Choice of Steel Material to Avoid Brittle Fracture for Hollow Section Structures

European cold-formed hollow sections in general exhibit better toughness properties than required by EN 10219. However, limits in applying the toughness related rules for the choice of steel material in EN 1993 1 10 to cold-formed hollow sections still constitute barriers to free marketing. By requests from European producers a conservative assessment procedure has been developed which is based on toughness measurements and a concept using effective strains. Due to the cold-forming process such plastic strains may occur in the bent areas of the profiles associated with a noticeable reduction in material toughness. For the degradation of these toughness properties an appropriate temperature shift Delta Tcf has been derived for both circular and rectangular hollow sections. In order to guarantee the proper application of this temperature shift Table 2.1 in EN 1993 1 10 had to be extended to lower temperatures down to -120 °C.JRC.G.5-European laboratory for structural assessmen

Treosulfan-fludarabine-thiotepa-based conditioning treatment before allogeneic hematopoietic stem cell transplantation for pediatric patients with hematological malignancies

Treosulfan-based conditioning prior to allogeneic transplantation has been shown to have myeloablative, immunosuppressive, and antineoplastic effects associated with reduced non-relapse mortality (NRM) in adults. Therefore, we prospectively evaluated the safety and efficacy of treosulfan-based conditioning in children with hematological malignancies in this phase II trial. Overall, 65 children with acute lymphoblastic leukemia (35.4%), acute myeloid leukemia (44.6%), myelodysplastic syndrome (15.4%), or juvenile myelomonocytic leukemia (4.6%) received treosulfan intravenously at a dose of 10 mg/m2/day (7.7%), 12 g/m2/day (35.4%), or 14 g/m2/day (56.9%) according to their individual body surface area in combination with fludarabine and thiotepa. The incidence of complete donor chimerism at day +28 was 98.4% with no primary and only one secondary graft failure. At 36 months, NRM was only 3.1%, while relapse incidence was 21.7%, and overall survival was 83.0%. The cumulative incidence of acute graft-vs.-host disease was 45.3% for grades I–IV and 26.6% for grades II–IV. At 36 months, 25.8% overall and 19.4% moderate/severe chronic graft-vs.-host disease were reported. These data confirm the safe and effective use of treosulfan-based conditioning in pediatric patients with hematological malignancies. Therefore, treosulfan/fludarabine/thiotepa can be recommended for myeloablative conditioning in children with hematological malignancies

Diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in pediatric patients. a new classification from the european society for blood and marrow transplantation

The advances in hematopoietic cell transplantation (HCT) over the last decade have led to a transplant-related mortality below 15%. Hepatic sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a life-threatening complication of HCT that belongs to a group of diseases increasingly identified as transplant-related, systemic endothelial diseases. In most cases, SOS/VOD resolves within weeks; however, severe SOS/VOD results in multi-organ dysfunction/failure with a mortality rate >80%. A timely diagnosis of SOS/VOD is of critical importance, given the availability of therapeutic options with favorable tolerability. Current diagnostic criteria are used for adults and children. However, over the last decade it has become clear that SOS/VOD is significantly different between the age groups in terms of incidence, genetic predisposition, clinical presentation, prevention, treatment and outcome. Improved understanding of SOS/VOD and the availability of effective treatment questions the use of the Baltimore and Seattle criteria for diagnosing SOS/VOD in children. The aim of this position paper is to propose new diagnostic and severity criteria for SOS/VOD in children on behalf of the European Society for Blood and Marrow Transplantation

Outcome of children relapsing after first allogeneic haematopoietic stem cell transplantation for acute myeloid leukaemia: a retrospective I-BFM analysis of 333 children

Outcome of 333 children with acute myeloid leukaemia relapsing after a first allogeneic haematopoietic stem cell transplantation was analyzed. Four-year probability of overall survival (4y-pOS) was 14%. 4y-pOS for 122 children receiving a second haematopoietic stem cell transplantation was 31% and 3% for those that did not (P = <0·0001). Achievement of a subsequent remission impacted survival (P = <0·0001). For patients receiving a second transplant survival with or without achieving a subsequent remission was comparable. Graft source (bone marrow vs. peripheral blood stem cells, P = 0·046) and donor choice (matched family vs. matched unrelated donor, P = 0·029) positively impacted survival after relapse. Disease recurrence and non-relapse mortality at four years reached 45% and 22%

Implementing Fault-tolerant Entangling Gates on the Five-qubit Code and the Color Code

We compare two different implementations of fault-tolerant entangling gates on logical qubits. In one instance, a twelve-qubit trapped-ion quantum computer is used to implement a non-transversal logical CNOT gate between two five qubit codes. The operation is evaluated with varying degrees of fault tolerance, which are provided by including quantum error correction circuit primitives known as flagging and pieceable fault tolerance. In the second instance, a twenty-qubit trapped-ion quantum computer is used to implement a transversal logical CNOT gate on two [[7,1,3]] color codes. The two codes were implemented on different but similar devices, and in both instances, all of the quantum error correction primitives, including the determination of corrections via decoding, are implemented during runtime using a classical compute environment that is tightly integrated with the quantum processor. For different combinations of the primitives, logical state fidelity measurements are made after applying the gate to different input states, providing bounds on the process fidelity. We find the highest fidelity operations with the color code, with the fault-tolerant SPAM operation achieving fidelities of 0.99939(15) and 0.99959(13) when preparing eigenstates of the logical X and Z operators, which is higher than the average physical qubit SPAM fidelities of 0.9968(2) and 0.9970(1) for the physical X and Z bases, respectively. When combined with a logical transversal CNOT gate, we find the color code to perform the sequence--state preparation, CNOT, measure out--with an average fidelity bounded by [0.9957,0.9963]. The logical fidelity bounds are higher than the analogous physical-level fidelity bounds, which we find to be [0.9850,0.9903], reflecting multiple physical noise sources such as SPAM errors for two qubits, several single-qubit gates, a two-qubit gate and some amount of memory error

Impact of conditioning regimen on outcomes for children with acute myeloid leukemia undergoing transplantation in first complete remission. An analysis on behalf of the Pediatric Disease Working Party of the European Group for Blood and Marrow Transplantation

Hematopoietic stem cell transplantation (HSCT) represents the cornerstone of treatment in pediatric high-risk and relapsed acute myeloid leukemia (AML). The aim of the present study was to compare outcomes of pediatric patients with AML undergoing HSCT using 3 different conditioning regimens: total body irradiation (TBI) and cyclophosphamide (Cy); busulfan (Bu) and Cy; or Bu, Cy, and melphalan (Mel). In this retrospective study, registry data for patients > 2 and <18 years age undergoing matched allogeneic HSCT for AML in first complete remission (CR1) in 204 European Group for Blood and Marrow Transplantation centers between 2000 and 2010 were analyzed. Data were available for 631 patients; 458 patients received stem cells from a matched sibling donor and 173 from a matched unrelated donor. For 440 patients, bone marrow was used as stem cell source, and 191 patients received peripheral blood stem cells. One hundred nine patients received TBICy, 389 received BuCy, and 133 received BuCyMel as their preparatory regimen. Median follow-up was 55 months. Patients receiving BuCyMel showed a lower incidence of relapse at 5 years (14.7% versus 31.5% in BuCy versus 30% in TBICy, P < .01) and higher overall survival (OS) (76.6% versus 64% versus 64.5%, P = .04) and leukemia-free survival (LFS) (74.5% versus 58% versus 61.9%, P < .01), with a comparable nonrelapse mortality (NRM) (10.8% versus 10.5% versus 8.1%, P = .79). Acute graft-versus-host disease (GVHD) grades III and IV but not chronic GVHD, was higher in patients receiving BuCyMel. Older age at HSCT had an adverse impact on NRM and the use of peripheral blood as stem cell source was associated with increased chronic GVHD and NRM as well as lower LFS and OS. Among pediatric patients receiving HSCT for AML in CR1, the use of BuCyMel conditioning proved superior to TBICy and BuCy in reducing relapse and improving LFS

BCL11A deletions result in fetal hemoglobin persistence and neurodevelopmental alterations

A transition from fetal hemoglobin (HbF) to adult hemoglobin (HbA) normally occurs within a few months after birth. Increased production of HbF after this period of infancy ameliorates clinical symptoms of the major disorders of adult ß-hemoglobin: ß-thalassemia and sickle cell disease. The transcription factor BCL11A silences HbF and has been an attractive therapeutic target for increasing HbF levels; however, it is not clear to what extent BCL11A inhibits HbF production or mediates other developmental functions in humans. Here, we identified and characterized 3 patients with rare microdeletions of 2p15-p16.1 who presented with an autism spectrum disorder and developmental delay. Moreover, these patients all exhibited substantial persistence of HbF but otherwise retained apparently normal hematologic and immunologic function. Of the genes within 2p15-p16.1, only BCL11A was commonly deleted in all of the patients. Evaluation of gene expression data sets from developing and adult human brains revealed that BCL11A expression patterns are similar to other genes associated with neurodevelopmental disorders. Additionally, common SNPs within the second intron of BCL11A are strongly associated with schizophrenia. Together, the study of these rare patients and orthogonal genetic data demonstrates that BCL11A plays a central role in silencing HbF in humans and implicates BCL11A as an important factor for neurodevelopment

Prevalence, clinical characteristics, and prognosis of GATA2-related myelodysplastic syndromes in children and adolescents

GermlineGATA2 mutations cause cellular deficiencieswith high propensity for myeloid disease. We investigated 426 children and adolescents with primary myelodysplastic syndrome (MDS) and 82 cases with secondary MDS enrolled in 2 consecutive prospective studies of the European Working Group of MDS in Childhood (EWOGMDS) conducted in Germany over a period of 15 years. Germline GATA2 mutations accounted for 15% of advanced and 7% of all primary MDS cases, but were absent in children with MDS secondary to therapy or acquired aplastic anemia. Mutation carriers were older at diagnosis and more likely to present with monosomy 7 and advanced disease compared with wild-type cases. For stratified analysis according to karyotype, 108 additional primary MDS patients registered with EWOG-MDS were studied. Overall, we identified 57 MDS patients with germline GATA2mutations. GATA2 mutations were highly prevalent among patients with monosomy 7 (37%, all ages) reaching its peak in adolescence (72%of adolescents withmonosomy 7).Unexpectedly, monocytosis was more frequent in GATA2-mutated patients. However, when adjusted for the selection bias from monosomy 7, mutational status had no effect on the hematologic phenotype. Finally, overall survival and outcome of hematopoietic stem cell transplantation (HSCT) were not influenced by mutational status. This study identifies GATA2 mutations as the most common germline defect predisposing to pediatric MDS with a very high prevalence in adolescents with monosomy 7. GATA2 mutations do not confer poor prognosis in childhood MDS. However, the high risk for progression to advanced diseasemust guide decision-making toward timely HSCT