Search

Abstract Ex-situ mineralization processes leverage the reaction of alkaline materials with CO2 to form solid carbonate minerals for carbon capture, utilization, and storage. Annually, enough alkaline waste is generated to reduce global CO2 emissions by a significant percentage via mineralization. However, while the reaction is thermodynamically favorable and occurs spontaneously, it is kinetically limited. Thus, a number of techniques have emerged to increase the efficiency of mineralization to achieve a scalable process. In this review, we discuss mineralization of waste streams with significant potential to scale to high levels of CO2 sequestration. Focus is placed on the effect of operating parameters on carbonation kinetics and efficiency, methods, cost, and current scale of technologies.

In Queensland, Australia, 31 of 96 Shiga toxin‒producing Escherichia coli cases during 2020–2022 were reported by a specialty pathology laboratory servicing alternative health practitioners. Those new cases were more likely to be asymptomatic or paucisymptomatic, prompting a review of the standard public health response.

Abstract The pathogenesis of exercise intolerance and persistent fatigue which can follow an infection with the SARS‐CoV‐2 virus (“long COVID”) is not fully understood. Cases were recruited from a long COVID clinic (N = 32; 44 ± 12 years; 10 (31%) men), and age‐/sex‐matched healthy controls (HC) (N = 19; 40 ± 13 years; 6 (32%) men) from University College London staff and students. We assessed exercise performance, lung and cardiac function, vascular health, skeletal muscle oxidative capacity, and autonomic nervous system (ANS) function. Key outcome measures for each physiological system were compared between groups using potential outcome means (95% confidence intervals) adjusted for potential confounders. Long COVID participant outcomes were compared to normative values. When compared to HC, cases exhibited reduced oxygen uptake efficiency slope (1847 (1679, 2016) vs. 2176 (1978, 2373) mL/min, p = 0.002) and anaerobic threshold (13.2 (12.2, 14.3) vs. 15.6 (14.4, 17.2) mL/kg/min, p

Abstract To explore the pathways and mechanisms driving inflammation and fibrosis in stented ureters. In total, six healthy female pigs underwent cystoscopic unilateral ureteral stent insertion (6 Fr). After 14 days indwelling time, ureteral tissue was harvested in three pigs, while the remaining three pigs had their stents removed, and were recovered for 7 days. Three separate pigs served as controls. Tissue from stented and contralateral ureters was analysed histologically to evaluate tissue remodelling and classify the degree of inflammation and fibrosis, while genome, proteome and immunohistochemistry analysis was performed to assess changes at the transcriptional and translational levels. Finally, immunofluorescence was used to characterize the cell composition of the immune response and pathways involved in inflammation and fibrosis. Statistical analysis was performed using GraphPad Prism and RStudio for Welch ANOVA, Kruskal–Wallis and Dunnett’s T3 multiple comparison test. Stents cause significant inflammation and fibrosis of ureters. Gene set enrichment analysis confirmed fibrotic changes and tissue proliferation and suggests that epithelial–mesenchymal transition is a driver of fibrosis. Moreover, IL-6/JAK/STAT and TNFα via NF-κB signalling might contribute to chronic inflammation promoting a profibrotic environment. Immunostaining confirmed epithelial–mesenchymal transition in the urothelium and NF-κB expression in ureters stented for 14 days. Tissue alterations do not fully recover after 7 days. Histological evaluation showed that contralateral, unstented ureters are affected by mild inflammation. Our study showed that stenting has a significant impact on the ureter. Chronic inflammation and epithelial–mesenchymal transition are drivers of fibrosis, potentially impairing ureteral functionality in the long term. Furthermore, we observed mild inflammation in contralateral, unstented ureters.

The present review summarizes the beneficial and detrimental roles of reactive oxygen species in myocardial ischemia/reperfusion injury and cardioprotection. In the first part, the continued need for cardioprotection beyond that by rapid reperfusion of acute myocardial infarction is emphasized. Then, pathomechanisms of myocardial ischemia/reperfusion to the myocardium and the coronary circulation and the different modes of cell death in myocardial infarction are characterized. Different mechanical and pharmacological interventions to protect the ischemic/reperfused myocardium in elective percutaneous coronary interventions and coronary artery bypass grafting, in acute myocardial infarction and in cardiotoxicity from cancer therapy are detailed. The second part keeps the focus on ROS providing a comprehensive overview of molecular and cellular mechanisms involved in ischemia/reperfusion injury. Starting from mitochondria as the main sources and targets of ROS in ischemic/reperfused myocardium, a complex network of cellular and extracellular processes is discussed, including relationships with Ca2+ homeostasis, thiol group redox balance, hydrogen sulfide modulation, cross-talk with NAPDH oxidases, exosomes, cytokines and growth factors. While mechanistic insights are needed to improve our current therapeutic approaches, advancements in knowledge of ROS-mediated processes indicate that detrimental facets of oxidative stress are opposed by ROS requirement for physiological and protective reactions. This inevitable contrast is likely to underlie unsuccessful clinical trials and limits the development of novel cardioprotective interventions simply based upon ROS removal.

Abstract Background Benign prostatic obstruction (BPO) due to benign prostatic hyperplasia (BPH) is a leading cause of morbidity in men over the age of 40. This study examined whether there was an association between body mass index (BMI) and pre-operative prostate volume and whether expression of two genes, alpha-2-macroglobulin (A2M) and transforming growth factor beta 3 (TGFB3), was correlated with BMI, pre-operative prostate volume, and age at surgery. Methods Medical records of patients who underwent holmium enucleation of the prostate surgery for treatment of BPO were retrospectively reviewed. Surgical specimens were obtained from formalin-fixed paraffin-embedded blocks, and expression of the targeted genes was quantified using a real time PCR approach. Linear regression analysis was performed to assess association between BMI and prostate volume adjusting for demographic characteristics and co-morbidity. Spearman’s correlation was used to examine whether gene expression was correlated with BMI, prostate volume, and age at surgery. Results A total of 278 patients were identified, including 62.9% European Americans (n = 175) and 27.7% Hispanic Americans (n = 77). BMI was significantly correlated with prostate volume (Spearman’s rho = 0.123, P = 0.045). In linear regression analysis, BMI was positively associated with prostate volume (β = 0.01, P = 0.004), while hyperlipidemia was negatively associated with prostate volume (β = −0.08, P = 0.02). A trend for a positive association was also observed for diabetes (β = 0.07, P = 0.099). In the race/ethnicity stratified analysis, age at surgery showed a trend for significantly positive association with prostate volume in European Americans (β = 0.005, P = 0.08), but not in Hispanic Americans. Expression of the A2M gene in the stroma was negatively correlated with age at surgery (P = 0.006). A2M expression in the gland was positively correlated with prostate volume among older men (Age ≥ 70, P = 0.01) and overweight men (BMI 25–30, P = 0.04). TGFB3 expression in the gland was positively correlated with BMI (P = 0.007) among older men. Conclusions This study demonstrated the positive correlation between BMI and prostate volume. Expression of TGFB3 and A2M was correlated with BMI, prostate volume, and age at surgery.

Early detection and diagnosis of coronary artery disease could reduce the risk of developing a heart attack. The coronary arteries are optimally visualised using computed tomography coronary angiography (CTCA) imaging. These images are reviewed by specialist radiologists who evaluate the coronary arteries for potential narrowing. A lack of radiologists in the UK is a constraint to timely diagnosis of coronary artery disease, particularly in the acute accident and emergency department setting. The development of automated methods by which coronary artery narrowing can be identified rapidly and accurately are therefore timely. Such complex computer based tools also need to be sufficiently computationally efficient that they can run on servers typically found in hospital settings, where graphical processing units for example are unavailable. We propose a fully automatic two-dimensional Unet model to segment the aorta and coronary arteries on CTCA images. Two models are trained to segment two regions of interest, (1) the aorta and the coronary arteries or (2) the coronary arteries alone. Our method achieves 91.20% and 88.80% dice similarity coefficient accuracy on regions of interest 1 and 2 respectively. Compared with a semi-automatic segmentation method, our model performs better when segmenting the coronary arteries alone. The performance of the proposed method is comparable to existing published two-dimensional or three-dimensional deep learning models. Importantly, the algorithmic and graphical processing unit memory efficiencies are maintained such that the model can be deployed without requiring graphical processing units, and therefore can be used in a hospital setting.

Monoclonal antibodies (mAbs) can be engineered to have “extended half‐life” and “catch and release” properties to improve target coverage. We have developed a mAb physiologically‐based pharmacokinetic model that describes intracellular trafficking, neonatal Fc receptor (FcRn) recycling, and nonspecific clearance of mAbs. We extended this model to capture target binding as a function of target affinity, expression, and turnover. For mAbs engineered to have an extended half‐life, the model was able to accurately predict the terminal half‐life (82% within 2‐fold error of the observed value) in the human FcRn transgenic (Tg32) homozygous mouse and human. The model also accurately captures the trend in pharmacokinetic and target coverage data for a set of mAbs with differing catch and release properties in the Tg32 mouse. The mechanistic nature of this model allows us to explore different engineering techniques early in drug discovery, potentially expanding the number of “druggable” targets.

Background: Acute myocardial damage is common in severe COVID-19. Post-mortem studies have implicated microvascular thrombosis, with cardiovascular magnetic resonance (CMR) demonstrating a high prevalence of myocardial infarction and myocarditis-like scar. The microcirculatory sequelae are incompletely characterized. Perfusion CMR can quantify the stress myocardial blood flow (MBF) and identify its association with infarction and myocarditis.Objectives: To determine the impact of the severe hospitalized COVID-19 on global and regional myocardial perfusion in recovered patients.Methods: A case-control study of previously hospitalized, troponin-positive COVID-19 patients was undertaken. The results were compared with a propensity-matched, pre-COVID chest pain cohort (referred for clinical CMR; angiography subsequently demonstrating unobstructed coronary arteries) and 27 healthy volunteers (HV). The analysis used visual assessment for the regional perfusion defects and AI-based segmentation to derive the global and regional stress and rest MBF.Results: Ninety recovered post-COVID patients {median age 64 [interquartile range (IQR) 54–71] years, 83% male, 44% requiring the intensive care unit (ICU)} underwent adenosine-stress perfusion CMR at a median of 61 (IQR 29–146) days post-discharge. The mean left ventricular ejection fraction (LVEF) was 67 ± 10%; 10 (11%) with impaired LVEF. Fifty patients (56%) had late gadolinium enhancement (LGE); 15 (17%) had infarct-pattern, 31 (34%) had non-ischemic, and 4 (4.4%) had mixed pattern LGE. Thirty-two patients (36%) had adenosine-induced regional perfusion defects, 26 out of 32 with at least one segment without prior infarction. The global stress MBF in post-COVID patients was similar to the age-, sex- and co-morbidities of the matched controls (2.53 ± 0.77 vs. 2.52 ± 0.79 ml/g/min, p = 0.10), though lower than HV (3.00 ± 0.76 ml/g/min, p< 0.01).Conclusions: After severe hospitalized COVID-19 infection, patients who attended clinical ischemia testing had little evidence of significant microvascular disease at 2 months post-discharge. The high prevalence of regional inducible ischemia and/or infarction (nearly 40%) may suggest that occult coronary disease is an important putative mechanism for troponin elevation in this cohort. This should be considered hypothesis-generating for future studies which combine ischemia and anatomical assessment.

Abstract Background Prostate cancer (PCa) is the most common malignant neoplasm among men in many countries. Since most precancerous and cancerous tissues show signs of inflammation, chronic bacterial prostatitis has been hypothesized to be a possible etiology. However, establishing a causal relationship between microbial inflammation and PCa requires a comprehensive analysis of the prostate microbiome. The aim of this study was to characterize the microbiome in prostate tissue of PCa patients and investigate its association with tumour clinical characteristics as well as host expression profiles. Results The metagenome and metatranscriptome of tumour and the adjacent benign tissues were assessed in 65 Chinese radical prostatectomy specimens. Escherichia, Propionibacterium, Acinetobacter and Pseudomonas were abundant in both metagenome and metatranscriptome, thus constituting the core of the prostate microbiome. The biodiversity of the microbiomes could not be differentiated between the matched tumour/benign specimens or between the tumour specimens of low and high Gleason Scores. The expression profile of ten Pseudomonas genes was strongly correlated with that of eight host small RNA genes; three of the RNA genes may negatively associate with metastasis. Few viruses could be identified from the prostate microbiomes. Conclusions This is the first study of the human prostate microbiome employing an integrated metagenomics and metatranscriptomics approach. In this Chinese cohort, both metagenome and metatranscriptome analyses showed a non-sterile microenvironment in the prostate of PCa patients, but we did not find links between the microbiome and local progression of PCa. However, the correlated expression of Pseudomonas genes and human small RNA genes may provide tantalizing preliminary evidence that Pseudomonas infection may impede metastasis.

Abstract Background There is increasing recognition in Canada and globally that a substantial proportion of health care delivered is inappropriate as evidenced by (1) harmful and/or ineffective practices being overused, (2) effective clinical practices being underused, and (3) other clinical practices being misused. Inappropriate health care leads to negative patient experiences, poor health outcomes, and inefficient use of scarce health care resources. The purpose of this study is to conduct a systematic review of inappropriate health care in Canada. Our specific objectives are to (1) systematically search and critically review published and grey literature for studies on inappropriate health care in Canada; (2) estimate the nature and magnitude of inappropriate health care in Canada and its provincial and territorial jurisdictions. Methods We will include all quantitative study designs reporting objective or subjective measurements of inappropriate health care in Canada over the last 10 years. We will search the following online databases: MEDLINE, Cochrane Central Register of Controlled Trials, EconLit, and ISI-Web of Knowledge, which contains Web of Science Core Collection-Citation Indexes, Science Citation Index Expanded, Conference Proceedings Citation Index-Science, and Conference Proceedings Citation Index-Social Science & Humanities. We will also search grey literature sources to identify provincial and national audits of inappropriate health care. Two authors will independently screen, assess data quality, and extract data for synthesis. Study findings will be synthesized narratively. We will organize our data into three care categorizations: preventive care, acute care, and chronic care. We will provide a compendium of inappropriate health care for each care category for Canada and each Canadian province and territory, where sufficient data exists, by calculating (1) overall medians of underuse, overuse, and misuse of clinical practices and (2) the range of medians of underuse, overuse, and misuse for each clinical practice investigated. Discussion This review will result in the first-ever evidence-based compendium of inappropriate health care in Canada. We will also develop detailed reports of inappropriate health care for each Canadian province and territory. Systematic review registration PROSPERO CRD42018093495

Introduction: High-fidelity simulation is frequently utilized in medical education. Its use in the neurosciences is limited by the inherent limitations of the manikin to simulate neurological changes. We report here the use of a hybrid simulation – a combination of lecture and high-fidelity manikin – in the education of neurosciences nurses, involved in care of neurocritical care patients. Methods: Neurosciences nurses from at the University of Missouri, Columbia, MO, USA, which is an academic, tertiary-care medical center participated in the simulation during Spring of 2016. The simulation involved a patient presenting with acute intracerebral hemorrhage (ICH) who neurologically deteriorated to brain death. Pre- and post-simulation questionnaires were administered using a questionnaire with five-point Liker scale. Results: Seventy-two responses were returned. The majority had 0-5 years of nursing experience with 83.8% having prior critical care experience. Pre-simulation, the majority of nurses (85.7%) agreed or strongly agreed with managing patients with ICH. When the responses of “agree” were compared to “strongly agree”, a significant improvement (p

Salmonella enterica is an important cause of foodborne illness in Australia, regularly causing high-profile outbreaks involving commercially-available foods. We used the national register of foodborne outbreaks to review the transmission pathways, settings, serotypes, and food vehicles of Salmonella outbreaks in Australia between 2001 and 2016. We examined trends over time of implicated food vehicles in outbreaks where there was statistical, microbiological, or descriptive evidence. Of the 990 Salmonella outbreaks reported, 79% (778/990) were suspected or confirmed to have been transmitted through contaminated food. Of these, 61% (472/778) occurred in food premises and 84% (656/778) were caused by Salmonella Typhimurium. Eggs and egg-containing foods were the most frequently identified food vehicle. Outbreaks due to egg-based sauces and Vietnamese style sandwiches, which often contain pâté and raw egg butter, increased, while outbreaks due to poultry meat, beef, pork, other sandwiches, and other desserts had a decreasing trend from 2001 to 2016. Identifying food vehicles and the Salmonella serotypes causing outbreaks in Australia provides important evidence for food regulation strategies and control measures.

Sea-level rise increasingly affects low-lying and exposed coastal communities due to climate change. These communities rely upon the delivery of stormwater and wastewater services which are often co-located underground in coastal areas. Due to sea-level rise and associated compounding climate-related hazards, managing these networks will progressively challenge local governments as climate change advances. Thus, responsible agencies must reconcile maintaining Levels of Service as the impacts of climate change worsen over the coming decades and beyond. A critical question is whether such networks can continue to be adapted/protected over time to retain Levels of Service, or whether eventual retreat may be the only viable adaptation option? If so, at what performance threshold? In this paper, we explore these questions for stormwater and wastewater, using a dynamic adaptive pathway planning (DAPP) approach designed to address thresholds and increasing risk over time. Involving key local stakeholders, we here use DAPP to identify thresholds for stormwater and wastewater services and retreat options, and for developing a comprehensive and area-specific retreat strategy comprising pathway portfolios, retreat phases, potential land use changes, and for exploring pathway conflicts and synergies. The result is a prototype for an area near Wellington, New Zealand, where a managed retreat of water infrastructure is being considered at some future juncture. Dynamic adaptive strategies for managed retreats can help to reduce future disruption from coastal flooding, signal land use changes early, inform maintenance, and allow for gradual budget adjustments by the agencies that can manage expenditure over time. We present this stepwise process in a pathway form that can be communicated spatially and visually, thereby making a retreat a more manageable, sequenced, adaptation option for water agencies, and the communities they serve.

More potent targeting of the androgen receptor (AR) in advanced prostate cancer is driving an increased incidence of neuroendocrine prostate cancer (NEPC), an aggressive and treatment-resistant AR-negative variant. Its molecular pathogenesis remains poorly understood but appears to require TP53 and RB1 aberration. We modeled the development of NEPC from conventional prostatic adenocarcinoma using a patient-derived xenograft and found that the placental gene PEG10 is de-repressed during the adaptive response to AR interference and subsequently highly upregulated in clinical NEPC. We found that the AR and the E2F/RB pathway dynamically regulate distinct post-transcriptional and post-translational isoforms of PEG10 at distinct stages of NEPC development. In vitro, PEG10 promoted cell-cycle progression from G0/G1 in the context of TP53 loss and regulated Snail expression via TGF-β signaling to promote invasion. Taken together, these findings show the mechanistic relevance of RB1 and TP53 loss in NEPC and suggest PEG10 as a NEPC-specific target.

Background: Neutrophil-to-lymphocyte ratio (NLR) was widely studied as a prognostic marker in various medical and surgical specialties, but its significance in nephrology is not yet established. Objective: We evaluated its accuracy as an inflammation biomarker in a dialysis population. Design setting: Single-center retrospective study. Patients: The records of all 550 patients who were treated with hemodialysis (HD) or peritoneal dialysis (PD) from September 2008 to March 2011 were included. Measurements: NLR was calculated from the monthly complete blood count. Methods: Association between NLR and markers of inflammation (C-reactive protein [CRP], serum albumin, and erythropoietin resistance index [ERI]) was measured using Spearman coefficient. Results: In total, 120 patients were eligible for the correlation analyses. We found a positive correlation between NLR and CRP (all patients: r = 0.45, P < .001; HD: r = 0.47, P < .001; PD: r = 0.48, P = .13). NLR and albumin were inversely correlated ( r = −0.51, P < .001). Finally, high NLR was associated with a nonsignificant increased ERI, but we have not demonstrated a direct correlation. Limitations: CRP and albumin are not measured routinely and were ordered for a specific clinical reason leading to an indication bias. Also, no relationship with clinical outcome was established. Conclusions: NLR seems to be a good inflammatory biomarker in dialysis in addition to being easily available. However, controlled studies should be conducted to properly assess and validate NLR levels that would be clinically significant and relevant, as well as its prognostic significance and utility in a clinical setting.

Introduction. Management of postoperative central diabetes insipidus (DI) can be challenging from changes in volume status and serum sodium levels. We report a case successfully using a dilute vasopressin bolus protocol in managing hypovolemic shock in acute, postoperative, central DI. Case Report. Patient presented after bifrontal decompressive craniotomy for severe traumatic brain injury. He developed increased urine output resulting in hypovolemia and hypernatremia. He was resuscitated with intravenous fluids including a dilute vasopressin bolus protocol. This protocol consisted of 1 unit of vasopressin in 1 liter of 0.45% normal saline. This protocol was given in boluses based on the formula: urine output minus one hundred. Initial serum sodium was 148 mmol/L, and one-hour urine output was 1 liter. After 48 hours, he transitioned to 1-desamino-8-D-arginine vasopressin (DDAVP). Pre-DDAVP serum sodium was 149 mmol/L and one-hour urine output 320 cc. Comparing the bolus protocol to the DDAVP protocol, the average sodium was 143.8 ± 3.2 and 149.6 ± 3.2 mmol/L (p=0.0001), average urine output was 433.2 ± 354.4 and 422.3 ± 276.0 cc/hr (p=0.90), and average specific gravity was 1.019 ± 0.009 and 1.016 ± 0.01 (p=0.42), respectively. Conclusion. A protocol using dilute vasopressin bolus can be an alternative for managing acute, central DI postoperatively, particularly in setting of hypovolemic shock resulting in a consistent control of serum sodium.

Introduction. Dedicated neurointensivists have been shown to improve outcome measurements in the neurosciences intensive care unit (NSICU). Quality outcome data in relation to patient and family satisfaction is lacking. This study evaluated the impact of newly appointed neurointensivists and creation of a neurocritical care team on quality outcome measures including patient satisfaction in a NSICU. Methods. This is a retrospective study of data over 36 months from a 14-bed NSICU evaluating quality outcome measures and anonymous patient satisfaction questionnaires before and after neurointensivists appointment. Results. After appointment of neurointensivists, patient acuity of the NSICU increased by 33.4% while LOS decreased by 3.5%. There was a decrease in neurosciences mortality (35.8%), catheter-associated urinary tract infection (50%), central line associated bloodstream infection (100%), and ventilator-associated pneumonia (50%). During the same time, patient satisfaction increased by 28.3% on physicians/nurses consistency (p=0.025), by 69.5% in confidence/trust in physicians (p

Abstract Objective: To evaluate the value of notification to public health units (PHUs) in the management of viral gastrointestinal outbreaks in residential care facilities (RCFs) in Queensland. Methods: Routine outbreak characteristics and control measures were collected at notification and conclusion of outbreaks notified between May and August 2008. This was supplemented with detailed interviews with RCFs and PHUs, including perceptions of the value of the RCF‐PHU interaction. Results: Norovirus was the confirmed aetiological agent in 39 (68%) of 60 outbreaks. A significant association was found between increased outbreak duration and longer (≥4 days) time to outbreak notification (p

Purpose. To review the literature and make recommendations for the use of anthracycline-based adjuvant chemotherapy in adult patients with soft tissue sarcoma (STS).

Purpose: A population-based cohort study of soft tissue sarcoma of the extremities (STSE) in Ontario, Canada was conducted using linked administrative databases.

“Momentos decisivos son ocasiones en las cuales los eventosse unen de forma tal, que el individuo se encuentra ante unaencrucijada en su existencia, o donde una persona adquiereinformación que trae consecuencias decisivas para él o ella”(1991: 113). Estos momentos pueden darse en puntos detransición reconocidos; pero, para Giddens, su importanciaradica en la interacción entre el riesgo y la oportunidad queellos representan, y en la necesidad que tiene el individuo desuperarlos por medio de un proyecto reflexivo del self. Esteproyecto reflexivo, es un proceso de construcción de identidad que acarrea el sostenimiento de una narrativa biográficaque a pesar del riesgo, la incertidumbre y la oportunidad, escoherente si es reexaminada continuamente.“Fateful moments are times when events come together insuch a way that an individual stands, as it were, at a crossroads in his existence; or where a person learns ofinformation with fateful consequences” (Giddens, 1991:113). These moments can occur at recognized transitionpoints, but for Giddens their importance lies in theinteraction of risk and opportunity which they represent,and the need for the individual to surmount them througha reflexive project of self. This reflexive project, a processof identity construction, entails sustaining a coherent, ifcontinuously revised, biographical narrativein the face of risk, uncertaintyand opportunity.