Objectives To examine health-related quality of life (HRQoL) among sibling pediatric hematopoietic stem cell donors from predonation through 1 year postdonation, to compare donor-reported HRQoL ...scores with proxy-reports by parents/guardians and those of healthy norms, and to identify predonation factors (including donor age) potentially associated with postdonation HRQoL, to better understand the physical and psychosocial effects of pediatric hematopoietic stem cell donation. Study design A random sample of 105 pediatric donors from US centers and a parent/guardian were interviewed by telephone predonation and 4 weeks and 1 year postdonation. The interview included sociodemographic, psychosocial, and HRQoL items. A sample of healthy controls matched to donors by age, gender, and race/ethnicity was generated. Results Key findings included (1) approximately 20% of donors at each time point had very poor HRQoL; (2) child self-reported HRQoL was significantly lower than parent proxy-reported HRQoL at all 3 time points and significantly lower than that of norms at predonation and 4 weeks postdonation; and (3) younger children were at particular risk of poor HRQoL. Conclusions Additional research to identify the specific sources of poorer HRQoL among at-risk donors (eg, the donation experience vs having a chronically ill sibling) and the reasons that parents may be overestimating HRQoL in their donor children is critical and should lead to interventions and policy changes that ensure positive experiences for these minor donors.
We analyze temporal trends of peroxyacetyl nitrate (PAN) retrievals from the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) during 2002–2011 in the altitude range 8–23 km over the ...Asian summer monsoon (ASM) region. The greatest enhancements of PAN mixing ratios in the upper troposphere and lower stratosphere (UTLS) are seen during the summer monsoon season from June to September. During the monsoon season, the mole fractions of PAN show statistically significant (at 2σ) positive trends from 0.2 ± 0.05 to 4.6 ± 3.1 ppt yr−1 (except between 12 and 14 km) which is higher than the annual mean trends of 0.1 ± 0.05 to 2.7 ± 0.8 ppt yr−1. These rising concentrations point to increasing NOx (= NO + NO2) and volatile organic compound (VOC) emissions from developing nations in Asia, notably India and China. We analyze the influence of monsoon convection on the distribution of PAN in UTLS with simulations using the global chemistry–climate model ECHAM5-HAMMOZ. During the monsoon, transport into the UTLS over the Asian region primarily occurs from two convective zones, one the South China Sea and the other over the southern flank of the Himalayas. India and China host NOx-limited regimes for ozone photochemical production, and thus we use the model to evaluate the contributions from enhanced NOx emissions to the changes in PAN, HNO3 and O3 concentrations in the UTLS. From a set of sensitivity experiments with emission changes in particular regions, it can be concluded that Chinese emissions have a greater impact on the concentrations of these species than Indian emissions. According to SCanning Imaging Absorption SpectroMeter for Atmospheric CHartographY (SCIAMACHY) NO2 retrievals NOx emissions increases over India have been about half of those over China between 2002 and 2011.
SALL1 is a multi-zinc finger transcription factor that regulates organogenesis and stem cell development, but the role of SALL1 in tumor biology and tumorigenesis remains largely unknown.
We analyzed ...SALL1 expression levels in human and murine breast cancer cells as well as cancer tissues from different types of breast cancer patients. Using both in vitro co-culture system and in vivo breast tumor models, we investigated how SALL1 expression in breast cancer cells affects tumor cell growth and proliferation, metastasis, and cell fate. Using the gain-of function and loss-of-function strategies, we dissected the molecular mechanism responsible for SALL1 tumor suppressor functions.
We demonstrated that SALL1 functions as a tumor suppressor in breast cancer, which is significantly down-regulated in the basal like breast cancer and in estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2) triple negative breast cancer patients. SALL1 expression in human and murine breast cancer cells inhibited cancer cell growth and proliferation, metastasis, and promoted cell cycle arrest. Knockdown of SALL1 in breast cancer cells promoted cancer cell growth, proliferation, and colony formation. Our studies revealed that tumor suppression was mediated by recruitment of the Nucleosome Remodeling and Deacetylase (NuRD) complex by SALL1, which promoted cancer cell senescence. We further demonstrated that the mechanism of inhibition of breast cancer cell growth and invasion by SALL1-NuRD depends on the p38 MAPK, ERK1/2, and mTOR signaling pathways.
Our studies indicate that the developmental control gene SALL1 plays a critical role in tumor suppression by recruiting the NuRD complex and thereby inducing cell senescence in breast cancer cells.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The objectives of this tutorial are as follows: 1) to help students and researchers develop a basic understanding of how pulsed-power systems are used to create high-energy-density (HED) matter; 2) ...to develop a basic understanding of a new, compact, and efficient pulsed-power technology called linear transformer drivers (LTDs); 3) to understand why LTDs are an attractive technology for driving HED physics (HEDP) experiments; 4) to contrast LTDs with the more traditional Marx-generator/pulse-forming-line approach to driving HEDP experiments; and 5) to briefly review the history of LTD technology as well as some of the LTD-driven HEDP research presently underway at universities and research laboratories across the globe. This invited tutorial is part of the Mini-Course on Charged Particle Beams and High-Powered Pulsed Sources, held in conjunction with the 44th International Conference on Plasma Science in May of 2017.
Economic Modeling and Inference takes econometrics to a
new level by demonstrating how to combine modern economic theory
with the latest statistical inference methods to get the most out
of economic ...data. This graduate-level textbook draws applications
from both microeconomics and macroeconomics, paying special
attention to financial and labor economics, with an emphasis
throughout on what observations can tell us about stochastic
dynamic models of rational optimizing behavior and equilibrium.
Bent Jesper Christensen and Nicholas Kiefer show how parameters
often thought estimable in applications are not identified even in
simple dynamic programming models, and they investigate the roles
of extensions, including measurement error, imperfect control, and
random utility shocks for inference. When all implications of
optimization and equilibrium are imposed in the empirical
procedures, the resulting estimation problems are often
nonstandard, with the estimators exhibiting nonregular asymptotic
behavior such as short-ranked covariance, superconsistency, and
non-Gaussianity. Christensen and Kiefer explore these properties in
detail, covering areas including job search models of the labor
market, asset pricing, option pricing, marketing, and retirement
planning. Ideal for researchers and practitioners as well as
students, Economic Modeling and Inference uses real-world
data to illustrate how to derive the best results using a
combination of theory and cutting-edge econometric techniques.
Covers identification and estimation of dynamic programming
models
Treats sources of error--measurement error, random utility, and
imperfect control
Features financial applications including asset pricing, option
pricing, and optimal hedging
Describes labor applications including job search, equilibrium
search, and retirement
Illustrates the wide applicability of the approach using micro,
macro, and marketing examples
The cognitive impact of psychological trauma can manifest as a range of post-traumatic stress symptoms that are often attributed to impairments in learning from positive and negative outcomes, aka ...reinforcement learning. Research on the impact of trauma on reinforcement learning has mainly been inconclusive. This study aimed to circumscribe the impact of psychological trauma on reinforcement learning in the context of neural response in time and frequency domains. Two groups of participants were tested - those who had experienced psychological trauma and a control group who had not - while they performed a probabilistic classification task that dissociates learning from positive and negative feedback during a magnetoencephalography (MEG) examination. While the exposure to trauma did not exhibit any effects on learning accuracy or response time for positive or negative feedback, MEG cortical activity was modulated in response to positive feedback. In particular, the medial and lateral orbitofrontal cortices (mOFC and lOFC) exhibited increased activity, while the insular and supramarginal cortices showed decreased activity during positive feedback presentation. Furthermore, when receiving negative feedback, the trauma group displayed higher activity in the medial portion of the superior frontal cortex. The timing of these activity changes occurred between 160 and 600 ms post feedback presentation. Analysis of the time-frequency domain revealed heightened activity in theta and alpha frequency bands (4–10 Hz) in the lOFC in the trauma group. Moreover, dividing the two groups according to their learning performance, the activity for the non-learner subgroup was found to be lower in lOFC and higher in the supramarginal cortex. These differences were found in the trauma group only. The results highlight the localization and neural dynamics of feedback processing that could be affected by exposure to psychological trauma. This approach and associated findings provide a novel framework for understanding the cognitive correlates of psychological trauma in relation to neural dynamics in the space, time, and frequency domains. Subsequent work will focus on the stratification of cognitive and neural correlates as a function of various symptoms of psychological trauma. Clinically, the study findings and approach open the possibility for neuromodulation interventions that synchronize cognitive and psychological constructs for individualized treatment.
Protonation by carbonic acid H2CO3 of the strong base methylamine CH3NH2 in a neutral contact pair in aqueous solution is followed via Car–Parrinello molecular dynamics simulations. Proton transfer ...(PT) occurs to form an aqueous solvent-stabilized contact ion pair within 100 fs, a fast time scale associated with the compression of the acid–base hydrogen-bond (H-bond), a key reaction coordinate. This rapid barrierless PT is consistent with the carbonic acid-protonated base pK a difference that considerably favors the PT, and supports the view of intact carbonic acid as potentially important proton donor in assorted biological and environmental contexts. The charge redistribution within the H-bonded complex during PT supports a Mulliken picture of charge transfer from the nitrogen base to carbonic acid without altering the transferring hydrogen’s charge from approximately midway between that of a hydrogen atom and that of a proton.
Purpose of Review
Although benign, renal angiomyolipoma (AML) may lead to serious complications without appropriate management. The purpose of this review is to describe the role of and evidence for ...interventional radiology techniques in the management of patients with AML.
Recent Findings
For patients with renal masses and non-diagnostic imaging studies, image-guided percutaneous biopsy is found to be highly accurate and useful in directing patient management. Once the diagnosis of AML has been made based on either imaging or biopsy, arterial embolization of tumors that are symptomatic or >4 cm has been demonstrated to reduce the risk of hemorrhage as well as tumor size. Percutaneous ablation devices have been proposed as alternative strategies but remain investigational.
Summary
The utility of interventional radiology techniques including percutaneous core needle biopsy and prophylactic super-selective arterial embolization is safe and effective management strategies for patients presenting with AML tumors.
The Asian summer monsoon involves complex transport patterns with large-scale redistribution of trace gases in the upper troposphere and lower stratosphere (UTLS). We employ the global ...chemistry–climate model ECHAM5–HAMMOZ in order to evaluate the transport pathways and the contributions of nitrogen oxide species peroxyacetyl nitrate (PAN), NOx and HNO3 from various monsoon regions, to the UTLS over southern Asia and vice versa. Simulated long-term seasonal mean mixing ratios are compared with trace gas retrievals from the Michelson Interferometer for Passive Atmospheric Sounding aboard ENVISAT(MIPAS-E) and aircraft campaigns during the monsoon season (June–September) in order to evaluate the model's ability to reproduce these transport patterns. The model simulations show that there are three regions which contribute substantial pollution to the South Asian UTLS: the Asian summer monsoon (ASM), the North American monsoon (NAM) and the West African monsoon (WAM). However, penetration due to ASM convection reaches deeper into the UTLS compared to NAM and WAM outflow. The circulation in all three monsoon regions distributes PAN into the tropical latitude belt in the upper troposphere (UT). Remote transport also occurs in the extratropical UT where westerly winds drive North American and European pollutants eastward where they can become part of the ASM convection and lifted into the lower stratosphere. In the lower stratosphere the injected pollutants are transported westward by easterly winds. Sensitivity experiments with ECHAM5–HAMMOZ for simultaneous NOx and non-methane volatile organic compounds (NMVOCs) emission change (−10 %) over ASM, NAM and WAM confirm similar transport. Our analysis shows that a 10 % change in Asian emissions transports ~ 5–30 ppt of PAN in the UTLS over Asia, ~ 1–10 ppt of PAN in the UTLS of northern subtropics and mid-latitudes, ~ 7–10 ppt of HNO3 and ~ 1–2 ppb of ozone in UT over Asia. Comparison of emission change over Asia, North America and Africa shows that the highest transport of HNO3 and ozone occurs in the UT over Asia and least over Africa. The intense convective activity in the monsoon regions is associated with lightning and thereby the formation of additional NOx. This also affects the distribution of PAN in the UTLS. Simulations with and without lightning show an increase in the concentrations of PAN (~ 40 %), HNO3 (75 %), NOx (70 %) and ozone (30 %) over the regions of convective transport. Lightning-induced production of these species is higher over equatorial Africa and America compared to the ASM region. This indicates that the contribution of anthropogenic emissions to PAN in the UTLS over the ASM is higher than that of lightning.
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