A phase 2 basket trial of combination therapy with trastuzumab and pertuzumab in patients with solid cancers harboring human epidermal growth factor receptor 2 amplification (JUPITER trial)

Introduction: Human epidermal growth factor receptor 2 (HER2) gene amplification and mutations have emerged as oncogenic drivers and therapeutic targets not limited to breast and gastric cancers, but also in a variety of cancers. However, even if an actionable gene alteration is found, the incidence of HER2 amplification in these cancers is less than 5%. It is too difficult to conduct a conventional randomized, controlled trial in a rare fraction. Therefore, we have designed a organ-agnostic basket study, which covers a variety of solid cancers harboring HER2 amplification, in 1 study protocol. Methods/Design: This trial is a multicenter, single-arm, basket phase 2 study in Japan. Patients with solid cancers harboring HER2 amplification that have progressed with standard treatment, or rare cancers for which there is no standard treatment, will be eligible. Target cancers include bile duct, urothelial, uterine, ovarian, and other solid cancers where HER2 amplification is detected by comprehensive genomic profiling using next-generation sequencing technology. A total of 38 patients will be treated with combination therapy with trastuzumab and pertuzumab every 3 weeks until disease progression, unmanageable toxicity, death, or patient refusal. The primary endpoint is the objective response rate, and secondary endpoints are progression-free survival, overall survival, and duration of response. Discussion: The aim of this trial is to evaluate the safety and efficacy of combination therapy with trastuzumab and pertuzumab in patients with locally advanced or metastatic, solid cancers harboring HER2 amplification. Instead of focusing on 1 organ type, our trial design uses a basket study focusing on HER2 amplification, regardless of the site or origin of the cancer. The results of our study will advance clinical and scientific knowledge concerning the treatment of locally advanced, rare solid cancers harboring HER2 amplification, using the combination of trastuzumab and pertuzumab. Trial registration: This trial was registered in Japan Registry of Clinical Trials (jCRT) on February 25, 2019, as jRCT2031180150

Solar Lyman-Alpha Polarization Observation of the Chromosphere and Transition Region by the Sounding Rocket Experiment CLASP

We are planning an international rocket experiment Chromospheric Lyman-Alpha Spectro-Polarimeter (CLASP) is (2015 planned) that Lyman line (Ly(alpha) line) polarization spectroscopic observations from the sun. The purpose of this experiment, detected with high accuracy of the linear polarization of the Ly(alpha) lines to 0.1% by using a Hanle effect is to measure the magnetic field of the chromosphere-transition layer directly. For polarization photometric accuracy achieved that approx. 0.1% required for CLASP, it is necessary to realize the monitoring device with a high throughput. On the other hand, Ly(alpha) line (vacuum ultraviolet rays) have a sensitive characteristics that is absorbed by the material. We therefore set the optical system of the reflection system (transmission only the wavelength plate), each of the mirrors, subjected to high efficiency of the multilayer coating in accordance with the role. Primary mirror diameter of CLASP is about 30 cm, the amount of heat about 30,000 J is about 5 minutes of observation time is coming mainly in the visible light to the telescope. In addition, total flux of the sun visible light overwhelmingly large and about 200 000 times the Ly(alpha) line wavelength region. Therefore, in terms of thermal management and 0.1% of the photometric measurement accuracy achieved telescope, elimination of the visible light is essential. We therefore, has a high reflectivity (> 50%) in Ly line, visible light is a multilayer coating be kept to a low reflectance (<5%) (cold mirror coating) was applied to the primary mirror. On the other hand, the efficiency of the polarization analyzer required chromospheric magnetic field measurement (the amount of light) Conventional (magnesium fluoride has long been known as a material for vacuum ultraviolet (MgF2) manufactured ellipsometer; Rs = 22%) about increased to 2.5 times were high efficiency reflective polarizing element analysis. This device, Bridou et al. (2011) is proposed "that is coated with a thin film of the substrate MgF2 and SiO2 fused silica." As a result of the measurement, Rs = 54.5%, to achieve a Rp = 0.3%, high efficiency, of course, capable of taking out only about s-polarized light. Other reflective optical elements (the secondary mirror, the diffraction gratingcollector mirror), subjected to high-reflection coating of Al + MgF2 (reflectance of about 80%), less than 5% in the entire optical system by these (CCD Science was achieved a high throughput as a device for a vacuum ultraviolet ray of the entire system less than 5% (CCD of QE is not included)

がん検診啓発活動を通しての看護学生の学び

がん医療の向上に向けて、地域でがんの検診啓発活動に取り組む看護学生の自主グループが誕生し、正課外活動として取り組んでいる。地域の健康課題「がん」に関する、啓発活動に取り組む看護学生の学びをインタビューから質的に分析し、明らかにした。学生は〈関係づくりとしてのネットワーク構築の重要性〉〈専門職者を目指した自己研鑽〉〈コミュニケーション能力の向上〉〈問題発見・解決と企画力の向上〉〈倫理観・責任感を伴った行動の必要性〉〈社会性形成と自己理解〉の6カテゴリー、30サブカテゴリーについて学んでいた。授業時間以外の自主的な学習を促進する正課外活動の重要性が示唆された

Effects of Metabotropic Glutamate Receptor 3 Genotype on Phonetic Mismatch Negativity

BACKGROUND: The genetic and molecular basis of glutamatergic dysfunction is one key to understand schizophrenia, with the identification of an intermediate phenotype being an essential step. Mismatch negativity (MMN) or its magnetic counterpart, magnetic mismatch field (MMF) is an index of preattentive change detection processes in the auditory cortex and is generated through glutamatergic neurotransmission. We have previously shown that MMN/MMF in response to phoneme change is markedly reduced in schizophrenia. Variations in metabotropic glutamate receptor (GRM3) may be associated with schizophrenia, and has been shown to affect cortical function. Here we investigated the effect of GRM3 genotypes on phonetic MMF in healthy men. METHODS: MMF in response to phoneme change was recorded using magnetoencephalography in 41 right-handed healthy Japanese men. Based on previous genetic association studies in schizophrenia, 4 candidate SNPs (rs6465084, rs2299225, rs1468412, rs274622) were genotyped. RESULTS: GRM3 rs274622 genotype variations significantly predicted MMF strengths (p = 0.009), with C carriers exhibiting significantly larger MMF strengths in both hemispheres compared to the TT subjects. CONCLUSIONS: These results suggest that variations in GRM3 genotype modulate the auditory cortical response to phoneme change in humans. MMN/MMF, particularly those in response to speech sounds, may be a promising and sensitive intermediate phenotype for clarifying glutamatergic dysfunction in schizophrenia

Diminished Medial Prefrontal Activity behind Autistic Social Judgments of Incongruent Information

Individuals with autism spectrum disorders (ASD) tend to make inadequate social judgments, particularly when the nonverbal and verbal emotional expressions of other people are incongruent. Although previous behavioral studies have suggested that ASD individuals have difficulty in using nonverbal cues when presented with incongruent verbal-nonverbal information, the neural mechanisms underlying this symptom of ASD remain unclear. In the present functional magnetic resonance imaging study, we compared brain activity in 15 non-medicated adult males with high-functioning ASD to that of 17 age-, parental-background-, socioeconomic-, and intelligence-quotient-matched typically-developed (TD) male participants. Brain activity was measured while each participant made friend or foe judgments of realistic movies in which professional actors spoke with conflicting nonverbal facial expressions and voice prosody. We found that the ASD group made significantly less judgments primarily based on the nonverbal information than the TD group, and they exhibited significantly less brain activity in the right inferior frontal gyrus, bilateral anterior insula, anterior cingulate cortex/ventral medial prefrontal cortex (ACC/vmPFC), and dorsal medial prefrontal cortex (dmPFC) than the TD group. Among these five regions, the ACC/vmPFC and dmPFC were most involved in nonverbal-information-biased judgments in the TD group. Furthermore, the degree of decrease of the brain activity in these two brain regions predicted the severity of autistic communication deficits. The findings indicate that diminished activity in the ACC/vmPFC and dmPFC underlies the impaired abilities of individuals with ASD to use nonverbal content when making judgments regarding other people based on incongruent social information

Corps et névrose chez Gustave Flaubert avant 1857

L objectif de cette thèse est de reconstituer l histoire de la jeunesse intellectuelle et littéraire de Flaubert, des années 1830 aux années 1850, en corrélation avec l évolution des représentations scientifiques et artistiques du corps et de la névrose durant la première moitié du XIXe siècle. L épistémologie du corporel et des nerfs est intimement liée, par ailleurs, à l épistémologie du sensible, du réel et de la rationalité, qui connurent des tournants cruciaux pendant cette période. L écrivain, comme son siècle, va de la lecture à l écriture : de la sémantique à la représentation, voire de l analyse ayant pour finalité l unité de la Nature à la décomposition et recomposition de l Objet défini et représenté comme tel. La relation qui se tisse entre le devenir d une écriture impersonnelle et la formation de la pensée objective, est une relation dirigée par une intention première et soumise au destin du sujet qui se réfléchit, s objective et se matérialise dans son imaginaire. Nous tenterons de recouper cette relation sous trois angles : biographique, épistémologique et thématique.ST DENIS-BU PARIS8 (930662101) / SudocSudocFranceF