| 1. |
- Frisoni, G. B., et al.
(författare)
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Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers
- 2017
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Ingår i: Lancet Neurology. - 1474-4422 .- 1474-4465. ; 16:8, s. 661-676
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Tidskriftsartikel (refereegranskat)abstract
- The diagnosis of Alzheimer's disease can be improved by the use of biological measures. Biomarkers of functional impairment, neuronal loss, and protein deposition that can be assessed by neuroimaging (ie, MRI and PET) or CSF analysis are increasingly being used to diagnose Alzheimer's disease in research studies and specialist clinical settings. However, the validation of the clinical usefulness of these biomarkers is incomplete, and that is hampering reimbursement for these tests by health insurance providers, their widespread clinical implementation, and improvements in quality of health care. We have developed a strategic five-phase roadmap to foster the clinical validation of biomarkers in Alzheimer's disease, adapted from the approach for cancer biomarkers. Sufficient evidence of analytical validity (phase 1 of a structured framework adapted from oncology) is available for all biomarkers, but their clinical validity (phases 2 and 3) and clinical utility (phases 4 and 5) are incomplete. To complete these phases, research priorities include the standardisation of the readout of these assays and thresholds for normality, the evaluation of their performance in detecting early disease, the development of diagnostic algorithms comprising combinations of biomarkers, and the development of clinical guidelines for the use of biomarkers in qualified memory clinics.
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| 2. |
- van Doorn, Ljcv, et al.
(författare)
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Improved Cerebrospinal Fluid-Based Discrimination between Alzheimer's Disease Patients and Controls after Correction for Ventricular Volumes
- 2017
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Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 56:2, s. 543-555
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Tidskriftsartikel (refereegranskat)abstract
- Cerebrospinal fluid (CSF) biomarkers may support the diagnosis of Alzheimer's disease (AD). We studied if the diagnostic power of AD CSF biomarker concentrations, i.e., A beta(42), total tau (t-tau), and phosphorylated tau (p-tau), is affected by differences in lateral ventricular volume (VV), using CSF biomarker data and magnetic resonance imaging (MRI) scans of 730 subjects, from 13 European Memory Clinics. We developed a Matlab-algorithm for standardized automated segmentation analysis of T1 weighted MRI scans in SPM8 for determining VV, and computed its ratio with total intracranial volume (TIV) as proxy for total CSF volume. The diagnostic power of CSF biomarkers (and their combination), either corrected for VV/TIV ratio or not, was determined by ROC analysis. CSF A beta(42) levels inversely correlated to VV/TIV in the whole study population (A beta(42): r = -0.28; p < 0.0001). For CSF t-tau and p-tau, this association only reached statistical significance in the combined MCI and AD group (t-tau: r = -0.15; p-tau: r = -0.13; both p < 0.01). Correction for differences in VV/TIV improved the differentiation of AD versus controls based on CSF A beta(42) alone (AUC: 0.75 versus 0.81) or in combination with t-tau (AUC: 0.81 versus 0.91). In conclusion, differences in VV may be an important confounder in interpreting CSF A beta(42) levels.
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| 6. |
- Minoia, F, et al.
(författare)
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Dissecting the heterogeneity of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis
- 2015
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Ingår i: The Journal of rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 42:6, s. 994-1001
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Tidskriftsartikel (refereegranskat)abstract
- To seek insights into the heterogeneity of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (sJIA) through the analysis of a large patient sample collected in a multinational survey.Methods.International pediatric rheumatologists and hemato-oncologists entered their patient data, collected retrospectively, in a Web-based database. The demographic, clinical, laboratory, histopathologic, therapeutic, and outcome data were analyzed in relation to (1) geographic location of caring hospital, (2) subspecialty of attending physician, (3) demonstration of hemophagocytosis, and (4) severity of clinical course.Results.A total of 362 patients were included by 95 investigators from 33 countries. Demographic, clinical, laboratory, and histopathologic features were comparable among patients seen in diverse geographic areas or by different pediatric specialists. Patients seen in North America were given biologics more frequently. Patients entered by pediatric hemato-oncologists were treated more commonly with biologics and etoposide, whereas patients seen by pediatric rheumatologists more frequently received cyclosporine. Patients with demonstration of hemophagocytosis had shorter duration of sJIA at MAS onset, higher prevalence of hepatosplenomegaly, lower levels of platelets and fibrinogen, and were more frequently administered cyclosporine, intravenous immunoglobulin (IVIG), and etoposide. Patients with severe course were older, had longer duration of sJIA at MAS onset, had more full-blown clinical picture, and were more commonly given cyclosporine, IVIG, and etoposide.Conclusion.The clinical spectrum of MAS is comparable across patients seen in different geographic settings or by diverse pediatric subspecialists. There was a disparity in the therapeutic choices among physicians that underscores the need to establish uniform therapeutic protocols.
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| 10. |
- Romagnoli, F, et al.
(författare)
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Windstorm impacts on European forest-related systems: an interdisciplinary perspective
- 2023
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Ingår i: Forest Ecology and Management. - 1872-7042 .- 0378-1127. ; 541
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Tidskriftsartikel (refereegranskat)abstract
- Windstorms are considered the main disturbing abiotic agent in European forests. They affect a multiplicity of forest-related dimensions, such as forest ecology, forest operations, geomorphology, economy, and socio-cultural aspects. Due to the complex dynamics set off by windstorms, the design of post-windstorm forest management should be characterized by an interdisciplinary approach able to address multiple environmental and social needs. However, scientific literature investigating the impacts of windstorms on forests appears mainly focused on specific aspects. An interdisciplinary and more comprehensive approach is needed to cope with such multi-facet phenomena and to address future forest research.We reviewed current literature analyzing consequences of windstorms on European forests focusing on interconnections and cascade effects among forest-related dimensions in post-windstorm dynamics. We performed an in-depth review of 111 articles to detect most recurrent direct and indirect impacts as well as cascade effects among ecological, geomorphological, operational, economic, socio-cultural, and institutional forest-related dimensions. Our analysis aimed at providing a detailed analysis of the state of the art of windstorm impacts on European forests reported in literature, and suggesting an innovative approach to analyze windstorm consequences at a systemic level to acquire a comprehensive overview of post-windstorm dynamics.Our results showed that most of the studies dealt with interactions among ecological components of forests, but links between ecology, geomorphology, and society have been poorly studied. These knowledge gaps reduce the comprehension of windstorm impacts in the short and long terms and overlook the influence of societal-related aspects in post-windstorm forest management. Moreover, our analysis suggested the need of a post-windstorm management acting at systemic and comprehensive level, supported by forest policies that promotes multifunctionality to overcome challenges derived by natural disturbances intensification.
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| 13. |
- Faccincani, R, et al.
(författare)
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Evaluation of Interaction Between Emergency Medical System and Hospital Network During a Train Derailment in Milano
- 2021
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Ingår i: Disaster medicine and public health preparedness. - : Cambridge University Press (CUP). - 1938-744X .- 1935-7893. ; 16:2, s. 829-834
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Tidskriftsartikel (refereegranskat)abstract
- On January 25, 2018 a 5-car train derailed in Pioltello, 10 kilometers North-East of Milano City. A standardized post-hoc form was distributed to the hospitals involved in the management of the victims and allowed for an evaluation of the response to the incident.The management of the incident by EMS (Emergency Medical System) was effective in terms of organization of the scene and distribution of the patients, although the time for the first severe patient to reach the closest appropriate hospital was very long (2 hours). This can be partially explained by the extrication time.None of the alerted hospitals exceeded their capacity, as patients were distributed carefully among the hospitals. The overall outcome was quite satisfactory; no deaths were reported except for those on scene. Some responding hospitals reported that there was an over-activation based on the services ultimately needed. However this is common in MCIs, as an over-activation is preferable to an under-estimation. To address this concern, as more data are available, activation should be scaled down based on a plan established prior to it; this mechanism of scaling down seems to have failed in this event.It is of note that the highest performing hospitals underwent recently to an educational program on MCI management.
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| 14. |
- McCann, Julie A., et al.
(författare)
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Connected Things Connecting Europe
- 2019
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Ingår i: Communications of the ACM. - : Association for Computing Machinery (ACM). - 0001-0782 .- 1557-7317. ; 62:4, s. 46-51
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Tidskriftsartikel (refereegranskat)
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| 15. |
- Mottola, Luca, et al.
(författare)
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MakeSense : Simplifying the Integration of Wireless Sensor Networks into Business Processes
- 2019
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Ingår i: IEEE Transactions on Software Engineering. - : Institute of Electrical and Electronics Engineers Inc.. - 0098-5589 .- 1939-3520. ; 45:6, s. 576-596
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Tidskriftsartikel (refereegranskat)abstract
- A wide gap exists between the state of the art in developing Wireless Sensor Network (WSN) software and current practices concerning the design, execution, and maintenance of business processes. WSN software is most often developed based on low-level OS abstractions, whereas business process development leverages high-level languages and tools. This state of affairs places WSNs at the fringe of industry. The makeSense system addresses this problem by simplifying the integration of WSNs into business processes. Developers use BPMN models extended with WSN-specific constructs to specify the application behavior across both traditional business process execution environments and the WSN itself, which is to be equipped with application-specific software. We compile these models into a high-level intermediate language-Also directly usable by WSN developers-And then into OS-specific deployment-ready binaries. Key to this process is the notion of meta-Abstraction, which we define to capture fundamental patterns of interaction with and within the WSN. The concrete realization of meta-Abstractions is application-specific; developers tailor the system configuration by selecting concrete abstractions out of the existing codebase or by providing their own. Our evaluation of makeSense shows that i) users perceive our approach as a significant advance over the state of the art, providing evidence of the increased developer productivity when using makeSense; ii) in large-scale simulations, our prototype exhibits an acceptable system overhead and good scaling properties, demonstrating the general applicability of makeSense; and, iii) our prototype-including the complete tool-chain and underlying system support-sustains a real-world deployment where estimates by domain specialists indicate the potential for drastic reductions in the total cost of ownership compared to wired and conventional WSN-based solutions.
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| 16. |
- Pinto, Rita, et al.
(författare)
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Identification of new cancer biomarkers based on aberrant mucin glycoforms by in situ proximity ligation
- 2012
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Ingår i: Journal of Cellular and Molecular Medicine (Print). - : Wiley. - 1582-1838 .- 1582-4934. ; 16:7, s. 1474-1484
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Tidskriftsartikel (refereegranskat)abstract
- Mucin glycoproteins are major secreted or membrane-bound molecules that, in cancer, show modifications in both the mucin proteins expression and in the O-glycosylation profile, generating some of the most relevant tumour markers in clinical use for decades. Thus far, the identification of these biomarkers has been based on the detection of either the protein or the O-glycan modifications. We therefore aimed to identify the combined mucin and O-glycan features, i.e. specific glycoforms, in an attempt to increase specificity of these cancer biomarkers. Using in situ proximity ligation assays (PLA) based on existing monoclonal antibodies directed to MUC1, MUC2, MUC5AC and MUC6 mucins and to cancer-associated carbohydrate antigens Tn, Sialyl-Tn (STn), T, Sialyl-Lea (SLea) and Sialyl-Lex (SLex) we screened a series of 28 mucinous adenocarcinomas from different locations (stomach, ampulla of Vater, colon, lung, breast and ovary) to detect specific mucin glycoforms. We detected Tn/STn/SLea/SLex-MUC1 and STn/SLea/SLex-MUC2 glycoforms in ≥50% of the cases, with a variable distribution among organs. Some new glycoforms – T/SLea-MUC2, STn/T/SLea/SLex-MUC5AC and STn/T/SLea/SLex-MUC6 – were identified for the first time in the present study in a variable percentage of cases from different organs. In conclusion, application of the PLA technique allowed sensitive detection of specific aberrant mucin glycoforms in cancer, increasing specificity to the use of antibodies either to the mucin protein backbone or the O-glycan haptens alone.
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| 17. |
- van Waalwijk van Doorn, Linda J C, et al.
(författare)
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Improved Cerebrospinal Fluid-Based Discrimination between Alzheimer's Disease Patients and Controls after Correction for Ventricular Volumes
- 2017
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 56:2, s. 543-555
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Tidskriftsartikel (refereegranskat)abstract
- Cerebrospinal fluid (CSF) biomarkers may support the diagnosis of Alzheimer's disease (AD). We studied if the diagnostic power of AD CSF biomarker concentrations, i.e., Aβ42, total tau (t-tau), and phosphorylated tau (p-tau), is affected by differences in lateral ventricular volume (VV), using CSF biomarker data and magnetic resonance imaging (MRI) scans of 730 subjects, from 13 European Memory Clinics. We developed a Matlab-algorithm for standardized automated segmentation analysis of T1 weighted MRI scans in SPM8 for determining VV, and computed its ratio with total intracranial volume (TIV) as proxy for total CSF volume. The diagnostic power of CSF biomarkers (and their combination), either corrected for VV/TIV ratio or not, was determined by ROC analysis. CSF Aβ42 levels inversely correlated to VV/TIV in the whole study population (Aβ42: r=-0.28; p<0.0001). For CSF t-tau and p-tau, this association only reached statistical significance in the combined MCI and AD group (t-tau: r=-0.15; p-tau: r=-0.13; both p<0.01). Correction for differences in VV/TIV improved the differentiation of AD versus controls based on CSF Aβ42 alone (AUC: 0.75 versus 0.81) or in combination with t-tau (AUC: 0.81 versus 0.91). In conclusion, differences in VV may be an important confounder in interpreting CSF Aβ42 levels.
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