688 research outputs found

    The Lyth Bound and the End of Inflation

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    We derive an extended version of the well-known Lyth Bound on the total variation of the inflaton field, incorporating higher order corrections in slow roll. We connect the field variation Δϕ\Delta\phi to both the spectral index of scalar perturbations and the amplitude of tensor modes. We then investigate the implications of this bound for ``small field'' potentials, where the field rolls off a local maximum of the potential. The total field variation during inflation is {\em generically} of order mPlm_{\rm Pl}, even for potentials with a suppressed tensor/scalar ratio. Much of the total field excursion arises in the last e-fold of inflation and in single field models this problem can only be avoided via fine-tuning or the imposition of a symmetry. Finally, we discuss the implications of this result for inflationary model building in string theory and supergravity.Comment: 10 pages, RevTeX, 2 figures (V3: version accepted for publication by JCAP

    A general approach for hysteresis-free, operationally stable metal halide perovskite field-effect transistors.

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    Despite sustained research, application of lead halide perovskites in field-effect transistors (FETs) has substantial concerns in terms of operational instabilities and hysteresis effects which are linked to its ionic nature. Here, we investigate the mechanism behind these instabilities and demonstrate an effective route to suppress them to realize high-performance perovskite FETs with low hysteresis, high threshold voltage stability (ΔVt 1 cm2/V·s at room temperature. We show that multiple cation incorporation using strain-relieving cations like Cs and cations such as Rb, which act as passivation/crystallization modifying agents, is an effective strategy for reducing vacancy concentration and ion migration in perovskite FETs. Furthermore, we demonstrate that treatment of perovskite films with positive azeotrope solvents that act as Lewis bases (acids) enables a further reduction in defect density and substantial improvement in performance and stability of n-type (p-type) perovskite devices

    Gender-dependent differences in plasma matrix metalloproteinase-8 elevated in pulmonary tuberculosis.

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    Tuberculosis (TB) remains a global health pandemic and greater understanding of underlying pathogenesis is required to develop novel therapeutic and diagnostic approaches. Matrix metalloproteinases (MMPs) are emerging as key effectors of tissue destruction in TB but have not been comprehensively studied in plasma, nor have gender differences been investigated. We measured the plasma concentrations of MMPs in a carefully characterised, prospectively recruited clinical cohort of 380 individuals. The collagenases, MMP-1 and MMP-8, were elevated in plasma of patients with pulmonary TB relative to healthy controls, and MMP-7 (matrilysin) and MMP-9 (gelatinase B) were also increased. MMP-8 was TB-specific (p<0.001), not being elevated in symptomatic controls (symptoms suspicious of TB but active disease excluded). Plasma MMP-8 concentrations inversely correlated with body mass index. Plasma MMP-8 concentration was 1.51-fold higher in males than females with TB (p<0.05) and this difference was not due to greater disease severity in men. Gender-specific analysis of MMPs demonstrated consistent increase in MMP-1 and -8 in TB, but MMP-8 was a better discriminator for TB in men. Plasma collagenases are elevated in pulmonary TB and differ between men and women. Gender must be considered in investigation of TB immunopathology and development of novel diagnostic markers

    A comparison of particle mass spectrometers during the 1999 Atlanta Supersite Project

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    During the Atlanta Supersite Project, four particle mass spectrometers were operated together for the first time: NOAA's Particle Analysis by Laser Mass Spectrometer (PALMS), University of California at Riverside's Aerosol Time-of-Flight Mass Spectrometer (ATOFMS), University of Delaware's Rapid Single-Particle Mass Spectrometer II (RSMS-II), and Aerodyne's Aerosol Mass Spectrometer (AMS). Although these mass spectrometers are generally classified as similar instruments, they clearly have different characteristics due to their unique designs. One primary difference is related to the volatilization/ionization method: PALMS, ATOFMS, and RSMS-II utilize laser desorption/ionization, whereas particles in the AMS instrument are volatilized by impaction onto a heated surface with the resulting components ionized by electron impact. Thus mass spectral data from the AMS are representative of the ensemble of particles sampled, and those from the laser-based instruments are representative of individual particles. In addition, the AMS instrument cannot analyze refractory material such as soot, sodium chloride, and crustal elements, and some sulfate or water-rich particles may not always be analyzed with every laser-based instrument. A main difference among the laser-based mass spectrometers is that the RSMS-II instrument can obtain size-resolved single particle composition information for particles with aerodynamic diameters as small as 15 nm. The minimum sizes analyzed by ATOFMS and PALMS are 0.2 and about 0.35 ÎŒm, respectively, in aerodynamic diameter. Furthermore, PALMS, ATOFMS, and RSMS-II use different laser ionization conditions. Despite these differences the laser-based instruments found similar individual particle classifications, and their relative fractions among comparable sized particles from Atlanta were broadly consistent. Finally, the AMS measurements of the nitrate/sulfate mole ratio were highly correlated with composite measurements (r^2 = 0.93). In contrast, the PALMS nitrate/sulfate ion ratios were only moderately correlated (r^2 ∌ 0.7)

    Proton Therapy for Breast Cancer:A Consensus Statement From the Particle Therapy Cooperative Group Breast Cancer Subcommittee

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    Radiation therapy plays an important role in the multidisciplinary management of breast cancer. Recent years have seen improvements in breast cancer survival and a greater appreciation of potential long-term morbidity associated with the dose and volume of irradiated organs. Proton therapy reduces the dose to nontarget structures while optimizing target coverage. However, there remain additional financial costs associated with proton therapy, despite reductions over time, and studies have yet to demonstrate that protons improve upon the treatment outcomes achieved with photon radiation therapy. There remains considerable heterogeneity in proton patient selection and techniques, and the rapid technological advances in the field have the potential to affect evidence evaluation, given the long latency period for breast cancer radiation therapy recurrence and late effects. In this consensus statement, we assess the data available to the radiation oncology community of proton therapy for breast cancer, provide expert consensus recommendations on indications and technique, and highlight ongoing trials' cost-effectiveness analyses and key areas for future research. (c) 2021 Elsevier Inc. All rights reserved

    First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

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    Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far

    Documentation of body mass index and control of associated risk factors in a large primary care network

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    <p>Abstract</p> <p>Background</p> <p>Body mass index (BMI) will be a reportable health measure in the United States (US) through implementation of Healthcare Effectiveness Data and Information Set (HEDIS) guidelines. We evaluated current documentation of BMI, and documentation and control of associated risk factors by BMI category, based on electronic health records from a 12-clinic primary care network.</p> <p>Methods</p> <p>We conducted a cross-sectional analysis of 79,947 active network patients greater than 18 years of age seen between 7/05 - 12/06. We defined BMI category as normal weight (NW, 18-24.9 kg/m<sup>2</sup>), overweight (OW, 25-29.9), and obese (OB, ≄ 30). We measured documentation (yes/no) and control (above/below) of the following three risk factors: blood pressure (BP) ≀130/≀85 mmHg, low-density lipoprotein (LDL) ≀130 mg/dL (3.367 mmol/L), and fasting glucose <100 mg/dL (5.55 mmol/L) or casual glucose <200 mg/dL (11.1 mmol/L).</p> <p>Results</p> <p>BMI was documented in 48,376 patients (61%, range 34-94%), distributed as 30% OB, 34% OW, and 36% NW. Documentation of all three risk factors was higher in obesity (OB = 58%, OW = 54%, NW = 41%, p for trend <0.0001), but control of all three was lower (OB = 44%, OW = 49%, NW = 62%, p = 0.0001). The presence of cardiovascular disease (CVD) or diabetes modified some associations with obesity, and OB patients with CVD or diabetes had low rates of control of all three risk factors (CVD: OB = 49%, OW = 50%, NW = 56%; diabetes: OB = 42%, OW = 47%, NW = 48%, p < 0.0001 for adiposity-CVD or diabetes interaction).</p> <p>Conclusions</p> <p>In a large primary care network BMI documentation has been incomplete and for patients with BMI measured, risk factor control has been poorer in obese patients compared with NW, even in those with obesity and CVD or diabetes. Better knowledge of BMI could provide an opportunity for improved quality in obesity care.</p

    Optimized low-dose combinatorial drug treatment boosts selectivity and efficacy of colorectal carcinoma treatment.

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    The current standard of care for colorectal cancer (CRC) is a combination of chemotherapeutics, often supplemented with targeted biological drugs. An urgent need exists for improved drug efficacy and minimized side effects, especially at late-stage disease. We employed the phenotypically driven therapeutically guided multidrug optimization (TGMO) technology to identify optimized drug combinations (ODCs) in CRC. We identified low-dose synergistic and selective ODCs for a panel of six human CRC cell lines also active in heterotypic 3D co-culture models. Transcriptome sequencing and phosphoproteome analyses showed that the mechanisms of action of these ODCs converged toward MAP kinase signaling and cell cycle inhibition. Two cell-specific ODCs were translated to in vivo mouse models. The ODCs reduced tumor growth by ~80%, outperforming standard chemotherapy (FOLFOX). No toxicity was observed for the ODCs, while significant side effects were induced in the group treated with FOLFOX therapy. Identified ODCs demonstrated significantly enhanced bioavailability of the individual components. Finally, ODCs were also active in primary cells from CRC patient tumor tissues. Taken together, we show that the TGMO technology efficiently identifies selective and potent low-dose drug combinations, optimized regardless of tumor mutation status, outperforming conventional chemotherapy
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