Review of visualising LCA results in the design process of buildings

Life Cycle Assessment (LCA) is increasingly used for decision-making in the design process of buildings and neighbourhoods. Therefore, visualisation of LCA results to support interpretation and decision-making becomes more important. The number of building LCA tools and the published literature has increased substantially in recent years. Most of them include some type of visualisation. However, there are currently no clear guidelines and no harmonised way of presenting LCA results. In this paper, we review the current state of the art in visualising LCA results to provide a structured overview. Furthermore, we discuss recent and potential future developments. The review results show a great variety in visualisation options. By matching them with common LCA goals we provide a structured basis for future developments. Case studies combining different kinds of visualisations within the design environment, interactive dashboards, and immersive technologies, such as virtual reality, show a big potential for facilitating the interpretation of LCA results and collaborative design processes. The overview and recommendations presented in this paper provide a basis for future development of intuitive and design-integrated visualisation of LCA results to support decision-making.ISSN:0360-1323ISSN:0360-132

Clinical, Genetic, and Pathological Studies in Two Brothers with Stress-Induced Childhood-Onset Neurodegeneration with Variable Ataxia and Seizures: A Case Report

Introduction: Stress-induced childhood-onset neurodegeneration with variable ataxia and seizures (CONDSIAS) is an autosomal recessive disorder caused by biallelic pathogenic variants in the ADPRS gene. Since its first description in 2018, less than fifty cases have been reported worldwide, but thus far, without histopathology of the nervous system. Case Presentation: We summarize the clinical, paraclinical, and genetic characteristics of the disease in the proband, and the pathological workup in his older brother who passed away more than a decade ago. The characteristics of CONDSIAS in the two brothers overlapped with those of Friedreich ataxia. A final clarification of the diagnosis was made possible by whole exome sequencing (WES) that identified the homozygous pathogenic variants in the ADPRS gene. Conclusion: CONDSIAS is a rare disorder with highly variable presentation. Based on solely clinical and even pathological workup, establishing a definite diagnosis may be challenging. In the two brothers, we observed clinical and histopathological features of the disease suggesting, though not completely fulfilling, the diagnosis of Friedreich’s ataxia. WES allowed us to rapidly identify the underlying genetic abnormality and to make a shortcut to the right diagnosis amongst recessive ataxias. As of today, no specific treatment for CONDSIAS is available. Repurposing of certain approved modalities that also target the affected pathway in CONDSIAS recently arose, though as yet without proven success. Knowing the biological relevance of the affected gene product offers potential targets for the development of disease-modifying drugs for this highly disabling disease in the near future

IEA EBC Annex 72: Assessing Life Cycle Related Environmental Impacts Caused by Buildings: Guidelines for design decision-makers:Energy in Buildings and Communities Technology Collaboration Programme

The purpose of this report is to provide support to the design decisions-makers during the design process. For each of the defined design step decision the important topics to consider were identified, the key stakeholders are declared and the purpose of LCA at the selected design step is defined. The report covers: The definition of the design steps, the definition of the tasks in each design step and an overview of the relevant milestones for performing LCA; An overview of the systematic building decomposition methods and the appropriate levels at each design step; An overview of the tools that can be used for LCA and a selection process for choosing the right LCA tool. A special emphasize is given to the topic of Building Information Modelling (BIM), how the BIM tools can facilitate the LCA assessment and what information should be implemented in the BIM model; Strategies on how to reduce the design-related uncertainties; An overview of the visualization of the LCA results and which are appropriate in the selected design steps

Hidden Cardiotoxicity of Rofecoxib Can be Revealed in Experimental Models of Ischemia/Reperfusion

Cardiac adverse effects are among the leading causes of the discontinuation of clinical trials and the withdrawal of drugs from the market. The novel concept of 'hidden cardiotoxicity' is defined as cardiotoxicity of a drug that manifests in the diseased (e.g. ischemic/reperfused), but not in the healthy heart or as a drug-induced deterioration of cardiac stress adaptation (e.g. ischemic conditioning). Here, we aimed to test if the cardiotoxicity of a selective COX-2 inhibitor rofecoxib that was revealed during its clinical use, i.e., increased occurrence of proarrhythmic and thrombotic events, could have been revealed in early phases of drug development by using preclinical models of ischemia/reperfusion (I/R) injury. Rats that were treated with rofecoxib or vehicle for four weeks were subjected to 30 min. coronary artery occlusion and 120 min. reperfusion with or without cardioprotection that is induced by ischemic preconditioning (IPC). Rofecoxib increased overall the arrhythmias including ventricular fibrillation (VF) during I/R. The proarrhythmic effect of rofecoxib during I/R was not observed in the IPC group. Rofecoxib prolonged the action potential duration (APD) in isolated papillary muscles, which was not seen in the simulated IPC group. Interestingly, while showing hidden cardiotoxicity manifested as a proarrhythmic effect during I/R, rofecoxib decreased the infarct size and increased the survival of adult rat cardiac myocytes that were subjected to simulated I/R injury. This is the first demonstration that rofecoxib increased acute mortality due to its proarrhythmic effect via increased APD during I/R. Rofecoxib did not interfere with the cardiprotective effect of IPC; moreover, IPC was able to protect against rofecoxib-induced hidden cardiotoxicity. These results show that cardiac safety testing with simple preclinical models of I/R injury uncovers hidden cardiotoxicity of rofecoxib and might reveal the hidden cardiotoxicity of other drugs

Vanishing White Matter Disease, a Rare Leukodystrophy with Mutation in the EIF2B5 Gene = Eltűnő fehérállomány-betegség, a leukodystrophiák ritka altípusa az EIF2B5 gén mutációjával

Background – Leukodystrophies, a heterogeneous group of brain and spinal cord disorders, often pose challenges in establishing molecular etiology. Vanishing White Matter Disease (VWMD) is a rare subtype of leukodystrophies presenting with characteristic clinical and MRI features, nevertheless, achieving diagnostic certainty requires genetic studies. Case presentation – Our patient is a nine year old girl, who developed progressive gait difficulties at around 3-4 years of age. Her brain MRI showed confluent lesions with in­creased signal intensity in the cerebral and cerebellar white matter on T2/FLAIR sequences, within which hypointense regions appeared with signal intensity resembling that of the cerebrospinal fluid on T1 sequences. Whole exome sequencing identified a homozygous likely pathogenic variant within the EIF2B5 gene in the proband, which was present in a heterozygous state in both asymptomatic parents. Having the clinical and molecular genetic diagnosis established, we explored therapeutic possibilities for the patient. Conclusion – VWMD is a severe form of leukodystrophies with little or no disease modifying therapy available until recently. A better understanding of its molecular pathogenesis offers some hope for new inventive therapies. Háttér – A leukodystrophiák az agy és a gerincvelő heterogén betegségei, gyakran diagnosztikai kihívásokkal szembesítik a vizsgálót a molekuláris etiológia meghatározásakor. A vanishing white matter disease (VWMD) vagy eltűnő fehérállomány-betegség a leukodystrophiák ritka altípusa, ami jellegzetes klinikai és MRI-sajátosságokkal rendelkezik, de a diagnosztikai bizonyosság érdekében genetikai vizsgálatok szükségesek. Esetbemutató – Betegünk egy kilencéves kislány, akinek 3-4 éves kora körül kezdődött progresszív járásproblémája. Az MRI-T2/FLAIR-szekvenciákon konfluens fokozott jelintenzitású elváltozások látszottak a hemisphaerialis és a kisagyi fehérállományban, amelyeken belül a T1 szekvenciákon a liquorhoz hasonló jelintenzitású hipointenzív régiók jelentek meg. A teljesexom-szekvenálás homozigóta, valószínű patogén variánst azonosított a proband EIF2B5 génjében, ami heterozigóta formában volt jelen a tünetmentes szülőkben. A klinikai és molekuláris genetikai diagnózis felállítása után megvizsgáltuk a beteg terápiás lehetőségeit. Következtetés – A VWMD a leukodystrophiák súlyos formája, amelyhez mostanáig alig vagy egyáltalán nem állt rendelkezésre betegségmódosító terápia. A molekuláris patogenezis jobb megértése reményt ad új innovatív terápiák bevezetéséhez

Affinity Purification and Comparative Biosensor Analysis of Citrulline-Peptide-Specific Antibodies in Rheumatoid Arthritis

Background: In rheumatoid arthritis (RA), anti-citrullinated protein/peptide antibodies (ACPAs) are responsible for disease onset and progression, however, our knowledge is limited on ligand binding affinities of autoantibodies with different citrulline-peptide specificity. Methods: Citrulline-peptide-specific ACPA IgGs were affinity purified and tested by ELISA. Binding affinities of ACPA IgGs and serum antibodies were compared by surface plasmon resonance (SPR) analysis. Bifunctional nanoparticles harboring a multi-epitope citrulline-peptide and a complement-activating peptide were used to induce selective depletion of ACPA-producing B cells. Results: KD values of affinity-purified ACPA IgGs varied between 10−6 and 10−8 M and inversely correlated with disease activity. Based on their cross-reaction with citrulline-peptides, we designed a novel multi-epitope peptide, containing Cit-Gly and Ala-Cit motifs in two–two copies, separated with a short, neutral spacer. This peptide detected antibodies in RA sera with 66% sensitivity and 98% specificity in ELISA and was recognized by 90% of RA sera, while none of the healthy samples in SPR. When coupled to nanoparticles, the multi-epitope peptide specifically targeted and depleted ACPA-producing B cells ex vivo. Conclusions: The unique multi-epitope peptide designed based on ACPA cross-reactivity might be suitable to develop better diagnostics and novel therapies for RA