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: Introduction: New South Wales (NSW) has one of the world's highest uptake rates of HIV pre‐exposure prophylaxis (PrEP). This uptake has been credited with sharp declines in HIV transmission, particularly among Australian‐born gay and bisexual men. Concerns have been raised around the potential for the emergence of tenofovir (TFV) and XTC (lamivudine/emtricitabine) resistance in settings of high PrEP use. Such an emergence could also increase treatment failure and associated clinical outcomes among people living with HIV (PLHIV). Despite low levels of nucleoside reverse‐transcriptase inhibitor (NRTI) resistance relating to PrEP use in clinical settings, there are few published studies describing the prevalence of NRTI resistance among people newly diagnosed with HIV in a setting of high PrEP use. Methods: Using HIV antiretroviral drug resistance data linked to NSW HIV notifications records of people diagnosed from 1 January 2015 to 31 December 2021 and with HIV attributed to male‐to‐male sex, we described trends in TFV and XTC resistance. Resistance was identified using the Stanford HIV Drug Resistance genotypic resistance interpretation system. To focus on transmitted drug resistance, resistance prevalence estimates were generated using sequences taken less than 3 months post‐HIV diagnosis. These estimates were stratified by timing of sequencing relative to the date of diagnosis, year of sequencing, birthplace, likely place of HIV acquisition, and stage of HIV at diagnosis. Results: Among 1119 diagnoses linked to HIV genomes sequenced less than 3 months following diagnosis, overall XTC resistance prevalence was 1.3%. Between 2015 and 2021, XTC resistance fluctuated between 0.5% to 2.9% and was 1.0% in 2021. No TFV resistance was found over the study period in any of the sequences analysed. Higher XTC resistance prevalence was observed among people with newly acquired HIV (evidence of HIV acquisition in the 12 months prior to diagnosis; 2.9%, p = 0.008). Conclusions: In this Australian setting, TFV and XTC resistance prevalence in new HIV diagnoses remained low. Our findings offer further evidence for the safe scale‐up of PrEP in high‐income settings, without jeopardizing the treatment of those living with HIV., INTRODUCTION Australia has made remarkable progress in its effort to meet the UNAIDS 2030 target of ending AIDS as a public health threat with HIV diagnoses attributed to male‐to‐male sex [...]

Introduction: Due to a lack of robust population denominators, Australia is unable to accurately monitor changes in the HIV epidemic for some populations. The ratio of HIV transmission relative to the number of people with HIV (an incidence prevalence ratio, or IPR) can measure such changes. The IPR is measured against an IPR benchmark derived from post‐HIV acquisition life expectancy, to indicate whether an HIV epidemic is shrinking or growing. Using IPRs and Australia‐specific IPR benchmarks, this study aims to describe the Australian HIV epidemic among three groups: men with HIV attributed to male‐to‐male sex, women with HIV and people with HIV attributed to injection drug use. Methods: Using mathematical modelling derived from HIV notifications, cohort and administrative data, IPRs were generated for each of the three groups. These IPRs were compared with IPR benchmarks derived from post‐HIV acquisition mortality estimates using abridged life tables for men, women and people who inject drugs. The IPR benchmark for men was applied to people with HIV attributed to male‐to‐male sex. Trends in the IPR over time were described for each reported population from 2015 to 2022. Results: Overall, the IPR fell by 80%, from 0.040 (range: 0.034−0.045) in 2015 to 0.008 (range: 0.003−0.013) in 2022 and fell below the benchmark (0.022) in 2020. Among people with HIV attributed to male‐to‐male sex, the IPR fell by 85%, from 0.041 (range: 0.034−0.047) in 2015 to 0.006 (range: 0.003−0.024) in 2022 and fell below the benchmark (0.022) in 2020. Among women with HIV, the IPR fell by 56%, from 0.032 (range: 0.026−0.039) in 2015 to 0.014 (range: 0.003−0.029) in 2022 and fell below the benchmark (0.022) in 2019. Among people with HIV attributed to injection drug use, the IPR fell by 61%, from 0.036 (range: 0.022−0.047) in 2015 to 0.014 (range: 0.002−0.057) in 2022 and fell below the benchmark (0.028) in 2019. Conclusions: Australian IPRs in all populations examined have dropped below the level required to sustain the HIV epidemic at current levels. By applying this method in other contexts, the changing scale of HIV epidemics may be better described for populations lacking robust population denominators. [ABSTRACT FROM AUTHOR]

Introduction: Decentralized molecular testing for infectious disease diagnosis at the point-of-care (POC) is critical to address inequities in access to timely, informed health care. The COVID-19 pandemic accelerated the demand, development and adoption of POC tests for infectious diseases globally. This has provided opportunities to maximize the individual benefits and public health impact of POC testing, particularly in remote and resource-limited primary care settings. Despite this, there remains a lack of harmonized, regulatory compliance and quality management frameworks for the delivery of molecular POC testing networks outside the laboratory setting. Areas Covered: This Perspective describes real-world lessons and experiences of delivering a fit-for-purpose, quality framework for one of the world's largest decentralized molecular POC testing programs for infectious disease across rural and remote Australian communities. Here we detail unique, key considerations to ensure the quality of POC testing in primary health settings with global application. Expert Opinion: There is an ethical and public health imperative to provide sustained access to decentralized POC testing for infectious disease in primary care. Genuine partnerships across stakeholders and disciplines are essential to deliver well governed, fit-for-purpose quality management POC testing frameworks and increase equitable access to timely, high-quality person-centered care. [ABSTRACT FROM AUTHOR]

: Introduction: Australia has set the goal for the virtual elimination of HIV transmission by the end of 2022, yet accurate information is lacking on the level of HIV transmission occurring among residents. We developed a method for estimating the timing of HIV acquisition among migrants, relative to their arrival in Australia. We then applied this method to surveillance data from the Australian National HIV Registry with the aim of ascertaining the level of HIV transmission among migrants to Australia occurring before and after migration, and to inform appropriate local public health interventions. Methods: We developed an algorithm incorporating CD4[sup.+] T‐cell decline back‐projection and enhanced variables (clinical presentation, past HIV testing history and clinician estimate of the place of HIV acquisition) and compared it to a standard algorithm which uses CD4[sup.+] T‐cell back‐projection only. We applied both algorithms to all new HIV diagnoses among migrants to estimate whether HIV infection occurred before or after arrival in Australia. Results: Between 1 January 2016 and 31 December 2020, 1909 migrants were newly diagnosed with HIV in Australia, 85% were men, and the median age was 33 years. Using the enhanced algorithm, 932 (49%) were estimated to have acquired HIV after arrival in Australia, 629 (33%) before arrival (from overseas), 250 (13%) close to arrival and 98 (5%) were unable to be classified. Using the standard algorithm, 622 (33%) were estimated to have acquired HIV in Australia, 472 (25%) before arrival, 321 (17%) close to arrival and 494 (26%) were unable to be classified. Conclusions: Using our algorithm, close to half of migrants diagnosed with HIV were estimated to have acquired HIV after arrival in Australia, highlighting the need for tailored culturally appropriate testing and prevention programmes to limit HIV transmission and achieve elimination targets. Our method reduced the proportion of HIV cases unable to be classified and can be adopted in other countries with similar HIV surveillance protocols, to inform epidemiology and elimination efforts., INTRODUCTION UNAIDS has set the ambitious target to eliminate the global transmission of HIV by 2030 [1] and Australia is aiming for “virtual elimination” by the end of 2022 [2]. [...]

Introduction: Elevations in serum ferritin and serum iron occur during pediatric extracorporeal membrane oxygenation (ECMO). Previous reports attribute the elevation to frequent red blood cell transfusions and/or hemolysis. Chronic transfusion can cause iron deposition in tissues leading to multisystem organ dysfunction. This study aims identify clinical factors associated with elevated ferritin and iron in pediatric ECMO patients, along with post-decannulation magnetic resonance imaging (MRI) assessment of iron deposition in liver and brain. Methods: Prospective, pilot study, using descriptive statistics to investigate potential associations between patient characteristics, serum ferritin and iron levels, and post-decannulation hepatic and basal ganglia iron deposition. Results: In this study, nine patients (100%) had elevated serum ferritin levels during ECMO. High ferritin levels were more common with veno-arterial than with veno-venous cannulation (p = 0.026) and were also associated with high plasma free hemoglobin levels (p < 0.001). Five patients presented with elevated serum iron levels. High serum iron levels were associated with higher daily (p = 0.016) and cumulative transfusion volumes (p = 0.013) as well ECMO duration beyond 7 days. MRI scans were performed on three patients with no evidence of abnormal iron deposition detected in the liver or brain. Conclusions: This pilot study shows that during pediatric ECMO, elevations in serum ferritin and serum iron occur and those elevations may be related to the cannulation modality, ECMO duration, amount of hemolysis, and volume of red blood cell transfusions. Further investigation is warranted to fully understand the implications of elevated serum iron and ferritin in pediatric ECMO. [ABSTRACT FROM AUTHOR]

Paleoclimate data assimilation (DA) is a novel tool for reconstructing past climates that directly integrates proxy records with climate model output. Despite the potential for DA to expand the scope of quantitative paleoclimatology, these methods remain difficult to implement in practice due to the multi-faceted requirements and data handling necessary for DA reconstructions, the diversity of DA methods, and the need for computationally efficient algorithms. Here, we present DASH, a MATLAB toolbox designed to facilitate paleoclimate DA analyses. DASH provides command line and scripting tools that implement common tasks in DA workflows. The toolbox is highly modular and is not built around any specific analysis, and thus DASH supports paleoclimate DA for a wide variety of time periods, spatial regions, proxy networks, and algorithms. DASH includes tools for integrating and cataloguing data stored in disparate formats, building state vector ensembles, and running proxy (system) forward models. The toolbox also provides optimized algorithms for implementing ensemble Kalman filters, particle filters, and optimal sensor analyses with variable and modular parameters. This paper reviews the key components of the DASH toolbox and presents examples illustrating DASH's use for paleoclimate DA applications. [ABSTRACT FROM AUTHOR]

Since both parties committed to adding women to the federal bench in the 1970s, Democratic and Republican presidents have sought out qualified women for judgeships. Diversifying the bench offers symbolic and substantive benefits to both parties, but those benefits come at the cost of finding non-traditional nominees. Presidents can take one of two different approaches to diversification: maintain existing diversity by anchoring women to a seat, or increase diversity by considering women for every opening. Given presidents consider many factors, including electoral benefits, when selecting potential judges, we expect partisan politics influence approach. Examining all lower court nominations made between 1981 and 2022, we find that Republican presidents tend to anchor while Democratic presidents expand diversity. Additionally, Senate diversity influences diversification, as women are more likely to get nominated when the relevant state Senate delegation includes a woman. Overall, we offer new perspectives on the mechanisms of judicial diversification. [ABSTRACT FROM AUTHOR]

Background: Potentially preventable hospitalizations (PPH) are defined as unplanned hospital admissions which could potentially have been prevented with the provision of effective, timely outpatient care. To better understand and ultimately reduce rates of PPH, a means of identifying those which are actually preventable is required. The Preventability Assessment Tool (PAT) was designed for use by hospital clinicians to assess the preventability of unplanned admissions for chronic conditions.Objective: The present study examined the ability of the PAT to distinguish between those unplanned admissions which are preventable and those which are not, compared to the assessments of an Expert Panel.Methods: Data were collected between November 2014 and June 2017 at three hospitals in NSW, Australia. Participants were community-dwelling patients with unplanned hospital admissions for congestive heart failure, chronic obstructive pulmonary disease, diabetes complications or angina pectoris. A nurse and a doctor caring for the patient made assessments of the preventability of the admission using the PAT. Expert Panels made assessments of the preventability of each admission based on a comprehensive case report and consensus process.Results: There was little concordance between the hospital doctors and nurses regarding the preventability of admissions, nor between the assessments of the Expert Panel and the hospital nurse or the Expert Panel and the hospital doctor.Conclusions: The PAT demonstrated poor concurrent validity and is not a valid tool for assessing the preventability of unplanned hospital admissions. The use of Expert Panels provides a more rigorous approach to assessing the preventability of such admissions. [ABSTRACT FROM AUTHOR]

Background: Elevated matrix metalloproteinase-9 production during inflammation may be deleterious to epithelial barrier function. Therefore we examined the effect of proinflammatory cytokines on the expression and regulation of matrix metalloproteinase-9 in a model renal epithelial cell system. Tight junctions limit diffusion between compartments and permit directional transport of solutes. Impairment of these junctional complexes by proteolysis may contribute to renal failure through loss of barrier function. Methods: The renal epithelial cell model, MDCK cells were employed to examine metalloproteinase activity and mRNA expression. Epithelial barrier function was determined using paracellular flux studies. Results: We found that matrix metalloproteinase-9 expression (MMP-9) and activity is markedly elevated in response to tumor necrosis factor-? exposure through a mitogen-activated protein kinase dependent pathway. The MMP-9 is predominately secreted into the apical compartment and elevated MMP-9 expression correlates with impaired cell barrier function that was restored using a specific inhibitor of MMP activity. Addition of recombinant MMP-9 to the apical compartment of MDCK cultures significantly elevated paracellular flux rate. Conclusions: We provide direct evidence for a MMP-9-mediated mechanism that produces junctional disruption. Collectively, these findings support the hypothesis that impaired epithelial barrier function due to activation of tissue/matrix degrading mechanisms occurs in response to specific inflammatory cues. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Infants undergoing ECMO may have elevated serum ferritin and iron levels, raising concerns about iron overload. Recent studies question the utility of these markers for acute vs. chronic iron overload during ECMO. This study evaluates iron content and localization in autopsy tissues from deceased infants who received or were considered for ECMO.This retrospective single-center case-control study analyzed paraffin-embedded tissues from the basal ganglia, liver, spleen, pancreas, and kidney. Tissue sections were stained to quantify iron deposition and an independent pathologist reviewed samples for iron accumulation.Eighteen deceased infants' tissues were analyzed: nine underwent ECMO, and nine were considered for it. Both groups showed multi-organ iron accumulation with no significant difference between ECMO and non-ECMO cohorts. Red blood cell transfusions were linked to increased iron content in adrenal (p = 0.004), hepatic (p = 0.042), and splenic (p = 0.013) tissues.ECMO exposure alone does not independently increase iron content in infants' organs. Multi-organ iron accumulation in both groups suggests iron deposition in critically ill pediatric patients irrespective of ECMO exposure. Further research is needed to understand the mechanisms and implications. [ABSTRACT FROM AUTHOR]

ECMO plays a crucial role in treating severe respiratory and cardiac failure in pediatric patients. However, its impact on the regulation of erythropoietin (EPO) and erythropoiesis remains poorly understood. Factors such as improved oxygenation, inflammation, and hemodilution associated with ECMO treatment may influence EPO production and erythropoiesis. This study aimed to examine the effects of ECMO on EPO regulation and erythropoiesis in pediatric patients.This retrospective study serially quantified EPO serum levels, measured markers of erythropoiesis, and tabulated clinical outcomes of pediatric ECMO patients. Descriptive statistics and Pearson correlation coefficients were used to identify associations between biomarkers and clinical care parameters.Preliminary findings suggest a disconnection between elevated EPO levels and reduced markers of erythropoiesis or iron metabolism, indicating ineffective erythropoiesis. Patients receiving more than 10 mL/kg/day of RBC transfusions had higher reticulocyte counts. Non-survivors had sustained elevations of EPO serum levels but reduced erythropoietic activity.In ECMO-treated pediatric patients, ineffective erythropoiesis is a significant concern and may be associated with higher mortality rates. Understanding the mechanisms behind this pathology could better inform clinical approaches and optimize management strategies. Further research is imperative to uncover the factors resulting in ineffective erythropoiesis in these patients and to develop targeted interventions. [ABSTRACT FROM AUTHOR]

Background: Elevated matrix metalloproteinase-9 production during inflammation may be deleterious to epithelial barrier function. Therefore we examined the effect of proinflammatory cytokines on the expression and regulation of matrix metalloproteinase-9 in a model renal epithelial cell system. Tight junctions limit diffusion between compartments and permit directional transport of solutes. Impairment of these junctional complexes by proteolysis may contribute to renal failure through loss of barrier function., Methods: The renal epithelial cell model, MDCK cells were employed to examine metalloproteinase activity and mRNA expression. Epithelial barrier function was determined using paracellular flux studies., Results: We found that matrix metalloproteinase-9 expression (MMP-9) and activity is markedly elevated in response to tumor necrosis factor-alpha exposure through a mitogen-activated protein kinase dependent pathway. The MMP-9 is predominately secreted into the apical compartment and elevated MMP-9 expression correlates with impaired cell barrier function that was restored using a specific inhibitor of MMP activity. Addition of recombinant MMP-9 to the apical compartment of MDCK cultures significantly elevated paracellular flux rate., Conclusions: We provide direct evidence for a MMP-9-mediated mechanism that produces junctional disruption. Collectively, these findings support the hypothesis that impaired epithelial barrier function due to activation of tissue/matrix degrading mechanisms occurs in response to specific inflammatory cues., (Copyright 2007 S. Karger AG, Basel.)