Short Interruptions Research Articles

Respiratory Outcomes of Interrupted Modulator Therapies in Children With Cystic Fibrosis.

Cystic fibrosis (CF) is a multisystemic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, resulting in defective synthesis or function of the CFTR protein. Historically, CF treatment focused on managing symptoms and complications. Fortunately, modulator drugs are now available to directly target the defective CFTR protein. However, in some countries, such as Turkey, these drugs are not covered by social insurance. Consequently, many CF patients face barriers to accessing modulatory therapies or must interrupt their treatment. This study demonstrates the impact of interrupting modulator therapy on pulmonary function, emphasizing the need for uninterrupted continuous treatment. In this study, 39 CF patients receiving elexacaftor-tezacaftor-ivacaftor (ETI) at our clinic were retrospectively analyzed. Among the patients, 18 experienced one or more interruptions, ranging from 15 to 210 days during ETI treatment. We analyzed pulmonary function test results from 27 interruption periods. At the beginning of the interruption, the mean percent predicted FEV1 (ppFEV1) was 69.59% ± 25.87%, which decreased to 64.96% ± 24.52% by the end of the interruption. There was a significant decrease with a mean change of 4.62 ± 8.49 (p = 0.008). However, no significant correlation was found between the interruption duration and FEV1 change. Our results demonstrate that pulmonary functions are adversely affected by interruption periods, regardless of their duration. Even short interruptions have a significant impact on pulmonary functions. This underscores the need for uninterrupted continuation of modulatory treatment and for improved policies to ensure equitable access to treatment.

Prospective cohort study identifying risk factors for sports injuries in adolescent athletes: the Healthy Injury-Free Adolescent Athletes (HIFAA) study

A high incidence of injuries has been reported in young athletes. Several factors have been associated with athletes’ sports injuries. However, scientific evidence is lacking, particularly for adolescent athletes. Hence,...

Impact of short lenvatinib interruptions in advanced thyroid cancer patients

Impact of short lenvatinib interruptions in advanced thyroid cancer patients

Self-compacting concrete with reduced formwork pressures

Self-compacting concrete (SCC) is normally characterized with high pressures exerted on the formwork during casting. The pressures can easily exceed bearing capacity of a regular formwork when casting a high structural member in one step. The contribution shows new ways of reducing the pressures using mineral additives based on calcinated clay minerals and clay nanoparticles whose addition together with interrupted casting process leads to a substantial reduction of the formwork pressures. Short interruptions in the casting lead to microstructural changes and flocculation, thixotropy and early strength evolution. The positive effects are studied systematically in microstructural studies performed on modified cement pastes using microscopy and viscosimetry. Rheological behavior of standard SCCs is improved towards thixotropy of the mixture by using the mineral additives. The newly developed recipes are tested on SCCs used on real construction sites. Examples of their practical utilization and on-site measurements show on up to 50 % pressure reductions in enriched SCCs compared to ordinary SCCs.

Effect of a process interruption on the mechanical properties of AlSi10Mg components produced by laser powder bed fusion (PBF-LB/M)

Due to various causes, process interruptions during powder bed fusion of metal with laser beam (PBF-LB/M) can occur. This can be performed deliberately, e.g. as part of sensor integration or hybrid manufacturing. However, unplanned interruptions are also possible, for example, due to a power outage. In particular, long-term interruptions may result in significant quality losses, making it necessary to cancel the build job. Depending on the extent of the print job and the location of the interruption, this can mean a major economic loss. Most of the previous studies have found only minor reduction of the mechanical properties. However, these studies often dealt with the effect of planned interruptions and relatively short interruptions of about 1 h. Significantly longer interruption times are also realistic, especially when they occur overnight or during weekends. The aim of this study is to investigate the effects on the component quality of a process interruption when the manufacturing process is continued several hours after the interruption. For this purpose, the effects of different interruption durations (1, 4, 10 and 16 h) on the microstructure, hardness, tensile strength and fatigue properties of the PBF-LB/M-fabricated components made of AlSi10Mg were investigated. In addition, the layer shift resulting from the interruption is measured and described geometrically. The results show that for AlSi10Mg specimens in which the layer shift was removed and which are not highly loaded, an unplanned long-term process interruption up to 10 h does not result in a significant loss of quality under the considered conditions. Furthermore, it is apparent that the procedure for restarting the process is very important for the resulting component quality.

“The Desert of Spoken Words”: Conversations of Bishop Márton Áron Recorded by the Securitate in 1956–1980

Márton Áron, bishop of the Catholic Diocese of Alba Iulia (1938–1980), came to the attention of the Securitate from the founding of this repressive institution until the autumn of 1980, when he passed away. The reasons for his surveillance were his popularity among the faithful, his outspoken anti-communism, his loyalty to the Vatican and the fact that he came from the country’s largest national minority. The results of this extended surveillance are reflected today in the bishop’s files in the Archive of the National Council for the Study of the Securitate Archives in Bucharest. One of the main methods used by the Securitate in the surveillance process was the use of microphones. They were installed in the bishop’s office in 1956 and operated with short interruptions until the end of his life. The transcripts of the recorded conversations are today in the bishop’s files and represent a “gold mine” for historians interested in the Catholic Church in Romania during the Communist regime.

Monitoring climatic impacts on the moisture uptake of the first Swiss wildlife bridge made of wood

Wildlife bridges represent a major component of any sustainable strategy to counteract the negative consequences of cutting the natural habitat of wildlife into disconnected parts by motorways and rail. This is especially true for a small and densely populated country such as Switzerland with diverse wildlife scattered through its territory. Up to now all wildlife bridges in Switzerland have been made of concrete with steel reinforcement. The wildlife bridge under investigation here is the first one in Switzerland made of wood-based materials. The idea of building a wildlife bridge by using wood-based materials represents besides a challenging technological endeavor also an ecological progress regarding embodied energy. A further advantage which resulted after realizing the construction, was the short interruption time it needed for installation on a motorway in operation. The most urgent question with respect to the wood-based elements is their moisture uptake when subjected to weather conditions. The present paper reports on a long-term monitoring of this wooden wildlife bridge over a period of approximately 2 years. Different kind of sensors, data from a nearby meteorological station, data regarding hourly number of different kind of vehicles passing beneath the wildlife bridge as well as lab measurements have been used to enable a robust and reliable statement on wooden wildlife bridges subjected to Swiss flatland weather conditions.

Computational Study of Fluidic-Valve Injectors for Detonation Engines

The performance of detonation engines depends on propellant injectors. This study investigates a fluidic-valve injector mounted to a detonation tube. The injector is equipped with a recessed cavity connecting to the fuel plenum. After verifying the theoretical and numerical framework, three cases (I, II, and III) are analyzed, each representing different combinations of initial injector conditions and fuel supply setups. In all cases, a detonation wave is initiated near the headend of the detonation tube. It propagates through the initial section of the tube and undergoes diffraction and deformation at the flush-wall orifice. Among the considered cases, Case III, featuring a pre-pressurized initial injector flowfield and a total-pressure-inlet boundary, demonstrates the best agreement with the experimental results. It reveals a strong interaction between the longitudinally traveling detonation wave and the transverse propellant plume expanding from the orifice, causing the detonation wave to split. One part continues within the tube, while the other diffracts into the injector, creating a recirculation zone. Shock waves propagate within the injector and reflect at the base of the cavity, generating pressure spikes similar to the experimental observations. However, the contact surface separating the burnt products and fresh propellant reaches only a limited distance into the injector, suggesting a short interruption time and rapid recovery of the propellant supply.

Spontaneous Eye Blinks Map the Probability of Perceptual Reinterpretation During Visual and Auditory Ambiguity.

Spontaneous eye blinks are modulated around perceptual events. Our previous study, using a visual ambiguous stimulus, indicated that blink probability decreases before a reported perceptual switch. In the current study, we tested our hypothesis that an absence of blinks marks a time in which perceptual switches are facilitated in- and outside the visual domain. In three experiments, presenting either a visual motion quartet in light or darkness or a bistable auditory streaming stimulus, we found a co-occurrence of blink rate reduction with increased perceptual switch probability. In the visual domain, perceptual switches induced by a short interruption of visual input (blank) allowed an estimate of the timing of the perceptual event with respect to the motor response. This provided the first evidence that the blink reduction was not a consequence of the perceptual switch. Importantly, by showing that the time between switches and the previous blink was significantly longer than the inter-blink interval, our studies allowed to conclude that perceptual switches did not happen at random but followed a prolonged period of nonblinking. Correspondingly, blink rate and switch rate showed an inverse relationship. Our study supports the idea that the absence or presence of blinks maps perceptual processes independent of the sensory modality.

Voltage Disturbances and Inrush Current of DC Power Supplies

The potential damaging effects of high inrush currents occurring after power quality disturbances on switch-mode dc power supplies (SMPS’) have been reported, but have not been studied in detail. This paper presents a new analytical model for the accurate representation and calculation of inrush currents of low-power SMPS devices. This model is verified against previously developed circuit-based simulation model and compared with the only other analytical model available in existing literature. The developed analytical model is also used to investigate device protection co-ordination, in order to demonstrate two important effects of high-inrush current: nuisance tripping of protection and damage of internal SMPS components. Key words. Inrush current, load modelling, analytical representation, switch-mode dc power supply (SMPS), power quality disturbance, short interruption, voltage sag

2008 Norwegian quality of supply survey - State of art and reported needs

This paper reports the findings in a national survey conducted in 2008/2009 on the quality of supply. The respondents are from distribution system operators (DSOs) and from the Norwegian Transmission system operator (TSO). The survey was implemented as a web based survey and covered all quality of supply phenomena defined in EN 50160 [1]. In addition some EMC issues also were included. The objective of the survey was to investigate which phenomena are the most important and what the utilities’ needs to improve quality of supply management. The phenomena causing most problems in Norway are: Supply voltage variations Short duration supply interruptions Voltage dips These phenomena are of highly ranked both by the Norwegian TSO and the DSOs responding to the survey. The most important need for quality of supply improvement according to the DSOs is to get advice concerning measurements and measurement equipment: The TSO sees basic technology transfer, national databases, advice concerning measurements/ measurement equipment and standardisation as important issues in general, but the needs are different for different phenomena.

A CASE STUDY ON HIGH POWER COMPENSATOR OF THE POWER GRID IRREGULARITIES FOR INDUSTRIAL APPLIANCES

The paper presents a case study on development of the high power compensator of the power grid irregularities. The compensator is dedicated for sensitive industrial installations protection against dips, sags and short duration interruptions in public power network. The energy for compensation will be stored in bank of high voltage stacked supercapacitors. The development of the new high power medium voltage compensator will be based on experience gained during the realisation in The Electrotechnical Institute Gdansk Branch a similar medium power low voltage device. The study includes: main power converter topology considerations with some preliminary simulation results including harmonic components discussion, the solution to the problem of fast identification of the grid voltage disturbances, the solution to the problem of compensator waveforms synchronization with the grid and the description of the main operational algorithm of the compensator.

Calibration of a Virtual Instrument for Power Quality Monitoring

The paper describes a virtual instrument for power quality monitoring based on NI LabVIEW™ platform and simultaneous measurements of electrical voltages and currents. The virtual power quality analyzer is realized by using National Instruments 9225 and 9227 modules for voltage and current measurements, respectively, NI cDAQ 9174, 4 slot USB chassis and a PC. The created virtual instrument measures power quality characteristics: power frequency, voltage variations, magnitude of rapid voltage changes, flicker severity, voltage unbalance, total harmonic distortion, as well as the elements of voltage dips, short interruptions, and long interruptions defined in the standard EN 50160 for voltage characteristics of supplied electricity. The measurement is according to the general guide on harmonics and interharmonics measurements IEC 61000-4-7. The calibration and verification of the power quality analyzer is a complex task and it is performed by using the laboratory calibrator FLUKE 5500A. The results of calibration and verification of the developed virtual instrument, as well as the results of power quality measurements near different lightning technologies are presented

Voltages in the network and inside industrial Plants. Case of PSA-Vigo

The main objective of this paper consists in presenting a survey of voltage sags and short interruptions in different places along the geography of Galicia measured throughout two years. Effects and the possible solutions of the voltage sags and short interruptions in one industrial installation, PSA-Vigo, that produce cars, are also addressed. Finally, we will establish the corresponding conclusions.

Multirate Modeling and Predictive Control for WBG-Device-Based High-Switching-Frequency Power Converters

With the growth of wide bandgap devices, it is necessary to exploit the high switching frequency benefits to improve the power converter's performance, thus requiring a higher sampling/interrupt frequency in digital signal processors. However, such a short interrupt time duration imposes big computational difficulty in the execution of programming code, especially using the model predictive control (MPC). Thus, most of the existing MPCs are applied with switching frequencies below 20 kilohertz, which cannot exploit the full potential of the wide bandgap device-based power converters. To solve this challenge, this article proposes a multi-rate MPC scheme, where the trigger of interrupt and switching device transition can be performed at different rates. Compared to conventional MPCs, the main uniqueness of the proposed multi-rate MPC is that the high-dimension control sequence is solved and applied within each interrupt interval. Therefore, the increased switching frequency objective can be easily achieved with a low sampling/interrupt frequency configuration, which also significantly relieves the digital execution of the heavy interrupt tasks. The proposed method shows a more optimized control input and higher computational efficiency over the multi-rate finite-control-set MPC counterpart. A silicon carbide inverter-fed AC motor drive system is used to verify the proposed multi-rate MPC. The results show the improved system performance with the combined advantages of both the high switching frequency and MPC strategy.

On dreaming a different world together?

The article provides some broad perspectives on what is happening in the global Reformed world today. It takes its point of departure in two recent editions of the Reformed World, the official journal of the World Communion of Reformed Churches that is again being published since 2021 after a short interruption in publication. It shows how these editions embody the present self-description of the global body, namely “Called to Communion; Committed to Justice” as well as its strategic vision, “Confessing the God of Life in a World Fallen Among Thieves.” In this process, a brief overview is offered of distinct Reformed emphases in four of the most important bilateral reports in which the World Communion participated in recent years. Based on this overview, four brief theological observations conclude the broad picture.

Oltenia and the Idea of Regionalization – A Historical Perspective

Bănia Craiovei, despite the fact that it represented an institution with a certain degree of autonomy, contributed to ensuring the interwar cohesion of Wallachia. Its dissolution was made in the context beginning an approach of a centralist paradigm, in the Romanian politics and administration, this manifesting itself after 1831, until the moment when King Carol II reintroduced the regions, in 1938, for a short time, and then to return to the centralized system (with a short interruption in 1952–1968), after 1968.The article offers a general perspective, historical and not only, on Oltenia.

EP0042, a Dual FLT3 and Aurora Kinase Inhibitor: Results from an Ongoing Phase I/IIa Dose-Finding/Dose Optimization Study in Patients with Relapsed/Refractory Acute Myeloid Leukemia

Background: EP0042 was developed as an orally bioavailable potent inhibitor of FLT3 and Aurora kinases. Aurora kinases play an important role in acute myeloid leukemia (AML) and have been implicated in the development of resistance to FLT3 inhibitors (Joshi S et al. Cancer Cell 2021;39:999-1014, 8). Dual inhibition of FLT3 and Aurora kinase has been shown to overcome acquired resistance to selective FLT3 inhibition both in vitro and in vivo (Moore A et al. Leukemia 2012;26:1462-70; Tariq M et al. Br J Cancer 2021;125:966-74). Preliminary data from this ongoing Phase 1 study of EP0042 in relapsed/refractory AML were presented previously (Taussig et al. Blood 2022:140(Supplement 1): 6222-6223). Here we present further data from the dose finding and dose optimisation cohorts from the study. Methods The primary objective of this phase I/IIa, multi-centre study is to investigate safety/tolerability and to establish both the MTD and optimal dose of EP0042 when used as monotherapy, or in combination with established standard treatments in patients with AML, myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) who have relapsed on or are refractory to previous therapy. Secondary objectives include PK characterisation and assessment of anti-tumour activity. Results As of July 13 th 2023, 38 patients (17 f/21 m) were enrolled across 9 different cohorts. Median age 72 years, range 25-84. Patients presented with relapsed/refractory AML (34), CMML (1) or MDS (3). 9 patients had FLT3 mutated AML at the point of entry (All FLT3 ITD). Patients were administered doses ranging from 40mg to 170mg, QD or BID, with different schedules, across 7 cohorts (Table 1). One Cycle = 28 days. 150mg BID 28/28 days was identified as the MTD with 2 DLTs identified, Grade 3 somnolence and ataxia, and Grade 3 encephalopathy. Two dose optimisation cohorts (Table 1) were subsequently initiated to further optimise the potential RP2D. These cohorts are currently ongoing. The median number of prior treatments was 2 (range 1-6). 12 patients received a prior FLT3 inhibitor including midostaurin, gilteritinib or sorafenib and 8/12 patients received ≥2 prior FLT3 inhibitors. 3 patients received prior ASCT. The most common treatment-emergent adverse events (TEAEs) ≥20% were: diarrhea (54.1%), fatigue (54.1%), febrile neutropenia (51.4%), decreased appetite (43.2%), dyspnea (35.1%), somnolence (29.7%), constipation (27.0%), ataxia (27.0%) and nausea (24.3%). 23.3% of TEAEs were > grade 3. The most common treatment related AEs (TRAEs, all grades ≥10%) were decreased appetite (29.7%), somnolence (29.7%), ataxia (27.0%), fatigue (24.3%), diarrhea (13.5%), nausea (13.5%) and dizziness (16.2%). No treatment-related death has been reported across all cohorts. Most events were manageable by temporary dose reductions and or/short interruptions. All events of ataxia and somnolence were reversible after a short treatment interruption. Across all cohorts, 18 patients achieved stable disease (SD) as best response (median no. of cycles = 3, range 1-11). 1 patient continued treatment for 11 cycles (100mg BID, FLT3wt) and another for 8 cycles (140 mg BID, FLT3-ITD) with clinical benefit. 1 patient achieved a best response of CR MRD- (150mg BID, FLT3wt) with aCRi first detected at C6D1 (2% blast, down from 38% at screening and 80% at C3D1) and confirmed with CR MRD- at C7D1 by flow cytometry. Treatment is still ongoing at C10 and patient remains transfusion independent for 4 months. Evidence of peripheral blast response was observed in 5 patients, with complete disappearance of peripheral blasts compared to baseline after a median time of 2 months on treatment. Data from the ongoing dose optimisation cohorts will be presented at the congress. Conclusions This extended data set confirms thatEP0042 has acceptable tolerability and safety. Two patient cohorts are ongoing to establish the optimum continuous dose regimen to take forward. Promising evidence of clinical benefit has been observed including a durable CR MRD-. This remission in a patient with FLT3 wild type AML indicates that EP0042 may have broader activity in AML, beyond FLT3 mutated disease. Dose optimisation cohorts are continuing to identify the RP2D. Further cohorts are planned for evaluation of EP0042 in combination with standard of care therapies.

Analysis of the transient dose rate effect on clock resources of JXCV5SX95T FPGA

This paper qualitatively investigates the transient dose rate effect (TDRE) on clock resources of the JXCV5SX95T FPGA, including DLL (Delay Locked Loop), PLL (Phase Locked Loop), and GCB (General Clock Buffer). Our previous experimental results showed that the sensitivity of different clock resources in the JXCV5SX95T FPGA presents prominent discrepancies. In particular, all input/outputs (IOs) present a simultaneous glitch during irradiations. And, the DLL and PLL would appear special short interrupt failures in some cases. However, the experimental results lack a mechanism analysis. In order to investigate the intrinsic mechanisms and in particular to compare the sensitivity differences between the PLL and DLL circuits, corresponding TCAD and SPICE simulations are performed. Both relevant DLL and PLL circuits are established in the SPICE simulator. The radiation-induced photocurrents are calculated by TCAD, and introduced into SPICE simulations. First, with an ideal power supply, the radiation performances of the DLL and PLL are simulated, and the influence of two factors are analyzed, including the substrate size of the TCAD model and the charge pump type of the DLL and PLL. Second, typical non-ideal power supply and IO models are used in the simulations. Simulation results indicate that the short interrupt of the PLL and DLL in experiments should result from the relevant power regulators in the FPGA. Last, piecewise linear voltage sources are applied to simulate the noise on the power supply in experiments, and their influence on the PLL, DLL, IOs are analyzed. Simulation results show that the simultaneous glitch in experiments may be mainly from the power supply noise, and the radiation effect of IOs would also contribute to this failure to some degree.

Spatial and temporal variability of saturated areas during rainfall-runoff events

Abstract Spatially distributed hydrological model Mike SHE was used as a diagnostic tool to provide information on possible overland flow source areas in the mountain catchment of Jalovecký Creek (area 22.2 km2, elevation range 820–2178 m a.s.l.) during different rainfall-runoff events. Selected events represented a sequence of several smaller, consecutive events, a flash flood event and two large events caused by frontal precipitation. Simulation of hourly runoff was better for runoff events caused by heavy rainfalls of longer duration than for the flash flood or consecutive smaller runoff events. Higher soil moisture was simulated near the streamflow network and larger possibly saturated areas were located mainly in the upper parts of mountain valleys. The most pronounced increase in the areal extent of possibly saturated areas (from 6.5% to 68.6% of the catchment area) was simulated for the event with high peak discharge divided by a short rainfall interruption. Rainfall depth exceeding 100 mm caused a large increase in the potentially saturated areas that covered subsequently half of the catchment area or more. A maximum integral connectivity scale representing the average distance over which individual pixels were connected varied for the selected events between 45 and 6327 m.