Symmetry breaking phase transitions play an important role in nature. When a system traverses such a transition at a finite rate, its causally disconnected regions choose the new broken symmetry ...state independently. Where such local choices are incompatible, topological defects can form. The Kibble-Zurek mechanism predicts the defect densities to follow a power law that scales with the rate of the transition. Owing to its ubiquitous nature, this theory finds application in a wide field of systems ranging from cosmology to condensed matter. Here we present the successful creation of defects in ion Coulomb crystals by a controlled quench of the confining potential, and observe an enhanced power law scaling in accordance with numerical simulations and recent predictions. This simple system with well-defined critical exponents opens up ways to investigate the physics of non-equilibrium dynamics from the classical to the quantum regime.
Effective prevention of deaths due to human rabies is currently hampered by a lack of understanding of the scale of the problem, and the distribution of both animal and human cases across countries, ...regions and continents. Unfortunately, despite the severity of the disease, accurate data on which to assess these questions and to prioritize and direct public health interventions are not available for many parts of the world. This survey sought to understand the current global situation regarding the surveillance of human rabies. Data were collected from 91 countries across all continents and all categories of human rabies risk, generating the most complete and representative global data set currently available. Respondents were asked key questions about whether human rabies was a notifiable disease, how the surveillance system for human rabies operated and whether the respondent considered that the surveillance system was working effectively. Across the 91 countries from which data were collated, human rabies was a notifiable disease in all but eight. Despite international guidance, surveillance systems were very varied. Even where rabies is a notifiable disease, many countries had surveillance system judged to be ineffective, almost all of these being high and moderate rabies risk countries in Africa and Asia. Overall, 41% of the population covered by this survey (around 2.5 billion people) live in countries where there is no or ineffective rabies surveillance. The lack of robust surveillance is hindering rabies control efforts. However, whilst worldwide rabies surveillance would be improved if rabies were notifiable in all countries, many other challenges to the implementation of effective global human rabies surveillance systems remain.
We study experimentally and theoretically the properties of structural defects (kink solitons) in two-dimensional ion Coulomb crystals. We show how different types of kink solitons with different ...physical properties can be realized, and transformed from one type into another by varying the aspect ratio of the trap confinement. Further, we discuss how impurities in ion Coulomb crystals, such as mass defects, can modify the dynamics of kink creation and their stability. For both pure and impure crystals, the experimentally observed kink dynamics are analysed in detail and explained theoretically by numerical simulations and calculations of the Peierls-Nabarro potential. Finally, we demonstrate that static electric fields provide a handle to vary the influence of mass defects on kinks in a controlled way and allow for deterministic manipulation and creation of kinks.
Abstract
Background: WISDOM is a 100,000 healthy women preference-tolerant, pragmatic study comparing annual to personalized risk-based breast screening. The novelty of WISDOM personalized screening ...is the integration of previously validated genetic and clinical risk factors (age, family history, breast biopsy results, ethnicity, mammographic density) into a single risk assessment model that directs the starting age, timing, and frequency of screening. The goal of WISDOM is to determine if personalized screening, compared to annual screening, is as safe, less morbid, enables prevention, and is preferred by women. The study is registered on ClinicalTrials.gov, NCT02620852.
Methods: Women aged 40-74 years with no history of breast cancer or DCIS, and no previous double mastectomy can join the study online at wisdomstudy.org. Participants can elect randomization or self-select a study arm, and provide electronic consent and Release for Medical Information using DocuSign. For all participants, 5-year risk of developing breast cancer is calculated according to the Breast Cancer Screening Consortium (BCSC) model. Participants in the personalized arm undergo panel-based mutation testing, and their 5-year risk is calculated using the BCSC score combined with a Polygenic Risk Score (BCSC-PRS) that includes 75 single nucleotide polymorphisms (SNPs, increase to 229) known to increase breast cancer risk. SNPs and mutations (BRCA1, BRCA2, TP53, PTEN, STK11, CDH1, ATM, PALB2, and CHEK2) are assessed by saliva-based testing through Color Genomics. 5-year risk level thresholds are used to stratify for low-, moderate- and high risk. Risk stratification determines age to start, stop, and frequency of screening.
Enrollment: As of July 2018, the WISDOM study is open to all eligible women in California, North Dakota, South Dakota, Minnesota and Iowa. To date, 23,329 eligible women have registered and 14,393 women have consented to participate in the trial. We analyzed 3,255 participants who have completed risk assessment in the personalized arm. The median age was 56 years. 82% were Caucasian, 1% African-American, and 6% Asian. 9% self-reported as Hispanic. We are partnering with health insurers and self-insured companies using coverage with evidence progression. To strengthen generalizability, we are expanding to other states. WISDOM enrollment will continue past 2019.
Feasibility: To evaluate the addition of PRS, we used paired statistical tests (McNemar) to compare the distributions of BCSC, and BCSC-PRS risk estimates around low-risk (<1.3%), and very-high risk (>6%) thresholds, the latter corresponding to 5-year risk of a BRCA mutation carrier. The median 5-year risk was 1.5% (IQR 1.0-2.1%) using the BCSC model, and 1.4% (IQR 0.8-2.5%) using the BCSC-PRS model. The BCSC-PRS model classified more women into the low (<1%) and very high (≥6%) risk categories compared to the BCSC model (p < 0.001).
Conclusions: Our findings demonstrate that incorporating genetic variants into a validated clinical model is feasible and impacts risk classification compared to a model without genetic risk factors. Results at 5 years will reveal if this classification improves healthcare value by reducing screen volumes and costs without jeopardizing outcomes.
Citation Format: Acerbi I, Shieh Y, Madlensky L, Tice J, Ziv E, Eklund M, Blanco A, DeRosa D, Tong B, Goodman D, Nassereddine L, Anderson N, Harvey H, Layton T, Park HL, Petruse A, Stewart S, Wernisch J, Risty L, Koenig B, Sarrafan S, Firouzian R, Kaplan C, Hiatt R, Parker BA, Wenger N, Lee V, Heditsian D, Brain S, Stover Fiscalini A, Borowsky AD, Anton-Culver H, Naeim A, Kaster A, Talley M, van 't Veer LJ, LaCroix A, Wisdom Study and Athena Breast Health Network Investigators and Advocate Partners, Esserman LJ. Personalized breast cancer screening in a population based study: Women Informed to Screen Depending On Measures of risk (WISDOM) abstract. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT2-08-01.
Abstract
The United States Preventive Services Task Force recommends that women who are at increased risk for breast cancer and at low risk for adverse medication effects should be offered ...risk-reducing medications, such as tamoxifen or raloxifene, by their clinicians. In addition, the National Comprehensive Cancer Network recommends risk counseling for women with a 5-year risk of ≥1.7% as calculated by the NCI-developed Breast Cancer Risk Assessment Tool (BCRAT, based on the Gail model) or other risk model. Thus, breast cancer risk assessment is important for the identification of women at "high risk" who should be offered risk counseling and potentially intervention. The Athena Breast Health Network, which has served >120,000 breast screening patients across California and the midwest, has integrated breast cancer risk assessment into its clinical breast screening programs. The goal of our study was to characterize breast cancer risk for >10,000 mammography patients in the University of California Irvine Athena Breast Health Network, overall and by race/ethnicity, using several different risk models, including the BCRAT, BCSC, and IBIS models. Our cohort was comprised of 47% non-Hispanic White, 13% non-Hispanic Asian, 38% Hispanic, and 2% women of other race/ethnicities. Using data collected from electronic medical records and self-completed questionnaires, we determined that, as expected, non-Hispanic White and Asian women had higher breast cancer risk scores than Hispanic women for all risk models (5-year risks = 1.51-1.68% and 1.22-1.40% vs. 0.95-1.05%, respectively). In addition, when women were categorized as "increased risk" according to a given risk model if their 5-year risk score was ≥1.7%, the percentages of women at "increased risk" were higher in White women (26.5–42.2%) than in Asian (15.8–28.6%) and Hispanic (6.2–10.7%) women. However, the correlations between risk models were low to moderate in our cohort, overall (Pearson's r = 0.47-0.62) and especially for Asian women (Pearson's r = 0.29-0.49). Our results indicate that using only one risk model in a clinical breast cancer risk assessment program to identify "high risk" women would miss a significant proportion of women who would have been considered "high risk" according to another risk model. Conversely, some women who are identified as "high risk" according to one model may not need risk counseling and intervention since they are not considered "high risk" according to two other models. As our cohort expands and incident breast cancers occur, we will be able to determine which risk model or combination of risk models will have the highest discriminatory accuracy for predicting breast cancer risk in women of different race/ethnicities, which will enable our risk assessment programs to have a more targeted approach to risk counseling and intervention.
Citation Format: Park HL, Columbus A, Athena Breast Health Network Investigators and Advocate Partners, Kelly R, Alvarez A, Goodman D, Larsen K, Ziogas A, Anton-Culver H. Breast cancer risk assessment in a multiethnic patient population abstract. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-09-07.
As relative systematic frequency uncertainties in trapped-ion spectroscopy are approaching the low \(10^{-18}\) range, motional frequency shifts account for a considerable fraction of the uncertainty ...budget. Micromotion, a driven motion fundamentally connected to the principle of the Paul trap, is a particular concern in these systems. In this article, we experimentally investigate at this level three common methods for minimizing and determining the micromotion amplitude. We develop a generalized model for a quantitative application of the photon-correlation technique, which is applicable in the commonly encountered regime where the transition linewidth is comparable to the rf drive frequency. We show that a fractional frequency uncertainty due to the 2nd-order Doppler shift below \(1\times 10^{-20}\) can be achieved. The quantitative evaluation is verified in an interleaved measurement with the conceptually simpler resolved sideband method. If not performed deep within the Lamb-Dicke regime, a temperature-dependent offset at the level of \(10^{-19}\) is observed in resolved sideband measurements due to sampling of intrinsic micromotion. By direct comparison with photon-correlation measurements, we show that the simple to implement parametric heating method is sensitive to micromotion at the level of \(1\times 10^{-20}\) as well.
Intermediate-risk patients with aortic stenosis were randomly assigned to undergo either transcatheter or surgical aortic-valve replacement. At 5 years, there was no significant difference between ...the two groups in the incidence of death or disabling stroke. The incidence of aortic regurgitation was higher with transcatheter AVR.
In a cluster-randomized trial conducted in five ICUs, a nurse-led family-support intervention did not affect surrogates’ scores for anxiety and depression 6 months after the patients’ ...hospitalization, but it improved surrogates’ ratings of the patient-centeredness of care.
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