Using spin to understand the formation of LIGO's black holes

With the detection of four candidate binary black hole (BBH) mergers by the Advanced LIGO detectors thus far, it is becoming possible to constrain the properties of the BBH merger population in order to better understand the formation of these systems. Black hole (BH) spin orientations are one of the cleanest discriminators of formation history, with BHs in dynamically formed binaries in dense stellar environments expected to have spins distributed isotropically, in contrast to isolated populations where stellar evolution is expected to induce BH spins preferentially aligned with the orbital angular momentum. In this work we propose a simple, model-agnostic approach to characterizing the spin properties of LIGO's BBH population. Using measurements of the effective spin of the binaries, which is LIGO's best constrained spin parameter, we introduce a simple parameter to quantify the fraction of the population that is isotropically distributed, regardless of the spin magnitude distribution of the population. Once the orientation characteristics of the population have been determined, we show how measurements of effective spin can be used to directly constrain the underlying BH spin magnitude distribution. Although we find that the majority of the current effective spin measurements are too small to be informative, with LIGO's four BBH candidates we find a slight preference for an underlying population with aligned spins over one with isotropic spins (with an odds ratio of 1.1). We argue that it will be possible to distinguish symmetric and anti-symmetric populations at high confidence with tens of additional detections, although mixed populations may take significantly more detections to disentangle. We also derive preliminary spin magnitude distributions for LIGO's black holes, under the assumption of aligned or isotropic populations

Preliminary results of proton radiotherapy for pediatric rhabdomyosarcoma: a multi-institutional study in Japan

To evaluate preliminary results of proton radiotherapy (PRT) for pediatric patients with rhabdomyosarcoma (RMS). From 1987 to 2014, PRT was conducted as initial radiotherapy in 55 patients (35 males, 20 females, median age 5 years, range 0–19) with RMS at four institutes in Japan. Thirty‐one, 18, and six patients had embryonal, alveolar, and other RMS, respectively. One, 11, 37, and six patients were in IRSG groups I, II, III, and IV, respectively, and the COG risk group was low, intermediate, and high for nine, 39, and seven patients, respectively. The irradiation dose was 36–60 GyE (median: 50.4 GyE). The median follow‐up period was 24.5 months (range: 1.5–320.3). The 1‐ and 2‐year overall survival rates were 91.9% (95% CI: 84.3–99.5%) and 84.8% (95% CI 75.2–94.3%), respectively, and these rates were 100% and 100%, 97.1% and 90.1%, and 57.1% and 42.9% for COG low‐, intermediate‐, and high‐risk groups, respectively. There were 153 adverse events of Grade ≥3, including 141 hematologic toxicities in 48 patients (87%) and 12 radiation‐induced toxicities in nine patients (16%). Proton‐specific toxicity was not observed. PRT has the same treatment effect as photon radiotherapy with tolerable acute radiation‐induced toxicity

Complete response to pembrolizumab in advanced hepatocellular carcinoma with microsatellite instability

Hepatocellular carcinoma (HCC) has limited systemic treatment options and a poor prognosis. The immune checkpoint inhibitor pembrolizumab was recently approved for the treatment of solid tumors with microsatellite instability (MSI). However, its clinical utility for the management of HCC remains to be clarified. Here, we present a case of unresectable HCC with MSI that showed an impressive response to pembrolizumab treatment. A 64-year-old man with chronic HCV infection was diagnosed with a large HCC. His severe liver dysfunction and poor performance status prevented any treatment option other than sorafenib. However, sorafenib failed after a few days due to the rapid progression of the tumor. Based on the finding of MSI in a biopsy specimen, immunotherapy using pembrolizumab was initiated. A dramatic improvement in his general condition and a reduction in tumor size were observed after the initiation of pembrolizumab treatment. Among a cohort of 50 consecutive patients with advanced HCC who were refractory to standard systemic therapy, MSI was found only in the present case. Immune checkpoint blockade therapy induced prominent anti-tumor effects in HCC with MSI. Screening for defects in DNA mismatch repair function may be warranted in HCC patients despite the low frequency of MSI

ADAR1 is a promising risk stratification biomarker of remnant liver recurrence after hepatic metastasectomy for colorectal cancer

Adenosine-to-inosine RNA editing is a process mediated by adenosine deaminases that act on the RNA (ADAR) gene family. It has been discovered recently as an epigenetic modification dysregulated in human cancers. However, the clinical significance of RNA editing in patients with liver metastasis from colorectal cancer (CRC) remains unclear. The current study aimed to systematically and comprehensively investigate the significance of adenosine deaminase acting on RNA 1 (ADAR1) expression status in 83 liver metastatic tissue samples collected from 36 patients with CRC. The ADAR1 expression level was significantly elevated in liver metastatic tissue samples obtained from patients with right-sided, synchronous, or RAS mutant-type CRC. ADAR1-high liver metastasis was significantly correlated with remnant liver recurrence after hepatic metastasectomy. A high ADAR1 expression was a predictive factor of remnant liver recurrence (area under the curve = 0.72). Results showed that the ADAR1 expression level could be a clinically relevant predictive indicator of remnant liver recurrence. Patients with liver metastases who have a high ADAR1 expression requires adjuvant chemotherapy after hepatic metastasectomy

Reference values for the locomotive syndrome risk test quantifying mobility of 8681 adults aged 20–89 years: A cross-sectional nationwide study in Japan

Background The locomotive syndrome risk test was developed to quantify the decrease in mobility among adults, which could eventually lead to disability. The purpose of this study was to establish reference values for the locomotive syndrome risk test for adults and investigate the influence of age and sex. Methods We analyzed 8681 independent community dwellers (3607 men, 5074 women). Data pertaining to locomotive syndrome risk test (the two-step test, the stand-up test, and the 25-question geriatric locomotive function scale [GLFS-25]) scores were collected from seven administrative areas of Japan. Results The reference values of the three test scores were generated and all three test scores gradually decreased among young-to-middle-aged individuals and rapidly decreased in individuals aged over 60 years. The stand-up test score began decreasing significantly from the age of 30 years. The trajectories of decrease in the two-step test score with age was slightly different between men and women especially among the middle-aged individuals. The two physical test scores were more sensitive to aging than the self-reported test score. Conclusion The reference values generated in this study could be employed to determine whether an individual has mobility comparable to independent community dwellers of the same age and sex

Deficiency of the DNA repair enzyme ATM in rheumatoid arthritis

In rheumatoid arthritis (RA), dysfunctional T cells sustain chronic inflammatory immune responses in the synovium. Even unprimed T cells are under excessive replication pressure, suggesting an intrinsic defect in T cell regeneration. In naive CD4 CD45RA+ T cells from RA patients, DNA damage load and apoptosis rates were markedly higher than in controls; repair of radiation-induced DNA breaks was blunted and delayed. DNA damage was highest in newly diagnosed untreated patients. RA T cells failed to produce sufficient transcripts and protein of the DNA repair kinase ataxia telangiectasia (AT) mutated (ATM). NBS1, RAD50, MRE11, and p53 were also repressed. ATM knockdown mimicked the biological effects characteristic for RA T cells. Conversely, ATM overexpression reconstituted DNA repair capabilities, response patterns to genotoxic stress, and production of MRE11 complex components and rescued RA T cells from apoptotic death. In conclusion, ATM deficiency in RA disrupts DNA repair and renders T cells sensitive to apoptosis. Apoptotic attrition of naive T cells imposes lymphopenia-induced proliferation, leading to premature immunosenescence and an autoimmune-biased T cell repertoire. Restoration of DNA repair mechanisms emerges as an important therapeutic target in RA

Long-term follow-up after proton beam therapy for pediatric tumors: a Japanese national survey

Proton beam therapy (PBT) is a potential new alternative to treatment with photon radiotherapy that may reduce the risk of late toxicity and secondary cancer, especially for pediatric tumors. The goal of this study was to evaluate the long-term benefits of PBT in cancer survivors. A retrospective observational study of pediatric patients who received PBT was performed at four institutions in Japan. Of 343 patients, 62 were followed up for 5 or more years. These patients included 40 males and 22 females, and had a median age of 10 years (range: 0–19 years) at the time of treatment. The irradiation dose ranged from 10.8 to 81.2 GyE (median: 50.4 GyE). The median follow-up period was 8.1 years (5.0–31.2 years). The 5-, 10- and 20-year rates for grade 2 or higher late toxicities were 18%, 35% and 45%, respectively, and those for grade 3 or higher late toxicities were 6%, 17% and 17% respectively. Univariate analysis showed that the irradiated site (head and neck, brain) was significantly associated with late toxicities. No malignant secondary tumors occurred within the irradiated field. The 10- and 20-year cumulative rates for all secondary tumors, malignant secondary tumors, and malignant nonhematologic secondary tumors were 8% and 16%, 5% and 13%, and 3% and 11%, respectively. Our data indicate that PBT has the potential to reduce the risk of late mortality and secondary malignancy. Longer follow-up is needed to confirm the benefits of PBT for pediatric tumors

Quality of life, depression, and productivity of city government employees in Japan : a comparison study using the Athens insomnia scale and insomnia severity index

Background:Insomnia has a high prevalence in modern society. Various tools have been developed to assess insomnia. We performed a direct comparison between the Insomnia Severity Index (ISI) and the Athens Insomnia Scale (AIS) in a Japanese population.Methods:A cross-sectional questionnaire-based study was conducted in September 2017 as part of the Night in Japan Home Sleep Monitoring Study. In addition to insomnia, assessed using the AIS and ISI, depression, sleepiness, quality of life, and work performance were assessed using the Patient Health Questionnaire (PHQ)-9, a Japanese version of the Epworth Sleepiness Scale, the Short Form-8 Health Survey Questionnaire (SF-8), and the World Health Organization Health and Work Performance Questionnaire, respectively. Receiver operating characteristic (ROC) curves were constructed to compare the outcomes of the AIS and the ISI.Results:A total of 1685 (81.9%) of all eligible employees were enrolled. The total scores of the AIS and ISI had a Pearson correlation coefficient (r) of 0.80 (p < 0.01). The area under the ROC curve for the AIS and ISI for the detection of depression (PHQ-9 ≥ 10) was 0.89 and 0.86, respectively. The prevalence of clinical insomnia (ISI ≥ 15) and definite insomnia (AIS ≥ 10) were 6.5 and 10.8%, respectively. Both the AIS and ISI showed a weak negative correlation with the physical component summary score of the SF-8 (r = − 0.37, p < 0.01 and r = − 0.32, p < 0.01, respectively) and absolute presenteeism (r = − 0.32, p < 0.01 and r = − 0.28, p < 0.01, respectively) and a moderate negative correlation with the mental component summary score of the SF-8 (r = − 0.53, p < 0.01 and r = − 0.43, p < 0.01, respectively).Conclusions:A strong positive correlation was found between the total scores of the AIS and ISI. Both the AIS and ISI were found to be associated with low physical and mental quality of life, depression, and productivity loss at work. Moreover, they had a moderate accuracy for detecting depression. Both the AIS and ISI may serve as useful screening tools for both insomnia and depression in the Japanese working population.Trial registration:UMIN-CTR (UMIN000028675, registered on 2017/8/15) and ClinicalTrials.gov (NCT03276585, registered on 2017/9/3)