Offering payment to clinical research subjects, in an effort to enhance recruitment by providing an incentive to take part or enabling subjects to participate without financial sacrifice, is a common ...yet uneven and contentious practice in the US. Concern exists regarding the potential for payment to unduly influence participation and thus obscure risks, impair judgment, or encourage misrepresentation. Heightening these concerns is the participation not only of adults but also of children in pediatric research trials. Thorough assessment of risks, careful eligibility screening, and attention to a participant's freedom to refuse all serve to reduce the possibility of compensation adversely affecting the individual and/or the study. Institutional review boards currently evaluate payment proposals with minimal guidance from federal regulations. Here, reasons for providing payment, payment models, ethical concerns, and areas for further research are examined.
We present ALMA observations of the 0.88 millimeter dust continuum and the 13CO and C18O J = 3-2 line emission of the circumbinary disk HD 142527 at a spatial resolution of ∼0 25. This system is ...characterized by a large central cavity of roughly 120 au in radius, and asymmetric dust and gas emission. By comparing the observations with theoretical models, we find that the azimuthal variations in gas and dust density reach a contrast of 54 for dust grains and 3.75 for CO molecules, with an extreme gas-to-dust ratio of 1.7 on the dust crescent. We point out that caution is required in interpreting continuum-subtracted maps of the line emission, as this process might result in removing a large fraction of the line emission. Radially, we find that both the gas and dust surface densities can be described by Gaussians, centered at the same disk radius, and with gas profiles wider than those for dust. These results strongly support a scenario in which millimeter dust grains are radially and azimuthally trapped toward the center of a gas pressure bump. Finally, our observations reveal a compact source of continuum and CO emission inside the dust-depleted cavity ∼50 au from the primary star. The kinematics of the CO emission from this region is different from that expected from material in Keplerian rotation around the binary system, and might instead trace a compact disk around a third companion. Higher angular resolution observations are required to investigate the nature of this source.
The spiraling cost of cancer care, in particular the cost of cancer therapeutics that achieve only marginal benefits, is under increasing scrutiny. Although health-care professionals avoid putting a ...value on a life, our limited resources require that society address what counts as a benefit, the extent to which cost should factor in deliberations, and who should be involved in these decisions. Professional societies, such as the American Society of Clinical Oncology, government agencies, including the Food and Drug Administration, and insurance companies should be involved. However, no segment of society is better qualified to address these issues than the oncology community. Oncologists must offer clear guidance for the conduct of research, interpretation of results, and prescription of chemotherapies. We review recent drug approvals and clinical trials and comment on their relevance to the issue of the spiraling cost of oncology therapeutics. We suggest some standards that would serve as a starting point for addressing these issues.
We present Atacama Large Millimeter Array observations at an angular resolution of 0 1-0 2 of the disk surrounding the young Herbig Ae star MWC 758. The data consist of images of the dust continuum ...emission recorded at 0.88 millimeter, as well as images of the 13CO and C18O J = 3-2 emission lines. The dust continuum emission is characterized by a large cavity of roughly 40 au in radius which might contain a mildly inner warped disk. The outer disk features two bright emission clumps at radii of ∼47 and 82 au that present azimuthal extensions and form a double-ring structure. The comparison with radiative transfer models indicates that these two maxima of emission correspond to local increases in the dust surface density of about a factor 2.5 and 6.5 for the south and north clumps, respectively. The optically thick 13CO peak emission, which traces the temperature, and the dust continuum emission, which probes the disk midplane, additionally reveal two spirals previously detected in near-IR at the disk surface. The spirals seen in the dust continuum emission present, however, a slight shift of a few au toward larger radii and one of the spirals crosses the south dust clump. Finally, we present different scenarios to explain the complex structure of the disk.
This study investigates the geography of racial disparities in low birthweight in New York City by focusing on racial residential segregation and its effect on the risk of low birthweight among ...African-American infants and mothers. This cross-sectional multilevel analysis uses birth records at the individual level (
n=96,882) and racial isolation indices at the census tract or neighborhood level (
n=2095) to measure their independent and cross-level effects on low birthweight. This study found that residential segregation and neighborhood poverty operate at different scales to increase the risk of low birthweight. At the neighborhood scale residential segregation is positively and significantly associated with low birthweight, after controlling for individual-level risk factors and neighborhood poverty. Residential segregation explains neighborhood variation in low birthweight means and race effects across census tracts, which cannot be accounted for by neighborhood poverty alone. At the individual scale-increasing levels of residential segregation does not significantly reduce or exacerbate individual-level risk factors for low birthweight; whereas increasing levels of neighborhood poverty significantly eliminates the race effect and reduces the protective effect of being foreign-born on low birthweight, after controlling for other individual-level risk factors and residential segregation. These findings are contradictory to previous health research that shows protective mechanisms associated with ethnic density in local areas. It is likely that structural factors underlying residential segregation, i.e., racial isolation, impose additional stressors on African-American women that may offset or disguise positive attributes associated with ethnic density. However, as poverty is concentrated within these neighborhoods, differences between races in low birthweight cease to exist. This study demonstrates that residential segregation and neighborhood poverty are important determinants of racial disparity in low birthweight in New York City.
The currently available comprehensive activated sludge models, ASM#1 (Grady et al., 1986) and its successor ASM#3 (Gujer et al., 1999), do not adequately describe nitrification and denitrification, ...with respect to ammonia oxidation inhibition, nitrite accumulation, or emissions of nitric oxide and nitrous oxide. A new comprehensive activated sludge process model, the Activated Sludge Model for Nitrogen (ASMN), is presented. The ASMN incorporates two nitrifying populations—ammoniaoxidizing bacteria and nitrite-oxidizing bacteria—using free ammonia and free nitrous acid, respectively, as their true substrates. The ASMN incorporates four-step denitrification (sequential reduction of nitrate to nitrogen gas via nitrite, nitric oxide, and nitrous oxide) using individual, reaction-specific parameters. Simulation results for ammonia, nitrate, soluble substrate, and biomass concentrations determined by using ASMN for three activated sludge process configurations under steady-state and dynamic municipal-type influent conditions are shown to be comparable with ASM#1 results.
Although the general population in China is physically active, only 45% of older adults meet the World Health Organization's recommendation for weekly moderate-to-vigorous exercise, to achieve health ...benefits. This percentage is even lower (9.8%) in urban China. It is, therefore, important to understand the pathways by which physical activity behaviors are impacted by the built environment. This study utilized a mixed methods approach—interviews (n = 42) and longitudinal (2010–2015) health survey data (n = 3094) for older people residing in three neighborhoods in Huainan, a mid-sized city in Anhui Province, central eastern China. First, a content analysis of interview data was used to identify individual and built environment factors (motivators and barriers) that impacted physical activity within older people's activity spaces. Second, a multilevel path analysis was conducted using the health survey data to demonstrate the pathways by which these motivators and barriers contributed to the initiation, regulation, and maintenance of physical activity. This study found (a) that the liveliness of an apartment building and its proximity to functional spaces (fast-food stores, farmer's markets, supermarkets, pharmacies, schools, hospitals, PA facilities and natural and man-made water bodies) were important factors in attracting sedentary older people to initiate physical activity; (b) the social networks of apartment neighbors helped to initiate, regulate, and maintain physical activity; and housing closeness to functional spaces was important in maintaining physical activity, particularly for those older people with chronic diseases. To increase older people's overall physical activity, future interventions should focus on residential form and access to functional spaces, prior to investing in large-scale urban design interventions.
•Sedentary people in lively apartments were more likely to initiate physical activity.•Physically active neighbors helped regulate/maintain individual physical activity.•Living close to functional spaces helped older people maintain physical activity.•Improving residential form and access to services can promote physical activity.
The architectural protein CTCF is a mediator of chromatin conformation, but how CTCF binding to DNA is orchestrated to maintain long-range gene expression is poorly understood. Here we perform RNAi ...knockdown to reduce CTCF levels and reveal a shared subset of CTCF-bound sites are robustly resistant to protein depletion. The 'persistent' CTCF sites are enriched at domain boundaries and chromatin loops constitutive to all cell types. CRISPR-Cas9 deletion of 2 persistent CTCF sites at the boundary between a long-range epigenetically active (LREA) and silenced (LRES) region, within the Kallikrein (KLK) locus, results in concordant activation of all 8 KLK genes within the LRES region. CTCF genome-wide depletion results in alteration in Topologically Associating Domain (TAD) structure, including the merging of TADs, whereas TAD boundaries are not altered where persistent sites are maintained. We propose that the subset of essential CTCF sites are involved in cell-type constitutive, higher order chromatin architecture.
Endocrine therapy resistance frequently develops in estrogen receptor positive (ER+) breast cancer, but the underlying molecular mechanisms are largely unknown. Here, we show that 3-dimensional (3D) ...chromatin interactions both within and between topologically associating domains (TADs) frequently change in ER+ endocrine-resistant breast cancer cells and that the differential interactions are enriched for resistance-associated genetic variants at CTCF-bound anchors. Ectopic chromatin interactions are preferentially enriched at active enhancers and promoters and ER binding sites, and are associated with altered expression of ER-regulated genes, consistent with dynamic remodelling of ER pathways accompanying the development of endocrine resistance. We observe that loss of 3D chromatin interactions often occurs coincidently with hypermethylation and loss of ER binding. Alterations in active A and inactive B chromosomal compartments are also associated with decreased ER binding and atypical interactions and gene expression. Together, our results suggest that 3D epigenome remodelling is a key mechanism underlying endocrine resistance in ER+ breast cancer.
Herbig Ae/Be stars are intermediate-mass pre-main sequence stars surrounded by circumstellar dust disks. Some are observed to produce jets, whose appearance as a sequence of shock fronts (knots) ...suggests a past episodic outflow variability. This “jet fossil record” can be used to reconstruct the outflow history. We present the first optical to near-infrared (NIR) spectra of the jet from the Herbig Ae star HD 163296, obtained with VLT/X-shooter. We determine the physical conditions in the knots and also their kinematic “launch epochs”. Knots are formed simultaneously on either side of the disk, with a regular interval of ~16 yr. The velocity dispersion versus jet velocity and the energy input are comparable between both lobes. However, the mass-loss rate, velocity,and shock conditions are asymmetric. We find Ṁjet/Ṁacc ~ 0.01−0.1, which is consistent with magneto-centrifugal jet launching models. No evidence of any dust is found in the high-velocity jet, suggesting a launch region within the sublimation radius (<0.5 au). The jet inclination measured from proper motions and radial velocities confirms that it is perpendicular to the disk. A tentative relation is found between the structure of the jet and the photometric variability of the central source. Episodes of NIR brightening were previously detected and attributed to a dusty disk wind. We report for the first time significant optical fadings lasting from a few days up to a year, coinciding with the NIR brightenings. These are very likely caused by dust lifted high above the disk plane, and this supports the disk wind scenario. The disk wind is launched at a larger radius than the high-velocity atomic jet, although their outflow variability may have a common origin. No significant relation between outflow and accretion variability could be established. Our findings confirm that this source undergoes periodic ejection events, which may be coupled with dust ejections above the disk plane.
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