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| 5. |
- Wunderer, C. B., et al.
(författare)
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Detector developments at DESY
- 2016
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Ingår i: Journal of Synchrotron Radiation. - 0909-0495 .- 1600-5775. ; 23, s. 111-117
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Tidskriftsartikel (refereegranskat)abstract
- With the increased brilliance of state-of-the-art synchrotron radiation sources and the advent of free-electron lasers (FELs) enabling revolutionary science with EUV to X-ray photons comes an urgent need for suitable photon imaging detectors. Requirements include high frame rates, very large dynamic range, single-photon sensitivity with low probability of false positives and (multi)-megapixels. At DESY, one ongoing development project-in collaboration with RAL/STFC, Elettra Sincrotrone Trieste, Diamond, and Pohang Accelerator Laboratory-is the CMOS-based soft X-ray imager PERCIVAL. PERCIVAL is a monolithic active-pixel sensor back-thinned to access its primary energy range of 250 eV to 1 keV with target efficiencies above 90%. According to preliminary specifications, the roughly 10 cm × 10 cm, 3.5k × 3.7k monolithic sensor will operate at frame rates up to 120 Hz (commensurate with most FELs) and use multiple gains within 27 μm pixels to measure 1 to ∼ 100000 (500 eV) simultaneously arriving photons. DESY is also leading the development of the AGIPD, a high-speed detector based on hybrid pixel technology intended for use at the European XFEL. This system is being developed in collaboration with PSI, University of Hamburg, and University of Bonn. The AGIPD allows singlepulse imaging at 4.5 MHz frame rate into a 352-frame buffer, with a dynamic range allowing single-photon detection and detection of more than 10000 photons at 12.4 keV in the same image. Modules of 65k pixels each are configured to make up (multi)megapixel cameras. This review describes the AGIPD and the PERCIVAL concepts and systems, including some recent results and a summary of their current status. It also gives a short overview over other FEL-relevant developments where the Photon Science Detector Group at DESY is involved. © 2016 International Union of Crystallography.
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| 6. |
- Lange, C., et al.
(författare)
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Perspectives for personalized therapy for patients with multidrug-resistant tuberculosis
- 2018
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Ingår i: Journal of Internal Medicine. - : WILEY. - 0954-6820 .- 1365-2796. ; 284:2, s. 163-188
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Forskningsöversikt (refereegranskat)abstract
- According to the World Health Organization (WHO), tuberculosis is the leading cause of death attributed to a single microbial pathogen worldwide. In addition to the large number of patients affected by tuberculosis, the emergence of Mycobacterium tuberculosis drug-resistance is complicating tuberculosis control in many high-burden countries. During the past 5years, the global number of patients identified with multidrug-resistant tuberculosis (MDR-TB), defined as bacillary resistance at least against rifampicin and isoniazid, the two most active drugs in a treatment regimen, has increased by more than 20% annually. Today we experience a historical peak in the number of patients affected by MDR-TB. The management of MDR-TB is characterized by delayed diagnosis, uncertainty of the extent of bacillary drug-resistance, imprecise standardized drug regimens and dosages, very long duration of therapy and high frequency of adverse events which all translate into a poor prognosis for many of the affected patients. Major scientific and technological advances in recent years provide new perspectives through treatment regimens tailor-made to individual needs. Where available, such personalized treatment has major implications on the treatment outcomes of patients with MDR-TB. The challenge now is to bring these adances to those patients that need them most.
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| 7. |
- Correa, J., et al.
(författare)
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On the Charge Collection Efficiency of the PERCIVAL Detector
- 2016
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Ingår i: Journal of Instrumentation. - : IOP. - 1748-0221. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- The PERCIVAL soft X-ray imager is being developed by DESY, RAL, Elettra, DLS, and PAL to address the challenges at high brilliance Light Sources such as new-generation Synchrotrons and Free Electron Lasers. Typical requirements for detector systems at these sources are high frame rates, large dynamic range, single-photon counting capability with low probability of false positives, high quantum efficiency, and (multi)-mega-pixel arrangements. PERCIVAL is a monolithic active pixel sensor, based on CMOS technology. It is designed for the soft X-ray regime and, therefore, it is post-processed in order to achieve high quantum efficiency in its primary energy range (250 eV to 1 keV) . This work will report on the latest experimental results on charge collection efficiency obtained for multiple back-side-illuminated test sensors during two campaigns, at the P04 beam-line at PETRA III, and the CiPo beam-line at Elettra, spanning most of the primary energy range as well as testing the performance for photon-energies below 250 eV . In addition, XPS surface analysis was used to cross-check the obtained results.
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| 8. |
- Correa, J., et al.
(författare)
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The PERCIVAL soft X-ray Detector
- 2018
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Ingår i: 2018 IEEE Nuclear Science Symposium and Medical Imaging Conference, NSS/MIC 2018 - Proceedings. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781538684948
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Konferensbidrag (refereegranskat)abstract
- The PERCIVAL collaboration to develop a soft X-ray imager able to address the challenges of high brilliance light sources, such as new-generation synchrotrons and Free Electron Lasers, has reached one of its major milestones: a full 2-MegaPixel (P2M) system (uninterrupted 4 × 4 cm2 active area) has already seen its first light.Smaller prototypes of the device, a monolithic active pixel sensor based on CMOS technology, have already been fully characterised, and have demonstrated high frame rate, large dynamic range, and relatively high quantum efficiency.The PERCIVAL modular layout allows for clover-leaf like arrangement of up to four P2M systems. Moreover, it will be post-processed in order to achieve a high quantum efficiency in its primary energy range (250 eV to 1 keV).We will present the P2M system, its status and newest results, bring these in context with achieved prototype performance, and outline future steps.
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| 9. |
- Khromova, A., et al.
(författare)
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Report on recent results of the PERCIVAL soft X-ray imager
- 2016
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Ingår i: Journal of Instrumentation. - : IOP. - 1748-0221. ; 11:November
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Tidskriftsartikel (refereegranskat)abstract
- The PERCIVAL (Pixelated Energy Resolving CMOS Imager, Versatile And Large) soft X-ray 2D imaging detector is based on stitched, wafer-scale sensors possessing a thick epi-layer, which together with back-thinning and back-side illumination yields elevated quantum efficiency in the photon energy range of 125–1000 eV. Main application fields of PERCIVAL are foreseen in photon science with FELs and synchrotron radiation. This requires high dynamic range up to 105 ph @ 250 eV paired with single photon sensitivity with high confidence at moderate frame rates in the range of 10–120 Hz. These figures imply the availability of dynamic gain switching on a pixel-by-pixel basis and a highly parallel, low noise analog and digital readout, which has been realized in the PERCIVAL sensor layout. Different aspects of the detector performance have been assessed using prototype sensors with different pixel and ADC types. This work will report on the recent test results performed on the newest chip prototypes with the improved pixel and ADC architecture. For the target frame rates in the 10–120 Hz range an average noise floor of 14e− has been determined, indicating the ability of detecting single photons with energies above 250 eV. Owing to the successfully implemented adaptive 3-stage multiple-gain switching, the integrated charge level exceeds 4 centerdot 106 e− or 57000 X-ray photons at 250 eV per frame at 120 Hz. For all gains the noise level remains below the Poisson limit also in high-flux conditions. Additionally, a short overview over the updates on an oncoming 2 Mpixel (P2M) detector system (expected at the end of 2016) will be reported.
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| 13. |
- Mansouri, L, et al.
(författare)
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Different prognostic impact of recurrent gene mutations in chronic lymphocytic leukemia depending on IGHV gene somatic hypermutation status: a study by ERIC in HARMONY
- 2023
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 37:2, s. 339-347
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Tidskriftsartikel (refereegranskat)abstract
- Recent evidence suggests that the prognostic impact of gene mutations in patients with chronic lymphocytic leukemia (CLL) may differ depending on the immunoglobulin heavy variable (IGHV) gene somatic hypermutation (SHM) status. In this study, we assessed the impact of nine recurrently mutated genes (BIRC3, EGR2, MYD88, NFKBIE, NOTCH1, POT1, SF3B1, TP53, and XPO1) in pre-treatment samples from 4580 patients with CLL, using time-to-first-treatment (TTFT) as the primary end-point in relation to IGHV gene SHM status. Mutations were detected in 1588 (34.7%) patients at frequencies ranging from 2.3–9.8% with mutations in NOTCH1 being the most frequent. In both univariate and multivariate analyses, mutations in all genes except MYD88 were associated with a significantly shorter TTFT. In multivariate analysis of Binet stage A patients, performed separately for IGHV-mutated (M-CLL) and unmutated CLL (U-CLL), a different spectrum of gene alterations independently predicted short TTFT within the two subgroups. While SF3B1 and XPO1 mutations were independent prognostic variables in both U-CLL and M-CLL, TP53, BIRC3 and EGR2 aberrations were significant predictors only in U-CLL, and NOTCH1 and NFKBIE only in M-CLL. Our findings underscore the need for a compartmentalized approach to identify high-risk patients, particularly among M-CLL patients, with potential implications for stratified management.
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| 14. |
- Niemann, C., Rosmej, F.B., Tauschwitz, A., Neff, S., Penache, D., Birkner, R., Constantin, C., Knobloch, R., Presura, R., Hoffmann, D.H.H., Yu, S.S., Lee, R.W.
(författare)
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pectroscopic density and temperature measurements and modelling of a discharge plasma for neutralized ion-beam transport.
- 2003
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Ingår i: J.Physics D-Appl. Physics. ; 36, s. 2102-9
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Tidskriftsartikel (refereegranskat)
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| 15. |
- Pinaroli, G., et al.
(författare)
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PERCIVAL : Possible applications in X-ray micro-tomography
- 2020
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 15:2
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Tidskriftsartikel (refereegranskat)abstract
- X-ray computed micro-tomography (μCT) is one of the most advanced and common non-destructive techniques in the field of medical imaging and material science. It allows recreating virtual models (3D models), without destroying the original objects, by measuring three-dimensional X-ray attenuation coefficient maps of samples on the (sub) micrometer scale. The quality of the images obtained using μCT is strongly dependent on the performance of the associated X-ray detector i.e. to the acquisition of information of the X-ray beam traversing the patient/sample being precise and accurate. Detectors for μCT have to meet the requirements of the specific tomography procedure in which they are going to be used. In general, the key parameters are high spatial resolution, high dynamic range, uniformity of response, high contrast sensitivity, fast acquisition readout and support of high frame rates. At present the detection devices in commercial μCT scanners are dominated by charge-coupled devices (CCD), photodiode arrays, CMOS acquisition circuits and more recently by hybrid pixel detectors. Monolithic CMOS imaging sensors, which offer reduced pixel sizes and low electronic noise, are certainly excellent candidates for μCT and may be used for the development of novel high-resolution imaging applications. The uses of monolithic CMOS based detectors such as the PERCIVAL detector are being recently explored for synchrotron and FEL applications. PERCIVAL was developed to operate in synchrotron and FEL facilities in the soft X-ray regime from 250 eV to 1 keV and it could offer all the aforementioned technical requirements needed in μCT experiments. In order to adapt the system for a typical tomography application, a scintillator is required, to convert incoming X-ray radiation (∼ tens of KeV) into visible light which may be detected with high efficiency. Such a taper-based scintillator was developed and mounted in front of the sensitive area of the PERCIVAL imager. In this presentation we will report the setup of the detector system and preliminary results of first μCTs of reference objects, which were performed in the TomoLab at ELETTRA.
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| 19. |
- Chatzikonstantinou, T, et al.
(författare)
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COVID-19 severity and mortality in patients with CLL: an update of the international ERIC and Campus CLL study
- 2021
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 35:12, s. 3444-3454
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Tidskriftsartikel (refereegranskat)abstract
- Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p < 0.001). Untreated patients had a lower risk of death (HR = 0.54, 95% CI:0.41–0.72). The risk of death was higher for older patients and those suffering from cardiac failure (HR = 1.03, 95% CI:1.02–1.04; HR = 1.79, 95% CI:1.04–3.07, respectively). Age, CLL-directed treatment, and cardiac failure were significant risk factors of OS. Untreated patients had a better chance of survival than those on treatment or recently treated.
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| 21. |
- Eskelund, Christian Winther, et al.
(författare)
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Detailed Long-Term Follow-Up of Patients Who Relapsed After the Nordic Mantle Cell Lymphoma Trials : MCL2 and MCL3
- 2021
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Ingår i: HemaSphere. - : Wolters Kluwer. - 2572-9241. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- Mantle cell lymphoma (MCL) is an incurable disease with a highly variable clinical course. The prognosis after relapse is generally poor, and no standard of care exists. We investigated the postrelapse outcomes of 149 patients who were initially treated in the Nordic Lymphoma Group trials, MCL2 or MCL3, both representing intensive cytarabine-containing frontline regimens including autologous stem cell transplant. Patients with progression of disease before 24 months (POD24, n = 51, 34%) displayed a median overall survival of 6.6 months compared with 46 months for patients with later POD (n = 98, 66%; P < 0.001). MCL international prognostic index, cell proliferation marker, blastoid morphology, and TP53 mutations showed independent prognostic value irrespective of POD24, and in a combined, exploratory risk score, patients with 0, 1, 2-3, or 4-5 high-risk markers, respectively, displayed a 5-year overall survival of 62%, 39%, 31%, and 0%. By a comparison of median progression-free survival of the different salvage therapies in the relapse setting, bendamustine-rituximab was superior to all other combination chemotherapy regimens; however, it was also associated with longer responses to last line of therapy. Collectively, we confirm the prognostic impact of POD24 and highlight the relevance of other biomarkers, and we emphasize the importance of novel therapies for patients with high-risk features at first POD.
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| 22. |
- Eskelund, Christian W., et al.
(författare)
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TP53 mutations identify younger mantle cell lymphoma patients who do not benefit from intensive chemoimmunotherapy
- 2017
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 130:17, s. 1903-1910
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Tidskriftsartikel (refereegranskat)abstract
- Despite recent advances in lymphoma treatment, mantle cell lymphoma (MCL) remains incurable, and we are still unable to identify patients who will not benefit from the current standard of care. Here, we explore the prognostic value of recurrent genetic aberrations in diagnostic bone marrow (BM) specimens from 183 younger patients with MCL from the Nordic MCL2 and MCL3 trials, which represent current standard-of-care regimens. In the univariate model, mutations of TP53 (11%) and NOTCH1 (4%), and deletions of TP53 (16%) andCDKN2A(20%),weresignificantly associatedwithinferioroutcomes(togetherwithMIPI, MIPI-c, blastoidmorphology, and Ki67 > 30%); however, inmultivariate analyses, only TP53 mutations (HR, 6.2; P <.0001) retained prognostic impact for overall survival (OS), whereas TP53 mutations (HR, 6.9; P <.0001) andMIPI-c high-risk (HR, 2.6; P5.003) had independent prognostic impact on time to relapse. TP53-mutated cases had a dismal outcome, with a median OS of 1.8 years, and 50% relapsed at 1.0 years, compared to a median OS of 12.7 years for TP53-unmutated cases (P <.0001). TP53 mutations were significantly associated with Ki67 > 30%, blastoid morphology, MIPI high-risk, and inferior responses to both induction- and high-dose chemotherapy. In conclusion, we show that TP53mutations identify a phenotypically distinct and highly aggressive form of MCL with poor or no response to regimens including cytarabine, rituximab, and autologous stem-cell transplant (ASCT). We suggest patients with MCL should be stratified according to TP53 status, and that patients with TP53 mutations should be considered for experimental frontline trials exploring novel agents.
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| 23. |
- Jerkeman, Mats, et al.
(författare)
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Ibrutinib, lenalidomide, and rituximab in relapsed or refractory mantle cell lymphoma (PHILEMON) : a multicentre, open-label, single-arm, phase 2 trial
- 2018
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Ingår i: Tha Lancet Haematology. - : ELSEVIER SCI LTD. - 2352-3026. ; 5:3, s. E109-E116
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Tidskriftsartikel (refereegranskat)abstract
- Background Regimens based on ibrutinib alone and lenalidomide and rituximab in combination show high activity in patients with relapsed or refractory mantle cell lymphoma. We hypothesised that the combination of all three drugs would improve efficacy compared with previously published data on either regimen alone. Methods In this multicentre, open-label, single-arm, phase 2 trial, we enrolled patients aged 18 years or older with relapsed or refractory mantle cell lymphoma who had previously been treated with at least one rituximab-containing regimen, an Eastern Cooperative Oncology Group performance status score of 0-3, and at least one site of measurable disease, and who met criteria for several laboratory-assessed parameters. Treatment was divided into an induction phase of 12 cycles of 28 days with all three drugs and a maintenance phase with ibrutinib and rituximab only (cycle duration 56 days), given until disease progression or unacceptable toxicity. In the induction phase, patients received intravenous (375 mg/m(2)) or subcutaneous (1400 mg) rituximab once a week during cycle 1 and then once every 8 weeks. Oral ibrutinib (560 mg once a day) was given to patients every day in the cycle, whereas oral lenalidomide (15 mg once a day) was given on days 1-21. The primary endpoint was overall response assessed in the intention-totreat population according to Lugano criteria. Safety analysis included all patients who received the treatment, irrespective of eligibility or duration of treatment. The trial is ongoing, but is no longer accruing patients, and is registered with ClinicalTrials. gov, number NCT02460276. Findings Between April 30, 2015, and June 1, 2016, we enrolled 50 patients with relapsed or refractory mantle cell lymphoma at ten centres in Sweden, Finland, Norway, and Denmark. At a median follow-up of 17.8 months (IQR 14.7-20.9), 38 (76%, 95% CI 63-86) patients had an overall response, including 28 (56%, 42-69) patients who had a complete response and ten (20%, 11-33) who had a partial response. The most common grade 3-4 adverse events were neutropenia (in 19 [38%] of 50 patients), infections (in 11 [22%] patients), and cutaneous toxicity (in seven [14%] patients). There were three treatment-related deaths during the study, two due to sepsis and one due to embolic stroke. Interpretation Our results provide preliminary evidence that the triplet combination of ibrutinib, lenalidomide, and rituximab is an active regimen in patients with relapsed or refractory mantle cell lymphoma, and should be evaluated in a prospective randomised controlled trial.
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| 24. |
- Kater, Arnon P., et al.
(författare)
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Minimal residual disease-guided stop and start of venetoclax plus ibrutinib for patients with relapsed or refractory chronic lymphocytic leukaemia (HOVON141/VISION) : primary analysis of an open-label, randomised, phase 2 trial
- 2022
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Ingår i: The Lancet Oncology. - : ELSEVIER SCIENCE INC. - 1470-2045 .- 1474-5488. ; 23:6, s. 818-828
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Tidskriftsartikel (refereegranskat)abstract
- Background Targeted time-limited treatment options are needed for patients with relapsed or refractory chronic lymphocytic leukaemia. The aim of this study was to investigate the efficacy of minimal residual disease (MRD)-guided, time-limited ibrutinib plus venetoclax treatment in this patient group. Methods HOVON141/VISION was an open-label, randomised, phase 2 trial conducted in 47 hospitals in Belgium, Denmark, Finland, the Netherlands, Norway, and Sweden. Eligible participants were aged 18 years or older with previously treated chronic lymphocytic leukaemia with or without TP53 aberrations; had not been exposed to Bruton tyrosine-kinase inhibitors or BCL2 inhibitors; had a creatinine clearance rate of 30 mL/min or more; and required treatment according to International Workshop on Chronic Lymphocytic Leukemia 2018 criteria. Participants with undetectable MRD (< 10(-4); less than one chronic lymphocytic leukaemia cell per 10 000 leukocytes) in peripheral blood and bone marrow after 15 28-day cycles of oral ibrutinib (420 mg once daily) plus oral venetoclax (weekly ramp-up 20 mg, 50 mg, 100 mg, 200 mg, up to 400 mg once daily) were randomly assigned (1:2) to ibrutinib maintenance or treatment cessation. Patients who were MRD positive continued to receive ibrutinib monotherapy. Patients who became MRD (> 10(-2)) during observation reinitiated treatment with ibrutinib plus venetoclax. The primary endpoint was progression-free survival at 12 months after random assignment in the treatment cessation group. Progression-free survival was analysed in the intention-to-treat population. All patients who received at least one dose of study drug were included in the safety assessment. The study is registered at ClinicalTrials.gov, NCT03226301, and is active but not recruiting. Findings Between July 12, 2017, and Jan 21, 2019, 230 patients were enrolled, 225 of whom were eligible. 188 (84%) of 225 completed treatment with ibrutinib plus venetoclax and were tested for MRD at cycle 15. After cycle 15, 78 (35%) patients had undetectable MRD and 72 (32%) were randomly assigned to a treatment group (24 to ibrutinib maintenance and 48 to treatment cessation). The remaining 153 patients were not randomly assigned and continued with ibrutinib monotherapy. Median follow-up of 208 patients still alive and not lost to follow-up at data cutoff on June 22, 2021, was 34middot4 months (IQR 30.6-37.9). Progression-free survival after 12 months in the treatment cessation group was 98% (95% CI 89-100). Infections (in 130 [58%] of 225 patients), neutropenia (in 91 [40%] patients), and gastrointestinal adverse events (in 53 [24%] patients) were the most frequently reported; no new safety signals were detected. Serious adverse events were reported in 46 (40%) of 116 patients who were not randomly assigned and who continued ibrutinib maintenance after cycle 15, eight (33%) of 24 patients in the ibrutinib maintenance group, and four (8%) of 48 patients in the treatment cessation group. One patient who was not randomly assigned had a fatal adverse event (bleeding) deemed possibly related to ibrutinib. Interpretation These data point to a favourable benefit-risk profile of MRD-guided, time-limited treatment with ibrutinib plus venetoclax for patients with relapsed or refractory chronic lymphocytic leukaemia, suggesting that MRD-guided cessation and reinitiation is feasible in this patient population. Copyright (C) 2022 Elsevier Ltd. All rights reserved.
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| 25. |
- Klaer, P., et al.
(författare)
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Electronic structure of the austenitic and martensitic state of magnetocaloric Ni-Mn-In Heusler alloy films
- 2013
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 88, s. 174414-
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Tidskriftsartikel (refereegranskat)abstract
- Changes of the electronic and magnetic structure near the martensitic phase transition of Ni-Mn-In Heusler alloys dopedwith Co are investigated by experiment and theory. The nonstoichiometric Ni48Co5Mn35In12 epitaxial film undergoes a transition from a weakly magnetic martensitic phase below T-m = 350 K to a ferromagnetic austenitic phase above T-m. Element-specific magnetic moments and the unoccupied density of states function is investigated using x-raymagnetic circular dichroism.We find an antiparallel alignment ofMnandNi/Comagnetic moments in both phases. The electronic structure is calculated using the SPR-KKR Green's function approach considering experimental results on the atomic disorder in the sample. The good agreement of experimental and theoretically simulated x-ray absorption spectra in both phases confirms that a band Jahn-Teller like lifting of a degenerate d state is the origin of the energetic preference of the martensitic phase at low temperatures.
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| 26. |
- Kontsevaya, Irina, et al.
(författare)
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Perspectives for systems biology in the management of tuberculosis
- 2021
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Ingår i: European Respiratory Review. - : European Respiratory Society (ERS). - 0905-9180 .- 1600-0617. ; 30:160
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Forskningsöversikt (refereegranskat)abstract
- Standardised management of tuberculosis may soon be replaced by individualised, precision medicine-guided therapies informed with knowledge provided by the field of systems biology. Systems biology is a rapidly expanding field of computational and mathematical analysis and modelling of complex biological systems that can provide insights into mechanisms underlying tuberculosis, identify novel biomarkers, and help to optimise prevention, diagnosis and treatment of disease. These advances are critically important in the context of the evolving epidemic of drug-resistant tuberculosis. Here, we review the available evidence on the role of systems biology approaches - human and mycobacterial genomics and transcriptomics, proteomics, lipidomics/metabolomics, immunophenotyping, systems pharmacology and gut microbiomes - in the management of tuberculosis including prediction of risk for disease progression, severity of mycobacterial virulence and drug resistance, adverse events, comorbidities, response to therapy and treatment outcomes. Application of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach demonstrated that at present most of the studies provide "very low" certainty of evidence for answering clinically relevant questions. Further studies in large prospective cohorts of patients, including randomised clinical trials, are necessary to assess the applicability of the findings in tuberculosis prevention and more efficient clinical management of patients.
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| 36. |
- Wilhein, T, et al.
(författare)
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Off-axis reflection zone plate for quantitative soft x-ray source characterization
- 1997
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 71:2, s. 190-192
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Tidskriftsartikel (refereegranskat)abstract
- A compact system for high-resolution spectroscopy and quantitative photon flux and brilliance measurements of pulsed soft x-ray sources is described. The calibrated system combines a novel elliptical off-axis reflection zone plate with charge-coupled device detection for simultaneous spectral and spatial measurements. Experiments on a water-window droplet-target laser-plasma source demonstrate lambda/Delta lambda greater than or equal to 1000 spectral resolution and absolute flux and brilliance measurements. (C) 1997 American Institute of Physics.
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| 37. |
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| 38. |
- Wunderer, C. B., et al.
(författare)
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The Percival 2-Megapixel monolithic active pixel imager
- 2019
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The peak brilliance reached by today's Free-Electron Laser and Synchrotron light sources requires photon detectors matching their output intensity and other characteristics in order to fully realize the sources' potential. The Pixellated Energy Resolving CMOS Imager, Versatile And Large (Percival) is a dedicated soft X-ray imager (0.25-1 keV) developed for this purpose by a collaboration of DESY, Rutherford Appleton Laboratory/STFC, Elettra Sincrotrone Trieste, Diamond Light Source, and Pohang Accelerator Laboratory. Following several generations of prototypes, the Percival "P2M" 2-Megapixel imager - a 4.5x5 cm monolithic, stitched sensor with an uninterrupted imaging area of 4x4 cm(2) (1408x1484 pixels of 27x27 mu m - was produced and has demonstrated basic functionality with a first-light image using visible light. It is currently being brought to full operation in a front-illuminated configuration. The readout system being commissioned in parallel has been developed specifically for this imager which will produce - at full 300 Hz frame rate - data at 20 Gbit/s. A first wafer with eight Percival P2M chips has undergone backthinning to enable soft X-ray detection. It has been diced and chips are currently being wirebonded. We summarize here the P2M system, the project status, and show the P2M sensor's first response to visible light.
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