| 1. |
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| 2. |
- Allaire, C., et al.
(författare)
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Beam test measurements of Low Gain Avalanche Detector single pads and arrays for the ATLAS High Granularity Timing Detector
- 2018
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Ingår i: Journal of Instrumentation. - : Institute of Physics (IOP). - 1748-0221. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- For the high luminosity upgrade of the LHC at CERN, ATLAS is considering the addition of a High Granularity Timing Detector (HGTD) in front of the end cap and forward calorimeters at vertical bar z vertical bar = 3:5 m and covering the region 2:4 < vertical bar eta vertical bar < 4 to help reducing the effect of pile-up. The chosen sensors are arrays of 50 mu m thin Low Gain Avalanche Detectors (LGAD). This paper presents results on single LGAD sensors with a surface area of 1.3 x 1.3 mm(2) and arrays with 2 x 2 pads with a surface area of 2 x 2 mm(2) or 3 x 3 mm(2) each and different implant doses of the p(+) multiplication layer. They are obtained from data collected during a beam test campaign in autumn 2016 with a pion beam of 120 GeV energy at the CERN SPS. In addition to several quantities measured inclusively for each pad, the gain, efficiency and time resolution have been estimated as a function of the position of the incident particle inside the pad by using a beam telescope with a position resolution of few mu m. Different methods to measure the time resolution are compared, yielding consistent results. The sensors with a surface area of 1.3 x 1.3 mm(2) have a time resolution of about 40 ps for a gain of 20 and of about 27 ps for a gain of 50 and fulfil the HGTD requirements. Larger sensors have, as expected, a degraded time resolution. All sensors show very good efficiency and time resolution uniformity.
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| 3. |
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| 4. |
- Cavallaro, Paul M., et al.
(författare)
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Patients Undergoing Ileoanal Pouch Surgery Experience a Constellation of Symptoms and Consequences Representing a Unique Syndrome: A Report from the Patient-Reported Outcomes After Pouch Surgery (PROPS) Delphi Consensus Study
- 2021
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Ingår i: Diseases of the Colon & Rectum. - : LIPPINCOTT WILLIAMS & WILKINS. - 0012-3706 .- 1530-0358. ; 64:7, s. 861-870
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Functional outcomes after ileoanal pouch creation have been studied; however, there is great variability in how relevant outcomes are defined and reported. More importantly, the perspective of patients has not been represented in deciding which outcomes should be the focus of research. OBJECTIVE: The primary aim was to create a patient-centered definition of core symptoms that should be included in future studies of pouch function. DESIGN: This was a Delphi consensus study. SETTING: Three rounds of surveys were used to select high-priority items. Survey voting was followed by a series of online patient consultation meetings used to clarify voting trends. A final online consensus meeting with representation from all 3 expert panels was held to finalize a consensus statement. PATIENTS: Expert stakeholders were chosen to correlate with the clinical scenario of the multidisciplinary team that cares for pouch patients, including patients, colorectal surgeons, and gastroenterologists or other clinicians. MAIN OUTCOME MEASURES: A consensus statement was the main outcome. RESULTS: One hundred ninety-five patients, 62 colorectal surgeons, and 48 gastroenterologists or nurse specialists completed all 3 Delphi rounds. Fifty-three patients participated in online focus groups. One hundred sixty-one stakeholders participated in the final consensus meeting. On conclusion of the consensus meeting, 7 bowel symptoms and 7 consequences of undergoing ileoanal pouch surgery were included in the final consensus statement. LIMITATIONS: The study was limited by online recruitment bias. CONCLUSIONS: This study is the first to identify key functional outcomes after pouch surgery with direct input from a large panel of ileoanal pouch patients. The inclusion of patients in all stages of the consensus process allowed for a true patient-centered approach in defining the core domains that should be focused on in future studies of pouch function. See Video Abstract at http://links.lww.com/DCR/B571.
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| 5. |
- Ghetti, R., et al.
(författare)
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Influence of multiple sources on the two-neutron correlation function in Ni-induced, intermediate energy, heavy ion reactions
- 2001
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Ingår i: Physical Review C. Nuclear Physics. - : American Physical Society. - 0556-2813 .- 1089-490X. ; 64:1
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Tidskriftsartikel (refereegranskat)abstract
- The strength of the neutron-neutron correlation function from the E=45AMeV58Ni+27Al, natNi, and 197Au reactions depends on the neutron parallel velocity. This indicates the presence of multiple sources of neutron emission. We find these sources consistent with a dissipative, binary reaction mechanism as it is described by, e.g., Boltzmann-Uehling-Uhlenbeck calculations.
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| 8. |
- Haschka, J, et al.
(författare)
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Identification of circulating microRNA patterns in patients in psoriasis and psoriatic arthritis
- 2023
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Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 62:10, s. 3448-3458
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivemiRNAs are small non-coding RNAs that control gene expression. Specific intra- and extracellular miRNA signatures have been identified in various diseases. Whether certain miRNA signatures are associated with psoriasis (PsO) and PsA is currently unknown. We aimed to search for circulating miRNA signatures associated with PsO and PsA patients.MethodsExpression of miRNAs was analysed by reverse transcription quantitative real-time PCR (RT-qPCR) in the serum of PsA, PsO patients and healthy controls. Demographic and disease-specific characteristics and imaging data from hand MRI were recorded. In the discovery phase, 192 miRNA assays were analysed in 48 samples (PsA, PsO, controls: each N = 16). For validation, 17 selected miRNAs were measured in the total population.ResultsA total of 141 patients and controls were analysed (51 PsA, 40 PsO, 50 controls). In the discovery phase 51 miRNAs in PsO and 64 miRNAs in PsA were down- or upregulated compared with controls, with 33 miRNAs being changed in both (adj. P < 0.05). The 17 top candidates from discovery were assessed in the validation phase, 9 of them discriminated PsA and PsO from controls [area under the curve (AUC) ≥0.70, all P < 0.05]. Four miRNAs (miR-19b-3p, miR-21-5p, miR-92a-3p and let-7b-5p) were significantly differently regulated between PsO and PsA. A combination of these miRNAs increased the AUC to 0.92 in multivariate regression model to discriminate PsO and PsA.ConclusionmiRNA signatures in PsA and PsO patients differ from controls. Nine miRNAs were differentially regulated in PsA and PsO patients, five of them previously reported to be involved in bone and cartilage metabolism, indicating an intimate association of psoriatic inflammation and bone/cartilage changes.
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| 9. |
- Cavallaro, Sara, et al.
(författare)
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Label-Free Surface Protein Profiling of Extracellular Vesicles by an Electrokinetic Sensor
- 2019
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Ingår i: ACS Sensors. - : AMER CHEMICAL SOC. - 2379-3694. ; 4:5, s. 1399-1408
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Tidskriftsartikel (refereegranskat)abstract
- Small extracellular vesicles (sEVs) generated from the endolysosomal system, often referred to as exosomes, have attracted interest as a suitable biomarker for cancer diagnostics, as they carry valuable biological information and reflect their cells of origin. Herein, we propose a simple and inexpensive electrical method for label-free detection and profiling of sEVs in the size range of exosomes. The detection method is based on the electrokinetic principle, where the change in the streaming current is monitored as the surface markers of the sEVs interact with the affinity reagents immobilized on the inner surface of a silica microcapillary. As a proof-of-concept, we detected sEVs derived from the non-small-cell lung cancer (NSCLC) cell line H1975 for a set of representative surface markers, such as epidermal growth factor receptor (EGFR), CD9, and CD63. The detection sensitivity was estimated to be similar to 175000 sEVs, which represents a sensor surface coverage of only 0.04%. We further validated the ability of the sensor to measure the expression level of a membrane protein by using sEVs displaying artificially altered expressions of EGFR and CD63, which were derived from NSCLC and human embryonic kidney (HEK) 293T cells, respectively. The analysis revealed that the changes in EGFR and CD63 expressions in sEVs can be detected with a sensitivity in the order of 10% and 3%, respectively, of their parental cell expressions. The method can be easily parallelized and combined with existing microfluidic-based EV isolation technologies, allowing for rapid detection and monitoring of sEVs for cancer diagnosis.
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| 10. |
- Cavallaro, Sara, et al.
(författare)
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Multiparametric Profiling of Single Nanoscale Extracellular Vesicles by Combined Atomic Force and Fluorescence Microscopy : Correlation and Heterogeneity in Their Molecular and Biophysical Features
- 2021
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Ingår i: Small. - : Wiley. - 1613-6810 .- 1613-6829. ; 17:14
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Tidskriftsartikel (refereegranskat)abstract
- Being a key player in intercellular communications, nanoscale extracellular vesicles (EVs) offer unique opportunities for both diagnostics and therapeutics. However, their cellular origin and functional identity remain elusive due to the high heterogeneity in their molecular and physical features. Here, for the first time, multiple EV parameters involving membrane protein composition, size and mechanical properties on single small EVs (sEVs) are simultaneously studied by combined fluorescence and atomic force microscopy. Furthermore, their correlation and heterogeneity in different cellular sources are investigated. The study, performed on sEVs derived from human embryonic kidney 293, cord blood mesenchymal stromal and human acute monocytic leukemia cell lines, identifies both common and cell line-specific sEV subpopulations bearing distinct distributions of the common tetraspanins (CD9, CD63, and CD81) and biophysical properties. Although the tetraspanin abundances of individual sEVs are independent of their sizes, the expression levels of CD9 and CD63 are strongly correlated. A sEV population co-expressing all the three tetraspanins in relatively high abundance, however, having average diameters of <100 nm and relatively low Young moduli, is also found in all cell lines. Such a multiparametric approach is expected to provide new insights regarding EV biology and functions, potentially deciphering unsolved questions in this field.
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| 11. |
- Cavallaro, Sara, et al.
(författare)
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Multiplexed electrokinetic sensor for detection and therapy monitoring of extracellular vesicles from liquid biopsies of non-small-cell lung cancer patients
- 2021
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Ingår i: Biosensors & bioelectronics. - : Elsevier. - 0956-5663 .- 1873-4235. ; 193
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Tidskriftsartikel (refereegranskat)abstract
- Liquid biopsies based on extracellular vesicles (EVs) represent a promising tool for treatment monitoring of tumors, including non-small-cell lung cancers (NSCLC). In this study, we report on a multiplexed electrokinetic sensor for surface protein profiling of EVs from clinical samples. The method detects the difference in the streaming current generated by EV binding to the surface of a functionalized microcapillary, thereby estimating the expression level of a marker. Using multiple microchannels functionalized with different antibodies in a parallel fluidic connection, we first demonstrate the capacity for simultaneous detection of multiple surface markers in small EVs (sEVs) from NSCLC cells. To investigate the prospects of liquid biopsies based on EVs, we then apply the method to profile sEVs isolated from the pleural effusion (PE) fluids of five NSCLC patients with different genomic alterations (ALK, KRAS or EGFR) and applied treatments (chemotherapy, EGFR- or ALKtyrosine kinase inhibitors). The vesicles were targeted against CD9, as well as EGFR and PD-L1, two treatment targets in NSCLC. The electrokinetic signals show detection of these markers on sEVs, highlighting distinct interpatient differences, e.g., increased EGFR levels in sEVs from a patient with EGFR mutation as compared to an ALK-fusion one. The sensors also detect differences in PD-L1 expressions. The analysis of sEVs from a patient prior and post ALK-TKI crizotinib treatment reveals significant increases in the expressions of some markers (EGFR and PD-L1). These results hold promise for the application of the method for tumor treatment monitoring based on sEVs from patient liquid biopsies.
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| 12. |
- Cochius-den Otter, S, et al.
(författare)
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The CoDiNOS trial protocol: an international randomised controlled trial of intravenous sildenafil versus inhaled nitric oxide for the treatment of pulmonary hypertension in neonates with congenital diaphragmatic hernia
- 2019
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 9:11, s. e032122-
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Tidskriftsartikel (refereegranskat)abstract
- Congenital diaphragmatic hernia (CDH) is a developmental defect of the diaphragm that impairs normal lung development, causing pulmonary hypertension (PH). PH in CDH newborns is the main determinant for morbidity and mortality. Different therapies are still mainly based on ‘trial and error’. Inhaled nitric oxide (iNO) is often the drug of first choice. However, iNO does not seem to improve mortality. Intravenous sildenafil has reduced mortality in newborns with PH without CDH, but prospective data in CDH patients are lacking.Methods and analysisIn an open label, multicentre, international randomised controlled trial in Europe, Canada and Australia, 330 newborns with CDH and PH are recruited over a 4-year period (2018–2022). Patients are randomised for intravenous sildenafil or iNO. Sildenafil is given in a loading dose of 0.4 mg/kg in 3 hours; followed by continuous infusion of 1.6 mg/kg/day, iNO is dosed at 20 ppm. Primary outcome is absence of PH on day 14 without pulmonary vasodilator therapy and/or absence of death within the first 28 days of life. Secondary outcome measures include clinical and echocardiographic markers of PH in the first year of life. We hypothesise that sildenafil gives a 25% reduction in the primary outcome from 68% to 48% on day 14, for which a sample size of 330 patients is needed. An intention-to-treat analysis will be performed. A p-value (two-sided) <0.05 is considered significant in all analyses.Ethics and disseminationEthics approval has been granted by the ethics committee in Rotterdam (MEC-2017-324) and the central Committee on Research Involving Human Subjects (NL60229.078.17) in the Netherlands. The principles of the Declaration of Helsinki, the Medical Research Involving Human Subjects Act and the national rules and regulations on personal data protection will be used. Parental informed consent will be obtained.Trial registration numberNTR6982; Pre-results.
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| 14. |
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| 15. |
- Ghetti, R, et al.
(författare)
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Characterization of nuclear sources via two-neutron intensity interferometry
- 1999
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Ingår i: NUCLEAR PHYSICS A. - : ELSEVIER SCIENCE BV. - 0375-9474. ; 660:1, s. 20-40
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Tidskriftsartikel (refereegranskat)abstract
- The neutron energy spectrum and the two-neutron correlation function have been measured for the E/A = 45 MeV Ni + Al reaction in order to assess the space-time characteristics of the neutron emitting source. When comparing the data to a statistical model,
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| 16. |
- Helldin, L., et al.
(författare)
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A functional comparison of patients with schizophrenia between the North and South of Europe
- 2012
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Ingår i: European psychiatry. - : Cambridge University Press (CUP). - 0924-9338 .- 1778-3585. ; 27:6, s. 442-444
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The main objective of this study was to compare clinical and functional outcomes of patients with schizophrenia in Italy and Sweden with a special focus on daily functioning performance and real life milestones. Also, to study if outcome is to be regarded as a consequence of premorbid function, the level of symptom control and functional capacity or if other influences, such as cultural differences, must parallel be considered. Method: Ninety-five patients from three centres, Milan and Naples in Italy and Trollhattan in Sweden were investigated. The Positive and Negative Syndrome Scale and the UCSD Performance-Based Skills Assessment - Brief version were used together with patients' school history and their status of accommodation and occupation. Results: Patients in Trollhattan were more likely to live independently and patients in Naples to have a work or take part in education. Differences in symptoms and the performance test were present but subtle. Discussion: Differences in real life milestones were not explained by corresponding differences in symptoms, premorbid function or the performance-based test. It is therefore not appropriate only to present functional outcome as an expression of how successful treatment has been. (C) 2011 Elsevier Masson SAS. All rights reserved.
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| 17. |
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| 18. |
- Sahu, Siddharth S., et al.
(författare)
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Exploiting Electrostatic Interaction for Highly Sensitive Detection of Tumor-Derived Extracellular Vesicles by an Electrokinetic Sensor
- 2021
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Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 13:36, s. 42513-42521
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Tidskriftsartikel (refereegranskat)abstract
- We present an approach to improve the detection sensitivity of a streaming current-based biosensor for membrane protein profiling of small extracellular vesicles (sEVs). The experimental approach, supported by theoretical investigation, exploits electrostatic charge contrast between the sensor surface and target analytes to enhance the detection sensitivity. We first demonstrate the feasibility of the approach using different chemical functionalization schemes to modulate the zeta potential of the sensor surface in a range -16.0 to -32.8 mV. Thereafter, we examine the sensitivity of the sensor surface across this range of zeta potential to determine the optimal functionalization scheme. The limit of detection (LOD) varied by 2 orders of magnitude across this range, reaching a value of 4.9 x 10(6) particles/mL for the best performing surface for CD9. We then used the optimized surface to profile CD9, EGFR, and PD-L1 surface proteins of sEVs derived from non-small cell lung cancer (NSCLC) cell-line H1975, before and after treatment with EGFR tyrosine kinase inhibitors, as well as sEVs derived from pleural effusion fluid of NSCLC adenocarcinoma patients. Our results show the feasibility to monitor CD9, EGFR, and PD-L1 expression on the sEV surface, illustrating a good prospect of the method for clinical application.
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| 19. |
- Urrata, M, et al.
(författare)
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Neutron-neutron Intensity Interferometry in E/A = 45 MeV 58Ni + 27Al, 58Ni and 197Au Reactions
- 2000
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Ingår i: Physical Review C. Nuclear Physics. - : American Institute of Physics (AIP). - 0556-2813 .- 1089-490X. ; 62
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Tidskriftsartikel (refereegranskat)abstract
- Small angle neutron-neutron correlations have been measured for the E/A=45 MeV 58Ni+27Al, natNi, and 197Au reactions. Two-neutron correlation functions, both integrated and gated on the total momentum of the neutron pair, have been constructed. In order to explain these data, a fraction of fast "dynamical" emission is needed in addition to slower evaporative emission. The overall emission time scale is shorter for the symmetric system, indicating that the dynamical component is stronger in this case.
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