Objectifs Un échec de traitement peut entraîner diverses conséquences à la fois pour le patient souffrant de schizophrénie mais aussi en terme de santé publique (arrêt du traitement, hospitalisation, ...addiction, arrestation/incarcération) 1–3 . Cette étude a comparé en vraie vie, les délais avant échec au traitement des patients souffrant de schizophrénie ayant des antécédents d’incarcération, traités soit par palmitate de paliperidone (PP) ou par des antipsychotiques oraux (APO). Méthodes Paliperidone Research In Demonstrating Effectiveness (PRIDE) est une étude en ouvert, prospective, randomisée, d’une durée de 15 mois, comparant le PP une fois par mois aux APO chez des sujets atteints de schizophrénie, avec des antécédents d’incarcération ( NCT01157351 ). Les sujets ont été randomisés (1:1) en deux groupes : – PP à doses flexibles (78–234 mg) administrées une fois par mois ou à ; – l’un des 7 APO couramment prescrits par l’investigateur. Le critère de jugement principal était le délai avant échec du traitement (défini comme arrestation/incarcération, hospitalisation, suicide, arrêt du traitement ou supplémentation par manque d’efficacité ou mauvaise tolérance et/ou besoin d’intensifier les soins psychiatriques) évalué par la méthode de Kaplan-Meier. Résultats Un total de 450 sujets ont été inclus (sexe masculin = 86,3 %). Le délai avant échec du traitement était significativement plus long avec le PP par rapport aux APO (médiane = 416 vs 226 jours avant arrêt du traitement ou supplémentation ; Rapport de risque IC95 % = 1,43 1,09, 1,88 ; p = 0,011). Les taux d’échecs du traitement étaient de 39,8 % avec le PP et de 53,7 % avec les APO. Des résultats similaires ont été observés pour le délai avant hospitalisation ou arrestation/incarcération (médiane ≥ 450 vs 274 jours ; rapport de risque IC95 % = 1,43 1,06, 1,93 ; p = 0,019). Les événements indésirables les plus fréquents (PP vs APO, ≥ 10 %) étaient : douleur au site d’injection (18,6 % vs 0 %) ; insomnie (16,8 % vs 11,5 %) ; prise de poids (11,9 % vs 6,0 %) ; akathisie (11,1 % vs 6,9 %) ; anxiété (10,6 % vs 7,3 %). Conclusion Le traitement mensuel par PP injectable retarde significativement le délai de survenue d’un large éventail de conséquences négatives de la schizophrénie en vie réelle.
Evidence of life on Earth is manifestly preserved in the rock record. However, the microfossil record only extends to ∼3.5 billion years (Ga), the chemofossil record arguably to ∼3.8 Ga, and the rock ...record to 4.0 Ga. Detrital zircons from Jack Hills, Western Australia range in age up to nearly 4.4 Ga. From a population of over 10,000 Jack Hills zircons, we identified one >3.8-Ga zircon that contains primary graphite inclusions. Here, we report carbon isotopic measurements on these inclusions in a concordant, 4.10 ± 0.01-Ga zircon. We interpret these inclusions as primary due to their enclosure in a crack-free host as shown by transmission X-ray microscopy and their crystal habit. Their δ13CPDB of −24 ± 5‰ is consistent with a biogenic origin and may be evidence that a terrestrial biosphere had emerged by 4.1 Ga, or ∼300 My earlier than has been previously proposed.
High-entropy alloys, near-equiatomic solid solutions of five or more elements, represent a new strategy for the design of materials with properties superior to those of conventional alloys. However, ...their phase space remains constrained, with transition metal high-entropy alloys exhibiting only face- or body-centered cubic structures. Here, we report the high-pressure synthesis of a hexagonal close-packed phase of the prototypical high-entropy alloy CrMnFeCoNi. This martensitic transformation begins at 14 GPa and is attributed to suppression of the local magnetic moments, destabilizing the initial fcc structure. Similar to fcc-to-hcp transformations in Al and the noble gases, the transformation is sluggish, occurring over a range of >40 GPa. However, the behaviour of CrMnFeCoNi is unique in that the hcp phase is retained following decompression to ambient pressure, yielding metastable fcc-hcp mixtures. This demonstrates a means of tuning the structures and properties of high-entropy alloys in a manner not achievable by conventional processing techniques.
HIAF (High Intensity heavy ion Accelerator Facility), a new facility planned in China for heavy ion related researches, consists of two ion sources, a high intensity Heavy Ion Superconducting Linac ...(HISCL), a 45 Tm Accumulation and Booster Ring (ABR-45) and a multifunction storage ring system. The key features of HIAF are unprecedented high pulse beam intensity and versatile operation mode. The HIAF project aims to expand nuclear and related researches into presently unreachable region and give scientists possibilities to conduct cutting-edge researches in these fields. The general description of the facility is given in this article with a focus on the accelerator design.
Pressure-induced changes in the electronic structure of two-dimensional Cu-based materials have been a subject of intense study. In particular, the possibility of suppressing the Jahn–Teller ...distortion of d9 Cu centers with applied pressure has been debated over a number of decades. We studied the structural and electronic changes resulting from the application of pressures up to ca. 60 GPa on a two-dimensional copper(II)–chloride perovskite using diamond anvil cells (DACs), through a combination of in situ powder X-ray diffraction, electronic absorption and vibrational spectroscopy, dc resistivity measurements, and optical observations. Our measurements show that compression of this charge-transfer insulator initially yields a first-order structural phase transition at ca. 4 GPa similar to previous reports on other CuII–Cl perovskites, during which the originally translucent yellow solid turns red. Further compression induces a previously unreported phase transition at ca. 8 GPa and dramatic piezochromism from translucent red-orange to opaque black. Two-probe dc resistivity measurements conducted within the DAC show the first instance of appreciable conductivity in CuII–Cl perovskites. The conductivity increases by 5 orders of magnitude between 7 and 50 GPa, with a maximum measured conductivity of 2.9 × 10–4 S·cm–1 at 51.4 GPa. Electronic absorption spectroscopy and variable-temperature conductivity measurements indicate that the perovskite behaves as a 1.0 eV band-gap semiconductor at 39.7 GPa and has an activation energy for electronic conduction of 0.232(1) eV at 40.2 GPa. Remarkably, all these changes are reversible: the material reverts to a translucent yellow solid upon decompression, and ambient pressure powder X-ray diffraction data taken before and after compression up to 60 GPa show that the original structure is maintained with minimal hysteresis.
Head and neck cancer is one of the most prevalent cancers around the world. Head and neck squamous cell carcinoma (HNSCC) accounts for nearly 90% of head and neck cancer. In recent years, significant ...advances have been made in immunotherapy for HNSCC. Although some clinical trials targeting immune checkpoints have shown success, the molecular mechanism for regulation of programmed death 1 (PD-1) and its ligand (PD-L1) is partially understood. In an effort to explore the effect of activation of signal transducers and activators of transcriptions (STAT3) on PD-1/PD-L1, the expression and correlation between phosphorylation of STAT3 and PD-1/PD-L1 were determined with immunostaining of human and mouse HNSCC tissue sections. PD-1/PD-L1 overexpression was found to be significantly associated with p-STAT3 in human and mouse HNSCC. Targeting STAT3 by a small molecule effectively inhibited the expression of PD-L1 in the CAL27 cell line. Furthermore, we found that blockade of STAT3 signaling downregulated PD-1/PD-L1 in a Tgfbr1/Pten 2cKO HNSCC mouse model. These findings suggest that STAT3 signaling plays an important role in PD-1/PD-L1 regulation and the antitumor immune response of HNSCC.
Bonding Changes in Compressed Superhard Graphite Mao, Wendy L.; Mao, Ho-kwang; Eng, Peter J. ...
Science (American Association for the Advancement of Science),
10/2003, Letnik:
302, Številka:
5644
Journal Article
Recenzirano
Compressed under ambient temperature, graphite undergoes a transition at ~17 gigapascals. The near K-edge spectroscopy of carbon using synchrotron x-ray inelastic scattering reveals that half of the ...π-bonds between graphite layers convert to σ-bonds, whereas the other half remain as π-bonds in the high-pressure form. The x-ray diffraction pattern of the high-pressure form is consistent with a distorted graphite structure in which bridging carbon atoms between graphite layers pair and form σ-bonds, whereas the nonbridging carbon atoms remain unpaired with π-bonds. The high-pressure form is superhard, capable of indenting cubic-diamond single crystals.
Hydrogen Storage in Molecular Compounds Mao, Wendy L.; Mao, Ho-kwang
Proceedings of the National Academy of Sciences,
01/2004, Letnik:
101, Številka:
3
Journal Article
Recenzirano
Odprti dostop
At low temperature (T) and high pressure (P), gas molecules can be held in ice cages to form crystalline molecular compounds that may have application for energy storage. We synthesized a hydrogen ...clathrate hydrate, H2(H2O)2, that holds 50 g/liter hydrogen by volume or 5.3 wt %. The clathrate, synthesized at 200-300 MPa and 240-249 K, can be preserved to ambient P at 77 K. The stored hydrogen is released when the clathrate is warmed to 140 K at ambient P. Low T also stabilizes other molecular compounds containing large amounts of molecular hydrogen, although not to ambient P, e.g., the stability field for H2(H2O) filled ice (11.2 wt % molecular hydrogen) is extended from 2,300 MPa at 300 K to 600 MPa at 190 K, and that for (H2)4CH
4(33.4 wt % molecular hydrogen) is extended from 5,000 MPa at 300 K to 200 MPa at 77 K. These unique characteristics show the potential of developing low-T molecular crystalline compounds as a new means for hydrogen storage.
The cycling of hydrogen influences the structure, composition, and stratification of Earth’s interior. Our recent discovery of pyrite-structured iron peroxide (designated as the P phase) and the ...formation of the P phase from dehydrogenation of goethite FeO₂H implies the separation of the oxygen and hydrogen cycles in the deep lower mantle beneath 1,800 km. Here we further characterize the residual hydrogen, x, in the P-phase FeO₂Hx. Using a combination of theoretical simulations and high-pressure–temperature experiments, we calibrated the x dependence of molar volume of the P phase. Within the current range of experimental conditions, we observed a compositional range of P phase of 0.39 < x < 0.81, corresponding to 19–61% dehydrogenation. Increasing temperature and heating time will help release hydrogen and lower x, suggesting that dehydrogenation could be approaching completion at the high-temperature conditions of the lower mantle over extended geological time. Our observations indicate a fundamental change in the mode of hydrogen release from dehydration in the upper mantle to dehydrogenation in the deep lower mantle, thus differentiating the deep hydrogen and hydrous cycles.
Diamond owes its unique mechanical, thermal, optical, electrical, chemical, and biocompatible materials properties to its complete sp
-carbon network bonding. Crystallinity is another major ...controlling factor for materials properties. Although other Group-14 elements silicon and germanium have complementary crystalline and amorphous forms consisting of purely sp
bonds, purely sp
-bonded tetrahedral amorphous carbon has not yet been obtained. In this letter, we combine high pressure and in situ laser heating techniques to convert glassy carbon into "quenchable amorphous diamond", and recover it to ambient conditions. Our X-ray diffraction, high-resolution transmission electron microscopy and electron energy-loss spectroscopy experiments on the recovered sample and computer simulations confirm its tetrahedral amorphous structure and complete sp
bonding. This transparent quenchable amorphous diamond has, to our knowledge, the highest density among amorphous carbon materials, and shows incompressibility comparable to crystalline diamond.Diamond's properties are dictated by its crystalline, fully tetrahedrally bonded structure. Here authors synthesize a bulk sp
-bonded amorphous form of carbon under high pressure and temperature, show that it has bulk modulus comparable to crystalline diamond and that it can be recovered under ambient conditions.
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