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Random forests are a powerful machine learning tool that capture complex relationships between independent variables and an outcome of interest. Trees built in a random forest are dependent on several hyperparameters, one of the more critical being the node size. The original algorithm of Breiman, controls for node size by limiting the size of the parent node, so that a node cannot be split if it has less than a specified number of observations. We propose that this hyperparameter should instead be defined as the minimum number of observations in each terminal node. The two existing random forest approaches are compared in the regression context based on estimated generalization error, bias-squared, and variance of resulting predictions in a number of simulated datasets. Additionally the two approaches are applied to type 2 diabetes data obtained from the National Health and Nutrition Examination Survey. We have developed a straightforward method for incorporating weights into the random forest analysis of survey data. Our results demonstrate that generalization error under the proposed approach is competitive to that attained from the original random forest approach when data have large random error variability. The R code created from this work is available and includes an illustration.

Irukandji syndrome (IS) is an extremely painful condition that causes a significant catecholamine surge and sympathetic autonomic response related to the envenomation from certain types of jellyfish. Current management involves intravenous fluids, magnesium sulphate and large doses of opioids for symptom control. Clonidine, a centrally acting alpha-2 agonist, is often used as an analgesic adjunct to reduce opioid requirements in acute pain. The present study explores the safety and efficacy of clonidine in reducing opioid requirements in IS.All patients diagnosed with IS at Cairns Hospital between 1 March 2016 and 30 April 2020, and participants from the Magnesium in Irukandji Study Trial, were included in this retrospective study (n = 114). Cases were separated into two groups depending on whether or not they received clonidine, and subsequently analysed according to pre- and post-intervention opioid requirements, clonidine dose administered and adverse effects.Notably, 39 patients with IS received ≥1 mcg/kg clonidine and the remaining 75 did not. There was no difference in oral morphine equivalent daily dose (oMEDD) between groups before clonidine administration; however, there was a significant reduction in oMEDD required after patients received clonidine (26.1 mg; 95% CI 4.6-47.7) compared with those who did not (66.6 mg; 95% CI 56.9-86.1) (F = 8.722, df = 1 × 224, P = 0.003). One episode of hypotension occurred following the intervention.Patients with IS who received clonidine required significantly lower opioid requirements than those who did not receive clonidine. Clonidine was safe to administer and should be considered early when treating IS. The optimal clonidine dose remains unclear and requires prospective studies to validate our findings.

Venom-induced consumption coagulopathy (VICC) is one of the most dangerous syndromes caused by snake envenomation and can be caused by several snake species worldwide, including the Australian coastal taipan. Rotational thromboelastometry (ROTEM) provides real-time point-of-care information on all stages of clot formation; however, it has yet to be formally evaluated in the assessment of VICC. We report three cases of Taipan envenomation causing VICC and the associated ROTEM results. The implications for future use of ROTEM in the assessment, management, and further research of VICC are discussed.

Anti-glomerular basement membrane (GBM) disease is a rare, aggressive vasculitis with no validated prediction tools to assist its management. We investigated a retrospective multicenter international cohort with the aim to transfer the Renal Risk Score (RRS) and to identify patients that benefit from rescue immunosuppressive therapy. Of a total 191 patients, 174 patients were included in the final analysis (57% female, median age 59 years). Using Cox and Kaplan-Meier methods, the RRS was found to be a strong and effective predictor for end stage kidney disease (ESKD) with a model concordance of C=0.760. The 36-month renal survival was 100%, 62.4%, and 20.7% in the low-, moderate-, and high-risk groups, respectively (P0.001). The need for renal replacement therapy (RRT) at diagnosis and the percentage of normal glomeruli in the biopsy were independent predictors of ESKD (P0.001, P0.001). Considering the 129 patients initially requiring RRT, the best predictor for renal recovery was the percentage of normal glomeruli (C=0.622; P0.001), a split either side of 10% providing good stratification. A model with the predictors RRT and normal glomeruli (N) achieved superior discrimination (C=0.840, P0.001). Dividing patients into four risk groups led to a 36-month renal survival of 96.4% (no RRT, N≥10%), 74.0% (no RRT, N10%), 42.3% (RRT, N≥10%) and 14.1% (RRT, N10%), respectively. In summary, we demonstrate that the RRS concept is transferrable to anti-GBM disease. Stratifying patients according to the need for RRT at diagnosis and renal histology improves prediction, highlighting the importance of normal glomeruli. Here, we propose a stratification to assist in the management of anti-GBM disease.

BACKGROUND AND AIMS Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a debilitating disease that can have a significant impact on a patient's quality of life. The aim of this study was to assess the longitudinal quality of life amongst those diagnosed with AAV using the EQ-5D instrument, which allows for calculation of quality-adjusted life years (QALYs.) METHOD A total of 343 patients with AAV participated in this study, of which 191 (55.7%) were male, resulting in 2746 episodes. The EQ-5D-5L standardised instrument was used to evaluate health-related quality of life in the domains of mobility, self-care, usual activities, pain/discomfort, anxiety/depression and to generate a summary index score. Overall health was also rated using a visual analogue scale (0–100). EQ-5D questionnaires were completed during routine nephrology clinic attendances and through a vasculitis patient support smartphone app. We used a random effects model to control for multiple entries relating to individual patients. RESULTS A lower quality of life was seen amongst those with AAV (median index value 0.80, overall population average 0.856). The mean visual analogue scale score was 75.6 ± 17.3 (overall population average 82.8, Fig. 1). Patients’ pain and discomfort level (mean 1.95) was most affected while self-care (mean 1.33) was least affected (Fig. 1). An increase in BVAS tightly correlated with a reduction in quality of life. Using the random effects model, the index score was seen to decrease with increasing age with a 2.7% reduction in index score per decade. A 7% reduction in index score was seen during periods of disease activity compared with periods of remission. Patients with end-stage kidney disease requiring dialysis had an 8% reduction in index score. A reduced quality of life was seen following COVID-19 lockdown with a 5% reduction in index score seen. Using a median survival rate of 6.16 years for patients with small vessel vasculitis, we calculated the QALYs for this population as 4.9 years. CONCLUSION We have defined for the first time the EQ-5D index value over the full disease course in patients with AAV. Notably, we have identified a reduction in quality of life during periods of disease activity. Other studies have demonstrated a reduction in quality of life during active disease using the AAV–PRO questionnaire and the Medical Outcomes Study Short Form-36. A decrease in work productivity has also been noted. Previously reported mean index values of 0.72 and 0.76 were lower than our observed values, although both are significantly reduced compared with population norms. In conclusion, this research highlights the negative impact of AAV on patients’ lives.

Purpose Planned interim analysis of GENESIS; a prospective pilot study investigating the role of genicular artery embolization (GAE) in patients with mild to moderate osteoarthritis of the knee using permanent microspheres. Methods Thirty-eight patients, median age = 60 (45–83), attended for GAE using 100–300 μm permanent microspheres. All patients had mild to moderate knee OA, resistant to conservative treatments over 6 months. Knee MRI was performed at baseline, and 12 months, enabling semi-quantitative analysis using Whole-Organ Magnetic Resonance Imaging Score (WORMS). Knee Injury and Osteoarthritis Outcome Score (KOOS) and visual analogue scale (VAS) (0–100 mm) were completed at baseline, 6 weeks, 3 months (n = 32), and 1-year (n = 16). Adverse events were recorded prospectively. Results Technical success of accessing and embolizing the target genicular arteries was 84%. Six patients were not embolized: four due to a presumed risk of non-target embolization, and two due to a lack of hyperaemic target. Mean VAS improved from 60 (SD = 20, 95% CI 53–66) at baseline to 36 (SD = 24, 95% CI 28–44) at 3 months (p p p = 0.06) at 1-year. Four patients experienced mild self-limiting skin discoloration over the embolized territory. One patient experienced a small self-limiting groin haematoma. WORMS scores at 1-year follow-up showed significant improvement in synovitis (p Conclusion GAE using permanent microspheres in patients with mild to moderate knee OA is safe, with potential efficacy at early follow-up.

To establish factors predictive of success prior to Prostate Artery Embolization (PAE) with MRI imaging. A prospective cohort study of 50 patients with Benign Prostatic Hyperplasia (BPH) were treated with PAE in a single institution. Patients had moderate to severe symptoms of BPH refractory to medical management for at least 6 months. Patients were imaged with multiparametric MRI imaging pre-PAE and at 3 months, 12 months and 24 months post-PAE. Clinical success was measured with IPSS, IIEF and EQ-5D-5L quality of life questionnaires. The technical success was 48/50 (96%).The mean age of the group was 67 (range 54–83). The mean IPSS score pre-PAE was 21 and at 24 months was 8 (p

Both Chironex fleckeri venom (CFV) and Carukia barnesi venoms (CBV) are known to cause significant cardiac morbidity and mortality. Many animal studies have demonstrated cardiac dysfunction with these venoms. This study specifically examines the systolic and diastolic cardiac functions using non-invasive pulse wave doppler. Mitral and aortic doppler sonograms of anaesthetised mice were obtained utilising a 10 MHz doppler probe. These continuous sonograms were analysed to ascertain changes in cardiac function before and after the parenteral administration of the test venoms. We found that CFV administration causes rapid cardiac dysfunction without a change in heart rate. Analysis of the resulting sonograms shows both systolic and diastolic dysfunction which together is suggestive of a progressively poorly compliant, contracted left ventricle. Additionally, the rapidity of cardiac dysfunction suggests a direct effect of CFV on myocardial cells. In contrast CBV showed a moderate immediate inotropic and chronotropic effect that was sustained until precipitous cardiac decompensation. This is consistent with the hypotheses of a toxin induced stress cardiomyopathy from sustained catecholaminergic activity.

Significance All plants and animals are associated with communities of viruses and microbes that interact via a suite of metabolites. These components play critical roles in the success of these assemblages; however, the role of individual components (i.e., bacteria, viruses, metabolites) and how these govern ecological interactions between macroorganisms is not understood. This study investigates the role of holobiont components in coral–turf algal interactions. The data demonstrate that an emergent microbiome and metabolome form at the interface between coral and turf algae in competitive interactions. Machine learning analyses show that this emergent community predicts the outcome of these interactions. These results provide insight into rules of community assembly in microbiomes and the roles of holobiont components in mediating ecological interactions., Viruses, microbes, and host macroorganisms form ecological units called holobionts. Here, a combination of metagenomic sequencing, metabolomic profiling, and epifluorescence microscopy was used to investigate how the different components of the holobiont including bacteria, viruses, and their associated metabolites mediate ecological interactions between corals and turf algae. The data demonstrate that there was a microbial assemblage unique to the coral-turf algae interface displaying higher microbial abundances and larger microbial cells. This was consistent with previous studies showing that turf algae exudates feed interface and coral-associated microbial communities, often at the detriment of the coral. Further supporting this hypothesis, when the metabolites were assigned a nominal oxidation state of carbon (NOSC), we found that the turf algal metabolites were significantly more reduced (i.e., have higher potential energy) compared to the corals and interfaces. The algae feeding hypothesis was further supported when the ecological outcomes of interactions (e.g., whether coral was winning or losing) were considered. For example, coral holobionts losing the competition with turf algae had higher Bacteroidetes-to-Firmicutes ratios and an elevated abundance of genes involved in bacterial growth and division. These changes were similar to trends observed in the obese human gut microbiome, where overfeeding of the microbiome creates a dysbiosis detrimental to the long-term health of the metazoan host. Together these results show that there are specific biogeochemical changes at coral–turf algal interfaces that predict the competitive outcomes between holobionts and are consistent with algal exudates feeding coral-associated microbes.

Presentation We present the case of a 48-year-old man with nasal cellulitis and subsequent oro-naso-sino-orbital-cutaneous fistula from prolonged cocaine use. Diagnosis Initial laboratory investigations reported a raised white cell count (WBC) and C-Reactive Protein (CRP) and subsequently a positive atypical anti-neutrophil cytoplasm antibodies (ANCA) and positive anti-proteinase (PR3). Perihilar lung nodularity on chest imaging raised the possibility of a systemic autoimmune response. His urinalysis was positive for cocaine. Treatment He was commenced on Augmentin, Amphotericin B and Prednisolone. An obturator was created to manage the oro-nasal fistula. A subsequent naso-cutaneous defect was re-approximated. Daily nasal saline douche and abstinence of cocaine were recommended. Discussion Cocaine use in the community is rising and poses a challenge to multiple facets of our health care system.

s from the 20th International Vasculitis and ANCA conference, held in Dublin on 3-6th April, Minor edits

Background: The current coronavirus disease 2019 (COVID-19) pandemic began in Ireland with the first confirmed positive case in March 2020. In the early stages of the pandemic clinicians and researchers in two affiliated Dublin hospitals identified the need for a COVID-19 biobanking initiative to support and enhance research into the disease. Through large scale analysis of clinical, regional, and genetic characteristics of COVID-19 patients, biobanks have helped identify, and so protect, at risk patient groups The STTAR Bioresource has been created to collect and store data and linked biological samples from patients with SARS-CoV-2 infection and healthy and disease controls. Aim: The primary objective of this study is to build a biobank, to understand the clinical characteristics and natural history of COVID-19 infection with the long-term goal of research into improved disease understanding, diagnostic tests and treatments. Methods: This is a prospective dual-site cohort study across two tertiary acute university teaching hospitals. Patients are recruited from inpatient wards or outpatient clinics. Patients with confirmed COVID-19 infection as well as healthy and specific disease control groups are recruited. Biological samples are collected and a case report form detailing demographic and medical background is entered into the bespoke secure online Dendrite database. Impact: The results of this study will be used to inform national and international strategy on health service provision and disease management related to COVID-19. In common with other biobanks, study end points evolve over time as new research questions emerge. They currently include patient survival, occurrence of severe complications of the disease or its therapy, occurrence of persistent symptoms following recovery from the acute illness and vaccine responses.

Rare disease data is often fragmented within multiple heterogeneous siloed regional disease registries, each containing a small number of cases. These data are particularly sensitive, as low subject counts make the identification of patients more likely, meaning registries are not inclined to share subject level data outside their registries. At the same time access to multiple rare disease datasets is important as it will lead to new research opportunities and analysis over larger cohorts. To enable this, two major challenges must therefore be overcome. The first is to integrate data at a semantic level, so that it is possible to query over registries and return results which are comparable. The second is to enable queries which do not take subject level data from the registries. To meet the first challenge, this paper presents the FAIRVASC ontology to manage data related to the rare disease anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV), which is based on the harmonisation of terms in seven European data registries. It has been built upon a set of key clinical questions developed by a team of experts in vasculitis selected from the registry sites and makes use of several standard classifications, such as Systematized Nomenclature of Medicine - Clinical Terms (SNOMED-CT) and Orphacode. It also presents the method for adding semantic meaning to AAV data across the registries using the declarative Relational to Resource Description Framework Mapping Language (R2RML). To meet the second challenge a federated querying approach is presented for accessing aggregated and pseudonymized data, and which supports analysis of AAV data in a manner which protects patient privacy. For additional security the federated querying approach is augmented with a method for auditing queries (and the uplift process) using the provenance ontology (PROV-O) to track when queries and changes occur and by whom. The main contribution of this work is the successful application of semantic web technologies and federated queries to provide a novel infrastructure that can readily incorporate additional registries, thus providing access to harmonised data relating to unprecedented numbers of patients with rare disease, while also meeting data privacy and security concerns.

Objectives To examine if the electronic N-acetyl cysteine (NAC) order reduced prescribing errors. Methods This was a retrospective chart review of all patients presenting over 2 years to Cairns Hospital ED with a discharge diagnosis of 'paracetamol overdose'. Data were collected for any patient who received i.v. NAC. Any error, and a description of the error such as dose, volume of fluid, time of infusion and incorrect patient weight was recorded. Results There were 172 presentations with paracetamol poisoning with 86 receiving i.v. NAC. In the 75 (87%) where the electronic NAC order was used, there were no errors in dose of NAC, volume of i.v. fluid and length of time of infusion. In the 11 presentations where the manual NAC order was used, there were multiple errors identified. Conclusion The use of this electronic NAC order removed errors in NAC prescription and should be considered for prescribing and administering i.v. NAC.

Polymeric semiconductors exhibit exceptionally long spin lifetimes, and recently observed micrometre spin diffusion lengths in conjugated polymers demonstrate the potential for organic spintronics devices. Weak spin–orbit and hyperfine interactions lie at the origin of their long spin lifetimes, but the coupling mechanism of a spin to its environment remains elusive. Here, we present a systematic study of polaron spin lifetimes in field-effect transistors with high-mobility conjugated polymers as an active layer. We demonstrate how spin relaxation is governed by the charges’ hopping motion at low temperatures, whereas an Elliott–Yafet-like relaxation due to a transient localization of the carrier wavefunctions is responsible for spin relaxation at high temperatures. In this regime, charge, spin and structural dynamics are intimately related and depend sensitively on the local conformation of polymer backbones and the crystalline packing of the polymer chains. The long spin lifetimes observed in polymeric semiconductors hold promise for potential applications. A careful study untangles the main mechanism behind them.

Objective: To examine the impact of a clinical toxicology service on toxicology patients admitted to an intensive care departmentMethods: The authors performed a retrospective chart audit of all pa...

PURPOSE Genicular artery embolisation (GAE) is a novel treatment for patients with knee osteoarthritis (OA). Cadaveric dissection was undertaken to provide a complete description of the relevant arterial anatomy in order to perform safe and effective GAE. MATERIALS Twenty human lower limb specimens were dissected. The morphology of the genicular arteries and presence of anastomotic connections was recorded and compared with angiographic images from patients having undergone GAE. Vessels were measured to investigate the risk of non-target embolisation (NTE), taking a diameter of 300 microns as the threshold for significance. RESULTS The descending genicular artery (DGA) is the dominant vessel in medial OA, with 95% of cases revealing vessel division into muscular, saphenous and osteoarticular branches from a single pedicle. The superior medial genicular artery (SMGA) had a shared origin with the middle genicular artery (MGA) in 25% of cases. NTE to the MGA may damage the cruciate ligaments. In 85% of cases, there was an anastomosis between the DGA and SMGA, often encountered at angiography. The mean diameter of the anastomoses was 850 micron, presenting a risk for NTE. An anastomosis between the Inferior Medial Genicular Artery (IMGA) and medial sural artery was found in 5% of cases; the medial sural artery supplies blood to the tibial nerve and should be avoided. The IMGA and inferior lateral genicular artery provided supply to the patellofemoral joint in 69% and 88% of cases, respectively. CONCLUSION An in-depth knowledge of genicular artery anatomy is required for interventional radiologists to perform safe and effective GAE in patients with knee osteoarthritis.

To control community transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the 2020 global pandemic, most countries implemented strategies based on direct human testing, face covering, and surface disinfection. Under the assumption that the main route of transmission includes aerosols and respiratory droplets, efforts to detect SARS-CoV-2 in fomites have focused on locations suspected of high prevalence (e.g., hospital wards, cruise ships, and mass transportation systems). To investigate the presence of SARS-CoV-2 on surfaces in the urban environment that are rarely cleaned and seldomly disinfected, 350 citizens were enlisted from the greater San Diego County. In total, these citizen scientists collected 4,080 samples. An online platform was developed to monitor sampling kit delivery and pickup, as well as to collect sample data. The sampling kits were mostly built from supplies available in pandemic-stressed stores. Samples were processed using reagents that were easy to access despite the recurrent supply shortage. The methods used were highly sensitive and resistant to inhibitors that are commonly present in environmental samples. The proposed experimental design and processing methods were successful at engaging numerous citizen scientists who effectively gathered samples from diverse surface areas. The workflow and methods described here are relevant to survey the urban environment for other viruses, which are of public health concern and pose a threat for future pandemics.

The effect of substituting o‐carborane into the most sterically hindered positions of phenanthrene and benzo(k)tetraphene is reported. Synthesised via a Bull–Hutchings–Quayle benzannulation, the crystal structures of these non‐linear acenes exhibited the highest aromatic deformation parameters observed for any reported carborane compound to date, and among the largest carboranyl C−C bond length of all organo‐substituted o‐carboranes. Photoluminescence studies of these compounds demonstrated efficient intramolecular charge‐transfer, leading to aggregation induced emission properties. Additionally, an unusual low‐energy excimer was observed for the phenanthryl compound. These are two new members of the family of carborane‐functionalised non‐linear acenes, notable for their peculiar structures and multi‐luminescent properties., o ‐Carborane‐functionalised phenanthrene and benzo(k)tetraphene are reported in this work; two highly sterically hindered structures, with the latter displaying the largest aromatic deformation parameters of any organo‐substituted o‐carborane compound, and amongst the longest carboranyl C−C bond. Functionalisation of these polycyclic aromatic hydrocarbons induces stimuli‐responsive luminescence properties, including aggregation‐induced emission.

The role of the carborane isomer is investigated on the structural and photophysical properties of molecules comprising a carborane cluster and a conjugated organic moiety is investigated by synthesizing isomeric o-, m-, and p-carboranyl-anthracene donor–acceptor dyads. While appending a carborane leads to emission from a low energy intramolecular charge transfer state for the o-isomer, as well as emission from an excited state localized on the anthracene, this is not the case for the m- and p-carborane derivatives. This difference is attributed to a lower electron affinity for the latter two isomers. However, adding both m- and p- deforms the aromatic backbone and increases its structural rigidity, reducing non-radiative decay pathways and hence enhancing photoluminescence quantum efficiency relative to anthracene.

The roles of prophages in disease have mainly considered human pathogens, while their role in marine pathogens has only recently been considered. This chapter reviews the relevant literature on what is known of prophages in marine ecosystems and provides a meta-analysis of the abundance and function of prophages in marine pathogenic bacteria. According to these results, bacterial pathogens in marine environments contain a significantly higher abundance of prophage DNA in their genomes than host-associated bacteria, which are non-pathogenic. The authors also surveyed the genetic content of the prophages that were associated with known pathogens and compared their functions to non-pathogens. Their findings suggest that horizontally acquired prophage-encoded DNA may play a large role in the ecology and evolution of marine diseases

Aims Presentations of intoxicated patients to hospital are frequent and increasing. We aimed to review the existing evidence that the presence of inpatient clinical toxicology services reduces use of resources without impacting on the care of these patients. Methods We conducted a literature search using the Cochrane Library, PubMed, and Embase for articles that measured length of stay (and other outcomes) for the target population, with toxicology services as an intervention. The articles were reviewed with respect to the ROBINS-I tool. Results Seven relevant articles were identified. Six of these studies demonstrated reduced hospital length of stay for intoxicated patients in hospitals with inpatient toxicology services. None of the articles demonstrated a detriment in morbidity or mortality. There were also improvements in other resource-related outcomes. Conclusions The presence of inpatient toxicology services appears to improve resource utilization, in reduction of length of stay, as well as a number of other related outcomes. It does this without compromising on patient morbidity or mortality. Thus, it should be considered as a potential model of care for future toxicology services, especially with current trends of increasing demand for service efficiency.

Three thiophene ring-terminated benzothieno[3,2-b]benzothiophene (BTBT) derivatives, C-C6-DBTTT, C-C12-DBTTT, and L-C12-DBTTT, were designed and synthesized, differing in the isomerization of alkyl...

The synthesis of a highly twisted chrysene derivative incorporating two electron deficient o‐carboranyl groups is reported. The molecule exhibits a complex, excitation‐dependent photoluminescence, including aggregation‐induced emission (AIE) with good quantum efficiency and an exceptionally long singlet excited state lifetime. Through a combination of detailed optical studies and theoretical calculations, the excited state species are identified, including an unusual excimer induced by the presence of o‐carborane. This is the first time that o‐carborane has been shown to induce excimer formation ab initio, as well as the first observation of excimer emission by a chrysene‐based small molecule in solution. Bis‐o‐carboranyl chrysene is thus an initial member of a new family of o‐carboranyl phenacenes exhibiting a novel architecture for highly‐efficient multi‐luminescent fluorophores.

A well-defined series of long and soluble isoindigo thienoacene oligomers have been synthesized from a novel electron deficient building block: benzo[1,2-b:4,5-b']bis[b]benzothiophene bislactams. Extension of the π-conjugated systems facilitates control of the optical, electronic and device characteristics.