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Long-Term outcome of infantile onset pompe disease patients treated with enzyme replacement therapy
(2024)
Background: Enzyme replacement therapy (ERT) with recombinant human alglucosidase alfa (rhGAA) was approved in Europe in 2006. Nevertheless, data on the long-term outcome of infantile onset Pompe disease (IOPD) patients at school age is still limited.
Objective: We analyzed in detail cardiac, respiratory, motor, and cognitive function of 15 German-speaking patients aged 7 and older who started ERT at a median age of 5 months.
Results: Starting dose was 20 mg/kg biweekly in 12 patients, 20 mg/kg weekly in 2, and 40 mg/kg weekly in one patient. CRIM-status was positive in 13 patients (86.7%) and negative or unknown in one patient each (6.7%). Three patients (20%) received immunomodulation. Median age at last assessment was 9.1 (7.0–19.5) years. At last follow-up 1 patient (6.7%) had mild cardiac hypertrophy, 6 (42.9%) had cardiac arrhythmias, and 7 (46.7%) required assisted ventilation. Seven patients (46.7%) achieved the ability to walk independently and 5 (33.3%) were still ambulatory at last follow-up. Six patients (40%) were able to sit without support, while the remaining 4 (26.7%) were tetraplegic. Eleven patients underwent cognitive testing (Culture Fair Intelligence Test), while 4 were unable to meet the requirements for cognitive testing. Intelligence quotients (IQs) ranged from normal (IQ 117, 102, 96, 94) in 4 patients (36.4%) to mild developmental delay (IQ 81) in one patient (9.1%) to intellectual disability (IQ 69, 63, 61, 3x < 55) in 6 patients (54.5%). White matter abnormalities were present in 10 out of 12 cerebral MRIs from 7 patients.
Open tracing tools
(2023)
Background: Coping with the rapid growing complexity in contemporary software architecture, tracing has become an increasingly critical practice and been adopted widely by software engineers. By adopting tracing tools, practitioners are able to monitor, debug, and optimize distributed software architectures easily. However, with excessive number of valid candidates, researchers and practitioners have a hard time finding and selecting the suitable tracing tools by systematically considering their features and advantages. Objective: To such a purpose, this paper aims to provide an overview of popular Open tracing tools via comparison. Methods: Herein, we first identified 30 tools in an objective, systematic, and reproducible manner adopting the Systematic Multivocal Literature Review protocol. Then, we characterized each tool looking at the 1) measured features, 2) popularity both in peer-reviewed literature and online media, and 3) benefits and issues. We used topic modeling and sentiment analysis to extract and summarize the benefits and issues. Specially, we adopted ChatGPT to support the topic interpretation. Results: As a result, this paper presents a systematic comparison amongst the selected tracing tools in terms of their features, popularity, benefits and issues. Conclusion: The result mainly shows that each tracing tool provides a unique combination of features with also different pros and cons. The contribution of this paper is to provide the practitioners better understanding of the tracing tools facilitating their adoption.
Vast amounts of oily wastewater are byproducts of the petrochemical and the shipping industry and to this day frequently discharged into water bodies either without or after insufficient treatment. To alleviate the resulting pollution, water treatment processes are in great demand. Bubble column humidifiers (BCHs) as part of humidification–dehumidification systems are predestined for such a task, since they are insensitive to different feed liquids, simple in design and have low maintenance requirements. While humidification in a bubble column has been investigated plentiful for desalination, a systematic investigation of oily wastewater treatment is missing in literature. We filled this gap by analyzing the treatment of an oil–water emulsion experimentally to derive recommendations for future design and operation of BCHs. Our humidity measurements indicate that the air stream is always saturated after humidification for a liquid height of only 10 cm. A residual water mass fraction of 3.5 wt% is measured after a batch run of six hours. Furthermore, continuous measurements show that an increase in oil mass fraction leads to a decrease in system productivity especially for high oil mass fractions. This decrease is caused by the heterogeneity of the liquid temperature profile. A lower liquid height mitigates this heterogeneity, therefore decreasing the heat demand and improving the overall efficiency. The oil content of the produced condensate is below 15 ppm, allowing discharge into various water bodies. The results of our systematic investigation prove suitability and indicate a strong future potential for the use of BCHs in oily wastewater treatment.
Organic acidurias (OAs), urea-cycle disorders (UCDs), and maple syrup urine disease (MSUD) belong to the category of intoxication-type inborn errors of metabolism (IT-IEM). Liver transplantation (LTx) is increasingly utilized in IT-IEM. However, its impact has been mainly focused on clinical outcome measures and rarely on health-related quality of life (HRQoL). Aim of the study was to investigate the impact of LTx on HrQoL in IT-IEMs. This single center prospective study involved 32 patients (15 OA, 11 UCD, 6 MSUD; median age at LTx 3.0 years, range 0.8–26.0). HRQoL was assessed pre/post transplantation by PedsQL-General Module 4.0 and by MetabQoL 1.0, a specifically designed tool for IT-IEM. PedsQL highlighted significant post-LTx improvements in total and physical functioning in both patients' and parents' scores. According to age at transplantation (≤3 vs. >3 years), younger patients showed higher post-LTx scores on Physical (p = 0.03), Social (p < 0.001), and Total (p =0.007) functioning. MetabQoL confirmed significant post-LTx changes in Total and Physical functioning in both patients and parents scores (p ≤ 0.009). Differently from PedsQL, MetabQoL Mental (patients p = 0.013, parents p = 0.03) and Social scores (patients p = 0.02, parents p = 0.012) were significantly higher post-LTx. Significant improvements (p = 0.001–0.04) were also detected both in self- and proxy-reports for almost all MetabQoL subscales. This study shows the importance of assessing the impact of transplantation on HrQoL, a meaningful outcome reflecting patients' wellbeing. LTx is associated with significant improvements of HrQol in both self- and parentreports. The comparison between PedsQL-GM and MetabQoL highlighted that MetabQoL demonstrated higher sensitivity in the assessment of diseasespecific domains than the generic PedsQL tool.
Highly-sensitive single-step sensing of levodopa by swellable microneedle-mounted nanogap sensors
(2023)
Microneedle (MN) sensing of biomarkers in interstitial fluid (ISF) can overcome the challenges of self-diagnosis of diseases by a patient, such as blood sampling, handling, and measurement analysis. However, the MN sensing technologies still suffer from poor measurement accuracy due to the small amount of target molecules present in ISF, and require multiple steps of ISF extraction, ISF isolation from MN, and measurement with additional equipment. Here, we present a swellable MN-mounted nanogap sensor that can be inserted into the skin tissue, absorb ISF rapidly, and measure biomarkers in situ by amplifying the measurement signals by redox cycling in nanogap electrodes. We demonstrate that the MN-nanogap sensor measures levodopa (LDA), medication for Parkinson disease, down to 100 nM in an aqueous solution, and 1 μM in both the skin-mimicked gelatin phantom and porcine skin.
The production of liquid-gas mixtures with desired properties still places high demands on process technology and is usually realized in bubble columns. The physical calculation models used have individual dimensionless factors which, depending on the application, are only valid for small ranges consisting of flow velocity, nozzle geometry and test setup. An iterative but time-consuming design of such dispersion processes is used in industry for producing a liquid-gas mixture according to desired requirements. In the present investigation, we accelerate the necessary design loops by setting up a physical model, which consists of several subsystems that are enriched by dedicated experiments to realize liquid-gas dispersions with low volume fraction and small air bubble diameters in oil. Our approach allows the extraction of individual dimensionless factors from maps of the introduced subsystems. These maps allow for targeted corrective measures of a production process for keeping the quality. The calculation-based approach avoids the need for performing iterative design loops. Overall, this approach supports the controlled generation of liquid-gas mixtures.
Praxisanleiter:innen nehmen eine entscheidende Rolle in der Ausbildung von Pflegepersonen wahr. Die Tätigkeit fordert eine Vielzahl von Kompetenzen. Die Weiterbildung Praxisanleitung bietet eine wichtige Grundlage für die Entwicklung dieser Kompetenzen – deren Rahmenbedingungen, Methoden und Inhalte in Österreich werden in dieser Studie untersucht.
X-ray microtomography is a nondestructive, three-dimensional inspection technique applied across a vast range of fields and disciplines, ranging from research to industrial, encompassing engineering, biology, and medical research. Phasecontrast imaging extends the domain of application of x-ray microtomography to classes of samples that exhibit weak attenuation, thus appearing with poor contrast in standard x-ray imaging. Notable examples are low-atomic-number materials, like carbon-fiber composites, soft matter, and biological soft tissues.We report on a compact and cost-effective system for x-ray phase-contrast microtomography. The system features high sensitivity to phase gradients and high resolution, requires a low-power sealed x-ray tube, a single optical element, and fits in a small footprint. It is compatible with standard x-ray detector technologies: in our experiments, we have observed that single-photon counting offered higher angular sensitivity, whereas flat panels provided a larger field of view. The system is benchmarked against knownmaterial phantoms, and its potential for soft-tissue three-dimensional imaging is demonstrated on small-animal organs: a piglet esophagus and a rat heart.We believe that the simplicity of the setupwe are proposing, combined with its robustness and sensitivity, will facilitate accessing quantitative x-ray phase-contrast microtomography as a research tool across disciplines, including tissue engineering, materials science, and nondestructive testing in general.
Activation of heat pump flexibilities is a viable solution to support balancing the grid via Demand Side Management measures and fulfill the need for flexibility options. Aggregators as interface between prosumers, distribution system operators and balance responsible parties face the challenge due to data privacy and technical restrictions to transform prosumer information into aggregated available flexibility to enable trading thereof. Thereby, literature lacks a generic, applicable and widely accepted flexibility estimation method for heat pumps,which incorporates reduced sensor and system information, system- and demand-dependent behaviour. In this paper, we adapt and extend a method from literature, by incorporating domain knowledge to overcome reduced sensor and system information. We apply data of five real-world heat pump systems, distinguish operation modes, estimate power and energy flexibility of each single heat pump system, proof transferability of the method, and aggregate the flexibilities available to showcase a small HP pool as a proof of concept.
Pooled data from published reports on infants with clinically diagnosed vitamin B12 (B12) deficiency were analyzed with the purpose of describing the presentation, diagnostic approaches, and risk factors for the condition to inform prevention strategies. An electronic (PubMed database) and manual literature search following the PRISMA approach was conducted (preregistration with the Open Science Framework, accessed on 15 February 2023). Data were described and analyzed using correlation analyses, Chi-square tests, ANOVAs, and regression analyses, and 102 publications (292 cases) were analyzed. The mean age at first symptoms (anemia, various neurological symptoms) was four months; the mean time to diagnosis was 2.6 months. Maternal B12 at diagnosis, exclusive breastfeeding, and a maternal diet low in B12 predicted infant B12, methylmalonic acid, and total homocysteine. Infant B12 deficiency is still not easily diagnosed. Methylmalonic acid and total homocysteine are useful diagnostic parameters in addition to B12 levels. Since maternal B12 status predicts infant B12 status, it would probably be advantageous to target women in early pregnancy or even preconceptionally to prevent infant B12 deficiency, rather than to rely on newborn screening that often does not reliably identify high-risk children.
Measuring what matters
(2023)
Patient reported outcomes (PROs) are generally defined as ‘any report of the status of a patient's health condition that comes directly from the patient, without interpretation of the patient's response by a clinician or anyone else’. A broader definition of PRO also includes ‘any information on the outcomes of health care obtained directly from patients without modification by clinicians or other health care professionals’. Following this approach, PROs encompass subjective perceptions of patients on how they function or feel not only in relation to a health condition but also to its treatment as well as concepts such as health-related quality of life (HrQoL), information on the functional status of a patient, signs and symptoms and symptom burden. PRO measurement instruments (PROMs) are mostly questionnaires and inform about what patients can do and how they feel. PROs and PROMs have not yet found unconditional acceptance and wide use in the field of inborn errors of metabolism. This review summarises the importance and usefulness of PROs in research, drug legislation and clinical care and informs about quality standards, development, and potential methodological shortfalls of PROMs. Inclusion of PROs measured with high-quality, well-selected PROMs into clinical care, drug legislation, and research helps to identify unmet needs, improve quality of care, and define outcomes that are meaningful to patients. The field of IEM should open to new methodological approaches such as the definition of core sets of variables including PROs to be systematically assessed in specific metabolic conditions and new collaborations with PRO experts, such as psychologists to facilitate the systematic collection of meaningful data.
A model is presented that allows for the calculation of the success probability by which a vanilla Evolution Strategy converges to the global optimizer of the Rastrigin test function. As a result a population size scaling formula will be derived that allows for an estimation of the population size needed to ensure a high convergence security depending on the search space dimensionality.
Zu Beginn des Forschungsprojektes „Neue Museumswelten“ wollten wir von Studierenden der Studiengänge Bachelor und Master InterMedia an der Fachhochschule Vorarlberg wissen, was sie mit dem Begriff „Museum“ verbinden. „Museum? Da gehe ich nur im Urlaub hin. Aber hier in Vorarlberg nicht“, war eine geläufige Aussage, die auf ein bestimmtes mentales Modell von Museum verweist. Viele Studierenden gehören also der Gruppe der Gelegenheits- oder Nichtbesucher:innen an. Wie sich in weiterer Folge herausstellte, handelt es sich dabei um eine durchaus heterogene Gruppe, die jedoch auch Gemeinsamkeiten aufweist: Alle Menschen, mit denen wir bisher im Zuge des Forschungsprojekts im Stadtraum, auf Events und im Museum sprachen, spielten und Zukunftsvisionen entwickelten, brachten ihre eigenen Bilder, Vorstellungen und Ideen zu Museen und möglichen Museumszukünften mit. Der Untersuchung genau dieser Bilder und Vorstellungen – der mentalen Modelle von Museum also –, widmet sich das von Interreg geförderte Forschungsprojekt unter Einbindung vielfältiger Perspektiven und Methoden aus Sozialforschung und Design. Es verfolgt den innovativen Weg, „Designerly Ways of Knowing“0 von Beginn an konsequent in den Forschungsprozess zu integrieren, um anstrebenswerte Museumszukünfte gemeinsam mit den Menschen auszuloten...
Grid-scale electrical energy storage (EES) is a key component in cost-effective transition scenarios to renewable energy sources. The requirement of scalability favors EES approaches such as pumped-storage hydroelectricity (PSH) or compressed-air energy storage (CAES), which utilize the cheap and abundant storage materials water and air, respectively. To overcome the site restriction and low volumetric energy densities attributed to PSH and CAES, liquid-air energy storage (LAES) has been devised; however, it suffers from a rather small round-trip efficiency (RTE) and challenging storage conditions. Aiming to overcome these drawbacks, a novel system for EES is developed using solidified air (i.e., clathrate hydrate of air) as the storable phase of air. A reference plant for solidified-air energy storage (SAES) is conceptualized and modeled thermodynamically using the software CoolProp for water and air as well as empirical data and first-order approximations for the solidified air (SA). The reference plant exhibits a RTE of 52% and a volumetric storage density of 47 kWh per m3 of SA. While this energy density relates to only one half of that in LAES plants, the modeled RTE of SAES is comparable already. Since improved thermal management and the use of thermodynamic promoters can further increase the RTEs in SAES, the technical potential of SAES is in place already. Yet, for a successful implementation of the concept - in addition to economic aspects - questions regarding the stability of SA must be first clarified and challenges related to the processing of SA resolved.
Bubble columns are recently used for the humidification of air in water treatment systems and fuel cells. They are well applicable due to their excellent heat and mass transfer and their low technical complexity. To design and operate such devices with high efficiency, the humidification process and the impact of the operating parameters need to be understood to a sufficient degree. To extend this knowledge, we use a refined and novel method to determine the volumetric air–liquid heat and mass transfer coefficients and the humidifier efficiency for various parametric settings. The volumetric transfer coefficients increase with both of the superficial air velocity and the liquid temperature. It is further shown that the decrease of vapor pressure with an increase of the salinity results in a corresponding decrease in the outlet humidity ratio. In contrast to previous studies, liquid heights smaller than 0.1 m are investigated and significant changes in the humidifier efficiency are seen in this range. We present the expected humidifier efficiency with respect to the superficial air velocity and the liquid height in an efficiency chart, such that optimal operating conditions can be determined. Based on this efficiency chart, recommendations for industrial applications as well as future scientific challenges are drawn.