Search

Introduction Pulmonary arterial hypertension (PAH) is a rare and severe disease for which most of the evidence about prognostic factors, evolution and treatment efficacy comes from cohorts, registries and clinical trials. We therefore aimed to develop and validate a new PAH identification algorithm that can be used in the French healthcare database “Système National des Données de Santé (SNDS)”. Methods We developed and validated the algorithm using the Grenoble Alpes University Hospital medical charts. We first identified PAH patients following a previously validated algorithm, using in-hospital ICD-10 (10th revision of the International Statistical Classification of Diseases) codes, right heart catheterisation procedure and PAH-specific treatment dispensing. Then, we refined the latter with the exclusion of chronic thromboembolic pulmonary hypertension procedures and treatment, the main misclassification factor. Second, we validated this algorithm using a gold standard review of in-hospital medical charts and calculated sensitivity, specificity, positive and negative predictive value (PPV and NPV) and accuracy. Finally, we applied this algorithm in the French healthcare database and described the characteristics of the identified patients. Results In the Grenoble University Hospital, we identified 252 unique patients meeting all the algorithm's criteria between 1 January 2010 and 30 June 2022, and reviewed all medical records. The sensitivity, specificity, PPV, NPV and accuracy were 91.0%, 74.3%, 67.9%, 93.3% and 80.6%, respectively. Application of this algorithm to the SNDS yielded the identification of 9931 patients with consistent characteristics compared to PAH registries. Conclusion Overall, we propose a new PAH identification algorithm developed and adapted to the French specificities that can be used in future studies using the French healthcare database.

Abstract Background The positive effects of goal-directed hemodynamic therapy (GDHT) on patient-orientated outcomes have been demonstrated in various clinical scenarios; however, the effects of fluid management in neurosurgery remain unclear. Therefore, this study was aimed at assessing the safety and feasibility of GDHT using non-invasive hemodynamic monitoring in elective neurosurgery. The incidence of postoperative complications was compared between GDHT and control groups. Methods We conducted a single-center randomized pilot study with an enrollment target of 34 adult patients scheduled for elective neurosurgery. We randomly assigned the patients equally into control and GDHT groups. The control group received standard therapy during surgery and postoperatively, whereas the GDHT group received therapy guided by an algorithm based on non-invasive hemodynamic monitoring. In the GDHT group, we aimed to achieve and sustain an optimal cardiac index by using non-invasive hemodynamic monitoring and bolus administration of colloids and vasoactive drugs. The number of patients with adverse events, feasibility criteria, perioperative parameters, and incidence of postoperative complications was compared between groups. Results We successfully achieved all feasibility criteria. The GDHT protocol was safe, because no patients in either group had unsatisfactory brain tissue relaxation after surgery or brain edema requiring therapy during surgery or 24 h after surgery. Major complications occurred in two (11.8%) patients in the GDHT group and six (35.3%) patients in the control group (p = 0.105). Conclusions Our results suggested that a large randomized trial evaluating the effects of GDHT on the incidence of postoperative complications in elective neurosurgery should be safe and feasible. The rate of postoperative complications was comparable between groups. Trial registration Trial registration: ClininalTrials.gov, registration number: NCT04754295, date of registration: February 15, 2021.

The mechanical components manufacturing industry is carried out through turning processes using CNC machines. Improving productivity and improving product quality in the CNC process is necessary. Automating operations at the CNC process with Industry 4.0 technology at low cost is a direction in the right direction with the development trend of Industry 4.0 technology. Making decisions to improve CNC processes at operations and implementing continuous improvement is an urgent activity. Industry 4.0 technology helps connect data between customer companies, business sectors, and supply chain partners in a more specific and simple way. Commonly connected data between companies helps decision-makers at each company have a common source of analytical data to make more effective production and business development decisions. Industry 4.0 technologies are the subject of much research, but it is important to consider how to integrate them into the manufacturing world in the most efficient and effective way possible. Manufacturers will benefit from this article’s additional insights to solve their problems more effectively. This paper proposes a Hybrid Six Sigma methodology based on Fuzzy TOPSIS and PLS-SEM methods. First, the Fuzzy TOPSIS method helps decision-makers to select problem points for improvement in an unknown environment to implement continuous improvement. Second, the PLS-SEM method evaluates the impact factors of the results of continuous improvement at the mechanical component factory. The Industry 4.0 technology is proposed to be designed, tested, and installed in the CNC manufacturing process. As a result of this study, the product length dimensional error rate decreased from 54.90% per month to zero defects, saving ${\$}9593$ in annual production costs. Research machines are semi-automatic and cannot increase or digitize their performance because of studies on the application of low-cost Industry 4.0 technology systems to increase the capacity of industrial processes. This study contributes by using Industry 4.0 technology’s low-cost way to improve manufacturing processes using the Hybrid DMAIC method in Six Sigma methodology. This hybrid approach is adaptable and can be used with different business process improvement models.

Customers’ requirements for product quality are increasing and more and more manufacturing companies are improving the quality of processing conditions at each production process by applying advances in Internet Technologies, Internet of Things, Big Data, Industry 4.0, Industrial Engineering Tools, Multi-objective optimization algorithms, Digital Numerical Control (DNC) method, and Six Sigma tools to improve productivity and quality of product. Continuous improvement of the manufacturing process presents a huge opportunity for the transformation of the normal production model to smart manufacturing. Manufacturing condition data, production data, quality of product data, and power quality data are measured and collected in real-time forming big data fed into operation analysis of the development strategy of the manufacturing company. In this study, the implementation of the Hybrid DMAIC (Define-Measure-Analyze-Improve-Control) method in six sigma is presented in detail based on the statistical hypothesis testing techniques for analyzing production data applied at the measurement phase, Multi-objective decision Fuzzy TOPSIS techniques applied to choose the best improvement solution applied at the analysis phase, Multi-objective optimization technique optimizes production conditions, and the DNC method performs automatically program call by RFID system applied at improvement phase, measurement technique, real-time measurement result collection and analysis by Industry 4.0 system and the method of phase shift is used to keep Total Harmonic Distortion (THD) and Total Demand Distortion (TDD) less than 5% within the international standard limits defined by IEEE 519:2022 and IEC 61000 applied at control phase. A common data system linking all activities at a particular manufacturing process and hybrid DMAIC in Six Sigma continuous improvement model is proposed in this study. This research’s results, the rate of occurrence of smaller-than-standard outer diameter defects decreased from 31.20% to 4.5% per month, the grinding process productivity achieved 610 pcs per day while the number of operators decreased from 4 people to 2 people per day, and productivity per person per hour increased from 15 PCS to 30 PCS. The profit is achieved at 11,184 USD per year. The Hybrid DMAIC method in Six Sigma is considered a model of continuous improvement that can be applied to production processes in manufacturing companies. The Hybrid DMAIC method in Six Sigma is simple to implement, easy to deploy into the real environment at production processes, and uses commercial software such as Minitab, LABVIEW, and SPSS. Manufacturing companies apply this research model to help improve competitiveness, improve business performance, and improve customer satisfaction.

Abstract Background Accumulation of lipid droplets (LDs) was recently observed in pyometra-affected uteri. As data about their nature and function are missing we intended to compare the localization, quality and quantity of LDs in canine healthy and pyometra-affected tissues and in an in vitro model. Methods and results We characterized LDs in healthy and pyometra uterine tissue samples as well as in canine endometrial epithelial cells (CEECs) in vitro by means of histochemistry, immunohistochemistry, transmission electron microscopy, western blot, and RT-qPCR. Oil Red O (ORO) staining and quantification as well as p-phenylenediamine staining showed a higher number of LDs in epithelial cells of pyometra samples. Immunohistochemistry revealed that the amount of LDs coated by perilipin2 (PLIN2) protein was also higher in pyometra samples. Transmission electron microscopy showed an increase of LD size in surface and glandular epithelial cells of pyometra samples. In cell culture experiments with CEECs, supplementation with oleic acid alone or in combination with cholesterol lead to an increased LD accumulation. The expression of PLIN2 at protein and mRNA level was also higher upon oleic acid supplementation. Most LDs were double positive for ORO and PLIN2. However, ORO positive LDs lacking PLIN2 coating or LDs positive for PLIN2 but containing a lipid class not detectable by ORO staining were identified. Conclusions We found differences in the healthy and pyometra-affected endometrium with respect to LDs size. Moreover, several kinds of LDs seem to be present in the canine endometrium. In vitro studies with CEECs could show their responsiveness to external lipids. Since epithelial cells reacted only to oleic acid stimulation, we assume that the cyclic lipid accumulation in the canine endometrium is based mainly on triglycerides and might serve as energy provision for the developing early embryo. Further studies are necessary to verify the complex role of lipids in the healthy and pyometra-affected canine endometrium.

This article presents a comprehensive system for testing and verifying shunt active power filter control methods. The aim of this experimental platform is to provide tools to a user to objectively compare the individual control methods. The functionality of the system was verified on a hardware platform using least mean squares and recursive least squares algorithms. In the experiments, an average relative suppression of the total harmonic distortion of 22% was achieved. This article describes the principle of the shunt active power filter, the used experimental platform of the controlled current injection source, its control system based on virtual instrumentation and control software and ends with experimental verification. The discussion of the paper outlines the extension of the experimental platform with the cRIO RTOS control system to reduce the latency of reference current generation and further planned research including motivation.

Purpose: Play is a critical aspect of children's development, and researchers have long argued that symbolic deficits in play may be diagnostic of developmental disabilities. This study examined whether deficits in play emerge as a function of developmental disabilities and whether our perceptions of play are colored by differences in language and behavioral presentations. Method: Ninety-three children participated in this study (typically developing [TD]; n = 23, developmental language disorders [DLD]; n = 24, attention-deficit/ hyperactivity disorder [ADHD]; n = 26, and autism spectrum disorder [ASD]; n = 20). Children were videotaped engaging in free-play. Children's symbolic play (imagination, organization, elaboration, and comfort) was scored under conditions of both audible language and no audible language to assess diagnostic group differences in play and whether audible language impacted raters' perception of play. Results: Significant differences in play were evident across diagnostic groups. The presence of language did not alter play ratings for the TD group, but differences were found among the other diagnostic groups. When language was audible, children with DLD and ASD (but not ADHD) were scored poorly on play compared to their TD peers. When language was not audible, children with DLD were perceived to play better than when language was audible. Conversely, children with ADHD showed organizational deficits when language was not available to support their play. Finally, children with ASD demonstrated poor play performance regardless of whether language was audible or not. Conclusions: Language affects our understanding of play skills in some young children. Parents, researchers, and clinicians must be careful not to underestimate or overestimate play based on language presentation. Differential skills in language have the potential to unduly influence our perceptions of play for children with developmental disabilities.

Human and non-human primates produce rhythmical sounds as soon as they are born. These early vocalizations are important for soliciting the attention of caregivers. How they develop remains a mystery. The orofacial movements necessary for producing these vocalizations have distinct spatiotemporal signatures. Therefore, their development could potentially be tracked over the course of prenatal life. We densely and longitudinally sampled fetal head and orofacial movements in marmoset monkeys using ultrasound imaging. We show that orofacial movements necessary for producing rhythmical vocalizations differentiate from a larger movement pattern that includes the entire head. We also show that signature features of marmoset infant contact calls emerge prenatally as a distinct pattern of orofacial movements. Our results establish that aspects of the sensorimotor development necessary for vocalizing occur prenatally, even before the production of sound.

Shunt Adaptive Power Filter (SAPF) is widely used in the performance of power quality improvement activities in the power supply industry for processing industries or civil power sources in the world today based on its simplicity, transparency, high reliability, efficiency, and reliability, and their powerful compensating current-providing nature. The PI controller integrated into the SAPF operation mechanism works with extra high efficiency in selecting the current to compensate for the lost current generated in the power supply due to harmonics generated by the Kp, Ki parameter values. The system operates by the PWM method for bridge rectifier circuits that perform the function of selecting the appropriate compensating current, providing correct compensation for the amount of current loss in the power supply. Adjusting the Kp, Ki parameter to reach the optimal value by different methods is a promising and popular research direction at present. The Kp, Ki parameter serves the right purpose for the PI controller to generate enough PWM pulses to excite the bridge rectifiers to generate just the right amount of compensating current and enough current to be compensated on the power supply. The commonly used Kp, Ki parameter adjustment methods include the Ziegler Nichols closed-loop vibration method, the P-Q theoretical method, and several other methods. This study conducts a comprehensive review of the literature on modern strategies for adjusting the Kp, Ki parameters in the PI controller in the SAPF suite by using the meta-heuristic optimization method. This study performs classification according to the operation mode of meta-heuristic optimization methods to adjust the Kp, Ki parameter to control the PI to select the correct PWM frequency to activate bridge rectifiers to select the most optimal compensation current to compensate for the loss of current on the power supply to meet the goal of improving power quality in accordance with IEEE 519-2022 standard, leading to the total harmonic distortion (THD) value is below 5%. The study presents in detail some meta-heuristic optimization algorithms, including applications, mathematical equations, and implementation of flow charts for SAPF and provides some open problems for future research. The main objective of this study is to provide an overview of applying meta-heuristic optimization algorithms to the Kp, Ki parameter tuning of PI controllers.

The present study aimed to establish novel canine osteosarcoma cell lines (COS3600, COS3600B, COS4074) and characterize the recently described COS4288 cells. The established D-17 cell line served as a reference. Analyzed cell lines differed notably in their biological characteristics. Calculated doubling times were between 22 h for COS3600B and 426 h for COS4074 cells. COS3600B and COS4288 cells produced visible colonies after anchorage-independent growth in soft agar. COS4288 cells were identified as cells with the highest migratory capacity. All cells displayed the ability to invade through an artificial basement membrane matrix. Immunohistochemical analyses revealed the mesenchymal origin of all COS cell lines as well as positive staining for the osteosarcoma-relevant proteins alkaline phosphatase and karyopherin α2. Expression of p53 was confirmed in all tested cell lines. Gene expression analyses of selected genes linked to cellular immune checkpoints (CD270, CD274, CD276), kinase activity (MET, ERBB2), and metastatic potential (MMP-2, MMP-9) as well as selected long non-coding RNA (MALAT1) and microRNAs (miR-9, miR-34a, miR-93) are provided. All tested cell lines were able to grow as multicellular spheroids. In all spheroids except COS4288, calcium deposition was detected by von Kossa staining. We believe that these new cell lines serve as useful biological models for future studies.

Protective layers include special weld deposits, utilizing e.g. ferrous, nickel or cobalt matrices in combination with tungsten carbide particles, which according to their properties belong among so-called composite materials, and which have slowly replaced conventional components produced from tool steels. A weld deposit with an iron-based matrix (Megafil A864M) was used, with tungsten carbide particles on steel S235JR+N. The high-level hardness of tungsten carbides together with a tough matrix allows achieving high resistance to different types of wear. This resistance significantly increases the lifetime of machine components and thus it reduces the costs of companies needed for repairs or the replacements of machine parts.

Patients with the most common and aggressive form of high-grade glioma, glioblastoma multiforme, have poor prognosis and few treatment options. In 2 immunocompetent mouse brain tumor models (CT26-BALB/c and Tu-2449-B6C3F1), we showed that a nonlytic retroviral replicating vector (Toca 511) stably delivers an optimized cytosine deaminase prodrug activating gene to the tumor lesion and leads to long-term survival after treatment with 5-fluorocytosine (5-FC). Survival benefit is dose dependent for both vector and 5-FC, and as few as 4 cycles of 5-FC dosing after Toca 511 therapy provides significant survival advantage. In the virally permissive CT26-BALB/c model, spread of Toca 511 to other tissues, particularly lymphoid tissues, is detectable by polymerase chain reaction (PCR) over a wide range of levels. In the Tu-2449-B6C3F1 model, Toca 511 PCR signal in nontumor tissues is much lower, spread is not always observed, and when observed, is mainly detected in lymphoid tissues at low levels. The difference in vector genome spread correlates with a more effective antiviral restriction element, APOBEC3, present in the B6C3F1 mice. Despite these differences, neither strain showed signs of treatment-related toxicity. These data support the concept that, in immunocompetent animals, a replicating retroviral vector carrying a prodrug activating gene (Toca 511) can spread through a tumor mass, leading to selective elimination of the tumor after prodrug administration, without local or systemic pathology. This concept is under investigation in an ongoing phase I/II clinical trial of Toca 511 in combination with 5-FC in patients with recurrent high-grade glioma (www.clinicaltrials.gov NCT01156584).