Genetic disorders, including haemochromatosis and thalassaemia, can lead to iron overload and related adverse health outcomes, such as liver and cardiovascular disease(1,2).

Thalassaemia is one of the most common genetic blood disorders worldwide(1). It is characterized by impaired production of haemoglobin resulting in chronic anaemia. This, in turn, leads to an upregulation of dietary iron absorption causing iron overload. Standard treatment therefore includes iron chelation therapy with frequency depending on the velocity of body iron accumulation(1).

Some polyphenolic compounds have strong iron-chelating properties(3,4). We recently showed that a polyphenol supplement (PPS) consisting of grape juice extract, black tea and cocoa powder taken with an iron-rich meal or iron-fortified drink reduces iron absorption by ∼40 % in European adults with haemochromatosis(5).

Here we investigated the effect of this natural PPS on iron absorption from an iron-rich meal or iron-fortified drink in Thai adults with non-transfusion-dependent thalassaemia.

We performed a single-blind, placebo-controlled, cross-over study in 20 Thai adults with ironloading, non-transfusion-dependent thalassaemia. Each participant consumed, in partially randomized order, an iron-rich test meal (8 mg native iron) or an iron-fortified test drink (8 mg iron as FeSO4) extrinsically labelled with a stable iron isotope (2 mg 58Fe or 57Fe as ferrous sulphate [FeSO4]) with the PPS (2 mg grape juice extract, black tea and cocoa powder in equal parts) or the placebo (2 g maltodextrin). Fractional iron absorption (FIA) from each of the four test conditions was determined by measuring the incorporation of stable iron isotopes into erythrocytes using inductively coupled plasma mass spectrometry (ICP-MS)(6). Effects of treatment and matrix, as well as treatment x matrix interactions, were determined using 2-factorial repeated-measures ANCOVA.

Median (IQR) age of participants (n = 12 female; n = 8 male) was 26 (20–34) years; 12 (60 %) were alpha-thalassaemia and 8 (40 %) were beta-thalassaemia carriers. The PPS lowered FIA from the iron-rich test meal and iron-fortified test drink by 70 % and 35 %, respectively (treatment, p = 0.016; matrix, p = 0.116; treatment x matrix, p = 0.089; model adjusted for baseline haemoglobin). Median (IQR) FIA from the test meal consumed with the PPS and placebo was 0.36 (0.12–3.44) % and 1.37 (0.68–2.64) %, respectively. FIA from the test drink consumed with the PPS and placebo was 4.22 (2.42–15.3) % and 6.47 (3.00–14.0) %, respectively.

The findings from our study suggest that intake of this natural PPS alongside meals or drinks high in iron has the potential to lower iron absorption in people with non-transfusion-dependent thalassaemia. It remains to be investigated if long-term use of the PPS can reduce body iron accumulation and frequency of iron chelation therapy, as well as elicit potential cardioprotective effects, in people with non-transfusion-dependent thalassaemia.

In the transitioning era towards the COVID-19 endemic, there is still a sizable population that has never been vaccinated against COVID-19 in the Netherlands. This study employs Bayesian spatio-temporal modelling to assess the relative chances of COVID-19 vaccination uptake – first, second, and booster doses – both at the municipal and regional (public health services) levels. Incorporating ecological regression modelling to consider socio-demographic factors, our study unveils a diverse spatio-temporal distribution of vaccination uptake. Notably, the areas located in or around the Dutch main urban area (Randstad) and regions that are more religiously conservative exhibit a below-average likelihood of vaccination. Analysis at the municipal level within public health service regions indicates internal heterogeneity. Additionally, areas with a higher proportion of non-Western migrants consistently show lower chances of vaccination across vaccination dose scenarios. These findings highlight the need for tailored national and local vaccination strategies. Particularly, more regional efforts are essential to address vaccination disparities, especially in regions with elevated proportions of marginalized populations. This insight informs ongoing COVID-19 campaigns, emphasizing the importance of targeted interventions for optimizing health outcomes during the second booster phase, especially in regions with a relatively higher proportion of marginalized populations.

Background: PET imaging of [11C]ABP688 shows reduced hippocampal mGluR5 availability in mesial temporal lobe epilepsy (MTLE) patients, however the relation with post-surgical outcomes is unclear. Here, we tested whether [11C]ABP688 binding in hippocampal subfields vulnerable to glutamate excitotoxicity is related to post-surgical outcome. Methods: [11C]ABP688-PET was obtained from 31 unilateral MTLE patients and 30 controls. Hippocampal subfields were automatically segmented into 1) CA1-3, 2) CA4/dentate gyrus (DG), 3) Subiculum and manually corrected. Partial volume corrected [11C]ABP688 non-displaceable binding potential (BPND) was calculated in the subfields and compared between seizure-free and non-seizure-free patients. Results: [11C]ABP688 BPND was significantly reduced in ipsilateral CA1-3 & CA4/DG (p<0.001) compared to controls. No difference was seen in Subiculum. Ipsilateral CA1-3 [11C]ABP688 BPND was lower in seizure-free (p=0.012; Engel Ia, n=13) vs non-seizure- free (Engel Ic-III, n=10) patients, and this effect was independent of subfield volume. In a subset of patients with [18F]FDG-PET, CA1-3 [11C]ABP688 BPND was significantly lower in seizure-free patients (p=0.03), while no difference was found for [18F]FDG uptake. Conclusions: Reduced CA1-3 mGluR5 availability was associated with post-surgical seizure-freedom independent of atrophy and hypometabolism. Thus, [11C]ABP688-PET may offer a potential biomarker for surgical outcomes and may be particularly relevant for pre-surgical workup in MRI- and [18F]FDG-negative MTLE patients.

Companies offer products in different variants to reach more customers. This increases internal variety and cost. However, reducing those cost is difficult due to complexity. Complexity arises from: combinatorics; many design variables interacting with each other; coupling of technical and economical perspectives. This paper presents an approach based on (1) building a complex system model of modular models; (2) identifying the potential for standardization from a technical perspective; (3) cost-optimizing the degree of standardization. A product family of electric vehicles was optimized.

Complexity in systems design can be reduced by computing permissible ranges for some crucial design variables that need to be defined in an early design phase. These ranges are calculated such that there is sufficient tolerance for the remaining design variables in later design phases, while still achieving the overall system design goals. A new algorithm for this approach is presented and applied to the design of a vehicle powertrain mount system. The results show large permissible ranges for mount positions while maintaining sufficient tolerance for mount stiffnesses.

A reason for the slow adoption of digital twins in industry is a lack of trust in the concept and between the stakeholders involved. This paper presents a Trust Framework for Digital Twins based on a literature review and an interview study, including seven recommendations: (1) explain your twin, (2) create a common incentive, (3) make only one step at a time, (4) ensure IP protection and IT security, (5) prove your quality, (6) ensure a uniform environment, and (7) document thoroughly. Together with 20 concrete measures it supports practitioners in improving trust in their Digital Twin.

A digital twin (DT) relies on a detailed, virtual representation of a physical product. Since uncertainties and deviations can lead to significant changes in the functionality and quality of products, they should be considered in the DT. However, valuable product properties are often hidden and thus difficult to integrate into a DT. In this work, a Bayesian inverse approach based on surrogate models is applied to infer hidden composite laminate ply angles from strain measurements. The approach is able to find the true values even for ill-posed problems and shows good results up to 6 plies.

Collaboration is common practice within design disciplines and beyond. Brainstorming, discussions, and prototyping tend to occur within the same physical space. The reduction of human interaction during the COVID-19 pandemic disrupted these practices. In this paper, we focus on the possibilities and challenges of remote prototyping of four student teams by combining a double diamond approach with tools to overcome remote work challenges. The results were analyzed to understand crucial tools, advantages, and obstacles. The key challenges and opportunities were then identified and examined.

In top-down design, optimal component requirements are difficult to derive, as the feasible components that satisfy these requirements are yet to be designed and hence unknown. Meta models that provide feasibility and mass estimates for component performance are used for optimal requirement decomposition in an existing approach. This paper (1) extends its applicability adapting it to varying design domains, and (2) increases its efficiency by active-learning. Applying it to the design of a robot arm produces a result that is 1% heavier than the reference obtained by monolithic optimization.

The design of service robots is typically treated as a mechatronic design problem aimed at implementation of its core technical functionalities. Intuitive operation and usability are ignored. We developed a trash-picking service robot with a strong focus on human-robot interaction (HRI) using the double diamond framework. The HRI-focussed hardware features were successfully implemented and tested. The results were shown to satisfy the ease of operation and usability requirements set as development goals for the robot.

Background: PET imaging of [11C]ABP688 shows reduced hippocampal mGluR5 availability in mesial temporal lobe epilepsy (MTLE) patients, however the relation with post-surgical outcomes is unclear. Here, we tested whether [11C]ABP688 binding in hippocampal subfields vulnerable to glutamate excitotoxicity is related to post-surgical outcome. Methods: [11C]ABP688-PET was obtained from 31 unilateral MTLE patients and 30 controls. Hippocampal subfields were automatically segmented into 1) CA1-3, 2) CA4/dentate gyrus (DG), and 3) Subiculum and manually corrected. Partial volume corrected [11C]ABP688 non-displaceable binding potential (BPND) was calculated in the subfields and compared between seizure-free and non-seizure-free patients. Results: [11C]ABP688 BPND was significantly reduced in ipsilateral CA1-3 & CA4/DG (p<0.001) compared to controls. No difference was seen in Subiculum. Ipsilateral CA1-3 [11C]ABP688 BPND was lower in seizure-free (p=0.012; Engel Ia, n=13) vs non-seizure-free (Engel Ic-III, n=10) patients, and this effect was independent of subfield volume. In a subset of patients with [18F]FDG-PET, CA1-3 [11C]ABP688 BPND was significantly lower in seizure-free patients (p=0.03), while no difference was found for [18F]FDG uptake. Conclusions: Reduced CA1-3 mGluR5 availability was associated with post-surgical seizure-freedom independent of atrophy and hypometabolism. Thus, [11C]ABP688-PET may offer a potential biomarker for surgical outcomes and may be particularly relevant for pre-surgical workup in MRI- and [18F]FDG-negative MTLE patients.

John Rawls (1921–2002) and his work are now squarely a subject for history. In the more than fifteen years since his death, a rich body of scholarship has emerged which attempts, in different ways, to understand the nature, development, and impact of Rawls's thought from a variety of historical perspectives. With 2021 marking fifty years since A Theory of Justice (1971) was first published, this special forum examines what we here call the “historical Rawls.”

As current vehicle development processes in the automotive industry are highly distributed, the interaction between design teams is limited. In this paper we use a simulation in order to investigate how the rate of design team interaction affects the solution quality and development cost. Results show, that in case of no limiting constraints, a low rate of interaction yields the best results regarding solution quality and development cost. If design activities are affected by constraints, however, the rate of interaction is subject to a conflict between solution quality and development cost.

Maximizing the number of shared components does not always produce cost-optimal product families. Shared components can yield economies of scale due to reuse of components, but also increases material cost due to over dimensioning. In this paper, we present an approach to identify a cost-optimal design for product families. It consists of two steps: (1) identifying a scheme to share components in the product family and (2) finding the cost optimal design for the product family.

A Digital Twin as a virtual representation of a physical system is becoming a key technology. While potential benefits are evident, there is no approach in literature or practice comprehensively supporting its introduction. In an industrial case study, a generic procedure model for the conception and implementation of a Digital Twin was developed. The relations between use cases, usage data, and virtual models resulted in a target concept as well as requirements for the implementation. Thereby, companies can access the potentials of a Digital Twin taking into account their specific situation.