The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

MET-Amplified Intramucosal Gastric Cancer Widely Metastatic after Complete Endoscopic Submucosal Dissection.

Intramucosal gastric cancer (IGC) is associated with a very low risk of lymph node metastasis; thus it is the main candidate for minimally invasive surgical procedures, such as endoscopic submucosal dissection (ESD). Herein, we document an extraordinary case of IGC, which showed a very aggressive clinical course. A 66-year-old female underwent ESD for early gastric cancer. Histologically, the tumor consisted mainly of moderately differentiated adenocarcinoma measuring 1.6 cm in diameter, and the tumor was confined to the mucosa. Despite annual esophagogastroduodenoscopic follow-up, the tumor recurred, with wide metastasis to multiple lymph nodes and bones throughout the body after three years. Fluorescence in situ hybridization study demonstrated MET gene amplification as well as low grade polysomy 7 in both original and recurrent tumors. The clinical characteristics of metastatic IGCs and the implication of MET amplification are discussed

Brain Structural Networks Associated with Intelligence and Visuomotor Ability

Increasing evidence indicates that multiple structures in the brain are associated with intelligence and cognitive function at the network level. The association between the grey matter (GM) structural network and intelligence and cognition is not well understood. We applied a multivariate approach to identify the pattern of GM and link the structural network to intelligence and cognitive functions. Structural magnetic resonance imaging was acquired from 92 healthy individuals. Source-based morphometry analysis was applied to the imaging data to extract GM structural covariance. We assessed the intelligence, verbal fluency, processing speed, and executive functioning of the participants and further investigated the correlations of the GM structural networks with intelligence and cognitive functions. Six GM structural networks were identified. The cerebello-parietal component and the frontal component were significantly associated with intelligence. The parietal and frontal regions were each distinctively associated with intelligence by maintaining structural networks with the cerebellum and the temporal region, respectively. The cerebellar component was associated with visuomotor ability. Our results support the parieto-frontal integration theory of intelligence by demonstrating how each core region for intelligence works in concert with other regions. In addition, we revealed how the cerebellum is associated with intelligence and cognitive functions

Evaluation of Anticancer Efficacy of D-α-Tocopheryl Polyethylene-Glycol Succinate and Soluplus® Mixed Micelles Loaded with Olaparib and Rapamycin Against Ovarian Cancer

Yu Been Shin,1,&ast; Ju-Yeon Choi,2,&ast; Moon Sup Yoon,1 Myeong Kyun Yoo,1 Dae Hwan Shin,1,3,&ast; Jeong-Won Lee4,5,&ast; 1College of Pharmacy, Chungbuk National University, Cheongju, 28160, Republic of Korea; 2Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; 3Chungbuk National University Hospital, Chungbuk National University, Cheongju, 28644, Republic of Korea; 4Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; 5Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University School of Medicine, Seoul, 06351, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Dae Hwan Shin, College of Pharmacy, Chungbuk National University, Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, 28160, Republic of Korea, Tel +82 43 261 2820, Fax +82 43 268 2732, Email [email protected] Jeong-Won Lee, Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, South Korea, Zip 06351, Tel\Fax +82-2-3410-1382, Email [email protected]: Ovarian cancer has the highest mortality rate and lowest survival rate among female reproductive system malignancies. There are treatment options of surgery and chemotherapy, but both are limited. In this study, we developed and evaluated micelles composed of D-α-tocopheryl polyethylene-glycol (PEG) 1000 succinate (TPGS) and Soluplus® (SOL) loaded with olaparib (OLA), a poly(ADP-ribose)polymerase (PARP) inhibitor, and rapamycin (RAPA), a mammalian target of rapamycin (mTOR) inhibitor in ovarian cancer.Methods: We prepared micelles containing different molar ratios of OLA and RAPA embedded in different weight ratios of TPGS and SOL (OLA/RAPA-TPGS/SOL) were prepared and physicochemical characterized. Furthermore, we performed in vitro cytotoxicity experiments of OLA, RAPA, and OLA/RAPA-TPGS/SOL. In vivo toxicity and antitumor efficacy assays were also performed to assess the efficacy of the mixed micellar system.Results: OLA/RAPA-TPGS/SOL containing a 4:1 TPGS:SOL weight ratio and a 2:3 OLA:RAPA molar ratio showed synergistic effects and were optimized. The drug encapsulation efficiency of this formulation was > 65%, and the physicochemical properties were sustained for 180 days. Moreover, the formulation had a high cell uptake rate and significantly inhibited cell migration (&ast;&ast;p < 0.01). In the in vivo toxicity test, no toxicity was observed, with the exception of the high dose group. Furthermore, OLA/RAPA-TPGS/SOL markedly inhibited tumor spheroid and tumor growth in vivo.Conclusion: Compared to the control, OLA/RAPA-TPGS/SOL showed significant tumor inhibition. These findings lay a foundation for the use of TPGS/SOL mixed micelles loaded with OLA and RAPA in the treatment of ovarian cancer. Keywords: mixed micelle, combination therapy, nanoformulation, IV formula, antitumor efficac

Successful emergency medical service training with virtual field trips using video during the COVID-19 pandemic: the Official Development Assistance Project in Uzbekistan

Purpose: The coronavirus disease 2019 pandemic saw many restrictions on the provision of emergency medical service (EMS) training through actual field trips (AFTs), requiring a search for alternatives. This study aimed to assess trainees' reactions to virtual field trips (VFTs) and determine the characteristics of instructional design for successful VFTs using edited videos and expert interviews. Methods: This study evaluated Uzbekistan trainees' reactions to the VFT of EMS training using questionnaires in three categories: satisfaction, relevance, and engagement. Factors of satisfaction and dissatisfaction were identified through open-ended questions. Results: A total of 286 trainees responded to the survey during 15 educational sessions conducted from 2020 to 2022. The trainees' responses to the VFT were positive. Overall mean scores were 4.65±0.49, 4.63±0.50, and 4.63±0.50 out of 5 points for satisfaction, relevance, and engagement, respectively. The trainees reported that the most interesting and helpful videos concerned the introduction of an EMS training curriculum and the observation of training facilities, such as the simulation centers of educational institutes. The leading causes of satisfaction were (1) authenticity of the VFTs, (2) easy-to-understand content, and (3) relevance to the job. The trainees suggested that Uzbek or Russian voice-overs would be better than subtitles in the video clip for focusing on VFT. Conclusion: In situations where AFTs are not available, VFTs using edited videos and expert interviews are a good alternative to EMS education. Based on these results, it is possible that AFTs could be replaced by VFTs using qualified videos with designed instructions as a distance learning method under specific conditions

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Skin Barrier Function Is Not Impaired and Kallikrein 7 Gene Polymorphism Is Frequently Observed in Korean X-linked Ichthyosis Patients Diagnosed by Fluorescence in Situ Hybridization and Array Comparative Genomic Hybridization

X-linked ichthyosis (XLI) is a recessively inherited ichthyosis. Skin barrier function of XLI patients reported in Western countries presented minimally abnormal or normal. Here, we evaluated the skin barrier properties and a skin barrier-related gene mutation in 16 Korean XLI patients who were diagnosed by fluorescence in situ hybridization and array comparative genomic hybridization analysis. Skin barrier properties were measured, cytokine expression levels in the stratum corneum (SC) were evaluated with the tape stripped specimen from skin surface, and a genetic test was done on blood. XLI patients showed significantly lower SC hydration, but normal basal trans-epidermal water loss and skin surface pH as compared to a healthy control group. Histopathology of ichthyosis epidermis showed no acanthosis, and levels of the pro-inflammatory cytokines in the corneal layer did not differ between control and lesional/non-lesional skin of XLI patients. Among the mutations in filaggrin (FLG), kallikrein 7 (KLK7), and SPINK5 genes, the prevalence of KLK7 gene mutations was significantly higher in XLI patients (50%) than in controls (0%), whereas FLG and SPINK5 prevalence was comparable. Korean XLI patients exhibited unimpaired skin barrier function and frequent association with the KLK7 gene polymorphism, which may differentiate them from Western XLI patients

Validation of Previous Spirometric Reference Equations and New Equations

BACKGROUND: Pulmonary functions are interpreted using predicted values from reference equations that vary with ethnicity, gender, age, height, and weight. The universally used Choi's reference equations are not validated for Korean populations, and the purpose of this study was to validate them and develop new reference equations. METHODS: Subjects with normal spirometry and chest radiographs, no co-morbidities, and non-smokers, from the Korean National Health and National Examination Survey (KNHANES)-VI were enrolled (n = 117). Intraclass correlation coefficient (ICC) was assessed for reliability of reference equations. New reference equations were developed using linear regression analysis. Differences between observed and predicted values were assessed to compare the reference equations from Choi's, Global Lung Function Initiative 2012, KNHANES-IV, and newly developed equations. RESULTS: The ICC of Choi's reference equations was 0.854 (P < 0.001). The new reference equations for men were: forced vital capacity (FVC) (L) = - 4.38775 - 0.01184 x age + 0.05547 x height, forced expiratory volume - 1 second (FEV(1)) (L) = - 2.40147 - 0.02134 x age + 0.04103 x height; and for women: FVC (L) = - 3.09063 + 0.003904 x age + 0.038694 x height; FEV(1) (L) = - 1.32933 - 0.00872 x age + 0.02762 x height. The differences between the predicted and observed means were largest in Choi's equations, but lowest in the new equations with highest goodness of fit. CONCLUSION: Because Choi's reference equations presented larger differences from the observed values, despite reliability, and the new reference equations showed better goodness of fit, we suggest the latter for Korean populations

Male current smokers have low awareness and optimistic bias about COPD: field survey results about COPD in Korea

BACKGROUND: Smoking is a major risk factor for COPD. However, there is low COPD awareness among smokers. We conducted a field survey to investigate COPD awareness, optimistic bias associated with COPD, and COPD prevalence (using handheld spirometry) among current male smokers. SUBJECTS AND METHODS: We enrolled currently smoking males aged over 40 years, who completed a self-administered questionnaire. The questionnaire consisted of six parts: 1) baseline demographics, 2) participants' awareness of COPD and pulmonary function tests, 3) presence of COPD-related respiratory symptoms and experience with pulmonary function testing, 4) optimistic bias about COPD, 5) willingness to change attitude toward respiratory health, and 6) preference of media for obtaining health-related information. Pulmonary function was assessed via handheld spirometry by two experienced pulmonary function laboratory technicians after completion of the questionnaire. RESULTS: We enrolled 105 participants. Only 24.8% knew of COPD. Awareness of pulmonary function testing was reported by 41.9% of participants, and 30.5% had previously undertaken pulmonary function tests. Among the subjects who had not previously undergone pulmonary function tests, 47% were not aware of their existence. The mean optimistic bias scores were 3.9 and 4.0, respectively, reflecting the general perception, among participants, that they were about as likely to develop COPD as similarly aged smokers and friends, respectively. A total of 40.0% of participants perceived personal COPD risk to be lower than COPD risk among their friends. Abnormal handheld spirometry results were observed in 28.6% of participants. Among the subjects with abnormal handheld spirometry results, 36.7% had FEV1 values <50% of the predicted value. CONCLUSION: In conclusion, current male smokers had poor awareness of COPD. Participants perceived their risk of developing COPD to be no higher than their friends' COPD risk. Strategies to increase COPD awareness among high-risk groups should be developed

COVID-19 vaccine type-dependent differences in immunogenicity and inflammatory response: BNT162b2 and ChAdOx1 nCoV-19

Evaluation of the safety and immunogenicity of new vaccine platforms is needed to increase public acceptance of coronavirus disease 2019 (COVID-19) vaccines. Here, we evaluated the association between reactogenicity and immunogenicity in healthy adults following vaccination by analyzing blood samples before and after sequential two-dose vaccinations of BNT162b2 and ChAdOx1 nCoV-19. Outcomes included anti-S IgG antibody and neutralizing antibody responses, adverse events, and proinflammatory cytokine responses. A total of 59 and 57 participants vaccinated with BNT162b2 and ChAdOx1 nCoV-19, respectively, were enrolled. Systemic adverse events were more common after the first ChAdOx1 nCoV-19 dose than after the second. An opposite trend was observed in BNT162b2 recipients. Although the first ChAdOx1 nCoV-19 dose significantly elevated the median proinflammatory cytokine levels, the second dose did not, and neither did either dose of BNT162b2. Grades of systemic adverse events in ChAdOx1 nCoV-19 recipients were significantly associated with IL-6 and IL-1β levels. Anti-S IgG and neutralizing antibody titers resulting from the second BNT162b2 dose were significantly associated with fever. In conclusion, systemic adverse events resulting from the first ChAdOx1 nCoV-19 dose may be associated with proinflammatory cytokine responses rather than humoral immune responses. Febrile reactions after second BNT162b2 dose were positively correlated with vaccine-induced immune responses rather than with inflammatory responses