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Ultra-processed food (UPF) intake has increased sharply over the last few decades and has been consistently asserted to be implicated in the development of non-communicable diseases. We aimed to evaluate and update the existing observational evidence for associations between ultra-processed food (UPF) consumption and human health. We searched Medline and Embase from inception to March 2023 to identify and update meta-analyses of observational studies examining the associations between UPF consumption, as defined by the NOVA classification, and a wide spectrum of health outcomes. For each health outcome, we estimated the summary effect size, 95% confidence interval (CI), between-study heterogeneity, evidence of small-study effects, and evidence of excess-significance bias. These metrics were used to evaluate evidence credibility of the identified associations. This umbrella review identified 39 meta-analyses on the associations between UPF consumption and health outcomes. We updated all meta-analyses by including 122 individual articles on 49 unique health outcomes. The majority of the included studies divided UPF consumption into quartiles, with the lowest quartile being the reference group. We identified 25 health outcomes associated with UPF consumption. For observational studies, 2 health outcomes, including renal function decline (OR: 1.25; 95% CI: 1.18, 1.33) and wheezing in children and adolescents (OR: 1.42; 95% CI: 1.34, 1.49), showed convincing evidence (Class I); and five outcomes were reported with highly suggestive evidence (Class II), including diabetes mellitus, overweight, obesity, depression, and common mental disorders. High UPF consumption is associated with an increased risk of a variety of chronic diseases and mental health disorders. At present, not a single study reported an association between UPF intake and a beneficial health outcome. These findings suggest that dietary patterns with low consumption of UPFs may render broad public health benefits. [Display omitted] [ABSTRACT FROM AUTHOR]

Recent research has shown the power of large-scale regional traffic simulations—such as MATSim—to model the systemic impacts and costs of capacity-reducing incidents. At the same time, observational studies have illustrated the potential for traffic Incident Management Teams (IMTs) to reduce these impacts and costs on a local scale; mathematical optimization models have also attempted to scale or locate these programs. In this research, we connect these two separate lines of scholarly inquiry by simulating the dynamic response of an IMT fleet to incidents arising on a metropolitan highway network. We introduce a MATSim module that handles stochastically-generated incidents of varying severity, dispatches IMT to clear the incidents based on path distance and availability, and measures excess user costs based on the incidents. We apply this module in a scenario with data from the Salt Lake City, Utah metropolitan region. We demonstrate the potential use of the module through an illustrative experiment increasing the IMT fleet size with a collection of simulated incident days. [ABSTRACT FROM AUTHOR]

Randomized controlled trials (RCTs) are a gold standard for estimating the benefits of clinical interventions, but their decision-making utility can be limited by relatively short follow-up time. Longer-term follow-up of RCT participants is essential to support treatment decisions. However, as time from randomization accrues, loss to follow-up and competing events can introduce biases and require covariate adjustment even for intention-to-treat effects. We describe a process for synthesizing expert knowledge and apply this to long-term follow-up of an RCT of treatments for meniscal tears in patients with knee osteoarthritis (OA). We identified 2 post-randomization events likely to impact accurate assessment of pain outcomes beyond 5 years in trial participants: loss to follow-up and total knee replacement (TKR). We conducted literature searches for covariates related to pain and TKR in individuals with knee OA and combined these with expert input. We synthesized the evidence into graphical models. We identified 94 potential covariates potentially related to pain and/or TKR among individuals with knee OA. Of these, 46 were identified in the literature review and 48 by expert panelists. We determined that adjustment for 50 covariates may be required to estimate the long-term effects of knee OA treatments on pain. We present a process for combining literature reviews with expert input to synthesize existing knowledge and improve covariate selection. We apply this process to the long-term follow-up of a randomized trial and show that expert input provides additional information not obtainable from literature reviews alone. [ABSTRACT FROM AUTHOR]

Patients with Loeys-Dietz syndrome demonstrate a heightened risk of distal thoracic aortic events after valve-sparing aortic root replacement. This study assesses the clinical risks and hemodynamic consequences of a prophylactic aortic arch replacement strategy in Loeys-Dietz syndrome and characterizes smooth muscle cell phenotype in Loeys-Dietz syndrome aneurysmal and normal-sized downstream aorta. Patients with genetically confirmed Loeys-Dietz syndrome (n = 8) underwent prophylactic aortic arch replacement during valve-sparing aortic root replacement. Four-dimensional flow magnetic resonance imaging studies were performed in 4 patients with Loeys-Dietz syndrome (valve-sparing aortic root replacement + arch) and compared with patients with contemporary Marfan syndrome (valve-sparing aortic root replacement only, n = 5) and control patients (without aortopathy, n = 5). Aortic tissues from 4 patients with Loeys-Dietz syndrome and 2 organ donors were processed for anatomically segmented single-cell RNA sequencing and histologic assessment. Patients with Loeys-Dietz syndrome valve-sparing aortic root replacement + arch had no deaths, major morbidity, or aortic events in a median of 2 years follow-up. Four-dimensional magnetic resonance imaging demonstrated altered flow parameters in patients with postoperative aortopathy relative to controls, but no clear deleterious changes due to arch replacement. Integrated analysis of aortic single-cell RNA sequencing data (>49,000 cells) identified a continuum of abnormal smooth muscle cell phenotypic modulation in Loeys-Dietz syndrome defined by reduced contractility and enriched extracellular matrix synthesis, adhesion receptors, and transforming growth factor-beta signaling. These modulated smooth muscle cells populated the Loeys-Dietz syndrome tunica media with gradually reduced density from the overtly aneurysmal root to the nondilated arch. Patients with Loeys-Dietz syndrome demonstrated excellent surgical outcomes without overt downstream flow or shear stress disturbances after concomitant valve-sparing aortic root replacement + arch operations. Abnormal smooth muscle cell–mediated aortic remodeling occurs within the normal diameter, clinically at-risk Loeys-Dietz syndrome arch segment. These initial clinical and pathophysiologic findings support concomitant arch replacement in Loeys-Dietz syndrome. [ABSTRACT FROM AUTHOR]

This paper is part of a broader program aimed at investigating the effects of co-firing clean fuels such as ammonia or hydrogen with hydrocarbons. The focus is on soot formation as well as flame stability in turbulent mixed-mode combustion, which is highly relevant in practical combustors. Ammonia substitution for nitrogen results in reduced flame stability, and this is correlated to differences in flame speed and extinction strain rate. While it is known that the addition of ammonia suppresses soot, visual inspection of compositionally inhomogeneous flames of ethylene-ammonia indicates a reduction in ammonia's ability to suppress soot formation. Measurements of soot volume fraction and laser-induced fluorescence in selected UV and visible bands are made along the centreline in selected flames to test this hypothesis. Experimental results are then compared to simulations in laminar diffusion flames, stratified counterflow flames, and partially premixed flames. All results confirm the soot-inhibiting ability of ammonia. Increasing inhomogeneity, leading to higher centreline mixture fractions, enhances soot formation, and the level of enhancement is greater for flames with ammonia than without. Moreover, it is found that partial premixing is ultimately responsible for determining the amount of soot formed as opposed to stratification of fuel mixtures near the pilot. [ABSTRACT FROM AUTHOR]

Disruption of endogenous glucocorticoid signalling in bone cells attenuates osteoarthritis (OA) in aged mice, however, the role of endogenous glucocorticoids in chondrocytes is unknown. Here, we investigated whether deletion of the glucocorticoid receptor, specifically in chondrocytes, also alters OA progression. Knee OA was induced by surgical destabilisation of the medial meniscus (DMM) in male 22-week-old tamoxifen-inducible glucocorticoid receptor knockout (chGRKO) mice and their wild-type (WT) littermates (n = 7–9/group). Mice were harvested 2, 4, 8 and 16 weeks after surgery to examine the spatiotemporal changes in molecular, cellular, and histological characteristics. At all time points following DMM, cartilage damage was significantly attenuated in chGRKO compared to WT mice. Two weeks after DMM, WT mice exhibited increased chondrocyte and synoviocyte hypoxia inducible factor (HIF)-2α expression resulting in extensive synovial activation characterised by synovial thickening and increased interleukin-1 beta expression. At 2 and 4 weeks after DMM, WT mice displayed pronounced chondrocyte senescence and elevated catabolic signalling (reduced Yes-associated protein 1 (YAP1) and increased matrix metalloprotease [MMP]-13 expression). Contrastingly, at 2 weeks after DMM, HIF-2α expression and synovial activation were much less pronounced in chGRKO than in WT mice. Furthermore, chondrocyte YAP1 and MMP-13 expression, as well as chondrocyte senescence were similar in chGRKO-DMM mice and sham-operated controls. Endogenous glucocorticoid signalling in chondrocytes promotes synovial activation, chondrocyte senescence and cartilage degradation by upregulation of catabolic signalling through HIF-2α in murine posttraumatic OA. These findings indicate that inhibition of glucocorticoid signalling early after injury may present a promising way to slow osteoarthritic cartilage degeneration. [ABSTRACT FROM AUTHOR]

Tumors of the pituitary gland, although mostly benign adenomas, are a cause of significant morbidity and even excess mortality due to local compressive effects (eg visual loss, hypopituitarism) and unregulated hormone secretion (eg acromegaly or Cushing Disease). Surgery, radiotherapy, and medical management (sometimes in combination) may be needed to mitigate the effects of tumor expansion and endocrine dysfunction. Magnetic resonance imaging (MRI) plays a central role in treatment planning for most patients. However, it does not always reliably identify the site(s) of primary or recurrent disease, especially where post-treatment remodeling results in indeterminate anatomical appearances. In these contexts, molecular imaging is a potential game-changer, allowing precise localization of sites of active disease and enabling safe and effective targeted intervention when patients would otherwise be consigned to expensive life-long medication. For pituitary and parasellar imaging, PET is the preferred modality due to its superior spatial resolution and sensitivity compared with SPECT, and an array of PET radioligands have been studied in different pituitary adenoma (PA) subtypes. While 18F-fluorodeoxyglucose (18F-FDG) is widely available, significant heterogeneity in tumoral uptake has limited its use. Instead, ligands targeting specific molecular pathways relevant to PA biology (eg somatostatin or dopamine receptor expression, amino acid uptake) are increasingly preferred and are beginning to find application in routine clinical practice. In addition, novel approaches to distinguish adenomatous tissue from normal gland (eg through comparison of images obtained with different radiotracers) and increase confidence that a suspected abnormal focus is indeed pathological (eg through subtraction imaging) have been proposed. It is likely therefore that molecular imaging will continue to find increasing application in the management of pituitary tumors just as it already does in other endocrine disorders. [ABSTRACT FROM AUTHOR]

Clinical examination of the hand requires a structured approach allowing the clinician the formulate an appropriate differential diagnosis for the purposes of further investigation and timely diagnosis and management. Eliciting a careful history and subsequently employing the examination principles of inspection, palpation, and movement, followed by targeted special tests, are key to assessing the various pathologies affecting the hand. This article discusses the key elements of history-taking and examination structure when assessing hand pathology, and reviews in detail the special tests involved in common pathology seen in the hand, including osteoarthritis, rheumatoid arthritis, carpal tunnel syndrome, cubital tunnel syndrome, Dupuytren's disease, and de Quervain's tenosynovitis. [ABSTRACT FROM AUTHOR]

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Objective: To examine the effects of infant sofa-sleeping, recent use by caregivers of alcohol, cannabis, and/or other drugs, and bed type and pillows, on the risk of sudden unexpected death in infancy (SUDI) in New Zealand.Study Design: A nationwide prospective case-control study was implemented between March 2012 and February 2015. Data were collected during interviews with parents/caregivers. "Hazards" were defined as infant exposure to 1 or more of sofa-sleeping and recent use by caregivers of alcohol, cannabis, and other drugs. The interaction of hazards with tobacco smoking in pregnancy and bed sharing, including for very young infants, and the difference in risk for Māori and non-Māori infants, also were assessed.Results: The study enrolled 132 cases and 258 controls. SUDI risk increased with infant sofa-sleeping (imputed aOR [IaOR] 24.22, 95% CI 1.65-356.40) and with hazards (IaOR 3.35, 95% CI 1.40-8.01). The SUDI risk from the combination of tobacco smoking in pregnancy and bed sharing (IaOR 29.0, 95% CI 10.10-83.33) increased with the addition of 1 or more hazards (IaOR 148.24, 95% CI 15.72-1398), and infants younger than 3 months appeared to be at greater risk (IaOR 450.61, 95% CI 26.84-7593.14).Conclusions: Tobacco smoking in pregnancy and bed sharing remain the greatest SUDI risks for infants and risk increases further in the presence of sofa-sleeping or recent caregiver use of alcohol and/or cannabis and other drugs. Continued implementation of effective, appropriate programs for smoking cessation, safe sleep, and supplying safe sleep beds is required to reduce New Zealand SUDI rates and SUDI disparity among Māori. [ABSTRACT FROM AUTHOR]

Two saltmarsh locations within Lake Macquarie, NSW, Australia were selected to investigate the uptake and partitioning of metal(loid)s Cu, Zn, As, Se, Cd and Pb in the Australian saltmarsh halophyte, Sarcocornia quinqueflora and the associated sub-lethal effects of metal(loid)s on plant health, including photosynthetic performance, biomass, and productivity. Metal(loid)s primarily accumulated to roots (BCF > 1). Barriers to transport were observed at the root to non-photosynthetic stem transition (TF < 1) for all metal(loid)s, suggesting this species is suitable for phytostabilisation. Sediment and plant tissue metal(loid) concentrations were significantly correlated with photosynthetic performance and plant biomass. As such, the action of sediment and tissue metal(loid)s on photosynthetic performance and the subsequent effect on biomass of S.quinqueflora appear to be suitable targets for molecular analyses to further elucidate mechanisms responsible for the observed adverse effects and the development of adverse outcome pathways. • S. quinqueflora suitable for phytostabilisation of metal(loid)s • Essential metals regulated whilst non-essential metals accumulated in S.quinqueflora • Roots suitable bioindicator of Cd and Pb contamination • Metal(loid)s in sediment or tissues correlated with Chl fluorescence and biomass • Chl fluorescence parameters correlated with S.quinqueflora biomass [ABSTRACT FROM AUTHOR]

Pegvisomant is a growth-hormone (GH) receptor antagonist that prevents the formation of the active heterotrimer of the dimerised GH receptor and the GH molecule necessary for downstream signal transduction. Over the past 20 years, it has become a key therapeutic option for physicians treating syndromes of GH/IGF-1 excess. Sufficient longitudinal follow-up data suggest that it can be deemed both safe and effective. It is the drug with the greatest potential for achieving an amelioration of the biochemical effects of GH excess with a corresponding normalisation of IGF-1 levels; however, insufficient dose titration has lessened real-world therapeutic outcomes. Theoretical concerns about stimulating tumour growth have been resolved as this has not been observed, while derangement of liver enzymes and local skin-related adverse reactions may occur in a minority of the patients. It may be a particularly impactful medication for the treatment of children, young people, and those with inherited disorders of GH excess, where other treatment modalities often fail. Combination therapy of pegvisomant with first- and second-generation somatostatin receptor ligands or with dopamine agonists remains an ongoing area of interest and research. High cost remains a barrier to the use of pegvisomant in many settings. [ABSTRACT FROM AUTHOR]

We report the case of an 80-year-old man with restrictive strabismus in lateral gaze following multiple oculoplastic procedures for idiopathic epiphora. Despite excellent initial response to nasal conjunctival recession with lysis of adhesions and a miminal recession of the medial rectus muscle, the patient suffered recurrence of diplopia associated with limitation of abduction due to aggressive, deep, subconjunctival scarring. Given the history of oral lichen planus (LP), the patient was diagnosed with ocular involvement of LP. He underwent a second conjunctival recession, this time accompanied by an intensive LP treatment regimen. Nine months after surgery, he remained diplopia free and orthophoric in primary gaze. Surgeons treating restrictive strabismus in patients with LP should consider implementing systemic and topical immunosuppressive treatment simultaneously with surgical management. [ABSTRACT FROM AUTHOR]

Objective: To determine whether good versus poor outcome trajectories and predictors of poor outcome obtained in a derivation study could be replicated in an independent sample of persons undergoing knee arthroplasty (KA).Methods: We used data from TRIO-POPULAR, a prospective cohort study of 926 participants who underwent KA in the United Kingdom. The participants were assessed preoperatively and 6-weeks, 6- and 12-months postoperatively. The Oxford Knee Score was the primary outcome and a variety of pre-operative predictors of outcome were selected. The outcome measure and the predictors were selected to most closely align with a previously published derivation study of good versus poor outcome. Confirmatory two-piece latent class growth curve analyses were used to model outcome and regression was used to identify predictors of outcome class.Results: Trajectories for the Oxford Knee Scores from TRIO-POPULAR replicated trajectories for WOMAC Pain and Function scores from the previously published derivation study. Multivariable predictors of poor outcome were pain catastrophizing (odds ratio = 1.125, 95% CI = 1.048, .206, p = 0.001) and comorbidity (odds ratio = 1.134, 95%CI = 1.049, 1.227, p = 0.002. Pain catastrophizing also predicted poor outcome in the derivation study.Conclusions: Good and poor outcome trajectories replicated those found in the previously published derivation study. Our model-based method produces stable outcome trajectories despite using data from different countries and participants with substantively different characteristics. Predictors of poor outcome were somewhat inconsistent between the cross-validation and derivation studies. Pain catastrophizing was the only consistent poor outcome predictor. [ABSTRACT FROM AUTHOR]

Background: Experience with implantable loop recorders (ILRs) in Brugada syndrome (BrS) is limited.Objective: The purpose of this study was to evaluate the indications and yield of ILR monitoring in a single-center BrS registry.Methods: Demographic, clinical and follow-up data of BrS patients with ILR were collected.Results: Of 415 BrS patients recruited consecutively, 50 (12%) received an ILR (58% male). Mean age at ILR implantation was 44 ± 15 years. Thirty-one (62%) had experienced syncopal or presyncopal episodes, and 23 (46%) had palpitations. During median follow-up of 28 months (range 1-68), actionable events were detected in 11 subjects (22%); 7 had recurrences of syncope/presyncope, with 4 showing defects in sinus node function or atrioventricular conduction. New supraventricular tachyarrhythmias were recorded in 6 subjects; a run of fast nonsustained ventricular tachycardia was detected in 1 patient. Patients implanted with an ILR were less likely to show a spontaneous type 1 pattern or depolarization electrocardiographic (ECG) abnormalities compared to those receiving a primary prevention implantable-cardioverter defibrillator. Age at implantation, gender, Shanghai score, and ECG parameters did not differ between subjects with and those without actionable events. ILR-related complications occurred in 3 cases (6%).Conclusion: In a large cohort of BrS patients, continuous ILR monitoring yielded a diagnosis of tachy- or bradyarrhythmic episodes in 22% of cases. Recurrences of syncope were associated with bradyarrhythmic events. Use of ILR can be helpful in guiding the management of low-/intermediate-risk BrS patients and ascertaining the cause of unexplained syncope. [ABSTRACT FROM AUTHOR]

Outcome after surgery is of interest to the patient, the surgeon and the healthcare institution. There is conclusive evidence that regional anaesthesia is associated with superior analgesic outcomes compared to opioid-based analgesic techniques and may also reduce chronic pain. While better pain control and avoiding a general anaesthetic may alone be regarded as significant outcome benefits, regional anaesthesia and analgesia may influence many other important outcomes. Regional anaesthesia clearly reduces postoperative nausea and vomiting and pulmonary complications compared to general anaesthesia. Regional anaesthesia independently reduces length of stay and is a common component of enhanced recovery packages. Contemporary, but less robust, data suggests that neuraxial anaesthesia, and to a lesser extent analgesia, may reduce blood transfusion requirements, surgical site infection, intensive care admission, cancer recurrence and maybe even mortality. Any functional outcome benefits secondary to regional anaesthesia appear to be short lived and are generally not sustained long term. [ABSTRACT FROM AUTHOR]

This paper provides a brief description of how computer programs are used to automatically interpret electrocardiograms (ECGs), and also provides a discussion regarding new opportunities. The algorithms that are typically used today in hospitals are knowledge engineered where a computer programmer manually writes computer code and logical statements which are then used to deduce a possible diagnosis. The computer programmer's code represents the criteria and knowledge that is used by clinicians when reading ECGs. This is in contrast to supervised machine learning (ML) approaches which use large, labelled ECG datasets to induct their own 'rules' to automatically classify ECGs. Although there are many ML techniques, deep neural networks are being increasingly explored as ECG classification algorithms when trained on large ECG datasets. Whilst this paper presents some of the pros and cons of each of these approaches, perhaps there are opportunities to develop hybridised algorithms that combine both knowledge and data driven techniques. In this paper, it is pointed out that open ECG data can dramatically influence what international ECG ML researchers focus on and that, ideally, open datasets could align with real world clinical challenges. In addition, some of the pitfalls and opportunities for ML with ECGs are outlined. A potential opportunity for the ECG community is to provide guidelines to researchers to help guide ECG ML practices. For example, whilst general ML guidelines exist, there is perhaps a need to recommend approaches for 'stress testing' and evaluating ML algorithms for ECG analysis, e.g. testing the algorithm with noisy ECGs and ECGs acquired using common lead and electrode misplacements. This paper provides a primer on ECG ML and discusses some of the key challenges and opportunities. [ABSTRACT FROM AUTHOR]

Radiation therapy offers distinct advantages over other currently available treatments for cutaneous malignancies in certain circumstances. Dermatologists and dermatologic surgeons should be familiar with the available radiation therapy techniques as well as their value and potential limitations in a variety of clinical scenarios. The first article in this 2-part continuing medical education series highlights the mechanisms, modalities, and applications of the most commonly used radiotherapy treatments as they relate to cutaneous oncology. We review the current indications for the use of radiation in the treatment of various cutaneous malignancies, the techniques commonly employed in modern radiotherapy, and the associated complications. [ABSTRACT FROM AUTHOR]

Radiation therapy may be performed for a variety of cutaneous malignancies, depending on patient health status, tumor clinical and histologic features, patient preference, and resource availability. Dermatologists should be able to recognize the clinical scenarios in which radiation therapy is appropriate, as this may reduce morbidity, decrease risk of disease recurrence, and improve quality of life. The second article in this 2-part continuing medical education series focuses on the most common indications for radiation therapy in the treatment of basal cell carcinoma, cutaneous squamous cell carcinoma, dermatofibrosarcoma protuberans, Merkel cell carcinoma, Kaposi sarcoma, angiosarcoma, cutaneous lymphoma, melanoma, undifferentiated pleomorphic sarcoma, and sebaceous carcinoma. [ABSTRACT FROM AUTHOR]

Long-term environmental exposure to metals e.g. zinc (Zn), may allow saltmarsh halophytes to develop metal tolerance to improve the chance of survival of their progeny in future metal-contaminated scenarios. Juncus acutus seeds were collected from mature parents (F 0) inhabiting a legacy Zn-contaminated location (Cockle Creek) and an uncontaminated reference location (Swansea) of Lake Macquarie, NSW, Australia. Seeds (J. acutus) were exposed to Zn (0.00 mM (control), 0.01 mM (effective concentration, EC 10) and 0.74 mM (EC 50)) and resultant germinants (F 1) were allowed to grow until 15 days. Seedling growth parameters i.e. biomass, root length and 1st leaf length, and seedling biochemical responses i.e. superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) antioxidant enzyme activity and lipid peroxidation products, malondialdehyde (MDA), were examined in order to assess if enzymes may be implicated in conferring tolerance to the offspring of metal-exposed parents. Control locations exhibited significantly greater declines in biomass and root length with Zn dose compared to seed from contaminated locations, suggesting F 1 offspring from contaminated parents were conferred tolerance to Zn. Furthermore, significant upregulation of CAT and GPx enzymes were evident in the seedlings derived from parents of contaminated locations. These are the antioxidative enzymes responsible for minimizing metal-induced oxidative stress, and may, in part, be responsible for increasing seedling fitness and observed tolerance. [Display omitted] • Differential Zn tolerance of offspring of J. acutus populations was examined. • Reference population seedlings showed declined growth in biomass and root length. • Metal impacted population seedlings exhibited upregulation of CAT and GPx. • F 1 offspring from the contaminated location was superior in subsequent Zn tolerance. • Upregulation of CAT and GPx activity partly contributed to F 1 offspring Zn tolerance. [ABSTRACT FROM AUTHOR]

In patients with axial spondyloarthritis (axSpA) or psoriatic arthritis (PsA) initiating secukinumab, we aimed to assess and compare the proportion of patients achieving 6-, 12- and 24-month patient-reported outcomes (PRO) remission and the 24-month retention rates. Patients with axSpA or PsA from 16 European registries, who initiated secukinumab in routine care were included. PRO remission rates were defined as pain, fatigue, Patient Global Assessment (PGA) ≤2 (Numeric Rating Scale (NRS) 0–10) and Health Assessment Questionnaire (HAQ) ≤0.5, for both axSpA and PsA, and were calculated as crude values and adjusted for drug adherence (LUNDEX). Comparisons of axSpA and PsA remission rates were performed using logistic regression analyses (unadjusted and adjusted for multiple confounders). Kaplan-Meier plots with log-rank test and Cox regression analyses were conducted to assess and compare secukinumab retention rates. We included 3087 axSpA and 3246 PsA patients initiating secukinumab. Crude pain, fatigue, PGA and HAQ remission rates were higher in axSpA than in PsA patients, whereas LUNDEX-adjusted remission rates were similar. No differences were found between the patient groups after adjustment for confounders. The 24-month retention rates were similar in axSpA vs. PsA in fully adjusted analyses (HR [95 %CI] = 0.92 [0.84–1.02]). In this large European real-world study of axSpA and PsA patients treated with secukinumab, we demonstrate for the first time a comparable effectiveness in PRO remission and treatment retention rates between these two conditions when adjusted for confounders. [ABSTRACT FROM AUTHOR]

The uptake and distribution of copper, zinc, arsenic, and lead was examined in two rare Australian saltmarsh species, Tecticornia pergranulata and Wilsonia backhousei. The bioconcentration factors and translocation factors were generally much lower than one, except for the Zn translocation factors for T. pergranulata. When compared to other Australian saltmarsh taxa, these species generally accumulated the lowest levels observed among taxa, especially in terms of their BCFs. Essential metals tended to be regulated, while non-essential metals increased in concentration with dose during transport among compartments, a pattern not previously observed in Australian saltmarsh taxa. The uptake of metals into roots was mainly explained by total sediment metal loads as well as more acidic pH, increased soil organic matter, and decreased salinity. The low uptake and limited translocation observed in these rare taxa may offer a competitive advantage for their establishment and survival in the last urbanised populations, where legacy metal contamination acts as a selective pressure. • Cu, Zn, As, Pb were examined in two rare saltmarsh plants in a contaminated estuary. • Metal(loid) partitioning patterns contrasted with other Australian saltmarsh species. • Uptake of both essential and non-essential metal(loid)s to roots was limited (BCF < 1). • Sediment pH, EC, and salinity influenced root metal(loid) concentrations. • Low BCF and high TF may confer competitive advantages in contaminated locations. [ABSTRACT FROM AUTHOR]

This study aims to assess the prevalence of electrocardiographic abnormalities based on the Minnesota code from a large sample of 1.01 m adult Brazilian primary care patients and to evaluate its association with age, sex, and cardiovascular risk factors. A large electrocardiogram (ECG) database of such patients aged ≥18 years (mean age 52 ± 17 years-old with 60.2% female). was analyzed and the results were stratified by sex and age. The prevalence of abnormalities was more common in men and the elderly population. Major electrocardiographic abnormalities were observed in 20.2% of adults and 43.1% of elderly patients, and minor abnormalities were found in 46.0% 39.4%, respectively. For adult patients, the number and percentage of major abnormalities rise depending on the number of cardiovascular risk factors. For elderly patients, the correlation between these variables is not clear, and the percentage of major abnormalities remains stable independently of the number of risk factors. [ABSTRACT FROM AUTHOR]

• We describe a patient presenting with persistent hiccups, who was found to have primary CNS lymphoma. • Persistent or intractable hiccups may reflect pathology within the brainstem, hypothalamic or supratentorial centres. • Appetite changes can be caused by hypothalamic tumour infiltration. • A first-order Horner's syndrome can arise from brainstem pathology. • A thorough neurological examination forms the cornerstone of localising neuropathology. We present a case of a 42-year-old male presenting with persistent hiccups and a Horner's syndrome, among other symptoms and signs of hypothalamic and brainstem dysfunction. He had a biopsy-proven diffuse infiltrative large primary CNS B-cell lymphoma involving the left fronto-temporal hemisphere, diencephalon and brainstem. The aim of this case report is to highlight key clinical and neuro-anatomical correlations that bring light to the art of the clinical examination. [ABSTRACT FROM AUTHOR]

The Fourth Universal Definition of Myocardial Infarction (FUDMI) [published simultaneously in 2018 in numerous journals including Circulation, Journal of the American College of Cardiology and European Heart Journal] focuses mainly on the distinction between non-ischemic myocardial injury and myocardial infarction (MI), along with the role of cardiovascular magnetic resonance, in order to define the etiology of myocardial injury. As a consequence, there is less emphasis on updating the parts of the definition concerning the electrocardiographic (ECG) changes related to MI. Evidence of myocardial ischemia is a prerequisite for the diagnosis of MI and the ECG is the main available tool for i) detecting acute ischemia, ii) triage and iii) risk stratification upon presentation. This review focuses on multiple aspects of ECG interpretation that we firmly believe should be considered for incorporation in any future update to the Universal Definition of MI. Our counterpoint view is that: a) the use of the ECG following coronary artery bypass surgery should be better explored and defined; b) the emphasis in the FUDMI on convex versus concave ST-elevation, which is questionable, should be balanced by the fact that many patients with true ST-elevation MI (STEMI) present with a concave form of ST elevation; c) reciprocal ST-depression in STEMI caused by right coronary artery or left circumflex artery occlusion, should be set against the fact that not all anterior STEMIs present with reciprocal ST-depression which can also be seen in cardiomyopathy and left ventricular hypertrophy; d) the "posterior" leads V7-V9 should be placed on a horizontal line from V4, rather than follow the 5th intercostal space; e) ST-depression in V1-V3 is not a manifestation of ischemia of the basal inferior segment, placed horizontally; f) Interpreting ST-T changes in patients with conduction abnormalities and pacemakers should be further defined. [ABSTRACT FROM AUTHOR]

This paper presents new measurements of species concentrations, temperature and mixture fraction in selected regions of a turbulent ethanol spray flame. The line-Raman–LIF–CO OH setup developed at the Sandia's Combustion Research Facility is utilised to probe regions of a spray flame where laser breakdown of liquid droplets is avoided and the remaining interferences can be corrected. The spray flame is stabilised on the piloted Sydney needle spray burner, where axial translation of the liquid injecting needle in the air-blast stream can transition the spray from dilute to dense. The solution to obtaining successful measurements is found to be multifaceted and includes: the appropriate selection of flame conditions; high sensitivity of the Raman detection system permitting reduced laser energies; development of a pre-processing algorithm to reject strong droplet interferences; and application of the hybrid matrix inversion method combined with wavelet denoising to account for interference corrections and noise at the very low signal levels obtained. Unique and necessary for the successful measurements reported in this paper, a pre-processing algorithm is outlined that removes data points corrupted with strong interferences from droplets. These interferences arise from a range of sources, but the most intense are due to the laser interaction with surrounding mist or liquid fragments, such that measurements near the jet centreline are corrupted and hence discarded. Reliable measurements of mixture fraction, temperature obtained from the sum of the species number densities, and species mole fractions are reported for regions in the flames sufficiently far from the centreline. The paper demonstrates the feasibility of the judicious use of Raman scattering in turbulent spray flames, the results of which will be extremely useful for validating numerical simulations. [ABSTRACT FROM AUTHOR]

To investigate immunomodulator use, risk factors and management for rheumatoid arthritis (RA) flares, and mortality for patients with pre-existing RA initiating immune checkpoint inhibitors (ICI) for cancer. We performed a retrospective cohort study of all patients with RA meeting 2010 ACR/EULAR criteria that initiated ICI for cancer at Mass General Brigham or Dana-Farber Cancer Institute in Boston, MA (2011–2022). We described immunomodulator use and changes at baseline of ICI initiation. We identified RA flares after baseline, categorized the severity, and described the management. Baseline factors were examined for RA flare risk using Fine and Gray competing risk models. We performed a landmark analysis to limit the potential for immortal time bias, where the analysis started 3 months after ICI initiation. Among those who survived at least 3 months, we examined whether RA flare within 3 months after ICI initiation was associated with mortality using Cox regression. Among 11,901 patients who initiated ICI for cancer treatment, we analyzed 100 pre-existing RA patients (mean age 70.3 years, 63 % female, 89 % on PD-1 monotherapy, 50 % lung cancer). At ICI initiation, 71 % were seropositive, 82 % had remission/low RA disease activity, 24 % were on glucocorticoids, 35 % were on conventional synthetic disease-modifying antirheumatic drugs (DMARDs), and 10 % were on biologic or targeted synthetic DMARDs. None discontinued glucocorticoids and 3/35 (9 %) discontinued DMARDs in anticipation of starting ICI. RA flares occurred in 46 % (incidence rate 1.84 per 1000 person-months, 95 % CI 1.30, 2.37); 31/100 flared within 3 months of baseline. RA flares were grade 1 in 16/46 (35 %), grade 2 in 25/46 (54 %), and grade 3 in 5/46 (11 %); 2/46 (4 %) required hospitalization for RA flare. Concomitant immune-related adverse events occurred in 15/46 (33 %) that flared. A total of 72/100 died during follow-up; 21 died within 3 months of baseline. Seropositivity had an age-adjusted sdHR of 1.95 (95 % CI 1.02, 3.71) for RA flare compared to seronegativity, accounting for competing risk of death. Otherwise, no baseline factors were associated with RA flare, including cancer type, disease activity, RA duration, and deformities. 9/46 (20 %) patients had their ICI discontinued/paused due to RA flares. In the landmark analysis among 79 patients who survived at least 3 months, RA flare in the first 3 months was not associated with lower mortality (adjusted HR 1.24, 95 % CI 0.71, 2.16) compared to no RA flare. Among patients with pre-existing RA, few changed immunomodulator medications in anticipation of starting ICI, but RA flares occurred in nearly half. RA flares were mostly mild and treated with typical therapies. Seropositivity was associated with RA flare risk. A minority had severe RA flares requiring disruption of ICI, and RA flares were not associated with mortality. [ABSTRACT FROM AUTHOR]

The process of self-management knowledge, behavior, and skill development in children with asthma from families with low income is understudied. Fifteen mothers of children with uncontrolled asthma participated in semistructured interviews exploring the transfer of asthma self-management responsibilities from parent to child. Team members performed thematic analysis of written transcripts. All participants were all the biological mothers and were impoverished, with most (73%) reporting an annual family income of less than $30,000. Their children ranged from 5 to 15 years old, were African American (100%), and had uncontrolled asthma based on national guidelines. Themes showed that child asthma self-management is difficult to achieve, that the transfer of asthma responsibility from mother to child is variable, and that mothers overestimate their child's developmental capacities for independent asthma self-management and have poor understanding of what well-controlled asthma means. Ongoing assessment and tailored guidance from health care providers are critical to support the pivotal role of mothers in their child's self-management development process. [ABSTRACT FROM AUTHOR]

Digital electrocardiographs are now widely available and a large number of digital electrocardiograms (ECGs) have been recorded and stored. The present study describes the development and clinical applications of a large database of such digital ECGs, namely the CODE (Clinical Outcomes in Digital Electrocardiology) study. ECGs obtained by the Telehealth Network of Minas Gerais, Brazil, from 2010 to 17, were organized in a structured database. A hierarchical free-text machine learning algorithm recognized specific ECG diagnoses from cardiologist reports. The Glasgow ECG Analysis Program provided Minnesota Codes and automatic diagnostic statements. The presence of a specific ECG abnormality was considered when both automatic and medical diagnosis were concordant; cases of discordance were decided using heuristisc rules and manual review. The ECG database was linked to the national mortality information system using probabilistic linkage methods. From 2,470,424 ECGs, 1,773,689 patients were identified. After excluding the ECGs with technical problems and patients <16 years-old, 1,558,415 patients were studied. High performance measures were obtained using an end-to-end deep neural network trained to detect 6 types of ECG abnormalities, with F1 scores >80% and specificity >99% in an independent test dataset. We also evaluated the risk of mortality associated with the presence of atrial fibrillation (AF), which showed that AF was a strong predictor of cardiovascular mortality and mortality for all causes, with increased risk in women. In conclusion, a large database that comprises all ECGs performed by a large telehealth network can be useful for further developments in the field of digital electrocardiography, clinical cardiology and cardiovascular epidemiology. [ABSTRACT FROM AUTHOR]

Continuing education is a requirement for most health professions including osteopaths in Australia and other jurisdictions around the world. Osteopaths need to be sure that the time and effort spent on their ongoing education translates to practice and meets their needs. Tutors on a postgraduate osteopathic course asked: as educators, how do we support students transfer skills developed from this program to their clinical setting? Students in postgraduate fee-paying osteopathic programs were asked to provide unidentified written responses to what advice or strategies they would use to transfer learning from a course to practice. Responses were collated, coded and analysed for themes to support a presentation outlining strategies to support learning transfer. Additional data collections underpinned review of the initial theme and category leading to saturation. The outcome was an over-arching theme: Expanding Options, supported by six categories that emerged from the data: Choice of Tools; Managing Time; Patient Selection, Developing Support Networks; Learning 'AT Stillness' and Building Trust & Confidence. The results were presented at a focus group type workshop on the post-graduate course. The themes generated may be applied to other training programs. However, the limitation of the small data set, the specific nature of the course and that it teaches in an area that generates controversy within the osteopathic profession need to be recognised when reflecting on the utility of outcome. [ABSTRACT FROM AUTHOR]

Six ECG patterns are found more frequently in healthy black adults than in whites. These patterns are presumably benign, but also may resemble those of malignant disease. 1) Healthy black adults show higher QRS voltage, and more often meet ECG criteria for left ventricular hypertrophy (LVH). Associated repolarization abnormalities can produce ST segment elevation (STE) that resembles ST elevation MI (STEMI). 2) The pattern of benign anterior STE, seen often in males, is more common in black subjects. Similar to LVH, this pattern may falsely suggest STEMI. 3) Both early repolarization (ER) and benign inferolateral STE are more common in black patients. Although they may convey a higher risk of fatal arrhythmias or cardiac death in white populations, it does not appear that black subjects with these patterns show a similar risk. 4) The persistent juvenile T wave inversion pattern shows asymmetric T wave inversion (TWI) in V1-V4, without ST segment deviations. It is most common in black females, and is considered benign. However, this pattern can also resemble the anterior TWI of arrhythmogenic right ventricular cardiomyopathy (ARVC). 5) A pattern of anterior TWI with associated J point elevation is a common finding in the black population, especially athletes. It could suggest hypertrophic cardiomyopathy, but can be presumed to be a benign finding in black athletes, when TWI is limited to V1-V4 and preceded by J point elevation. 6) TWI in the lateral precordial leads, usually associated with end-QRS slurring or notches is seen much more often in apparently healthy black subjects than white subjects. Unlike the anterior TWI pattern, however, it cannot be presumed benign. In conclusion, awareness of these ECG patterns may help to avoid unnecessary diagnostic or therapeutic interventions, but also encourage appropriate investigations. [ABSTRACT FROM AUTHOR]

• APT cycling is a safe and feasible exercise option for moderate to severe MS. • Four weeks of APT training improved total distance cycled, speed and power output. • Self reported spasticity was reduced in both intervention and control groups. • Objective measures of spasticity showed no change. • Investigating the effect of APT cycling was challenging in an in-patient setting. Exercise options for those with moderate to high levels of disability are limited. The aim of the study was to evaluate the feasibility of a progressive, four week lower limb cycling programme using active-passive trainers (APT's) on spasticity, cardiovascular fitness, function and quality of life in people with moderate to severe MS. Participants were in-patients in the Physical Disability Rehabilitation Unit, Queen Elizabeth University Hospital, Glasgow, UK and randomised to APT + usual care or usual care only. The APT group received 30 min of APT (2 min passive warm up, 26 min active cycling, 2 min passive cool down), five days per week for 4 weeks. Outcome measures; Oxygen Uptake Efficiency Slope, Modified Ashworth Scale, Multiple Sclerosis Spasticity Scale, Functional Independence Measure, Timed 25 foot walk test and the MSQOL-54, were taken before and after the intervention period. Symmetry, distance cycled and active participation were also recorded for each cycling session. 24 participants were recruited, 15 to the intervention and 9 to the control group. There was a 100% adherence to the intervention and a significant increase in average speed, power output and distance cycled (p < 0.001 for each) over the four weeks. There were no adverse events and both groups improved in average scores for all outcome measures. APT cycling was well tolerated, while the cycling parameters improved it was difficult to separate the effects of the therapy programme and APT cycling. A longer duration, fully powered trial in a community setting is merited. [ABSTRACT FROM AUTHOR]

Purpose: Bundled payments have been touted as mechanisms to optimize quality and costs. A recent feasibility study evaluating bundled payments for screening mammography episodes predated widespread adoption of digital breast tomosynthesis (DBT). We explore a similar model reflecting emerging acceptance of DBT in breast cancer screening.Methods: Using 4-year data for 59,094 screening episodes from two large facilities within a large academic health system, we utilized published methodology to calibrate Medicare national allowable reference prices for women undergoing screening mammography before and after practice-wide implementation of DBT.Results: Excluding DBT, Medicare-normalized bundled prices for traditional breast imaging 364 days downstream to screening mammography are extremely similar pre- and post-DBT implementation ($182.86 in 2013; $182.68 in 2015). The addition of DBT increased a DBT-inclusive bundled price by $53.16 (an amount lower than the $56.13 Medicare allowable fee for screening DBT) but was associated with significantly reduced recall rates (13.0% versus 9.4%; P < .0001). Without or with DBT, screening episode bundled prices remained sensitive to bundle-included services and varied little by patient age, race, or insurance status.Conclusions: Prior non-DBT approaches to bundled payment models for breast cancer screening remain viable as DBT becomes the standard of care, with bundle prices varying little by patient age, race, or insurance status. Higher DBT-inclusive bundled prices, however, highlight the need to explore societal costs more broadly (eg, reduced time away from work from fewer recalls) as bundled payment models evolve. [ABSTRACT FROM AUTHOR]

Fibromyalgia (FM) is a common chronic pain disorder that presents diagnostic challenges for clinicians. Several classification, diagnostic and screening criteria have been developed over the years, but there continues to be a need to develop criteria that reflect the current understanding of FM and are practical for use by clinicians and researchers. The Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks (ACTTION) public-private partnership with the U.S. Food and Drug Administration (FDA) and the American Pain Society (APS) initiated the ACTTION-APS Pain Taxonomy (AAPT) to develop a diagnostic system that would be clinically useful and consistent across chronic pain disorders. The AAPT established an international FM working group consisting of clinicians and researchers with expertise in FM to generate core diagnostic criteria for FM and apply the multidimensional diagnostic framework adopted by AAPT to FM. The process for developing the AAPT criteria and dimensions included literature reviews and synthesis, consensus discussions, and analyses of data from large population-based studies conducted in the United Kingdom. The FM working group established a revised diagnosis of FM and identified risk factors, course, prognosis, and pathophysiology of FM. Future studies will assess the criteria for feasibility, reliability, and validity. Revisions of the dimensions will also be required as research advances our understanding of FM. PERSPECTIVE: The ACTTION-APS FM taxonomy provides an evidence-based diagnostic system for FM. The taxonomy includes diagnostic criteria, common features, comorbidities, consequences, and putative mechanisms. This approach might improve the recognition of FM in clinical practice. [ABSTRACT FROM AUTHOR]

Estrogenic endocrine disrupting chemicals (EDCs) are natural hormones, synthetic compounds or industrial chemicals that mimic estrogens due to their structural similarity with estrogen's functional moieties. They typically enter aquatic environments through wastewater treatment plant effluents or runoff from intensive livestock operations. Globally, most natural and synthetic estrogens in receiving aquatic environments are in the low ng/L range, while industrial chemicals (such as bisphenol A, nonylphenol and octylphenol) are present in the μg to low mg/L range. These environmental concentrations often exceed laboratory-based predicted no effect concentrations (PNECs) and have been evidenced to cause negative reproductive impacts on resident aquatic biota. In vertebrates, such as fish, a well-established indicator of estrogen-mediated endocrine disruption is overexpression of the egg yolk protein precursor vitellogenin (Vtg) in males. Although the vertebrate Vtg has high sensitivity and specificity to estrogens, and the molecular basis of its estrogen inducibility has been well studied, there is growing ethical concern over the use of vertebrate animals for contaminant monitoring. The potential utility of the invertebrate Vtg as a biomonitor for environmental estrogens has therefore gained increasing attention. Here we review evidence providing support that the molluscan Vtg holds promise as an invertebrate biomarker for exposure to estrogens. Unlike vertebrates, estrogen signalling in invertebrates remains largely unclarified and the classical genomic pathway only partially explains estrogen-mediated activation of Vtg. In light of this, in the latter part of this review, we summarise recent progress towards understanding the molecular mechanisms underlying the activation of the molluscan Vtg gene by estrogens and present a hypothetical model of the interplay between genomic and non-genomic pathways in the transcriptional regulation of the gene. Image 1 • Environmental concentrations of estrogenic EDCs exceed lab-based PNECs. • Estrogenic EDCs impart negative reproductive impacts on resident aquatic biota. • Molluscan Vtg is induced upon exposure to estrogens in the lab and field. • Estrogens likely induce Vtg via receptor mediated non-genomic & genomic mechanisms. • More research establishing reliability of the molluscan Vtg biomarker is required. Molluscan vitellogenin holds promise as a biomarker for exposure and effect of estrogenic EDCs, but the molecular mechanisms of estrogen-mediated vitellogenesis require elucidation. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Oxidized alginate hydrogels are appealing alternatives to natural alginate due to their favourable biodegradability profiles and capacity to self-crosslink with amine containing molecules facilitating functionalization with extracellular matrix cues, which enable modulation of stem cell fate, achieve highly viable 3-D cultures, and promote cell growth. Stem cell metabolism is at the core of cellular fate (proliferation, differentiation, death) and metabolomics provides global metabolic signatures representative of cellular status, being able to accurately identify the quality of stem cell differentiation. Herein, umbilical cord blood mesenchymal stem cells (UCB MSCs) were encapsulated in novel oxidized alginate hydrogels functionalized with the glycine-histidine-lysine (GHK) peptide and differentiated towards the osteoblastic lineage. The ADA-GHK hydrogels significantly improved osteogenic differentiation compared to gelatin-containing control hydrogels, as demonstrated by gene expression, alkaline phosphatase activity and bone extracellular matrix deposition. Metabolomics revealed the high degree of metabolic heterogeneity in the gelatin-containing control hydrogels, captured the enhanced osteogenic differentiation in the ADA-GHK hydrogels, confirmed the similar metabolism between differentiated cells and primary osteoblasts, and elucidated the metabolic mechanism responsible for the function of GHK. Our results suggest a novel paradigm for metabolomics-guided biomaterial design and robust stem cell bioprocessing. Statement of Significance Producing high quality engineered bone grafts is important for the treatment of critical sized bone defects. Robust and sensitive techniques are required for quality assessment of tissue-engineered constructs, which result to the selection of optimal biomaterials for bone graft development. Herein, we present a new use of metabolomics signatures in guiding the development of novel oxidised alginate-based hydrogels with umbilical cord blood mesenchymal stem cells and the glycine-histidine-lysine peptide, demonstrating that GHK induces stem cell osteogenic differentiation. Metabolomics signatures captured the enhanced osteogenesis in GHK hydrogels, confirmed the metabolic similarity between differentiated cells and primary osteoblasts, and elucidated the metabolic mechanism responsible for the function of GHK. In conclusion, our results suggest a new paradigm of metabolomics-driven design of biomaterials. [ABSTRACT FROM AUTHOR]

Background: Healthcare worker (HCW) hand hygiene compliance is key to patient safety; however, compliance is suboptimal. Nevertheless hand hygiene compliance is not well studied in the long-term care setting.Aim: To apply a behaviour change framework, the Theoretical Domains Framework (TDF), to identify modifiable facilitators and barriers for HCW hand hygiene compliance in long-term care settings.Methods: HCW hand hygiene compliance facilitators and barriers were examined using a questionnaire for HCWs from long-term care homes in Ontario, Canada. The questionnaire was informed by the TDF, which is based on a synthesis of constructs from a number of relevant psychological theories of behaviour change.Findings: Barriers identified from the questionnaire aligned with the TDF domain environmental context and resources (time pressure, workload, and environmental controls). Facilitators identified from questionnaire results aligned with the TDF domains social/professional role and identity (it is what is expected of HCWs), and beliefs about consequences (risk of transmission of micro-organisms to self or others).Conclusion: There are several barriers to hand hygiene compliance that persist in long-term care. A behaviour change theory-informed framework such as the TDF can be helpful to identify those barriers. This study identified several key behavioural constructs aligned with the TDF that can be targeted when developing novel hand hygiene interventions. [ABSTRACT FROM AUTHOR]

Abstract This paper explores turbulent autoignition and flame stabilisation for a range of fuels, utilising a jet in a hot coflow burner. Jet fuels including: hydrogen, dimethyl ether and hydrocarbons ranging from CH 4 to C 4 H 8 are investigated with the influence of partial premixing, dilution and hot coflow temperature. Simultaneous acoustic emission measurements and high-speed chemiluminescence imaging at 10 kHz are performed; investigating the flame lift-off dynamics and to study the initiation and evolution of autoignition kernels. For all fuels studied, a common trend is found for increasing coflow temperatures; where a transition from high lift-off flames exhibiting an autoignition kernel dominated flame stabilisation mechanism, to lower lift-off flames exhibiting a premixed flame propagation stabilisation mechanism. Three key findings are reported: (i) common to all fuels studied for the high lift-off flames, the lift-off height vs. time follows a sawtooth-like trend. The leading edge of the main flame body (flame base) drifts downstream with near constant velocity, whilst upstream of the flame base autoignition kernels form and grow rapidly merging with the flame base; thereby lowering the tip of the flame base. (ii) High amplitude acoustic emission events correlate well with auto-ignition kernel flame base merging events for high lift-off flames, for the fuels studied. The ethylene flames produced the highest sound levels for a given mean lift-off height. (iii) In the high lift-off height regime, the lift-off height for all fuels scales well with corresponding simple 0-D auto-ignition delay calculations. The good correlation of the lift-off height scaling with the computed autionition delay implies that chemical kinetics, rather than turbulent mixing controls the processes at the base of these flames for higher lift-off height flames, indicating that autoignition is the dominant stabilising mode. [ABSTRACT FROM AUTHOR]

Abstract The state of practice for noise assessment utilizes established standards for emission and propagation modelling of linear and point sources. Recently, land use regression (LUR) modelling has emerged as an alternative method due to relatively low data and computing resource demands. However, a limitation of LUR modelling is that is does not account for noise attenuation and reflections by features of the built environment. This study demonstrates and validates a method that combines the two modelling frameworks to exploit their respective strengths: Emission and propagation based prediction of traffic noise, the predominant source of noise at the level of streetscapes, and a LUR-based correction for noise sources that vary on spatial scales beyond the streetscape. Multi-criteria analysis, location-allocation modelling and stakeholder consultation identified 220 monitoring sites with optimal coverage for a 1-week sampling period. A subset of sites was used to validate a road traffic noise emission and propagation model and to specify a LUR model that predicted the contribution of other sources. The equivalent 24-h sound pressure level (LAeq) for all sites was 62.9 dBA (SD 6.4). This varied by time of day, weekday, types of roads and land uses. The traffic noise emission model demonstrated a high level of covariance with observed noise levels, with R 2 values of 0.58, 0.60 and 0.59 for daytime, nighttime and 24-h periods, respectively. Combined with LUR models to correct for other noise sources, the hybrid models R 2 values were 0.64, 0.71 and 0.67 for the respective time periods. The study showed that road traffic noise emissions account for most of the variability of total environmental noise in Toronto. The combined approach to predict fine resolution noise exposures with emission and receptor-based models presents an effective alternative to noise modelling approaches based on emission and propagation or LUR modelling. Graphical abstract Image Highlights • Propagation modelling of traffic noise to represent streetscape environment. • Land use regression (LUR) modelling of noise to assess variance throughout city. • Combined propagation and LUR modelling validated as effective new method. • Road traffic explains most of variation of urban environmental noise. • Environmental noise levels in Toronto exceed recommended levels. [ABSTRACT FROM AUTHOR]

Abstract Outcome after surgery is of interest to the patient, the surgeon and the healthcare institution. There is conclusive evidence that regional anaesthesia is associated with superior analgesic outcomes compared to opioid-based analgesic techniques and may also reduce chronic pain. While better pain control and avoiding a general anaesthetic may alone be regarded as significant outcome benefits, regional anaesthesia and analgesia may influence many other important outcomes. Regional anaesthesia clearly reduces postoperative nausea and vomiting and pulmonary complications compared to general anaesthesia. Regional anaesthesia independently reduces length of stay and is a common component of enhanced recovery packages. Contemporary, but less robust, data suggests that neuraxial anaesthesia, and to a lesser extent analgesia, may reduce blood transfusion requirements, surgical site infection, intensive care admission, cancer recurrence and maybe even mortality. Any functional outcome benefits secondary to regional anaesthesia appear to be short lived and are generally not sustained long term. [ABSTRACT FROM AUTHOR]

Background: Automated measurements of electrocardiographic (ECG) intervals by current-generation digital electrocardiographs are critical to computer-based ECG diagnostic statements, to serial comparison of ECGs, and to epidemiological studies of ECG findings in populations. A previous study demonstrated generally small but often significant systematic differences among 4 algorithms widely used for automated ECG in the United States and that measurement differences could be related to the degree of abnormality of the underlying tracing. Since that publication, some algorithms have been adjusted, whereas other large manufacturers of automated ECGs have asked to participate in an extension of this comparison.Methods: Seven widely used automated algorithms for computer-based interpretation participated in this blinded study of 800 digitized ECGs provided by the Cardiac Safety Research Consortium. All tracings were different from the study of 4 algorithms reported in 2014, and the selected population was heavily weighted toward groups with known effects on the QT interval: included were 200 normal subjects, 200 normal subjects receiving moxifloxacin as part of an active control arm of thorough QT studies, 200 subjects with genetically proved long QT syndrome type 1 (LQT1), and 200 subjects with genetically proved long QT syndrome Type 2 (LQT2).Results: For the entire population of 800 subjects, pairwise differences between algorithms for each mean interval value were clinically small, even where statistically significant, ranging from 0.2 to 3.6milliseconds for the PR interval, 0.1 to 8.1milliseconds for QRS duration, and 0.1 to 9.3milliseconds for QT interval. The mean value of all paired differences among algorithms was higher in the long QT groups than in normals for both QRS duration and QT intervals. Differences in mean QRS duration ranged from 0.2 to 13.3milliseconds in the LQT1 subjects and from 0.2 to 11.0milliseconds in the LQT2 subjects. Differences in measured QT duration (not corrected for heart rate) ranged from 0.2 to 10.5milliseconds in the LQT1 subjects and from 0.9 to 12.8milliseconds in the LQT2 subjects.Conclusions: Among current-generation computer-based electrocardiographs, clinically small but statistically significant differences exist between ECG interval measurements by individual algorithms. Measurement differences between algorithms for QRS duration and for QT interval are larger in long QT interval subjects than in normal subjects. Comparisons of population study norms should be aware of small systematic differences in interval measurements due to different algorithm methodologies, within-individual interval measurement comparisons should use comparable methods, and further attempts to harmonize interval measurement methodologies are warranted. [ABSTRACT FROM AUTHOR]

Objective Immune checkpoint inhibitors are effective cancer therapies that have been associated with immune-related adverse events (irAEs). Recent reports of irAEs describe symptoms resembling classic rheumatologic syndromes, most notably associated with cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor blockade. Though cases have been described, there are fewer reports of rheumatologic disease associated with programmed cell death protein-1 (PD-1) inhibitors. Here, we describe a series of four patients presenting to the Brigham and Women’s Hospital (BWH) Arthritis Center with de novo polymyalgia rheumatica (PMR)-type conditions and/or peripheral synovitis after treatment with PD-1/PD-Ligand 1 (PD-L1) pathway inhibitors. Methods Patients with metastatic renal cell carcinoma (RCC) who were treated with PD-1/PD-L1 pathway inhibitors and subsequently developed complaints of new joint pain were referred to the BWH Arthritis Center as part of routine care and identified retrospectively. The electronic medical record was reviewed for cancer history and treatment, rheumatologic symptoms, physical exam, laboratory testing, and clinical course. Results All four patients developed irAEs consistent with a PMR-type syndrome and/or peripheral synovitis. Symptoms persisted despite discontinuation of the PD-1/PD-L1 pathway inhibitors; however, three of the patients responded well to oral glucocorticoids alone while one patient required the addition of oral methotrexate. All patients had an eventual decline in inflammatory markers. Conclusion These cases highlight the need for both oncologists and rheumatologists to recognize the development of rheumatologic disease during treatment with immune checkpoint blockade. Further investigation is needed to optimize the management of irAEs, particularly considering the increasing use of checkpoint inhibitors to treat malignancies. [ABSTRACT FROM AUTHOR]