Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

ホルモン抵抗性前立腺癌に対するリン酸エストラムスチン, エトポシド療法

A total of 42 patients with hormone-refractory prostate cancer received E-E therapy. Oral estramustine phosphate (EMP) was administered twice daily for a total daily dose of 560 mg every day and oral etoposide (E-E therapy, 50 mg/body/day) was given on days 1-21 and stopped on days 22-35. Treatment was continued until the disease progression was confirmed radiographically or PSA had increased from base line of at least 25%. The median follow-up period after E-E therapy was 77.4 months (range : 12.5 to 122.3). Nineteen patients (43%) achieved a PSA decrease of 50% or greater. The median survival time of the patients who had a decrease of 50% or greater in the PSA value (PSA responder) was 29.3 months and the patients who did not (PSA non-responder) was 14.1 months (p = 0.01). There were no significant differences between PSA responders and non-responders when taking into account variables. Excluding those patients with only PSA elevation, the survival time was 14.9 months with no significant difference between PSA responders and non-responders. The toxicities (grade 3 or more) were identified as anemia, leukocytopenia thrombocytopenia, cardiovascular events, and gastrointestinal and hepatic disorders, which occurred in 0, 5, 2, 2, 14, and 2% of the patients, respectively. E-E therapy was considered to be an active oral regimen and well-tolerated for outpatients with hormone-refractory prostate cancer in Japanese patients.【目的】日本人における再燃前立腺癌に対する経口リン酸エストラムスチン(EMP), エトポシド(VP-16)併用療法(EE療法)の効果および副作用について検討した。【方法】1995年以降, EE療法が施行された再燃前立腺癌患者42例が対象。EMP:560mgを連日投与, VP-16:50mgを21日投与し14日休薬を1サイクルとした。PSAが50%以上低下したものをresponderとし, 治療は画像上の増悪またはPSAが基準値より25%を認めるまで継続した。【結果】観察期間は77.4ヵ月。19例がresponderであった。42例の生存中央値は20.5ヵ月でありresponderでは29.3ヵ月, non-responderで14.1ヵ月(p=0.008)であった。群間でresponseに寄与する因子は存在しなかった。Grade 3以上の副作用は白血球減少(5%)が2例, 血小板減少(2%)が1例, 悪心が6例(14%), 肝機能障害が1例(2%), 深部静脈血栓症(2%)が1例に認めた。【結語】EE療法は抗腫瘍効果もあり, 副作用も容認でき日本人にも施行可能であった。(著者抄録

PTRF/Cavin-1 Deficiency Causes Cardiac Dysfunction Accompanied by Cardiomyocyte Hypertrophy and Cardiac Fibrosis

<div><p>Mutations in the <i>PTRF/Cavin-1</i> gene cause congenital generalized lipodystrophy type 4 (CGL4) associated with myopathy. Additionally, long-QT syndrome and fatal cardiac arrhythmia are observed in patients with CGL4 who have homozygous <i>PTRF</i>/<i>Cavin-1</i> mutations. PTRF/Cavin-1 deficiency shows reductions of caveolae and caveolin-3 (Cav3) protein expression in skeletal muscle, and Cav3 deficiency in the heart causes cardiac hypertrophy with loss of caveolae. However, it remains unknown how loss of PTRF/Cavin-1 affects cardiac morphology and function. Here, we present a characterization of the hearts of <i>PTRF</i>/<i>Cavin-1</i>-null (<i>PTRF</i>^−/−) mice. Electron microscopy revealed the reduction of caveolae in cardiomyocytes of <i>PTRF</i>^−/− mice. <i>PTRF</i>^−/− mice at 16 weeks of age developed a progressive cardiomyopathic phenotype with wall thickening of left ventricles and reduced fractional shortening evaluated by echocardiography. Electrocardiography revealed that <i>PTRF</i>^−/− mice at 24 weeks of age had low voltages and wide QRS complexes in limb leads. Histological analysis showed cardiomyocyte hypertrophy accompanied by progressive interstitial/perivascular fibrosis. Hypertrophy-related fetal gene expression was also induced in <i>PTRF</i>^−/− hearts. Western blotting analysis and quantitative RT-PCR revealed that Cav3 expression was suppressed in <i>PTRF</i>^−/− hearts compared with that in wild-type (WT) ones. ERK1/2 was activated in <i>PTRF</i>^−/− hearts compared with that in WT ones. These results suggest that loss of PTRF/Cavin-1 protein expression is sufficient to induce a molecular program leading to cardiomyocyte hypertrophy and cardiomyopathy, which is partly attributable to Cav3 reduction in the heart.</p></div