vasopressin- and oxytocin-like hormones) produce contractions of gestational smooth muscle to produce labour. RESULTS: Histological analysis of the seahorse brood pouch reveals only scattered small smooth muscle bundles in the brood pouch, and in-vitro application of isotocin (a teleost nonapeptide hormone) to the brood pouch do not produce measurable muscle contractions. Micro-computed tomography shows differences in size and orientation of the anal fin assembly between male and female pot-bellied seahorses, and histological analysis reveals large skeletal muscle bundles attached to the anal fin bones at the male brood pouch opening. DISCUSSION: We conclude that seahorse parturition may be facilitated by contraction of these muscles, which, in combination with body movements, serves to gape open the pouch and expel the neonates. Future biomechanical studies are needed to test this hypothesis.

A new mixture copula model for spatially correlated multiple variables with an environmental application.

In environmental monitoring, multiple spatial variables are often sampled at a geographical location that can depend on each other in complex ways, such as non-linear and non-Gaussian spatial dependence. We propose a new mixture copula model that can capture those complex relationships of spatially correlated multiple variables and predict univariate variables while considering the multivariate spatial relationship. The proposed method is demonstrated using an environmental application and compared with three existing methods. Firstly, improvement in the prediction of individual variables by utilising multivariate spatial copula compares to the existing univariate pair copula method. Secondly, performance in prediction by utilising mixture copula in the multivariate spatial copula framework compares with an existing multivariate spatial copula model that uses a non-linear principal component analysis. Lastly, improvement in the prediction of individual variables by utilising the non-linear non-Gaussian multivariate spatial copula model compares to the linear Gaussian multivariate cokriging model. The results show that the proposed spatial mixture copula model outperforms the existing methods in the cross-validation of actual and predicted values at the sampled locations.

Screening, Diagnosis and Management of Sarcopenia and Frailty in Hospitalized Older Adults: Recommendations from the Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Expert Working Group.

Sarcopenia and frailty are highly prevalent conditions in older hospitalized patients, which are associated with a myriad of adverse clinical outcomes. This paper, prepared by a multidisciplinary expert working group from the Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR), provides an up-to-date overview of current evidence and recommendations based on a narrative review of the literature for the screening, diagnosis, and management of sarcopenia and frailty in older patients within the hospital setting. It also includes suggestions on potential pathways to implement change to encourage widespread adoption of these evidence-informed recommendations within hospital settings. The expert working group concluded there was insufficient evidence to support any specific screening tool for sarcopenia and recommends an assessment of probable sarcopenia/sarcopenia using established criteria for all older (≥65 years) hospitalized patients or in younger patients with conditions (e.g., comorbidities) that may increase their risk of sarcopenia. Diagnosis of probable sarcopenia should be based on an assessment of low muscle strength (grip strength or five times sit-to-stand) with sarcopenia diagnosis including low muscle mass quantified from dual energy X-ray absorptiometry, bioelectrical impedance analysis or in the absence of diagnostic devices, calf circumference as a proxy measure. Severe sarcopenia is represented by the addition of impaired physical performance (slow gait speed). All patients with probable sarcopenia or sarcopenia should be investigated for causes (e.g., chronic/acute disease or malnutrition), and treated accordingly. For frailty, it is recommended that all hospitalized patients aged 70 years and older be screened using a validated tool [Clinical Frailty Scale (CFS), Hospital Frailty Risk Score, the FRAIL scale or the Frailty Index]. Patients screened as positive for frailty should undergo further clinical assessment using the Frailty Phenotype, Frailty Index or information collected from a Comprehensive Geriatric Assessment (CGA). All patients identified as frail should receive follow up by a health practitioner(s) for an individualized care plan. To treat older hospitalized patients with probable sarcopenia, sarcopenia, or frailty, it is recommended that a structured and supervised multi-component exercise program incorporating elements of resistance (muscle strengthening), challenging balance, and functional mobility training be prescribed as early as possible combined with nutritional support to optimize energy and protein intake and correct any deficiencies. There is insufficient evidence to recommend pharmacological agents for the treatment of sarcopenia or frailty. Finally, to facilitate integration of these recommendations into hospital settings organization-wide approaches are needed, with the Spread and Sustain framework recommended to facilitate organizational culture change, with the help of 'champions' to drive these changes. A multidisciplinary team approach incorporating awareness and education initiatives for healthcare professionals is recommended to ensure that screening, diagnosis and management approaches for sarcopenia and frailty are embedded and sustained within hospital settings. Finally, patients and caregivers' education should be integrated into the care pathway to facilitate adherence to prescribed management approaches for sarcopenia and frailty.

Feline immunodeficiency virus (FIV) infection in domestic pet cats in Australia and New Zealand: Guidelines for diagnosis, prevention and management.

Despite the passage of over 30 years since its discovery, the importance of feline immunodeficiency virus (FIV) on the health and longevity of infected domestic cats is hotly debated amongst feline experts. Notwithstanding the absence of good quality information, Australian and New Zealand (NZ) veterinarians should aim to minimise the exposure of cats to FIV. The most reliable way to achieve this goal is to recommend that all pet cats are kept exclusively indoors, or with secure outdoor access (e.g., cat enclosures, secure gardens), with FIV testing of any in-contact cats. All animal holding facilities should aim to individually house adult cats to limit the spread of FIV infection in groups of animals that are stressed and do not have established social hierarchies. Point-of-care (PoC) FIV antibody tests are available in Australia and NZ that can distinguish FIV-infected and uninfected FIV-vaccinated cats (Witness™ and Anigen Rapid™). Although testing of whole blood, serum or plasma remains the gold standard for FIV diagnosis, PoC testing using saliva may offer a welfare-friendly alternative in the future. PCR testing to detect FIV infection is not recommended as a screening procedure since a negative PCR result does not rule out FIV infection and is only recommended in specific scenarios. Australia and NZ are two of three countries where a dual subtype FIV vaccine (Fel-O-Vax® FIV) is available and offers a further avenue for disease prevention. Since FIV vaccination only has a reported field effectiveness of 56% in Australia, and possibly lower in NZ, FIV-vaccinated cats should undergo annual FIV testing prior to annual FIV re-vaccination using a suitable PoC kit to check infection has not occurred in the preceding year. With FIV-infected cats, clinicians should strive to be even more thorough than usual at detecting early signs of disease. The most effective way to enhance the quality of life and life expectancy of FIV-infected cats is to optimise basic husbandry and to treat any concurrent conditions early in the disease course. Currently, no available drugs are registered for the treatment of FIV infection. Critically, the euthanasia of healthy FIV-infected cats, and sick FIV-infected cats without appropriate clinical investigations, should not occur.

Comparative accuracy of two veterinary-calibrated point-of-care glucometres for measurement of blood glucose concentration in dogs.

OBJECTIVES: To investigate and compare the accuracy of two veterinary portable blood glucose metres (AccuTell; AccubioTech; and AlphaTrak2; Abbott Laboratories). MATERIALS AND METHODS: One hundred twenty venous blood samples were obtained for immediate whole blood glucose concentration measurement using two portable blood glucose metres designed for use in dogs. Plasma glucose concentration was measured by a laboratory analyser using a hexokinase reaction method. Packed cell volume was measured for each sample. Linear regression analysis was performed and Bland-Altman plots constructed with International Standards Organisation 15197:2013 standards applied to assess relationship and agreement between results of portable blood glucose metres and laboratory analyser methods, respectively. Clarke's error grid analysis was used to assess clinical accuracy and usefulness. RESULTS: The AccuTell and the AlphaTrak2 had mean differences of -0.69 ± 0.70 mmol/L (bias ±sd) and -1.09 ± 1.22 mmol/L (bias ± sd) with the reference analyser, respectively. Eighty-eight of 120 (73.3%) samples for the AccuTell, and 73 of 120 (60.8%) samples for the AlphaTrak2 were plotted in the zone of the error grid analysis that indicated less clinical risk of misdiagnosis of glucose status. Neither device fulfilled the International Standards Organisation 15197:2013 standards for system accuracy. A statistically significant effect of packed cell volume was identified on the difference between blood glucose concentration obtained by the AlphaTrak2 and the hexokinase reaction method, but not for the AccuTell. CLINICAL SIGNIFICANCE: Both devices do not meet International Standards Organisation 15197:2013 standards. Users should expect 95% of the samples measured with the AccuTell to be between -0.7 and +2.1 mmol/L higher than actual values, and 95% of the samples measured with the AlphaTrak2 to be between -1.3 and +3.5 mmol/L higher than actual values.

Phenotypic variation in urban environments: mechanisms and implications.

In the past decade, numerous studies have explored how urbanisation affects the mean phenotypes of populations, but it remains unknown how urbanisation impacts phenotypic variation, a key target of selection that shapes, and is shaped by, eco-evolutionary processes. Our review suggests that urbanisation may often increase intraspecific phenotypic variation through several processes; a conclusion aligned with results from our illustrative analysis on tit morphology across 13 European city/forest population pairs. Urban-driven changes in phenotypic variation will have immense implications for urban populations and communities, particularly through urbanisation's effects on individual fitness, species interactions, and conservation. We call here for studies that incorporate phenotypic variation in urban eco-evolutionary research alongside advances in theory.

Retrospective identification of latent subgroups of emergency department patients: A machine learning approach.

OBJECTIVE: This research aims to (i) identify latent subgroups of ED presentations in Australian public EDs using a data-driven approach and (ii) compare clinical, socio-demographic and time-related characteristics of ED presentations broadly using the subgroups. METHODS: We examined presentations to four public hospital EDs in Queensland from 2009 to 2014. An unsupervised machine learning algorithm, Clustering Large Applications, was used to cluster ED presentations. RESULTS: There were six subgroups common across the EDs, primarily distinguishable by age, and subsequently by triage category, ED length of stay, arrival mode, departure status and several time-related attributes. Around 10% to 30% of the total presentations had high resource utilisation, with half of these from older patients (55+ years). ED resource utilisation per population was highest among the oldest cohort (75+ years). Children and young adults more frequently presented to the ED outside general-practitioner hours, mostly on Sundays. Older persons were more likely to present at any time, rather than specific hours, days or seasons. ED service performance measured against commonly used access-target indicators were rarely satisfied for older people and frequently satisfied for children. CONCLUSION: Clustering Large Applications is effective in finding latent groups in large-scale mixed-type data, as demonstrated in the present study. Six types of ED presentations were identified and described using clinically relevant characteristics. The present study provides evidence for policy makers in Australia to develop alternative ED models of care tailored around the care needs of the differing groups of patients and thereby supports the sustainable delivery of acute healthcare.

Structural changes to the brood pouch of male pregnant seahorses (Hippocampus abdominalis) facilitate exchange between father and embryos.

INTRODUCTION: Embryonic growth and development require efficient respiratory gas exchange. Internal incubation of developing young thus presents a significant physiological challenge, because respiratory gas diffusion to embryos is impeded by the additional barrier of parental tissue between the embryo and the environment. Therefore, live-bearing species exhibit a variety of adaptations facilitating respiratory gas exchange between the parent (usually the mother) and embryos. Syngnathid fishes are the only vertebrates to exhibit male pregnancy, allowing comparative studies of the biology and evolution of internal incubation of embryos, independent of the female reproductive tract. Here, we examine the fleshy, sealed, seahorse brood pouch, and provide the first quantification of structural changes to this gestational organ across pregnancy. METHODS: We used histological analysis and morphometrics to quantify the surface area for exchange across the brood pouch epithelium, and the structure of the vascular bed of the brood pouch. RESULTS: We show dramatic remodelling of gestational tissues as pregnancy progresses, including an increase in tortuosity of the gestational epithelium, an increase in capillary density, and a decrease in diffusion distance between capillaries and the pouch lumen. DISCUSSION: These changes produce an increased surface area and expansion of the vascular bed of the placenta that likely facilitates respiratory gas exchange. These changes mirror the remodelling of gestational tissue in viviparous amniotes and elasmobranchs, and provide further evidence of the convergence of adaptations to support pregnancy in live-bearing animals.

Circulating tumour DNA for clinicians: current and future clinical applications.

This review introduces clinicians to the basic concepts of the biology of circulating tumour DNA (ctDNA), which is required to understand clinical use of ctDNA technology. We provide an overview of how new technology has improved the sensitivity of ctDNA detection over the last decade and the available techniques for ctDNA analysis including whole-genome sequencing (WGS), targeted cancer-associated gene panels, and methylation analysis. We discuss the most recent evidence from clinical trials for ctDNA in patient care including precision treatment of advanced cancers, disease monitoring, improving adjuvant treatment, and screening for early detection of cancer. Finally, we outline how ctDNA is likely to directly impact radiologists, and identify further research required for ctDNA to progress into routine clinical application.

Are fathers a good substitute for mothers? Paternal care and growth rates in Shodagor children.

Biparental care is a hallmark of human social organization, though paternal investment varies between and within societies. The facultative nature of paternal care in humans suggests males should invest when their care improves child survival and/or quality, though testing this prediction can be challenging because of the difficulties of empirically isolating paternal effects from those of other caregivers. Additionally, the broader context in which care is provided, vis-à-vis care from mothers and others, may lead to different child outcomes. Here, we examine the effects of paternal care on child growth among Shodagor fisher-traders, where fathers provide high levels of both additive and substitutive care, relative to mothers. We modeled seasonal z-scores and velocities for height, weight, and body mass index (BMI) outcomes using linear mixed models. Our evidence indicates that, as predicted, the context of paternal care is an important predictor of child outcomes. Results show that environmental seasonality and alloparental help contribute to a nuanced understanding of the impact of Shodagor paternal care on child physiology.