Antarctic calving loss rivals ice-shelf thinning.

Antarctica's ice shelves help to control the flow of glacial ice as it drains into the ocean, meaning that the rate of global sea-level rise is subject to the structural integrity of these fragile, floating extensions of the ice sheet1-3. Until now, data limitations have made it difficult to monitor the growth and retreat cycles of ice shelves on a large scale, and the full impact of recent calving-front changes on ice-shelf buttressing has not been understood. Here, by combining data from multiple optical and radar satellite sensors, we generate pan-Antarctic, spatially continuous coastlines at roughly annual resolution since 1997. We show that from 1997 to 2021, Antarctica experienced a net loss of 36,701 ± 1,465 square kilometres (1.9 per cent) of ice-shelf area that cannot be fully regained before the next series of major calving events, which are likely to occur in the next decade. Mass loss associated with ice-front retreat (5,874 ± 396 gigatonnes) has been approximately equal to mass change owing to ice-shelf thinning over the past quarter of a century (6,113 ± 452 gigatonnes), meaning that the total mass loss is nearly double that which could be measured by altimetry-based surveys alone. We model the impacts of Antarctica's recent coastline evolution in the absence of additional feedbacks, and find that calving and thinning have produced equivalent reductions in ice-shelf buttressing since 2007, and that further retreat could produce increasingly significant sea-level rise in the future.

Rate of mass loss from the Greenland Ice Sheet will exceed Holocene values this century.

The Greenland Ice Sheet (GIS) is losing mass at a high rate1. Given the short-term nature of the observational record, it is difficult to assess the historical importance of this mass-loss trend. Unlike records of greenhouse gas concentrations and global temperature, in which observations have been merged with palaeoclimate datasets, there are no comparably long records for rates of GIS mass change. Here we reveal unprecedented mass loss from the GIS this century, by placing contemporary and future rates of GIS mass loss within the context of the natural variability over the past 12,000 years. We force a high-resolution ice-sheet model with an ensemble of climate histories constrained by ice-core data2. Our simulation domain covers southwestern Greenland, the mass change of which is dominated by surface mass balance. The results agree favourably with an independent chronology of the history of the GIS margin3,4. The largest pre-industrial rates of mass loss (up to 6,000 billion tonnes per century) occurred in the early Holocene, and were similar to the contemporary (AD 2000-2018) rate of around 6,100 billion tonnes per century5. Simulations of future mass loss from southwestern GIS, based on Representative Concentration Pathway (RCP) scenarios corresponding to low (RCP2.6) and high (RCP8.5) greenhouse gas concentration trajectories6, predict mass loss of between 8,800 and 35,900 billion tonnes over the twenty-first century. These rates of GIS mass loss exceed the maximum rates over the past 12,000 years. Because rates of mass loss from the southwestern GIS scale linearly5 with the GIS as a whole, our results indicate, with high confidence, that the rate of mass loss from the GIS will exceed Holocene rates this century.

Understanding of Contemporary Regional Sea-Level Change and the Implications for the Future.

Global sea level provides an important indicator of the state of the warming climate, but changes in regional sea level are most relevant for coastal communities around the world. With improvements to the sea-level observing system, the knowledge of regional sea-level change has advanced dramatically in recent years. Satellite measurements coupled with in situ observations have allowed for comprehensive study and improved understanding of the diverse set of drivers that lead to variations in sea level in space and time. Despite the advances, gaps in the understanding of contemporary sea-level change remain and inhibit the ability to predict how the relevant processes may lead to future change. These gaps arise in part due to the complexity of the linkages between the drivers of sea-level change. Here we review the individual processes which lead to sea-level change and then describe how they combine and vary regionally. The intent of the paper is to provide an overview of the current state of understanding of the processes that cause regional sea-level change and to identify and discuss limitations and uncertainty in our understanding of these processes. Areas where the lack of understanding or gaps in knowledge inhibit the ability to provide the needed information for comprehensive planning efforts are of particular focus. Finally, a goal of this paper is to highlight the role of the expanded sea-level observation network-particularly as related to satellite observations-in the improved scientific understanding of the contributors to regional sea-level change.

MYH9-related disorders display heterogeneous kidney involvement and outcome.

BACKGROUND: MYH9-related diseases (MYH9-RD) are autosomal dominant disorders caused by mutations of the MYH9 gene encoding the non-muscle myosin heavy chain IIA. They are characterized by congenital thrombocytopenia, giant platelets and leucocyte inclusions. Hearing impairment, pre-senile cataract and nephropathy can also occur. We aimed to evaluate renal involvement and outcome in MYH9-RD patients followed-up by nephrologists. METHODS: We conducted a retrospective multicentre observational study of 13 patients among 9 families with MYH9 mutation diagnosed by genetic testing and immunofluorescence assay referred to nephrologists. RESULTS: At initial referral, median age was 30 (range 14-76) years. Median estimated glomerular filtration rate was 66 mL/min/1.73 m2 (0-141) and two patients had already end-stage renal disease (ESRD). Renal presentation associated proteinuria (n = 12), haematuria (n = 6) and hypertension (n = 6). Three patients developed a rapid onset ESRD whereas five others had a relatively stable kidney function over a 3-year median follow-up (1-34). Extra-renal features varied widely, with hearing impairment in six patients, cataract in two and mild liver dysfunction in seven. Thrombocytopenia existed at referral in 11 patients. Time to diagnosis varied from 0 to 29 years (median 3 years). Initial diagnoses such as idiopathic thrombocytopenic purpura (n = 4) and focal segmental glomerulosclerosis (n = 1) led to corticosteroid administration (n = 4), intravenous immunoglobulins (n = 3), cyclophosphamide (n = 1) and splenectomy (n = 1). CONCLUSIONS: Renal involvement and outcome in MYH9-RD are heterogeneous. The diagnosis is often delayed and misdiagnoses can lead to unnecessary treatments. MYH9-RD should be considered in any patient with glomerular involvement associated with a low or slightly decreased platelet count and/or hearing loss and liver dysfunction.

Novel ACTN1 variants in cases of thrombocytopenia.

The ACTN1 gene has been implicated in inherited macrothrombocytopenia. To decipher the spectrum of variants and phenotype of ACTN1-related thrombocytopenia, we sequenced the ACTN1 gene in 272 cases of unexplained chronic or familial thrombocytopenia. We identified 15 rare, monoallelic, nonsynonymous and likely pathogenic ACTN1 variants in 20 index cases from 20 unrelated families. Thirty-one family members exhibited thrombocytopenia. Targeted sequencing was carried out on 12 affected relatives, which confirmed presence of the variant. Twenty-eight of 32 cases with monoallelic ACTN1 variants had mild to no bleeding complications. Eleven cases harbored 11 different unreported ACTN1 variants that were monoallelic and likely pathogenic. Nine variants were located in the α-actinin-1 (ACTN1) rod domain and were predicted to hinder dimer formation. These variants displayed a smaller increase in platelet size compared with variants located outside the rod domain. In vitro expression of the new ACTN1 variants induced actin network disorganization and led to increased thickness of actin fibers. These findings expand the repertoire of ACTN1 variants associated with thrombocytopenia and highlight the high frequency of ACTN1-related thrombocytopenia cases. The rod domain, like other ACTN1 functional domains, may be mutated resulting in actin disorganization in vitro and thrombocytopenia with normal platelet size in most cases.

Design and results of the ice sheet model initialisation experiments initMIP-Greenland: an ISMIP6 intercomparison.

Earlier large-scale Greenland ice sheet sea-level projections (e.g., those run during the ice2sea and SeaRISE initiatives) have shown that ice sheet initial conditions have a large effect on the projections and give rise to important uncertainties. The goal of the initMIP-Greenland intercomparison exercise is to compare, evaluate and improve the initialisation techniques used in the ice sheet modelling community and to estimate the associated uncertainties in modelled mass changes. initMIP-Greenland is the first in a series of ice sheet model intercomparison activities within ISMIP6 (the Ice Sheet Model Intercomparison Project for CMIP6), which is the primary activity within the Coupled Model Intercomparison Project - phase 6 (CMIP6) focusing on the ice sheets. Two experiments for the large-scale Greenland ice sheet have been designed to allow intercomparison between participating models of 1) the initial present-day state of the ice sheet and 2) the response in two idealised forward experiments. The forward experiments serve to evaluate the initialisation in terms of model drift (forward run without additional forcing) and in response to a large perturbation (prescribed surface mass balance anomaly), and should not be interpreted as sea-level projections. We present and discuss results that highlight the diversity of data sets, boundary conditions and initialisation techniques used in the community to generate initial states of the Greenland ice sheet. We find good agreement across the ensemble for the dynamic response to surface mass balance changes in areas where the simulated ice sheets overlap, but differences arising from the initial size of the ice sheet. The model drift in the control experiment is reduced for models that participated in earlier intercomparison exercises.

Bleeding risk of surgery and its prevention in patients with inherited platelet disorders.

Excessive bleeding at surgery is a feared complication in patients with inherited platelet disorders. However, very few studies have evaluated the frequency of surgical bleeding in these hemorrhagic disorders. We performed a worldwide, multicentric, retrospective study to assess the bleeding complications of surgery, the preventive and therapeutic approaches adopted, and their efficacy in patients with inherited platelet disorders: the Surgery in Platelet disorders And Therapeutic Approach (SPATA) study. We rated the outcome of 829 surgical procedures carried out in 423 patients with well-defined forms of inherited platelet disorders: 238 inherited platelet function disorders and 185 inherited platelet number disorders. Frequency of surgical bleeding was high in patients with inherited platelet disorders (19.7%), with a significantly higher bleeding incidence in inherited platelet function disorders (24.8%) than in inherited platelet number disorders (13.4%). The frequency of bleeding varied according to the type of inherited platelet disorder, with biallelic Bernard Soulier syndrome having the highest occurrence (44.4%). Frequency of bleeding was predicted by a pre-operative World Health Organization bleeding score of 2 or higher. Some types of surgery were associated with a higher bleeding incidence, like cardiovascular and urological surgery. The use of pre-operative pro-hemostatic treatments was associated with a lower bleeding frequency in patients with inherited platelet function disorders but not in inherited platelet number disorders. Desmopressin, alone or with antifibrinolytic agents, was the preventive treatment associated with the lowest bleedings. Platelet transfusions were used more frequently in patients at higher bleeding risk. Surgical bleeding risk in inherited platelet disorders is substantial, especially in inherited platelet function disorders, and bleeding history, type of disorder, type of surgery and female sex are associated with higher bleeding frequency. Prophylactic pre-operative pro-hemostatic treatments appear to be required and are associated with a lower bleeding incidence.

ANKRD26 normocytic thrombocytopenia: a family report.

We report the identification of a new case of familial non syndromic severe thrombocytopenia. Bleeding was mild and no extra-haematological symptoms were found. Platelet morphology was normal as well as the quantitative expression of platelet membrane glycoproteins. Platelet functions could not be studied due to the intensity of the thrombocytopenia. Molecular analysis identified a mutation located in the promoter of the ankyrin repeat domain 26 (ANKRD26) gene, c.-127A>T, recently reported to be responsible of normocytic thrombocytopenia, but also of a possible increased risk of leukemia/myelodysplasia. Actual knowledge on this new type of inherited thrombocytopenia is also presented.

Mutation spectrum and genotype-phenotype correlations in a large French cohort of MYH9-Related Disorders.

MYH9-Related Disorders are a group of rare autosomal dominant platelet disorders presenting as nonsyndromic forms characterized by macrothrombocytopenia with giant platelets and leukocyte inclusion bodies or as syndromic forms combining these hematological features with deafness and/or nephropathy and/or cataracts. They are caused by mutations in the MYH9 gene encoding the nonmuscle myosin heavy chain II-A (NMMHC-IIA). Until now, at least 49 MYH9 mutations have been reported in isolated cases or small series but only rarely in large series. We report the results of an 8-year study of a large cohort of 109 patients from 37 sporadic cases and 39 unrelated families. We have identified 43 genetic variants, 21 of which are novel to our patients. A majority, 33 (76.7%), were missense mutations and six exons were preferentially targeted, as previously published. The other alterations were three deletions of one nucleotide, one larger deletion of 21 nucleotides, and one duplication. For the first time, a substitution T>A was found in the donor splice site of intron 40 (c.5765+2T>A). Seven patients, four from the same family, had two genetic variants. The analysis of the genotype-phenotype relationships enabled us to improve the knowledge of this heterogeneous but important rare disease.

Cochlear implantation is safe and effective in patients with MYH9-related disease.

BACKGROUND: MYH9-related disease (MYH9-RD) is a rare syndromic disorder deriving from mutations in MYH9, the gene for the heavy chain of non-muscle myosin IIA. Patients present with congenital thrombocytopenia and giant platelets and have a variable risk of developing sensorineural deafness, kidney damage, presenile cataract, and liver abnormalities. Almost all MYH9-RD patients develop the hearing defect, which, in many individuals, progresses to severe to profound deafness with high impact on quality of life. These patients are potential candidates for cochlear implantation (CI), however, no consistent data are available about the risk to benefit ratio of CI in MYH9-RD. The only reported patient who received CI experienced perisurgery complications that have been attributed to concurrent platelet defects and/or MYH9 protein dysfunction. METHODS: By international co-operative study, we report the clinical outcome of 10 patients with MYH9-RD and severe to profound deafness who received a CI at 8 institutions. RESULTS: Nine patients benefited from CI: in particular, eight of them obtained excellent performances with restoration of a practically normal hearing function and verbal communication abilities. One patient had a slightly worse performance that could be explained by the very long duration of severe deafness before CI. Finally, one patient did not significantly benefit from CI. No adverse events attributable to MYH9-RD syndrome were observed, in particular no perisurgery bleeding complications due to the platelet defects were seen. Patients' perioperative management is described and discussed. CONCLUSIONS: CI is safe and effective in most patients with MYH9-RD and severe to profound deafness and should be offered to these subjects, possibly as soon as they develop the criteria for candidacy.

Analysis of 339 pregnancies in 181 women with 13 different forms of inherited thrombocytopenia.

Pregnancy in women with inherited thrombocytopenias is a major matter of concern as both the mothers and the newborns are potentially at risk of bleeding. However, medical management of this condition cannot be based on evidence because of the lack of consistent information in the literature. To advance knowledge on this matter, we performed a multicentric, retrospective study evaluating 339 pregnancies in 181 women with 13 different forms of inherited thrombocytopenia. Neither the degree of thrombocytopenia nor the severity of bleeding tendency worsened during pregnancy and the course of pregnancy did not differ from that of healthy subjects in terms of miscarriages, fetal bleeding and pre-term births. The degree of thrombocytopenia in the babies was similar to that in the mother. Only 7 of 156 affected newborns had delivery-related bleeding, but 2 of them died of cerebral hemorrhage. The frequency of delivery-related maternal bleeding ranged from 6.8% to 14.2% depending on the definition of abnormal blood loss, suggesting that the risk of abnormal blood loss was increased with respect to the general population. However, no mother died or had to undergo hysterectomy to arrest bleeding. The search for parameters predicting delivery-related bleeding in the mother suggested that hemorrhages requiring blood transfusion were more frequent in women with history of severe bleedings before pregnancy and with platelet count at delivery below 50 × 10(9)/L.

Platelet counting.

Platelet counting is a daily basic hematological analysis of crucial interest in many clinical situations. Historical manual techniques (phase-contrast microscopy) have been replaced by automated techniques (impedance or optical analyzers) more rapid and precise. More recently, flow cytometry techniques using labeled monoclonal antibodies have been proposed as reference techniques. Nevertheless, pre-analytical and analytical variables should be respected to obtain reliable results and avoid validation pitfalls.

Platelet morphology analysis.

Platelets are very small blood cells (1.5-3 µm), which play a major role in primary haemostasis and in coagulation mechanisms. Platelet characterization requires their counting (see Chapter 15 ) associated with accurate morphology analysis. We describe the major steps in order to correctly obtain stained blood films, which can be analyzed by optical microscope. Platelet morphology abnormalities are found in acquired malignant hematological diseases such myeloproliferative or myelodysplastic syndromes and acute megakaryoblastic leukemia. A careful analysis of the platelet size and morphology, by detecting either normal platelets with or without excessive anisocytosis, microplatelets, or large/giant platelets, will contribute to inherited thrombocytopenia diagnosis and gather substantial data when looking for an acquired platelet disorders.

Mirroring of a simple motor behavior in disorders of consciousness.

OBJECTIVE: In patients suffering from Disorders of Consciousness (DOC) electrophysiological recordings at bedside could serve as a complimentary and economical tool to improve diagnosis. We utilized a motor observation and imagination paradigm to gain new insights on preserved cognitive processing in DOC. METHODS: EEG brain oscillations were analyzed in 10 VS/UWS (Vegetative State/Unresponsive Wakefulness Syndrome) patients and 7 MCS (Minimally Conscious State) patients and 21 controls during observation and imagination of a grasping movement and group statistics were conducted. RESULTS: While control subjects showed a typical desynchronization at 8-15Hz during observation of a movement, MCS patients presented an analogue response at 8-10Hz, but exhibited a synchronization at 12-15Hz. The VS group did not show a systematic response. Imagery-related activation was only sustained for 1500ms even in control subjects, therefore, limiting conclusions regarding the ability to follow an instruction. Furthermore, a clinically diagnosed VS patient exhibited EEG responses indicative for MCS. CONCLUSION: Results indicate that MCS patients are still able to process an observed motor behavior on a basic sensory and perhaps even pre-motoric level, but seem not to be capable of "mirroring" the movement like healthy participants. SIGNIFICANCE: "Real-world" tasks as presented here carry the potential to identify residual cognitive functioning in DOC patients and may ultimately help to lower misdiagnosis rates.

[The activity levels and prevalence of deficiency of protein C, protein S and antithrombin in Chinese Han population].

OBJECTIVE: To explore the distribution and influence factors of protein C (PC), protein S (PS) and antithrombin (AT) activities and to determine the prevalence of their deficiencies in the Chinese Han healthy population. METHODS: Healthy volunteers including blood donors and individuals for routine check-up were recruited from 4 Chinese medical centers. The plasma levels of PC, PS and AT activities were measured. The plasma levels of activities were measured by chromogenic substrate assay (AT and PC) and clotting assay (PS). RESULTS: A total of 3493 healthy Chinese adults had been recruited in this study. Males had higher PS and PC activities than females, especially for PS (P < 0.01). PC activities increased with age in both sexes but decreased in men after 50 years old. There was no significant change with age were of PS in 50 years old, while there was a decline in males and a rise in females above 50 years old. AT tended to increase with age in women but decreased with age in men after 50 years old. Based on the age and gender, the general prevalence of PC, PS and AT deficiencies in the general Chinese Han population were 1.15%, 1.49% and 2.29%, respectively. CONCLUSION: PC, PS and AT activities have correlation with age and gender in Chinese Han population. Reference range should be laid down and deficiencies should be identified

Oscillatory brain activity in vegetative and minimally conscious state during a sentence comprehension task.

Patients with altered states of consciousness continue to constitute a major challenge in terms of clinical assessment, treatment and daily management. Furthermore, the exploration of brain function in severely brain-damaged patients represents a unique lesional approach to the scientific study of consciousness. Electroencephalography is one means of identifying covert behaviour in the absence of motor activity in these critically ill patients. Here we focus on a language processing task which assesses whether vegetative (n=10) and minimally conscious state patients (n=4) (vs control subjects, n=14) understand semantic information on a sentence level ("The opposite of black is... white/yellow/nice"). Results indicate that only MCS but not VS patients show differential processing of unrelated ("nice") and antonym ("white") words in the form of parietal alpha (10-12Hz) event-related synchronization and desynchronization (ERS/ERD), respectively. Controls show a more typical pattern, characterized by alpha ERD in response to unrelated words and alpha ERS in response to antonyms.

Normal ranges and genetic variants of antithrombin, protein C and protein S in the general Chinese population. Results of the Chinese Hemostasis Investigation on Natural Anticoagulants Study I Group.

BACKGROUND: Inherited deficiency of antithrombin, protein C and protein S, three important, naturally occurring coagulation inhibitors, might play a major role in the occurrence of venous thromboembolism in Chinese. The establishment of age- and gender-related normal ranges of these inhibitors is crucial for an accurate diagnosis of these deficiencies. DESIGN AND METHODS: We designed a prospective cross-sectional study recruiting healthy adults from four university-affiliated hospitals in China. Antithrombin, protein C and protein S were studied by measuring their activity. Gene analysis was performed when natural anticoagulant deficiency was suspected. Polymorphisms of the factor V gene were searched for among subjects who were positive for activated protein C resistance. RESULTS: In 3493 healthy Chinese adults (1734 men, 1759 women; age 17-83 years), we found higher age-adjusted activities for protein C and protein S in men than in women but no sex difference for antithrombin. In women, mean protein C and protein S activities increased with age. In men, mean protein C levels increased with age up to the age of 49 but decreased after 50 years old; mean protein S levels decreased after 50 years of age. Antithrombin levels remained stable over time in women but decreased significantly after 50 years of age in men. Reference values according to age and sex allowed the identification of 15 genetic variants (protein C:10, antithrombin:3, protein S:2) in subjects with protein activity below the 1(st) percentile. CONCLUSIONS: This is the largest survey ever conducted in the healthy general Chinese population. These normal ranges provide the essential basis for the diagnosis and treatment of thrombosis in Chinese.

Thrombophilia and pregnancy complications.

The implications of currently available data on the association of gestational vascular complications with thrombophilia are presented in this consensus report. Screening is recommended for women with the following previous complications: fetal loss including three or more first trimester loss, two or more second trimester loss, or any stillbirth; early, severe or recurrent preeclampsia and severe intrauterine growth restriction. Maternal antithrombotic therapy is currently evaluated in women with thrombophilia and previous complications.