Cardiovascular conditions are serious long-term complications of childhood acute leukemia. However, few studies have investigated the risk of metabolic syndrome, a known predictor of cardiovascular ...disease, in patients treated without hematopoietic stem cell transplantation. We describe the overall and age-specific prevalence, and the risk factors for metabolic syndrome and its components in the L.E.A. (Leucémie de l'Enfant et de l'Adolescent) French cohort of childhood acute leukemia survivors treated without hematopoietic stem cell transplantation. The study included 650 adult patients (mean age at evaluation: 24.2 years; mean follow-up after leukemia diagnosis: 16.0 years). The prevalence of metabolic syndrome was 6.9% (95% CI 5.1-9.2). The age-specific cumulative prevalence at 20, 25, 30 and 35 years of age was 1.3%, 6.1%, 10.8% and 22.4%, respectively. The prevalence of decreased high-density lipoprotein cholesterol, increased triglycerides, increased fasting glucose, increased blood pressure and increased abdominal circumference was 26.8%, 11.7%, 5.8%, 36.7% and 16.7%, respectively. Risk factors significantly associated with metabolic syndrome in the multivariate analysis were male sex (OR 2.64; 95% CI 1.32-5.29), age at last evaluation (OR 1.10; 95% CI 1.04-1.17) and body mass index at diagnosis (OR 1.15; 95% CI 1.01-1.32). The cumulative steroid dose was not a significant risk factor. Irradiated and non-irradiated patients exhibited different patterns of metabolic abnormalities, with more frequent abdominal obesity in irradiated patients and more frequent hypertension in non-irradiated patients. Survivors of childhood acute leukemia are at risk of metabolic syndrome, even when treated without hematopoietic stem cell transplantation or central nervous system irradiation. A preventive approach with regular screening for cardiovascular risk factors is recommended. clinicaltrials.gov identifier:01756599.
Long-term outcome after hematopoietic stem cell transplantation including late transplant-related events is of increasing interest. The aim of this study was to evaluate the incidence of ...cardiovascular events after allogeneic HSCT and to search for their risk factors.
This is a retrospective multicenter European Group of Blood and Marrow Transplantation (EBMT) analysis, including 548 long-term survivors treated in ten EBMT transplant centers, who underwent hematopoietic stem cell transplantation between 1990 and 1995 and survived >or=1 year after the transplant. All arterial events occurring after hematopoietic stem cell transplantation (cerebral, coronary, peripheral) were reported.
Twenty (3.6%) out of 548 patients had a cardiovascular event in at least one arterial territory. The median age at occurrence of cardiovascular events was 54 years (range, 41-70). The cumulative incidence of a first arterial event 15 years after hematopoietic stem cell transplantation was 6% (95% CI, 3%-10%). The cumulative incidence for patients with a high global cardiovascular risk score, defined as having >or=50% of the risk factors (arterial hypertension, diabetes, dys-lipidemia, increased body-mass index, physical inactivity, smoking) was 17%, as compared to 4% in those with a low risk score. In multivariate analysis age older than 30 years at last follow-up, and a high global cardiovascular risk score were associated with, respectively, 6.4-fold and 9.8-fold increases in the risk of an arterial event.
Long-term survivors after allogeneic hematopoietic stem cell transplantation are likely to have an increased risk of premature cardiovascular accidents.
Summary
In children, lymphoblastic lymphomas represent 30% of Non‐Hodgkin lymphomas (NHL), and approximately 15% are precursor B‐cell lymphomas (PBLL). Our study evaluated their main clinical ...characteristics, evolution, and prognosis in three trials. From 1989 to 2008, 53 children with PBLL (median age 7·75 years) were included in three protocols: Malignant Lymphoma Therapy (LMT) 96, European Organization for Research and Treatment of Cancer (EORTC) 58881, and EORTC 58951 using Berlin‐Frankfürt‐Münster‐derived acute lymphoblastic leukaemia (ALL) therapy. There were 10 stage I disease, 9 stage II, 9 stage III and 25 stage IV. Clinical presentation was heterogeneous with a majority of bone lesions and cutaneous or subcutaneous manifestations. At diagnosis 23 patients had bone marrow involvement, and only three had central nervous system involvement. The median follow‐up was 74 months. At last follow‐up, 45 patients were in continuous complete remission, whereas eight had progressed or had relapsed (7 Stages IV and 1 Stage III) and died. Two patients had a secondary neoplasia, and are still alive. Disease stage was a major prognostic factor, with better overall survival (OS) and event‐free survival (EFS) (P < 0·05) rates observed in patients with Stage I to III as compared to those with Stage IV. Treatment with protocols derived from ALL therapy are efficient with an 82% EFS and an 85% OS at 5 years.
Results on Martin’s Conjecture Lutz, Patrick
The bulletin of symbolic logic,
06/2021, Letnik:
27, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Abstract
Martin’s conjecture is an attempt to classify the behavior of all definable functions on the Turing degrees under strong set theoretic hypotheses. Very roughly it says that every such ...function is either eventually constant, eventually equal to the identity function or eventually equal to a transfinite iterate of the Turing jump. It is typically divided into two parts: the first part states that every function is either eventually constant or eventually above the identity function and the second part states that every function which is above the identity is eventually equal to a transfinite iterate of the jump. If true, it would provide an explanation for the unique role of the Turing jump in computability theory and rule out many types of constructions on the Turing degrees.
In this thesis, we will introduce a few tools which we use to prove several cases of Martin’s conjecture. It turns out that both these tools and these results on Martin’s conjecture have some interesting consequences both for Martin’s conjecture and for a few related topics.
The main tool that we introduce is a basis theorem for perfect sets, improving a theorem due to Groszek and Slaman. We also introduce a general framework for proving certain special cases of Martin’s conjecture which unifies a few pre-existing proofs. We will use these tools to prove three main results about Martin’s conjecture: that it holds for regressive functions on the hyperarithmetic degrees (answering a question of Slaman and Steel), that part 1 holds for order preserving functions on the Turing degrees, and that part 1 holds for a class of functions that we introduce, called measure preserving functions.
This last result has several interesting consequences for the study of Martin’s conjecture. In particular, it shows that part 1 of Martin’s conjecture is equivalent to a statement about the Rudin-Keisler order on ultrafilters on the Turing degrees. This suggests several possible strategies for working on part 1 of Martin’s conjecture, which we will discuss.
The basis theorem that we use to prove these results also has some applications outside of Martin’s conjecture. We will use it to prove a few theorems related to Sacks’ question about whether it is provable in
$\mathsf {ZFC}$
that every locally countable partial order of size continuum embeds into the Turing degrees. We will show that in a certain extension of
$\mathsf {ZF}$
(which is incompatible with
$\mathsf {ZFC}$
), this holds for all partial orders of height two, but
not
for all partial orders of height three. Our proof also yields an analogous result for Borel partial orders and Borel embeddings in
$\mathsf {ZF}$
, which shows that the Borel version of Sacks’ question has a negative answer.
We will end the thesis with a list of open questions related to Martin’s conjecture, which we hope will stimulate further research.
Abstract prepared by Patrick Lutz.
E-mail
:
pglutz@berkeley.edu
We report an enantioselective Ni-catalyzed cross coupling of arylzinc reagents with pyridiniumions formed
from pyridine and a chloroformate. This reaction provides enantioenriched ...2-aryl-1,2-dihydropyridine products that can be elaborated to numerous piperidine derivatives with little or no loss in ee. This method is notable for its use of pyridine, a feedstock chemical, to build a versatile, chiral heterocycle in a single synthetic step.
Asparaginase is an essential component of combination chemotherapy for childhood acute lymphoblastic leukemia and non-Hodgkin lymphoma. The value of asparaginase was further addressed in a group of ...non-very high-risk patients by comparing prolonged (long-asparaginase)
standard (short-asparaginase) native
asparaginase treatment in a randomized part of the phase III 58951 trial of the European Organization for Research and Treatment of Cancer Children's Leukemia Group. The main endpoint was disease-free survival. Overall, 1,552 patients were randomly assigned to long-asparaginase (775 patients) or short-asparaginase (777 patients). Patients with grade ≥2 allergy to native
asparaginase were switched to equivalent doses of
or pegylated
asparaginase. The 8-year disease-free survival rate (±standard error) was 87.0±1.3% in the long-asparaginase group and 84.4±1.4% in the short-asparaginase group (hazard ratio: 0.87;
=0.33) and the 8-year overall survival rate was 92.6±1.0% and 91.3±1.2% respectively (hazard ratio: 0.89;
=0.53). An exploratory analysis suggested that the impact of long-asparaginase was beneficial in the National Cancer Institute standard-risk group with regards to disease-free survival (hazard ratio: 0.70;
=0.057), but far less so with regards to overall survival (hazard ratio: 0.89). The incidences of grade 3-4 infection during consolidation (25.2%
14.4%) and late intensification (22.6%
15.9%) and the incidence of grade 2-4 allergy were higher in the long-asparaginase arm (30%
21%). Prolonged native
asparaginase therapy in consolidation and late intensification for our non-very high-risk patients did not improve overall outcome but led to an increase in infections and allergy.
The layer-by-layer formation of core/alloy nanoparticles is described. Using presynthesized gold nanoparticle cores, Au x Ag1‑x alloy shells were deposited and annealed with subnanometer precision ...using a microwave irradiation (MWI) mediated hydrothermal processing method. The alloy composition, thickness, and nanoparticle morphology governed the surface plasmon resonance characteristics of the particles, as well as growth characteristics. The mechanism for alloy deposition, annealing, and interdiffusion was explored using two gold precursors, AuBr4− and AuCl4−, and two hydrothermal temperatures (120, 160 °C). Findings indicate that use of AuCl4− results in significant galvanic displacement, leading to nonuniform alloy formation and phase segregation at low annealing temperatures, which leads to loss of morphology control at intermediate compositions (x ≈ 0.25–0.75). In contrast, use of AuBr4− results in alloy shells with low galvanic interactions, leading to optimum alloy distribution and high fidelity control of alloy-shell thickness that, in combination with higher hydrothermal processing temperatures, leads to uniform and monodisperse core/alloy microstructure across all compositions. The alloy deposition and core/alloy nanoparticle growth was followed in situ by monitoring the change in surface plasmon resonance (SPR) signatures by UV–vis, which were unique to alloy shell thickness, as well as composition, and morphology. The interfacial alloy composition was probed by modeling the SPR with discrete dipole approximation, the results of which suggest the final alloy shells are Au-rich compared to the feed ratios, owing in large part to both galvanic displacements as well as core-to-shell alloy interdiffusion.
Thyroid complications are known side effects of irradiation. However, the risk of such complications in childhood acute leukemia survivors who received either central nervous system irradiation or ...hematopoietic stem cell transplantation is less described. We prospectively evaluated the incidence and risk factors for thyroid dysfunction and tumors in survivors of childhood acute myeloid or lymphoid leukemia. A total of 588 patients were evaluated for thyroid function, and 502 individuals were assessed for thyroid tumors (median follow-up duration: 12.6 and 12.5 years, respectively). The cumulative incidence of hypothyroidism was 17.3% (95% CI: 14.1-21.1) and 24.6% (95% CI: 20.4-29.6) at 10 and 20 years from leukemia diagnosis, respectively. Patients who received total body irradiation (with or without prior central nervous system irradiation) were at higher risk of hypothyroidism (adjusted HR: 2.87; P=0.04 and 2.79, P=0.01, respectively) as compared with transplanted patients who never received any irradiation. Patients transplanted without total body irradiation who received central nervous system irradiation were also at higher risk (adjusted HR: 3.39; P=0.02). Patients irradiated or transplanted at older than 10 years of age had a lower risk (adjusted HR: 0.61; P=0.02). Thyroid malignancy was found in 26 patients (5.2%). Among them, two patients had never received any type of irradiation: alkylating agents could also promote thyroid cancer. The cumulative incidence of thyroid malignancy was 9.6% (95% CI: 6.0-15.0) at 20 years. Women were at higher risk than men (adjusted HR: 4.74; P=0.002). In conclusion, thyroid complications are frequent among patients who undergo transplantation after total body irradiation and those who received prior central nervous system irradiation. Close monitoring is thus warranted for these patients. Clinicaltrials.gov identifier: NCT 01756599.
This report describes a three-component, Ni-catalyzed reductive coupling that enables the convergent synthesis of tertiary benzhydryl amines, which are challenging to access by traditional reductive ...amination methodologies. The reaction makes use of iminium ions generated in situ from the condensation of secondary N-trimethylsilyl amines with benzaldehydes, and these species undergo reaction with several distinct classes of organic electrophiles. The synthetic value of this process is demonstrated by a single-step synthesis of antimigraine drug flunarizine (Sibelium) and high yielding derivatization of paroxetine (Paxil) and metoprolol (Lopressor). Mechanistic investigations support a sequential oxidative addition mechanism rather than a pathway proceeding via α-amino radical formation. Accordingly, application of catalytic conditions to an intramolecular reductive coupling is demonstrated for the synthesis of endo- and exocyclic benzhydryl amines.
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