Exhumation of the Sierra de Cameros (Iberian Range, Spain): constraints from low-temperature thermochronology

We present new fission-track and (U–Th)/He data from apatite and zircon in order to reconstruct the exhumation of the Sierra de Cameros, in the northwestern part of Iberian Range, Spain. Zircon fission-track ages from samples from the depocentre of the basin were reset during the metamorphic peak at approximately 100 Ma. Detrital apatites from the uppermost sediments retain fission-track age information that is older than the sediment deposition age, indicating that these rocks have not exceeded 110 8C. Apatites from deeper in the stratigraphic sequence of the central part of the basin have fission-track ages of around 40 Ma, significantly younger than the stratigraphic age, recording the time of cooling after peak metamorphic conditions. Apatite (U–Th)/He ages in samples from these sediments are 31–40 Ma and record the last period of cooling during Alpine compression. The modelled thermal history derived from the uppermost sediments indicates that the thermal pulse associated with peak metamorphism was rapid, and that the region has cooled continuously to the present. The estimated palaeogeothermal gradient is around 86 8C km21 and supports a tectonic model with a thick sedimentary fill (c. 8 km) and explains the origin of the low-grade metamorphism observed in the oldest sediments

Assessing Ozone-Related Health Impacts under a Changing Climate

Climate change may increase the frequency and intensity of ozone episodes in future summers in the United States. However, only recently have models become available that can assess the impact of climate change on O(3) concentrations and health effects at regional and local scales that are relevant to adaptive planning. We developed and applied an integrated modeling framework to assess potential O(3)-related health impacts in future decades under a changing climate. The National Aeronautics and Space Administration–Goddard Institute for Space Studies global climate model at 4° × 5° resolution was linked to the Penn State/National Center for Atmospheric Research Mesoscale Model 5 and the Community Multiscale Air Quality atmospheric chemistry model at 36 km horizontal grid resolution to simulate hourly regional meteorology and O(3) in five summers of the 2050s decade across the 31-county New York metropolitan region. We assessed changes in O(3)-related impacts on summer mortality resulting from climate change alone and with climate change superimposed on changes in O(3) precursor emissions and population growth. Considering climate change alone, there was a median 4.5% increase in O(3)-related acute mortality across the 31 counties. Incorporating O(3) precursor emission increases along with climate change yielded similar results. When population growth was factored into the projections, absolute impacts increased substantially. Counties with the highest percent increases in projected O(3) mortality spread beyond the urban core into less densely populated suburban counties. This modeling framework provides a potentially useful new tool for assessing the health risks of climate change

Poincare Semigroup Symmetry as an Emergent Property of Unstable Systems

The notion that elementary systems correspond to irreducible representations of the Poincare group is the starting point for this paper, which then goes on to discuss how a semigroup for the time evolution of unstable states and resonances could emerge from the underlying Poincare symmetry. Important tools in this analysis are the Clebsch-Gordan coefficients for the Poincare group.Comment: 17 pages, 1 figur

High-dose imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: High rates of rapid cytogenetic and molecular responses

Purpose: Long-term clinical outcome data have established imatinib 400 mg/d as standard front-line treatment for newly diagnosed patients with chronic myeloid leukemia (CML). Patients and Methods: The Rationale and Insight for Gleevec High-Dose Therapy (RIGHT) trial is a multicenter study of imatinib 400 mg twice a day as initial therapy in 115 patients (70% Sokal low risk) with newly diagnosed CML in chronic phase who were observed for both molecular and cytogenetic responses for up to 18 months. Eighty-three patients (72%) completed the study, 10 patients (9%) discontinued the study because of adverse events, and six patients (5%) discontinued because of unsatisfactory therapeutic effect. Results: Polymerase chain reaction analysis demonstrated rapid kinetics of major molecular response (MMR), with 48% of patients achieving MMR by 6 months, 54% by 12 months, and 63% by 18 months. Corresponding complete molecular response rates were 39%, 44%, and 55%, respec- tively. Median dose-intensity was 98%. Overall, 79% of patients who received at least 90% dose-intensity achieved MMR. The most frequent adverse events included myelosuppression, rash, fatigue, and musculoskeletal symptoms. Conclusion: This study suggests that imatinib 400 mg twice a day results in more rapid reduction in tumor burden than imatinib 400 mg/d with minimal added toxicit

A phase 1 clinical trial of vorinostat in combination with decitabine in patients with acute myeloid leukaemia or myelodysplastic syndrome

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108599/1/bjh13016.pd

Selective C-H Activation at a Molecular Rhodium Sigma-Alkane Complex by Solid/Gas Single-Crystal to Single-Crystal H/D Exchange

The controlled catalytic functionalization of alkanes via the activation of C-H bonds is a significant challenge. Although C-H activation by transition metal catalysts is often suggested to operate via intermediate σ-alkane complexes, such transient species are difficult to observe due to their instability in solution. This instability may be controlled by use of solid/gas synthetic techniques that enable the isolation of single-crystals of well-defined σ-alkane complexes. Here we show that, using this unique platform, selective alkane C-H activation occurs, as probed by H/D exchange using D2, and that five different isotopomers/isotopologues of the σ-alkane complex result, as characterized by single-crystal neutron diffraction studies for three examples. Low-energy fluxional processes associated with the σ-alkane ligand are identified using variable-temperature X-ray diffraction, solid-state NMR spectroscopy, and periodic DFT calculations. These observations connect σ-alkane complexes with their C-H activated products, and demonstrate that alkane-ligand mobility, and selective C-H activation, are possible when these processes occur in the constrained environment of the solid-state

Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy

AbstractAlthough imatinib induces marked responses in patients with chronic myeloid leukemia (CML), resistance is increasingly problematic, and treatment options for imatinib-resistant or -intolerant CML are limited. Dasatinib, a novel, highly potent, oral, multitargeted kinase inhibitor of BCR-ABL and SRC family kinases, induced cytogenetic responses in a phase 1 study in imatinib-resistant or -intolerant CML and was well tolerated. Initial results are presented from a phase 2 study of 186 patients with imatinib-resistant or -intolerant chronic-phase CML (CML-CP) designed to further establish the efficacy and safety of dasatinib (70 mg twice daily). At 8-months' follow-up, dasatinib induced notable responses, with 90% and 52% of patients achieving complete hematologic and major cytogenetic responses (MCyR), respectively. Responses were long lasting: only 2% of patients achieving MCyR progressed or died. Importantly, comparable responses were achieved by patients carrying BCR-ABL mutations conferring imatinib resistance. Dasatinib also induced molecular responses, reducing BCR-ABL/ABL transcript ratios from 66% at baseline to 2.6% at 9 months. Nonhematologic adverse events were generally mild to moderate, and most cytopenias were effectively managed with dose modifications. Cross-intolerance with imatinib was not evident. To conclude, dasatinib induces notable responses in imatinib-resistant or -intolerant CML-CP, is well tolerated, and represents a promising therapeutic option for these patients. This trial was registered at www.clinicaltrials.gov as CA180013

Sensitization in Transplantation: Assessment of Risk (STAR) 2017 Working Group Meeting Report

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144684/1/ajt14752_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144684/2/ajt14752.pd