Adult Comorbidity Evaluation 27 score as a predictor of survival in endometrial cancer patients

BACKGROUND The incidence of endometrial cancer increases with age and is associated with medical comorbidities such as obesity and diabetes. While a few cohort studies of less than 500 patients showed an association between comorbidity and survival in endometrial cancer patients, the degree of association needs to be better described. The Adult Comorbidity Evaluation 27 (ACE-27) is a validated comorbidity instrument that provides a score (0–3) based on the number and severity of medical comorbidities. OBJECTIVE This study was performed to explore the association between medical comorbidities and survival of endometrial cancer patients. STUDY DESIGN Patients diagnosed with endometrial cancer from 2000–2012 were identified from the prospectively maintained Siteman Cancer Center tumor registry. Patients undergoing primary surgical treatment for endometrioid, serous and clear cell endometrial carcinoma were included. Patients primarily treated with radiation, chemotherapy or hormone therapy were excluded. Patients with uterine sarcomas or neuroendocrine tumors were excluded. Patients with missing ACE-27 scores were also excluded from analysis. Information including patient demographics, ACE-27 score, tumor characteristics, adjuvant treatment and survival data were extracted from the database. The association of ACE-27 and overall as well as recurrence-free survival was explored in a multivariable Cox regression analysis after controlling for variables found to be significantly associated with survival in univariable analysis. RESULTS A total of 2073 patients with a median age of 61 years (range 20–94) at diagnosis were identified. ACE-27 score was 0, 1, 2 and 3 in 22%, 38%, 28% and 12% of patients, respectively. Stage distribution was I (73%), II (5%), III (15%) and IV (7%) and grade distribution was 1 (52%), 2 (23%) and 3 (25%). Most patients had endometrioid histology (87%) followed by serous (11%) and clear cell (3%). The median OS for the entire cohort was 54 months [95% confidence interval (CI) 3, 154 months] and median PFS was 50 months [95% CI 2, 154 months]., On univariable analysis, age, race, marital status, stage, grade, histology and treatment type were significantly associated with overall survival and recurrence-free survival. After adjusting for these covariates, patients with ACE-27 score of 2 had a 52% higher risk of death [95% CI 1.16, 2.00] and patients with ACE-27 score of 3 had a 2.35-fold increased risk of death [95% CI 1.73, 3.21] compared to patients with an ACE-27 score of 0. Similarly, patients with ACE-27 score of 2 had a 38% higher risk of recurrence [95% CI 1.07, 1.78] and patients with ACE-27 score of 3 had a 2.05-fold increased risk of recurrence [95% CI 1.53, 2.75] compared to patients with an ACE-27 score of 0. We found no interaction between ACE-27 score and age, stage or treatment type. CONCLUSIONS Our findings demonstrate the importance of comorbidities in estimating the prognosis of endometrial cancer patients, even after adjusting for age and known tumor-specific prognostic factors like stage, grade, histology and adjuvant treatment

Blood pressure monitoring in high-risk pregnancy to improve the detection and monitoring of hypertension (the BUMP 1 and 2 trials): protocol for two linked randomised controlled trials.

INTRODUCTION: Self-monitoring of blood pressure (BP) in pregnancy could improve the detection and management of pregnancy hypertension, while also empowering and engaging women in their own care. Two linked trials aim to evaluate whether BP self-monitoring in pregnancy improves the detection of raised BP during higher risk pregnancies (BUMP 1) and whether self-monitoring reduces systolic BP during hypertensive pregnancy (BUMP 2). METHODS AND ANALYSES: Both are multicentre, non-masked, parallel group, randomised controlled trials. Participants will be randomised to self-monitoring with telemonitoring or usual care. BUMP 1 will recruit a minimum of 2262 pregnant women at higher risk of pregnancy hypertension and BUMP 2 will recruit a minimum of 512 pregnant women with either gestational or chronic hypertension. The BUMP 1 primary outcome is the time to the first recording of raised BP by a healthcare professional. The BUMP 2 primary outcome is mean systolic BP between baseline and delivery recorded by healthcare professionals. Other outcomes will include maternal and perinatal outcomes, quality of life and adverse events. An economic evaluation of BP self-monitoring in addition to usual care compared with usual care alone will be assessed across both study populations within trial and with modelling to estimate long-term cost-effectiveness. A linked process evaluation will combine quantitative and qualitative data to examine how BP self-monitoring in pregnancy is implemented and accepted in both daily life and routine clinical practice. ETHICS AND DISSEMINATION: The trials have been approved by a Research Ethics Committee (17/WM/0241) and relevant research authorities. They will be published in peer-reviewed journals and presented at national and international conferences. If shown to be effective, BP self-monitoring would be applicable to a large population of pregnant women. TRIAL REGISTRATION NUMBER: NCT03334149.This work is funded from a National Institute for Health Research (NIHR) Programme grant for applied research (RP-PG- 1209-10051) and an NIHR Professorship awarded to RJM (NIHR-RP- R2- 12-015). RJM and KLT receive funding from the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care Oxford at Oxford Health NHS Foundation Trust. JS is a National Institute for Health Research (NIHR) Senior Investigator and supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care South London (NIHR CLAHRC South London) at King’s College Hospital NHS Foundation Trust. Service support costs will be administered through the NIHR Clinical Research Network

Development of the Migrant Friendly Maternity Care Questionnaire (MFMCQ) for migrants to Western societies: an international Delphi consensus process

Background Through the World Health Assembly Resolution, ‘Health of Migrants’, the international community has identified migrant health as a priority. Recommendations for general hospital care for international migrants in receiving-countries have been put forward by the Migrant Friendly Hospital Initiative; adaptations of these recommendations specific to maternity care have yet to be elucidated and validated. We aimed to develop a questionnaire measuring migrant-friendly maternity care (MFMC) which could be used in a range of maternity care settings and countries. Methods This study was conducted in four stages. First, questions related to migrant friendly maternity care were identified from existing questionnaires including the Migrant Friendliness Quality Questionnaire, developed in Europe to capture recommended general hospital care for migrants, and the Mothers In a New Country (MINC) Questionnaire, developed in Australia and revised for use in Canada to capture the maternity care experiences of migrant women, and combined to create an initial MFMC questionnaire. Second, a Delphi consensus process in three rounds with a panel of 89 experts in perinatal health and migration from 17 countries was undertaken to identify priority themes and questions as well as to clarify wording and format. Third, the draft questionnaire was translated from English to French and Spanish and back-translated and subsequently culturally validated (assessed for cultural appropriateness) by migrant women. Fourth, the questionnaire was piloted with migrant women who had recently given birth in Montreal, Canada. Results A 112-item questionnaire on maternity care from pregnancy, through labour and birth, to postpartum care, and including items on maternal socio-demographic, migration and obstetrical characteristics, and perceptions of care, has been created - the Migrant Friendly Maternity Care Questionnaire (MFMCQ) – in three languages (English, French and Spanish). It is completed in 45 minutes via interview administration several months post-birth. Conclusions A 4-stage process of questionnaire development with international experts in migrant reproductive health and research resulted in the MFMCQ, a questionnaire measuring key aspects of migrant-sensitive maternity care. The MFMCQ is available for further translation and use to examine and compare care and perceptions of care within and across countries, and by key socio-demographic, migration, and obstetrical characteristics of migrant women

Rational selection of syngeneic preclinical tumor models for immunotherapeutic drug discovery

Murine syngeneic tumor models are critical to novel immuno-based therapy development, but the molecular and immunologic features of these models are still not clearly defined. The translational relevance of differences between the models is not fully understood, impeding appropriate preclinical model selection for target validation, and ultimately hindering drug development. Across a panel of commonly used murine syngeneic tumor models, we showed variable responsiveness to immunotherapies. We used array comparative genomic hybridization, whole-exome sequencing, exon microarray analysis, and flow cytometry to extensively characterize these models, which revealed striking differences that may underlie these contrasting response profiles. We identified strong differential gene expression in immune-related pathways and changes in immune cell-specific genes that suggested differences in tumor immune infiltrates between models. Further investigation using flow cytometry showed differences in both the composition and magnitude of the tumor immune infiltrates, identifying models that harbor "inflamed" and "noninflamed" tumor immune infiltrate phenotypes. We also found that immunosuppressive cell types predominated in syngeneic mouse tumor models that did not respond to immune-checkpoint blockade, whereas cytotoxic effector immune cells were enriched in responsive models. A cytotoxic cell-rich tumor immune infiltrate has been correlated with increased efficacy of immunotherapies in the clinic, and these differences could underlie the varying response profiles to immunotherapy between the syngeneic models. This characterization highlighted the importance of extensive profiling and will enable investigators to select appropriate models to interrogate the activity of immunotherapies as well as combinations with targeted therapies in vivo

Readout of a quantum processor with high dynamic range Josephson parametric amplifiers

We demonstrate a high dynamic range Josephson parametric amplifier (JPA) in which the active nonlinear element is implemented using an array of rf-SQUIDs. The device is matched to the 50 $\Omega$ environment with a Klopfenstein-taper impedance transformer and achieves a bandwidth of 250-300 MHz, with input saturation powers up to -95 dBm at 20 dB gain. A 54-qubit Sycamore processor was used to benchmark these devices, providing a calibration for readout power, an estimate of amplifier added noise, and a platform for comparison against standard impedance matched parametric amplifiers with a single dc-SQUID. We find that the high power rf-SQUID array design has no adverse effect on system noise, readout fidelity, or qubit dephasing, and we estimate an upper bound on amplifier added noise at 1.6 times the quantum limit. Lastly, amplifiers with this design show no degradation in readout fidelity due to gain compression, which can occur in multi-tone multiplexed readout with traditional JPAs.Comment: 9 pages, 8 figure

Materializing digital collecting: an extended view of digital materiality

If digital objects are abundant and ubiquitous, why should consumers pay for, much less collect them? The qualities of digital code present numerous challenges for collecting, yet digital collecting can and does occur. We explore the role of companies in constructing digital consumption objects that encourage and support collecting behaviours, identifying material configuration techniques that materialise these objects as elusive and authentic. Such techniques, we argue, may facilitate those pleasures of collecting otherwise absent in the digital realm. We extend theories of collecting by highlighting the role of objects and the companies that construct them in materialising digital collecting. More broadly, we extend theories of digital materiality by highlighting processes of digital material configuration that occur in the pre-objectification phase of materialisation, acknowledging the role of marketing and design in shaping the qualities exhibited by digital consumption objects and consequently related consumption behaviours and experiences

Suppressing quantum errors by scaling a surface code logical qubit

Practical quantum computing will require error rates that are well below what is achievable with physical qubits. Quantum error correction offers a path to algorithmically-relevant error rates by encoding logical qubits within many physical qubits, where increasing the number of physical qubits enhances protection against physical errors. However, introducing more qubits also increases the number of error sources, so the density of errors must be sufficiently low in order for logical performance to improve with increasing code size. Here, we report the measurement of logical qubit performance scaling across multiple code sizes, and demonstrate that our system of superconducting qubits has sufficient performance to overcome the additional errors from increasing qubit number. We find our distance-5 surface code logical qubit modestly outperforms an ensemble of distance-3 logical qubits on average, both in terms of logical error probability over 25 cycles and logical error per cycle ($2.914\%\pm 0.016\%$ compared to $3.028\%\pm 0.023\%$). To investigate damaging, low-probability error sources, we run a distance-25 repetition code and observe a $1.7\times10^{-6}$ logical error per round floor set by a single high-energy event ($1.6\times10^{-7}$ when excluding this event). We are able to accurately model our experiment, and from this model we can extract error budgets that highlight the biggest challenges for future systems. These results mark the first experimental demonstration where quantum error correction begins to improve performance with increasing qubit number, illuminating the path to reaching the logical error rates required for computation.Comment: Main text: 6 pages, 4 figures. v2: Update author list, references, Fig. S12, Table I

Non-Abelian braiding of graph vertices in a superconducting processor

Indistinguishability of particles is a fundamental principle of quantum mechanics. For all elementary and quasiparticles observed to date - including fermions, bosons, and Abelian anyons - this principle guarantees that the braiding of identical particles leaves the system unchanged. However, in two spatial dimensions, an intriguing possibility exists: braiding of non-Abelian anyons causes rotations in a space of topologically degenerate wavefunctions. Hence, it can change the observables of the system without violating the principle of indistinguishability. Despite the well developed mathematical description of non-Abelian anyons and numerous theoretical proposals, the experimental observation of their exchange statistics has remained elusive for decades. Controllable many-body quantum states generated on quantum processors offer another path for exploring these fundamental phenomena. While efforts on conventional solid-state platforms typically involve Hamiltonian dynamics of quasi-particles, superconducting quantum processors allow for directly manipulating the many-body wavefunction via unitary gates. Building on predictions that stabilizer codes can host projective non-Abelian Ising anyons, we implement a generalized stabilizer code and unitary protocol to create and braid them. This allows us to experimentally verify the fusion rules of the anyons and braid them to realize their statistics. We then study the prospect of employing the anyons for quantum computation and utilize braiding to create an entangled state of anyons encoding three logical qubits. Our work provides new insights about non-Abelian braiding and - through the future inclusion of error correction to achieve topological protection - could open a path toward fault-tolerant quantum computing