Soft sensor for content prediction in an integrated continuous pharmaceutical formulation line based on the residence time distribution of unit operations

In this study, a concentration predicting soft sensor was achieved based on the Residence Time Distribution (RTD) of an integrated, three-step pharmaceutical formulation line. The RTD was investigated with color-based tracer experiments using image analysis. Twin-screw wet granulation (TSWG) was directly coupled with a horizontal fluid bed dryer and an oscillating mill. Based on integrated measurement, we proved that it is also possible to couple the unit operations in silico. Three surrogate tracers were produced with a coloring agent to investigate the separated unit operations and the solid and liquid inputs of the TSWG. The soft sensor’s prediction was compared to validating experiments of a 0.05 mg/g (15% of the nominal) concentration change with High-Performance Liquid Chromatography (HPLC) reference measurements of the active ingredient proving the adequacy of the soft sensor (RMSE < 4%)

Biológiai jelek információjának diagnosztikai célú kutatása rendszerelméleti megközelítéssel = System theory approach of the information of the biological signals for diagnostics

Kidolgoztunk egy új magzati fonokardiográfiás mérési és jelfeldolgozási módszert az FHR hosszú távú robusztus meghatározására. Létrehoztunk egy neurális hálzatokat alkalmazó légzési rendellenesség felismerő rendszert. Megalkottuk számos, a csecsemősírás jellemzésére szolgáló paraméter meghatározásának módszerét, és összehasonlítottuk több száz csecsemő sírását e paraméterek alapján. Több betegségcsoportnál jellemző eltéréseket tapasztaltunk. Neurolingvisztikai kutatásunk során megvalósítottunk egy lingvisztikai adatbázis-struktúrát és a hozzá tartozó adatbázis-kezelő segédprogramot. Nyelvi adatbázisunk struktúráját kiterjesztettük, valamint megvalósítottunk néhány új algoritmust, melyek lehetővé teszik a terápiás gyakorlatok során magasabb nyelvi modalitások felhasználását is. | We've worked out a novel vital phonocardiographic measurement ad signal processing method to determine robustly the longterm fetal heart rate (FHR). We'v created system to recognize respiration disorders containing a neural network. We developed new algorithms and methods in the analysis of the infant cry to check disorders during infancy. We analysed the crying sound from hundreds of infanst and found differences between healthy and unhealthy infants. In our neurolinguistic research we created a novel computer-aided training and rehabilitaion approach to the therapy of aphasia. The system helps to treat and overcome the most severe consequences of this language disorder. The developed system is embedded into a tele-rehabilitation framework, which offers a uniform interface for various telecare applications

Process Design of Continuous Powder Blending Using Residence Time Distribution and Feeding Models

The present paper reports a thorough continuous powder blending process design of acetylsalicylic acid (ASA) and microcrystalline cellulose (MCC) based on the Process Analytical Technology (PAT) guideline. A NIR-based method was applied using multivariate data analysis to achieve in-line process monitoring. The process dynamics were described with residence time distribution (RTD) models to achieve deep process understanding. The RTD was determined using the active pharmaceutical ingredient (API) as a tracer with multiple designs of experiment (DoE) studies to determine the effect of critical process parameters (CPPs) on the process dynamics. To achieve quality control through material diversion from feeding data, soft sensor-based process control tools were designed using the RTD model. The operation block model of the system was designed to select feasible experimental setups using the RTD model, and feeder characterizations as digital twins, therefore visualizing the output of theoretical setups. The concept significantly reduces the material and instrumental costs of process design and implementation

Akut, kritikus alsó végtagi ischaemia kezelése katéteres thrombolysissel

Bevezetés: Az akut alsó végtagi ischaemia nagy klinikai jelentőségét gyakori előfordulása és súlyos szövődményei (amputáció, halálozás) okozzák. A műtéti megoldás mellett a katéterrel végzett thrombolysis jelent terápiás lehetőséget, használata azonban nem terjedt el széles körben hazánkban. Célkitűzés: A katéterrel végzett thrombolysis hatékonyságának és biztonságosságának megállapítása akut alsó végtagi ischaemia esetén. Módszer: A Semmelweis Egyetem Városmajori Szív- és Érgyógyászati Klinikáján 2012. 03. 01. és 2019. 12. 31. kö- zött akut alsó végtagi ischaemia miatt katéteres thrombolysisen átesett 40 beteg (átlagéletkor: 64 év, SD: ±11,79; 25 férfi, 62,5%) adatait elemeztük retrospektív vizsgálat során. Eredmények: 40 páciens esetében 42 katéteres lysist hajtottunk végre. A medián alteplázbolus 5 mg (IQR: 5), a medián folyamatos dózis 2 mg/h (IQR: 0,8) volt. A lysisek közül 23 (54,76%) volt sikeres, ebből 16 (69,57%) esetben végeztünk kiegészítő percutan beavatkozást. Vérzés miatt 5 (11,9%), elzáródás miatt 3 (7,14%) betegen végeztünk sürgős beavatkozást. A leggyakoribb posztoperatív szövődmény az amputáció (17,5%), a haematoma (11,9%) és a distalis embolisatio (7,14%) volt. 16 (40%) esetben végeztünk a lizált érszakaszon később beavatkozást. 11 (27,5%) betegnél történt major amputáció. A posztoperatív 30 napon belüli mortalitás 2,5% volt. Az átlagos beavatkozásmentes időszak 1626 nap (SD: ±1710), az átlagos amputációmentes túlélés 2038 nap (SD: ±1665) volt. A lysis alatt adott intravénás heparin nem befolyásolta a nyitva maradást és az amputációt. Következtetés: A katéterrel végzett thrombolysis terápiás lehetőség akut alsó végtagi ischaemia esetén. Sikeres lysis esetén is gyakran kell endovascularis intervenciót végezni. Katéteres thrombolysis alkalmazásakor számolni kell a gyakori korai szövődmény és a késői reintervenció veszélyével. A pontos terápiás protokoll kialakításához további vizsgálatokra van szükség

Quiescent-Interval Single-Shot Magnetic Resonance Angiography May Outperform Carbon-Dioxide Digital Subtraction Angiography in Chronic Lower Extremity Peripheral Arterial Disease

Nephroprotective imaging in peripheral arterial disease (PAD) is often crucial. We compared the diagnostic performance of non-contrast Quiescent-interval single-shot magnetic resonance angiography (QISS MRA) and carbon-dioxide digital subtraction angiography (CO2 DSA) in chronic lower extremity PAD patients. A 19-segment lower extremity arterial model was used to assess the degree of stenosis (none, &lt;50%, 50&ndash;70%, &gt;70%) and the image quality (5-point Likert scale: 1-non-diagnostic, 5-excellent image quality). Intra-class correlation coefficient (ICC) was calculated for inter-rater reliability. Diagnostic accuracy and interpretability were evaluated using CO2 DSA as a reference standard. 523 segments were evaluated in 28 patients (11 male, mean age: 71 &plusmn; 9 years). Median and interquartile range of subjective image quality parameters for QISS MRA were significantly better compared to CO2 DSA for all regions: (aortoiliac: 4 [4&ndash;5] vs. 3 [3&ndash;4]; femoropopliteal: 4 [4&ndash;5] vs. 4 [3&ndash;4]; tibioperoneal: 4 [3&ndash;5] vs. 3 [2&ndash;3]; all regions: 4 [4&ndash;5] vs. 3 [3&ndash;4], all p &lt; 0.001). QISS MRA out-performed CO2 DSA regarding interpretability (98.3% vs. 86.0%, p &lt; 0.001). Diagnostic accuracy parameters of QISS MRA for the detection of obstructive luminal stenosis (70%&lt;) as compared to CO2 DSA were as follows: sensitivity 82.6%, specificity 96.9%, positive predictive value 89.1%, negative predictive value 94.8%. Regarding the degree of stenosis, interobserver variability for all regions was 0.97 for QISS MRA and 0.82 for CO2 DSA. QISS MRA proved to be superior to CO2 DSA regarding subjective image quality and interpretability for the imaging of chronic lower extremity PAD

Finding the optimal access for proximal upper limb artery (PULA) interventions: Lessons learned from the PULA multicenter registry

Objective The multicenter proximal upper limb artery (PULA) Registry was created to study the optimal puncture sites for the interventions involving the subclavian, axillary, and innominate arteries. Background Little is known about the optimal vascular access for PULA interventions, despite the well-known technical complexity of these procedures. Methods We performed the retrospective analysis of consecutive patients treated for symptomatic steno-occlusive disease of the proximal upper limb arteries between January 2015 and December 2019 in three high-volume centers. Acute thrombotic occlusions were excluded from the study. Results Two hundred and seventy-two patients were treated for significant stenosis and 108 for total occlusion. The baseline patient's characteristics were similar, except for the higher median age of the stenotic patients: 68.5 years (31.1; 90.0) versus 64 years (38.0; 86.0) p = 0.0015. Successful revascularization rate was higher in the stenotic group 93.75% (255/272) versus 86.11% (93/108) p = 0.0230, while the procedure length 27 min (8; 133) versus 46 min (7; 140) p = 0.0001 and fluoroscopy times 439 s (92; 2993) versus 864 s (86; 4176) p = 0.0001 were higher in the occlusion group. The main adverse event rate was similarly low. Dual access was used more often to treat occlusions (60.19% (65/108) vs. 11.40% (31/272) p = 0.0001) without significantly increasing the complication rate. The safest access was ultrasound-guided distal radial artery puncture, significantly better than conventional radial access with 0% (0/31) versus 13.6% (18/131) p = 0.0253 complication. Conclusions The percutaneous revascularization of proximal upper limb arteries is a safe and effective. Dual access can be applied to increase treatment efficacy, without significantly compromising safety