Search results for: Gabriele I. Stangl
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 17

Search results for: Gabriele I. Stangl

17 Prenatal Paraben Exposure Impacts Infant Overweight Development and in vitro Adipogenesis

Authors: Beate Englich, Linda Schlittenbauer, Christiane Pfeifer, Isabel Kratochvil, Michael Borte, Gabriele I. Stangl, Martin von Bergen, Thorsten Reemtsma, Irina Lehmann, Kristin M. Junge

Abstract:

The worldwide production of endocrine disrupting compounds (EDC) has risen dramatically over the last decades, as so has the prevalence for obesity. Many EDCs are believed to contribute to this obesity epidemic, by enhancing adipogenesis or disrupting relevant metabolism. This effect is most tremendous in the early prenatal period when priming effects find a highly vulnerable time window. Therefore, we investigate the impact of parabens on childhood overweight development and adipogenesis in general. Parabens are ester of 4-hydroxy-benzoic acid and part of many cosmetic products or food packing. Therefore, ubiquitous exposure can be found in the westernized world, with exposure already starting during the sensitive prenatal period. We assessed maternal cosmetic product consumption, prenatal paraben exposure and infant BMI z-scores in the prospective German LINA cohort. In detail, maternal urinary concentrations (34 weeks of gestation) of methyl paraben (MeP), ethyl paraben (EtP), n-propyl paraben (PrP) and n-butyl paraben (BuP) were quantified using UPLC-MS/MS. Body weight and height of their children was assessed during annual clinical visits. Further, we investigated the direct influence of those parabens on adipogenesis in-vitro using a human mesenchymal stem cell (MSC) differentiation assay to mimic a prenatal exposure scenario. MSC were exposed to 0.1 – 50 µM paraben during the entire differentiation period. Differentiation outcome was monitored by impedance spectrometry, real-time PCR and triglyceride staining. We found that maternal cosmetic product consumption was highly correlated with urinary paraben concentrations at pregnancy. Further, prenatal paraben exposure was linked to higher BMI Z-scores in children. Our in-vitro analysis revealed that especially the long chained paraben BuP stimulates adipogenesis by increasing the expression of adipocyte specific genes (PPARγ, ADIPOQ, LPL, etc.) and triglyceride storage. Moreover, we found that adiponectin secretion is increased whereas leptin secretion is reduced under BuP exposure in-vitro. Further mechanistic analysis for receptor binding and activation of PPARγ and other key players in adipogenesis are currently in process. We conclude that maternal cosmetic product consumption is linked to prenatal paraben exposure of children and contributes to the development of infant overweight development by triggering key pathways of adipogenesis.

Keywords: adipogenesis, endocrine disruptors, paraben, prenatal exposure

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16 Sourcing and Compiling a Maltese Traffic Dataset MalTra

Authors: Gabriele Borg, Alexei De Bono, Charlie Abela

Abstract:

There on a constant rise in the availability of high volumes of data gathered from multiple sources, resulting in an abundance of unprocessed information that can be used to monitor patterns and trends in user behaviour. Similarly, year after year, Malta is also constantly experiencing ongoing population growth and an increase in mobilization demand. This research takes advantage of data which is continuously being sourced and converting it into useful information related to the traffic problem on the Maltese roads. The scope of this paper is to provide a methodology to create a custom dataset (MalTra - Malta Traffic) compiled from multiple participants from various locations across the island to identify the most common routes taken to expose the main areas of activity. This use of big data is seen being used in various technologies and is referred to as ITSs (Intelligent Transportation Systems), which has been concluded that there is significant potential in utilising such sources of data on a nationwide scale.

Keywords: Big Data, vehicular traffic, traffic management, mobile data patterns

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15 Experimental Chip/Tool Temperature FEM Model Calibration by Infrared Thermography: A Case Study

Authors: Riccardo Angiuli, Michele Giannuzzi, Rodolfo Franchi, Gabriele Papadia

Abstract:

Temperature knowledge in machining is fundamental to improve the numerical and FEM models used for the study of some critical process aspects, such as the behavior of the worked material and tool. The extreme conditions in which they operate make it impossible to use traditional measuring instruments; infrared thermography can be used as a valid measuring instrument for temperature measurement during metal cutting. In the study, a large experimental program on superduplex steel (ASTM A995 gr. 5A) cutting was carried out, the relevant cutting temperatures were measured by infrared thermography when certain cutting parameters changed, from traditional values to extreme ones. The values identified were used to calibrate a FEM model for the prediction of residual life of the tools. During the study, the problems related to the detection of cutting temperatures by infrared thermography were analyzed, and a dedicated procedure was developed that could be used during similar processing.

Keywords: machining, infrared thermography, FEM, temperature measurement

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14 Vr-GIS and Ar-GIS In Education: A Case Study

Authors: Ilario Gabriele Gerloni, Vincenza Carchiolo, Alessandro Longheu, Ugo Becciani, Eva Sciacca, Fabio Vitello

Abstract:

ICT tools and platforms endorse more and more educational process. Many models and techniques for people to be educated and trained about specific topics and skills do exist, as classroom lectures with textbooks, computers, handheld devices and others. The choice to what extent ICT is applied within learning contexts is related to personal access to technologies as well as to the infrastructure surrounding environment. Among recent techniques, the adoption of Virtual Reality (VR) and Augmented Reality (AR) provides significant impulse in fully engaging users senses. In this paper, an application of AR/VR within Geographic Information Systems (GIS) context is presented. It aims to provide immersive environment experiences for educational and training purposes (e.g. for civil protection personnel), useful especially for situations where real scenarios are not easily accessible by humans. First acknowledgments are promising for building an effective tool that helps civil protection personnel training with risk reduction.

Keywords: education, virtual reality, augmented reality, GIS, civil protection

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13 Age-Dependent Anatomical Abnormalities of the Amygdala in Autism Spectrum Disorder and their Implications for Altered Socio-Emotional Development

Authors: Gabriele Barrocas, Habon Issa

Abstract:

The amygdala is one of various brain regions that tend to be pathological in individuals with autism spectrum disorder (ASD). ASD is a prevalent and heterogeneous developmental disorder affecting all ethnic and socioeconomic groups and consists of a broad range of severity, etiology, and behavioral symptoms. Common features of ASD include but are not limited to repetitive behaviors, obsessive interests, and anxiety. Neuroscientists view the amygdala as the core of the neural system that regulates behavioral responses to anxiogenic and threatening stimuli. Despite this consensus, many previous studies and literature reviews on the amygdala’s alterations in individuals with ASD have reported inconsistent findings. In this review, we will address these conflicts by highlighting recent studies which reveal that anatomical and related socio-emotional differences detected between individuals with and without ASD are highly age-dependent. We will specifically discuss studies using functional magnetic resonance imaging (fMRI), structural MRI, and diffusion tensor imaging (DTI) to provide insights into the neuroanatomical substrates of ASD across development, with a focus on amygdala volumes, cell densities, and connectivity.

Keywords: autism, amygdala, development, abnormalities

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12 Graph Based Traffic Analysis and Delay Prediction Using a Custom Built Dataset

Authors: Gabriele Borg, Alexei Debono, Charlie Abela

Abstract:

There on a constant rise in the availability of high volumes of data gathered from multiple sources, resulting in an abundance of unprocessed information that can be used to monitor patterns and trends in user behaviour. Similarly, year after year, Malta is also constantly experiencing ongoing population growth and an increase in mobilization demand. This research takes advantage of data which is continuously being sourced and converting it into useful information related to the traffic problem on the Maltese roads. The scope of this paper is to provide a methodology to create a custom dataset (MalTra - Malta Traffic) compiled from multiple participants from various locations across the island to identify the most common routes taken to expose the main areas of activity. This use of big data is seen being used in various technologies and is referred to as ITSs (Intelligent Transportation Systems), which has been concluded that there is significant potential in utilising such sources of data on a nationwide scale. Furthermore, a series of traffic prediction graph neural network models are conducted to compare MalTra to large-scale traffic datasets.

Keywords: graph neural networks, traffic management, big data, mobile data patterns

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11 Loan Supply and Asset Price Volatility: An Experimental Study

Authors: Gabriele Iannotta

Abstract:

This paper investigates credit cycles by means of an experiment based on a Kiyotaki & Moore (1997) model with heterogeneous expectations. The aim is to examine how a credit squeeze caused by high lender-level risk perceptions affects the real prices of a collateralised asset, with a special focus on the macroeconomic implications of rising price volatility in terms of total welfare and the number of bankruptcies that occur. To do that, a learning-to-forecast experiment (LtFE) has been run where participants are asked to predict the future price of land and then rewarded based on the accuracy of their forecasts. The setting includes one lender and five borrowers in each of the twelve sessions split between six control groups (G1) and six treatment groups (G2). The only difference is that while in G1 the lender always satisfies borrowers’ loan demand (bankruptcies permitting), in G2 he/she closes the entire credit market in case three or more bankruptcies occur in the previous round. Experimental results show that negative risk-driven supply shocks amplify the volatility of collateral prices. This uncertainty worsens the agents’ ability to predict the future value of land and, as a consequence, the number of defaults increases and the total welfare deteriorates.

Keywords: Behavioural Macroeconomics, Credit Cycle, Experimental Economics, Heterogeneous Expectations, Learning-to-Forecast Experiment

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10 The Adaptation and Evaluation of a Psychoeducational Program for Patients with Depression in General Practices in Germany

Authors: Feyza Gökce, Jochen Gensichen, Antonius Schneider, Karolina de Valerio, Gabriele Pitschel-Walz

Abstract:

People with depressive symptoms often first consult a General Practitioner (GP) before making use of other treatment options. The present study shows the adaptation and evaluation of a psychoeducational program for patients with depressive symptoms that are treated by GPs in Bavaria, Germany. The adaptation of an existing psychoeducational program, that is used in inpatient psychiatric settings, was performed in exchange with experts (psychotherapists, general practitioners, and a patient representative). As a result, a program consisting of 4 psychoeducational sessions was developed, which is carried out in individual settings in GP practices by the practitioners themselves. This program will be compared to treatment as usual that patients with depression receive by GPs. Data is collected at 3 measurement points (baseline, 3-months-follow-up, 6-months-follow-up) using different questionnaires (BDI-II, D-Lit-R German, FERUS, PAM13-D, PHQ-9, GAD-7, PHQ-15, PC-PTSD-5). In addition to the change in depressive symptoms, changes in depression knowledge, self-efficacy, and patient activation will be analyzed, and the feasibility of the program and the subjective benefit for GPs and patients will be assessed. By now, 84 patients have been recruited by 20 cluster-randomized GP practices, with 73.5% of the participants being female and 26.5% being males. The average age was M= 50.1 (SD= 14.67) years. The change in depression symptoms over the 3-month period will be compared between the two study conditions by using a linear mixed model by the end of data collection (December 2023). The subjective benefit for the patients and GPs will be assessed via feedback questionnaires. Results will be presentable by the beginning of 2024 and will provide indications for further development and barriers to the implementation of such a program for GP practices.

Keywords: depression, general practice, psychoeducation, primary care

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9 Study of Expatriation as Countermeasure to Citizenship-Based Taxation

Authors: Gabriele Palumbo

Abstract:

This research empirically examines some of the reasons behind the fact that recently the number of people giving up their American citizenship for tax purposes has recently increased drastically. The United States Jurisdiction represents a unicum in the practice of taxing worldwide income not only to residents of the United States but also to U.S. citizens living abroad. The worldwide income taxation also affects people defined as “Accidental Americans” who are unaware that they are U.S. citizens. Those people are considered Americans even though they have not been to the United States. American residents abroad can rely on United States income tax treaties and some national law provisions, such as the exclusion of foreign income and foreign tax credits, which are designed specifically to avoid double taxation. However, this mechanism may prove unsatisfactory for people who have not been linked anymore or individuals who have never had relations with the United States. U.S. citizens who are determined to cut all of the ties between themselves and the United States, especially those that involve tax implications, can renounce their U.S. citizenship with the expatriation procedure. The expatriation process represents the extrema ratio and implicates several steps which must be followed carefully. This paper shows the complexity of the procedure that a U.S. citizen who is resident in a foreign country would have to follow to relinquish U.S. citizenship for tax purposes. The mechanism is intended to discourage people from renounce. Going beyond the question of whether U.S. tax regulation is fair or not, this principle nowadays characterizes a popular topic that many scholars and lawyers are discussing. The outcome provides interesting implications that could induce the Congress to rethink the definition of citizenship for both fiscal and nationality law purposes. Indeed, even if a sort of checks and balances has the task of mitigating the renunciation of U.S. citizenship, more and more U.S. citizens desire to get rid of their citizenship.

Keywords: double taxation, expatriation tax, international taxation, relinquishment of United States citizenship

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8 Nanoscale Mapping of the Mechanical Modifications Occurring in the Brain Tumour Microenvironment by Atomic Force Microscopy: The Case of the Highly Aggressive Glioblastoma and the Slowly Growing Meningioma

Authors: Gabriele Ciasca, Tanya E. Sassun, Eleonora Minelli, Manila Antonelli, Massimiliano Papi, Antonio Santoro, Felice Giangaspero, Roberto Delfini, Marco De Spirito

Abstract:

Glioblastoma multiforme (GBM) is an extremely aggressive brain tumor, characterized by a diffuse infiltration of neoplastic cells into the brain parenchyma. Although rarely considered, mechanical cues play a key role in the infiltration process that is extensively mediated by the tumor microenvironment stiffness and, more in general, by the occurrence of aberrant interactions between neoplastic cells and the extracellular matrix (ECM). Here we provide a nano-mechanical characterization of the viscoelastic response of human GBM tissues by indentation-type atomic force microscopy. High-resolution elasticity maps show a large difference between the biomechanics of GBM tissues and the healthy peritumoral regions, opening possibilities to optimize the tumor resection area. Moreover, we unveil the nanomechanical signature of necrotic regions and anomalous vasculature, that are two major hallmarks useful for glioma staging. Actually, the morphological grading of GBM relies mainly on histopathological findings that make extensive use of qualitative parameters. Our findings have the potential to positively impact on the development of novel quantitative methods to assess the tumor grade, which can be used in combination with conventional histopathological examinations. In order to provide a more in-depth description of the role of mechanical cues in tumor progression, we compared the nano-mechanical fingerprint of GBM tissues with that of grade-I (WHO) meningioma, a benign lesion characterized by a completely different growth pathway with the respect to GBM, that, in turn hints at a completely different role of the biomechanical interactions.

Keywords: AFM, nano-mechanics, nanomedicine, brain tumors, glioblastoma

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7 Numerical Model of Low Cost Rubber Isolators for Masonry Housing in High Seismic Regions

Authors: Ahmad B. Habieb, Gabriele Milani, Tavio Tavio, Federico Milani

Abstract:

Housings in developing countries have often inadequate seismic protection, particularly for masonry. People choose this type of structure since the cost and application are relatively cheap. Seismic protection of masonry remains an interesting issue among researchers. In this study, we develop a low-cost seismic isolation system for masonry using fiber reinforced elastomeric isolators. The elastomer proposed consists of few layers of rubber pads and fiber lamina, making it lower in cost comparing to the conventional isolators. We present a finite element (FE) analysis to predict the behavior of the low cost rubber isolators undergoing moderate deformations. The FE model of the elastomer involves a hyperelastic material property for the rubber pad. We adopt a Yeoh hyperelasticity model and estimate its coefficients through the available experimental data. Having the shear behavior of the elastomers, we apply that isolation system onto small masonry housing. To attach the isolators on the building, we model the shear behavior of the isolation system by means of a damped nonlinear spring model. By this attempt, the FE analysis becomes computationally inexpensive. Several ground motion data are applied to observe its sensitivity. Roof acceleration and tensile damage of walls become the parameters to evaluate the performance of the isolators. In this study, a concrete damage plasticity model is used to model masonry in the nonlinear range. This tool is available in the standard package of Abaqus FE software. Finally, the results show that the low-cost isolators proposed are capable of reducing roof acceleration and damage level of masonry housing. Through this study, we are also capable of monitoring the shear deformation of isolators during seismic motion. It is useful to determine whether the isolator is applicable. According to the results, the deformations of isolators on the benchmark one story building are relatively small.

Keywords: masonry, low cost elastomeric isolator, finite element analysis, hyperelasticity, damped non-linear spring, concrete damage plasticity

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6 Quantum Graph Approach for Energy and Information Transfer through Networks of Cables

Authors: Mubarack Ahmed, Gabriele Gradoni, Stephen C. Creagh, Gregor Tanner

Abstract:

High-frequency cables commonly connect modern devices and sensors. Interestingly, the proportion of electric components is rising fast in an attempt to achieve lighter and greener devices. Modelling the propagation of signals through these cable networks in the presence of parameter uncertainty is a daunting task. In this work, we study the response of high-frequency cable networks using both Transmission Line and Quantum Graph (QG) theories. We have successfully compared the two theories in terms of reflection spectra using measurements on real, lossy cables. We have derived a generalisation of the vertex scattering matrix to include non-uniform networks – networks of cables with different characteristic impedances and propagation constants. The QG model implicitly takes into account the pseudo-chaotic behavior, at the vertices, of the propagating electric signal. We have successfully compared the asymptotic growth of eigenvalues of the Laplacian with the predictions of Weyl law. We investigate the nearest-neighbour level-spacing distribution of the resonances and compare our results with the predictions of Random Matrix Theory (RMT). To achieve this, we will compare our graphs with the generalisation of Wigner distribution for open systems. The problem of scattering from networks of cables can also provide an analogue model for wireless communication in highly reverberant environments. In this context, we provide a preliminary analysis of the statistics of communication capacity for communication across cable networks, whose eventual aim is to enable detailed laboratory testing of information transfer rates using software defined radio. We specialise this analysis in particular for the case of MIMO (Multiple-Input Multiple-Output) protocols. We have successfully validated our QG model with both TL model and laboratory measurements. The growth of Eigenvalues compares well with Weyl’s law and the level-spacing distribution agrees so well RMT predictions. The results we achieved in the MIMO application compares favourably with the prediction of a parallel on-going research (sponsored by NEMF21.)

Keywords: eigenvalues, multiple-input multiple-output, quantum graph, random matrix theory, transmission line

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5 Influence of Mothers’ Knowledge, Attitude and Behavior on Diet and Physical Activity of Their Pre-School Children: A Cross-Sectional Study from a Semi-Urban Area of Nepal

Authors: Natalia Oli, Abhinav Vaidya, Katja Pahkala, Gabriele Eiben, Alexandra Krettek

Abstract:

The nutritional transition towards a high fat and energy dense diet, decreasing physical activity level, and poor cardiovascular health knowledge contributes to a rising burden of cardiovascular diseases in Nepal. Dietary and physical activity behaviors are formed early in life and influenced by family, particularly by mothers in the social context of Nepal. The purpose of this study was to explore knowledge, attitude and behavior of mothers regarding diet and physical activity of their pre-school children. Cross-sectional study was conducted in the semi-urban area of Duwakot and Jhaukhel communities near the capital Kathmandu. Between August and November 2014, nine trained enumerators interviewed all mothers having children aged 2 to 7 years in their homes. Questionnaire contained information about mothers’ socio-demographic characteristics; their knowledge, attitude, and behavior regarding diet and physical activity as well as their children’s diet and physical activity. Knowledge, attitude and behavior responses were scored. SPSS version 22.0 was used for data analyses. Out of the 1,052 eligible mothers, 962 consented to participate in the study. The mean age was 28.9 ± 4.5 years. The majority of them (73%) were housewives. Mothers with higher education and income had higher knowledge, attitude, and behavior scores (All p < 0.001) whereas housewives and farmers had low knowledge score (p < 0.001). They, along with laborers, also exhibited lower attitude (p<0.001) and behavior scores (p < 0.001). Children’s diet score increased with mothers’ level of education (p <0.001) and income (p=0.041). Their physical activity score, however, declined with increasing level of their mothers’ education (p < 0.001) and income (p < 0.001). Children’s overall behavior score correlated poorly with mothers’ knowledge (r = 0.009, p=0.003), attitude (r =0.012, p=0.001), and behavior (r = 0.007, p= 0.008). Such poor correlation can be due to existence of the barriers among mothers. Mothers reported such barriers as expensive healthy food, difficulty to give up favorite food, taste preference of others family members and lack of knowledge on healthy food. Barriers for physical activity were lack of leisure time, lack of parks and playgrounds, being busy by caring for children and old people, feeling lazy and embarrassed in front of others. Additionally, among the facilitators for healthy lifestyle, mentioned by mothers, were better information, family eating healthy food and supporting physical activity, advice of medical personnel regarding healthy lifestyle and own ill health. The study demonstrated poor correlation of mothers’ knowledge and attitude with children’s behavior regarding diet and physical activity. Hence improving mothers’ knowledge or attitude may not be enough to improve dietary and physical activity habits of their children. Barriers and facilitators that affect mothers’ practices towards their children should also be addressed due to future intervention.

Keywords: attitude, behavior, diet, knowledge, mothers, physical activity

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4 Mapping the Early History of Common Law Education in England, 1292-1500

Authors: Malcolm Richardson, Gabriele Richardson

Abstract:

This paper illustrates how historical problems can be studied successfully using GIS even in cases in which data, in the modern sense, is fragmentary. The overall problem under investigation is how early (1300-1500) English schools of Common Law moved from apprenticeship training in random individual London inns run in part by clerks of the royal chancery to become what is widely called 'the Third University of England,' a recognized system of independent but connected legal inns. This paper focuses on the preparatory legal inns, called the Inns of Chancery, rather than the senior (and still existing) Inns of Court. The immediate problem studied in this paper is how the junior legal inns were organized, staffed, and located from 1292 to about 1500, and what maps tell us about the role of the chancery clerks as managers of legal inns. The authors first uncovered the names of all chancery clerks of the period, most of them unrecorded in histories, from archival sources in the National Archives, Kew. Then they matched the names with London property leases. Using ArcGIS, the legal inns and their owners were plotted on a series of maps covering the period 1292 to 1500. The results show a distinct pattern of ownership of the legal inns and suggest a narrative that would help explain why the Inns of Chancery became serious centers of learning during the fifteenth century. In brief, lower-ranking chancery clerks, always looking for sources of income, discovered by 1370 that legal inns could be a source of income. Since chancery clerks were intimately involved with writs and other legal forms, and since the chancery itself had a long-standing training system, these clerks opened their own legal inns to train fledgling lawyers, estate managers, and scriveners. The maps clearly show growth patterns of ownership by the chancery clerks for both legal inns and other London properties in the areas of Holborn and The Strand between 1450 and 1417. However, the maps also show that a royal ordinance of 1417 forbidding chancery clerks to live with lawyers, law students, and other non-chancery personnel had an immediate effect, and properties in that area of London leased by chancery clerks simply stop after 1417. The long-term importance of the patterns shown in the maps is that while the presence of chancery clerks in the legal inns likely created a more coherent education system, their removal forced the legal profession, suddenly without a hostelry managerial class, to professionalize the inns and legal education themselves. Given the number and social status of members of the legal inns, the effect on English education was to free legal education from the limits of chancery clerk education (the clerks were not practicing common lawyers) and to enable it to become broader in theory and practice, in fact, a kind of 'finishing school' for the governing (if not noble) class.

Keywords: GIS, law, London, education

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3 Analysis and Comparison of Asymmetric H-Bridge Multilevel Inverter Topologies

Authors: Manel Hammami, Gabriele Grandi

Abstract:

In recent years, multilevel inverters have become more attractive for single-phase photovoltaic (PV) systems, due to their known advantages over conventional H-bridge pulse width-modulated (PWM) inverters. They offer improved output waveforms, smaller filter size, lower total harmonic distortion (THD), higher output voltages and others. The most common multilevel converter topologies, presented in literature, are the neutral-point-clamped (NPC), flying capacitor (FC) and Cascaded H-Bridge (CHB) converters. In both NPC and FC configurations, the number of components drastically increases with the number of levels what leads to complexity of the control strategy, high volume, and cost. Whereas, increasing the number of levels in case of the cascaded H-bridge configuration is a flexible solution. However, it needs isolated power sources for each stage, and it can be applied to PV systems only in case of PV sub-fields. In order to improve the ratio between the number of output voltage levels and the number of components, several hybrids and asymmetric topologies of multilevel inverters have been proposed in the literature such as the FC asymmetric H-bridge (FCAH) and the NPC asymmetric H-bridge (NPCAH) topologies. Another asymmetric multilevel inverter configuration that could have interesting applications is the cascaded asymmetric H-bridge (CAH), which is based on a modular half-bridge (two switches and one capacitor, also called level doubling network, LDN) cascaded to a full H-bridge in order to double the output voltage level. This solution has the same number of switches as the above mentioned AH configurations (i.e., six), and just one capacitor (as the FCAH). CAH is becoming popular, due to its simple, modular and reliable structure, and it can be considered as a retrofit which can be added in series to an existing H-Bridge configuration in order to double the output voltage levels. In this paper, an original and effective method for the analysis of the DC-link voltage ripple is given for single-phase asymmetric H-bridge multilevel inverters based on level doubling network (LDN). Different possible configurations of the asymmetric H-Bridge multilevel inverters have been considered and the analysis of input voltage and current are analytically determined and numerically verified by Matlab/Simulink for the case of cascaded asymmetric H-bridge multilevel inverters. A comparison between FCAH and the CAH configurations is done on the basis of the analysis of the DC and voltage ripple for the DC source (i.e., the PV system). The peak-to-peak DC and voltage ripple amplitudes are analytically calculated over the fundamental period as a function of the modulation index. On the basis of the maximum peak-to-peak values of low frequency and switching ripple voltage components, the DC capacitors can be designed. Reference is made to unity output power factor, as in case of most of the grid-connected PV generation systems. Simulation results will be presented in the full paper in order to prove the effectiveness of the proposed developments in all the operating conditions.

Keywords: asymmetric inverters, dc-link voltage, level doubling network, single-phase multilevel inverter

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2 Scientific and Regulatory Challenges of Advanced Therapy Medicinal Products

Authors: Alaa Abdellatif, Gabrièle Breda

Abstract:

Background. Advanced therapy medicinal products (ATMPs) are innovative therapies that mainly target orphan diseases and high unmet medical needs. ATMP includes gene therapy medicinal products (GTMP), somatic cell therapy medicinal products (CTMP), and tissue-engineered therapies (TEP). Since legislation opened the way in 2007, 25 ATMPs have been approved in the EU, which is about the same amount as the U.S. Food and Drug Administration. However, not all of the ATMPs that have been approved have successfully reached the market and retained their approval. Objectives. We aim to understand all the factors limiting the market access to very promising therapies in a systemic approach, to be able to overcome these problems, in the future, with scientific, regulatory and commercial innovations. Further to recent reviews that focus either on specific countries, products, or dimensions, we will address all the challenges faced by ATMP development today. Methodology. We used mixed methods and a multi-level approach for data collection. First, we performed an updated academic literature review on ATMP development and their scientific and market access challenges (papers published between 2018 and April 2023). Second, we analyzed industry feedback from cell and gene therapy webinars and white papers published by providers and pharmaceutical industries. Finally, we established a comparative analysis of the regulatory guidelines published by EMA and the FDA for ATMP approval. Results: The main challenges in bringing these therapies to market are the high development costs. Developing ATMPs is expensive due to the need for specialized manufacturing processes. Furthermore, the regulatory pathways for ATMPs are often complex and can vary between countries, making it challenging to obtain approval and ensure compliance with different regulations. As a result of the high costs associated with ATMPs, challenges in obtaining reimbursement from healthcare payers lead to limited patient access to these treatments. ATMPs are often developed for orphan diseases, which means that the patient population is limited for clinical trials which can make it challenging to demonstrate their safety and efficacy. In addition, the complex manufacturing processes required for ATMPs can make it challenging to scale up production to meet demand, which can limit their availability and increase costs. Finally, ATMPs face safety and efficacy challenges: dangerous adverse events of these therapies like toxicity related to the use of viral vectors or cell therapy, starting material and donor-related aspects. Conclusion. As a result of our mixed method analysis, we found that ATMPs face a number of challenges in their development, regulatory approval, and commercialization and that addressing these challenges requires collaboration between industry, regulators, healthcare providers, and patient groups. This first analysis will help us to address, for each challenge, proper and innovative solution(s) in order to increase the number of ATMPs approved and reach the patients

Keywords: advanced therapy medicinal products (ATMPs), product development, market access, innovation

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1 Rheolaser: Light Scattering Characterization of Viscoelastic Properties of Hair Cosmetics That Are Related to Performance and Stability of the Respective Colloidal Soft Materials

Authors: Heitor Oliveira, Gabriele De-Waal, Juergen Schmenger, Lynsey Godfrey, Tibor Kovacs

Abstract:

Rheolaser MASTER™ makes use of multiple scattering of light, caused by scattering objects in a continuous medium (such as droplets and particles in colloids), to characterize the viscoelasticity of soft materials. It offers an alternative to conventional rheometers to characterize viscoelasticity of products such as hair cosmetics. Up to six simultaneous measurements at controlled temperature can be carried out simultaneously (10-15 min), and the method requires only minor sample preparation work. Conversely to conventional rheometer based methods, no mechanical stress is applied to the material during the measurements. Therefore, the properties of the exact same sample can be monitored over time, like in aging and stability studies. We determined the elastic index (EI) of water/emulsion mixtures (1 ≤ fat alcohols (FA) ≤ 5 wt%) and emulsion/gel-network mixtures (8 ≤ FA ≤ 17 wt%) and compared with the elastic/sorage mudulus (G’) for the respective samples using a TA conventional rheometer with flat plates geometry. As expected, it was found that log(EI) vs log(G’) presents a linear behavior. Moreover, log(EI) increased in a linear fashion with solids level in the entire range of compositions (1 ≤ FA ≤ 17 wt%), while rheometer measurements were limited to samples down to 4 wt% solids level. Alternatively, a concentric cilinder geometry would be required for more diluted samples (FA > 4 wt%) and rheometer results from different sample holder geometries are not comparable. The plot of the rheolaser output parameters solid-liquid balance (SLB) vs EI were suitable to monitor product aging processes. These data could quantitatively describe some observations such as formation of lumps over aging time. Moreover, this method allowed to identify that the different specifications of a key raw material (RM < 0.4 wt%) in the respective gel-network (GN) product has minor impact on product viscoelastic properties and it is not consumer perceivable after a short aging time. Broadening of a RM spec range typically has a positive impact on cost savings. Last but not least, the photon path length (λ*)—proportional to droplet size and inversely proportional to volume fraction of scattering objects, accordingly to the Mie theory—and the EI were suitable to characterize product destabilization processes (e.g., coalescence and creaming) and to predict product stability about eight times faster than our standard methods. Using these parameters we could successfully identify formulation and process parameters that resulted in unstable products. In conclusion, Rheolaser allows quick and reliable characterization of viscoelastic properties of hair cosmetics that are related to their performance and stability. It operates in a broad range of product compositions and has applications spanning from the formulation of our hair cosmetics to fast release criteria in our production sites. Last but not least, this powerful tool has positive impact on R&D development time—faster delivery of new products to the market—and consequently on cost savings.

Keywords: colloids, hair cosmetics, light scattering, performance and stability, soft materials, viscoelastic properties

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