A Pilot Clinical and Technical Validation of an Immersive Virtual Reality Platform for 3D Anatomical Modeling and Contouring in Support of Surgical and Radiation Oncology Treatment Planning.

The aim of this study was to validate a novel medical virtual reality (VR) platform used for medical image segmentation and contouring in radiation oncology and 3D anatomical modeling and simulation for planning medical interventions, including surgery. The first step of the validation was to verify quantitatively and qualitatively that the VR platform can produce substantially equivalent 3D anatomical models, image contours, and measurements to those generated with existing commercial platforms. To achieve this, a total of eight image sets and 18 structures were segmented using both VR and reference commercial platforms. The image sets were chosen to cover a broad range of scanner manufacturers, modalities, and voxel dimensions. The second step consisted of evaluating whether the VR platform could provide efficiency improvements for target delineation in radiation oncology planning. To assess this, the image sets for five pediatric patients with resected standard-risk medulloblastoma were used to contour target volumes in support of treatment planning of craniospinal irradiation, requiring complete inclusion of the entire cerebral-spinal volume. Structures generated in the VR and the commercial platforms were found to have a high degree of similarity, with dice similarity coefficient ranging from 0.963 to 0.985 for high-resolution images and 0.920 to 0.990 for lower resolution images. Volume, cross-sectional area, and length measurements were also found to be in agreement with reference values derived from a commercial system, with length measurements having a maximum difference of 0.22 mm, angle measurements having a maximum difference of 0.04°, and cross-sectional area measurements having a maximum difference of 0.16 mm2. The VR platform was also found to yield significant efficiency improvements, reducing the time required to delineate complex cranial and spinal target volumes by an average of 50% or 29 min.

A novel gain-of-function phosphorylation site modulates PTPN22 inhibition of TCR signaling.

Protein Tyrosine Phosphatase Non-receptor type 22 (PTPN22) is encoded by a major autoimmunity gene and is a known inhibitor of T cell receptor (TCR) signaling and drug target for cancer immunotherapy. However, little is known about PTPN22 post-translational regulation. Here we characterize a phosphorylation site at Ser325 situated C-terminal to the catalytic domain of PTPN22, and its roles in altering protein function. In human T cells, Ser325 is phosphorylated by Glycogen Synthase Kinase-3 (GSK3) following TCR stimulation, which promotes its TCR-inhibitory activity. Signaling through the major TCR-dependent pathway under PTPN22 control was enhanced by CRISPR/Cas9 mediated suppression of Ser325 phosphorylation and inhibited by mimicking it via glutamic acid substitution. Global phospho-mass spectrometry showed Ser325 phosphorylation state alters downstream transcriptional activity through enrichment of Swi3p, Rsc8p and Moira (SWIRM) domain binding proteins, and next-generation sequencing (NGS) revealed it differentially regulates the expression of chemokines and T cell activation pathways. Moreover, in vitro kinetic data suggest the modulation of activity depends on a cellular context. Finally, we begin to address the structural and mechanistic basis for the influence of Ser325 phosphorylation on the protein's properties by Deuterium Exchange Mass Spectrometry (DX/MS) and Nuclear Magnetic Resonance (NMR) spectroscopy. In conclusion, this study explores the function of a novel phosphorylation site of PTPN22 that is involved in complex regulation of TCR signaling and provides details that might inform the future development of allosteric modulators of PTPN22. Significance statement The tyrosine phosphatase PTPN22 serves as a negative regulator in T cells, and its phosphorylation is a major regulatory process for controlling its function. Here, we uncovered a novel phosphorylation site at Ser325 on PTPN22 that allosterically regulates its activity leading to impaired TCR-dependent pathways. Biophysical methods identify multiple regions affected upon Ser325 phosphorylation, which can be the basis for future mechanistic studies of PTPN22 activators or inhibitors.

Predictors of early versus delayed neurological deterioration after thrombolysis for ischemic stroke: ENCHANTED study.

BACKGROUND AND PURPOSE: We aimed to determine predictors of early (END) and delayed neurological deterioration (DND) and their association with functional outcome in patients with acute ischemic stroke (AIS) who participated in the international Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). METHODS: END and DND were defined as scores of a ≥2 point increase on the National Institutes of Health Stroke Scale (NIHSS) or ≥1 point decrease on Glasgow coma scale, or death, from baseline to 24 hours and 24 hours to 72 hours, respectively. Multivariable logistic regression models were used to determine independent predictors of END and DND and their association with 90-day outcomes (dichotomous scores on the modified Rankin scale [mRS] of 2-6 vs 0-1 and 3-6 vs 0-2, and death). RESULTS: Of 4496 patients, 871 (19.4%) and 302 (8.4%) patients experienced END and DND, respectively. Higher baseline NIHSS score, older age, large artery occlusion due to significant atheroma, cardioembolic stroke subtype, hemorrhagic infarction and parenchymatous hematoma within 24 hours, were all independent predictors for both END (all P ≤0.01) and DND (all P ≤0.024). Moreover, higher baseline systolic blood pressure (BP) (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.02-1.12), higher diastolic BP variability within 24 hours (OR 1.07, 95% CI 1.04-1.09), patients from Asia (OR 1.25, 95% CI 1.03-1.52) were the only independent predictors for END. However, Asian ethnicity was negatively associated with DND (OR 0.64, 95% CI 0.47-0.86). Hemorrhagic infarction and parenchymatous hematoma within 24 hours were the key predictor of END across all stroke subtypes. END and DND were all associated with a poor functional outcome at 90 days (all P<0.001). CONCLUSIONS: We identified overlapping and unique demographic and clinical predictors of END and DND after thrombolysis for acute ischemic stroke. Both END and DND predict unfavorable outcomes at 90 days.

Towards the standardisation of adult person-reported outcome domains in diabetes research: A Consensus Statement development panel.

Diabetes is unique among chronic diseases because clinical outcomes are intimately tied to how the person living with diabetes reacts to and implements treatment recommendations. It is further characterised by widespread social stigma, judgement and paternalism. This physical, social and psychological burden collectively influences self-management behaviours. It is widely recognised that the individual's perspective about the impact of trying to manage the disease and the burden that self-management confers must be addressed to achieve optimal health outcomes. Standardised, rigorous assessment of mental and behavioural health status, in interaction with physical health outcomes is crucial to aid understanding of person-reported outcomes (PROs). Whilst tempting to conceptualise PROs as an issue of perceived quality of life (QoL), in fact health-related QoL is multi-dimensional and covers indicators of physical or functional health status, psychological and social well-being. This complexity is illuminated by the large number of person reported outcome measures (PROMs) that have been developed across multiple psychosocial domains. Often measures are used inappropriately or because they have been used in the scientific literature rather than based on methodological or outcome assessment rigour. Given the broad nature of psychosocial functioning/mental health, it is important to broadly define PROs that are evaluated in the context of therapeutic interventions, real-life and observational studies. This report summarises the central themes and lessons derived in the assessment and use of PROMs amongst adults with diabetes. Effective assessment of PROMs routinely in clinical research is crucial to understanding the true impact of any intervention. Selecting appropriate measures, relevant to the specific factors of PROs important in the research study will provide valuable data alongside physical health data.

Nanostructured Niobium and Titanium Carbonitrides as Electrocatalyst Supports.

Nanostructured niobium-titanium carbonitrides, (Nb,Ti)C1-xNx, with the cubic-rock salt structure are prepared without the use of reactive gases via thermal treatment (700-1200 °C) under nitrogen of mixtures of guanidine carbonate and ammonium niobate (V) oxalate hydrate, with addition of ammonium titanyl oxalate monohydrate as a titanium source. The bulk structure and chemical composition of the materials are characterized using powder X-ray diffraction (XRD) and powder neutron diffraction, elemental homogeneity is studied using energy dispersive spectroscopy (EDS) mapping using transmission electron microscopy (TEM), and surface chemical analysis is examined using X-ray photoelectron spectroscopy (XPS). Nanoscale crystallites of between 10 and 50 nm are observed by TEM, where EDS reveals the homogeneity of metal distribution for the mixed-metal materials. Titanium carbonitrides are found to be air sensitive, reacting with air under ambient conditions, while titanium-niobium carbonitrides are found to degrade in aqueous sulfuric acid. The niobium carbonitrides, however, show some stability toward acidic solutions. Materials are produced with composition NbC1-xNx with x between 0.35 and 0.45, and more carbon-rich materials (x ≈ 0.35) are found as the synthesis temperature is increased, as proven by Rietveld refinement of crystal structure against powder neutron diffraction data. Despite phase purity seen by diffraction and negligible bulk carbon content, XPS shows a complex surface chemistry for the NbC1-xNx materials, with evidence for Nb2O5-like oxide species in a carbon-rich environment. The NbC1-xNx prepared at 900 °C has a surface area around 50 m2 g-1, making it suitable as a catalyst support. Loading with iridium provides a material active for the oxygen evolution reaction in 0.1 M sulfuric acid, with minimal leaching of either Nb or Ir after 1000 cycles.

Combining Double-Dose and High-Dose Pulsed Dapsone Combination Therapy for Chronic Lyme Disease/Post-Treatment Lyme Disease Syndrome and Co-Infections, Including Bartonella: A Report of 3 Cases and a Literature Review.

Three patients with relapsing and remitting borreliosis, babesiosis, and bartonellosis, despite extended anti-infective therapy, were prescribed double-dose dapsone combination therapy (DDDCT) for 8 weeks, followed by one or several two-week courses of pulsed high-dose dapsone combination therapy (HDDCT). We discuss these patients' cases to illustrate three important variables required for long-term remission. First, diagnosing and treating active co-infections, including Babesia and Bartonella were important. Babesia required rotations of multiple anti-malarial drug combinations and herbal therapies, and Bartonella required one or several 6-day HDDCT pulses to achieve clinical remission. Second, all prior oral, intramuscular (IM), and/or intravenous (IV) antibiotics used for chronic Lyme disease (CLD)/post-treatment Lyme disease syndrome (PTLDS), irrespective of the length of administration, were inferior in efficacy to short-term pulsed biofilm/persister drug combination therapy i.e., dapsone, rifampin, methylene blue, and pyrazinamide, which improved resistant fatigue, pain, headaches, insomnia, and neuropsychiatric symptoms. Lastly, addressing multiple factors on the 16-point multiple systemic infectious disease syndrome (MSIDS) model was important in achieving remission. In conclusion, DDDCT with one or several 6-7-day pulses of HDDCT, while addressing abnormalities on the 16-point MSIDS map, could represent a novel effective clinical and anti-infective strategy in CLD/PTLDS and associated co-infections including Bartonella.

Across two phylogeographic breaks: Quaternary evolutionary history of a mountain aspen (Populus rotundifolia) in the Hengduan Mountains.

Biogeographical barriers to gene flow are central to plant phylogeography. In East Asia, plant distribution is greatly influenced by two phylogeographic breaks, the Mekong-Salween Divide and Tanaka-Kaiyong Line, however, few studies have investigated how these barriers affect the genetic diversity of species that are distributed across both. Here we used 14 microsatellite loci and four chloroplast DNA fragments to examine genetic diversity and distribution patterns of 49 populations of Populus rotundifolia, a species that spans both the Mekong-Salween Divide and the Tanaka-Kaiyong Line in southwestern China. Demographic and migration hypotheses were tested using coalescent-based approaches. Limited historical gene flow was observed between the western and eastern groups of P. rotundifolia, but substantial flow occurred across both the Mekong-Salween Divide and Tanaka-Kaiyong Line, manifesting in clear admixture and high genetic diversity in the central group. Wind-borne pollen and seeds may have facilitated the dispersal of P. rotundifolia following prevalent northwest winds in the spring. We also found that the Hengduan Mountains, where multiple genetic barriers were detected, acted on the whole as a barrier between the western and eastern groups of P. rotundifolia. Ecological niche modeling suggested that P. rotundifolia has undergone range expansion since the last glacial maximum, and demographic reconstruction indicated an earlier population expansion around 600 Ka. The phylogeographic pattern of P. rotundifolia reflects the interplay of biological traits, wind patterns, barriers, niche differentiation, and Quaternary climate history. This study emphasizes the need for multiple lines of evidence in understanding the Quaternary evolution of plants in topographically complex areas.

Enhancing photocatalytic tetracycline degradation through the fabrication of high surface area CeO2 from a cerium-organic framework.

Water pollution is a global environmental issue, and the presence of pharmaceutical compounds, such as tetracyclines (TCs), in aquatic ecosystems has raised growing concerns due to the potential risks to both the environment and human health. A high surface area CeO2 was prepared via atmospheric thermal treatment of a metal-organic framework of cerium and benzene-1,3,5-tricarboxylate. The effects of calcination temperature on the morphology, structure, light absorption properties and tetracycline removal efficiency were studied. The best activity of the photocatalysts could be achieved when the heat treatment temperature is 300 °C, which enhances the photocatalytic degradation performance towards tetracycline under visible light. The resulting CeO2 particles have high capacity for adsorbing TCs from aqueous solution: 90 mg g-1 for 60 mg L-1 TCs. As a result, 98% of the initial TC can be removed under simulated sunlight irradiation. The cooperation of moderate defect concentration and disordered structure showed tetracycline removal activity about 10 times higher than the initial Ce-MOF. An embryotoxicity assessment on zebrafish revealed that treatment with CeO2 particles significantly decreased the toxicity of TC solutions.

RNA quality control factors nucleate Clr4/SUV39H and trigger constitutive heterochromatin assembly.

In eukaryotes, the Suv39 family of proteins tri-methylate lysine 9 of histone H3 (H3K9me) to form constitutive heterochromatin. However, how Suv39 proteins are nucleated at heterochromatin is not fully described. In the fission yeast, current models posit that Argonaute1-associated small RNAs (sRNAs) nucleate the sole H3K9 methyltransferase, Clr4/SUV39H, to centromeres. Here, we show that in the absence of all sRNAs and H3K9me, the Mtl1 and Red1 core (MTREC)/PAXT complex nucleates Clr4/SUV39H at a heterochromatic long noncoding RNA (lncRNA) at which the two H3K9 deacetylases, Sir2 and Clr3, also accumulate by distinct mechanisms. Iterative cycles of H3K9 deacetylation and methylation spread Clr4/SUV39H from the nucleation center in an sRNA-independent manner, generating a basal H3K9me state. This is acted upon by the RNAi machinery to augment and amplify the Clr4/H3K9me signal at centromeres to establish heterochromatin. Overall, our data reveal that lncRNAs and RNA quality control factors can nucleate heterochromatin and function as epigenetic silencers in eukaryotes.

Influence of Stroke Onset Location on the Efficacy of Endovascular Thrombectomy: Comparison of Outcomes Between In-hospital vs. Community-Onset Strokes.

BACKGROUND AND PURPOSE: Previous studies have suggested that patients suffering an in-hospital stroke (IHS) may face delays in treatment and worse outcomes compared to patients with community-onset strokes (COS). However, most studies occurred when intravenous thrombolysis was the primary treatment. This study aimed to examine the outcomes of patients experiencing an IHS in the endovascular thrombectomy (EVT) era. MATERIALS AND METHODS: Single-center retrospective cohort study of patients older than 18 years with acute ischemic stroke (AIS) treated with EVT within 12 hours of stroke onset from January 1, 2015, to April 30, 2021. Patients were classified into two groups: in-hospital strokes (IHS) and community-onset strokes (COS). We compared time metrics of stroke care delivery, rate of successful reperfusion, and functional outcome as scored using the modified Rankin Scale (mRS) score at 90 days (favorable outcome was defined as mRS 0-2). Differences in proportions were assessed using Fisher's exact and Chi-Square tests as appropriate. For continuous variables, differences in medians between groups were evaluated using Mann-Whitney U tests. RESULTS: A total of 676 consecutive patients were included, with 69 (10%) comprising the IHS group. IHS patients were more likely to have diabetes (36% vs. 18%, p=0.02) and less likely to receive thrombolysis (25% vs 68%, p<0.001) than the COS group but were otherwise similar. IHS patients had significantly faster overall time metrics, most notably from stroke recognition to imaging (median [IQR], 70 [38-141] min vs 121 [74-228] min, p<0.001). Successful recanalization was achieved in > 75% in both groups (p=0.39), with a median NIHSS at discharge <4 (p=0.18). The 90-day mRS was similar in both groups, with a trend of higher in-hospital mortality in the IHS group (p=0.06). CONCLUSIONS: IHS patients had shorter workflow delays to initiation of EVT compared to their community counterparts but with a similar rate of successful recanalization and clinical outcomes. Importantly, 90 day mortality and mRS scores were equivalent between IHS and COS. ABBREVIATIONS: AIS = acute ischemic stroke; LVO = large vessel occlusion; IHS= in-hospital stroke; COS= community-onset stroke; EVT= endovascular thrombectomy; CSC= comprehensive stroke center; TOAST= Trial of Org 10172 in Acute Stroke Treatment.

Nuclear receptor signaling via NHR-49/MDT-15 regulates stress resilience and proteostasis in response to reproductive and metabolic cues.

The ability to sense and respond to proteotoxic insults declines with age, leaving cells vulnerable to chronic and acute stressors. Reproductive cues modulate this decline in cellular proteostasis to influence organismal stress resilience in Caenorhabditis elegans We previously uncovered a pathway that links the integrity of developing embryos to somatic health in reproductive adults. Here, we show that the nuclear receptor NHR-49, an ortholog of mammalian peroxisome proliferator-activated receptor α (PPARα), regulates stress resilience and proteostasis downstream from embryo integrity and other pathways that influence lipid homeostasis and upstream of HSF-1. Disruption of the vitelline layer of the embryo envelope, which activates a proteostasis-enhancing intertissue pathway in somatic cells, triggers changes in lipid catabolism gene expression that are accompanied by an increase in fat stores. NHR-49, together with its coactivator, MDT-15, contributes to this remodeling of lipid metabolism and is also important for the elevated stress resilience mediated by inhibition of the embryonic vitelline layer. Our findings indicate that NHR-49 also contributes to stress resilience in other pathways known to change lipid homeostasis, including reduced insulin-like signaling and fasting, and that increased NHR-49 activity is sufficient to improve proteostasis and stress resilience in an HSF-1-dependent manner. Together, our results establish NHR-49 as a key regulator that links lipid homeostasis and cellular resilience to proteotoxic stress.

Genomic variation, environmental adaptation and feralization in ramie, an ancient fiber crop.

Feralization is an important evolutionary process, but the mechanisms behind it remain poorly understood. Here, we use the ancient fiber crop, ramie (Boehmeria nivea (L.) Gaudich.) as a model to investigate genomic changes associated with both domestication and fertilization. We first produced a chromosome-scale de novo genome assembly of feral ramie and investigated structural variations between feral and domesticated ramie genomes. Next, 915 accessions from 20 countries were gathered, comprising cultivars, major landraces, feral populations and wild progenitor. Based on whole genome resequencing of these accessions, the most comprehensive ramie genomic variation map to date was constructed. Phylogenetic, demographic, and admixture signal detection analyses indicate that feral ramie is of exoferal or exo-endo origin, i.e., descended from hybridization between domesticated ramie and wild progenitor or ancient landraces. Feral ramie has greater genetic diversity than wild or domesticated ramie, and genomic regions affected by natural selection during feralization are different from those under selection during domestication. Ecological analyses showed that feral and domesticated ramie have similar ecological niches which are substantially different from the niche of the wild progenitor, and three environmental variables were associated with habitat-specific adaptation in feral ramie. Our findings advance our understanding of feralization, providing a scientific basis for the excavation of new crop germplasm resources and offering novel insights into the evolution of feralization in nature.

The Interplay of Electronic Configuration and Anion Ordering on the Magnetic Behavior of Hydroxyfluoride Diaspores.

We report a new nickel hydroxyfluoride diaspore Ni(OH)F prepared using hydrothermal synthesis from NiCl2·6H2O and NaF. Magnetic characterization reveals that, contrary to other reported transition-metal hydroxyfluoride diaspores, Ni(OH)F displays weak ferromagnetism below the magnetic ordering temperature. To understand this difference, neutron diffraction is used to determine the long-range magnetic structure. The magnetic structure is found to be distinct from those reported for other hydroxyfluoride diaspores and shows an antiferromagnetic spin ordering in which ferromagnetic canting is allowed by symmetry. Furthermore, neutron powder diffraction on a deuterated sample, Ni(OD)F, reveals partial anion ordering that is distinctive to what has previously been reported for Co(OH)F and Fe(OH)F. Density functional theory calculations show that OH/F ordering can have a directing influence on the lowest energy magnetic ground state. Our results point toward a subtle interplay between the sign of magnetic exchange interactions, the electronic configuration, and anion disordering.

Influence of Time of Admission on Endovascular Thrombectomy (EVT): Comparison of Outcomes During Business Hours Versus Off-Business Hours.

Purpose:To investigate the differences in endovascular thrombectomy (EVT) outcomes of patients treated for acute ischaemic stroke (AIS) during business versus off-business hours. Methods: A single-centre retrospective cohort study of patients with AIS treated with EVT from February 1, 2015, to May 31, 2021, was performed at a comprehensive stroke centre (CSC). Patients were divided into business (Monday to Friday, 8 AM-5 PM) versus off-business hours groups. The primary outcome was functional neurological disability, scored using the modified Rankin Scale (mRS) at 90 days. Secondary outcomes included the rate of successful reperfusion and procedural workflow time delays. Differences in proportions were assessed using Fisher's exact and Chi-Square tests as appropriate. For continuous variables, differences in medians between groups were assessed using Mann-Whitney U tests. Results: A total of 676 patients were included, with 399 patients (59%) comprising the off-business-hour group. No significant differences were seen in age, sex, ASPECTS score, or NIHSS at arrival. Off-business hours strokes had a longer delay between CSC arrival to groin puncture (minutes: 81 vs 44, P < .0001) and between imaging to groin puncture (minutes: 67 vs 32, P < .0001) compared to the business hours strokes. There were no differences in the rate of successful reperfusion (mTICI ≥2b) between groups (82% vs 83%, P = .61). At 90 days, 65% of patients in both groups had an mRS ≤2 (P = .91). Conclusion: Despite workflow delays in initiating EVT during off-business hours, there were no differences in the rate of successful reperfusion or functional outcomes.

Oxygen Isotopologues Resolved from Water Oxidation Electrocatalysis by Electron Paramagnetic Resonance Spectroscopy.

Electrocatalytic water oxidation is a key transformation in many strategies designed to harness solar energy and store it as chemical fuels. Understanding the mechanism(s) of the best electrocatalysts for water oxidation has been a fundamental chemical challenge for decades. Here, we quantitate evolved dioxygen isotopologue composition via gas-phase EPR spectroscopy to elucidate the mechanisms of water oxidation on metal oxide electrocatalysts with high precision. Isotope fractionation is paired with computational and kinetic modeling, showing that this technique is sensitive enough to differentiate O-O bond-forming steps. Strong agreement between experiment and theory indicates that for the nickel-iron layered double hydroxide─one of the best earth-abundant electrocatalysts to be studied─water oxidation proceeds via a dioxo coupling mechanism to form a side-bound peroxide rather than a hydroxide attack to form an end-bound peroxide.

The effect of diabetes management on the workload of district and community nursing teams in the UK.

AIMS: The number of older people with diabetes requiring care from district nursing teams is increasing. The role of district nursing teams in diabetes management has expanded to involve diagnosis, treatment and medication administration. As the complexity of caseloads increases, the current model is likely unsustainable. This study aims to understand the current diabetes workload of district nursing teams. METHODS: An online survey was distributed via social media and key stakeholder networks to district nursing teams. Survey items were designed by the researchers prior to pilot testing with potential participants. Descriptive statistical and qualitative analyses were conducted. Data are median ± IQR. RESULTS: 159 district nursing teams completed the survey. The median caseload per team was 300 (IQR 176-407) patients including 21 with diabetes (IQR 14-40; 8.7% (4-20%)). 1.09 home visits per day per person with diabetes lasting 13.8 minutes (excluding travel time) were needed, with most requiring insulin administration. 96% of nursing teams undertake multiple daily visits for some patients. 91% reported workloads relating to diabetes management had increased over the last 2 years; 76% stated current diabetes workloads were unsustainable. More insulin usage, more referrals and a lack of ability or willingness to self-administer insulin has increased the diabetes workload. Possible solutions include better collaboration between healthcare professionals, simplification of insulin administration and glucose monitoring, better training and upskilling of healthcare assistants and promotion of self-efficacy. CONCLUSIONS: Diabetes management forms an increasing component of district nursing workload and is likely to be unsustainable unless new models are found.

Hypernatremia in Hyperglycemia: Clinical Features and Relationship to Fractional Changes in Body Water and Monovalent Cations during Its Development.

In hyperglycemia, the serum sodium concentration ([Na]S) receives influences from (a) the fluid exit from the intracellular compartment and thirst, which cause [Na]S decreases; (b) osmotic diuresis with sums of the urinary sodium plus potassium concentration lower than the baseline euglycemic [Na]S, which results in a [Na]S increase; and (c), in some cases, gains or losses of fluid, sodium, and potassium through the gastrointestinal tract, the respiratory tract, and the skin. Hyperglycemic patients with hypernatremia have large deficits of body water and usually hypovolemia and develop severe clinical manifestations and significant mortality. To assist with the correction of both the severe dehydration and the hypovolemia, we developed formulas computing the fractional losses of the body water and monovalent cations in hyperglycemia. The formulas estimate varying losses between patients with the same serum glucose concentration ([Glu]S) and [Na]S but with different sums of monovalent cation concentrations in the lost fluids. Among subjects with the same [Glu]S and [Na]S, those with higher monovalent cation concentrations in the fluids lost have higher fractional losses of body water. The sum of the monovalent cation concentrations in the lost fluids should be considered when computing the volume and composition of the fluid replacement for hyperglycemic syndromes.

The prototype of a frailty learning health system: The HARMONY Model.

Introduction: Rapid translation of research findings into clinical practice through innovation is critical to improve health systems and patient outcomes. Access to efficient systems of learning underpinned with real-time data are the future of healthcare. This type of health system will decrease unwarranted clinical variation, accelerate rapid evidence translation, and improve overall healthcare quality. Methods: This paper aims to describe The HARMONY model (acHieving dAta-dRiven quality iMprovement to enhance frailty Outcomes using a learNing health sYstem), a new frailty learning health system model of implementation science and practice improvement. The HARMONY model provides a prototype for clinical quality registry infrastructure and partnership within health care. Results: The HARMONY model was applied to the Western Sydney Clinical Frailty Registry as the prototype exemplar. The model networks longitudinal frailty data into an accessible and useable format for learning. Creating local capability that networks current data infrastructures to translate and improve quality of care in real-time. Conclusion: This prototype provides a model of registry data feedback and quality improvement processes in an inpatient aged care and rehabilitation hospital setting to help reduce clinical variation, enhance research translation capacity, and improve care quality.

Deep learning prediction of renal anomalies for prenatal ultrasound diagnosis.

Deep learning algorithms have demonstrated remarkable potential in clinical diagnostics, particularly in the field of medical imaging. In this study, we investigated the application of deep learning models in early detection of fetal kidney anomalies. To provide an enhanced interpretation of those models' predictions, we proposed an adapted two-class representation and developed a multi-class model interpretation approach for problems with more than two labels and variable hierarchical grouping of labels. Additionally, we employed the explainable AI (XAI) visualization tools Grad-CAM and HiResCAM, to gain insights into model predictions and identify reasons for misclassifications. The study dataset consisted of 969 ultrasound images from unique patients; 646 control images and 323 cases of kidney anomalies, including 259 cases of unilateral urinary tract dilation and 64 cases of unilateral multicystic dysplastic kidney. The best performing model achieved a cross-validated area under the ROC curve of 91.28% ± 0.52%, with an overall accuracy of 84.03% ± 0.76%, sensitivity of 77.39% ± 1.99%, and specificity of 87.35% ± 1.28%. Our findings emphasize the potential of deep learning models in predicting kidney anomalies from limited prenatal ultrasound imagery. The proposed adaptations in model representation and interpretation represent a novel solution to multi-class prediction problems.

Risk of Major Adverse Cardiovascular Events After Emergency Department Visits for Hypertensive Urgency.

BACKGROUND: Chronic hypertension is an established long-term risk factor for major adverse cardiovascular events (MACEs). However, little is known about short-term MACE risk after hypertensive urgency, defined as an episode of acute severe hypertension without evidence of target-organ damage. We sought to evaluate the short-term risk of MACE after an emergency department (ED) visit for hypertensive urgency resulting in discharge to home. METHODS: We performed a case-crossover study using deidentified administrative claims data. Our case periods were 1-week intervals from 0 to 12 weeks before hospitalization for MACE. We compared ED visits for hypertensive urgency during these case periods versus equivalent control periods 1 year earlier. Hypertensive urgency and MACE components were all ascertained using previously validated International Classification of Diseases, Tenth Revision Clinical Modification codes. We used McNemar test for matched data to calculate risk ratios. RESULTS: Among 2 225 722 patients with MACE, 1 893 401 (85.1%) had a prior diagnosis of hypertension. There were 4644 (0.2%) patients who had at least 1 ED visit for hypertensive urgency during the 12 weeks preceding their MACE hospitalization. An ED visit for hypertensive urgency was significantly more common in the first week before MACE compared with the same chronological week 1 year earlier (risk ratio, 3.5 [95% CI, 2.9-4.2]). The association between hypertensive urgency and MACE decreased in magnitude with increasing temporal distance from MACE and was no longer significant by 11 weeks before MACE (risk ratio, 1.2 [95% CI, 0.99-1.6]). CONCLUSIONS: ED visits for hypertensive urgency were associated with a substantially increased short-term risk of subsequent MACE.