Patient-reported reasons for declining or discontinuing statin therapy: Insights from the PALM registry

Background: Many adults eligible for statin therapy for cardiovascular disease prevention are untreated. Our objective was to investigate patient‐reported reasons for statin underutilization, including noninitiation, refusal, and discontinuation.Methods and Results: This study included the 5693 adults recommended for statin therapy in the PALM (Patient and Provider Assessment of Lipid Management) registry. Patient surveys evaluated statin experience, reasons for declining or discontinuing statins, and beliefs about statins and cardiovascular disease risk. Overall, 1511 of 5693 adults (26.5%) were not on treatment. Of those not on a statin, 894 (59.2%) reported never being offered a statin, 153 (10.1%) declined a statin, and 464 (30.7%) had discontinued therapy. Women (relative risk: 1.22), black adults (relative risk: 1.48), and those without insurance (relative risk: 1.38) were most likely to report never being offered a statin. Fear of side effects and perceived side effects were the most common reasons cited for declining or discontinuing a statin. Compared with statin users, those who declined or discontinued statins were less likely to believe statins are safe (70.4% of current users vs. 36.9% of those who declined and 37.4% of those who discontinued) or effective (86.3%, 67.4%, and 69.1%, respectively). Willingness to take a statin was high; 67.7% of those never offered and 59.7% of patients who discontinued a statin would consider initiating or retrying a statin.Conclusions: More than half of patients eligible for statin therapy but not on treatment reported never being offered one by their doctor. Concern about side effects was the leading reason for statin refusal or discontinuation. Many patients were willing to reconsider statin therapy if offered

Towards Real-time, On-board, Hardware-Supported Sensor and Software Health Management for Unmanned Aerial Systems

Unmanned aerial systems (UASs) can only be deployed if they can effectively complete their missions and respond to failures and uncertain environmental conditions while maintaining safety with respect to other aircraft as well as humans and property on the ground. In this paper, we design a real-time, on-board system health management (SHM) capability to continuously monitor sensors, software, and hardware components for detection and diagnosis of failures and violations of safety or performance rules during the flight of a UAS. Our approach to SHM is three-pronged, providing: (1) real-time monitoring of sensor and/or software signals; (2) signal analysis, preprocessing, and advanced on the- fly temporal and Bayesian probabilistic fault diagnosis; (3) an unobtrusive, lightweight, read-only, low-power realization using Field Programmable Gate Arrays (FPGAs) that avoids overburdening limited computing resources or costly re-certification of flight software due to instrumentation. Our implementation provides a novel approach of combining modular building blocks, integrating responsive runtime monitoring of temporal logic system safety requirements with model-based diagnosis and Bayesian network-based probabilistic analysis. We demonstrate this approach using actual data from the NASA Swift UAS, an experimental all-electric aircraft

Towards Real-Time, On-Board, Hardware-Supported Sensor and Software Health Management for Unmanned Aerial Systems

For unmanned aerial systems (UAS) to be successfully deployed and integrated within the national airspace, it is imperative that they possess the capability to effectively complete their missions without compromising the safety of other aircraft, as well as persons and property on the ground. This necessity creates a natural requirement for UAS that can respond to uncertain environmental conditions and emergent failures in real-time, with robustness and resilience close enough to those of manned systems. We introduce a system that meets this requirement with the design of a real-time onboard system health management (SHM) capability to continuously monitor sensors, software, and hardware components. This system can detect and diagnose failures and violations of safety or performance rules during the flight of a UAS. Our approach to SHM is three-pronged, providing: (1) real-time monitoring of sensor and software signals; (2) signal analysis, preprocessing, and advanced on-the-fly temporal and Bayesian probabilistic fault diagnosis; and (3) an unobtrusive, lightweight, read-only, low-power realization using Field Programmable Gate Arrays (FPGAs) that avoids overburdening limited computing resources or costly re-certification of flight software. We call this approach rt-R2U2, a name derived from its requirements. Our implementation provides a novel approach of combining modular building blocks, integrating responsive runtime monitoring of temporal logic system safety requirements with model-based diagnosis and Bayesian network-based probabilistic analysis. We demonstrate this approach using actual flight data from the NASA Swift UAS

Estimation of the hydraulic parameters of unsaturated samples by electrical resistivity tomography

In situ and laboratory experiments have shown that electrical resistivity tomography (ERT) is an effective tool to image transient phenomena in soils. However, its application in quantifying soil hydraulic parameters has been limited. In this study, experiments of water inflow in unsaturated soil samples were conducted in an oedometer equipped to perform three-dimensional electrical measurements. Reconstructions of the electrical conductivity at different times confirmed the usefulness of ERT for monitoring the evolution of water content. The tomographic reconstructions were subsequently used in conjunction with a finite-element simulation to infer the water retention curve and the unsaturated hydraulic conductivity. The parameters estimated with ERT agree satisfactorily with those determined using established techniques, hence the proposed approach shows good potential for relatively fast characterisations. Similar experiments could be carried out on site to study the hydraulic behaviour of the entire soil deposi

Androgen receptor as a mediator and biomarker of radioresistance in triple-negative breast cancer.

Increased rates of locoregional recurrence have been observed in triple-negative breast cancer despite chemotherapy and radiation therapy. Thus, approaches that combine therapies for radiosensitization in triple-negative breast cancer are critically needed. We characterized the radiation therapy response of 21 breast cancer cell lines and paired this radiation response data with high-throughput drug screen data to identify androgen receptor as a top target for radiosensitization. Our radiosensitizer screen nominated bicalutamide as the drug most effective in treating radiation therapy-resistant breast cancer cell lines. We subsequently evaluated the expression of androgen receptor in >2100 human breast tumor samples and 51 breast cancer cell lines and found significant heterogeneity in androgen receptor expression with enrichment at the protein and RNA level in triple-negative breast cancer. There was a strong correlation between androgen receptor RNA and protein expression across all breast cancer subtypes (R2 = 0.72, p < 0.01). In patients with triple-negative breast cancer, expression of androgen receptor above the median was associated with increased risk of locoregional recurrence after radiation therapy (hazard ratio for locoregional recurrence 2.9-3.2)) in two independent data sets, but there was no difference in locoregional recurrence in triple-negative breast cancer patients not treated with radiation therapy when stratified by androgen receptor expression. In multivariable analysis, androgen receptor expression was most significantly associated with worse local recurrence-free survival after radiation therapy (hazard ratio of 3.58) suggesting that androgen receptor expression may be a biomarker of radiation response in triple-negative breast cancer. Inhibition of androgen receptor with MDV3100 (enzalutamide) induced radiation sensitivity (enhancement ratios of 1.22-1.60) in androgen receptor-positive triple-negative breast cancer lines, but did not affect androgen receptor-negative triple-negative breast cancer or estrogen-receptor-positive, androgen receptor-negative breast cancer cell lines. androgen receptor inhibition with MDV3100 significantly radiosensitized triple-negative breast cancer xenografts in mouse models and markedly delayed tumor doubling/tripling time and tumor weight. Radiosensitization was at least partially dependent on impaired dsDNA break repair mediated by DNA protein kinase catalytic subunit. Our results implicate androgen receptor as a mediator of radioresistance in breast cancer and identify androgen receptor inhibition as a potentially effective strategy for the treatment of androgen receptor-positive radioresistant tumors

Nuclear spin-spin coupling in La_{2-x}Sr_{x}CuO_{4} studied by stimulated echo decay

We have performed copper NQR experiments in high temperature superconductors YBa_{2}Cu_{4}O_{8}, YBa_{2}Cu_{3}O_{7}, and La_{2-x}Sr_{x}CuO_{4} (x=0.12 and 0.15), using the stimulated echo technique. The stimulated echo intensity is analyzed by a model that includes the spin-lattice relaxation process (T_ {1 }-process) and the fluctuating local field due to nuclear spin-spin coupling. The model gives quantitative account of the experimental results in Y-based compounds using the known values of 1/T_{1} and 1/T_{2G}, the gaussian decay rate of the spin echo intensity. The same model applied to LSCO enables us to extract the value of T_{2G}. Our results indicate that T_{1}T/T_{2G} is independent of temperature, implying that the dynamic exponent is one in La_{2-x}Sr_{x}CuO_{4}.Comment: 14 pages, 11 fugures, The bibliography field is correcte

Random Packings of Frictionless Particles

We study random packings of frictionless particles at T=0. The packing fraction where the pressure becomes nonzero is the same as the jamming threshold, where the static shear modulus becomes nonzero. The distribution of threshold packing fractions narrows and its peak approaches random close-packing as the system size increases. For packing fractions within the peak, there is no self-averaging, leading to exponential decay of the interparticle force distribution.Comment: 4 pages, 3 figure

Multi-phonon Resonant Raman Scattering Predicted in LaMnO3 from the Franck-Condon Process via Self-Trapped Excitons

Resonant behavior of the Raman process is predicted when the laser frequency is close to the orbital excitation energy of LaMnO3 at 2 eV. The incident photon creates a vibrationally excited self-trapped ``orbiton'' state from the orbitally-ordered Jahn-Teller (JT) ground state. Trapping occurs by local oxygen rearrangement. Then the Franck-Condon mechanism activates multiphonon Raman scattering. The amplitude of the $n$-phonon process is first order in the electron-phonon coupling $g$. The resonance occurs {\it via} a dipole forbidden $d$ to $d$ transition. We previously suggested that this transition (also seen in optical reflectivity) becomes allowed because of asymmetric oxygen fluctuations. Here we calculate the magnitude of the corresponding matrix element using local spin-density functional theory. This calculation agrees to better than a factor of two with our previous value extracted from experiment. This allows us to calculate the absolute value of the Raman tensor for multiphonon scattering. Observation of this effect would be a direct confirmation of the importance of the JT electron-phonon term and the presence of self-trapped orbital excitons, or ``orbitons''.Comment: 8 pages and 3 embedded figures. The earlier short version is now replaced by a more complete paper with a slightly different title. This version includes a caculation by density-functional theory of the dipole matrix element for exciting the self-trapped orbital exciton which activates the multiphonon Raman signal

Diagnosis and Treatment of Pediatric Acquired Aplastic Anemia (AAA): An Initial Survey of the North American Pediatric Aplastic Anemia Consortium (NAPAAC)

BackgroundRandomized clinical trials in pediatric aplastic anemia (AA) are rare and data to guide standards of care are scarce. ProcedureEighteen pediatric institutions formed the North American Pediatric Aplastic Anemia Consortium to foster collaborative studies in AA. The initial goal of NAPAAC was to survey the diagnostic studies and therapies utilized in AA. ResultsOur survey indicates considerable variability among institutions in the diagnosis and treatment of AA. There were areas of general consensus, including the need for a bone marrow evaluation, cytogenetic and specific fluorescent in situ hybridization assays to establish diagnosis and exclude genetic etiologies with many institutions requiring results prior to initiation of immunosuppressive therapy (IST); uniform referral for hematopoietic stem cell transplantation as first line therapy if an HLA-identical sibling is identified; the use of first-line IST containing horse anti-thymocyte globulin and cyclosporine A (CSA) if an HLA-identical sibling donor is not identified; supportive care measures; and slow taper of CSA after response. Areas of controversy included the need for telomere length results prior to IST, the time after IST initiation defining a treatment failure; use of hematopoietic growth factors; the preferred rescue therapy after failure of IST; the use of specific hemoglobin and platelet levels as triggers for transfusion support; the use of prophylactic antibiotics; and follow-up monitoring after completion of treatment. ConclusionsThese initial survey results reflect heterogeneity in diagnosis and care amongst pediatric centers and emphasize the need to develop evidence-based diagnosis and treatment approaches in this rare disease. Pediatr Blood Cancer 2014;61:869-874. (c) 2013 Wiley Periodicals, Inc

Preparation of anti-vicinal amino alcohols: asymmetric synthesis of D-erythro-Sphinganine, (+)-spisulosine and D-ribo-phytosphingosine

Two variations of the Overman rearrangement have been developed for the highly selective synthesis of anti-vicinal amino alcohol natural products. A MOM-ether directed palladium(II)-catalyzed rearrangement of an allylic trichloroacetimidate was used as the key step for the preparation of the protein kinase C inhibitor D-erythro-sphinganine and the antitumor agent (+)-spisulosine, while the Overman rearrangement of chiral allylic trichloroacetimidates generated by asymmetric reduction of an alpha,beta-unsaturated methyl ketone allowed rapid access to both D-ribo-phytosphingosine and L-arabino-phytosphingosine