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IMPORTANCE: Although immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1) and PD-1 ligand 1 have improved the outcome for many cancer types, the majority of patients fails to respond to ICI monotherapy. Hypofractionated radiotherapy has the potential to improve the therapeutic ratio of ICIs. OBJECTIVE: To assess the addition of radiotherapy to ICIs compared with ICI monotherapy in patients with advanced solid tumors. DESIGN, SETTING, AND PARTICIPANTS: This open-label, multicenter, randomized phase 2 trial was conducted in 5 Belgian hospitals and enrolled participants between March 2018 and October 2020. Patients 18 years or older with locally advanced or metastatic melanoma, renal cell carcinoma, urothelial carcinoma, head and neck squamous cell carcinoma, or non–small cell lung carcinoma were eligible. A total of 99 patients were randomly assigned to either the control arm (n = 52) or the experimental arm (n = 47). Of those, 3 patients (1 in the control arm vs 2 in the experimental arm) withdrew consent and thus were not included in the analysis. Data analyses were performed between April 2022 and March 2023. INTERVENTIONS: Patients were randomized (1:1) to receive anti–PD-1/PD-1 ligand 1 ICIs alone as per standard of care (control arm) or combined with stereotactic body radiotherapy 3 × 8 gray to a maximum of 3 lesions prior to the second or third ICI cycle, depending on the frequency of administration (experimental arm). Randomization was stratified according to tumor histologic findings and disease burden (3 and fewer or more than 3 cancer lesions). MAIN OUTCOMES AND MEASURES: The primary end point was progression-free survival (PFS) as per immune Response Evaluation Criteria in Solid Tumors. Key secondary end points included overall survival (OS), objective response rate, local control rate, and toxic effects. Efficacy was assessed in the intention-to-treat population, while safety was evaluated in the as-treated population. RESULTS: Among 96 patients included in the analysis (mean age, 66 years; 76 [79%] female), 72 (75%) had more than 3 tumor lesions and 65 (68%) had received at least 1 previous line of systemic treatment at time of inclusion. Seven patients allocated to the experimental arm did not complete the study-prescribed radiotherapy course due to early disease progression (n = 5) or intercurrent illness (n = 2). With a median (range) follow-up of 12.5 (0.7-46.2) months, median PFS was 2.8 months in the control arm compared with 4.4 months in the experimental arm (hazard ratio, 0.95; 95% CI, 0.58-1.53; P = .82). Between the control and experimental arms, no improvement in median OS was observed (11.0 vs 14.3 months; hazard ratio, 0.82; 95% CI, 0.48-1.41; P = .47), and objective response rate was not statistically significantly different (22% vs 27%; P = .56), despite a local control rate of 75% in irradiated patients. Acute treatment-related toxic effects of any grade and grade 3 or higher occurred in 79% and 18% of patients in the control arm vs 78% and 18% in the experimental arm, respectively. No grade 5 adverse events occurred. CONCLUSIONS AND RELEVANCE: This phase 2 randomized clinical trial demonstrated that while safe, adding subablative stereotactic radiotherapy of a limited number of metastatic lesions to ICI monotherapy failed to show improvement in PFS or OS. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03511391

The systems of transferable development rights in the USA and France are studied. The system has encountered limited success in the USA due to differences in practice with Western European countries. The mechanism of these systems must be specific owing to the differences in practical and theoretical issues.

Van der Waals heterojunctions composed of graphene and transition metal dichalcogenides have gain much attention because of the possibility to control and tailor band structure, promising applications in two-dimensional optoelectronics and electronics. In this report, we characterized the van der Waals heterojunction MoSe2/few-layer graphene with a high-quality interface using cutting-edge surface techniques scaling from atomic to microscopic range. These surface analyses gave us a complete picture of the atomic structure and electronic properties of the heterojunction. In particular, we found two important results: the commensurability between the MoSe2and few-layer graphene lattices and a band-gap opening in the few-layer graphene. The band gap is as large as 250 meV, and we ascribed it to an interface charge transfer that results in an electronic depletion in the few-layer graphene. This conclusion is well supported by electron spectroscopy data and density functional theory calculations. The commensurability between the MoSe2and graphene lattices as well as the band-gap opening clearly show that the interlayer interaction goes beyond the simple van der Waals interaction. Hence, stacking two-dimensional materials in van der Waals heterojunctions enables us to tailor the atomic and electronic properties of individual layers. It also permits the introduction of a band gap in few-layer graphene by interface charge transfer.

We use a non-intrusive technique based on a polarization scheme to probe the periodic alignment of the CO2and N2molecules induced by a strong laser pulse linearly polarized. A weak probe field experiences the birefringence resulting from the alignment of the molecules. By comparing the probe depolarization signal with the numerical simulation of the time-dependent Schrödinger equation, it is possible to quantify the alignment of the molecular sample. The modelling takes into account the spatial profile of the pump intensity. It allows from the alignment signal to determine the onset of saturation due to ionization, despite the intrinsic saturation of the alignment arising for about the same laser intensity.

WE report here preliminary results from the detailed sampling of granitic basement at a depth of 4,000 m at the lower edge of the Armorican continental margin near 48°N and 12°W. We consider that we have sampled here the extreme lateral limit of the continental crust where local exposures emerge from under a cover of Cainozoic, Mesozoic and probable Palaeozoic sediments.

Detailed bathymetric investigations were performed in four zones of the Hellenic trench system in 1978, using the multi-narrow beam echo-sounder “Sea-Beam” on R.V. “Jean Charcot”. In 1979, a field-study using the 3000 m submersible “Cyana” was conducted in three of the four sites covered by Sea-Beam. We summarize here the principal tectonic results of these studies and publish the corresponding Sea-Beam maps. It is shown that compressional structures affect the sedimentary cover of the outer wall and trench whereas extensional tectonics is present on the inner wall. In addition, there is evidence that most of the upper sedimentary cover is not subducted but rather piles up in front of the trench to form the Mediterranean ridge. We suggest that the surface limit of the zone of mechanical decoupling occurs near the base of the inner wall. We show that the gross structure of the trench as well as the strain pattern observed is controlled by the kinematics of subduction and we discuss its evolution since its initiation about 13 m.y. ago.

Short Sea-Beam survey cruises were conducted by the R.V. “Jean Charcot” in march 1980 along the Middle America Trench between Panama and Acapulco, with particular emphasis on the IPOD Legs 66 and 67 areas. These detailed mappings have revealed that the Cocos horst- and graben pattern, related to the bending of the oceanic plate, strikes generally 20°–30° oblique to the trench direction. This en-échelon pattern, closely parallel to the magnetic anomalies, is here proposed as being due to the reactivation of inherited fractures generated at the East Pacific Rise. Sea-Beam data, together with UTMSI multichannel seismic reflection profiles and IPOD drilling results, clearly show that at least two distinct geodynamic processes are presently working along the same trench: accretion and no accretion. They also show a relative structural homogeneity of the oceanic side of the trench in contrast to the dual aspect of the continental side.

Navigation by Loran-C was evaluated in comparison with GPS's data during the Jean Charcot cruise for the French-Japanese cooperative project, Kaiko. Simple overlapping mean of Loran-C positions for five minutes showed a good relative accuracy of about 50 meters. Loran-C positions, however, showed systematic shift up to one kilometer due to propagation delay of Loran-C wave through land area. The value of the shift was measured in the south off the Japanese Islands; it was found that the shift of Loran-C position can be corrected within an accuracy of about 100 meters in most cases by use of the correction table prepared by the Hydrographic Department of Japan. In a special case as the Loran-C wave propagates over a high mountain area or along a long coastal line, the recommended correction procedure for propagation delay should be improved to correct the local effects (∼200m).

The Mid America Trench, off the Pacific coast of southern Mexico and central America, is the site of northeastward subduction of the Cocos oceanic plate under the North America and Caribbean plates1(Fig. 1). In Guatemala, the North America and Caribbean plates are separated by the Polochic–Motagua left-lateral strike-slip faults (Fig. 1). The trench itself appears to be divided into two distinct sections at its intersection with the Tehuantepec Ridge. To the south the margin of the trench is wide and consists of a well developed shelf basin2bounded on the east by a huge volcanic cordillera parallel with the trench axis at a distance of ∼200 km. In contrast, to the north, the margin is narrow and devoid of shelf basin; landwards, the trans-Mexican volcanic belt trends oblique to the trench. This volcanic chain would be anomalous if it were related to the subduction of the Cocos plate off southern Mexico. In 1979, as part of the International Phase of Ocean Drilling (IPOD) of the Deep Sea Drilling Project, Legs 66 and 67 respectively explored the northern (off Acapulco, Mexico) and southern (off San Jose, Guatemala) section of the Mid America Trench3–6(Fig. 1). Since then short topographical surveys of the trench have been carried out by RV Jean Charcot8using the sea-beam technique7. We report here that both sets of data, together with UTMSI multichannel seismic profiles10,11can be used to reconstruct the processes of subduction along the Mid America Trench.

This paper describes a pop-up ocean bottom seismograph designed primarily for refraction surveys both on the continental shelf and in deep sea. Its development is the extension of our system based on seismic detectors located on the sea floor with radio transmission of seismic signals and used for seismic refraction studies on the continental shelf. The seismic detectors (vertical geophone or hydrophone and two orthogonally mounted horizontal geophones) are located outside of the pressure vessel on the main frame. Optionally, the seismic sensors may be decoupled from the main frame assembly. This decoupling is performed by a mobile arm positioning the separate three component sensor package on the sea floor.

The field-free alignment of CO_2 produced in response to the excitation of a molecule by a high-intensity femtosecond pump pulse is measured with a simple coronography-like technique. The technique is based on the defocusing of a time-delayed probe pulse produced by the spatial distribution of aligned molecules. In the intensity regime explored here, the technique is shown to give valuable information about dynamic alignment. With the help of simulations, the degree of alignment is extracted from the data.

Despite the promising potential of nanomaterials, their co-integration with CMOS, especially in interconnection levels, remains challenging because their fabrication has to be done within severe constrains. These nanomaterials can be grown by catalytic Chemical Vapor Deposition but the catalyst should be compatible with Back-End-Of-Line (BEOL) processes. Moreover, synthesis temperatures have to be lower than 450°C. This paper discusses two examples of CVD grown nanomaterials using BEOL compatible processes. First, we investigate the growth of a composite made of carbon nanotubes capped by few graphene layers. By using appropriate catalyst and gaseous carbon precursor, we show that carbon nanotubes can grow epitaxially under the graphene layers at compatible temperatures. Then, we describe a method to grow silicon nanowires using BEOL-compatible copper-based catalysts. In this case, oxidation of copper prior to growth allows reducing silicon nanowire synthesis temperature below 450°C.

We present the results of several multi-narrow-beam (Sea-Beam) traverses of the Mediterranean ridge on board R.V. “Jean Charcot”. These results can be considered to be complementary, in resolution and coverage, to the previously published long-range side-scan sonar (Gloria) results. A characteristic of the Mediterranean ridge is the presence over about half of its surface of an extensive fold system affecting the Messinian and Plio-Quaternary cover, which is dissected by conjugate strike-slip faults. The resolution of Sea-Beam was used to map the main characteristics of folding and faulting. This analysis, together with previously available data, enables us to define the strain pattern over the Mediterranean ridge. We thus now have an overall view of the strain pattern from a marginal basin (Aegea) through the Hellenic trench and adjacent sea-floor to the opposite continent. The bottom of the Hellenic trench is a boundary between an extensional domain to the north and a compressional one to the south. The southern domain is strongly affected by the presence of the Lybian promontary. It is related to the formation of an accretionary ridge due to the inability of the upper 3–4 km of sediments to subduct. This ridge is similar to the accretionary prism but it is much wider with respect to its height, probably because of the existence of a decollement over a level of overpressure. The Hellenic trench then is in the situation of a fore-arc basin. Its origin is due to the fact that the Aegean continental slope is not vertical but rather has a small 4° dip. As a result, a sedimentary wedge, symmetric but shorter than the main accretionary wedge develops over the buried portion of the slope. It is characterized by landward thrusts. Such an origin probably applies to fore-arc basins in general.