Search

An open prospective, multicenter study enrolled 48 selected patients with chronic immune thrombocytopenia who achieved complete response for 1 year on thrombopoietin receptor agonists, half of the patients maintained a sustained response off treatment 4 years after treatment discontinuation. NCT03119974., (Copyright © 2024 American Society of Hematology.)

We present a glacial-related lake inventory for a region spanning 41.5° - 47° S in Patagonian Andes, where information on past glacier lake outburst floods (GLOF's) has hitherto remained significantly underreported. Analyzing remotely sensed images, we obtained data on 702 glacial-related lakes. Through detailed geomorphic assessments and manual supervision, we revised current inventories and added 35 GLOFs triggered from moraine/bedrock dammed lakes failures. The regional GLOF inventory presented contains information on 71 historical failures of moraine/bedrock dammed glacial lakes. From this database we analyzed outburst timing and managed to constrain 37 events occurrences within a period of 1 year. Around 40 % of them have occurred since the early 2000's, most of them originating from lakes probably formed as a delayed response to the glacial retreat imposed by the end of the Little Ice Age. On the other hand, we analyzed meteorological conditions for a sub-set of 10 events constrained within a 10-days period, finding a strong link between atmospheric rivers, cut-off lows impacting the southern Andes, and GLOFs. Only one case is likely to have been triggered by a Mw 4.9 earthquake. Based on topographic potential for avalanching, we estimated GLOF hazard potential, recognizing at least 3 subregions with high hazard, which moreover can be highly susceptible to climate conditions that regionally affect GLOF occurrence., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

The primary goal of paleoflood hydrology is to estimate the frequency and magnitude of past floods. Botanical evidence, and particularly scars on trees, has been used repeatedly as paleostage indicators to reconstruct peak discharges and flood height. Yet, these reconstructions depend on the presence of visible scars on tree stems which tend to be masked as trees grow older. Here, we estimated flood magnitude using an alternative approach based on growth disturbances in tree-ring series, tree positions and the minimal discharge necessary to submerge the root collar of a tree as estimated by hydraulic modeling. We tested the reliability of this newly developed approach by using the traditional scar-based reconstruction as a benchmark. To this end, we sampled 60 trees showing evidence of flood damage on their stems along a 787-m long segment of the Asco river (Corsica, France). Based on 440 growth disturbances dated in tree-ring series, we reconstructed 28 floods between 1759 and 2020 and 18 during the 20th century. Using the two-dimensional Iber hydraulic model and detailed topographic data of the study site obtained from UAV imagery, we estimated that peak discharges of the 28 reconstructed events ranged between 10 and 210 m 3 s -1 , with 200 m 3 s -1 being considered as the threshold for extreme floods. Not only do the scar-based and root collar submersion approaches yield similar results, findings are also clearly in line with the sparse information available from historical archives and short gauge station records on past floods. The unprecedented length and depth of the record presented here opens new avenues for climate change and flood impact research., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Markus Stoffel reports financial support was provided by Chinese Scholarship Council., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Sustained response off treatment (SROT) after thrombopoietin receptor agonist (TPO-RA) discontinuation has been reported in immune thrombocytopenia (ITP). This prospective multicenter interventional study enrolled adults with persistent or chronic primary ITP and complete response (CR) on TPO-RAs. The primary end point was the proportion of patients achieving SROT (platelet count >30 × 109/L and no bleeding) at week 24 (W24) with no other ITP-specific medications. Secondary end points included the proportion of sustained CR off-treatment (SCROT, platelet count >100 × 109/L and no bleeding) and SROT at W52, bleeding events, and pattern of response to a new course of TPO-RAs. We included 48 patients with a median age of 58.5 years; 30 of 48 had chronic ITP at TPO-RA initiation. In the intention-to-treat analysis, 27 of 48 achieved SROT, 15 of 48 achieved SCROT at W24; 25 of 48 achieved SROT, and 14 of 48 achieved SCROT at W52. No severe bleeding episode occurred in patients who relapsed. Among patients rechallenged with TPO-RA, 11 of 12 achieved CR. We found no significant clinical predictors of SROT at W24. Single-cell RNA sequencing revealed enrichment of a tumor necrosis factor α signaling via NF-κB signature in CD8+ T cells of patients with no sustained response after TPO-RA discontinuation, which was further confirmed by a significant overexpression of CD69 on CD8+ T cells at baseline in these patients as compared with those achieving SCROT/SROT. Our results strongly support a strategy based on progressive tapering and discontinuation of TPO-RAs for patients with chronic ITP who achieved a stable CR on treatment. This trial was registered at www.clinicaltrials.gov as #NCT03119974., (© 2023 by The American Society of Hematology.)

The risk of immune thrombocytopenia (ITP) worsening during pregnancy and neonatal ITP (NITP) have never been prospectively studied. We included 180 pregnant and 168 nonpregnant women with ITP in a prospective, multicenter, observational cohort study. A total of 131 pregnant women with ITP were matched to 131 nonpregnant women with ITP by history of splenectomy, ITP status (no response, response, complete response), and duration. Groups were followed for 15 months. The primary outcome was the first occurrence of ITP worsening defined by a composite end point including bleeding events and/or severe thrombocytopenia (<30 × 109/L) and/or ITP treatment modification. We also studied the recurrence of ITP worsening and the incidence of NITP and risk factors. The first occurrence of ITP worsening did not differ between pregnant and nonpregnant women with ITP (53.4 per 100 person-years [95% confidence interval {CI}, 40.8-69.9] vs 37.1 [95% CI, 27.5-50.0]; hazard ratio {HR}, 1.35 [95% CI, 0.89-2.03], P = .16). Pregnant women with ITP were more likely to have recurrence of severe thrombocytopenia and treatment modification (HR, 2.71 [95% CI, 1.41-5.23], P = .003; HR, 2.01 [95% CI, 1.14-3.57], P = .017, respectively). However, recurrence of severe bleeding events was not different between groups (P = .4). Nineteen (14%) neonates showed NITP <50 × 109/L. By multivariable analysis, NITP was associated with a previous offspring with NITP and maternal platelet count <50 × 109/L within 3 months before delivery (adjusted odds ratio, 5.55 [95% CI, 1.72-17.89], P = .004 and 4.07 [95% CI, 1.41-11.73], P = .009). To conclude, women with ITP do not increase their risk of severe bleeding during pregnancy. NITP is associated with NITP history and the severity of maternal ITP during pregnancy. These results will be useful for counseling women with ITP., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

In September 2014, the Kashmir valley (north-west India) experienced a massive flood causing significant economic losses and fatalities. This disaster underlined the high vulnerability of the local population and raised questions regarding the resilience of Kashmiris to future floods. Although the magnitude of the 2014 flood has been considered unprecedented within the context of existing measurements, we argue that the short flow series may lead to spurious misinterpretation of the probability of such extreme events. Here we use a millennium-long record of past floods in Kashmir based on historical and tree-ring records to assess the probability of 2014-like flood events in the region. Our flood chronology (635 CE-nowadays) provides key insights into the recurrence of flood disasters and propels understanding of flood variability in this region over the last millennium, showing enhanced activity during the Little Ice Age. We find that high-impact floods have frequently disrupted the Kashmir valley in the past. Thus, the inclusion of historical records reveals large flood hazard levels in the region. The newly gained information also underlines the critical need to take immediate action in the region, so as to reduce the exposure of local populations and to increase their resilience, despite existing constraints in watershed management related to the Indus Water Treaty., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We investigate the sensitivity of the relict, endemic Cretan tree species Zelkova abelicea (Lam.) Boiss. (Ulmaceae) to several climate variables (temperature, precipitation and drought). For this purpose, we establish the first centennial tree-ring chronology for the species, and the first ever tree-ring chronology for a broadleaved species on Crete. We demonstrate the strong sensitivity of Z. abelicea towards precipitation and drought in late spring to early summer and the absence of a significant response to abundant precipitation occurring during winter or early spring. Whereas the late spring sensitivity is strong and consistent through time, the species seems to be experiencing a loss of signal towards early summer conditions since the 1970s, interpreted as an earlier cessation of cambial activity due to the increase in summer drought conditions on Crete. However, despite a reduced vegetative period, no significant decrease in radial growth of Z. abelicea was observed in the tree-ring series for the last decades, thus highlighting the capacity of Z. abelicea to withstand changing environmental conditions., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Ring width (TRW) chronologies from Siberian (Pinus sibirica) and Scots (Pinus sylvestris) pine trees were sampled at Mukhrino - a large mire complex in central-western Siberia - to evaluate the impacts of hydroclimatic variability on tree growth over the last three centuries. For this purpose, we compared climate-growth correlation profiles from trees growing on peat soils with those growing on adjacent mineral soils. Tree growth at both peat and mineral soils was positively correlated to air temperature during the vegetation period. This finding can be explained by (i) the positive influence of temperature on plant physiological processes (i.e. growth control) during the growing season and (ii) the indirect impact of air temperatures on water table fluctuations. We observe also a strong link between TRW and the winter Palmer Drought Severity Index (PDSI), especially in Siberian pine, reflecting the isolating effect of snow and limited freezing damage in roots. Significant negative relations were, by contrast, observed between bog TRW chronologies and hydroclimatic indices during spring and summer; they are considered an expression of the negative impacts of high water levels and moist peat soils on root development. Some unusually old bog pines - exhibiting >500 growth rings - apparently colonized the site at the beginning of the Little Ice Age, and therefore seem to confirm that (i) peat conditions may have been drier in Siberia than in most other regions of western Europe during this period. At the same time, the bog trees also point to (ii) their strong dependence on surface conditions., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Most mouse models of hepatocellular carcinoma have expressed growth factors and oncogenes under the control of a liver-specific promoter. In contrast, we describe here the formation of liver tumors in transgenic mice overexpressing human fibroblast growth factor 19 (FGF19) in skeletal muscle. FGF19 transgenic mice had elevated hepatic alpha-fetoprotein mRNA as early as 2 months of age, and hepatocellular carcinomas were evident by 10 months of age. Increased proliferation of pericentral hepatocytes was demonstrated by 5-bromo-2'-deoxyuridine incorporation in the FGF19 transgenic mice before tumor formation and in nontransgenic mice injected with recombinant FGF19 protein. Areas of small cell dysplasia were initially evident pericentrally, and dysplastic/neoplastic foci throughout the hepatic lobule were glutamine synthetase-positive, suggestive of a pericentral origin. Consistent with chronic activation of the Wingless/Wnt pathway, 44% of the hepatocellular tumors from FGF19 transgenic mice had nuclear staining for beta-catenin. Sequencing of the tumor DNA encoding beta-catenin revealed point mutations that resulted in amino acid substitutions. These findings suggest a previously unknown role for FGF19 in hepatocellular carcinomas.