Revisiting the bis(dimethylamido) metallocene complexes of thorium and uranium: improved syntheses, structure, spectroscopy, and redox energetics of (C5Me5)2An(NMe2)2 (An = Th, U).

The reaction of (C5Me5)2AnCl2 (An = Th, U) with 2.8 or 4 equivalents of LiNMe2, respectively, affords (C5Me5)2An(NMe2)2 in high yields. In addition to improved syntheses, the solid-state structures, voltammetric data, and UV-visible-NIR spectra for these classic actinide bis(dimethylamido) complexes are presented for the first time.

Mitoxantrone, etoposide and cytarabine following epigenetic priming with decitabine in adults with relapsed/refractory acute myeloid leukemia or other high-grade myeloid neoplasms: a phase 1/2 study.

DNA methyltransferase inhibitors sensitize leukemia cells to chemotherapeutics. We therefore conducted a phase 1/2 study of mitoxantrone, etoposide and cytarabine following 'priming' with 5-10 days of decitabine (dec/MEC) in 52 adults (median age 55 (range: 19-72) years) with relapsed/refractory acute myeloid leukemia (AML) or other high-grade myeloid neoplasms. During dose escalation in cohorts of 6-12 patients, all dose levels were well tolerated. As response rates appeared similar with 7 and 10 days of decitabine, a 7-day course was defined as the recommended phase 2 dose (RP2D). Among 46 patients treated at/above the RP2D, 10 (22%) achieved a complete remission (CR), 8 without measurable residual disease; five additional patients achieved CR with incomplete platelet recovery, for an overall response rate of 33%. Seven patients (15%) died within 28 days of treatment initiation. Infection/neutropenic fever, nausea and mucositis were the most common adverse events. While the CR rate compared favorably to a matched historic control population (observed/expected CR ratio=1.77), CR rate and survival were similar to two contemporary salvage regimens used at our institution (G-CLAC (granulocyte colony-stimulating factor (G-CSF); clofarabine; cytarabine) and G-CLAM (G-CSF; cladribine; cytarabine; mitoxantrone)). Thus, while meeting the prespecified efficacy goal, we found no evidence that dec/MEC is substantially better than other cytarabine-based regimens currently used for relapsed/refractory AML.

Investigation of the physical properties of the tetragonal CeMAl4Si2 (M = Rh, Ir, Pt) compounds.

The synthesis, crystal structure and physical properties studied by means of x-ray diffraction, magnetic, thermal and transport measurements of CeMAl4Si2 (M = Rh, Ir, Pt) are reported, along with the electronic structure calculations for LaMAl4Si2 (M = Rh, Ir, Pt). These materials adopt a tetragonal crystal structure (space group P4/mmm) comprised of BaAl4 blocks, separated by MAl2 units, stacked along the c-axis. Both CeRhAl4Si2 and CeIrAl4Si2 order antiferromagnetically below TN1 = 14 and 16 K, respectively, and undergo a second antiferromagnetic transitition at lower temperature (TN2 = 9 and 14 K, respectively). CePtAl4Si2 orders ferromagnetically below TC = 3 K with an ordered moment of µsat = 0.8 µB for a magnetic field applied perpendicular to the c-axis. Electronic structure calculations reveal quasi-2D character of the Fermi surface.

Anisotropic thermal conductivity in uranium dioxide.

The thermal conductivity of uranium dioxide has been studied for over half a century, as uranium dioxide is the fuel used in a majority of operating nuclear reactors and thermal conductivity controls the conversion of heat produced by fission events to electricity. Because uranium dioxide is a cubic compound and thermal conductivity is a second-rank tensor, it has always been assumed to be isotropic. We report thermal conductivity measurements on oriented uranium dioxide single crystals that show anisotropy from 4 K to above 300 K. Our results indicate that phonon-spin scattering is important for understanding the general thermal conductivity behaviour, and also explains the anisotropy by coupling to the applied temperature gradient and breaking cubic symmetry.

Challenging conventional f-element separation chemistry--reversing uranyl(VI)/lanthanide(III) solvent extraction selectivity.

The water soluble tetradentate Schiff base, N,N'-bis(5-sulfonatosalicylidene)-diaminoethane (H2salen-SO3), will readily coordinate to the uranyl(VI) cation, but not to the same extent to trivalent lanthanide cations. This allows for the reversal of conventional solvent extraction properties and opens the possibility for novel separation processes.

Nucleation and growth of epitaxial metal-oxide films based on polymer-assisted deposition.

Polymer-assisted deposition (PAD) is one of the chemical solution deposition methods which have been successfully used to grow films, form coatings, and synthesize nanostructured materials. In comparison with other conventional solution-based deposition techniques, PAD differs in its use of water-soluble polymers in the solution that prevent the metal ions from unwanted chemical reactions and keep the solution stable. Furthermore, filtration to remove non-coordinated cations and anions in the PAD process ensures well controlled nucleation, which enables the growth of high quality epitaxial films with desired structural and physical properties. The precursor solution is prepared by mixing water-soluble polymer(s) with salt(s). Thermal treatment of the precursor films in a controlled environment leads to the formation of desired materials. Using BaTiO3 grown on SrTiO3 and LaMnO3 on LaAlO3 as model systems, we show the effect of filtration on the nucleation and growth of epitaxial complex metal-oxide films based on the PAD process.

Single crystal study of antiferromagnetic CePd3Al9.

Single crystal x-ray diffraction, magnetic susceptibility (M), heat capacity (C), and electrical resistivity (ρ) measurements are reported for specimens of the new tetragonal compound CePd3Al9, which forms in a new structure type. X-ray diffraction measurements reveal that the nearest neighbor Ce-Ce distances are large (d(Ce-Ce) = 5.272 Å), suggesting that this compound may be described as a stoichiometric dilute Kondo lattice. Thermodynamic and transport measurements reveal antiferromagnetic order near T(N) = 0.9 K. The ordered ground state emerges from a lattice of localized Ce ions that are weakly hybridized with the conduction electrons, as revealed by the moderate electronic coefficient of the specific heat γ ≈ 45 mJ mol(-1) K(-2) (extrapolated from above T(N)) and the lack of evidence for Kondo coherence in the magnetic susceptibility and electrical resistivity. The application of a magnetic field initially suppresses the magnetic order at a rate of -0.04 K kOe(-1), but Zeeman splitting of the doublet ground state produces a nonmagnetic singlet before TN reaches zero. The data additionally reveal that chemical/structural disorder plays an important role, as evidenced by results from single crystal x-ray diffraction, the broadness of the peak at TN in the heat capacity, and the small residual resistivity ratio RRR = ρ(300 K)/ρ0 = 1.3.

Dynamic surface enhanced Raman spectroscopy (SERS): extracting SERS from normal Raman scattering.

We have demonstrated two significant benefits of dynamic surface enhanced raman spectroscopy (DSERS) measurements: removal of instrumental and normal Raman interferences in surface enhanced raman spectroscopy (SERS) spectroscopy and site-selective spectroscopy of adsorbate populations on SERS-active particles. Our first example of shelled nanoparticles at very low concentrations confirmed the benefit of DSERS for removal of an overwhelmingly strong solvent spectral interference. The second benefit, site selection, was demonstrated with 4-mercaptopyridine on bare Au nanoparticles to observe a small population of molecules that were spectroscopically unique from the large population of molecules on the particles. The DSERS spectrum originated from excess variance between a small population of adsorbates on the ensemble of nanoparticles.

Localized 5f electrons in superconducting PuCoIn5: consequences for superconductivity in PuCoGa5.

The physical properties of the first In analog of the PuMGa(5) (M = Co, Rh) family of superconductors, PuCoIn(5), are reported. With its unit cell volume being 28% larger than that of PuCoGa(5), the characteristic spin-fluctuation energy scale of PuCoIn(5) is three to four times smaller than that of PuCoGa(5), which suggests that the Pu 5f electrons are in a more localized state relative to PuCoGa(5). This raises the possibility that the high superconducting transition temperature T(c) = 18.5 K of PuCoGa(5) stems from the proximity to a valence instability, while the superconductivity at T(c) = 2.5 K of PuCoIn(5) is mediated by antiferromagnetic spin fluctuations associated with a quantum critical point.

Allogeneic hematopoietic cell transplantation in patients with myelodysplastic syndrome and concurrent lymphoid malignancy.

Allogeneic hematopoietic cell transplantation (HCT) can be curative for both myelodysplastic syndromes (MDS) and lymphoid malignancies. Little is known about the efficacy of allogeneic HCT in patients in whom both myeloid and lymphoid disorders are present at the time of HCT. We analyzed the outcomes in 21 patients with MDS and concurrent lymphoid malignancy when undergoing allogeneic HCT. A total of 17 patients had previously received extensive cytotoxic chemotherapy, including autologous HCT in 7, for non-Hodgkin lymphoma (NHL, n=7), Hodgkin lymphoma (HL, n=2), CLL (n=5), NHL plus HL (n=1), multiple myeloma (n=1) or T-cell ALL (n=1), and had presumably developed MDS as a consequence of therapy. Four previously untreated patients had CLL. A total of 19 patients were conditioned with high-dose (n=14) or reduced-intensity regimens (n=5), and were transplanted from HLA-matched or one Ag/allele mismatched related (n=10) or unrelated (n=9) donors; two patients received HLA-haploidentical related transplants, following a modified conditioning regimen. Currently, 2 of 4 previously untreated and 2 of 17 previously treated patients are surviving in remission of both MDS and lymphoid malignancies. However, the high non-relapse mortality among previously treated patients, even with reduced-intensity conditioning regimens, indicates that new transplant strategies need to be developed.

Single crystal study of the heavy-fermion antiferromagnet CePt2In7.

We report the synthesis, structure, and physical properties of single crystals of CePt(2)In(7). Single crystal x-ray diffraction analysis confirms the tetragonal I4/mmm structure of CePt(2)In(7) with unit cell parameters a = 4.5886(6) Å, c = 21.530(6) Å and V = 453.32(14) Å(3). The magnetic susceptibility, heat capacity, Hall effect and electrical resistivity measurements are all consistent with CePt(2)In(7) undergoing an antiferromagnetic order transition at T(N) = 5.5 K, which is field independent up to 9 T. Above T(N), the Sommerfeld coefficient of specific heat is γ ≈ 300 mJ mol(-1) K(-2), which is characteristic of an enhanced effective mass of itinerant charge carriers. The electrical resistivity is typical of heavy-fermion behavior and gives a residual resistivity ρ(0) ∼ 0.2 µΩ cm, indicating good crystal quality. CePt(2)In(7) also shows moderate anisotropy of the physical properties that is comparable to structurally related CeMIn(5) (M = Co, Rh, Ir) heavy-fermion superconductors.

Synthesis, structure and physical properties of YbNi3Al9.23.

The physical properties of YbNi(3)Al(9.23(1)), including the crystal structure, magnetization, specific heat, valence, and electrical resistivity, are reported. Single crystal x-ray diffraction reveals that the compound crystallizes with the rhombohedral space group R32 and has unit cell parameters a = 7.2443(3) Å and c = 27.251(3) Å with some crystallographic disorder at Al sites. The compound orders antiferromagnetically at T(N) = 3 K despite the presence of strong ferromagnetic correlations, accompanied by a spin-flop-like transition to a moment-aligned state above 0.1 T. X-ray absorption spectroscopy and magnetic susceptibility measurements indicate a localized Yb(3+) electronic configuration, while the Sommerfeld coefficient for the magnetically ordered state was determined as approximately 135 mJ mol(-1) K(-2), suggesting moderately heavy fermion behavior. Therefore, these data indicate a balance between competing Ruderman-Kittel-Kasuya-Yosida (RKKY) and Kondo interactions in YbNi(3)Al(9.23(1)) with a somewhat dominant RKKY interaction that leads to a relatively high ordering temperature.

Magnetic order in Pu2M3Si5 (M = Co, Ni).

The physical properties including magnetic susceptibility, specific heat, and electrical resistivity of two new plutonium compounds Pu2M3Si5 (M = Co, Ni) are reported. Pu2Ni3Si5 crystallizes in the orthorhombic U2Co3Si5 structure type, which can be considered a variant of the BaAl4 tetragonal structure, while Pu2Co3Si5 adopts the closely related monoclinic Lu2Co3Si5 type. Magnetic order is observed in both compounds, with Pu2Ni3Si5 ordering ferromagnetically at T(C) = 65 K then undergoing a transition into an antiferromagnetic state below T(N) = 35 K. Two successive magnetic transitions are also observed at T(mag1) = 38 K and T(mag2) = 5 K in Pu2Co3Si5. Specific heat measurements reveal that these two materials have a moderately enhanced Sommerfeld coefficient γ ∼ 100 mJ/mol Pu K(2) in the magnetic state with comparable RKKY and Kondo energy scales.

Results of donor lymphocyte infusions for relapsed myelodysplastic syndrome after hematopoietic cell transplantation.

Allogeneic hematopoietic cell transplantation (HCT) represents a potentially curative approach for patients with myelodysplastic syndromes (MDSs). While a large proportion of HCT recipients become long-term disease-free survivors, recurrence of MDS remains the leading cause of mortality after HCT. The role of donor lymphocyte infusion (DLI) in patients with relapsed MDS after HCT is unclear. We report results among 16 patients treated with DLI for relapsed MDS after HCT at a single institution between March 1993 and February 2004. The cohort contained 10 men and 6 women with a median age of 49 (range, 22-67) years. CR with resolution of cytopenias and prior disease markers occurred in 3 of 14 patients who could be evaluated. Two patients survived without MDS for 68 and 65 months after DLI, respectively, but died with pneumonia. Grades II-IV acute GVHD and chronic GVHD occurred after DLI in 6 (43%) and 5 (36%) patients, respectively. All three responders developed grades III-IV acute GVHD and extensive chronic GVHD after DLI. Our results confirm prior reports that DLI can result in CR in some patients with recurrent MDS after transplant, but long-term survival is infrequent.

Optimization of allogeneic transplant conditioning: not the time for dogma.

Numerous reduced-intensity conditioning regimens for allogeneic hematopoietic cell transplantation are currently being explored, primarily in older patients and in individuals with comorbid conditions who are not eligible for conventional myeloablative conditioning regimens. There is agreement that these approaches have reduced early transplant-related (non-relapse) toxicity and mortality. It is unclear, however, whether these strategies improve long-term survival. Furthermore, as most trials with reduced-intensity regimens have enrolled older patients and patients with comorbid conditions, it is not appropriate to compare the results of these trials to those obtained with more conventional approaches. It remains to be determined whether younger patients, and patients without comorbid conditions, will derive significant long-term benefits from reduced-intensity regimens when compared to conventional strategies. It may be that the different approaches are complementary and in the end will preferentially serve specific patient populations based on age, comorbid conditions and malignancy type. To determine the role of reduced-intensity approaches, controlled prospective trials are needed, with enrolled patients being stratified according to comorbid conditions, disease characteristics, pre-transplant therapy and source of stem cells, at a minimum.

Myeloablative vs nonmyeloablative allogeneic transplantation for patients with myelodysplastic syndrome or acute myelogenous leukemia with multilineage dysplasia: a retrospective analysis.

Transplant outcome was analyzed in 150 patients with myelodysplastic syndrome (MDS) or acute myelogenous leukemia transformed from MDS (tAML) conditioned with nonmyeloablative or myeloablative regimens. A total of 38 patients received nonmyeloablative regimens of 2 Gy total body irradiation alone (n=2) or with fludarabine (n=36), 90mg/m2. A total of 112 patients received a myeloablative regimen of busulfan, 16mg/ kg (targeted to 800-900 ng/ml), and cyclophosphamide 120 mg/ kg. Nonmyeloablative patients were older (median age 62 vs 52 years, P<0.001), more frequently had progressed to tAML (53 vs 31%, P=0.06), had higher risk disease by the International Prognostic Scoring System (53 vs 30%, P=0.004), had higher transplant specific comorbidity indices (68 vs 42%, P=0.01) and more frequently had durable complete responses to induction chemotherapy (58 vs 14%). Three-year overall survival (27%/48% (P=0.56)), progression-free survival (28%/4 44%, (P=0.60)), and nonrelapse mortality (41%/34%, (P=0.94)) did not differ significantly between nonmyeloblative/myeloablative conditioning. Overall (HR=0.9, P=0.84) and progression-free survivals (HR=1, P=0.93) were similar for patients with chemotherapy-induced remissions irrespective of conditioning intensity. Graft vs leukemia effects may be more important than conditioning intensity in preventing progression in patients in chemotherapy-induced remissions at the time of transplantation. Randomized prospective studies are needed to further address the optimal choice of transplant conditioning intensity in myeloid neoplasms.

Family-based case-control study of cigarette smoking and Parkinson disease.

OBJECTIVE: To determine whether people with Parkinson disease (PD) are less likely to report a history of cigarette smoking than their unaffected siblings. BACKGROUND: Previous studies reported that individuals with PD are half as likely to have smoked as those unaffected by PD. Other studies reported that smoking modified the risk of PD due to polymorphisms in the MAO-B and nNOS genes. Thus, genetic studies of PD should consider confounding or interaction with smoking history as well. The authors have collected detailed smoking histories on a family-based case-control sample ascertained for genetic studies of PD. METHODS: In a matched case-control study of 140 sibships, individuals with PD (n = 143) were compared to sibling controls (n = 168). Cigarette smoking history was collected by a structured telephone interview. Conditional logistic regression was used to examine the relationship between smoking and PD while controlling for confounding by age and sex. RESULTS: Ever smoking, current smoking, and increasing duration (in years), dose (in packs/day), and intensity (in pack-years) of smoking were significantly inversely associated with PD (p < 0.05). The association was not modified by sex, age at onset, or recency of exposure. CONCLUSIONS: Consistent with previous studies, individuals with Parkinson disease are significantly less likely to have smoked regularly than their unaffected siblings. This association was detected even though discordant sibling pairs are more likely to be overmatched for environmental exposures than unmatched case and control groups.

Genetic polymorphisms of the N-acetyltransferase genes and risk of Parkinson's disease.

Recently, the authors demonstrated linkage in idiopathic PD to a region on chromosome 8p that contains the N-acetyltransferase genes, NAT1 and NAT2. The authors examined NAT1 and NAT2 for association with PD using family-based association methods and single nucleotide polymorphisms (SNPs). The authors did not find evidence for association with increased risk for PD between any individual NAT1 or NAT2 SNP or acetylation haplotype (N = 397 families, 1,580 individuals).

Plutonium-based superconductivity with a transition temperature above 18 K.

Plutonium is a metal of both technological relevance and fundamental scientific interest. Nevertheless, the electronic structure of plutonium, which directly influences its metallurgical properties, is poorly understood. For example, plutonium's 5f electrons are poised on the border between localized and itinerant, and their theoretical treatment pushes the limits of current electronic structure calculations. Here we extend the range of complexity exhibited by plutonium with the discovery of superconductivity in PuCoGa5. We argue that the observed superconductivity results directly from plutonium's anomalous electronic properties and as such serves as a bridge between two classes of spin-fluctuation-mediated superconductors: the known heavy-fermion superconductors and the high-T(c) copper oxides. We suggest that the mechanism of superconductivity is unconventional; seen in that context, the fact that the transition temperature, T(c) approximately 18.5 K, is an order of magnitude greater than the maximum seen in the U- and Ce-based heavy-fermion systems may be natural. The large critical current displayed by PuCoGa5, which comes from radiation-induced self damage that creates pinning centres, would be of technological importance for applied superconductivity if the hazardous material plutonium were not a constituent.

Complete genomic screen in Parkinson disease: evidence for multiple genes.

CONTEXT: The relative contribution of genes vs environment in idiopathic Parkinson disease (PD) is controversial. Although genetic studies have identified 2 genes in which mutations cause rare single-gene variants of PD and observational studies have suggested a genetic component, twin studies have suggested that little genetic contribution exists in the common forms of PD. OBJECTIVE: To identify genetic risk factors for idiopathic PD. DESIGN, SETTING, AND PARTICIPANTS: Genetic linkage study conducted 1995-2000 in which a complete genomic screen (n = 344 markers) was performed in 174 families with multiple individuals diagnosed as having idiopathic PD, identified through probands in 13 clinic populations in the continental United States and Australia. A total of 870 family members were studied: 378 diagnosed as having PD, 379 unaffected by PD, and 113 with unclear status. MAIN OUTCOME MEASURES: Logarithm of odds (lod) scores generated from parametric and nonparametric genetic linkage analysis. RESULTS: Two-point parametric maximum parametric lod score (MLOD) and multipoint nonparametric lod score (LOD) linkage analysis detected significant evidence for linkage to 5 distinct chromosomal regions: chromosome 6 in the parkin gene (MLOD = 5.07; LOD = 5.47) in families with at least 1 individual with PD onset at younger than 40 years, chromosomes 17q (MLOD = 2.28; LOD = 2.62), 8p (MLOD = 2.01; LOD = 2.22), and 5q (MLOD = 2.39; LOD = 1.50) overall and in families with late-onset PD, and chromosome 9q (MLOD = 1.52; LOD = 2.59) in families with both levodopa-responsive and levodopa-nonresponsive patients. CONCLUSIONS: Our data suggest that the parkin gene is important in early-onset PD and that multiple genetic factors may be important in the development of idiopathic late-onset PD.