We report high-fidelity state readout of a trapped ion qubit using a trap-integrated photon detector. We determine the hyperfine qubit state of a single ^{9}Be^{+} ion held in a surface-electrode rf ...ion trap by counting state-dependent ion fluorescence photons with a superconducting nanowire single-photon detector fabricated into the trap structure. The average readout fidelity is 0.9991(1), with a mean readout duration of 46 μs, and is limited by the polarization impurity of the readout laser beam and by off-resonant optical pumping. Because there are no intervening optical elements between the ion and the detector, we can use the ion fluorescence as a self-calibrated photon source to determine the detector quantum efficiency and its dependence on photon incidence angle and polarization.
The field of quantum computing has grown from concept to demonstration devices over the past 20 years. Universal quantum computing offers efficiency in approaching problems of scientific and ...commercial interest, such as factoring large numbers, searching databases, simulating intractable models from quantum physics, and optimizing complex cost functions. Here, we present an 11-qubit fully-connected, programmable quantum computer in a trapped ion system composed of 13
Yb
ions. We demonstrate average single-qubit gate fidelities of 99.5Formula: see text, average two-qubit-gate fidelities of 97.5Formula: see text, and SPAM errors of 0.7Formula: see text. To illustrate the capabilities of this universal platform and provide a basis for comparison with similarly-sized devices, we compile the Bernstein-Vazirani and Hidden Shift algorithms into our native gates and execute them on the hardware with average success rates of 78Formula: see text and 35Formula: see text, respectively. These algorithms serve as excellent benchmarks for any type of quantum hardware, and show that our system outperforms all other currently available hardware.
Objective To examine the effect of surgeon sex on postoperative outcomes of patients undergoing common surgical procedures.Design Population based, retrospective, matched cohort study from 2007 to ...2015.Setting Population based cohort of all patients treated in Ontario, Canada.Participants Patients undergoing one of 25 surgical procedures performed by a female surgeon were matched by patient age, patient sex, comorbidity, surgeon volume, surgeon age, and hospital to patients undergoing the same operation by a male surgeon.Interventions Sex of treating surgeon.Main outcome measure The primary outcome was a composite of death, readmission, and complications. We compared outcomes between groups using generalised estimating equations.Results 104 630 patients were treated by 3314 surgeons, 774 female and 2540 male. Before matching, patients treated by female doctors were more likely to be female and younger but had similar comorbidity, income, rurality, and year of surgery. After matching, the groups were comparable. Fewer patients treated by female surgeons died, were readmitted to hospital, or had complications within 30 days (5810 of 52 315, 11.1%, 95% confidence interval 10.9% to 11.4%) than those treated by male surgeons (6046 of 52 315, 11.6%, 11.3% to 11.8%; adjusted odds ratio 0.96, 0.92 to 0.99, P=0.02). Patients treated by female surgeons were less likely to die within 30 days (adjusted odds ratio 0.88; 0.79 to 0.99, P=0.04), but there was no significant difference in readmissions or complications. Stratified analyses by patient, physician, and hospital characteristics did not significant modify the effect of surgeon sex on outcome. A retrospective analysis showed no difference in outcomes by surgeon sex in patients who had emergency surgery, where patients do not usually choose their surgeon.Conclusions After accounting for patient, surgeon, and hospital characteristics, patients treated by female surgeons had a small but statistically significant decrease in 30 day mortality and similar surgical outcomes (length of stay, complications, and readmission), compared with those treated by male surgeons. These findings support the need for further examination of the surgical outcomes and mechanisms related to physicians and the underlying processes and patterns of care to improve mortality, complications, and readmissions for all patients.
Novel second-line treatments are needed for patients with advanced urothelial cancer (UC). Interim analysis of the phase III KEYNOTE-045 study showed a superior overall survival (OS) benefit of ...pembrolizumab, a programmed death 1 inhibitor, versus chemotherapy in patients with advanced UC that progressed on platinum-based chemotherapy. Here we report the long-term safety and efficacy outcomes of KEYNOTE-045.
Adult patients with histologically/cytologically confirmed UC whose disease progressed after first-line, platinum-containing chemotherapy were enrolled. Patients were randomly assigned 1 : 1 to receive pembrolizumab 200mg every 3weeks (Q3W) or investigator’s choice of paclitaxel (175mg/m2 Q3W), docetaxel (75mg/m2 Q3W), or vinflunine (320mg/m2 Q3W). Primary end points were OS and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by blinded independent central radiology review (BICR). A key secondary end point was objective response rate per RECIST v1.1 by BICR.
A total of 542 patients were enrolled (pembrolizumab, n=270; chemotherapy, n=272). Median follow-up as of 26 October 2017 was 27.7months. Median 1- and 2-year OS rates were higher with pembrolizumab (44.2% and 26.9%, respectively) than chemotherapy (29.8% and 14.3%, respectively). PFS rates did not differ between treatment arms; however, 1- and 2-year PFS rates were higher with pembrolizumab. The objective response rate was also higher with pembrolizumab (21.1% versus 11.0%). Median duration of response to pembrolizumab was not reached (range 1.6+ to 30.0+ months) versus chemotherapy (4.4months; range 1.4+ to 29.9+ months). Pembrolizumab had lower rates of any grade (62.0% versus 90.6%) and grade ≥3 (16.5% versus 50.2%) treatment-related adverse events than chemotherapy.
Long-term results (>2 years’ follow-up) were consistent with those of previously reported analyses, demonstrating continued clinical benefit of pembrolizumab over chemotherapy for efficacy and safety for treatment of locally advanced/metastatic, platinum-refractory UC.
ClinicalTrials.gov: NCT02256436.
Immunotherapy agents are an innovative oncological treatment modality and as a result their use has expanded widely. Understanding the treatment-related adverse events (AEs) of these drugs compared ...with traditional chemotherapy is crucial for clinical practice.
A systematic review of studies indexed in Medline (PubMed), Embase, Web of Science, and the Cochrane Databases from January 2000 to 14 February 2019 was conducted. Randomized clinical trials comparing immunotherapy cytotoxic T-lymphocyte protein-4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed death-ligand 1 (PD-L1) with standard-of-care chemotherapy in the treatment of advanced solid-organ neoplasms were included if AEs were reported as an outcome. Primary outcome was AEs ≥ grade 3 in severity. Secondary outcomes were proportion of overall AEs, treatment discontinuation due to AEs, deaths due to AEs, and specific AEs fatigue, diarrhea, acute kidney injury (AKI), colitis, pneumonitis, and hypothyroidism. Paule–Mandel pooling and a random effects model were used to produce odds ratios (ORs) for measures of effects.
Among 10 598 abstracts screened, we included 22 studies involving 12 727 patients. In the immunotherapy group, 16.5% of patients developed an AE ≥ grade 3 in severity, compared with 41.09% in the chemotherapy arm OR = 0.26, 95% confidence interval (CI) 0.19–0.35, I2 = 92%. Patients receiving immunotherapy also had lower odds of developing an AE overall (OR = 0.35, 95% CI 0.28–0.44; I2 = 77%), terminating therapy due to an AE (OR = 0.55, 95% CI 0.39–0.78, I2 = 80%), or dying from a treatment-related AE (OR = 0.67, 95% CI 0.46–0.98, I2 = 0%). When treated with chemotherapy versus immunotherapy, patients more frequently experienced fatigue (25.10% versus 15.83%), diarrhea (14.97% versus 11.13%), and AKI (1.79% versus 1.31%). However, colitis (1.02% versus 0.26%), pneumonitis (3.36% versus 0.36%), and hypothyroidism (6.82% versus 0.37%) were more common in those treated with immunotherapy.
Treatment of advanced solid-organ malignancies with immunotherapy compared with traditional chemotherapy is associated with a lower risk of AEs.
•22 trials involving 12,727 patients with advanced solid organ malignancies were included in this meta-analysis.•Patients receiving immunotherapy were less likely to develop severe adverse events than those receiving chemotherapy.•Fewer terminations due to adverse events or deaths due to adverse events occurred in the immunotherapy group.•Fatigue and diarrhea were more likely to occur in patients treated with chemotherapy.
Objective To determine the association between exposure to radiotherapy for the treatment of prostate cancer and subsequent second malignancies (second primary cancers).Design Systematic review and ...meta-analysis of observational studies.Data sources Medline and Embase up to 6 April 2015 with no restrictions on year or language.Study selection Comparative studies assessing the risk of second malignancies in patients exposed or unexposed to radiotherapy in the course of treatment for prostate cancer were selected by two reviewers independently with any disagreement resolved by consensus.Data extraction and synthesis Two reviewers independently extracted study characteristics and outcomes. Risk of bias was assessed with the Newcastle-Ottawa scale. Outcomes were synthesized with random effects models and Mantel-Haenszel weighting. Unadjusted odds ratios and multivariable adjusted hazard ratios, when available, were pooled.Main outcome measures Second cancers of the bladder, colorectal tract, rectum, lung, and hematologic system.Results Of 3056 references retrieved, 21 studies were selected for analysis. Most included studies were large multi-institutional reports but had moderate risk of bias. The most common type of radiotherapy was external beam; 13 studies used patients treated with surgery as controls and eight used patients who did not undergo radiotherapy as controls. The length of follow-up among studies varied. There was increased risk of cancers of the bladder (four studies; adjusted hazard ratio 1.67, 95% confidence interval 1.55 to 1.80), colorectum (three studies; 1.79, 1.34 to 2.38), and rectum (three studies; 1.79, 1.34 to 2.38), but not cancers of the hematologic system (one study; 1.64, 0.90 to 2.99) or lung (two studies; 1.45, 0.70 to 3.01), after radiotherapy compared with the risk in those unexposed to radiotherapy. The odds of a second cancer varied depending on type of radiotherapy: treatment with external beam radiotherapy was consistently associated with increased odds while brachytherapy was not. Among the patients who underwent radiotherapy, from individual studies, the highest absolute rates reported for bladder, colorectal, and rectal cancers were 3.8%, 4.2%, and 1.2%, respectively, while the lowest reported rates were 0.1%, 0.3%, and 0.3%.Conclusion Radiotherapy for prostate cancer was associated with higher risks of developing second malignancies of the bladder, colon, and rectum compared with patients unexposed to radiotherapy, but the reported absolute rates were low. Further studies with longer follow-up are required to confirm these findings.
Abstract Context To date, there is no Level 1 evidence comparing the efficacy of radical prostatectomy and radiotherapy for patients with clinically-localized prostate cancer. Objective To conduct a ...meta-analysis assessing the overall and prostate cancer-specific mortality among patients treated with radical prostatectomy or radiotherapy for clinically-localized prostate cancer. Evidence acquisition We searched Medline, EMBASE, and the Cochrane Library through June 2015 without year or language restriction, supplemented with hand search, using Preferred Reporting Items for Systematic Reviews and Meta-Analysis and Meta-analysis of Observational Studies in Epidemiology guidelines. We used multivariable adjusted hazard ratios (aHRs) to assess each endpoint. Risk of bias was assessed using the Newcastle-Ottawa scale. Evidence synthesis Nineteen studies of low to moderate risk of bias were selected and up to 118 830 patients were pooled. Inclusion criteria and follow-up length varied between studies. Most studies assessed patients treated with external beam radiotherapy, although some included those treated with brachytherapy separately or with the external beam radiation therapy group. The risk of overall (10 studies, aHR 1.63, 95% confidence interval 1.54–1.73, p < 0.00001; I2 = 0%) and prostate cancer-specific (15 studies, aHR 2.08, 95% confidence interval 1.76–2.47, p < 0.00001; I2 = 48%) mortality were higher for patients treated with radiotherapy compared with those treated with surgery. Subgroup analyses by risk group, radiation regimen, time period, and follow-up length did not alter the direction of results. Conclusions Radiotherapy for prostate cancer is associated with an increased risk of overall and prostate cancer-specific mortality compared with surgery based on observational data with low to moderate risk of bias. These data, combined with the forthcoming randomized data, may aid clinical decision making. Patient summary We reviewed available studies assessing mortality after prostate cancer treatment with surgery or radiotherapy. While the studies used have a potential for bias due to their observational design, we demonstrated consistently higher mortality for patients treated with radiotherapy rather than surgery.
We demonstrate superconducting nanowire single photon detectors with 76 ± 4% system detection efficiency at a wavelength of 315 nm and an operating temperature of 3.2 K, with a background count rate ...below 1 count per second at saturated detection efficiency. We propose integrating these detectors into planar surface electrode radio-frequency Paul traps for use in trapped ion quantum information processing. We operate detectors integrated into test ion trap structures at 3.8 K both with and without typical radio-frequency trapping electric fields. The trapping fields reduce system detection efficiency by 9%, but do not increase background count rates.
Conflicting evidence exists for the association between testosterone replacement therapy and mortality and cardiovascular events. The US Food and Drug Administration recently cautioned that ...testosterone replacement therapy might increase risk of heart attack and stroke, based on evidence from studies with short treatment duration and follow-up. No previous study has assessed the effect of duration of testosterone treatment on these outcomes. We aimed to assess the association between long-term use of testosterone replacement therapy and mortality, cardiovascular events, and prostate cancer diagnoses, using a time-varying exposure analysis.
We did a population-based matched cohort study of men aged 66 years or older newly treated with testosterone replacement therapy and controls matched for age, region of residence, comorbidity, diabetes status, and index year from 2007-12 in Ontario, Canada, using data from the Ontario Drug Benefit database, the Canadian Institute for Health Information (CIHI) Discharge Abstract Database, the CIHI National Ambulatory Care Reporting System, the Ontario Health Insurance Plan database, the Ontario Myocardial Infarction Database, the Ontario Diabetes Database, the Ontario Cancer Registry, and the Registered Persons database. We assessed the association between cumulative testosterone replacement therapy exposure and mortality, cardiovascular events, and prostate cancer using marginal models with a time-varying testosterone exposure.
We included 10 311 men treated with testosterone replacement therapy and 28 029 controls between Jan 1, 2007, and June 30, 2012. Over a median follow-up of 5·3 years (IQR 3·6-7·5) in the testosterone replacement therapy group and 5·1 years (3·4-7·4) in the control group, patients treated with testosterone replacement therapy had lower mortality than did controls (hazard ratio HR 0·88, 95% CI 0·84-0·93). Patients in the lowest tertile of testosterone exposure had increased risk of mortality (HR 1·11, 95% CI 1·03-1·20) and cardiovascular events (HR 1·26, 95% CI 1·09-1·46) compared with controls. By contrast, those in the highest tertile of testosterone exposure had decreased risk of mortality (HR 0·67, 95% CI 0·62-0·73) and cardiovascular events (HR 0·84, 95% CI 0·72-0·98), with a significant trend across tertiles (p<0·0001). Risk of prostate cancer diagnosis was decreased for those with the highest tertile of exposure (HR 0·60, 95% CI 0·45-0·80) compared with controls, but not for those with the shortest exposure.
Long-term exposure to testosterone replacement therapy was associated with reduced risks of mortality, cardiovascular events, and prostate cancer. However, testosterone replacement therapy increased the risk of mortality and cardiovascular events with short durations of therapy. In view of the limitations of observational data and the potential for selection bias, these results warrant confirmation in a randomised trial.
Physicians' Services Incorporated Foundation and Ajmera Family Chair in Urologic Oncology.
We perform a series of molecular dynamics simulations of the uniaxial compression of cylindrical gold nanopillars. Yield occurs via Shockley partial dislocation nucleation at the surface. Dislocation ...nucleation is preceded, in some cases (depending on the interatomic potential), by an elastic instability of the nanopillars, either Euler buckling or shears folding. For some potentials, this buckling is related to compressive stress-driven face-centered cubic-hexagonal close-packed phase transitions in the bulk. In cases in which dislocation nucleation is not preceded by an elastic instability (this depends on the choice of the interatomic potential and loading direction), the yield stress is found to be either a parabolic (i.e. described by the relationship
A
-
B
T
with
A,
B
=
const) or linear function of temperature,
T. We suggest that Shockley partial dislocation nucleation at the surface of the nanopillar occurs at a critical strain, where the local strain has contributions from the homogeneous elastic strain and an atomic-level thermal strain (associated with the thermal vibrations). This model explains the observed temperature dependence of the yield stress of the compressed nanopillars.
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