64 research outputs found
De Privatis Et Publicis Delictis : Disputatio Septima. De Homicidio, Veneficio Et Parricidio
No full textQuam, D.D.D. & D. Praeside ... Dn. Sigismvndo Flach ... Ventilandam publice proponit Author Michael Michaelis Itzehoa Holsatus ... ad diem 28. August
Optimized structural design of Plug & Play Core© modular stadia during preliminary design
No full textModular construction is the on-site assembly (installation and connection) of factory made units (Lawson et al., 2014). It allows fabrication of structural components to be moved from the building site to controlled environments. Ballast Nedam adopted modular construction as a key business strategy for the future (Ballast Nedam, 2014). Plug & Play Core is the modular and reusable structural core of a stadium. After realization, the inner core of the stadium can be easily disassembled, transported to another location and reused. Various stadium layouts can be realized, making the concept easily adaptable to the (varying) demands of the client/architect. The Plug & Play Core structural design needs to be easily adaptable to changing (tender) demands. At the same time the design process needs to be quick(er), resulting in more time for actual integral design. The design itself should primarily comply with safety codes, while the financial consequences of structural design decisions on other integral design aspects should be clear. An optimized design process in the form of a structural design tool is proposed to solve these challenges. The design tool should integrate FEM software for structural verification. First a literature search is performed to obtain necessary background information. After, a short summary of key design aspects regarding Plug & Play Core is presented. Then the design tool called Toolbox is explained in the form of a design manual. The main part of the report is ended with a case study of a demountable upper tier for the FIFA WC2022 Al-Wakrah stadium in Qatar. In that chapter the Toolbox design tool is applied to real project data. It is found that the integral design process of Plug & Play Core modular stadia can be optimized by the use of a design tool like the Toolbox. Early-stage consideration of full life-cycle design aspects via a cost analysis in combination with standardized structural analysis, makes the design process quick(er) and allows the designer to generate various design alternatives in a relatively short amount of time. This results in more time for integral optimization of the design. The case study insinuates that cost savings could be achieved by application of the Toolbox, making Plug & Play Core modular stadia more appealing regarding traditional construction alternatives.Design & Construction / Structural and Building EngineeringStructural EngineeringCivil Engineering and Geoscience
Energy users’ social drivers to transition from natural gas: A Dutch municipality case study
No full textDutch municipalities have a vital role in creating policy concerning natural gas replacement with sustainable sources in the built environment by 2050, i.e., the so-called heat transition. Over the years, information provision from research and consultants to municipal policymaking in the heat transition has covered mainly the techno-economic dimension. However, a gap remains in the social information provision which enables more comprehensive and inclusive decision-making. This study answers the following research question: What social aspects do municipal policymakers need to consider in municipal heat transition policymaking? We first conducted a systematic literature review concerning energy users' social drivers to transition from natural gas. Second, we conducted a single case study on the policymaking process of heat transition projects in the municipality of Zoetermeer in the Netherlands. The case study involved heat transition actors with various roles in municipal decision-making, including municipal policymakers, researchers, corporations and citizens. Then we developed a framework of the social drivers of energy users to transition from natural gas. Finally, this framework was enriched in an ex-ante evaluation in a semi-structured workshop. Our study shows that energy users' social drivers can be categorized as behavioural belief, normative belief, and control belief. These social drivers combined with the techno-economic aspects shape the energy users' participation in the heat transformation.Information and Communication TechnologyEnergy and Industr
Atypical, milder presentation in a child with CC2D2A and KIDINS220 variants
No full textWith the increasing availability and clinical use of exome and whole-genome sequencing, reverse phenotyping is now becoming common practice in clinical genetics. Here, we report a patient identified through the Wellcome Trust Deciphering Developmental Disorders study who has homozygous pathogenic variants in CC2D2A and a de-novo heterozygous pathogenic variant in KIDINS220. He presents with developmental delay, intellectual disability, and oculomotor apraxia. Reverse phenotyping has demonstrated that he likely has a composite phenotype with contributions from both variants. The patient is much more mildly affected than those with Joubert Syndrome or Spastic paraplegia, intellectual disability, nystagmus, and obesity, the conditions associated with CC2D2A and KIDINS220 respectively, and therefore, contributes to the phenotypic variability associated with the two conditions
De novo, heterozygous, loss-of-function mutations inSYNGAP1cause a syndromic form of intellectual disability
No full textDe novo mutations (DNM) in SYNGAP1, encoding Ras/Rap GTPase-activating protein SynGAP, have been reported in individuals with nonsyndromic intellectual disability (ID). We identified 10 previously unreported individuals with SYNGAP1 DNM; seven via the Deciphering Developmental Disorders (DDD) Study, one through clinical analysis for copy number variation and the remaining two (monozygotic twins) via a research multi-gene panel analysis. Seven of the nine heterozygous mutations are likely to result in loss-of-function (3 nonsense; 3 frameshift; 1 whole gene deletion). The remaining two mutations, one of which affected the monozygotic twins, were missense variants. Each individual carrying a DNM in SYNGAP1 had moderate-to-severe ID and 7/10 had epilepsy; typically myoclonic seizures, absences or drop attacks. 8/10 had hypotonia, 5/10 had significant constipation, 7/10 had wide-based/unsteady gait, 3/10 had strabismus, and 2/10 had significant hip dysplasia. A proportion of the affected individuals had a similar, myopathic facial appearance, with broad nasal bridge, relatively long nose and full lower lip vermilion. A distinctive behavioral phenotype was also observed with aggressive/challenging behavior and significant sleep problems being common. 7/10 individuals had MR imaging of the brain each of which was reported as normal. The clinical features of the individuals reported here show significant overlap with those associated with 6p21.3 microdeletions, confirming that haploinsufficiency for SYNGAP1 is responsible for both disorder
Radioguided interventions and surgery: Interventional Nuclear Medicine
No full textPreoperative imaging of solid tumors is the cornerstone of adequate staging in cancer diagnosis. Patients with cN0 or preoperative staging imaging without lymph node involvement (iN0M0) may undergo curative surgery. In many solid tumors, the sentinel lymph node procedure (SN) helps to determine if micrometastatic lymph nodes are involved, leading to adequate staging and appropriate treatment choices.During surgical procedures, the surgeon explores the operating field for target lesions of interest; both the primary tumor and the SN. In the bloodied operating field, small targets, such as the SN, are not always easy to find. Especially not in areas with difficult anatomy or richly vascularized and nerve-fed areas. Searching for this SN in these challenging areas can lead to unnecessary removal of healthy tissue with associated morbidities, incomplete resections (R1 resections), or a longer duration of surgery.Accurate preoperative imaging, surgical planning, and intraoperative tools to guide the surgeon to the desired lesion can overcome these problems. Hybrid SN tracers have been shown to offer the best in both pre- and intraoperative lesion detection.Section 1 of this thesis focuses on clinical application with combined pre- and intraoperative imaging, using the hybrid SN-tracer ICG-99mTc-nanocolloid, alone orin comparison to other radioactive tracers, for novel potential clinical indications. This section also focuses on 99mTc-Tilmanocept, a new generation SN tracer. Chapter 2 provides an overview of interventional nuclear medicine using existing and new tracers and different detection modalities that discuss the needs for and key indications of radioguided surgery (e.g., lymphatic mapping, creator delivery, and targeted tracer development) with respect to chemical and engineering initiatives. Chapters 3 and 4 compare other radiocolloids of different particle sizes with the hybrid tracer ICG-99mTc nanocolloid, which is based on the most widely used colloid particle size in Europe. In the clinical study, described in Chapter 3, lymphoscintigraphic drainage patterns, including SN and non-SLN of 99mTc-Senti-Scint and the standard tracer ICG-99mTc-nanocolloid, are compared in patients with melanoma of the head and neck and truck.In Chapter 4, drainage patterns, SN visualization and non-SN visualization of a relatively new kid on the block, 99mTc-Tilmanocept, a manose receptor binding tracer, are presented and discussed for SN procedures in patients with breast cancer and melanoma. Based on a prospective pilot study in patients with muscle-invasive bladder cancer, Chapter 5 describes the feasibility of SN targeting using the hybrid tracer indocyaninegreen (ICG)99mTc-nanocolloid for preoperative imaging and concomitant intraoperative radioconduction and fluorescence conduction. Section 2 describes innovations in the field of radioguided surgery. In a preclinical setting, Chapter 6 describes the sensitivity of using a freehand mobile SPECT gamma camera with 3D navigation to identify 99mTc-HDP positive lesions in bone scintigraphy. Furthermore, the possible use for future radioguided biopsy osseous and non-osseous applications is discussed. Chapter 7 describes the preclinical tracer development of a novel hybrid tracer for liver surgery. This approach is based on fluorescence-guided minimally invasive hepatobiliary surgery for liver cancer, including the use of preoperative imaging to visualize the lesions well in advance. Section 2 concludes with future perspectives in radioguided surgery as discussed in Chapter 8, which also contains additional suggestions for expanding the hybrid surgical guidance concept in robot-assisted surgery. In conclusion, radioguided surgery (RGS) has led to better preoperative surgical planning and a more personalized surgery approach for the patient. The development of tracers and instruments for the pre- as well as the intraoperative procedure has contributed to standardize SN biopsy, replacing extended lymph node dissections in numerous malignancies; this has led to significantly reduce complications such as nerve damage, bleeding, lymphedema and lymphatic leakage. RGS stands and falls with the proper use of tracer for both pre- and intraoperative purposes. Hybrid versions of the radiotracer shows the additional value of visual input during surgery besides the preoperative imaging and intraoperative radioguidance. Nowadays, some surgeons prefer the fluorescent SN procedure as single modality instead of the hybrid version. However, the use of fluorescence alone shows a trend of removing, in addition to the SN, a greater number of resected nodes than needs, drifting away from personalized surgery. In this context, the use of a hybrid approach with bimodal detection technology may solve the limitations of fluorescence alone. For the radioactive component the logistics is the same as used for radioguided surgery and additional investments in this regard are not necessary. Nevertheless, either resting on novel devices or original radiotracers gradual technological advances and subsequent clinical validations are necessary for continuous improving radioguided precision surgery in the future.The results described in this thesis demonstrate the added value of hybrid imaging in various indications and the potential of new hybrid tracers and medical devicesin the operating room. Current expansion of use in other indications, development of targeted hybrid tracers and intra-operative devices will further increase the fieldof RGS and interventional Nuclear Imaging.The rise of IGR offers the field of IMI unique (out-of-the-box) growth capabilities. Not only in the traditional terms of (radio)pharmaceuticals, engineering, physicsand expanding clinical indications, but also in terms of embracing up-and-coming digital-, performance-guided, and autonomous-surgery paradigms. Exploration of these opportunities will expand the impact that nuclear medicine and molecular imaging have on the future of patient care.Curium Pharma, Sirtex Medical Europe GmbHLUMC / Geneeskund
Exploring the association between SRPX2 variants and neurodevelopment: How causal is it?
No full textThe SRPX2 gene (Sushi-repeat-containing protein, X-linked, 2, OMIM*300642), located on Xq22.1, encodes a secreted protein that is highly expressed in neurons of cerebral cortex. SRPX2 was first implicated in neurodevelopment, learning and rolandic seizure when two patients with potentially pathogenic variants, c.980A>G (p.Asn327Ser) and c.215A>C (p.Tyr72Ser), in SRPX2 gene were identified. Subsequent experimental studies demonstrated that SRPX2 is needed for vocalization and synapse formation in mice, and that both silencing SRPX2 and injecting (p.Asn327Ser) in mouse models results in alteration in neuronal migration in cerebral cortex and epilepsy. A number of studies demonstrated that SRPX2 interacts with FOXP2 (Foxhead box protein P2), a gene responsible for speech and language disorder, and that FoxP2 controls timing and level of expression of SRPX2. Despite the supportive evidence for the role of SRPX2 in speech and language development and disorders, there are questions over its definitive association with neurodevelopmental disorders and epilepsy.
In this paper, the role of SRPX2 as one in a network of many genes involved in speech and language is discussed. The goal of this paper is to examine the role of SRPX2 variants through describing two patients with potentially pathogenic variants in SRPX2, c.751G>C (p.Ala251Pro) and c.762G>T (p.Lys254Asn) presenting with language and motor delay, intellectual disability as well as congenital anomalies. We explore the contribution of SRPX2 variants to clinical phenotype in our patients and conclude that these variants at least partially explain the phenotype. Further studies are necessary to establish and confirm the association between SRPX2 and neurodevelopment particularly speech and language development
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