Large-scale arrays of quantum-dot spin qubits in Si/SiGe quantum wells require large or tunable energy splittings of the valley states associated with degenerate conduction band minima. Existing ...proposals to deterministically enhance the valley splitting rely on sharp interfaces or modifications in the quantum well barriers that can be difficult to grow. Here, we propose and demonstrate a new heterostructure, the "Wiggle Well", whose key feature is Ge concentration oscillations inside the quantum well. Experimentally, we show that placing Ge in the quantum well does not significantly impact our ability to form and manipulate single-electron quantum dots. We further observe large and widely tunable valley splittings, from 54 to 239 μeV. Tight-binding calculations, and the tunability of the valley splitting, indicate that these results can mainly be attributed to random concentration fluctuations that are amplified by the presence of Ge alloy in the heterostructure, as opposed to a deterministic enhancement due to the concentration oscillations. Quantitative predictions for several other heterostructures point to the Wiggle Well as a robust method for reliably enhancing the valley splitting in future qubit devices.
We present improved black hole masses for 35 active galactic nuclei (AGNs) based on a complete and consistent reanalysis of broad emission-line reverberation-mapping data. From objects with multiple ...line measurements, we find that the highest precision measure of the virial product c tau Delta V super(2)/G, where tau is the emission-line lag relative to continuum variations and Delta V is the emission-line width, is obtained by using the cross-correlation function centroid (as opposed to the cross-correlation function peak) for the time delay and the line dispersion (as opposed to FWHM) for the line width and by measuring the line width in the variable part of the spectrum. Accurate line-width measurement depends critically on avoiding contaminating features, in particular the narrow components of the emission lines. We find that the precision (or random component of the error) of reverberation-based black hole mass measurements is typically around 30%, comparable to the precision attained in measurement of black hole masses in quiescent galaxies by gas or stellar dynamical methods. Based on results presented in a companion paper by Onken et al., we provide a zero-point calibration for the reverberation-based black hole mass scale by using the relationship between black hole mass and host-galaxy bulge velocity dispersion. The scatter around this relationship implies that the typical systematic uncertainties in reverberation-based black hole masses are smaller than a factor of 3. We present a preliminary version of a mass-luminosity relationship that is much better defined than any previous attempt. Scatter about the mass-luminosity relationship for these AGNs appears to be real and could be correlated with either Eddington ratio or object inclination.
Each decade, the American Heart Association (AHA) develops an Impact Goal to guide its overall strategic direction and investments in its research, quality improvement, advocacy, and public health ...programs. Guided by the AHA’s new Mission Statement, to be a relentless force for a world of longer, healthier lives, the 2030 Impact Goal is anchored in an understanding that to achieve cardiovascular health for all, the AHA must include a broader vision of health and well-being and emphasize health equity. In the next decade, by 2030, the AHA will strive to equitably increase healthy life expectancy beyond current projections, with global and local collaborators, from 66 years of age to at least 68 years of age across the United States and from 64 years of age to at least 67 years of age worldwide. The AHA commits to developing additional targets for equity and well-being to accompany this overarching Impact Goal. To attain the 2030 Impact Goal, we recommend a thoughtful evaluation of interventions available to the public, patients, providers, healthcare delivery systems, communities, policy makers, and legislators. This presidential advisory summarizes the task force’s main considerations in determining the 2030 Impact Goal and the metrics to monitor progress. It describes the aspiration that these goals will be achieved by working with a diverse community of volunteers, patients, scientists, healthcare professionals, and partner organizations needed to ensure success.
STUDY QUESTION
Do reproductive risk factor associations differ across subgroups of invasive epithelial ovarian cancer (EOC) defined by the dualistic model (type I/II) or a histologic pathway-based ...classification?
SUMMARY ANSWER
Associations with parity, history of endometriosis, tubal ligation and hysterectomy were found to differ in the context of the type I/II and the histologic pathways classification of ovarian cancer.
WHAT IS KNOWN ALREADY
Shared molecular alterations and candidate precursor lesions suggest that tumor histology and grade may be used to classify ovarian tumors into likely etiologic pathways.
DESIGN
This case–control study included 1571 women diagnosed with invasive EOC and 2100 population-based controls that were enrolled from 1992 to 2008. Reproductive risk factors as well as other putative risk factors for ovarian cancer were assessed through in-person interviews.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Eligible cases were diagnosed with incident ovarian cancer, were aged 18 and above and resided in eastern Massachusetts or New Hampshire, USA. Controls were identified through random digit dialing, drivers' license and town resident lists and were frequency matched with the cases based on age and study center.
MAIN RESULTS AND THE ROLE OF CHANCE
We used polytomous logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for type I/II EOC or using a pathway-based grouping of histologic subtypes. In multivariate analyses, we observed that having a history of endometriosis (OR = 1.92, 95% CI: 1.36–2.71) increased the risk for a type I tumor. Factors that were strongly inversely associated with risk for a type I tumor included parity (≥3 versus 0 children, OR = 0.15, 95% CI: 0.11–0.21), having a previous tubal ligation (OR = 0.40, 95% CI: 0.26–0.60) and more weakly hysterectomy (OR = 0.71, 95% CI: 0.45–1.13). In analyses of histologic pathways, parity (≥3 versus 0 children, OR = 0.13, 95% CI: 0.10–0.18) and having a previous tubal ligation (OR = 0.41, 95% CI: 0.28–0.60) or hysterectomy (OR = 0.54, 95% CI: 0.34–0.86) were inversely associated with risk of endometrioid/clear cell tumors. Having a history of endometriosis strongly increased the risk for endometrioid/clear cell tumors (OR = 2.41, 95% CI: 1.78–3.26). We did not observe significant differences in the risk associations across these tumor classifications for age at menarche, menstrual cycle length or infertility.
LIMITATIONS, REASONS FOR CAUTION
A potential limitation of this study is that dividing the cases into subgroups may limit the power of these analyses, particularly for the less common tumor types. Since cases were enrolled after their diagnosis, it is possible that the most aggressive cases were not included in the study.
WIDER IMPLICATIONS OF THE FINDINGS
This study provides insights about the role of reproductive factors in relation to risk of pathway-based subgroups of ovarian cancer that with further confirmation may assist with the development of improved strategies for the prevention of these different tumor types.
STUDY FUNDING/COMPETING INTEREST(S)
This research is funded by grants from the National Cancer Institute, the Department of Defense Ovarian Cancer Research Program and the Ovarian Cancer Research Fund. The authors have no competing interests to declare.
TRIAL REGISTRATION NUMBER
Not applicable.
Objective To determine safety and pharmacodynamics/efficacy of teduglutide in children with intestinal failure associated with short bowel syndrome (SBS-IF). Study design This 12-week, open-label ...study enrolled patients aged 1-17 years with SBS-IF who required parenteral nutrition (PN) and showed minimal or no advance in enteral nutrition (EN) feeds. Patients enrolled sequentially into 3 teduglutide cohorts (0.0125 mg/kg/d n = 8, 0.025 mg/kg/d n = 14, 0.05 mg/kg/d n = 15) or received standard of care (SOC, n = 5). Descriptive summary statistics were used. Results All patients experienced ≥1 treatment-emergent adverse event; most were mild or moderate. No serious teduglutide-related treatment-emergent adverse events occurred. Between baseline and week 12, prescribed PN volume and calories (kcal/kg/d) changed by a median of −41% and −45%, respectively, with 0.025 mg/kg/d teduglutide and by −25% and −52% with 0.05 mg/kg/d teduglutide. In contrast, PN volume and calories changed by 0% and −6%, respectively, with 0.0125 mg/kg/d teduglutide and by 0% and −1% with SOC. Per patient diary data, EN volume increased by a median of 22%, 32%, and 40% in the 0.0125, 0.025, and 0.05 mg/kg/d cohorts, respectively, and by 11% with SOC. Four patients achieved independence from PN, 3 in the 0.05 mg/kg/d cohort and 1 in the 0.025 mg/kg/d cohort. Study limitations included its short-term, open-label design, and small sample size. Conclusions Teduglutide was well tolerated in pediatric patients with SBS-IF. Teduglutide 0.025 or 0.05 mg/kg/d was associated with trends toward reductions in PN requirements and advancements in EN feeding in children with SBS-IF. Trial registration ClinicalTrials.gov: NCT01952080 ; EudraCT: 2013-004588-30.
The energies of valley-orbit states in silicon quantum dots are determined by an as yet poorly understood interplay between interface roughness, orbital confinement, and electron interactions. Here, ...we report measurements of one- and two-electron valley-orbit state energies as the dot potential is modified by changing gate voltages, and we calculate these same energies using full configuration interaction calculations. The results enable an understanding of the interplay between the physical contributions and enable a new probe of the quantum well interface.
Nematicity is ubiquitous in electronic phases of high-T_{c} superconductors, particularly in the Fe-based systems. We used inelastic x-ray scattering to extract the temperature-dependent nematic ...correlation length ξ from the anomalous softening of acoustic phonon modes in FeSe, underdoped Ba(Fe_{0.97}Co_{0.03})_{2}As_{2}, and optimally doped Ba(Fe_{0.94}Co_{0.06})_{2}As_{2}. In all cases, we find that ξ is well described by a power law (T-T_{0})^{-1/2} extending over a wide temperature range. Combined with the previously reported Curie-Weiss behavior of the nematic susceptibility, these results point to the mean-field character of the nematic transition, which we attribute to a sizable nematoelastic coupling that is likely detrimental to superconductivity.
The involvement of host immunity in the gut microbiota-mediated colonization resistance to Clostridioides difficile infection (CDI) is incompletely understood. Here, we show that interleukin (IL)-22, ...induced by colonization of the gut microbiota, is crucial for the prevention of CDI in human microbiota-associated (HMA) mice. IL-22 signaling in HMA mice regulated host glycosylation, which enabled the growth of succinate-consuming bacteria Phascolarctobacterium spp. within the gut microbiome. Phascolarctobacterium reduced the availability of luminal succinate, a crucial metabolite for the growth of C. difficile, and therefore prevented the growth of C. difficile. IL-22-mediated host N-glycosylation is likely impaired in patients with ulcerative colitis (UC) and renders UC-HMA mice more susceptible to CDI. Transplantation of healthy human-derived microbiota or Phascolarctobacterium reduced luminal succinate levels and restored colonization resistance in UC-HMA mice. IL-22-mediated host glycosylation thus fosters the growth of commensal bacteria that compete with C. difficile for the nutritional niche.
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