The field of regenerative medicine holds considerable promise for treating diseases that are currently intractable. Although many researchers are adopting the strategy of cell transplantation for ...tissue repair, an alternative approach to therapy is to manipulate the stem cell microenvironment, or niche, to facilitate repair by endogenous stem cells. The niche is highly dynamic, with multiple opportunities for intervention. These include administration of small molecules, biologics or biomaterials that target specific aspects of the niche, such as cell-cell and cell-extracellular matrix interactions, to stimulate expansion or differentiation of stem cells, or to cause reversion of differentiated cells to stem cells. Nevertheless, there are several challenges in targeting the niche therapeutically, not least that of achieving specificity of delivery and responses. We envisage that successful treatments in regenerative medicine will involve different combinations of factors to target stem cells and niche cells, applied at different times to effect recovery according to the dynamics of stem cell-niche interactions.
Is Tax Avoidance Related to Firm Risk? Guenther, David A.; Matsunaga, Steven R.; Williams, Brian M.
The Accounting review,
01/2017, Letnik:
92, Številka:
1
Journal Article
Recenzirano
We test whether tax avoidance strategies are associated with greater firm risk. We find that low tax rates tend to be more persistent than high tax rates and that measures of tax avoidance commonly ...used in the literature are generally not associated with either future tax rate volatility or future overall firm risk. Our evidence suggests that, on average, corporate tax avoidance is accomplished using strategies that are persistent and do not increase firm risk. We also find that the volatility of cash tax rates is associated with future stock volatility, suggesting that tax rate volatility and overall firm risk are related.
Almost without exception, everything human beings undertake involves a choice. In recent years there has been a growing interest in the development and application of quantitative statistical methods ...to study choices made by individuals with the purpose of gaining a better understanding both of how choices are made and of forecasting future choice responses. In this primer the authors provide an unintimidating introduction to the main techniques of choice analysis and include detail on themes such as data collection and preparation, model estimation and interpretation and the design of choice experiments. A companion website to the book provides practice data sets and software to estimate the main discrete choice models such as multinomial logit, nested logit and mixed logit. This primer will be an invaluable resource to students as well as of immense value to consultants and professionals, researchers and anyone else interested in choice analysis and modelling.
Limited level 1 evidence is available on the omission of radiotherapy after breast-conserving surgery in older women with hormone receptor-positive early breast cancer receiving adjuvant endocrine ...therapy.
We performed a phase 3 randomized trial of the omission of irradiation; the trial population included women 65 years of age or older who had hormone receptor-positive, node-negative, T1 or T2 primary breast cancer (with tumors ≤3 cm in the largest dimension) treated with breast-conserving surgery with clear excision margins and adjuvant endocrine therapy. Patients were randomly assigned to receive whole-breast irradiation (40 to 50 Gy) or no irradiation. The primary end point was local breast cancer recurrence. Regional recurrence, breast cancer-specific survival, distant recurrence as the first event, and overall survival were also assessed.
A total of 1326 women were enrolled; 658 were randomly assigned to receive whole-breast irradiation and 668 to receive no irradiation. The median follow-up was 9.1 years. The cumulative incidence of local breast cancer recurrence within 10 years was 9.5% (95% confidence interval CI, 6.8 to 12.3) in the no-radiotherapy group and 0.9% (95% CI, 0.1 to 1.7) in the radiotherapy group (hazard ratio, 10.4; 95% CI, 4.1 to 26.1; P<0.001). Although local recurrence was more common in the group that did not receive radiotherapy, the 10-year incidence of distant recurrence as the first event was not higher in the no-radiotherapy group than in the radiotherapy group, at 1.6% (95% CI, 0.4 to 2.8) and 3.0% (95% CI, 1.4 to 4.5), respectively. Overall survival at 10 years was almost identical in the two groups, at 80.8% (95% CI, 77.2 to 84.3) with no radiotherapy and 80.7% (95% CI, 76.9 to 84.3) with radiotherapy. The incidence of regional recurrence and breast cancer-specific survival also did not differ substantially between the two groups.
Omission of radiotherapy was associated with an increased incidence of local recurrence but had no detrimental effect on distant recurrence as the first event or overall survival among women 65 years of age or older with low-risk, hormone receptor-positive early breast cancer. (Funded by the Chief Scientist Office of the Scottish Government and the Breast Cancer Institute, Western General Hospital, Edinburgh; ISRCTN number, ISRCTN95889329.).
Abstract
We report here radio follow-up observations of the optical tidal disruption event (TDE) AT 2019azh. Previously reported X-ray observations of this TDE showed variability at early times and a ...dramatic increase in luminosity, by a factor of ∼10, about 8 months after optical discovery. The X-ray emission is mainly dominated by intermediate hard-soft X-rays and is exceptionally soft around the X-ray peak, which is
L
X
∼ 10
43
erg s
−1
. The high cadence 15.5 GHz observations reported here show an early rise in radio emission followed by an approximately constant light curve, and a late-time flare. This flare starts roughly at the time of the observed X-ray peak luminosity and reaches its peak about 110 days after the peak in the X-ray, and a year after optical discovery. The radio flare peaks at
ν
L
ν
∼ 10
38
erg s
−1
, a factor of two higher than the emission preceding the flare. In light of the late-time radio and X-ray flares, and the X-ray spectral evolution, we speculate a possible transition in the accretion state of this TDE, similar to the observed behavior in black hole X-ray binaries. We compare the radio properties of AT 2019azh to other known TDEs, and focus on the similarities to the late-time radio flare of the TDE ASASSN-15oi.
There is increasing recognition that many if not most common chronic pain conditions are heterogeneous with a high degree of overlap or coprevalence of other common pain conditions along with ...influences from biopsychosocial factors. At present, very little attention is given to the high degree of overlap of many common pain conditions when recruiting for clinical trials. As such, many if not most patients enrolled into clinical studies are not representative of most chronic pain patients. The failure to account for the heterogeneous and overlapping nature of most common pain conditions may result in treatment responses of small effect size when these treatments are administered to patients with chronic overlapping pain conditions (COPCs) represented in the general population. In this brief review we describe the concept of COPCs and the putative mechanisms underlying COPCs. Finally, we present a series of recommendations that will advance our understanding of COPCs.
This brief review describes the concept of COPCs. A mechanism-based heuristic model is presented and current knowledge and evidence for COPCs are presented. Finally, a set of recommendations is provided to advance our understanding of COPCs.
Photoinduced electron transfer (PET) is a phenomenon whereby the absorption of light by a chemical species provides an energetic driving force for an electron-transfer reaction
. This mechanism is ...relevant in many areas of chemistry, including the study of natural and artificial photosynthesis, photovoltaics and photosensitive materials. In recent years, research in the area of photoredox catalysis has enabled the use of PET for the catalytic generation of both neutral and charged organic free-radical species. These technologies have enabled previously inaccessible chemical transformations and have been widely used in both academic and industrial settings. Such reactions are often catalysed by visible-light-absorbing organic molecules or transition-metal complexes of ruthenium, iridium, chromium or copper
. Although various closed-shell organic molecules have been shown to behave as competent electron-transfer catalysts in photoredox reactions, there are only limited reports of PET reactions involving neutral organic radicals as excited-state donors or acceptors. This is unsurprising because the lifetimes of doublet excited states of neutral organic radicals are typically several orders of magnitude shorter than the singlet lifetimes of known transition-metal photoredox catalysts
. Here we document the discovery, characterization and reactivity of a neutral acridine radical with a maximum excited-state oxidation potential of -3.36 volts versus a saturated calomel electrode, which is similarly reducing to elemental lithium, making this radical one of the most potent chemical reductants reported
. Spectroscopic, computational and chemical studies indicate that the formation of a twisted intramolecular charge-transfer species enables the population of higher-energy doublet excited states, leading to the observed potent photoreducing behaviour. We demonstrate that this catalytically generated PET catalyst facilitates several chemical reactions that typically require alkali metal reductants and can be used in other organic transformations that require dissolving metal reductants.
Abstract
Recently, the accretion geometry of the black hole X-ray binary Cyg X-1 was probed with the X-ray polarization. The position angle of the X-ray-emitting flow was found to be aligned with the ...position angle of the radio jet in the plane of the sky. At the same time, the observed high polarization degree could be obtained only for a high inclination of the X-ray-emitting flow, indicating a misalignment between the binary axis and the black hole spin. The jet, in turn, is believed to be directed by the spin axis; hence, a similar misalignment is expected between the jet and binary axes. We test this hypothesis using very long (up to about 26 yr) multiband radio observations. We find a misalignment of 20°–30°. However, contrary to the earlier expectations, the jet and binary viewing angles are found to be similar, while the misalignment is seen between the position angles of the jet and the binary axis on the plane of the sky. Furthermore, the presence of the misalignment calls into question our understanding of the evolution of this binary system.
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