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Introduction: Molecular profiling of NSCLC is essential for optimising treatment decisions, but often incomplete. We assessed the efficacy of protocolised molecular profiling in the current standard-of-care (SoC) in a prospective observational study in the Netherlands and measured the effect of providing standardised diagnostic procedures. We also explored the potential of plasma-based molecular profiling in the primary diagnostic setting. Methods: This multi-centre prospective study was designed to explore the performance of current clinical practice during the run-in phase using local SoC tissue profiling procedures. The subsequent phase was designed to investigate the extent to which comprehensive molecular profiling (CMP) can be maximized by protocolising tumour profiling. Successful molecular profiling was defined as completion of at least EGFR and ALK testing. Additionally, PD-L1 tumour proportions scores were explored. Lastly, the additional value of centralised plasma-based testing for EGFR and KRAS mutations using droplet digital PCR was evaluated. Results: Total accrual was 878 patients, 22.0% had squamous cell carcinoma and 78.0% had non-squamous NSCLC. Stage I-III was seen in 54.0%, stage IV in 46.0%. Profiling of EGFR and ALK was performed in 69.9% of 136 patients included in the run-in phase, significantly more than real-world data estimates of 55% (p<0.001). Protocolised molecular profiling increased the rate to 77.0% (p = 0.049). EGFR and ALK profiling rates increased from 77.9% to 82.1% in non-squamous NSCLC and from 43.8% to 57.5% in squamous NSCLC. Plasma-based testing was feasible in 98.4% and identified oncogenic driver mutations in 7.1% of patients for whom tissue profiling was unfeasible. Conclusion: This study shows a high success rate of tissue-based molecular profiling that was significantly improved by a protocolised approach. Tissue-based profiling remains unfeasible for a substantial proportion of patients. Combined analysis of tumour tissue and circulating tumour DNA is a promising approach to allow adequate molecular profiling of more patients. [ABSTRACT FROM AUTHOR]

Introduction: Haemorrhoidal disease (HD) is a common condition with significant epidemiologic and economic implications. While it is possible to treat symptomatic grade 1–2 haemorrhoids with rubber band ligation (RBL) or sclerotherapy (SCL), the effectiveness of these treatments compatible with current standards has not yet been investigated with a randomised controlled trial. The hypothesis is that SCL is not inferior to RBL in terms of symptom reduction (patient-related outcome measures (PROMs)), patient experience, complications or recurrence rate. Methods and analysis: This protocol describes the methodology of a non-inferiority, multicentre, randomised controlled trial comparing rubber band ligation and sclerotherapy for symptomatic grade 1–2 haemorrhoids in adults (> 18 years). Patients are preferably randomised between the two treatment arms. However, patients with a strong preference for one of the treatments and refuse randomisation are eligible for the registration arm. Patients either receive 4 cc Aethoxysklerol 3% SCL or 3 × RBL. The primary outcome measures are symptom reduction by means of PROMs, recurrence and complication rates. Secondary outcome measures are patient experience, number of treatments and days of sick leave from work. Data are collected at 4 different time points. Discussion: The THROS trial is the first large multicentre randomised trial to study the difference in effectivity between RBL and SCL for the treatment of grade 1–2 HD. It will provide information as to which treatment method (RBL or SCL) is the most effective, gives fewer complications and is experienced by the patient as the best option. Ethics and dissemination: The study protocol has been approved by the Medical Ethics Review Committee of the Amsterdam University Medical Centers, location AMC (nr. 2020_053). The gathered data and results will be submitted for publication in peer-reviewed journals and spread to coloproctological associations and guidelines. Trial registration: Dutch Trial Register NL8377. Registered on 12–02-2020. [ABSTRACT FROM AUTHOR]

Electrostatic confinement in semiconductors provides a flexible platform for the emulation of interacting electrons in a two-dimensional lattice, including in the presence of gauge fields. This combination offers the potential to realize a wide host of quantum phases. Capacitance spectroscopy provides a technique that allows one to directly probe the density of states of such two-dimensional electron systems. Here, we present a measurement and fabrication scheme that builds on capacitance spectroscopy and allows for the independent control of density and periodic potential strength imposed on a two-dimensional electron gas. We characterize disorder levels and (in)homogeneity and develop and optimize different gating strategies at length scales where interactions are expected to be strong. A continuation of these ideas might see to fruition the emulation of interaction-driven Mott transitions or Hofstadter butterfly physics. [ABSTRACT FROM AUTHOR]

Purpose: Hospitals performing a certain bariatric procedure in high volumes may have better outcomes. However, they could also have worse outcomes for some patients who are better off receiving another procedure. This study evaluates the effect of hospital preference for a specific type of bariatric procedure on their overall weight loss results. Methods: All hospitals performing bariatric surgery were included from the nationwide Dutch Audit for Treatment of Obesity. For each hospital, the expected (E) numbers of sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and one-anastomosis gastric bypass (OAGB) were calculated given their patient-mix. These were compared with the observed (O) numbers as the O/E ratio in a funnel plot. The 95% control intervals were used to identify outlier hospitals performing a certain procedure significantly more often than expected given their patient-mix (defined as hospital preference for that procedure). Similarly, funnel plots were created for the outcome of patients achieving ≥ 25% total weight loss (TWL) after 2 years, which was linked to each hospital's preference. Results: A total of 34,558 patients were included, with 23,154 patients completing a 2-year follow-up, of whom 79.6% achieved ≥ 25%TWL. Nine hospitals had a preference for RYGB (range O/E ratio [1.09–1.53]), with 1 having significantly more patients achieving ≥ 25%TWL (O/E ratio [1.06]). Of 6 hospitals with a preference for SG (range O/E ratio [1.10–2.71]), one hospital had significantly fewer patients achieving ≥ 25%TWL (O/E ratio [0.90]), and from two hospitals with a preference for OAGB (range O/E ratio [4.0–6.0]), one had significantly more patients achieving ≥ 25%TWL (O/E ratio [1.07]). One hospital had no preference for any procedure but did have significantly more patients achieving ≥ 25%TWL (O/E ratio [1.10]). Conclusion: Hospital preference is not consistently associated with better overall weight loss results. This suggests that even though experience with a procedure may be slightly less in hospitals not having a preference, it is still sufficient to achieve similar weight loss outcomes when surgery is provided in centralized high-volume bariatric institutions. [ABSTRACT FROM AUTHOR]

NMi Van Swinden Laboratory, Thijsseweg 11, 2629 JA Delft, The Netherlands We experimentally demonstrate that a stabilized femtosecond frequency comb can be applied as a tool for distance measurement in an interferometric scheme. A proof of principle of this method, as proposed by Ye [5], is provided by measuring a displacement of about 15 cm in air and comparing it to a reference value from a calibrated laser interferometer. The experiment shows that the new scheme easily achieves an accuracy better than one optical fringe.

BACKGROUND Size of fruit is an important issue in determining yield at harvest. Even under controlled conditions, variation between fruit and trusses can be considerable. As an easy to measure indication of size, the diameter of tomatoes growing in trusses was assessed in three experiments with different number of tomatoes per truss, as well as cultivars, and also by varying the level of ions in the recirculated drain water. RESULTS: By applying the von Bertalanffy growth model, more than 99% of the variation present could be explained by the time of fruit set for all tomatoes growing anywhere in the trusses. A linear relationship between time of fruit set and the biological shift factor, an indication of developmental age, was observed. Integrating this linear relationship in the analysis of the diameter data removed one stochastic variable (biological shift factor), effectively halving the number of parameters to be estimated. CONCLUSION: The results of the present study indicate that the major part of the variation present in the diameter of tomatoes growing in trusses is the result of variation in the time of fruit set of individual fruits. The position within the greenhouse (i.e. local differences in assimilates supply) exerted only a minor effect on diameter development. Accordingly, the time of fruit set largely determines fruit size. Likely, growing conditions before fruit set are crucial for final fruit size. The time of fruit set of each tomato in the truss and the local growing conditions within the greenhouse that affect assimilate supply need to be assessed accurately for a reliable size prediction. [ABSTRACT FROM AUTHOR]

More than 50 years ago, John Bell proved that no theory of nature that obeys locality and realism can reproduce all the predictions of quantum theory: in any local-realist theory, the correlations between outcomes of measurements on distant particles satisfy an inequality that can be violated if the particles are entangled. Numerous Bell inequality tests have been reported; however, all experiments reported so far required additional assumptions to obtain a contradiction with local realism, resulting in 'loopholes'. Here we report a Bell experiment that is free of any such additional assumption and thus directly tests the principles underlying Bell's inequality. We use an event-ready scheme that enables the generation of robust entanglement between distant electron spins (estimated state fidelity of 0.92 ± 0.03). Efficient spin read-out avoids the fair-sampling assumption (detection loophole), while the use of fast random-basis selection and spin read-out combined with a spatial separation of 1.3 kilometres ensure the required locality conditions. We performed 245 trials that tested the CHSH-Bell inequality S ≤ 2 and found S = 2.42 ± 0.20 (where S quantifies the correlation between measurement outcomes). A null-hypothesis test yields a probability of at most P = 0.039 that a local-realist model for space-like separated sites could produce data with a violation at least as large as we observe, even when allowing for memory in the devices. Our data hence imply statistically significant rejection of the local-realist null hypothesis. This conclusion may be further consolidated in future experiments; for instance, reaching a value of P = 0.001 would require approximately 700 trials for an observed S = 2.4. With improvements, our experiment could be used for testing less-conventional theories, and for implementing device-independent quantum-secure communication and randomness certification. [ABSTRACT FROM AUTHOR]

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OBJECTIVE:: Examination of the relationship of impairment to disability in the work psychiatry context and identification of practical strategies for occupational physicians to apply to screening, management, and appropriate referral. METHODS:: Medical literature review. RESULTS:: The determination and differentiation of impairment and disability is a complex psychiatric task which requires consideration of the type of employment, assessment of depression-related functional impairments that can create disability for a particular occupation, and individual factors. CONCLUSIONS:: The authors propose a new and more consistent strategy for identifying impairment severity and its impact on employment, including simple procedures to screen for depression and guidelines to minimize role and boundary confusion. [ABSTRACT FROM AUTHOR]

In electro-optic detection of terahertz transients, the photodiodes of a differential detector are often illuminated with optical powers on the order of several milliwatts. We present measurements that show that the response of the photodiodes at these power levels is distorted, giving rise to frequency-dependent amplitude and phase changes in the electrical signal from these diodes. We find that these distortions significantly reduce the ability of the detector to suppress laser amplitude noise. Surprisingly, this occurs at power levels at which the dc output of each photodiode shows no sign of saturation. Based on our measurements, we provide experimenters with recommendations to improve the amplitude noise suppression of a differential detector under high levels of illumination. [ABSTRACT FROM AUTHOR]

We have built a relatively simple, highly efficient, THz emission and detection system centered around a 15 fs Ti:sapphire laser. In the system, 200 mW of laser power is focused to a 120 µm diam spot between two silverpaint electrodes on the surface of a semi-insulating GaAs crystal, kept at a temperature near 300 K, biased with a 50 kHz, ±400 V square wave. Using rapid delay scanning and lock-in detection at 50 kHz, we obtain probe laser quantum-noise limited signals using a standard electro-optic detection scheme with a 1-mm-thick (110) oriented ZnTe crystal or a (110) oriented 0.1-mm-thick GaP crystal. The maximum THz-induced differential signal that we observe is ΔI/I=7×10[sup -3], corresponding to a THz peak amplitude of 95 V/cm. The THz average power was measured to be about 40 µW, to our knowledge, the highest power reported so far generated with Ti:sapphire oscillators as a pump source. The system uses off-the-shelf electronics and requires no microfabrication techniques. [ABSTRACT FROM AUTHOR]

Objectives: This report describes successful anaesthesia and electroconvulsive therapy (ECT) in a patient with an unruptured basilar artery aneurysm. ECT is associated with a hyperdynamic state characterised by arterial hypertension, tachycardia, and considerably increased cerebral blood flow rate and velocity. These responses pose an increased risk for subarachnoid haemorrhage when an intracranial aneurysm coexists.Methods: A 54 year old woman presented for ECT. She had a 20 year history of major depression which was unresponsive to three different antidepressant drugs. There was also an unruptured 5 mm saccular aneurysm at the basilar tip, which had been documented by cerebral angiography, but its size had remained unchanged for the previous four years. After she declined surgical intervention, she gave informed consent for ECT. During a series of seven ECT sessions middle cerebral artery flow velocity was recorded by a pulsed transcranial Doppler ultrasonography system. She was pretreated with 50 mg oral atenolol daily, continuing up to the day of the last ECT and immediately before each treatment, sodium nitroprusside was infused at a rate of 30 microg/min, to reduce systolic arterial pressure to 90-95 mm Hg.Results: Systolic flow velocity during the awake state ranged from 62-75 cm/s, remaining initially unchanged with sodium nitroprusside infusion. After induction of anaesthesia (0.5 mg/kg methohexitone and 0.9 mg/kg succinylcholine), flow velocities decreased to 39-54 cm/s, reaching maximal values of 90 cm/s (only 20% above baseline) after ECT. These flow velocities recorded post-ECT were considerably below the more than twofold increase recorded when no attenuating drugs were used. Systolic arterial blood pressure reached maximal values of 110-140 mm Hg and heart rate did not exceed 66 bpm. Rapid awakening followed each treatment, no focal or global neurological signs were apparent, and the patient was discharged in remission.Conclusion: In a patient with major depression and a coexisting intracerebral saccular aneurysm who was treated with ECT, the combination of beta blockade with atenolol and intravenous infusion of sodium nitroprusside prevented tachycardia and hypertension, and greatly attenuated the expected increase in flow velocity in the middle cerebral artery. [ABSTRACT FROM AUTHOR]

We present experimental results on the crosstalk between two ac-operated dispersive bifurcation detectors, implemented in a circuit for high-fidelity readout of two strongly coupled flux qubits. Both phase-dependent and phase-independent contributions to the crosstalk are analyzed. For proper tuning of the phase the measured crosstalk is 0.1% and the correlation between the measurement outcomes is less than 0.05%. These results show that bifurcative readout provides a reliable and generic approach for multipartite correlation experiments. [ABSTRACT FROM AUTHOR]

We fabricated and tested a squelch circuit consisting of a copper powder filter with an embedded Josephson junction connected to ground. For small signals (squelch ON), the small junction inductance attenuates strongly from dc to at least 1 GHz, while for higher frequencies dissipation in the copper powder increases the attenuation exponentially with frequency. For large signals (squelch OFF), the circuit behaves as a regular metal powder filter. The measured ON/OFF ratio is larger than 50 dB up to 50 MHz. This squelch can be applied in low temperature measurement and control circuitry for quantum nanostructures, such as superconducting qubits and quantum dots. [ABSTRACT FROM AUTHOR]

The authors employ a cryogenic high electron mobility transistor (HEMT) amplifier to increase the bandwidth of a charge detection setup with a quantum point contact (QPC) charge sensor. The HEMT is operating at 1 K and the circuit has a bandwidth of 1 MHz. The noise contribution of the HEMT at high frequencies is only a few times higher than that of the QPC shot noise. The authors use this setup to monitor single-electron tunneling to and from an adjacent quantum dot. The authors measure fluctuations in the dot occupation as short as 400 ns, 20 times faster than in previous work. [ABSTRACT FROM AUTHOR]

The authors have studied low-frequency resistance fluctuations in shadow-evaporated Al/AlOx/Al tunnel junctions. Between 300 and 5 K the spectral density follows a 1/f law. Below 5 K, individual defects distort the 1/f shape of the spectrum. The spectral density decreases linearly with temperature between 150 and 1 K and saturates below 0.8 K. At 4.2 K, it is about two orders of magnitude lower than expected from a recent survey [D. J. Van Harlingen et al., Phys. Rev. B 70, 064510 (2004)]. Due to saturation below 0.8 K the estimated qubit dephasing times at 100 mK are only about two times longer than calculated by Van Harlingen et al. [ABSTRACT FROM AUTHOR]

We observe individual tunnel events of a single electron between a quantum dot and a reservoir, using a nearby quantum point contact (QPC) as a charge meter. The QPC is capacitively coupled to the dot, and the QPC conductance changes by about 1% if the number of electrons on the dot changes by one. The QPC is voltage biased and the current is monitored with a current–voltage (I–V) convertor at room temperature. We can resolve tunnel events separated by only 8 μs, limited by noise from the I–V convertor. Shot noise in the QPC sets a 25 ns lower bound on the accessible timescales. [ABSTRACT FROM AUTHOR]

The tunnelling of quasiparticles across Josephson junctions in superconducting quantum circuits is an intrinsic decoherence mechanism for qubit degrees of freedom. Understanding the limits imposed by quasiparticle tunnelling on qubit relaxation and dephasing is of theoretical and experimental interest, particularly as improved understanding of extrinsic mechanisms has allowed crossing the 100 microsecond mark in transmon-type charge qubits. Here, by integrating recent developments in high-fidelity qubit readout and feedback control in circuit quantum electrodynamics, we transform a state-of-the-art transmon into its own real-time charge-parity detector. We directly measure the tunnelling of quasiparticles across the single junction and isolate the contribution of this tunnelling to qubit relaxation and dephasing, without reliance on theory. The millisecond timescales measured demonstrate that quasiparticle tunnelling does not presently bottleneck transmon qubit coherence, leaving room for yet another order of magnitude increase. [ABSTRACT FROM AUTHOR]