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| 2. |
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| 3. |
- Abdesselam, A., et al.
(author)
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The ATLAS semiconductor tracker end-cap module
- 2007
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In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 575:3, s. 353-389
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Journal article (peer-reviewed)abstract
- The challenges for the tracking detector systems at the LHC are unprecedented in terms of the number of channels, the required read-out speed and the expected radiation levels. The ATLAS Semiconductor Tracker. (SCT) end-caps have a total of about 3 million electronics channels each reading out every 25 ns into its own on-chip 3.3 mu s buffer. The highest anticipated dose after 10 years operation is 1.4x10(14) cm(-2) in units of 1 MeV neutron equivalent (assuming the damage factors scale with the non-ionising energy loss). The forward tracker has 1976 double-sided modules, mostly of area similar to 70 cm(2), each having 2 x 768 strips read out by six ASICs per side. The requirement to achieve an average perpendicular radiation length of 1.5% X-0, while coping with up to 7 W dissipation per module (after irradiation), leads to stringent constraints on the thermal design. The additional requirement of 1500e(-) equivalent noise charge (ENC) rising to only 1800e(-) ENC after irradiation, provides stringent design constraints on both the high-density Cu/Polyimide flex read-out circuit and the ABCD3TA read-out ASICs. Finally, the accuracy of module assembly must not compromise the 16 mu m (r phi) resolution perpendicular to the strip directions or 580 mu m radial resolution coming from the 40 mrad front-back stereo angle. A total of 2210 modules were built to the tight tolerances and specifications required for the SCT. This was 234 more than the 1976 required and represents a yield of 93%. The component flow was at times tight, but the module production rate of 40-50 per week was maintained despite this. The distributed production was not found to be a major logistical problem and it allowed additional flexibility to take advantage of where the effort was available, including any spare capacity, for building the end-cap modules. The collaboration that produced the ATLAS SCT end-cap modules kept in close contact at all times so that the effects of shortages or stoppages at different sites could be rapidly resolved.
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| 4. |
- Abate, E., et al.
(author)
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Combined performance tests before installation of the ATLAS Semiconductor and Transition Radiation Tracking Detectors
- 2008
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In: Journal of Instrumentation. - 1748-0221. ; 3
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Journal article (peer-reviewed)abstract
- The ATLAS (A Toroidal LHC ApparatuS) Inner Detector provides charged particle tracking in the centre of the ATLAS experiment at the Large Hadron Collider (LHC). The Inner Detector consists of three subdetectors: the Pixel Detector, the Semiconductor Tracker (SCT), and the Transition Radiation Tracker (TRT). This paper summarizes the tests that were carried out at the final stage of SCT+TRT integration prior to their installation in ATLAS. The combined operation and performance of the SCT and TRT barrel and endcap detectors was investigated through a series of noise tests, and by recording the tracks of cosmic rays. This was a crucial test of hardware and software of the combined tracker detector systems. The results of noise and cross-talk tests on the SCT and TRT in their final assembled configuration, using final readout and supply hardware and software, are reported. The reconstruction and analysis of the recorded cosmic tracks allowed testing of the offline analysis chain and verification of basic tracker performance parameters, such as efficiency and spatial resolution, in combined operation before installation.
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| 5. |
- Abdesselam, A., et al.
(author)
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The barrel modules of the ATLAS semiconductor tracker
- 2006
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In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 568:2, s. 642-671
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Journal article (peer-reviewed)abstract
- This paper describes the silicon microstrip modules in the barrel section of the SemiConductor Tracker (SCT) of the ATLAS experiment at the CERN Large Hadron Collider (LHC). The module requirements, components and assembly techniques are given, as well as first results of the module performance on the fully assembled barrels that make up the detector being installed in the ATLAS experiment.
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| 6. |
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| 9. |
- Abe, O, et al.
(author)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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In: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
-
Journal article (peer-reviewed)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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| 10. |
- Bruzzi, M, et al.
(author)
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Radiation-hard semiconductor detectors for SuperLHC
- 2005
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In: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002. ; 541:1-2, s. 189-201
-
Journal article (peer-reviewed)abstract
- An option of increasing the luminosity of the Large Hadron Collider (LHC) at CERN to 1035 cm-2 s-1 has been envisaged to extend the physics reach of the machine. An efficient tracking down to a few centimetres from the interaction point will be required to exploit the physics potential of the upgraded LHC. As a consequence, the semiconductor detectors close to the interaction region will receive severe doses of fast hadron irradiation and the inner tracker detectors will need to survive fast hadron fluences of up to above 1016cm-2. The CERN-RD50 project "Development of Radiation Hard Semiconductor Devices for Very High Luminosity Colliders" has been established in 2002 to explore detector materials and technologies that will allow to operate devices up to, or beyond, this limit. The strategies followed by RD50 to enhance the radiation tolerance include the development of new or defect engineered detector materials (SiC, GaN, Czochralski and epitaxial silicon, oxygen enriched Float Zone silicon), the improvement of present detector designs and the understanding of the microscopic defects causing the degradation of the irradiated detectors. The latest advancements within the RD50 collaboration on radiation hard semiconductor detectors will be reviewed and discussed in this work.
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| 11. |
- Vos, Theo, et al.
(author)
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Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
- 2015
-
In: The Lancet. - 1474-547X .- 0140-6736. ; 386:9995, s. 743-800
-
Journal article (peer-reviewed)abstract
- Background Up-to-date evidence about levels and trends in disease and injury incidence, prevalence, and years lived with disability (YLDs) is an essential input into global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013), we estimated these quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013. Methods Estimates were calculated for disease and injury incidence, prevalence, and YLDs using GBD 2010 methods with some important refinements. Results for incidence of acute disorders and prevalence of chronic disorders are new additions to the analysis. Key improvements include expansion to the cause and sequelae list, updated systematic reviews, use of detailed injury codes, improvements to the Bayesian meta-regression method (DisMod-MR), and use of severity splits for various causes. An index of data representativeness, showing data availability, was calculated for each cause and impairment during three periods globally and at the country level for 2013. In total, 35 620 distinct sources of data were used and documented to calculated estimates for 301 diseases and injuries and 2337 sequelae. The comorbidity simulation provides estimates for the number of sequelae, concurrently, by individuals by country, year, age, and sex. Disability weights were updated with the addition of new population-based survey data from four countries. Findings Disease and injury were highly prevalent; only a small fraction of individuals had no sequelae. Comorbidity rose substantially with age and in absolute terms from 1990 to 2013. Incidence of acute sequelae were predominantly infectious diseases and short-term injuries, with over 2 billion cases of upper respiratory infections and diarrhoeal disease episodes in 2013, with the notable exception of tooth pain due to permanent caries with more than 200 million incident cases in 2013. Conversely, leading chronic sequelae were largely attributable to non-communicable diseases, with prevalence estimates for asymptomatic permanent caries and tension-type headache of 2.4 billion and 1.6 billion, respectively. The distribution of the number of sequelae in populations varied widely across regions, with an expected relation between age and disease prevalence. YLDs for both sexes increased from 537.6 million in 1990 to 764.8 million in 2013 due to population growth and ageing, whereas the age-standardised rate decreased little from 114.87 per 1000 people to 110.31 per 1000 people between 1990 and 2013. Leading causes of YLDs included low back pain and major depressive disorder among the top ten causes of YLDs in every country. YLD rates per person, by major cause groups, indicated the main drivers of increases were due to musculoskeletal, mental, and substance use disorders, neurological disorders, and chronic respiratory diseases; however HIV/AIDS was a notable driver of increasing YLDs in sub-Saharan Africa. Also, the proportion of disability-adjusted life years due to YLDs increased globally from 21.1% in 1990 to 31.2% in 2013. Interpretation Ageing of the world's population is leading to a substantial increase in the numbers of individuals with sequelae of diseases and injuries. Rates of YLDs are declining much more slowly than mortality rates. The non-fatal dimensions of disease and injury will require more and more attention from health systems. The transition to non-fatal outcomes as the dominant source of burden of disease is occurring rapidly outside of sub-Saharan Africa. Our results can guide future health initiatives through examination of epidemiological trends and a better understanding of variation across countries.
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| 12. |
- Naghavi, Mohsen, et al.
(author)
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Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
- 2015
-
In: The Lancet. - 1474-547X .- 0140-6736. ; 385:9963, s. 117-171
-
Journal article (peer-reviewed)abstract
- Background Up-to-date evidence on levels and trends for age-sex-specifi c all-cause and cause-specifi c mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specifi c all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specifi c causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65.3 years (UI 65.0-65.6) in 1990, to 71.5 years (UI 71.0-71.9) in 2013, while the number of deaths increased from 47.5 million (UI 46.8-48.2) to 54.9 million (UI 53.6-56.3) over the same interval. Global progress masked variation by age and sex: for children, average absolute diff erences between countries decreased but relative diff erences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative diff erences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10.7%, from 4.3 million deaths in 1990 to 4.8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specifi c mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.
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| 13. |
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| 14. |
- Parati, G, et al.
(author)
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MASked-unconTrolled hypERtension management based on office BP or on ambulatory blood pressure measurement (MASTER) Study: a randomised controlled trial protocol
- 2018
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In: BMJ open. - : BMJ. - 2044-6055. ; 8:12, s. e021038-
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Journal article (peer-reviewed)abstract
- Masked uncontrolled hypertension (MUCH) carries an increased risk of cardiovascular (CV) complications and can be identified through combined use of office (O) and ambulatory (A) blood pressure (BP) monitoring (M) in treated patients. However, it is still debated whether the information carried by ABPM should be considered for MUCH management. Aim of the MASked-unconTrolled hypERtension management based on OBP or on ambulatory blood pressure measurement (MASTER) Study is to assess the impact on outcome of MUCH management based on OBPM or ABPM.Methods and analysisMASTER is a 4-year prospective, randomised, open-label, blinded-endpoint investigation. A total of 1240 treated hypertensive patients from about 40 secondary care clinical centres worldwide will be included -upon confirming presence of MUCH (repeated on treatment OBP <140/90 mm Hg, and at least one of the following: daytime ABP ≥135/85 mm Hg; night-time ABP ≥120/70 mm Hg; 24 hour ABP ≥130/80 mm Hg), and will be randomised to a management strategy based on OBPM (group 1) or on ABPM (group 2). Patients in group 1 will have OBP measured at 0, 3, 6, 12, 18, 24, 30, 36, 42 and 48 months and taken as a guide for treatment; ABPM will be performed at randomisation and at 12, 24, 36 and 48 months but will not be used to take treatment decisions. Patients randomised to group 2 will have ABPM performed at randomisation and all scheduled visits as a guide to antihypertensive treatment. The effects of MUCH management strategy based on ABPM or on OBPM on CV and renal intermediate outcomes (changing left ventricular mass and microalbuminuria, coprimary outcomes) at 1 year and on CV events at 4 years and on changes in BP-related variables will be assessed.Ethics and disseminationMASTER study protocol has received approval by the ethical review board of Istituto Auxologico Italiano. The procedures set out in this protocol are in accordance with principles of Declaration of Helsinki and Good Clinical Practice guidelines. Results will be published in accordance with the CONSORT statement in a peer-reviewed scientific journal.Trial registration numberNCT02804074; Pre-results.
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| 15. |
- Schiller, D, et al.
(author)
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The Human Affectome
- 2024
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In: Neuroscience and biobehavioral reviews. - 1873-7528. ; 158, s. 105450-
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Journal article (peer-reviewed)
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| 16. |
- Allaire, C., et al.
(author)
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Beam test measurements of Low Gain Avalanche Detector single pads and arrays for the ATLAS High Granularity Timing Detector
- 2018
-
In: Journal of Instrumentation. - : Institute of Physics (IOP). - 1748-0221. ; 13
-
Journal article (peer-reviewed)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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| 17. |
- Ferrari, A. C., et al.
(author)
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Science and technology roadmap for graphene, related two-dimensional crystals, and hybrid systems
- 2015
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In: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3372 .- 2040-3364. ; 7:11, s. 4598-4810
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Journal article (peer-reviewed)abstract
- We present the science and technology roadmap for graphene, related two-dimensional crystals, and hybrid systems, targeting an evolution in technology, that might lead to impacts and benefits reaching into most areas of society. This roadmap was developed within the framework of the European Graphene Flagship and outlines the main targets and research areas as best understood at the start of this ambitious project. We provide an overview of the key aspects of graphene and related materials (GRMs), ranging from fundamental research challenges to a variety of applications in a large number of sectors, highlighting the steps necessary to take GRMs from a state of raw potential to a point where they might revolutionize multiple industries. We also define an extensive list of acronyms in an effort to standardize the nomenclature in this emerging field.
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| 18. |
- Li, S. Y., et al.
(author)
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Universal toxin-based selection for precise genome engineering in human cells
- 2021
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
-
Journal article (peer-reviewed)abstract
- Prokaryotic restriction enzymes, recombinases and Cas proteins are powerful DNA engineering and genome editing tools. However, in many primary cell types, the efficiency of genome editing remains low, impeding the development of gene- and cell-based therapeutic applications. A safe strategy for robust and efficient enrichment of precisely genetically engineered cells is urgently required. Here, we screen for mutations in the receptor for Diphtheria Toxin (DT) which protect human cells from DT. Selection for cells with an edited DT receptor variant enriches for simultaneously introduced, precisely targeted gene modifications at a second independent locus, such as nucleotide substitutions and DNA insertions. Our method enables the rapid generation of a homogenous cell population with bi-allelic integration of a DNA cassette at the selection locus, without clonal isolation. Toxin-based selection works in both cancer-transformed and non-transformed cells, including human induced pluripotent stem cells and human primary T-lymphocytes, as well as it is applicable also in vivo, in mice with humanized liver. This work represents a flexible, precise, and efficient selection strategy to engineer cells using CRISPR-Cas and base editing systems. Genome engineering in cell lines or human stem cells often has poor efficiency, limiting the development of research and therapeutic applications. Here, the authors use a toxin-based selection system for precise bi-allelic engineering in cells and in vivo.
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| 19. |
- Tremblin, P., et al.
(author)
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Site testing for submillimetre astronomy at Dome C, Antarctica
- 2011
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 535:A112
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Journal article (peer-reviewed)abstract
- Aims. Over the past few years a major effort has been put into the exploration of potential sites for the deployment of submillimetre astronomical facilities. Amongst the most important sites are Dome C and Dome A on the Antarctic Plateau, and the Chajnantor area in Chile. In this context, we report on measurements of the sky opacity at 200 mu m over a period of three years at the French-Italian station, Concordia, at Dome C, Antarctica. We also present some solutions to the challenges of operating in the harsh polar environment.Methods. The 200-mu m atmospheric opacity was measured with a tipper. The forward atmospheric model MOLIERE (Microwave Observation LIne Estimation and REtrieval) was used to calculate the atmospheric transmission and to evaluate the precipitable water vapour content (PWV) from the observed sky opacity. These results have been compared with satellite measurements from the Infrared Atmospheric Sounding Interferometer (IASI) on Metop-A, with balloon humidity sondes and with results obtained by a ground-based microwave radiometer (HAMSTRAD). In addition, a series of experiments has been designed to study frost formation on surfaces, and the temporal and spatial evolution of thermal gradients in the low atmosphere.Results. Dome C offers exceptional conditions in terms of absolute atmospheric transmission and stability for submillimetre astronomy. Over the austral winter the PWV exhibits long periods during which it is stable and at a very low level (0.1 to 0.3 mm). Higher values (0.2 to 0.8 mm) of PWV are observed during the short summer period. Based on observations over three years, a transmission of around 50% at 350 mu m is achieved for 75% of the time. The 200-mu m window opens with a typical transmission of 10% to 15% for 25% of the time.Conclusions. Dome C is one of the best accessible sites on Earth for submillimetre astronomy. Observations at 350 or 450 mu m are possible all year round, and the 200-mu m window opens long enough and with a sufficient transparency to be useful. Although the polar environment severely constrains hardware design, a permanent observatory with appropriate technical capabilities is feasible. Because of the very good astronomical conditions, high angular resolution and time series (multi-year) observations at Dome C with a medium size single dish telescope would enable unique studies to be conducted, some of which are not otherwise feasible even from space.
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| 20. |
- Aquila, A., et al.
(author)
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The linac coherent light source single particle imaging road map
- 2015
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In: Structural Dynamics. - : AIP Publishing. - 2329-7778. ; 2:4
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Journal article (peer-reviewed)abstract
- Intense femtosecond x-ray pulses from free-electron laser sources allow the imag-ing of individual particles in a single shot. Early experiments at the Linac CoherentLight Source (LCLS) have led to rapid progress in the field and, so far, coherentdiffractive images have been recorded from biological specimens, aerosols, andquantum systems with a few-tens-of-nanometers resolution. In March 2014, LCLSheld a workshop to discuss the scientific and technical challenges for reaching theultimate goal of atomic resolution with single-shot coherent diffractive imaging. This paper summarizes the workshop findings and presents the roadmap towardreaching atomic resolution, 3D imaging at free-electron laser sources.
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| 21. |
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| 22. |
- Garibaldi, F., et al.
(author)
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A PET scanner employing CsI films as photocathode
- 2004
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In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 525:1-2, s. 263-267
-
Journal article (peer-reviewed)abstract
- Medical imaging is a fundamental tool in the diagnosis, treatments, and monitoring of disease processes as cancer. Detectors of large area and high Field Of View are necessary to scan the whole body in a reasonable time. Relatively large area photodetectors are necessary even for imaging of small mice and rats with high sensitivities and spatial resolutions, generally obtained by using pinhole or multipinhole collimators. Standard PET scanners, with scintillators coupled to photomultipliers, have generally a limited detector area due to the high costs of both scintillators and photomultipliers. In this respect, the replacement of photomultipliers with gaseous photodetectors represents a possible solution of the problem and brings the additional advantage to provide devices with sensitive areas free from dead regions. In this paper we report on a PET scanner equipped with a multiwire proportional chamber with a CsI thin film as photoconverter. A similar approach has already been successfully pursued in nuclear and particle physics experiments. A prototype of such a PET detector has been designed and built, and will be tested soon. Possible solutions for increasing the photoelectron number, and thus the detector performance, are presented.
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| 23. |
- Grasselli, Giacomo, et al.
(author)
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ESICM guidelines on acute respiratory distress syndrome : definition, phenotyping and respiratory support strategies
- 2023
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In: Intensive Care Medicine. - : Springer Nature. - 0342-4642 .- 1432-1238. ; 49, s. 727-759
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Journal article (peer-reviewed)abstract
- The aim of these guidelines is to update the 2017 clinical practice guideline (CPG) of the European Society of Intensive Care Medicine (ESICM). The scope of this CPG is limited to adult patients and to non-pharmacological respiratory support strategies across different aspects of acute respiratory distress syndrome (ARDS), including ARDS due to coronavirus disease 2019 (COVID-19). These guidelines were formulated by an international panel of clinical experts, one methodologist and patients' representatives on behalf of the ESICM. The review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and grade recommendations and the quality of reporting of each study based on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network guidelines. The CPG addressed 21 questions and formulates 21 recommendations on the following domains: (1) definition; (2) phenotyping, and respiratory support strategies including (3) high-flow nasal cannula oxygen (HFNO); (4) non-invasive ventilation (NIV); (5) tidal volume setting; (6) positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM); (7) prone positioning; (8) neuromuscular blockade, and (9) extracorporeal life support (ECLS). In addition, the CPG includes expert opinion on clinical practice and identifies the areas of future research.
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| 24. |
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| 25. |
- Petkevicius, K., et al.
(author)
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TLCD1 and TLCD2 regulate cellular phosphatidylethanolamine composition and promote the progression of non-alcoholic steatohepatitis
- 2022
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
-
Journal article (peer-reviewed)abstract
- The regulation of cellular phosphatidylethanolamine (PE) acyl chain composition is poorly understood. Here, the authors show that TLCD1 and TLCD2 proteins mediate the formation of monounsaturated fatty acid-containing PE species and promote the progression of non-alcoholic steatohepatitis. The fatty acid composition of phosphatidylethanolamine (PE) determines cellular metabolism, oxidative stress, and inflammation. However, our understanding of how cells regulate PE composition is limited. Here, we identify a genetic locus on mouse chromosome 11, containing two poorly characterized genes Tlcd1 and Tlcd2, that strongly influences PE composition. We generated Tlcd1/2 double-knockout (DKO) mice and found that they have reduced levels of hepatic monounsaturated fatty acid (MUFA)-containing PE species. Mechanistically, TLCD1/2 proteins act cell intrinsically to promote the incorporation of MUFAs into PEs. Furthermore, TLCD1/2 interact with the mitochondria in an evolutionarily conserved manner and regulate mitochondrial PE composition. Lastly, we demonstrate the biological relevance of our findings in dietary models of metabolic disease, where Tlcd1/2 DKO mice display attenuated development of non-alcoholic steatohepatitis compared to controls. Overall, we identify TLCD1/2 proteins as key regulators of cellular PE composition, with our findings having broad implications in understanding and treating disease.
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| 26. |
- Rousseau-Nepton, L., et al.
(author)
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SIGNALS : I. Survey description
- 2019
-
In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 489:4, s. 5530-5546
-
Journal article (peer-reviewed)abstract
- SIGNALS, the Star formation, Ionized Gas, and Nebular Abundances Legacy Survey, is a large observing programme designed to investigate massive star formation and HII regions in a sample of local extended galaxies. The programme will use the imaging Fourier transform spectrograph SITELLE at the Canada-France-Hawaii Telescope. Over 355 h (54.7 nights) have been allocated beginning in fall 2018 for eight consecutive semesters. Once completed, SIGNALS will provide a statistically reliable laboratory to investigate massive star formation, including over 50 000 resolved HII regions: the largest, most complete, and homogeneous data base of spectroscopically and spatially resolved extragalactic HII regions ever assembled. For each field observed, three datacubes covering the spectral bands of the filters SN1 (363386 nm), SN2 (482-513 nm), and SN3 (647-685 nm) are gathered. The spectral resolution selected for each spectral band is 1000, 1000, and 5000, respectively. As defined, the project sample will facilitate the study of small-scale nebular physics and many other phenomena linked to star formation at a mean spatial resolution of similar to 20 pc. This survey also has considerable legacy value for additional topics, including planetary nebulae, diffuse ionized gas, and supernova remnants. The purpose of this paper is to present a general outlook of the survey, notably the observing strategy, galaxy sample, and science requirements.
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| 27. |
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| 28. |
- Belliato, M., et al.
(author)
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An experimental model of veno-venous arterial extracorporeal membrane oxygenation
- 2019
-
In: International Journal of Artificial Organs. - : SAGE Publications Ltd. - 0391-3988 .- 1724-6040.
-
Journal article (peer-reviewed)abstract
- Introduction: Veno-venous arterial extracorporeal membrane oxygenation is a hybrid-modality of extracorporeal membrane oxygenation combining veno-venous and veno-arterial extracorporeal membrane oxygenation. It may be applied to patients with both respiratory and cardio-circulatory failure. Aim: To describe a computational spreadsheet regarding an ex vivo experimental model of veno-venous arterial extracorporeal membrane oxygenation to determine the return of cannula pairs in a single pump–driven circuit. Methods: We developed an ex vivo model of veno-venous arterial extracorporeal membrane oxygenation with a single pump and two outflow cannulas, and a glucose solution was used to mimic the features of blood. We maintained a fixed aortic impedance and physiological pulmonary resistance. Both flow and pressure data were collected while testing different pairs of outflow cannulas. Six simulations of different cannula pairs were performed, and data were analysed by a custom-made spreadsheet, which was able to predict the flow partition at different flow levels. Results: In all simulations, the flow in the arterial cannula gradually increased differently depending on the cannula pair. The best cannula pair was a 19-Fr/18-cm arterial with a 17-Fr/50-cm venous cannula, where we observed an equal flow split and acceptable flow into the arterial cannula at a lower flow rate of 4 L/min. Conclusion: Our computational spreadsheet identifies the suitable cannula pairing set for correctly splitting the outlet blood flow into the arterial and venous return cannulas in a veno-venous arterial extracorporeal membrane oxygenation configuration without the use of external throttles. Several limitations were reported regarding fixed aortic impedance, central venous pressure and the types of cannulas tested; therefore, further studies are mandatory to confirm our findings.
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| 29. |
- Benitez, V., et al.
(author)
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Sensors for the End-cap prototype of the Inner Tracker in the ATLAS Detector Upgrade
- 2016
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In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 833, s. 226-232
-
Journal article (peer-reviewed)abstract
- The new silicon microstrip sensors of the End-cap part of the HL-LHC ATLAS Inner Tracker (ITk) present a number of challenges due to their complex design features such as the multiple different sensor shapes, the varying strip pitch, or the built-In stereo angle. In order to investigate these specific problems, the "petalet" prototype was defined as a small End-cap prototype. The sensors for the petalet prototype include several new layout and technological solutions to investigate the issues, they have been tested in detail by the collaboration. The sensor description and detailed test results are presented in this paper. New software tools have been developed for the automatic layout generation of the complex designs. The sensors have been fabricated, characterized and delivered to the institutes in the collaboration for their assembly on petalet prototypes. This paper describes the lessons learnt from the design and tests of the new solutions implemented on these sensors, which are being used for the full petal sensor development. This has resulted in the ITIc strip, community acquiring the necessary expertise to develop the full End-cap structure, the petal.
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| 30. |
- Borges, João Batista, et al.
(author)
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Zero expiratory pressure and low oxygen concentration promote heterogeneity of regional ventilation and lung densities
- 2016
-
In: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 60:7, s. 958-968
-
Journal article (peer-reviewed)abstract
- BackgroundIt is not well known what is the main mechanism causing lung heterogeneity in healthy lungs under mechanical ventilation. We aimed to investigate the mechanisms causing heterogeneity of regional ventilation and parenchymal densities in healthy lungs under anesthesia and mechanical ventilation. MethodsIn a small animal model, synchrotron imaging was used to measure lung aeration and regional-specific ventilation (sV.). Heterogeneity of ventilation was calculated as the coefficient of variation in sV. (CVsV.). The coefficient of variation in lung densities (CVD) was calculated for all lung tissue, and within hyperinflated, normally and poorly aerated areas. Three conditions were studied: zero end-expiratory pressure (ZEEP) and FIO2 0.21; ZEEP and FIO2 1.0; PEEP 12 cmH(2)O and F(I)O(2)1.0 (Open Lung-PEEP = OLP). ResultsThe mean tissue density at OLP was lower than ZEEP-1.0 and ZEEP-0.21. There were larger subregions with low sV. and poor aeration at ZEEP-0.21 than at OLP: 12.9 9.0 vs. 0.6 +/- 0.4% in the non-dependent level, and 17.5 +/- 8.2 vs. 0.4 +/- 0.1% in the dependent one (P = 0.041). The CVsV. of the total imaged lung at PEEP 12 cmH(2)O was significantly lower than on ZEEP, regardless of FIO2, indicating more heterogeneity of ventilation during ZEEP (0.23 +/- 0.03 vs. 0.54 +/- 0.37, P = 0.049). CVD changed over the different mechanical ventilation settings (P = 0.011); predominantly, CVD increased during ZEEP. The spatial distribution of the CVD calculated for the poorly aerated density category changed with the mechanical ventilation settings, increasing in the dependent level during ZEEP. ConclusionZEEP together with low FIO2 promoted heterogeneity of ventilation and lung tissue densities, fostering a greater amount of airway closure and ventilation inhomogeneities in poorly aerated regions.
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| 31. |
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| 32. |
- Cinti, M. N., et al.
(author)
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Innovative LuYAP:Ce array for PET imaging
- 2017
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In: Journal of Instrumentation. - : Institute of Physics Publishing (IOPP). - 1748-0221. ; 12:3
-
Journal article (peer-reviewed)abstract
- We present an imaging characterization of a 10 x 10 LuYAP array (2 x 2 x 10 mm3 pixels) with an innovative dielectric coating insulation (0.015 mm thick), in view of its possible use in a gamma camera for imaging positron emission tomography (PET) or in similar applications, e.g. as γ-prompt detector in hadron therapy. The particular assembly of this array was realized in order to obtain a packing fraction of 98%, improving detection efficiency and light collection. For imaging purpose, the array has been coupled with a selected Hamamatsu H10966-100 Multi Anode Photomultiplier read out by a customized 64 independent channels electronics. This tube presents a superbialkali photocathode with 38% of quantum efficiency, permitting to enhance energy resolution and consequently image quality. A pixel identification of about 0.5 mm at 662 keV was obtained, highlighting the potentiality of this detector in PET applications.
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| 33. |
- Davidsson, Åke, 1956-, et al.
(author)
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Positive identification in situ of mRNA expression of IL-6, and IL-12, and the chemotactic cytokine RANTES in patients with chronic sinusitis and polypoid disease. Clinical relevance and relation to allergy
- 1996
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In: Acta Oto-Laryngologica. - Oxfordshire, United Kingdom : Taylor & Francis. - 0001-6489 .- 1651-2251. ; 116:4, s. 604-610
-
Journal article (peer-reviewed)abstract
- Interleukins 6 (IL-6) and 12 (IL-12), and the chemoattractant chemokine RANTES were studied in ethmoidal mucosa, using reverse transcriptase polymerase chain reaction. The 49 patients had chronic sinusitis or nasal/paranasal polyposis, and some also allergy. To the best of our knowledge, this is the first study that demonstrates RANTES and IL-12 on mRNA level in human sinonasal mucosa in situ. mRNA for IL-6, IL-12 and RANTES were detected in 2, 8 and 6 patients with chronic sinusitis, respectively, and in mucosa from patients with polyposis a positive expression was observed in 4, 14 and 10 cases. There were no statistically significant differences. Analysing the entire group of 49 patients, disregarding type of mucosal disease, the number of patients with positive RANTES was significantly higher than that for IL-6. Similarly, IL-12 positivity was more frequently expressed than IL-6. mRNA for IL-6 was expressed in only 2 of the allergic patients. The cytokine production studied thus seems to be unrelated to the clinically defined entities. There is thus a local production in human diseased sinonasal mucosa of RANTES, as well as of IL-6 and IL-12. The local production of RANTES is an important prerequisite for recruitment and migration of inflammatory cells into the tissue. IL-12 is a co-stimulator of antigen-specific responses of established T helper 1 (Th1) clones, and regulates the responsiveness of the clones to a number of T cell growth factors. The study supports a shift towards Th1 cells in these disease entities.
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| 34. |
- Gensous, N, et al.
(author)
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A Targeted Epigenetic Clock for the Prediction of Biological Age
- 2022
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In: Cells. - : MDPI AG. - 2073-4409. ; 11:24
-
Journal article (peer-reviewed)abstract
- Epigenetic clocks were initially developed to track chronological age, but accumulating evidence indicates that they can also predict biological age. They are usually based on the analysis of DNA methylation by genome-wide methods, but targeted approaches, based on the assessment of a small number of CpG sites, are advisable in several settings. In this study, we developed a targeted epigenetic clock purposely optimized for the measurement of biological age. The clock includes six genomic regions mapping in ELOVL2, NHLRC1, AIM2, EDARADD, SIRT7 and TFAP2E genes, selected from a re-analysis of existing microarray data, whose DNA methylation is measured by EpiTYPER assay. In healthy subjects (n = 278), epigenetic age calculated using the targeted clock was highly correlated with chronological age (Spearman correlation = 0.89). Most importantly, and in agreement with previous results from genome-wide clocks, epigenetic age was significantly higher and lower than expected in models of increased (persons with Down syndrome, n = 62) and decreased (centenarians, n = 106; centenarians’ offspring, n = 143; nutritional intervention in elderly, n = 233) biological age, respectively. These results support the potential of our targeted epigenetic clock as a new marker of biological age and open its evaluation in large cohorts to further promote the assessment of biological age in healthcare practice.
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| 35. |
- Gudmundsson, Magni, et al.
(author)
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Atelectasis is inversely proportional to transpulmonary pressure during weaning from ventilator support in a large animal model
- 2018
-
In: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 62:1, s. 94-104
-
Journal article (peer-reviewed)abstract
- BackgroundIn mechanically ventilated, lung injured, patients without spontaneous breathing effort, atelectasis with shunt and desaturation may appear suddenly when ventilator pressures are decreased. It is not known how such a formation of atelectasis is related to transpulmonary pressure (P-L) during weaning from mechanical ventilation when the spontaneous breathing effort is increased. If the relation between P-L and atelectasis were known, monitoring of P-L might help to avoid formation of atelectasis and cyclic collapse during weaning. The main purpose of this study was to determine the relation between P-L and atelectasis in an experimental model representing weaning from mechanical ventilation. MethodsDynamic transverse computed tomography scans were acquired in ten anaesthetized, surfactant-depleted pigs with preserved spontaneous breathing, as ventilator support was lowered by sequentially reducing inspiratory pressure and positive end expiratory pressure in steps. The volumes of gas and atelectasis in the lungs were correlated with P-L obtained using oesophageal pressure recordings. Work of breathing (WOB) was assessed from Campbell diagrams. ResultsGradual decrease in P-L in both end-expiration and end-inspiration caused a proportional increase in atelectasis and decrease in the gas content (linear mixed model with an autoregressive correlation matrix; P<0.001) as the WOB increased. However, cyclic alveolar collapse during tidal ventilation did not increase significantly. ConclusionWe found a proportional correlation between atelectasis and P-L during the weaning process' in experimental mild lung injury. If confirmed in the clinical setting, a gradual tapering of ventilator support can be recommended for weaning without risk of sudden formation of atelectasis.
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| 36. |
- Heslop, James A., et al.
(author)
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Concise Review : Workshop Review: Understanding and Assessing the Risks of Stem Cell-Based Therapies
- 2015
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In: Stem Cells Translational Medicine. - : Oxford University Press (OUP). - 2157-6564 .- 2157-6580. ; 4:4, s. 389-400
-
Research review (peer-reviewed)abstract
- The field of stem cell therapeutics is moving ever closer to widespread application in the clinic. However, despite the undoubted potential held by these therapies, the balance between risk and benefit remains difficult to predict. As in any new field, a lack of previous application in man and gaps in the underlying science mean that regulators and investigators continue to look for a balance between minimizing potential risk and ensuring therapies are not needlessly kept from patients. Here, we attempt to identify the important safety issues, assessing the current advances in scientific knowledge and how they may translate to clinical therapeutic strategies in the identification and management of these risks. We also investigate the tools and techniques currently available to researchers during preclinical and clinical development of stem cell products, their utility and limitations, and how these tools may be strategically used in the development of these therapies. We conclude that ensuring safety through cutting-edge science and robust assays, coupled with regular and open discussions between regulators and academic/industrial investigators, is likely to prove the most fruitful route to ensuring the safest possible development of new products.
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| 37. |
- Iaffaldano, P, et al.
(author)
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Early treatment delays long-term disability accrual in RRMS: Results from the BMSD network
- 2021
-
In: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 27:10, s. 1543-1555
-
Journal article (peer-reviewed)abstract
- The optimal timing of treatment starts for achieving the best control on the long-term disability accumulation in multiple sclerosis (MS) is still to be defined. Objective: The aim of this study was to estimate the optimal time to start disease-modifying therapies (DMTs) to prevent the long-term disability accumulation in MS, using a pooled dataset from the Big Multiple Sclerosis Data (BMSD) network. Methods: Multivariable Cox regression models adjusted for the time to first treatment start from disease onset (in quintiles) were used. To mitigate the impact of potential biases, a set of pairwise propensity score (PS)-matched analyses were performed. The first quintile, including patients treated within 1.2 years from onset, was used as reference. Results: A cohort of 11,871 patients (median follow-up after treatment start: 13.2 years) was analyzed. A 3- and 12-month confirmed disability worsening event and irreversible Expanded Disability Status Scale (EDSS) 4.0 and 6.0 scores were reached by 7062 (59.5%), 4138 (34.9%), 3209 (31.1%), and 1909 (16.5%) patients, respectively. The risk of reaching all the disability outcomes was significantly lower ( p < 0.0004) for the first quintile patients’ group. Conclusion: Real-world data from the BMSD demonstrate that DMTs should be commenced within 1.2 years from the disease onset to reduce the risk of disability accumulation over the long term.
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| 38. |
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| 39. |
- Kolosenko, Iryna, et al.
(author)
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Cell crowding induces interferon regulatory factor 9, which confers resistance to chemotherapeutic drugs
- 2015
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 136:4, s. E51-E61
-
Journal article (peer-reviewed)abstract
- The mechanism of multicellular drug resistance, defined as the reduced efficacy of chemotherapeutic drugs in solid tumors is incompletely understood. Here we report that colon carcinoma cells cultured as 3D microtissues (spheroids) display dramatic increases in the expression of a subset of type I interferon-(IFN)-stimulated genes (ISGs). A similar gene signature was associated previously with resistance to radiation and chemotherapy, prompting us to examine the underlying biological mechanisms. Analysis of spheroids formed by different tumor cell lines and studies using knock-down of gene expression showed that cell crowding leads to the induction of IFN regulatory factor-9 (IRF9) which together with STAT2 and independently of IFNs, is necessary for ISG upregulation. Increased expression of IRF9 alone was sufficient to induce the ISG subset in monolayer cells and to confer increased resistance to clinically used cytotoxic drugs. Our data reveal a novel mechanism of regulation of a subset of ISGs, leading to drug resistance in solid tumors. What's new? Drug resistance remains a major challenge in the management of cancer patients. Using a 3D model of tumor cells the authors identify cell crowding and the interferon response as important mediators of drug resistance. They demonstrate that interferon regulatory factor 9 (IRF9) and a panel of interferon-stimulated genes are induced by cell crowding in this model. These results link unexpected new molecular mechanisms with the therapy resistance of solid tumors.
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| 40. |
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| 41. |
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| 42. |
- Lis, D. C., et al.
(author)
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Widespread Rotationally Hot Hydronium Ion in the Galactic Interstellar Medium
- 2014
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In: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 785:2, s. A135, pp. 1-9
-
Journal article (peer-reviewed)abstract
- We present new Herschel observations of the (6,6) and (9,9) inversion transitions of the hydronium ion toward Sagittarius B2(N) and W31C. Sensitive observations toward Sagittarius B2(N) show that the high, ~500 K, rotational temperatures characterizing the population of the highly excited metastable H3O+ rotational levels are present over a wide range of velocities corresponding to the Sagittarius B2 envelope, as well as the foreground gas clouds between the Sun and the source. Observations of the same lines toward W31C, a line of sight that does not intersect the Central Molecular Zone but instead traces quiescent gas in the Galactic disk, also imply a high rotational temperature of ~380 K, well in excess of the kinetic temperature of the diffuse Galactic interstellar medium. While it is plausible that some fraction of the molecular gas may be heated to such high temperatures in the active environment of the Galactic center, characterized by high X-ray and cosmic-ray fluxes, shocks, and high degree of turbulence, this is unlikely in the largely quiescent environment of the Galactic disk clouds. We suggest instead that the highly excited states of the hydronium ion are populated mainly by exoergic chemical formation processes and the temperature describing the rotational level population does not represent the physical temperature of the medium. The same arguments may be applicable to other symmetric top rotors, such as ammonia. This offers a simple explanation of the long-standing puzzle of the presence of a pervasive, hot molecular gas component in the central region of the Milky Way. Moreover, our observations suggest that this is a universal process not limited to the active environments associated with galactic nuclei.
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| 43. |
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| 44. |
- Mancina, Rosellina Margherita, et al.
(author)
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PSD3 downregulation confers protection against fatty liver disease.
- 2022
-
In: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 4:1, s. 60-75
-
Journal article (peer-reviewed)abstract
- Fatty liver disease (FLD) is a growing health issue with burdening unmet clinical needs. FLD has a genetic component but, despite the common variants already identified, there is still a missing heritability component. Using a candidate gene approach, we identify a locus (rs71519934) at the Pleckstrin and Sec7 domain-containing 3 (PSD3) gene resulting in a leucine to threonine substitution at position 186 of the protein (L186T) that reduces susceptibility to the entire spectrum of FLD in individuals at risk. PSD3 downregulation by short interfering RNA reduces intracellular lipid content in primary human hepatocytes cultured in two and three dimensions, and in human and rodent hepatoma cells. Consistent with this, Psd3 downregulation by antisense oligonucleotides in vivo protects against FLD in mice fed a non-alcoholic steatohepatitis-inducing diet. Thus, translating these results to humans, PSD3 downregulation might be a future therapeutic option for treating FLD.
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| 45. |
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| 46. |
- Muller, C., et al.
(author)
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Terbium-161 for PSMA-targeted radionuclide therapy of prostate cancer
- 2019
-
In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 46:9, s. 1919-1930
-
Journal article (peer-reviewed)abstract
- PurposeThe prostate-specific membrane antigen (PSMA) has emerged as an interesting target for radionuclide therapy of metastasized castration-resistant prostate cancer (mCRPC). The aim of this study was to investigate Tb-161 (T-1/2=6.89days; E beta(?)(av)=154keV) in combination with PSMA-617 as a potentially more effective therapeutic alternative to Lu-177-PSMA-617, due to the abundant co-emission of conversion and Auger electrons, resulting in an improved absorbed dose profile.Methods(161)Tb was used for the radiolabeling of PSMA-617 at high specific activities up to 100MBq/nmol. Tb-161-PSMA-617 was tested in vitro and in tumor-bearing mice to confirm equal properties, as previously determined for Lu-177-PSMA-617. The effects of Tb-161-PSMA-617 and Lu-177-PSMA-617 on cell viability (MTT assay) and survival (clonogenic assay) were compared in vitro using PSMA-positive PC-3 PIP tumor cells. Tb-161-PSMA-617 was further investigated in therapy studies using PC-3 PIP tumor-bearing mice.Results(161)Tb-PSMA-617 and Lu-177-PSMA-617 displayed equal in-vitro properties and tissue distribution profiles in tumor-bearing mice. The viability and survival of PC-3 PIP tumor cells were more reduced when exposed to Tb-161-PSMA-617 as compared to the effect obtained with the same activities of Lu-177-PSMA-617 over the whole investigated concentration range. Treatment of mice with Tb-161-PSMA-617 (5.0MBq/mouse and 10MBq/mouse, respectively) resulted in an activity-dependent increase of the median survival (36 vs 65days) compared to untreated control animals (19days). Therapy studies to compare the effects of Tb-161-PSMA-617 and Lu-177-PSMA-617 indicated the anticipated superiority of Tb-161 over Lu-177.Conclusion(161)Tb-PSMA-617 showed superior in-vitro and in-vivo results as compared to Lu-177-PSMA-617, confirming theoretical dose calculations that indicate an additive therapeutic effect of conversion and Auger electrons in the case of Tb-161. These data warrant more preclinical research for in-depth investigations of the proposed concept, and present a basis for future clinical translation of Tb-161-PSMA-617 for the treatment of mCRPC.
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| 47. |
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| 48. |
- Pani, R., et al.
(author)
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A study of response of a LuYAP : Ce array with innovative assembling for PET
- 2015
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In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 795, s. 82-87
-
Journal article (peer-reviewed)abstract
- We propose the characterization of a first array of 10×10 Lutetium Yttrium Orthoaluminate Perovskite (LuYAP:Ce) crystals, 2 mm×2 mm×10 mm pixel size, with an innovative assembling designed to enhance light output, uniformity and detection efficiency. The innovation consists of the use of 0.015 mm thick dielectric coating as inter-pixel light-insulators, manufactured by Crytur (Czech Republic) intended to improve crystal insulation and then light collection. Respect to the traditional treatment with 0.2 mm of white epoxy, a thinner pixel gap enhances packing fraction up to 98% with a consequent improvement of detection efficiency. Spectroscopic characterization of the array was performed by a Hamamatsu R6231 photomultiplier tube. A pixel-by-pixel scanning with a collimated 99mTc radioisotope (140 keV photon energy) highlighted a deviation in pulse height close to 3.5% respect to the overall mean value. Meanwhile, in term of energy resolution a difference between the response of single pixel and the array of about 10% was measured. Results were also supported and validated by Monte Carlo simulations performed with GEANT4. Although the dielectric coating pixel insulator cannot overcome the inherent limitations of LuYAP crystal due to its self-absorption of light (still present), this study demonstrated that the new coating treatment allows better light collection (nearly close to the expected one) with in addition a very good uniformity between different pixels. These results confirm the high potentiality of this coating for any other crystal array suited for imaging application and new expectations for the use of LuYAP for PET systems.
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| 49. |
- Pellegrini, G., et al.
(author)
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Technology development of 3D detectors for high-energy physics and imaging
- 2002
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In: Nuclear Instruments and Methods in Physics Research Section A. - 0168-9002 .- 1872-9576. ; 487:02-jan, s. 19-26
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Journal article (peer-reviewed)abstract
- Various fabrications routes to create '3D' detectors have been investigated and the electrical characteristics of these structures have been compared to simulations. The geometry of the detectors is hexagonal with a central anode surrounded by six cathode contacts. A uniform electric field is obtained with the maximum drift and depletion distance set by electrode spacings rather than detector thickness. This should improve the ability of silicon to operate in the presence of the severe bulk radiation damage expected in high-energy colliders. Moreover, 3D detectors made with other materials (e.g. GaAs, SiC) may be used, for example, in X-ray detection for medical imaging. Holes in the substrate were made either by etching with an inductively coupled plasma machine, by laser drilling or by photochemical etching. A number of different hole diameters and thickness have been investigated. Experimental characteristics have been compared to MEDICI simulations.
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| 50. |
- Perchiazzi, G, et al.
(author)
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Robustness of two different methods of monitoring respiratory system compliance during mechanical ventilation.
- 2017
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In: Medical and Biological Engineering and Computing. - : Springer Science and Business Media LLC. - 0140-0118 .- 1741-0444. ; 55:10, s. 1819-1828
-
Journal article (peer-reviewed)abstract
- Robustness measures the performance of estimation methods when they work under non-ideal conditions. We compared the robustness of artificial neural networks (ANNs) and multilinear fitting (MLF) methods in estimating respiratory system compliance (C RS) during mechanical ventilation (MV). Twenty-four anaesthetized pigs underwent MV. Airway pressure, flow and volume were recorded at fixed intervals after the induction of acute lung injury. After consecutive mechanical breaths, an inspiratory pause (BIP) was applied in order to calculate CRS using the interrupter technique. From the breath preceding the BIP, ANN and MLF had to compute CRS in the presence of two types of perturbations: transient sensor disconnection (TD) and random noise (RN). Performance of the two methods was assessed according to Bland and Altman. The ANN presented a higher bias and scatter than MLF during the application of RN, except when RN was lower than 2% of peak airway pressure. During TD, MLF algorithm showed a higher bias and scatter than ANN. After the application of RN, ANN and MLF maintain a stable performance, although MLF shows better results. ANNs have a more stable performance and yield a more robust estimation of C RS than MLF in conditions of transient sensor disconnection.
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