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Contains fulltext : 292920.pdf (Publisher’s version ) (Open Access) Women tend to make a decision about participation in breast cancer screening and adhere to this for future invitations. Therefore, our study aimed to provide high-quality information on cumulative risks of false-positive (FP) recall and screen-detected breast cancer over multiple screening examinations. Individual Dutch screening registry data (2005-2018) were gathered on subsequent screening examinations of 92 902 women age 49 to 51 years in 2005. Survival analyses were used to calculate cumulative risks of a FP and a true-positive (TP) result after seven examinations. Data from 66 472 women age 58 to 59 years were used to extrapolate to 11 examinations. Participation, detection and additional FP rates were calculated for women who previously received FP results compared to women with true negative (TN) results. After 7 examinations, the cumulative risk of a TP result was 3.7% and the cumulative risk of a FP result was 9.1%. After 11 examinations, this increased to 7.1% and 13.5%, respectively. Following a FP result, participation was lower (71%-81%) than following a TN result (>90%). In women with a FP result, more TP results (factor 1.59 [95% CI: 1.44-1.72]), more interval cancers (factor 1.66 [95% CI: 1.41-1.91]) and more FP results (factor 1.96 [95% CI: 1.87-2.05]) were found than in women with TN results. In conclusion, due to a low recall rate in the Netherlands, the cumulative risk of a FP recall is relatively low, while the cumulative risk of a TP result is comparable. Breast cancer diagnoses and FP results were more common in women with FP results than in women with TN results, while participation was lower.

OBJECTIVES: The headroom analysis is an early economic evaluation that quantifies the highest price at which an intervention may still be cost effective. Currently, there is no comprehensive review on how it is applied. This study investigated the application of the headroom analysis, specifically (1) how the headroom analysis is framed (2) the analytical approach and sources of evidence used, and (3) how expert judgement is used and reported. METHODS: A systematic search was conducted in PubMed, Embase, Web of Science, EconLit, and Google Scholar on 28 April 2022. Studies were eligible if they reported an application of the headroom analysis. Data were presented in tabular form and summarised descriptively. RESULTS: We identified 42 relevant papers. The headroom analysis was applied to medicines (29%), diagnostic or screening tests (29%), procedures, programmes and systems (21%), medical devices (19%), and a combined test and device (2%). All studies used model-based analyses, with 40% using simple models and 60% using more comprehensive models. Thirty-three percent of the studies assumed perfect effectiveness of the health technology, while 67% adopted realistic assumptions. Ten percent of the studies calculated an effectiveness-seeking headroom instead of a cost-seeking headroom. Expert judgement was used in 71% of the studies; 23 studies (55%) used expert opinion, 6 studies (14%) used expert elicitation, and 1 study (2%) used both. CONCLUSIONS: Because the application of the headroom analysis varies considerably, we recommend its appropriate use and clear reporting of analytical approaches, level of evidence available, and the use of expert judgement.

Significance π-stacking of polynuclear aromatic rings encompasses fundamental scientific phenomena in chemical bonding and photophysics with strong impacts on societal aspects that include electronic devices, DNA/RNA intercalation, and optical sensing of environmental pollutants. This work describes unusually strong π-stacking in a recently synthesized naphthalene-diimide derivative, as well as a prototypical π-stacked molecule, pyrene. The infinite/cooperative π-stacking in the former and dimer stacking in the latter are much stronger than previously thought to be possible for this type of supramolecular interaction, reaching ∼50 and 20 kcal ⋅ mol −1 , respectively. This has led to unusually large anisotropic thermal expansion and multicycle/multicolor thermochromism in BNDI-T, whereas multiple unusual binding and photophysical properties have been discovered for the classical organic chromophore pyrene.

In recent years, the introduction of the E‑Health Act and the relaxation of the ban on remote treatment has improved the framework for telemedicine in Germany.The aim of this article is to present an overview of the evidence of different areas of application for teledermatology.A narrative review of national and international studies and projects on the use of teledermatology for diagnosis, monitoring of diseases, triage between primary care physicians (PCPs) and dermatologists, and its use in facilities with reduced organizational and/or geographical access to specialist care was conducted.Diagnostic applications allow teledermatological assessment in a large proportion of cases, with high concordance of diagnosis and patient satisfaction. For the monitoring of patients, the majority of studies demonstrated no difference in effectiveness between on-site and remote consultation, while patients are spared travel distance and waiting time. For programs enabling triage most of the patients with dermatologic conditions were able to remain with the PCP, while acute patients requiring direct referral to a dermatologist were identified. In special facilities, such as prisons, dermatological teleconsultations are successfully utilized.An adequate framework and promising evidence for the use of teledermatology exist. The areas of application are described in detail within the German S2k guideline for teledermatology. However, there is a potential risk for decreased access to telemedicine services for certain population groups.HINTERGRUND: In den letzten Jahren wurden mit dem E‑Health-Gesetz und der Lockerung des Fernbehandlungsverbotes die Rahmenbedingungen für die Telemedizin in Deutschland verbessert.Das Ziel dieses Beitrags ist es, eine Übersicht wichtiger Anwendungsgebiete der Teledermatologie darzustellen.Erstellt wurde eine narrative Übersichtsarbeit von nationalen und internationalen Studien und Projekten zum Einsatz der Teledermatologie für die Diagnosestellung, die Verlaufskontrolle, die Triage zwischen Haus- und Hautärzten sowie den Einsatz in Einrichtungen mit organisatorisch und/oder geografisch erschwertem Zugang zu fachmedizinischer Versorgung.Diagnostische Anwendungen ermöglichen in einem Großteil der Fälle die teledermatologische Beurteilung bei hoher Konkordanz der Diagnose und Patientenzufriedenheit. In der Versorgung chronischer Patienten wurde in der Mehrzahl von Studien nachgewiesen, dass kein Unterschied in der Effektivität der Behandlung zwischen der Präsenz- und Fernbehandlung vorliegt und Patienten Anfahrtswege und Wartezeiten einsparen. Bei dermatologischen Fällen, die mithilfe der Teletriage evaluiert wurden, konnte ein Großteil beim Hausarzt verbleiben. Gleichzeitig wurden Patienten identifiziert, die schnellstmöglich beim Hautarzt vorstellig werden sollten. In besonderen Einrichtungen wie Justizvollzugsanstalten werden dermatologische Telekonsile erfolgreich eingesetzt.Für die Nutzung der Teledermatologie in Deutschland liegen hinreichende Rahmenbedingungen und eine befriedigende Evidenz vor. Die Anwendungsbereiche sind detailliert in der S2k-Leitlinie der Teledermatologie abgebildet. Es besteht das Risiko, dass der Zugang zur Telemedizin für bestimmte Bevölkerungsgruppen erschwert sein könnte.

Dynamically-tunable impedance matching is a key feature in numerous radio-frequency (RF) applications at high frequencies (10 s of MHz) and power levels (100s–1000 s of Watts and above). This work develops techniques that enable the design of high power tunable matching networks (TMN) that can be tuned orders of magnitude faster than with conventional tunable impedance matching techniques, while realizing the high power levels required for many industrial applications. This is achieved by leveraging an emerging technique – known as phase-switched impedance modulation (PSIM), which involves switching passive elements at the rf operating frequency – that has previously been demonstrated at rf frequencies at up to a few hundred Watts. In this paper, we develop design approaches that enable it to be practically used at up to many kilowatts of power at frequencies in the 10 s of MHz. A detailed analysis of the factors affecting the losses as well as the tradeoffs of a basic PSIM-based element is provided. Furthermore, it is shown how incorporating additional stages to the PSIM-based element, including impedance scaling and / or the addition of series or shunt passive elements, influences the losses and enables the efficient processing of high power levels given the limitations of available switches. A PSIM-based TMN that matches load impedances to 50 $\,\Omega$ and delivers up to 1.5 kW of power at frequencies centered around 13.56 MHz is implemented and tested over a load impedance range suitable for various industrial plasma processes.

This article provides a third manifestation of a new tradition by which the editors of Comments on Inorganic Chemistry wish to lead by example, whereby we start publishing original research content...

Aim To determine the prevalence of undiagnosed bicuspid aortic valve (BAV) and isolated aortic dilatation in first-degree relatives (FDRs) of patients with isolated BAV and to explore the recurrence risk of BAV in different subgroups of probands with BAV. Recent American College of Cardiology (ACC)/American Heart Association (AHA) Guidelines recommend family screening in patients with associated aortopathy only. Methods During follow-up visits, patients with isolated BAV received a printed invitation for their FDRs advising cardiac screening. Results From 2012–2019, 257 FDRs of 118 adult BAV patients were screened, among whom 63 (53%) index patients had undergone aortic valve surgery (AVS), including concomitant aortic replacement in 25 (21%). Of the non-operated index patients, 31 (26%) had aortic dilatation (> 40 mm). Mean age of the FDRs was 48 years (range 4–83) and 42% were male. The FDR group comprised 20 parents, 103 siblings and 134 offspring. Among these FDRs, 12 (4.7%) had a previously undiagnosed BAV and 23 (8.9%) had an isolated aortic dilatation. FDRs of the probands with previous AVS (n = 147) had a risk ratio for BAV of 2.25 (95% confidence interval (CI) 0.62–8.10). FDRs of the probands with BAV and repaired or unrepaired aortic dilatation (n = 127) had a risk ratio for BAV of 0.51 (95% CI 0.16–1.66). Conclusion Screening FDRs of patients with isolated BAV resulted in a reasonable yield of 14% new cases of BAV or isolated aortic dilatation. A trend towards an increased risk of BAV in FDRs was observed in the probands with previous AVS, whereas this risk seemed to be diminished in the probands with associated aortic dilatation. This latter finding does not support the restrictive ACC/AHA recommendation.

This paper investigates and compares the performance of three-phase inverters and sets of single-phase full-bridge inverters for motor drive applications. Comparisons are made for a given semiconductor device area and equal rms phase current ripple and the regions of the design space in which each topology is advantageous are identified. It is found that separate full-bridge inverters are preferable for designs in which switching losses are dominant, whereas three-phase inverters are preferable for designs in which conduction losses are dominant. This result suggests that individual phase drive is desirable in applications requiring high switching frequencies, as in highspeed, low-inductance machines.

Background Bicuspid aortic valve (BAV) may frequently lead to aortic dilatation with risk of aortic dissection. In patients with BAV both familial clustering and aortic dilatation in first-degree relatives (FDR) without BAV has been demonstrated. Based on these findings the ESC Aortic Guidelines recommend to consider screening of FDR, while the ACC/AHA Guidelines on Valvular Heart Diseases consider screening of FDR only if the index patient has associated aortopathy. Currently, no data about the effectiveness of screening is available. Purpose To investigate the yield of screening FDR of patients with isolated BAV and to explore subgroups with FDR of patients who had needed surgery or of patients with aortic dilatation. We hypothesized that aortic dilatation (>40mm) in the index patient is not a risk factor for BAV in FDR. Methods From 2012, patients with BAV visiting the outpatient clinic of a teaching hospital, received information advising cardiac screening of FDR. FDR of patients with isolated BAV who were referred, were included. From the 10 index patients from other hospitals, information was retrieved. [Fig.1] Results Referred were FDR from 118 index patients (mean age 60 years, standard deviation [SD] 14, range 15–90 years, 82 males [70%]). Of all index patients 63 (53%) had undergone aortic valve replacement, including concomitant ascending aorta replacement in 25 (21%). In the non-operated index patients, 31 (26%) had dilatation (>40mm) of sinus of Valsalva and/or tubular ascending aorta. Screened were 257 FDR (median 2 per index patient) comprising 20 parents (8%), 103 siblings (40%) and 134 offspring (52%). Mean age of FDR was 48 years (SD16, range 4–83 years) and 89 subjects (42%) were male. The diagnostic imaging modality was echocardiography in 240 cases (93%) and MRI in 17 cases. Ten FDR had an already known BAV and were not included in the screening. Among the 257 FDR, we diagnosed 12 new BAV (4.7%, 95% confidence interval [CI]2.9–8.0%) (mean age 44 years, 50% male). Additionally, we diagnosed 23 new isolated aorta dilatations (8.9%; 95% CI 6.0–13%) at level of sinus of Valsalva and/or tubular ascending aorta (mean age 57 years, 18 [78%] were male) [Fig. 1]. Among them, 11 had hypertension. FDR (n=147) of index patients with BAV and previous aortic valve surgery (n=63), had a risk ratio (RR) of 2.25 (95% CI 0.62–8.10) of having a BAV. FDR (n=126) of index patients with BAV and repaired or unrepaired aortic dilatation (n=56) had RR 0.35 (95% CI 0.10–1.25) of having a BAV. Conclusions Screening FDR of patients with isolated BAV resulted in a reasonable yield of 14% new cases with BAV or isolated aortic dilatation. The RR of the subgroup with aorta dilatation did not justify the limitation of the FDR as suggested in the ACC/AHA Guidelines. Figure 1. Flowchart of screening and result Funding Acknowledgement Type of funding source: None

Background: As part of a coordinated effort to expand research activity around rigor, reproducibility, and transparency (RRT) across scientific disciplines, a team of investigators at the Indiana University School of Public Health-Bloomington hosted a workshop in October 2019 with international leaders to discuss key opportunities for RRT research. Objective: The workshop aimed to identify research priorities and opportunities related to RRT. Design: Over two-days, workshop attendees gave presentations and participated in three working groups: (1) Improving Education & Training in RRT, (2) Reducing Statistical Errors and Increasing Analytic Transparency, and (3) Looking Outward: Increasing Truthfulness and Accuracy of Research Communications. Following small-group discussions, the working groups presented their findings, and participants discussed the research opportunities identified. The investigators compiled a list of research priorities, which were circulated to all participants for feedback. Results: Participants identified the following priority research questions: (1) Can RRT-focused statistics and mathematical modeling courses improve statistics practice?; (2) Can specialized training in scientific writing improve transparency?; (3) Does modality (e.g. face to face, online) affect the efficacy RRT-related education?; (4) How can automated programs help identify errors more efficiently?; (5) What is the prevalence and impact of errors in scientific publications (e.g., analytic inconsistencies, statistical errors, and other objective errors)?; (6) Do error prevention workflows reduce errors?; (7) How do we encourage post-publication error correction?; (8) How does ‘spin’ in research communication affect stakeholder understanding and use of research evidence?; (9) Do tools to aid writing research reports increase comprehensiveness and clarity of research reports?; and (10) Is it possible to inculcate scientific values and norms related to truthful, rigorous, accurate, and comprehensive scientific reporting? Conclusion: Participants identified important and relatively unexplored questions related to improving RRT. This list may be useful to the scientific community and investigators seeking to advance meta-science (i.e. research on research).

Objective: The goal of this work was to create implantable stimulator systems that could be used in animal experiments on laryngeal paralysis, including “closed-loop” stimulation of impaired muscles triggered by electromyographic (EMG) potentials from healthy muscles. Study Design: Iterative device design and testing. Methods: A series of microcontroller-based implantable devices were built that incorporated increasingly sophisticated features for stimulation, EMG recording, and communication across the skin. Specific engineering challenges included minimizing power consumption, achieving charge-balanced and relatively high stimulation capacity, implementing noninvasive communication across the skin, providing real-time processing of EMG signals, and mitigating effects of shock artifacts. Bench testing was used to verify performance. Results: Two prototypes are described in detail. Each system is based on an “implant” and an external “communication adapter” that interfaces both with the implant and with external computers for adjustments and monitoring. The first version described is inductively powered and referred to as the “inductive laryngeal stimulator.” It uses inductive coupling for both power and communication and performs EMG processing in the communication adapter module. The second version, a “battery-powered laryngeal stimulator,” consists of an autonomous battery-powered implant with onboard EMG processing and artifact control; it communicates by infrared light with the external communication adapter for setup and monitoring. Conclusions: The devices met design and performance specifications and have proved useful in the animal experiments that are described in Part 2 of this series. Detailed descriptions of the circuits and their firmware are made available in the Appendix. Level of Evidence: NA

This article provides a second manifestation of a new tradition by which the editors of Comments on Inorganic Chemistry wish to lead by example, whereby we start publishing original research conten...

A method for modeling permanent magnet motors including saturation effects on cogging and motive torque is described. This method rivals the accuracy of finite element analyses but solves 4–5 orders of magnitude faster, depending on several factors. Simulation results match well with laboratory measurements.

This paper presents the design and implementation of a large-step-down soft-switched dc-dc converter based on the active bridge technique which overcomes some of the limitations of the conventional Dual Active Bridge (DAB) converter. The topology comprises a double stacked-bridge inverter coupled to a reconfigurable rectifier through a special three-winding leakage transformer. This particular combination of stages enable the converter to run in an additional low-power mode that greatly increases light-load efficiency by reducing core loss and extending the zero-voltage switching (ZVS) range. The converter is implemented with a single compact magnetic component, providing power combining, voltage transformation, isolation, and energy transfer inductance. A 175 kHz, 300 W, 380 V to 12 V GaN-based prototype converter achieves 95.9% efficiency at full load, a peak efficiency of 97.0%, an efficiency above 92.7% down to 10% load and an efficiency above 79.8% down to 3.3% load.

Although personalization of cancer care is recommended, current follow-up after the curative treatment of breast cancer is consensus-based and not differentiated for base-line risk. Every patient receives annual follow-up for 5 years without taking into account the individual risk of recurrence. The aim of this study was to introduce personalized follow-up schemes by stratifying for age. Using data from the Netherlands Cancer Registry of 37 230 patients with early breast cancer between 2003 and 2006, the risk of recurrence was determined for four age groups (70). Follow-up was modeled with a discrete-time partially observable Markov decision process. The decision to test for recurrences was made two times per year. Recurrences could be detected by mammography as well as by self-detection. For all age groups, it was optimal to have more intensive follow-up around the peak in recurrence risk in the second year after diagnosis. For the first age group (