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Recent studies have explored the influence of obesity and critical illness on ciprofloxacin pharmacokinetics. However, variation across the subpopulation of individuals with obesity admitted to the intensive care unit (ICU) with varying renal function remains unexamined. This study aims to characterize ciprofloxacin pharmacokinetics in ICU patients with obesity and provide dose recommendations for this special population. Individual patient data of 34 ICU patients with obesity (BMI >30 kg/m2) from four studies evaluating ciprofloxacin pharmacokinetics in ICU patients were pooled and combined with data from a study involving 10 individuals with obesity undergoing bariatric surgery. All samples were collected after intravenous administration. Non‐linear mixed effects modeling and simulation were used to develop a population pharmacokinetic model and describe ciprofloxacin exposure in plasma. Model‐based dose evaluations were performed using a pharmacokinetic/pharmacodynamic target of AUC/MIC >125. The data from patients with BMI ranging from 30.2 to 58.1 were best described by a two‐compartment model with first‐order elimination and a proportional error model. The inclusion of Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) as a covariate on clearance reduced inter‐individual variability from 57.3% to 38.5% (P <.001). Neither body weight nor ICU admission significantly influenced clearance or volume of distribution. Renal function is a viable predictor for ciprofloxacin clearance in ICU patients with obesity, while critical illness and body weight do not significantly alter clearance. As such, body weight and critical illness do not need to be accounted for when dosing ciprofloxacin in ICU patients with obesity. Individuals with CKD‐EPI >60 mL/min/1.73 m2 may require higher dosages for the treatment of pathogens with minimal inhibitory concentration ≥0.25 mg/L. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate an in vitro dynamic bioreactor model by evaluating the antimicrobial effect of clinically relevant amoxicillin doses on polymicrobial microcosm biofilms derived from subgingival plaque. Methods: Biofilms from pooled subgingival plaque were grown for 108 hours in control and experimental dynamic biofilm reactors. Amoxicillin was subsequently infused into the experimental reactor to simulate the pharmacokinetic profile of a standard 500 mg thrice‐daily dosing regimen over 5 days and biofilms were assessed by live/dead staining, scanning electron microscopy, and quantitative polymerase chain reaction. Results: Following establishment of the oral microcosm biofilms, confocal imaging analysis showed a significant increase in dead bacteria at 8 hours (p = 0.0095), 48 hours (p = 0.0070), 96 hours (p = 0.0140), and 120 hours (p < 0.0001) in the amoxicillin‐treated biofilms compared to the control biofilms. Nevertheless, viable bacteria remained in the center of the biofilm at all timepoints. Significant reductions/elimination in Campylobacter rectus, Tannerella forsythia, Aggregatibacter actinomycetemcomitans, and Peptostreptococcus anaerobius was observed among the amoxicillin‐treated biofilms at the 96 and 120 hour timepoints. Conclusion: A novel in vitro dynamic model of oral microcosm biofilms was effective in modeling the antimicrobial effect of a pharmacokinetically simulated clinically relevant dose of amoxicillin. [ABSTRACT FROM AUTHOR]

Accurate detection of acute kidney injury (AKI) in clinical trials is important. Using a 'baseline' creatinine from trial enrolment may not be ideal for understanding a participant's true baseline kidney function. We aimed to determine if a 'pre‐trial baseline creatinine' resulted in comparable creatinine concentrations to a 'trial baseline creatinine', and how the timing of baseline creatinine affected the incidence of AKI in the Combination Antibiotic therapy for MEthicillin Resistant Staphylococcus aureus (CAMERA2) randomised trial. Study sites retrospectively collected a pre‐trial baseline creatinine from up to 1 year before CAMERA2 trial enrolment ideally when the patient was medically stable. Baseline creatinine from CAMERA2 (the 'trial baseline creatinine'), was the highest creatinine measurement in the 24 h preceding trial randomisation. We used Wilcoxon sign rank test to compare pre‐trial and trial baseline creatinine concentrations. We included 217 patients. The median pre‐trial baseline creatinine was significantly lower than the median trial baseline creatinine (82 μmol/L [IQR 65–104 μmol/L] versus 86 μmol/L [IQR 66–152 μmol/L] p = <0.001). Using pre‐trial baseline creatinine, 48 of 217 patients (22%) met criteria for an AKI at CAMERA2 enrolment and only 5 of these patients met criteria for an AKI using the CAMERA2 study protocol (using baseline creatinine from trial entry). Using a baseline creatinine from the time of trial enrolment failed to detect many patients with AKI. Trial protocols should consider the optimal timing of baseline creatinine and the limitations of using a baseline creatinine during an acute illness. Summary at a glance: The choice of timing of baseline creatinine in clinical trials affects the reported incidence of AKI. Using baseline creatinine at the time of acute illness underestimated overall AKI in this post hoc analysis. [ABSTRACT FROM AUTHOR]

Ziziphus mauritiana is an economically detrimental and environmentally destructive plant in non‐native areas where it has escaped cultivation. It forms dense, impenetrable thickets that restrict the movement of livestock across the landscape and has the capacity to alter various ecological functions at the site of invasion, all of which contribute towards land degradation and the reduction of economic profitability. Although there are several management strategies implemented to control Z. mauritiana, it is clear that no single‐method approach will effectively control the species in the long‐term. Whilst chemical and mechanical methods appear to show promising results, they tend to be restricted to areas that are easily accessible and, even so, can be challenging and laborious to treat evenly across dense thicket areas. Several prospective biological control agents have been identified for Z. mauritiana, although further investigations are required to ascertain the host specificity, and to explore and identify their climatic and environmental suitability of host specific agents for release in non‐native regions. Ecological burning alone is not effective in controlling Z. mauritiana and will likely increase its emergence. As such, it could be adopted as part of an integrated management approach to assist other methods for long‐term control, but again the development of such an approach requires further investigation. To contribute towards the control of Z. mauritiana, this review explores its biology, distribution and management challenges whilst identifying areas of research that will assist in the long‐term and confident control of the species, with an emphasis on its invasion in Australia. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a major health concern with a growing disease burden and inequalities in access to treatments. Glomerular filtration rate (GFR) is accepted as the best overall measure of kidney function and is considered the most important measure for medications cleared by the kidneys. In clinical practice, equations that estimate GFR using validated prediction equations are routinely used. This practice update was developed by a Working Group comprising clinical pharmacists representing the Society of Hospital Pharmacists of Australia (SHPA) Specialty Practice streams of Nephrology, Oncology and haematology, Critical care and Infectious diseases. It is intended to provide practical recommendations for clinical pharmacists who use equations to estimate GFR for medication dosing decisions. The limitations of the various equations in use — such as the Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI), the Cockcroft–Gault equation and Modification of Diet in Renal Disease — are summarised and compared to direct measures of kidney function using exogenous markers. The CKD‐EPI equation is recommended to be used routinely as a primary measure of kidney function. Dose adjustments should also consider medication‐specific, patient‐related, and disease‐related characteristics. Kidney function and the response to therapy should be continuously assessed by monitoring the signs, symptoms and disease outcomes, the emergence of adverse reactions or medication‐induced disorders and use therapeutic drug monitoring (if available) to adjust doses accordingly. [ABSTRACT FROM AUTHOR]

Study Objective: The aim of this study was to compare the achievement of therapeutic pharmacokinetic–pharmacodynamic (PK‐PD) exposure targets for beta‐lactam antibiotics using product information dosing or guideline‐based dosing for the treatment of serious infections. Design: In silico study. Data Source: ID‐ODSTM (Individually Designed Optimum Dosing Strategies). Patients and Intervention: None. Measurements and Main Results: In silico product information and guideline‐based dosing simulations for cefepime, ceftazidime, flucloxacillin, meropenem, and piperacillin/tazobactam were performed using pharmacokinetic models from seriously ill patient populations. The median simulated concentration at 48 and 96 h was used to measure the probability of target attainment (PTA) to achieve predefined therapeutic and toxicity PK‐PD targets. A multiple linear regression model was constructed to identify the effect of guideline‐based dosing covariates on achieving pre‐defined therapeutic targets. In total, 480 dosing simulations were performed. The PTA percentage with guideline‐based dosing at 48 and 96 h was 80% and 68%, respectively, yielding significantly higher results when compared to product information dosing (48.45% and 49%, respectively), p < 0.001 at both time points. At 48 h, predefined toxicity thresholds were exceeded in 4.7% and 0% of simulations for guideline‐based and product information‐based dosing, respectively (p = 0.002). eGFR was significantly associated with the % PTA by guideline‐based dosing, with eGFR values of 20 and 50 ml/min both statistically significant in leading to an increase in PTA. Conclusions: Our study demonstrated that achievement of PK‐PD exposures associated with an increased likelihood of effectiveness was more likely to occur with guideline‐based dosing; especially at 48 h. [ABSTRACT FROM AUTHOR]

Study objective: The primary objective was to evaluate the performance of the Cockcroft‐Gault (CG) equation with different body weights (BWs) compared to a measured creatinine clearance (mCrCl) in an intensive care unit (ICU) population with and without augmented renal clearance (ARC). Design: Multicenter, retrospective cohort. Setting: Two ICUs in the United States and four ICUs from a previous international observational analysis. Patients Adult ICU patients admitted from January 1, 2010 to July 30, 2020 with at least one mCrCl collected within the initial 10 days of hospitalization were eligible for inclusion. Measurements and main results: The primary outcome was the performance of the CG equation in ARC (mCrCl≥130 ml/min/1.73 m2) and non‐ARC (mCrCl<130 ml/min/1.73 m2) patients. Correlation was analyzed by Pearson's correlation coefficient, bias by mean difference, and accuracy by the percentage of patients within 30% of the mCrCl. A total of 383 patients were included, which provided 1708 mCrCl values. The majority were male (n = 239, 62%), median age of 55 years [IQR 40–65] with a surgical diagnosis (n = 239, 77%). ARC was identified in 229 (60%) patients. The ARC group had lower Scr values (0.6 [0.5–0.7] vs. 0.7 [0.6–0.9] mg/dl, p < 0.001) and higher mCrCl (172.8 (SD 39.1) vs. 89.9 mL/min/1.73 m2 (SD 25.4), p < 0.001) compared with the non‐ARC group, respectively. Among non‐ARC patients there was a moderate correlation (r = 0.33–0.39), moderate accuracy (range 48–58%), and low bias (range of −12.9 to 17.1) among the different BW estimations with the adjusted BW having the better performance. Among ARC patients there was low correlation (r = 0.24–0.28), low to moderate accuracy (range 38–70%), and high bias (range of −58.5 to −21.6). Conclusions: The CG‐adjusted BW had the best performance in the non‐ARC patients, while CG performed poorly with any BW in ARC patients. Although the CG equation remains the standard equation for estimating CrCl in the ICU setting, a new, validated equation is needed for patients with ARC. [ABSTRACT FROM AUTHOR]

Objectives: Type 1 laryngeal clefts (LC1) and deep interarytenoid grooves contribute to pediatric feeding disorders. Management of these defects remains heterogeneous among surgeons and interarytenoid injection augmentation (IIA) is not always offered as a treatment option. This study evaluated IIA outcomes among a pediatric patient cohort comprised mostly of those with deep interarytenoid grooves. Methods: A single‐institution retrospective chart review featured children under the age of 5 years presenting for aspiration, dysphagia, or choking. Over the period of 7 years (January 2014–October 2021), 39 met inclusion criteria and had sufficient follow‐up data. Descriptive statistics and subgroup analyses were performed. Results: Of the 39 included patients, 76.92% had clinical improvement post‐injection, with the mean time to follow‐up being 47 days. Within the deep interarytenoid groove group, improvement rates were 82.76%. Bronchoscopy findings revealed 29 (74.36%) patients with a DIG, 3 (7.69%) with LC1, 3 (7.69%) with no anatomic abnormality, and 4 (10.26%) with vocal cord paralysis. There were no adverse events. There were no associations with the outcomes based on subgroup analysis and logistic regression. Conclusions: IIA is an effective and safe treatment for pediatric feeding disorders. No covariates were associated with symptom improvement. Within the deep interarytenoid groove diagnosis subgroup, IIA effectively improved symptoms. Further investigations are needed to explore predictors of success with IIA in this population. Level of Evidence: VI. [ABSTRACT FROM AUTHOR]

Intravenous β‐lactam antibiotics remain a cornerstone in the management of bacterial infections due to their broad spectrum of activity and excellent tolerability. β‐lactams are well established to display time‐dependent bactericidal activity, where reductions in bacterial burden are directly associated with the time that free drug concentrations remain above the minimum inhibitory concentration (MIC) of the pathogen during the dosing interval. In an effort to take advantage of these bactericidal characteristics, prolonged (extended and continuous) infusions (PI) can be applied during the administration of intravenous β‐lactams to increase time above the MIC. PI dosing regimens have been implemented worldwide, but implementation is inconsistent. We report consensus therapeutic recommendations for the use of β‐lactam PI developed by an expert international panel with representation from clinical pharmacy and medicine. This consensus guideline provides recommendations regarding pharmacokinetic and pharmacodynamic targets, therapeutic drug monitoring considerations, and the use of PI β‐lactam therapy in the following patient populations: severely ill and nonseverely ill adult patients, pediatric patients, and obese patients. These recommendations provide the first consensus guidance for the use of β‐lactam therapy administered as PIs and have been reviewed and endorsed by the American College of Clinical Pharmacy (ACCP), the British Society for Antimicrobial Chemotherapy (BSAC), the Cystic Fibrosis Foundation (CFF), the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the Infectious Diseases Society of America (IDSA), the Society of Critical Care Medicine (SCCM), and the Society of Infectious Diseases Pharmacists (SIDP). [ABSTRACT FROM AUTHOR]

Aim: Understanding the distribution of marine organisms is essential for effective management of highly mobile marine predators that face a variety of anthropogenic threats. Recent work has largely focused on modelling the distribution and abundance of marine mammals in relation to a suite of environmental variables. However, biotic interactions can largely drive distributions of these predators. We aim to identify how biotic and abiotic variables influence the distribution and abundance of a particular marine predator, the bottlenose dolphin (Tursiops truncatus), using multiple modelling approaches and conducting an extensive literature review. Location: Western North Atlantic continental shelf. Methods: We combined widespread marine mammal and fish and invertebrate surveys in an ensemble modelling approach to assess the relative importance and capacity of the environment and other marine species to predict the distribution of both coastal and offshore bottlenose dolphin ecotypes. We corroborate the modelled results with a systematic literature review on the prey of dolphins throughout the region to help explain patterns driven by prey availability, as well as reveal new ones that may not necessarily be a predator–prey relationship. Results: We find that coastal bottlenose dolphin distributions are associated with one family of fishes, the Sciaenidae, or drum family, and predictions slightly improve when using only fish versus only environmental variables. The literature review suggests that this tight coupling is likely a predator–prey relationship. Comparatively, offshore dolphin distributions are more strongly related to environmental variables, and predictions are better for environmental‐only models. As revealed by the literature review, this may be due to a mismatch between the animals caught in the fish and invertebrate surveys and the predominant prey of offshore dolphins, notably squid. Main Conclusions: Incorporating prey species into distribution models, especially for coastal bottlenose dolphins, can help inform ecological relationships and predict marine predator distributions. [ABSTRACT FROM AUTHOR]

Do interpersonal relationships among and between representatives and senators affect legislative collaboration in the contemporary Congress? The extant literature on Congress suggests interpersonal dimensions of life on Capitol Hill should play a minimal role in the legislative process. However, research in other fields, including psychology, finds that relationships are crucially important within organizations. In addition, many contemporary accounts of congressional deal‐making highlight the role of personal relationships. Drawing on interviews with high‐level congressional staff, and data on CODEL trips taken by members of Congress, we show that interpersonal relationships help promote collaboration across the aisle. These findings have implications for how we understand the contours of conflict and cooperation on Capitol Hill. [ABSTRACT FROM AUTHOR]

Adaptive approaches are needed to effectively manage dynamic marine systems, and ecological forecasts can help managers anticipate when and where conservation issues are likely to arise in the future. The recent development of subseasonal global environmental forecasts provides an opportunity to inform management by forecasting species distributions in advance over operational timeframes. We demonstrate the utility of environmental forecasts for managing marine mammals by integrating species distribution models with subseasonal forecasts to predict the arrival of migratory humpback whales (Megaptera novaeangliae) at foraging grounds in the Northeast US. Environmental forecasts showed high model skill at lead times of up to 2 weeks and resulting humpback whale models performed well in predicting humpback arrival. Forecasts of whale distribution can shape management efforts to minimize both impacts on whales and economic costs. Applying subseasonal forecasts to anticipate future risk presents a powerful tool for the dynamic management of marine mammals. Front Ecol Environ 2022; [ABSTRACT FROM AUTHOR]

Mpox is a zoonotic disease caused by monkeypox virus (MPXV) from the Orthopoxvirus genus. Unprecedented transmission events have led to more than 70 000 cases reported worldwide by October 2022. The change in mpox epidemiology has raised concerns of its ability to establish endemicity beyond its traditional geographical locations. In this review, we discuss the current understanding of mpox virology and viral dynamics that are relevant to mpox diagnostics. A synopsis of the traditional and emerging laboratory technologies useful for MPXV detection and in guiding "elimination" strategies is outlined in this review. Importantly, development in MPXV genomics has rapidly advanced our understanding of the role of viral evolution and adaptation in the current outbreak. [ABSTRACT FROM AUTHOR]

Solanum elaeagnifolium Cav (silverleaf nightshade) is a deep‐rooted, multi‐stemmed, perennial, herbaceous woody plant that has been observed to threaten agricultural and native biodiversity worldwide. It is widely agreed that without efficient integrated management, S. elaeagnifolium will continue to cause significant economic and environmental damage across multiple scales. It is estimated that the annual economic impact of S. elaeagnifolium in Australia exceeds AUD $62 million, with this figure likely to be much higher in other countries invaded by this plant. It can also tolerate a high level of abiotic stress and survive in a range of temperatures (below freezing point to 34°C) and areas with an average yearly rainfall between 250 and 600 mm. Its extensive deep taproot system is capable of regenerating asexually and with its many seed dispersal mechanisms; it can quickly spread and establish itself within a region. This makes containment and management of the species especially challenging. Previous management has largely been focused on biological control, competition, essential oils, grazing pressure, herbicide application and manual removal. Despite the large range of available management techniques, there has been little success in the long‐term control of S. elaeagnifolium, and only a handful of methods such as essential oils and herbicide application have shown reasonable success for controlling this weed. Therefore, this review aims to synthesise the identified and potentially useful approaches to control S. elaeagnifolium that have been recorded in the literature which deal with its biology, distribution and management. It also explores previous and current management techniques to ascertain the research gaps and knowledge required to assist in the effective and economically sustainable management of this invasive weed. [ABSTRACT FROM AUTHOR]

Background: Limited consensus exists on the optimal use of antifungal agents to prevent invasive fungal infection in the early post allogeneic hematopoietic stem cell transplant (alloHCT) period, particularly when patients cannot tolerate oral medication administration. Methods: We undertook a retrospective observational cohort study to assess the tolerability, efficacy, and cost of a new antifungal prophylaxis pathway at a major tertiary alloHCT centre. Patients aged ≥16 years who underwent alloHCT between February 2018 and October 2019 (cohort 1) or between April 2020 and November 2021 (cohort 2) were included. In both cohorts, first line prophylactic therapy was oral posaconazole. The second line drugs where oral therapy was unable to be administered were intravenous voriconazole (cohort 1) versus intravenous posaconazole (cohort 2). Results: There were 142 patients enrolled in the study, 71 in each cohort. The proportion of patients remaining on first‐line prophylaxis or progressing to second‐, third‐, and fourth‐line options was 22.5%, 39.4%, 29.6%, and 8.5% in cohort 1 and 39.4%, 59.2%, 1.4%, and 0% in cohort 2, respectively. The frequency of neuropsychiatric adverse events was significantly higher in cohort 1 compared to cohort 2 (49.3% vs. 19.8%, p =.0004). Occurrence of proven and probable fungal infections was not significantly different between cohorts. Antifungal drug expenditure was $359 935 (AUD) more in cohort 1 ($830 486 AUD) compared to cohort 2 ($477 149 AUD). Conclusion: The antifungal prophylaxis pathway used in cohort 2 resulted in reduced antifungal‐associated adverse effects, less patients requiring progression to 3rd and 4th line prophylaxis and reduced antifungal drug costs. [ABSTRACT FROM AUTHOR]

Antarctic geothermal heat flow (GHF) affects the thermal regime of ice sheets and simulations of ice and subglacial meltwater discharge to the ocean, but remains poorly constrained. We use an ice sheet model to investigate the impact of GHF anomalies on subglacial meltwater production in the Aurora Subglacial Basin, East Antarctica. We find that spatially‐variable GHF fields produce more meltwater than a constant GHF with the same background mean, and meltwater production increases as the resolution of GHF anomalies increases. Our results suggest that model simulations of this region systematically underestimate meltwater production using current GHF models. We determine the minimum basal heating required to bring the basal ice temperature to the pressure melting point, which should be taken together with the scale‐length of likely local variability in targeting in‐situ GHF field campaigns. Plain Language Summary: Geothermal heat flow (GHF) is important in controlling both the ice temperature and the production of meltwater at the base of the Antarctic Ice Sheet, which impacts how rapidly ice flows. However, GHF estimates are generally low resolution and highly uncertain. This uncertainty in GHF impacts the reliability of model simulations of the flow of ice and meltwater into the ocean, which in turn impacts estimates of the contribution of ice sheets to future sea level rise. We use an ice sheet model to investigate how spatial variations in GHF impact meltwater production in the Aurora Subglacial Basin (ASB), East Antarctica. GHF fields with spatial variations lead to consistently higher melt rates at the ice sheet base than a constant GHF field with the same mean value. We determine the minimum heat at the ice sheet base in the ASB required to cause the ice to melt, and highlight regions where small variations in GHF will have greater impacts on ice melting. These results show where measurements to constrain GHF should be prioritized to improve ice sheet model simulations. Key Points: We present simulations of subglacial melt in the Aurora Subglacial Basin using various geothermal heat flow (GHF) fieldsSpatially‐variable GHF enhances simulated subglacial melt compared with constant GHFWe highlight where GHF measurements should be prioritized for improved estimates of subglacial melt [ABSTRACT FROM AUTHOR]

Background: Severe community‐acquired pneumonia (SCAP) has high mortality and morbidity. Aims: To describe the epidemiology and microbiology of SCAP in Central Australia. Methods: A retrospective epidemiological study describing the characteristics, incidence rates (IR) and microbiological aetiology of SCAP in Central Australia. Adult patients admitted to Alice Springs Hospital Intensive Care Unit (ICU) between 2011 and 2014 that fitted the Infectious Diseases Society of America and American Thoracic Society definition of SCAP were included. Medical records were reviewed and compared between indigenous and non‐indigenous patients. Primary outcomes were incidence rate and microbiological aetiology of SCAP. Secondary outcomes were 30‐day mortality, and ICU and hospital length of stay (LoS). Results: A total of 185 patents were included (156 indigenous; 29 non‐indigenous). The overall SCAP IR per 1000 person‐years was 3.24 (3.75 indigenous; 1.87 non‐indigenous) with an IR difference of 2.71 after adjustment (P < 0.001). Those aged ≥50 years had an IR 74.8% higher than those younger. Male IR was 50% higher than females. There was a significant difference between indigenous and non‐indigenous groups for age (48 vs 64 years), but not for 30‐day mortality (7.7% vs 10.3%), ICU LoS (4.8 vs 4.6 days) and hospital LoS (10.9 vs 15.1 days) respectively. Likely causative pathogen(s) were identified in 117 patients; Streptococcus pneumoniae was the most common pathogen (28.2%), followed by Haemophilus influenzae (19.7%), Influenza A/B (16.2%) and Staphylococcus aureus (14.5%). Conclusion: A high incidence of SCAP was observed in Central Australia, disproportionately affecting the indigenous population. Prevention strategies are imperative, as well as early identification of SCAP and appropriate empiric antibiotic regimens. [ABSTRACT FROM AUTHOR]

Amaranthus palmeri S. Watson (Palmer amaranth) is an invasive agricultural weed that has quickly risen from a state of relative obscurity to now being globally regarded as one of the most economically destructive and difficult to manage weed species. It is now found in more than 45 countries where it poses a serious threat to agricultural production systems. Amaranthus palmeri is known to aggressively compete against crop plants for resources such as light, space, nutrients and soil moisture, all of which can result in significant crop yield reduction or even lead to crop failure. It has also been reported that A. palmeri is highly prone to evolve herbicide resistance; this makes management exceedingly challenging. Whilst there have been several control approaches introduced to manage the spread and impact of A. palmeri, many of them require more specific and focused research for their successful local and widespread application. In this regard, this global review explores the species' biology and global distribution patterns, together with previous and current management strategies. It also explores and identifies promising areas of research that still require further investigation to more confidently assist in the control and containment of this globally concerning weed. [ABSTRACT FROM AUTHOR]

The article reports that the journals shifted subtly in response to how science was conducted and reported moving from predominantly observations and case descriptions to the publication of carefully designed, methodically rigorous, studies. Topics include examines concurrent with an emergence of new, sophisticated, study designs such as Randomized Controlled Trials was the sprouting of society-owned journals published under license by a number of publishing houses.

An editorial is presented on the Oral antivirals are a potential ‘game changer' for healthcare provision during the ongoing coronavirus disease 2019 (COVID-19) pandemic. It discusses how parenteral treatments have been shown to prevent early disease progression including casirivimab plus imdevimab, remdesivir and sotrovimab the organisational requirements for oral treatment regimens can be more feasibly and expediently prescribed, dispensed and administered.

Cabomba caroliniana [A. Gray] (Cabombaceae), also known as Carolina fanwort, is a native of South America which has now become a serious invasive threat to aquatic systems across the world. Its capacity to inundate a water column with active fragments and seeds makes the containment and management of C. caroliniana a challenging task and an ecological and economic necessity. Previous and current management efforts have been largely focussed on biological control, drawdown methods, herbicide application, manual removal, shading and the use of a concentrated urea solution. Although these methods have shown some success in reducing large infestations, they are generally considered to be unreliable when used alone since they are unable to contain or reduce the species in the long term with a single‐use treatment protocol. It is feared that, without effective, improved and integrated management strategies, C. caroliniana will continue to invade aquatic ecosystems beyond its already wide current distribution, thus causing increased global economic and environmental damage. This review will therefore explore the biology and distribution of C. caroliniana and examine the current and previous attempts for its global management. It will also evaluate the most successful current treatments and clarify where research efforts are urgently needed for the improved long‐term extirpation of this aquatic invader. [ABSTRACT FROM AUTHOR]

Background: The COVID‐19 pandemic has generated significant debate about how emerging infections can be treated in the absence of evidence‐based therapies to combat disease. In particular, the use of off‐label therapies outside of a clinical trial setting has been controversial. Aim: To longitudinally study policies and prescribing practices pertaining to therapies for COVID‐19 in Australian health services during 2020. Methods: Prospective data were collected from participating Australian health services who may care for patients with COVID‐19 via an electronic portal. A single informant from each health service was emailed a survey link at regular intervals. Information was sought regarding changes to COVID‐19 policy at their service and use of therapies for COVID‐19. Results: Overall, 78 hospitals were represented from 39 respondents with longitudinal data collection from May to December 2020. All Australian states/territories were represented with the majority (34/39; 87%) of respondents located in a major city. Just over half (20/39) of respondents had a written policy for COVID‐19 therapy use at their health service at survey enrolment and policies changed frequently throughout the pandemic. Therapy use outside of a clinical trial was reported in 54% of health services, most frequently in Victoria, correlating with higher numbers of COVID‐19 cases. At study commencement, hydroxychloroquine was most frequently used, with corticosteroids and remdesivir use increasingly throughout the study period. Conclusion: Our results reflect the reactive nature of prescribing of therapies for COVID‐19 and highlight the importance of evidence‐based guidelines to assist prescribers. [ABSTRACT FROM AUTHOR]

Aims: The purpose of the study was to assess the status of emerging therapeutic drug monitoring (TDM) of anti‐infective agents in Australian hospitals. Methods: A nationwide cross‐sectional survey of all Australian hospitals operating in the public and private health sector was conducted between August and September 2019. The survey consisted of questions regarding institutional TDM practice for anti‐infective agents and clinical vignettes specific to β‐lactam antibiotics. Results: Responses were received from 82 unique institutions, representing all Australian states and territories. All 29 (100%) of principal referral (major) hospitals in Australia participated. Five surveys were partially complete. Only 25% (20/80) of hospitals had TDM testing available on‐site for any of the eight emerging TDM candidates considered: β‐lactam antibiotics, anti‐tuberculous agents, flucytosine, fluoroquinolones, ganciclovir, human immunodeficiency virus (HIV) drugs, linezolid and teicoplanin. A considerable time lag was noted between TDM sampling and reporting of results. With respect to β‐lactam antibiotic TDM, variable indications, pharmacodynamic targets and sampling times were identified. The three greatest barriers to local TDM performance were found to be (1) lack of timely assays/results, (2) lack of institutional‐wide expertise and/or training and (3) lack of guidelines to inform ordering of TDM and interpretation of results. The majority of respondents favoured establishing national TDM guidelines and increasing access to dose prediction software, at rates of 89% and 96%, respectively. Conclusion: Translating emerging TDM evidence into daily clinical practice is slow. Concerted efforts are required to address the barriers identified and facilitate the implementation of standardised practice. [ABSTRACT FROM AUTHOR]

This article is a response to a comment made about a meta-analysis on the use of prolonged-infusion β-lactams. The authors acknowledge the errors in the original analysis and have conducted a revised meta-analysis with corrected numbers. The overall point estimates remain similar to the original report, and the quality of evidence and strength of recommendation remain unaffected. The authors have also updated their loading dose subgroup analyses and corresponding text, which do not alter their overall recommendation on the use of a loading dose. A conflict of interest statement is provided, and an erratum will be issued. [Extracted from the article]

A personal narrative is presented which explores the authors experience of showing research and advocacy influencing global health care.

The bathymetry under the Amery Ice Shelf steers the flow of ocean currents transporting ocean heat, and thus is a prerequisite for precise modeling of ice‐ocean interactions. However, hampered by thick ice, direct observations of sub‐ice‐shelf bathymetry are rare, limiting our ability to quantify the evolution of this sector and its future contribution to global mean sea level rise. We estimated the bathymetry of this region from airborne gravity anomaly using simulated annealing. Unlike the current model which shows a comparatively flat seafloor beneath the calving front, our estimation results reveal a 255‐m‐deep shoal at the western side and a 1,050‐m‐deep trough at the eastern side, which are important topographic features controlling the ocean heat transport into the sub‐ice cavity. The new model also reveals previously unknown depressions and sills that are critical to an improved modeling of the sub‐ice‐shelf ocean circulation and induced basal melting. Plain Language Summary: The ocean currents are strongly steered by the seafloor topography. Therefore, the seafloor topography should be represented at fine resolution to study how the warm water melts the ice shelf from below. However, the seafloor beneath the largest ice shelf in East Antarctica remains poorly known, because the thick floating ice blocks direct bathymetric observations. We used gravity measured by airplane to infer the shape of the seafloor beneath the floating ice. The gravity‐inferred seafloor topography model is substantially improved over the existing BedMachine Antarctica model, and reveals previously unknown topographic features. The newly identified seafloor topographic features could improve our knowledge about how much ocean heat enters the sub‐ice cavity and how the ocean currents flow beneath the ice shelf. With this knowledge, scientists could more accurately project the response of the Amery Ice Shelf to ocean forcing and this region's future contribution to global mean sea level rise. Key Points: The seafloor topography beneath the Amery Ice Shelf, East Antarctica, is estimated from airborne gravity using simulated annealingEstimation results present updated ice front geometry, an important factor controlling the ocean heat transport into sub‐ice cavityThe model reveals previously unknown depressions at the western flank that are critical to an improved modeling of ocean circulation [ABSTRACT FROM AUTHOR]

Jatropha gossypiifolia (Bellyache bush) is an evergreen, perennial, invasive woody shrub that globally threatens agricultural and native landscapes. The species is native to North and South America, but is currently found in over 52 countries; in many of these countries, it is listed as invasive, due to its aggressive and competitive growth. These behaviour traits are characterised by its quick flowering and seed production that make the species difficult to contain and control, as it forms dense monocultures and restricts the growth of many native and pastoral species through aggressive competition for resources, such as soil moisture and nutrients. Infestation by J. gossypiifolia results in a loss of biodiversity in the affected area and disrupts the maintenance of sustainable land systems. It has been reported that J. gossypiifolia is used in many countries as a traditional medicine to treat a range of diseases, illnesses and injuries. However, despite these claims of its positive use, J. gossypiifolia leaves, seeds and stems are highly toxic to grazing animals and humans, leading to disruption and significant increases in the cost of agricultural production through the loss of production and the instituting of necessary management efforts. Around the world, there have been various attempts to control J. gossypiifolia, but these have widely varied in their success. The most common and successful treatments to control J. gossypiifolia, including herbicide application (cut stump application), fire management and mechanical control; however, when each is applied as a single treatment, long‐term success is often limited. Consequently, this review explores the biology and distribution of J. gossypiifolia, together with previous and current control attempts, and synthesises potentially useful approaches to control this noxious weed, whilst identifying areas of future research to improve effective and long‐term sustainable management strategies for this noxious species. [ABSTRACT FROM AUTHOR]

Antifungal agents can have complex dosing and the potential for drug interaction, both of which can lead to subtherapeutic antifungal drug concentrations and poorer clinical outcomes for patients with haematological malignancy and haemopoietic stem cell transplant recipients. Antifungal agents can also be associated with significant toxicities when drug concentrations are too high. Suboptimal dosing can be minimised by clinical assessment, laboratory monitoring, avoidance of interacting drugs, and dose modification. Therapeutic drug monitoring (TDM) plays an increasingly important role in antifungal therapy, particularly for antifungal agents that have an established exposure‐response relationship with either a narrow therapeutic window, large dose‐exposure variability, cytochrome P450 gene polymorphism affecting drug metabolism, the presence of antifungal drug interactions or unexpected toxicity, and/or concerns for non‐compliance or inadequate absorption of oral antifungals. These guidelines provide recommendations on antifungal drug monitoring and TDM‐guided dosing adjustment for selected antifungal agents, and include suggested resources for identifying and analysing antifungal drug interactions. Recommended competencies for optimal interpretation of antifungal TDM and dose recommendations are also provided. [ABSTRACT FROM AUTHOR]

This article introduces the fourth update of the Australian and New Zealand consensus guidelines for the management of invasive fungal disease and use of antifungal agents in the haematology/oncology setting. These guidelines are comprised of nine articles as presented in this special issue of the Internal Medicine Journal. This introductory chapter outlines the rationale for the current update and the steps taken to ensure implementability in local settings. Given that 7 years have passed since the previous iteration of these guidelines, pertinent contextual changes that impacted guideline content and recommendations are discussed, including the evolution of invasive fungal disease (IFD) definitions. We also outline our approach to guideline development, evidence grading, review and feedback. Highlights of the 2021 update are presented, including expanded scope to provide more detailed coverage of common and emerging fungi such as Aspergillus and Candida species, and emerging fungi, and a greater focus on the principles of antifungal stewardship. We also introduce an entirely new chapter dedicated to helping healthcare workers convey important concepts related to IFD, infection prevention and antifungal therapy, to patients. [ABSTRACT FROM AUTHOR]

Ulex europaeus (Gorse) is one of the most invasive shrubs in the world, being now found in more than 50 countries where it economically and environmentally degrades the land. This highly versatile shrub can live more than 30 years and produce over 18,000 fertile seeds annually that can remain viable for over 30 years. Ulex europaeus spread is facilitated by its ability to germinate in a wide range of conditions, quick growth and maturing rate and several seed dispersal mechanisms. Despite extensive research and attempts at managing U. europaeus, current rates of control are not adequate to limit the species' competitiveness and impact on the environment. This has resulted in the species altering soil and landscape dynamics in areas of major invasion, inhibiting the growth of agricultural and native species, creating shelter for pest species and reducing the richness of competing species at a site, all of which contribute to the economic and environmental degradation of the land. This review highlights that herbicide application is the most successful technique used to control U. europaeus, although it has shown varying success across different climatic regions. In this regard, future research should investigate the possibility of integrating a range of techniques (competition, fire management, grazing, manual removal and mycoherbicides) to increase control success and reduce any potential risk of herbicide resistance. Further research is also required on the maintenance of longer‐term viable populations of biological control agents to limit the success of this invasive species. Bridging the identified research gaps will help to facilitate the improved long‐term management of U. europaeus and help land managers confidently to maintain sustainable land systems. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has resulted in an unprecedented need for diagnostic testing that is critical in controlling the spread of COVID‐19. We propose a portable infrared spectrometer with purpose‐built transflection accessory for rapid point‐of‐care detection of COVID‐19 markers in saliva. Initially, purified virion particles were characterized with Raman spectroscopy, synchrotron infrared (IR) and AFM‐IR. A data set comprising 171 transflection infrared spectra from 29 subjects testing positive for SARS‐CoV‐2 by RT‐qPCR and 28 testing negative, was modeled using Monte Carlo Double Cross Validation with 50 randomized test and model sets. The testing sensitivity was 93 % (27/29) with a specificity of 82 % (23/28) that included positive samples on the limit of detection for RT‐qPCR. Herein, we demonstrate a proof‐of‐concept high throughput infrared COVID‐19 test that is rapid, inexpensive, portable and utilizes sample self‐collection thus minimizing the risk to healthcare workers and ideally suited to mass screening. [ABSTRACT FROM AUTHOR]

The purpose of many wildlife population studies is to estimate density, movement, or demographic parameters. Linking these parameters to covariates, such as habitat features, provides additional ecological insight and can be used to make predictions for management purposes. Line‐transect surveys, combined with distance sampling methods, are often used to estimate density at discrete points in time, whereas capture–recapture methods are used to estimate movement and other demographic parameters. Recently, open population spatial capture–recapture models have been developed, which simultaneously estimate density and demographic parameters, but have been made available only for data collected from a fixed array of detectors and have not incorporated the effects of habitat covariates. We developed a spatial capture–recapture model that can be applied to line‐transect survey data by modeling detection probability in a manner analogous to distance sampling. We extend this model to a) estimate demographic parameters using an open population framework and b) model variation in density and space use as a function of habitat covariates. The model is illustrated using simulated data and aerial line‐transect survey data for North Atlantic right whales in the southeastern United States, which also demonstrates the ability to integrate data from multiple survey platforms and accommodate differences between strata or demographic groups. When individuals detected from line‐transect surveys can be uniquely identified, our model can be used to simultaneously make inference on factors that influence spatial and temporal variation in density, movement, and population dynamics. [ABSTRACT FROM AUTHOR]

Eragrostis curvula (African Lovegrass) is an invasive C4 perennial grass that is threatening natural ecosystems globally. Native to Africa, this species can tolerate a wide range of environmental conditions, from acidic soils to areas with low rainfall and regions with frequent fires, which assists in its widespread distribution. With its large production of small seeds (0.3 to 0.7 mm) and quick seed germination, it has the ability to form dense swards which can limit the recruitment of other more desirable species in the landscape. Due to its invasive behaviour, E. curvula can now be found in several countries (Australia, Japan, New Zealand and the United States of America) where it causes environmental and economic degradation of the land, particularly if appropriate management is not applied. Previous management on the species has been focused on restoring competitive grasslands and pastures, grazing management, herbicide application, large‐scale burning and manual removal; however, in many regions there has been little to no long‐term success in reducing the species spread. Therefore, this review aimed to synthesise the existing research into the biology, distribution and management of E. curvula, whilst identifying any research gaps which may help improve the effective management of the species. [ABSTRACT FROM AUTHOR]

The article presents the Standard of Practice in Infectious Diseases for Pharmacy Services from the Society of Hospital Pharmacists of Australia (SHPA). Topics include the complementarity of the standard with the National Competency Standards Framework for Pharmacists in Australia, and the topics of the standard like the basic rights of patients and consumers when accessing healthcare services like information, privacy, and safety.

Aim: The research aim was to conduct a systematic review of the literature regarding the pharmacokinetics (PK) and dosing of antimicrobials in prolonged intermittent renal replacement therapy (PIRRT), a hybrid form of dialysis becoming increasingly utilised in critical care. Methods: A literature review was performed using PubMed from database inception to October 2020 according to the PRISMA guidelines. All papers published in English language were included in the review. Two researchers independently conducted literature searches, screened abstracts and full text and came to agreement as to which articles were suitable for inclusion before compiling the relevant data into a spreadsheet. The types of papers retrieved varied between case reports, single and multiple dose pharmacokinetic studies and Monte Carlo simulations. Results: A total of 149 articles were found in the initial literature review and via other sources. Of these papers, 50 articles were deemed eligible for inclusion. These studies included one to 34 patients. PIRRT settings varied between institutions, including filter surface area, duration of PIRRT and type of dialyser used. With the exception of vancomycin and meropenem, few antimicrobials had sufficient data available from which reasonable empiric dosing regimens can be recommended. Conclusion: There is limited data to guide dosing of antimicrobials during PIRRT. More studies are required to understand how dosing can be optimised in this population of critically ill patients. [ABSTRACT FROM AUTHOR]

Aim: To summarise the evidence on pharmacist‐led antifungal stewardship (AFS) programs in the hospital setting and to evaluate their impact on the quality of antifungal prescribing and infection management, antifungal usage and clinical outcomes. Data sources: A systematic review of English‐language studies identified in MEDLINE and EMBASE was performed on 27 November 2020 and conducted in accordance with PRISMA. Search terms included 'antifungal agent', 'invasive fungal infection', 'antimicrobial stewardship', 'patient care bundles' and 'pharmacist'. Study selection: Eligible studies describing pharmacist‐led quality improvement intervention(s) implemented in the hospital setting targeted at optimising systemic antifungal prescribing. Results: Six hundred and forty‐six studies were identified, and seven met inclusion criteria. Five were dedicated to optimising candidaemia management, one at optimising intensive care unit prescribing of caspofungin and one on antifungal prescribing in haematology and oncology units. All studies measured varied metrics relating to quality of prescribing and infection management, reporting improvement in proportion of effective antifungal therapy (n = 1/1), appropriate antifungal selection (n = 1/1), dosing (n = 2/3), management of drug–drug interactions (n = 1/1) and reduced time to antifungal initiation (n = 4/4). Studies that implemented a candidaemia bundle of care reported improvements in composite bundle adherence (n = 2/2), with greatest improvement in ophthalmological consultation (n = 4/4), echocardiography (n = 2/2) and infectious diseases consultation (n = 3/3). There was reduction in antifungal expenditure (n = 4/4) and consumption (n = 2/4). Pharmacist‐led AFS programs did not influence clinical outcomes. Conclusion: Available evidence suggests that pharmacist‐led AFS interventions can improve the quality and timeliness of antifungal prescribing and reduce antifungal usage. Further research is required to assess the impact on clinical and microbiological outcomes. [ABSTRACT FROM AUTHOR]

The article presents the standard of practice in intensive care for pharmacy services in 2021. Topics discussed include the purpose and definitions, evidence of pharmacist impact in intensive care unit (ICU) and paediatric ICU (PICU) services, objectives of the pharmacy service, and the scope of standard of practice. Also noted are the policies, procedures and governance in pharmacist practice.

Model‐informed drug development (MIDD) has a long and rich history in infectious diseases. This review describes foundational principles of translational anti‐infective pharmacology, including choice of appropriate measures of exposure and pharmacodynamic (PD) measures, patient subpopulations, and drug‐drug interactions. Examples are presented for state‐of‐the‐art, empiric, mechanistic, interdisciplinary, and real‐world evidence MIDD applications in the development of antibacterials (review of minimum inhibitory concentration‐based models, mechanism‐based pharmacokinetic/PD (PK/PD) models, PK/PD models of resistance, and immune response), antifungals, antivirals, drugs for the treatment of global health infectious diseases, and medical countermeasures. The degree of adoption of MIDD practices across the infectious diseases field is also summarized. The future application of MIDD in infectious diseases will progress along two planes; "depth" and "breadth" of MIDD methods. "MIDD depth" refers to deeper incorporation of the specific pathogen biology and intrinsic and acquired‐resistance mechanisms; host factors, such as immunologic response and infection site, to enable deeper interrogation of pharmacological impact on pathogen clearance; clinical outcome and emergence of resistance from a pathogen; and patient and population perspective. In particular, improved early assessment of the emergence of resistance potential will become a greater focus in MIDD, as this is poorly mitigated by current development approaches. "MIDD breadth" refers to greater adoption of model‐centered approaches to anti‐infective development. Specifically, this means how various MIDD approaches and translational tools can be integrated or connected in a systematic way that supports decision making by key stakeholders (sponsors, regulators, and payers) across the entire development pathway. [ABSTRACT FROM AUTHOR]

Augmented renal clearance (ARC, creatinine clearance > 130 mL/minute) makes difficult achievement of effective concentrations of renally cleared antibiotics in critically ill patients. This study examined the synergistic killing and resistance suppression for meropenem‐ciprofloxacin combination dosage regimens against Pseudomonas aeruginosa isolates within the context of ARC. Clinically relevant meropenem and ciprofloxacin concentrations, alone and in combinations, were studied against three clinical isolates with a range of susceptibilities to each of the antibiotics. Isolate Pa1280 was susceptible to both meropenem and ciprofloxacin, Pa1284 had intermediate susceptibility to meropenem and was susceptible to ciprofloxacin, and CR380 was resistant to meropenem and had intermediate susceptibility to ciprofloxacin. Initially, isolates were studied in 72‐hour static‐concentration time‐kill (SCTK) studies. Subsequently, the pharmacokinetic profiles expected in patients with ARC receiving dosage regimens, including at the highest approved daily doses (meropenem 6 g daily divided and administered as 0.5‐hour infusions every 8 hours, or as a continuous infusion; ciprofloxacin 0.4 g as 1‐hour infusions every 8 hours), were examined in a dynamic hollow‐fiber infection model (HFIM) over 7–10 days. In both SCTK and HFIM, combination regimens were generally synergistic and suppressed growth of less‐susceptible subpopulations, these effects being smaller for isolate CR380. The time‐courses of total and less‐susceptible bacterial populations in the HFIM were well‐described by mechanism‐based models, which enabled conduct of Monte Carlo simulations to predict likely effectiveness of approved dosage regimens at different creatinine clearances. Optimized meropenem‐ciprofloxacin combination dosage regimens may be a viable consideration for P. aeruginosa infections in critically ill patients with ARC. [ABSTRACT FROM AUTHOR]

This article discusses the challenges of constructing pharmacotherapy regimens in the intensive care unit (ICU) due to the complexities and heterogeneity of critically ill patients. The article highlights the need for precision medicine in the ICU, which involves using genomic, lifestyle, and environmental information to provide targeted, individualized care. The themed edition of Pharmacotherapy focuses on providing precision medicine in the ICU, with contributions from international experts and research on optimizing dosing strategies. The article emphasizes the importance of embracing precision medicine to identify the right therapy for each patient in the ICU. [Extracted from the article]

Keywords: ganciclovir; lung transplantation; PIRRT; prolonged intermittent renal replacement therapy; valganciclovir; voriconazole EN ganciclovir lung transplantation PIRRT prolonged intermittent renal replacement therapy valganciclovir voriconazole 1 3 3 04/08/22 20220401 NES 220401 Dear Editor, Acute kidney injury (AKI) requiring haemodialysis is a common complication following lung transplantation.1 Prolonged intermittent renal replacement therapy (PIRRT) has emerged as a hybrid dialytic therapy that provides clearance rates and treatment times (6-12 h every 1-3 days) in between the traditional therapies of intermittent haemodialysis (IHD) and continuous renal replacement therapy (CRRT). DISCUSSION The PK modelling of ganciclovir concentrations taken during and after PIRRT suggests that it is effectively cleared to levels of 1-2 mg/L, which may be adequate for CMV prophylaxis and indicates that the valganciclovir dose of 450 mg every 48 h may be satisfactory to prevent clinically significant CMV viremia, as borne out in this case. Trough concentrations of 1-2 mg/L for prophylaxis and 2-4 mg/L for treatment have been proposed.7 Voriconazole is a mould-active triazole antifungal agent. [Extracted from the article]

Introduction: Septal accessory pathway (AP) ablation can be challenging due to the complex anatomy of the septal region. The decision to access the left atrium (LA) is often made after failure of ablation from the right. We sought to establish whether the difference between ventriculo‐atrial (VA) time during right ventricular (RV) apical pacing versus the VA during tachycardia would help establish the successful site for ablation of septal APs. Methods: Intracardiac electrograms of patients with orthodromic reciprocating tachycardia (ORT) using a septal AP with successful catheter ablation were reviewed. The ∆VA was the difference between the VA interval during RV apical pacing and the VA interval during ORT. The difference in the VA interval during right ventricular entrainment and ORT (StimA–VA) was also measured. Results: The median ∆VA time was significantly less in patients with a septal AP ablated on the right side compared with patients with a septal AP ablated on the left side (12 ± 19 vs. 56 ± 10 ms, p <.001). The StimA–VA was significantly different between the two groups (22 ± 14 vs. 53 ± 9 ms, p <.001). The ∆VA and StimA–VA were always ≤40 ms in patients with non‐decremental septal APs ablated from the right side and always greater than 40 ms in those with septal APs ablated from the left. Conclusion: ΔVA and StimA–VA values identified with RV apical pacing in the setting of ORT involving a septal AP predict when left atrial access will be necessary for successful ablation. [ABSTRACT FROM AUTHOR]

Inherited arrhythmia syndromes have traditionally been viewed as monogenic forms of disease whose pathophysiology is driven by a single highly penetrant rare genetic variant. Although an accurate depiction of a proportion of genetic variants, the variable penetrance frequently noted in genotype positive families and the presence of sporadic genotype negative cases have long highlighted a more nuanced truth being operative. Coupled with our more recent recognition that many rare variants implicated in inherited arrhythmia syndromes possess unexpectedly high allele frequencies within the general population, these observations have contributed to the realization that a spectrum of pathogenicity exists among clinically relevant genetic variants. Notably, variable mutation pathogenicity and corresponding variable degrees of penetrance emphasize a limitation of contemporary guidelines, which attempt to dichotomize genetic variants as pathogenic or benign. Recognition of the existence of low and intermediate penetrant variants insufficient to be causative for disease in isolation has served to emphasize the importance of additional genetic, clinical, and environmental factors in the pathogenesis of rare inherited arrhythmia syndromes. Despite being rare, it has also become increasingly evident that common genetic variants play critical roles in both heritable channelopathies and cardiomyopathies and in aggregate may even be the primary drivers in certain instances, such as genotype negative Brugada syndrome. Our growing realization that the genetic substrates of inherited arrhythmia syndromes have intricacies that extend beyond traditionally perceived monogenic paradigms has highlighted a potential value of leveraging more comprehensive genomic risk scores for predicting disease development and arrhythmic risk. [ABSTRACT FROM AUTHOR]

Forecasting the responses of biodiversity to global change has never been more important. However, many ecologists faced with limited sample sizes and shoestring budgets often resort to extrapolating predictive models beyond the range of their data to support management actions in data‐deficient contexts. This can lead to error‐prone inference that has the potential to misdirect conservation interventions and undermine decision‐making. Despite the perils associated with extrapolation, little guidance exists on the best way to identify it when it occurs, leaving users questioning how much credence they should place in model outputs. To address this, we present dsmextra, a new R package for measuring, summarizing and visualizing extrapolation in multivariate environmental space.dsmextra automates the process of conducting quantitative, spatially explicit assessments of extrapolation on the basis of two established metrics: the Extrapolation Detection (ExDet) tool and the percentage of data nearby (%N). The package provides user‐friendly functions to (a) calculate these metrics, (b) create tabular and graphical summaries, (c) explore combinations of covariate sets as a means of informing covariate selection and (d) produce visual displays in the form of interactive html maps.dsmextra implements a model‐agnostic approach to extrapolation detection that is applicable across taxonomic groups, modelling techniques and datasets. We present a case study fitting a density surface model to visual detections of pantropical spotted dolphins Stenella attenuata in the Gulf of Mexico.Predictive modelling seeks to deliver actionable information about the states and trajectories of ecological systems, yet model performance can be strongly impaired out of sample. By assessing conditions under which models are likely to fail or succeed in extrapolating, ecologists may gain a better understanding of biological patterns and their underlying drivers. Critical to this is a concerted effort to standardize best practice in model evaluation, with an emphasis on extrapolative capacity. [ABSTRACT FROM AUTHOR]

High‐quality aeromagnetic data are important in guiding new knowledge of the solid earth in frontier regions, such as Antarctica, where these data are often among the first data collected. The difficulties of data collection in remote regions often lead to less than ideal data collection, leading to data that are sparse and four‐dimensional in nature. Standard aeromagnetic data collection procedures are optimized for the (nearly) 2‐D data that are collected in industry standard surveys. In this work we define and apply a robust magnetic data correction approach that is optimized to these four‐dimensional data. Data are corrected in three phases, with phase 1 operations on point data, correcting for spatiotemporal geomagnetic conditions, then phase 2 operations on line data, adjusting for elevation differences along and between lines and in phase 3, a line‐based leveling approach to bring lines into agreement while preserving data integrity. For a large‐scale East Antarctic survey, the overall median cross‐tie error reduction error reduction is 93%, reaching a final median error of 5 nT. Error reduction is spread evenly between phases 1 and 3. Phase 2 does not reduce error directly but permits a stronger error reduction in phase 3. Residual errors are attributed to limitations in the ability to model 4‐D geomagnetic conditions and also some limitations of the inversion process used in phase 2. Data have improved utility for geological interpretation and modeling, in particular quantitative approaches, which are enabled with less bias and more confidence. Plain Language Summary: Observations of the Earth's magnetic field underpin our knowledge of geology and tectonics and are often among the first data collected in frontier regions. This work focuses on the problems experienced in remote surveys, including observation periods extending over years, and flying heights that vary over kilometers. Conventional approaches are designed for more tightly constrained survey collection and can be inappropriate for these data. A new way to process airborne observations of magnetic field intensity is developed and tested. Applied to a data set in East Antarctica, the data quality is substantially improved and the data better reveals the geology hidden beneath the ice of Antarctica. Key Points: A new approach to correcting four‐dimensional aeromagnetic data is developed and tested with the large‐scale ICECAP data set from East AntarcticaSubstantial improvements in data quality and reliability are seen and error thresholds are well definedThese improvements in data quality support the investigation of subglacial geology and tectonics in magnetic data [ABSTRACT FROM AUTHOR]

The distributions of highly mobile marine species such as cetaceans are increasingly modeled at basin scale by combining data from multiple regions. However, these basin‐wide models often overlook geographical variations in species habitat relationships between regions. We tested for geographical variations in habitat relationships for a suite of cetacean taxa between the two sides of the North Atlantic basin. Using cetacean visual survey data and remote sensing data from the western and eastern basin in summer, we related the probability of presence of twelve cetacean taxa from three guilds to seafloor depth, sea surface temperature and primary productivity. In a generalized additive model framework, we fitted 1) basin‐wide (BW) models, assuming a single global relationship, 2) region‐specific intercepts (RI) models, assuming relationships with the same shape in both regions, but allowing a region‐specific intercept and 3) region‐specific shape (RS) models, assuming relationships with different shapes between regions. RS models mostly yielded significantly better fits than BW models, indicating cetacean occurrences were better modeled with region‐specific than with global relationships. The better fits of RS models over RI models further provided statistical evidence for differences in the shapes of region‐specific relationships. Baleen whales showed striking differences in both the shapes of relationships and their mean presence probabilities between regions. Deep diving whales and delphinoids showed contrasting relationships between regions with few exceptions (e.g. non‐statistically different shapes of region‐specific relationships for harbor porpoise and beaked whales with depth). Our findings stress the need to account for geographical differences in habitat relationships between regions when modeling species distributions from combined data at the basin scale. Our proposed hypotheses offer a roadmap for understanding why habitat relationships may geographically vary in cetaceans and other highly mobile marine species. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygenation (ECMO) therapy could affect drug concentrations via adsorption onto the oxygenator and/or associated circuit. We describe a case of a 33‐year‐old man with severe respiratory failure due to Pneumocystis jirovecii infection on a background of recently diagnosed human immunodeficiency virus infection. He required venovenous ECMO therapy for refractory respiratory failure. Intravenous sulfamethoxazole‐trimethoprim (100 and 20 mg/kg/day) was administered in a dosing regimen every 6 hours. Pre‐oxygenator, post‐oxygenator, and arterial blood samples were collected after antibiotic administration and were analyzed for total sulfamethoxazole and trimethoprim concentrations. The peak sulfamethoxazole and trimethoprim concentrations were 122 mg/L and 5.3 mg/L, respectively. The volume of distribution for sulfamethoxazole was 0.37 and 2.30 L/kg for trimethoprim. The clearance for sulfamethoxazole was 0.35 ml/minute/kg and for trimethoprim was 1.64 ml/minute/kg. The pharmacokinetics of sulfamethoxazole and trimethoprim appear not to be affected by ECMO therapy, and dosing adjustment may not be required. [ABSTRACT FROM AUTHOR]