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- Khoury, J. D., et al.
(författare)
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The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms
- 2022
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 36, s. 1703-1719
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Tidskriftsartikel (refereegranskat)abstract
- The upcoming 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours is part of an effort to hierarchically catalogue human cancers arising in various organ systems within a single relational database. This paper summarizes the new WHO classification scheme for myeloid and histiocytic/dendritic neoplasms and provides an overview of the principles and rationale underpinning changes from the prior edition. The definition and diagnosis of disease types continues to be based on multiple clinicopathologic parameters, but with refinement of diagnostic criteria and emphasis on therapeutically and/or prognostically actionable biomarkers. While a genetic basis for defining diseases is sought where possible, the classification strives to keep practical worldwide applicability in perspective. The result is an enhanced, contemporary, evidence-based classification of myeloid and histiocytic/dendritic neoplasms, rooted in molecular biology and an organizational structure that permits future scalability as new discoveries continue to inexorably inform future editions.
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- Bock, O., et al.
(författare)
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Use of GNSS Tropospheric Products for Climate Monitoring (Working Group 3)
- 2020
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Ingår i: Advanced GNSS Tropospheric Products for Monitoring Severe Weather Events and Climate. - Cham : Springer International Publishing. - 9783030139001 ; , s. 267-402
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- There has been growing interest in recent years in the use of homogeneously reprocessed ground-based GNSS, VLBI, and DORIS measurements for climate applications. Existing datasets are reviewed and the sensitivity of tropospheric estimates to the processing details is discussed. The uncertainty in the derived IWV estimates and linear trends is around 1 kg m^2 RMS and ± 0.3 kg m^2 per decade, respectively. Standardized methods for ZTD outlier detection and IWV conversion are proposed. The homogeneity of final time series is limited however by changes in the stations equipment and environment. Various homogenization algorithms have been evaluated based on a synthetic benchmark dataset. The uncertainty of trends estimated from the homogenized times series is estimated to ±0.5 kg m^2 per decade. Reprocessed GNSS IWV data are analysed along with satellites data, reanalyses and global and regional climate model simulations. A selection of global and regional reprocessed GNSS datasets and ERA-interim reanalysis are made available through the GOP-TropDB tropospheric database and online service. A new tropo SINEX format, providing new features and simplifications, was developed and it is going to be adopted by all the IAG services.
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- Davenne, Tamara, et al.
(författare)
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SAMHD1 Limits the Efficacy of Forodesine in Leukemia by Protecting Cells against the Cytotoxicity of dGTP.
- 2020
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Ingår i: Cell Reports. - : Elsevier. - 2211-1247. ; 31:6
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Tidskriftsartikel (refereegranskat)abstract
- The anti-leukemia agent forodesine causes cytotoxic overload of intracellular deoxyguanosine triphosphate (dGTP) but is efficacious only in a subset of patients. We report that SAMHD1, a phosphohydrolase degrading deoxyribonucleoside triphosphate (dNTP), protects cells against the effects of dNTP imbalances. SAMHD1-deficient cells induce intrinsic apoptosis upon provision of deoxyribonucleosides, particularly deoxyguanosine (dG). Moreover, dG and forodesine act synergistically to kill cells lacking SAMHD1. Using mass cytometry, we find that these compounds kill SAMHD1-deficient malignant cells in patients with chronic lymphocytic leukemia (CLL). Normal cells and CLL cells from patients without SAMHD1 mutation are unaffected. We therefore propose to use forodesine as a precision medicine for leukemia, stratifying patients by SAMHD1 genotype or expression.
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- McCollum, ED, et al.
(författare)
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Defining hypoxaemia from pulse oximeter measurements of oxygen saturation in well children at low altitude in Bangladesh: an observational study
- 2021
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Ingår i: BMJ open respiratory research. - : BMJ. - 2052-4439. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- WHO defines hypoxaemia, a low peripheral arterial oxyhaemoglobin saturation (SpO2), as <90%. Although hypoxaemia is an important risk factor for mortality of children with respiratory infections, the optimal SpO2 threshold for defining hypoxaemia is uncertain in low-income and middle-income countries (LMICs). We derived a SpO2 threshold for hypoxaemia from well children in Bangladesh residing at low altitude.MethodsWe prospectively enrolled well, children aged 3–35 months participating in a pneumococcal vaccine evaluation in Sylhet district, Bangladesh between June and August 2017. Trained health workers conducting community surveillance measured the SpO2 of children using a Masimo Rad-5 pulse oximeter with a wrap sensor. We used standard summary statistics to evaluate the SpO2 distribution, including whether the distribution differed by age or sex. We considered the 2.5th, 5th and 10th percentiles of SpO2 as possible lower thresholds for hypoxaemia.ResultsOur primary analytical sample included 1470 children (mean age 18.6±9.5 months). Median SpO2 was 98% (IQR 96%–99%), and the 2.5th, 5th and 10th percentile SpO2 was 91%, 92% and 94%. No child had a SpO2 <90%. Children 3–11 months had a lower median SpO2 (97%) than 12–23 months (98%) and 24–35 months (98%) (p=0.039). The SpO2 distribution did not differ by sex (p=0.959).ConclusionA SpO2 threshold for hypoxaemia derived from the 2.5th, 5th or 10th percentile of well children is higher than <90%. If a higher threshold than <90% is adopted into LMIC care algorithms then decision-making using SpO2 must also consider the child’s clinical status to minimise misclassification of well children as hypoxaemic. Younger children in lower altitude LMICs may require a different threshold for hypoxaemia than older children. Evaluating the mortality risk of sick children using higher SpO2 thresholds for hypoxaemia is a key next step.
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