INTRODUCTION MATERIALS AND METHODS

High-voltage direct current (HVDC) circuit breaker development and deployment strongly depend on the testing process, which ensures that the HVDC circuit breakers will satisfy design requirements. This article presents an HVDC circuit breaker test bench circuit configuration that can provide controllable large output currents to simulate different fault conditions for the current breaking test and high output voltage for the dielectric withstand test. The current breaking test circuit is based on multiple cascaded power converters connected in parallel to provide the necessary output current capability. Each cascaded power converter is composed of multiple cells that are operated by a phase-shifted pulsewidth-modulated signal for greater controllability and higher quality of the output waveform. The dielectric withstand test circuit is a simple high-voltage source with a low power rating that can also be used to charge the test bench and the internal circuitry of the circuit breaker that is to be tested. The proposed test bench ensures that fault conditions can be replicated accurately and offers greater flexibility by being able to test mechanical, semiconductor-based, or hybrid HVDC circuit breakers with different current and voltage ratings on the same hardware without any changes. The idea and the operating principle of the proposed test bench are verified experimentally on a downscaled system that consists of three cascaded power converters connected in parallel with three cells per cascaded power converter and with a total equivalent switching frequency of 92.5 kHz.

Objective. To identify the type of the non-invasive ventilatory treatment for patients diagnosed with chronic obstructive pulmonary disease (COPD), with respiratory status deteriorated by COVID-19 pneumonia, and in need of treatment in the Intensive Care Unit (ICU). Materials and Methods. This cross-sectional study was conducted over a one-year period in the medical intensive care units of two hospitals. As the patients’ clinical condition deteriorated and the parameters of the arterial blood gas (ABG) analysis worsened, oxygen support was applied via a high flow nasal cannula (HFNC) or by non-invasive positive pressure ventilation (NPPV). According to the control values of the arterial oxygen saturation (SaO2) and the parameters of ABG, the patients were enabled to be transferred between the two types of non-invasive ventilatory support. The primary outcome was the length of hospital stay, while secondary outcomes were the rate of intubation, the mortality rate, and respiratory support-free days. Results. Out of 21 critical patients with COPD and COVID-19, 11 (52.4%) were initially treated with NPPV and 10 (47.6%) with HFNC. The ages (67±9.79 in NPPV group vs. 70.10±10.25 in HFNC group) and severity of illness (SOFA score 5 (3.5) in NPPV group vs. 5 (2.8) in HFNC group) were similar between the two groups. Switching the mode of respiratory support was more common in NPPV (58.3% in survivor group vs. 41.7% in non-survivor group). Patients treated with NPPV compared to HFNC had a nominally longer length of stay (15 (11) vs. 11.5 (4.25)), and higher risk of intubation (66.7% vs. 33.3%) and mortality (66.7% vs. 33.3%), but the comparisons did not reach statistical significance. Survivors had significantly longer Medical Intensive Care Unit and hospital stays, but significantly lower FiO2 (0.60 vs.1) and higher values of PaO2/FiO2 (78(32.4) vs. 56.3(17.8)) than non-survivors. All patients were treated with corticosteroids, and the duration of treatment was similar between groups. Conclusion. In critically ill patients with COPD and COVID-19, both HFNC and NPPV were commonly used as the initial mode of ventilation. Switching to a different mode and adverse patient outcomes were more frequent in patients initially treated with NPPV. Survivors had higher values of PaO2/FiO2 than non-survivors.

Abstract This scientific paper examines the relationship between macroeconomic variables whose performance is measured under the implementation of Quantitative Easing in the US, by estimating vector autoregression (VAR) and Impulse Response Function with monthly data from US Federal Reserve, observed during the period January 1994-January 2022. Variables include: Consumer Price Index (CPIAUCSL); Industrial Production (INDPRO); Unemployment Rate (UNRATE); Interest Rates, Government Securities, Government Bonds (INTGSBUSM193N); Volatility Index (VIXCLS), Real Broad Effective Exchange Rate (RBUSBIS), Federal Surplus or Deficit (MTSDS133FMS), Money Supply M1 (WM1NS), M2 (WMNS), M3 (MABMM301USM189S). An evidence on macroeconomic variables of Consumer Price Index and Industrial Production when evaluating the effectiveness of QE is provided.

Introduction Systemic corticosteroids are the mainstay of treatment for immune checkpoint inhibitor induced (CPI) colitis but are associated with complications including life-threatening infection. The topically acting oral corticosteroid beclomethasone dipropionate (BD) is an effective treatment for mild to moderate flares of ulcerative colitis, and has fewer side effects than systemic corticosteroids. We hypothesized that BD would be an effective treatment for CPI-induced colitis. Methods We performed a retrospective analysis of all patients who started BD for CPI-induced colitis at three UK cancer centers between November 2017 and October 2020. All patients underwent endoscopic assessment and biopsy. The initial regimen of BD was 5 mg once daily for 28 days. Data were collected from electronic patient records. Clinical outcomes were assessed at 28 days after initiation of treatment. Results Twenty-two patients (14 male) with a median age of 64 (range 45–84) with CPI-induced colitis were treated with BD. At baseline, the median number of loose stools in a 24-hour period was six (common terminology criteria for adverse events, CTCAE grade diarrhea=2). Thirteen patients (59%) were dependent on systemic corticosteroids prior to starting BD. Baseline sigmoidoscopy showed moderate inflammation (Mayo Endoscopic Score (MES) = 2) in two patients (9%), mild inflammation (MES=1) in nine patients (41%) and normal findings (MES=0) in eleven patients (50%). Twenty patients (91%) had histopathological features of inflammation. All 22 patients (100%) had a clinical response to BD and 21 (95%) achieved clinical remission with a return to baseline stool frequency (CTCAE diarrhea=0). Ten patients (45%) had symptomatic relapse on cessation of BD, half within 7 days of stopping. All patients recaptured response on restarting BD. No adverse events were reported in patients treated with BD. Conclusions Topical BD represents an appealing alternative option to systemic immunosuppressive treatments to treat colonic inflammation. In this study, BD was effective and safe at inducing remission in CPI-induced colitis, which was refractory to systemic corticosteroids. Further randomized studies are needed to confirm these findings and determine the optimum dosing regimen.

Reliable power system operation with 100% inverter-based resources (IBRs) is an unsolved and challenging problem. One of the most challenging factors is ensuring power system stability after N-1 contingencies. This paper presents a promising solution using an operator support system (OSS) to enable stable operation of power system with up to 100% IBR generation. The OSS consists of two components. First is dynamic security assessment to evaluate the system resiliency, and identify critical N-1 contingencies that could endanger the system. The second component, as the key technology behind the OSS, is dynamic security optimization (DSO). The DSO optimizes the control parameters of generators and inverters to improve the stability of the system towards the identified N-1 contingencies. The key to system with 100% IBRs, as emphasized in many recent studies, is to establish the grid frequency reference using grid-forming (GFM) inverters. We show through high-fidelity Electro-Magnetic-Transient (EMT) simulations of the future generation models of Hawai‘i Island system with 100% IBR capacity that a system with 100% IBRs can be operated stably with the help of GFM inverters, and appropriate controller parameters can be found by DSO for the inverters. The DSO is verified via 28 critical N-1 contingencies of Hawai‘i Island system identified by Hawaiian Electric. The simulation results verify the effectiveness of DSO, and show significant stability improvement from DSO.

The integration of renewable generation in electrical power systems is exponentially increasing for multiple reasons. First, a fast decarbonization of the electrical energy system is a critical milestone to slow climate change and facilitate the decarbonization of other energy sectors, such as transportation and heat. Second, renewable generation from wind and solar have become much cheaper compared to conventional sources like gas, coal, and nuclear. Third, renewable generation is in many cases decentralized, which increases the resilience of the energy system, for example, in the face of natural disasters.

Abstract The present study proposes the conceptual model, which traces the role of consumers’ high-quality consciousness, perceived brand equity, and luxury value perceptions on the intention to purchase masstige brands and tests it for the moderating role of generational cohort membership (X-ers, Y-ers, and Z-ers). To explore the relationship between variables of interest, we used a quantitative survey-based research design and emphasised a single product category – consumer electronics and a single masstige brand – Apple. The online survey questionnaire was developed on the Google platform and distributed among residents of Bosnia and Herzegovina using a snowball sampling technique. In the end, we received 354 usable responses. We used structural equation modelling and multigroup analysis to test the proposed conceptual model. Our findings suggest that quality consciousness is the most significant predictor of consumers’ intentions to buy a masstige brand, followed by perceived brand equity. Also, our results indicate that the relationships between independent variables (consumer-based brand equity, quality consciousness, overall luxury value) and dependent variables (intention to purchase a masstige brand) are contingent on generational differences. The present study deepens our scholarly understanding of masstige consumption and contributes to the theoretical notion of generation cohort theory in the context of masstige consumption.

Background: In the academic world, the debate continues on the subject of how far a lack of vitamin D can affect the healing of various wounds. Objective: To determine if basal serum levels of vitamin D significantly influence clinical parameters linked to post-extraction wound healing after surgical removal of impacted/semi-impacted third molars. Methods: A total of 23 patients were included in this study. Clinical outcome parameters were: edema, trismus, pain, soft tissue healing, and dry socket signs. The research was divided into four stages. Results: Due to the high prevalence of hypovitaminosis D (91%), patients were classified into an insufficient (≥ 20 ng/ml) or a deficient group (<20 ng/ml). The results showed no statistically significant differences in pain, edema, trismus, or soft tissue healing between those two groups. A slight statistical interaction was observed in the clinical parameters related to edema and trismus assessment, but not statistically significant. We did not notice signs of “dry socket” on any of the patients. Conclusion: Within its limitations (low number of patients, high prevalence of vitamin D deficiency), this pilot study failed to find a significant influence of serum vitamin D concentrations in wound healing or post-surgery symptom (pain, edema, trismus) development after third molar extraction. Further clinical investigations are necessary to elaborate on this function of vitamin D more precisely.

Objective. The objective of this non-interventional post-marketing clinical trial was to analyze the antihypertensive effect and safety of a fixed combination of perindopril and indapamide in the treatment of unregulated essential hypertension. Patients and Methods. The prospective clinical trial included patients aged 20 to 75 years with essential hypertension and blood pressure values ≥140/90 mmHg at baseline. On the basis of the investigator’s decision, patients received 2 mg perindopril + 0.625 mg indapamide (group 2+0.625) or 4 mg perindopril + 1.25 mg indapamide (group 4+1.25). Results. The study included 1173 patients (426 patients in group 2+0.625 and 747 patients in group 4+1.25) at 27 investigational centers in Bosnia and Herzegovina. Mean blood pressure values at baseline and visits after nine months were significantly higher in the 4+1.25 group compared to the 2+0.625 group. There was a significant drop in systolic and diastolic blood pressure in both groups. The target values of systolic and diastolic blood pressure, according to the European Society of Cardiology (2018), were reached after nine months of therapy by more than 80% of patients in the 2+0.625 group, and this number was significantly higher compared to the 4+1.25 group where more than 60% of patients reached target values. Newly diagnosed patients had a better response to therapy. The percentage of patients receiving additional antihypertensive therapy decreased by the end of the study. Age, gender and the existence of diabetes mellitus were identified as negative predictors of target blood pressure achievement. The therapy showed a good safety profile. Conclusion. A fixed combination of perindopril and indapamide was effective and safe in the treatment of unregulated essential hypertension.

In the present review, we briefly discuss the breakthrough advances in precision medicine using a tumor-agnostic approach and focus on BRAF treatment modalities, the mechanisms of resistance and the diagnostic approach in cancers with BRAF mutations. Tumor-type agnostic drug therapies work across cancer types and present a significant novel shift in precision cancer medicine. They are the consequence of carefully designed clinical trials that showed the value of tumor biomarkers, not just in diagnosis but in therapy guidance. Six tumor-agnostic drugs (with seven indications) have been approved through October 2022 by FDA. The first tumor-agnostic treatment modality was pembrolizumab for MSI-H/dMMR solid tumors, approved in 2017. This was followed by approvals of larotrectinib and entrectinib for cancers with NTRK fusions without a known acquired resistance mutation. In 2020, pembrolizumab was approved for all TMB-high solid cancers, while a PD-L1 inhibitor dostarlimab-gxly was approved for dMMR solid cancers in 2021. A combination of BRAF/MEK inhibitors (dabrafenib/trametinib) was approved as a tumor-agnostic therapy in June 2022 for all histologic types of solid metastatic cancers harboring BRAFV600E mutations. In September 2022, RET inhibitor selpercatinib was approved for solid cancers with RET gene fusions. Conclusion. Precision cancer medicine has substantially improved cancer diagnostics and treatment. Tissue type-agnostic drug therapies present a novel shift in precision cancer medicine. This approach rapidly expands to provide treatments for patients with different cancers harboring the same molecular alteration.