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Familial idiopathic basal ganglia calcification (IBGC) or Fahr's disease is a rare neurodegenerative disorder characterized by calcium deposits in the basal ganglia and other brain regions, which is associated with neuropsychiatric and motor symptoms. Familial IBGC is genetically heterogeneous and typically transmitted in an autosomal dominant fashion. We performed a mutational analysis of SLC20A2, the first gene found to cause IBGC, to assess its genetic contribution to familial IBGC. We recruited 218 subjects from 29 IBGC-affected families of varied ancestry and collected medical history, neurological exam, and head CT scans to characterize each patient's disease status. We screened our patient cohort for mutations in SLC20A2. Twelve novel (nonsense, deletions, missense, and splice site) potentially pathogenic variants, one synonymous variant, and one previously reported mutation were identified in 13 families. Variants predicted to be deleterious cosegregated with disease in five families. Three families showed nonsegregation with clinical disease of such variants, but retrospective review of clinical and neuroimaging data strongly suggested previous misclassification. Overall, mutations in SLC20A2 account for as many as 41% of our familial IBGC cases. Our screen in a large series expands the catalog of SLC20A2 mutations identified to date and demonstrates that mutations in SLC20A2 are a major cause of familial IBGC. Non-perfect segregation patterns of predicted deleterious variants highlight the challenges of phenotypic assessment in this condition with highly variable clinical presentation.

Abstract Background During the COVID-19 pandemic, many intensive care units (ICUs) halted research to focus on COVID-19-specific studies. Objective To describe the conduct of an international randomized trial of stress ulcer prophylaxis (Re-Evaluating the Inhibition of Stress Erosions in the ICU [REVISE]) during the pandemic, addressing enrolment patterns, center engagement, informed consent processes, data collection, a COVID-specific substudy, patient transfers, and data monitoring. Methods REVISE is a randomized trial among mechanically ventilated patients, comparing pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important upper gastrointestinal bleeding and the primary safety outcome of 90-day mortality. We documented protocol implementation status from March 11th 2020-August 30th 2022. Results The Steering Committee did not change the scientific protocol. From the first enrolment on July 9th 2019 to March 10th 2020 (8 months preceding the pandemic), 267 patients were enrolled in 18 centers. From March 11th 2020-August 30th 2022 (30 months thereafter), 41 new centers joined; 59 were participating by August 30th 2022 which enrolled 2961 patients. During a total of 1235 enrolment-months in the pandemic phase, enrolment paused for 106 (8.6%) months in aggregate (median 3 months, interquartile range 2;6). Protocol implementation involved a shift from the a priori consent model pre-pandemic (188, 58.8%) to the consent to continue model (1615, 54.1%, p

Mg-stabilised Na-β’’-alumina solid electrolyte (Mg-BASE) for Na-ion batteries was synthesised and fabricated into 3D structures via direct ink writing (DIW), an extrusion-based additive manufacturing process. To produce a water-based ink with optimum viscoelastic properties and supreme printing quality, a comprehensive investigation of ink formulation and printing parameters was conducted. The sintered 3D structures of Mg-BASE, fabricated via direct ink writing, achieved relative density of 98.0 ± 1.1 % with β’’ phase fraction of 99.7 wt% whilst bulk ionic conductivity of 0.081 S⋅cm−1 at 350 °C was obtained. XRD results indicated that Mg-BASE fabricated via DIW may have different c-axis orientation than conventional dry-pressed pellets, leading to the improved bulk ionic conductivity.

In response to the growing complexity and unbalanced nature of future distribution systems, this paper presents a comprehensive evaluation of the recently proposed multi-phase line-wise power flow (MPLW PF) method across various benchmark systems. The MPLW PF approach effectively models unbalanced power systems with different topologies and phase configurations. This study extends the application of MPLW PF by testing its accuracy, convergence, and computational efficiency on a wide range of AC multi-phase and three-phase systems, including radial and meshed configurations. The MPLW PF method is tested on several benchmark systems, demonstrating its accuracy, scalability, and significant run-time reduction compared to traditional bus-wise (BW) method and OpenDSS as a commercial software.

By 2050, zero-carbon electric power systems will rely heavily on innumerable distributed energy resources (DERs), such as wind and solar. Accurate estimation of the aggregate connected DER capacity becomes pivotal in such a landscape. However, forecasting, power flow analysis, and optimization of feeders for operational decision-making by individually modeling each of these numerous renewables in the absence of complete information are operationally challenging and technically impractical. In response, we introduce a method to accurately estimate the aggregate capacities of the connected DERs on distribution feeders and a near-term forecasting method. Our proposal comprises: 1) ovel deep learning-based architecture with a few convolutional neural network and long short-term memory (CNN-LSTM) modules to represent feeder connected aggregate models of DERs and loads and associated training algorithms; 2) method for estimating aggregate capacities of connected renewables and loads; and 3) method for short-term (hourly) high-resolution forecasting. This step of estimation of the aggregate capacities of connected DERs, is a sequel to solving feeder hosting capacity problem. The method is tested using a North American utility feeder data, achieving an average accuracy of 95.56% for forecasting aggregate load power, 93.70% for feeder flow predictions, and 97.53% for estimating the aggregate capacity of DERs.

As prices for energy storage (ES) decline, merchant-owned ES units have an opportunity to be profitable if they earn revenue from multiple streams. Most papers in the literature provide a simplistic view, and do not capture practical tariff structure of commercial customers connected via load meters billed via net-metering scheme. In this paper, we present a flexible and comprehensive mathematical model to enable merchant-owned ES owners to maximize their profits by considering multiple revenue streams. The main contribution is a model that fully captures the economic picture by including displaced electricity costs, i.e., net-metering scheme, for behind-the-meter installations. It also includes operating costs, annual investment costs, and ES connected to the distribution system. The inclusion of net metering is novel, as well as simultaneously including all of ancillary services, energy costs, investment costs, net metering, and local generation. These elements can be crucial in building the business case for ES in Ontario to ensure profitability. We test our model on a large commercial customer. The load has a peak load of 1,500 kW and a solar generation capacity of 2,500 kW connected on a 13.8 kV feeder, with a limit of 5,000 kW capacity. The results show two cases. The first considers only energy arbitrage and costs ${\$}4,812,909$ , which is less than the cost without storage at ${\$}9,299,623$ . The second scenario allows for energy arbitrage and revenue via participation in local and bulk system ancillary services and yields a total benefit of ${\$}11,004,225$ . Both scenarios indicate benefits from purchase of storage. The second scenario is clearly more beneficial when storage investment is considered and opportunity is available. We also provide a stochastic implementation to consider uncertainty in any input parameter and demonstrate this method with energy prices.

Abstract Background The REVISE (Re-Evaluating the Inhibition of Stress Erosions in the ICU) trial will evaluate the impact of the proton pump inhibitor pantoprazole compared to placebo in invasively ventilated critically ill patients. Objective To outline the statistical analysis plan for the REVISE trial. Methods REVISE is a randomized clinical trial ongoing in intensive care units (ICUs) internationally. Patients ≥ 18 years old, receiving invasive mechanical ventilation, and expected to remain ventilated beyond the calendar day after randomization are allocated to either 40 mg pantoprazole intravenously or placebo while mechanically ventilated. Results The primary efficacy outcome is clinically important upper GI bleeding; the primary safety outcome is 90-day mortality. Secondary outcomes are ventilator-associated pneumonia, Clostridioides difficile infection, new renal replacement therapy, ICU and hospital mortality, and patient-important GI bleeding. Tertiary outcomes are total red blood cells transfused, peak serum creatinine concentration, and duration of mechanical ventilation, ICU, and hospital length of stay. Following an interim analysis of results from 2400 patients (50% of 4800 target sample size), the data monitoring committee recommended continuing enrolment. Conclusions This statistical analysis plan outlines the statistical analyses of all outcomes, sensitivity analyses, and subgroup analyses. REVISE will inform clinical practice and guidelines worldwide. Trial registration www.ClinicalTrials.gov NCT03374800. November 21, 2017.

Abstract Objective To report trends in Australian hospitalisations coded for sepsis and their associated costs. Design Retrospective analysis of Australian national hospitalisation data from 2002 to 2021. Methods Sepsis-coded hospitalisations were identified using the Global Burden of Disease study sepsis-specific ICD-10 codes modified for Australia. Costs were calculated using Australian-Refined Diagnosis Related Group codes and National Hospital Cost Data Collection. Results Sepsis-coded hospitalisations increased from 36,628 in 2002-03 to 131,826 in 2020-21, an annual rate of 7.8%. Principal admission diagnosis codes contributed 13,843 (37.8%) in 2002-03 and 44,186 (33.5%) in 2020-21; secondary diagnosis codes contributed 22,785 (62.2%) in 2002-03 and 87,640 (66.5%) in 2020-21. Unspecified sepsis was the most common sepsis code, increasing from 15,178 hospitalisations in 2002-03 to 68,910 in 2020-21. The population-based incidence of sepsis-coded hospitalisations increased from 18.6 to 10,000 population (2002-03) to 51.3 per 10,000 (2021-21); representing an increase from 55.1 to 10,000 hospitalisations in 2002-03 to 111.4 in 2020-21. Sepsis-coded hospitalisations occurred more commonly in the elderly; those aged 65 years or above accounting for 20,573 (55.6%) sepsis-coded hospitalisations in 2002-03 and 86,135 (65.3%) in 2020-21. The cost of sepsis-coded hospitalisations increased at an annual rate of 20.6%, from AUD199M (€127 M) in financial year 2012 to AUD711M (€455 M) in 2019. Conclusion Hospitalisations coded for sepsis and associated costs increased significantly from 2002 to 2021 and from 2012 to 2019, respectively.