We report time-of-flight measurements on electrons traveling in quantum Hall edge states. Hot-electron wave packets are emitted one per cycle into edge states formed along a depleted sample boundary. ...The electron arrival time is detected by driving a detector barrier with a square wave that acts as a shutter. By adding an extra path using a deflection barrier, we measure a delay in the arrival time, from which the edge-state velocity v is deduced. We find that v follows 1/B dependence, in good agreement with the Eover →×Bover → drift. The edge potential is estimated from the energy dependence of v using a harmonic approximation.
The Galactic center supermassive black hole Sagittarius A* (Sgr A*) is one of the most promising targets to study the dynamics of black hole accretion and outflow via direct imaging with very long ...baseline interferometry (VLBI). At 3.5 mm (86 GHz), the emission from Sgr A* is resolvable with the Global Millimeter VLBI Array (GMVA). We present the first observations of Sgr A* with the phased Atacama Large Millimeter/submillimeter Array (ALMA) joining the GMVA. Our observations achieve an angular resolution of ∼87 as, improving upon previous experiments by a factor of two. We reconstruct a first image of the unscattered source structure of Sgr A* at 3.5 mm, mitigating the effects of interstellar scattering. The unscattered source has a major-axis size of 120 34 as (12 3.4 Schwarzschild radii) and a symmetrical morphology (axial ratio of ), which is further supported by closure phases consistent with zero within 3 . We show that multiple disk-dominated models of Sgr A* match our observational constraints, while the two jet-dominated models considered are constrained to small viewing angles. Our long-baseline detections to ALMA also provide new constraints on the scattering of Sgr A*, and we show that refractive scattering effects are likely to be weak for images of Sgr A* at 1.3 mm with the Event Horizon Telescope. Our results provide the most stringent constraints to date for the intrinsic morphology and refractive scattering of Sgr A*, demonstrating the exceptional contribution of ALMA to millimeter VLBI.
Abstract Objective Review of studies published in the last 10 years about women seeking gynecological- or obstetrical care and physician's gender in relation to patient preferences, differences in ...communication style and patient satisfaction. Methods Studies were identified by searching the online databases PubMed, PsycINFO, Embase and the Cochrane Library. The search strategies ‘gender’; ‘obstetrics’ and ‘gynecology’ were combined with ‘communication’; ‘physician–patient relations’; ‘patient preference’ and ‘patient satisfaction’. Results After screening title and abstract, evaluating full text and quality assessment, 9 articles were included in this review. Most patients preferred a female rather than a male gynecologist–obstetrician. This was partly explained by a more patient-centered communication style used by female gynecologists–obstetricians. Also experience and clinical competence were important factors in choosing a gynecologist–obstetrician. It was not clear whether patient's age or ethnicity influenced patients gender preference. Patient satisfaction increased when gynecologists–obstetricians used a patient-centered communication style. Conclusion Preference for a female gynecologist–obstetrician might be explained by a more patient-centered communication style used by female gynecologists–obstetricians. Using a patient-centered communication style increases patient satisfaction. Practice implications To increase patient satisfaction, gynecologists–obstetricians should learn to integrate patient-centered communication style into the consultation.
The calibration and analysis of polarization observations in very long baseline interferometry (VLBI) requires the use of specific algorithms that suffer from several limitations, closely related to ...assumptions in the data properties that may not hold in observations taken with new-generation VLBI equipment. Currently, the instantaneous bandwidth achievable with VLBI backends can be as high as several gigahertz, covering several radio bands simultaneously. In addition, the sensitivity of VLBI observations with the most updated equipment may reach dynamic ranges of tens of thousands, both in total intensity and polarization. In this paper, we discuss the impact of the limitations of common VLBI polarimetry algorithms on narrow-field observations taken with modern VLBI arrays, from the VLBI Global Observing System to the Event Horizon Telescope, and present new software that overcomes these limitations. In particular, our software is able to perform a simultaneous fit of multiple calibrator sources, include nonlinear terms in the model of the instrumental polarization and use a self-calibration approach for the estimate of the polarization leakage in the antenna receivers.
Current antibody-drug conjugates (ADCs) target internalising receptors on cancer cells leading to intracellular drug release. Typically, only a subset of patients with solid tumours has sufficient ...expression of such a receptor, while there are suitable non-internalising receptors and stroma targets. Here, we demonstrate potent therapy in murine tumour models using a non-internalising ADC that releases its drugs upon a click reaction with a chemical activator, which is administered in a second step. This was enabled by the development of a diabody-based ADC with a high tumour uptake and very low retention in healthy tissues, allowing systemic administration of the activator 2 days later, leading to efficient and selective activation throughout the tumour. In contrast, the analogous ADC comprising the protease-cleavable linker used in the FDA approved ADC Adcetris is not effective in these tumour models. This first-in-class ADC holds promise for a broader applicability of ADCs across patient populations.
BK polyomavirus (BKPyV) infection is widespread and typically asymptomatic during childhood, but may cause nephropathy in kidney transplant recipients. However, there is only limited knowledge on ...BKPyV‐specific immunity in children and adults, and its role in BKPyV‐replication and disease posttransplant. We therefore characterized BKPyV‐specific immunity from 122 immunocompetent individuals (1–84 years), 38 adult kidney recipients with (n = 14) and without BKPyV‐associated complications (n = 24), and 25 hemodialysis (HD) patients. Blood samples were stimulated with overlapping peptides of BKPyV large‐T antigen and VP1 followed by flow‐cytometric analysis of activated CD4 T cells expressing interferon‐γ, IL‐2 and tumor necrosis factor‐α. Antibody‐levels were determined using enzyme‐linked immunosorbent assay. Both BKPyV‐IgG levels and BKPyV‐specific CD4 T cell frequencies were age‐dependent (p = 0.0059) with maximum levels between 20 and 30 years (0.042%, interquartile range 0.05%). Transplant recipients showed a significantly higher BKPyV‐specific T cell prevalence (57.9%) compared to age‐matched controls (21.7%) or HD patients (28%, p = 0.017). Clinically relevant BKPyV‐replication was associated with elevated frequencies of BKPyV‐specific T cells (p = 0.0002), but decreased percentage of cells expressing multiple cytokines (p = 0.009). In conclusion, BKPyV‐specific cellular immunity reflects phases of active BKPyV‐replication either after primary infection in childhood or during reactivation after transplantation. Combined analysis of BKPyV‐specific T cell functionality and viral loads may improve individual risk assessment.
The authors characterize BK virus–specific cellular and humoral immunity in immunocompetent controls across a wide age range and in renal transplant recipients, and show that the level of immunity reflects phases of active viral replication either after primary infection in childhood or during reactivation after transplantation.
Unreliable predictions can occur when an artificial intelligence (AI) system is presented with data it has not been exposed to during training. We demonstrate the use of conformal prediction to ...detect unreliable predictions, using histopathological diagnosis and grading of prostate biopsies as example. We digitized 7788 prostate biopsies from 1192 men in the STHLM3 diagnostic study, used for training, and 3059 biopsies from 676 men used for testing. With conformal prediction, 1 in 794 (0.1%) predictions is incorrect for cancer diagnosis (compared to 14 errors 2% without conformal prediction) while 175 (22%) of the predictions are flagged as unreliable when the AI-system is presented with new data from the same lab and scanner that it was trained on. Conformal prediction could with small samples (N = 49 for external scanner, N = 10 for external lab and scanner, and N = 12 for external lab, scanner and pathology assessment) detect systematic differences in external data leading to worse predictive performance. The AI-system with conformal prediction commits 3 (2%) errors for cancer detection in cases of atypical prostate tissue compared to 44 (25%) without conformal prediction, while the system flags 143 (80%) unreliable predictions. We conclude that conformal prediction can increase patient safety of AI-systems.
Summary Background Intravenous saline is recommended in clinical practice guidelines as the cornerstone for preventing contrast-induced nephropathy in patients with compromised renal function. ...However, clinical-effectiveness and cost-effectiveness of this prophylactic hydration treatment in protecting renal function has not been adequately studied in the population targeted by the guidelines, against a group receiving no prophylaxis. This was the aim of the AMACING trial. Methods AMACING is a prospective, randomised, phase 3, parallel-group, open-label, non-inferiority trial of patients at risk of contrast-induced nephropathy according to current guidelines. High-risk patients (with an estimated glomerular filtration rate eGFR of 30–59 mL per min/1·73 m2 ) aged 18 years and older, undergoing an elective procedure requiring iodinated contrast material administration at Maastricht University Medical Centre, the Netherlands, were randomly assigned (1:1) to receive intravenous 0·9% NaCl or no prophylaxis. We excluded patients with eGFR lower than 30 mL per min/1·73 m2 , previous dialysis, or no referral for intravenous hydration. Randomisation was stratified by predefined risk factors. The primary outcome was incidence of contrast-induced nephropathy, defined as an increase in serum creatinine from baseline of more than 25% or 44 μmol/L within 2–6 days of contrast exposure, and cost-effectiveness of no prophylaxis compared with intravenous hydration in the prevention of contrast-induced nephropathy. We measured serum creatinine immediately before, 2–6 days, and 26–35 days after contrast-material exposure. Laboratory personnel were masked to treatment allocation. Adverse events and use of resources were systematically recorded. The non-inferiority margin was set at 2·1%. Both intention-to-treat and per-protocol analyses were done. This trial is registered with ClinicalTrials.gov , number NCT02106234. Findings Between June 17, 2014, and July 17, 2016, 660 consecutive patients were randomly assigned to receive no prophylaxis (n=332) or intravenous hydration (n=328). 2–6 day serum creatinine was available for 307 (92%) of 332 patients in the no prophylaxis group and 296 (90%) of 328 patients in the intravenous hydration group. Contrast-induced nephropathy was recorded in eight (2·6%) of 307 non-hydrated patients and in eight (2·7%) of 296 hydrated patients. The absolute difference (no hydration vs hydration) was −0·10% (one-sided 95% CI −2·25 to 2·06; one-tailed p=0·4710). No hydration was cost-saving relative to hydration. No haemodialysis or related deaths occurred within 35 days. 18 (5·5%) of 328 patients had complications associated with intravenous hydration. Interpretation We found no prophylaxis to be non-inferior and cost-saving in preventing contrast-induced nephropathy compared with intravenous hydration according to current clinical practice guidelines. Funding Stichting de Weijerhorst.
Government agencies are becoming more data-driven and need high-quality data to fulfill their roles in society. In the past, each agency organized its own data exchange system according to its own ...needs. Today, data is distributed over many organizations, and government agencies need to adopt an ecosystem approach for data exchange. Fundamental in the ecosystem approach is the dependence on other parties for the execution of stewardship strategies. Data-driven government agencies increasingly depend on other organizations for high-quality data and data stewardship across organizations is becoming more critical. While there is ample research on data stewardship within organizations, little is known about data stewardship in ecosystems. More specifically, it is unclear which data stewardship strategies government agencies can employ in ecosystems. The main goal of this explorative paper is to identify and compare data stewardship strategies used in empirical government-business ecosystems. Following an explorative case study approach, this paper reveals three different configurations of inter-organizational data stewardship: 1) the government-led ecosystem, 2) the government-business-led ecosystem, and 3) the regulation-led ecosystem. The case studies expose a wide array of data stewardship strategies across ecosystems. While the ecosystem approach provides advantages such as cost-sharing and innovation by private parties, government agencies become increasingly dependent on private parties to gain high-quality data and provide distributed infrastructure components. Maximizing the benefits and minimizing the risks of the ecosystem approach requires government agencies to be cautious when selecting a specific ecosystem configuration.
•We developed an analytical framework to analyze different empirical data stewardship configurations and data strategies.•Centralized digital infrastructures are replaced by a negotiated framework of data exchange agreements.•Government agencies become increasingly dependent on market parties.•In these frameworks governments need to focus on data stewardship and form a data stewardship strategy.•Data stewardship must be extended to include governance and system quality.
Eliminated without a trace: The fastest click reaction, the highly selective inverse‐electron‐demand Diels–Alder reaction, has been modified to enable selective bioorthogonal release. Thus, the click ...reaction of a tetrazine with a drug‐bound trans‐cyclooctene caused the instantaneous release of the drug and CO2 (see scheme). One possible application is the chemically triggered release, and thereby activation, of a drug from a tumor‐bound antibody–drug conjugate.
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