| 1. |
- Baumann, Henrikke, 1964, et al.
(författare)
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Does the Production of an Airbag Injure more People than the Airbag Saves in Traffic?: Opting for an Empirically Based Approach to Social Life Cycle Assessment
- 2013
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Ingår i: Journal of Industrial Ecology. - : Wiley. - 1530-9290 .- 1088-1980. ; 17:4, s. 517-527
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Tidskriftsartikel (refereegranskat)abstract
- Social life cycle assessment (S-LCA) has been discussed for some years in the LCA community. We raise two points of criticism against current S-LCA approaches. First, the development of S-LCA methodology has not, to date, been based on experience with actual case studies. Second, for social impacts to be meaningfully assessed in a life cycle perspective, social indicators need to be unambiguously interpreted in all social contexts along the life cycle. We here discuss an empirically based approach to S-LCA, illustrated by a case study of an automobile airbag system. The aim of the case study is to compare the injuries and lives lost during the product life cycle of the airbag system (excluding waste handling impacts) with the injuries prevented and lives saved during its use. The indicator used for assessing social impacts in this study is disability-adjusted life years (DALY). The results from this study indicate that the purpose of an airbag system, which is to save lives and prevent injuries, is justified also in a life cycle perspective.
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| 2. |
- Baumann, Henrikke, 1964, et al.
(författare)
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Life Cycle Assessment on Life and Death: Comparing Lives Saved by an Airbag with Lives Lost during Its Production
- 2011
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Ingår i: 6th International Conference on Industrial Ecology, Berkley, California, June 7-10, 2011.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Recently, a framework for including social impacts of a products life cycle has been developed by United Nations Environmental Programme and the Society of Environmental Toxicology and Chemistry. That framework includes impact categories such as human rights, working conditions and governance. Here, we present a different approach that balances impacts with benefits: lives saved by the product during the life cycle minus lives lost during the life cycle as impact category. The study object, and also the functional unit of the study, is an air bag with its electronic control system. The main object of an airbag is to save lives. However, during the production of the airbag and its control systems, lives may be lost, for instance in the production of pyrotechnical content of the airbag and in the mining of metals for the electronic control unit. The mining of metals often takes place in developing countries with poor legislation for working conditions and sometimes conflict areas. The impact is characterized as the average number of lives saved per functional unit minus the casualties believed to occur during production of one functional unit. This is a convenient indicator since it easy to interpret and comprehend. It also gives a quantitative estimate of whether the airbag is reasonable from a social point of view from a life cycle perspective, or if it just exports the casualties to other parts of the world. We also discuss in the study when there is a benefit to gain from investigating social impacts along a life cycle. The study is currently ongoing, and results will be ready to for presentation by the time of the conference.
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| 3. |
- Abolhassani, Hassan, et al.
(författare)
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X-Linked TLR7 Deficiency Underlies Critical COVID-19 Pneumonia in a Male Patient with Ataxia-Telangiectasia
- 2022
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Ingår i: Journal of Clinical Immunology. - : Springer Science and Business Media LLC. - 0271-9142 .- 1573-2592. ; 42:1, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Background Coronavirus disease 2019 (COVID-19) exhibits a wide spectrum of clinical manifestations, ranging from asymptomatic to critical conditions. Understanding the mechanism underlying life-threatening COVID-19 is instrumental for disease prevention and treatment in individuals with a high risk.Objectives We aimed to identify the genetic cause for critical COVID-19 pneumonia in a patient with a preexisting inborn error of immunity (IEI).Methods Serum levels of specific antibodies against the virus and autoantibodies against type I interferons (IFNs) were measured. Whole exome sequencing was performed, and the impacts of candidate gene variants were investigated. We also evaluated 247 ataxia-telangiectasia (A-T) patients in the Iranian IEI registry.Results We report a 7-year-old Iranian boy with a preexisting hyper IgM syndrome who developed critical COVID-19 pneumonia. IgM only specific COVID-19 immune response was detected but no autoantibodies against type I IFN were observed. A homozygous deleterious mutation in the ATM gene was identified, which together with his antibody deficiency, radiosensitivity, and neurological signs, established a diagnosis of A-T. Among the 247 A-T patients evaluated, 36 had SARS-CoV-2 infection, but all had mild symptoms or were asymptomatic except the index patient. A hemizygous deleterious mutation in the TLR7 gene was subsequently identified in the patient.Conclusions We report a unique IEI patient with combined ATM and TLR7 deficiencies. The two genetic defects underlie A-T and critical COVID-19 in this patient, respectively.
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| 4. |
- Camponeschi, Alessandro, et al.
(författare)
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Dissecting Integrin Expression and Function on Memory B Cells in Mice and Humans in Autoimmunity.
- 2019
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Immunological memory ensures life-long protection against previously encountered pathogens, and in mice and humans the spleen is an important reservoir for long-lived memory B cells (MBCs). It is well-established that integrins play several crucial roles in lymphocyte survival and trafficking, but their involvement in the retention of MBCs in secondary lymphoid organs, and differences between B cell subsets in their adhesion capacity to ICAM-1 and/or VCAM-1 have not yet been confirmed. Here, we use an autoimmune mouse model, where MBCs are abundant, to show that the highest levels of LFA-1 and VLA-4 amongst B cells are found on MBCs. In vivo blockade of VLA-4 alone or in combination with LFA-1, but not LFA-1 alone, causes a release of MBCs from the spleen into the blood stream. In humans, we find that in peripheral blood, spleens, and tonsils from healthy donors the highest expression levels of the integrins LFA-1 and VLA-4 are also found on MBCs. Consistent with this, we found MBCs to have a higher capacity to adhere to ICAM-1 and VCAM-1 than naïve B cells. In patients with the autoimmune disease rheumatoid arthritis, it is the MBCs that have the highest levels of LFA-1 and VLA-4; moreover, compared with healthy donors, naïve B and MBCs of patients receiving anti-TNF medication have enhanced levels of the active form of LFA-1. Commensurate levels of the active αL subunit can be induced on B cells from healthy donors by exposure to the integrin ligands. Thus, our findings establish the selective use of the integrins LFA-1 and VLA-4 in the localization and adhesion of MBCs in both mice and humans.
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| 5. |
- Cansby, Emmelie, 1984, et al.
(författare)
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Silencing of STE20-type kinase STK25 in human aortic endothelial and smooth muscle cells is atheroprotective
- 2022
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies highlight the importance of lipotoxic damage in aortic cells as the major pathogenetic contributor to atherosclerotic disease. Since the STE20-type kinase STK25 has been shown to exacerbate ectopic lipid storage and associated cell injury in several metabolic organs, we here investigate its role in the main cell types of vasculature. We depleted STK25 by small interfering RNA in human aortic endothelial and smooth muscle cells exposed to oleic acid and oxidized LDL. In both cell types, the silencing of STK25 reduces lipid accumulation and suppresses activation of inflammatory and fibrotic pathways as well as lowering oxidative and endoplasmic reticulum stress. Notably, in smooth muscle cells, STK25 inactivation hinders the shift from a contractile to a synthetic phenotype. Together, we provide several lines of evidence that antagonizing STK25 signaling in human aortic endothelial and smooth muscle cells is atheroprotective, highlighting this kinase as a new potential therapeutic target for atherosclerotic disease.
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| 6. |
- Mou, Haiwei, et al.
(författare)
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CRISPR-induced exon skipping of β-catenin reveals tumorigenic mutants driving distinct subtypes of liver cancer
- 2023
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Ingår i: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 259:4, s. 415-427
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Tidskriftsartikel (refereegranskat)abstract
- CRISPR/Cas9-driven cancer modeling studies are based on the disruption of tumor suppressor genes by small insertions or deletions (indels) that lead to frame-shift mutations. In addition, CRISPR/Cas9 is widely used to define the significance of cancer oncogenes and genetic dependencies in loss-of-function studies. However, how CRISPR/Cas9 influences gain-of-function oncogenic mutations is elusive. Here, we demonstrate that single guide RNA targeting exon 3 of Ctnnb1 (encoding β-catenin) results in exon skipping and generates gain-of-function isoforms in vivo. CRISPR/Cas9-mediated exon skipping of Ctnnb1 induces liver tumor formation in synergy with YAPS127A in mice. We define two distinct exon skipping-induced tumor subtypes with different histological and transcriptional features. Notably, ectopic expression of two exon-skipped β-catenin transcript isoforms together with YAPS127A phenocopies the two distinct subtypes of liver cancer. Moreover, we identify similar CTNNB1 exon-skipping events in patients with hepatocellular carcinoma. Collectively, our findings advance our understanding of β-catenin-related tumorigenesis and reveal that CRISPR/Cas9 can be repurposed, in vivo, to study gain-of-function mutations of oncogenes in cancer.
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| 7. |
- Vazquez, Sara E., et al.
(författare)
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Autoantibody discovery across monogenic, acquired, and COVID-19-associated autoimmunity with scalable PhIP-seq
- 2022
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Phage immunoprecipitation sequencing (PhIP-seq) allows for unbiased, proteome-wide autoantibody discovery across a variety of disease settings, with identification of disease-specific autoantigens providing new insight into previously poorly understood forms of immune dysregulation. Despite several successful implementations of PhIP-seq for autoantigen discovery, including our previous work (Vazquez et al., 2020), current protocols are inherently difficult to scale to accommodate large cohorts of cases and importantly, healthy controls. Here, we develop and validate a high throughput extension of PhIP-seq in various etiologies of autoimmune and inflammatory diseases, including APS1, IPEX, RAG1/2 deficiency, Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C), and finally, mild and severe forms of COVID-19. We demonstrate that these scaled datasets enable machine-learning approaches that result in robust prediction of disease status, as well as the ability to detect both known and novel autoantigens, such as prodynorphin (PDYN) in APS1 patients, and intestinally expressed proteins BEST4 and BTNL8 in IPEX patients. Remarkably, BEST4 antibodies were also found in two patients with RAG1/2 deficiency, one of whom had very early onset IBD. Scaled PhIP-seq examination of both MIS-C and KD demonstrated rare, overlapping antigens, including CGNL1, as well as several strongly enriched putative pneumonia-associated antigens in severe COVID-19, including the endosomal protein EEA1. Together, scaled PhIP-seq provides a valuable tool for broadly assessing both rare and common autoantigen overlap between autoimmune diseases of varying origins and etiologies.
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