Prognostic significance of absolute lymphocyte count in patients with metastatic renal cell carcinoma receiving first-line combination immunotherapies: results from the International Metastatic Renal Cell Carcinoma Database Consortium.

BACKGROUND: Lymphocytes are closely linked to mechanisms of action of immuno-oncology (IO) agents. We aimed to assess the prognostic significance of absolute lymphocyte count (ALC) in patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: Using the International mRCC Database Consortium (IMDC), patients receiving first-line IO-based combination therapy were analysed. Baseline patient characteristics, objective response rates (ORRs), time to next treatment (TTNT), and overall survival (OS) were compared. RESULTS: Of 966 patients included, 195 (20%) had lymphopenia at baseline, and they had a lower ORR (37% versus 45%; P < 0.001), shorter TTNT (10.1 months versus 24.3 months; P < 0.001), and shorter OS (30.4 months versus 48.2 months; P < 0.001). Among 125 patients with lymphopenia at baseline, 52 (42%) experienced ALC recovery at 3 months, and they had longer OS (not reached versus 30.4 months; P = 0.012). On multivariable analysis for OS, lymphopenia was an independent adverse prognostic factor (hazard ratio 1.68; P < 0.001). Incorporation of lymphopenia into the IMDC criteria improved OS prediction accuracy (C-index from 0.688 to 0.707). CONCLUSIONS: Lymphopenia was observed in one-fifth of treatment-naive patients with mRCC and may serve as an indicator of unfavourable oncologic outcomes in the contemporary IO era.

Strain-Gradient Position Mapping of Semiconductor Quantum Dots.

We introduce a nondestructive method to determine the position of randomly distributed semiconductor quantum dots (QDs) integrated in a solid photonic structure. By setting the structure in an oscillating motion, we generate a large stress gradient across the QDs plane. We then exploit the fact that the QDs emission frequency is highly sensitive to the local material stress to map the position of QDs deeply embedded in a photonic wire antenna with an accuracy ranging from ±35 nm down to ±1 nm. In the context of fast developing quantum technologies, this technique can be generalized to different photonic nanostructures embedding any stress-sensitive quantum emitters.

The coupled atom transistor.

We describe the first implementation of a coupled atom transistor where two shallow donors (P or As) are implanted in a nanoscale silicon nanowire and their electronic levels are controlled with three gate voltages. Transport spectroscopy through these donors placed in series is performed both at zero and microwave frequencies. The coherence of the charge transfer between the two donors is probed by Landau-Zener-Stückelberg interferometry. Single-charge transfer at zero bias (electron pumping) has been performed and the crossover between the adiabatic and non-adiabatic regimes is studied.

Bidimensional nano-optomechanics and topological backaction in a non-conservative radiation force field.

Optomechanics, which explores the fundamental coupling between light and mechanical motion, has made important advances in manipulating macroscopic mechanical oscillators down to the quantum level. However, dynamical effects related to the vectorial nature of the optomechanical interaction remain to be investigated. Here we study a nanowire with subwavelength dimensions coupled strongly to a tightly focused beam of light, enabling an ultrasensitive readout of the nanoresonator dynamics. We determine experimentally the vectorial structure of the optomechanical interaction and demonstrate that a bidimensional dynamical backaction governs the nanowire dynamics. Moreover, the spatial topology of the optomechanical interaction is responsible for novel canonical signatures of strong coupling between mechanical modes, which leads to a topological instability that underlies the non-conservative nature of the optomechanical interaction. These results have a universal character and illustrate the increased sensitivity of nanomechanical devices towards spatially varying interactions, opening fundamental perspectives in nanomechanics, optomechanics, ultrasensitive scanning force microscopy and nano-optics.

Synchronizing the dynamics of a single nitrogen vacancy spin qubit on a parametrically coupled radio-frequency field through microwave dressing.

A hybrid spin-oscillator system in parametric interaction is experimentally emulated using a single nitrogen vacancy (NV) spin qubit immersed in a radio frequency (rf) field and probed with a quasiresonant microwave (MW) field. We report on the MW-mediated locking of the NV spin dynamics onto the rf field, appearing when the MW-driven Rabi precession frequency approaches the rf frequency and for sufficiently large rf amplitudes. These signatures are analogous to a phononic Mollow triplet in the MW rotating frame for the parametric interaction and promise to have impact in spin-dependent force detection strategies.

Strain-mediated coupling in a quantum dot-mechanical oscillator hybrid system.

Recent progress in nanotechnology has allowed the fabrication of new hybrid systems in which a single two-level system is coupled to a mechanical nanoresonator. In such systems the quantum nature of a macroscopic degree of freedom can be revealed and manipulated. This opens up appealing perspectives for quantum information technologies, and for the exploration of the quantum-classical boundary. Here we present the experimental realization of a monolithic solid-state hybrid system governed by material strain: a quantum dot is embedded within a nanowire that features discrete mechanical resonances corresponding to flexural vibration modes. Mechanical vibrations result in a time-varying strain field that modulates the quantum dot transition energy. This approach simultaneously offers a large light-extraction efficiency and a large exciton-phonon coupling strength g0. By means of optical and mechanical spectroscopy, we find that g0/2 π is nearly as large as the mechanical frequency, a criterion that defines the ultrastrong coupling regime.

Coherent coupling of two dopants in a silicon nanowire probed by Landau-Zener-Stückelberg interferometry.

We report on microwave-driven coherent electron transfer between two coupled donors embedded in a silicon nanowire. By increasing the microwave frequency we observe a transition from incoherent to coherent driving revealed by the emergence of a Landau-Zener-Stückelberg quantum interference pattern of the measured current through the donors. This interference pattern is fitted to extract characteristic parameters of the double-donor system. In particular we estimate a charge dephasing time of 0.3±0.1 ns, comparable to other types of charge-based two-level systems. The demonstrated coherent coupling between two dopants is an important step towards donor-based quantum computing devices in silicon.

A two-atom electron pump.

With the development of single-atom transistors, consisting of single dopants, nanofabrication has reached an extreme level of miniaturization. Promising functionalities for future nanoelectronic devices are based on the possibility of coupling several of these dopants to each other. This already allowed to perform spectroscopy of the donor state by d.c. electrical transport. The next step, namely manipulating a single electron over two dopants, remains a challenge. Here we demonstrate electron pumping through two phosphorus donors in series implanted in a silicon nanowire. While quantized pumping is achieved in the low-frequency adiabatic regime, we observe remarkable features at higher frequency when the charge transfer is limited either by the tunnelling rates to the electrodes or between the two donors. The transitions between quantum states are modelled involving a Landau-Zener transition, allowing to reproduce in detail the characteristic signatures observed in the non-adiabatic regime.

Detection of a large valley-orbit splitting in silicon with two-donor spectroscopy.

We measure a large valley-orbit splitting for shallow isolated phosphorus donors in a silicon gated nanowire. This splitting is close to the bulk value and well above previous reports in silicon nanostructures. It was determined using a double dopant transport spectroscopy which eliminates artifacts induced by the environment. Quantitative simulations taking into account the position of the donors with respect to the Si/SiO2 interface and electric field in the wire show that the values found are consistent with the device geometry.

[Familial primary disseminated amyloidosis (a new clinical form?)]. / Amylose disséminée primitive familiale (nouvelle forme clinique?).

This report concerns two siblings we observed, one male the other female, who presented with primary disseminated amyloidosis. Repeated blood and urine examinations failed to demonstrate dysglobulinaemia. The brother developed, at the age of 51, extensive cutaneous amyloidosis with xanthochromia of the entire upper part of his body. His dermis contained a potassium permanganate-resistant amyloid substance. One year later, he presented with amyloid cardiomyopathy confirmed by biopsy. Owing to the intractable cardiac failure, heart transplantation was performed, but the patient died post-operatively. At autopsy, amyloid deposits were found to be present in the heart, liver, spleen and adrenal glands. His sister developed, at the age of 40, cutaneous amyloidosis in the form of yellowish and purpuric papules and plaques disseminated over the upper part of her body. Histological examination and electron microscopy of the skin showed large potassium permanganate-resistant amyloid deposits. In addition, endoscopy and histology demonstrated the presence of amyloid substance deposits in her larynx, oesophagus and rectum. Echocardiography revealed amyloid cardiomyopathy. She now has moderate cardiac failure, and heart transplantation is being contemplated. Like her brother, she has no renal of neurological amyloid lesions. There is no abnormality of serum or urinary globulins, and her SAA protein is present in normal concentrations. These cases do not fit in with the known nosological framework of amyloidosis. Clinically, both patients had disseminated amyloidosis of the AL type, and their disease clearly differed from familial systemic amyloidosis with neuropathy or nephropathy. To our knowledge, no case of familial primary amyloidosis of the AL type without dysglobulinaemia has yet been reported.