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Introduction Survival of childhood cancer has increased over the past decades. This has led to the development of strategies aiming to enhance follow-up care and research, for which priorities may vary globally. We explored perspectives of an international healthcare workers panel. Methods Attendants of a meet-the-expert session on childhood cancer survivorship at the 2018 SIOP conference completed a survey about their view on important follow-up care and research aspects for survivors below and over 18 years. We analysed overarching categories and subtopics, and compared Asian versus European and North American healthcare workers. Results A total of 58 participants from different medical specialties (67.2% paediatric oncologists) and continents (48.3% Asia, 39.7% Europe/North America) responded. Follow-up care priorities for survivors below and over 18 years included physical care (39.3% ≤18 years, 35.9% >18 years) and healthcare structure (29.4%, 26.0%). Physical care was also the most important research aspect for both age groups (52.5%, 50.7%). Psychological support was the most frequently reported subtopic. Asian clinicians (n = 22) primarily prioritized physical care aspects of follow-up care, whereas European/North American (n = 19) clinicians underscored the importance of healthcare structure. Conclusion Physical care is the most important aspect of survivorship care and research according to clinicians from several continents. Asian and European/North American respondents shared most priorities, however, healthcare structure was a more important category for European/North American clinicians. The most common subtopic was psychological support, underlining also the need to involve psychologists in follow-up.

Non-invasive biological samples benefit studies that investigate rare, elusive, endangered, and/or dangerous species. Integrating genomic techniques that use non-invasive biological samples with advances in computational approaches can benefit and inform wildlife conservation and management. Here we present a molecular pipeline that uses non-invasive fecal DNA samples to generate low- to medium-coverage genomes (e.g., >90% of the complete nuclear genome at 6X coverage) and metagenomic sequences, combining in a novel fashion widely available and accessible DNA collection cards with commonly used DNA extraction and library building approaches. DNA preservation cards are easy to transport and can be stored non-refrigerated, avoiding cumbersome and/or costly sample methods. The genomic library construction and shotgun sequencing approach did not require enrichment or targeted DNA amplification. The utility and potential of the data generated by this pipeline was demonstrated by the application of genome-scale analysis and metagenomics to zoo and free-ranging African savanna elephants (Loxodonta africana). Fecal samples collected from free-ranging individuals contained an average of 12.41% (5.54-21.65%) endogenous elephant DNA. Clustering of these elephants with others from the same geographic region was demonstrated by a principal component analysis of genetic variation using nuclear genome-wide SNPs. Metagenomic analyses generated compositional taxon classifications that included Loxodonta, green plants, fungi, arthropods, bacteria, viruses and archaea, showcasing the utility of our approach for addressing complementary questions based on host-associated DNA, e.g., pathogen and parasite identification. The molecular pipeline presented here extends applications beyond what has previously been shown for target-enriched datasets and contributes towards the expansion and application of genomic techniques to conservation science and practice.

Funding Acknowledgements Type of funding sources: None. Introduction Catheter ablation (CA) of frequent premature ventricular contractions (PVC) is increasingly performed in older patients as the population ages. Purpose The purpose of this study was to assess the impact of age on procedural characteristics, safety and efficacy on PVC ablations. Methods Consecutive patients with symptomatic PVCs undergoing CA between 2015 and 2020 were evaluated. Acute ablation success was defined as the elimination of PVCs at the end of the procedure. Sustained success was defined as an elimination of symptoms, and ≥80% reduction of PVC burden determined by Holter-ECG during long-term follow. Patients were sub-grouped based on age (< 65 years vs. ≥ 65 years). Results A total of 114 patients were enrolled (median age 64 years, 71% males) and followed up for a median duration of 228 days. Baseline and procedural data were similar in both age groups. A left-sided origin of PVCs was more frequently observed in the elderly patient group compared to younger patients (83% vs. 67%, p = 0.04, Figure 1). The median procedure time was significantly shorter in elderly patients (160 min vs. 193 min, p = 0.02). The rates of both acute (86% vs. 92%, p = 0.32) and sustained success (70% vs. 71%, p = 0.90) were similar between groups. Complications rates (3.7%) did not differ between the two groups. Conclusion In a large series of patients with a variety of underlying arrhythmia substrates, similar rates of acute procedural success, complications, and ventricular arrhythmia-free-survival were observed after CA of PVCs. Older age alone should not be a reason to withhold CA of PVCs. Abstract Figure 1

Helical distortion of the core part of tokamak plasma, which is called a helical core or a long-lived mode, is investigated by means of three-dimensional magnetohydrodynamic equilibrium calculations. It is found that the magnitude of the helical distortion strongly depends on the shape of the plasma boundary for weakly reversed shear plasmas. The triangularity of the boundary enhances the amplitude of helical distortion. In addition, reversed D-shape plasmas also exhibit a helical core. It is also found that the triangularity lowers the critical β for the onset of a helical core; furthermore, the critical β vanishes when the triangularity exceeds a certain value. On the other hand, the influence of the ellipticity on the amplitude of helical distortion strongly depends on β. The ellipticity enhances the amplitude at high β, while it reduces the amplitude at low β.

Gamma-cyclodextrin (γCD) is a cyclic oligosaccharide consisting of eight α-(1,4)-linked glucopyranose subunits, which is often used in the food and pharmaceutical industries. However, little is known regarding the metabolic activity of "empty" γCD per se. Therefore, in the present study young C57BL/6 male mice received a control diet (CON) or an experimental diet that was supplemented with 12.88% γCD exchanged against corn starch. After 6 weeks of treatment, the voluntary wheel running activity was monitored and the muscle strength of mice was measured by employing Kondziela's inverted screen test and forelimb grip strength assay. The γCD-treated mice covered a significantly larger distance per night (CON 8.6 km, γCD 12.4 km) and were significantly longer active (CON 340 min, γCD 437 min). Moreover, γCD-treated mice significantly performed better at the inverted screen test indicated by an enhanced Kondziela score (CON 3.10, γCD 4.63). These data suggest that dietary γCD leads to an increased endurance. We also found a slightly anti-glycemic effect of γCD during oral glucose tolerance test. However, our mice from the γCD group exhibited no difference in terms of GLUT2 protein level in ileum tissue nor increased muscle glycogen storage. Furthermore, γCD exhibited no DPP-4 inhibitory activity in vitro. By analysing candidate muscle genes and proteins related to endurance and muscle performance we did not observe any differences in terms of Sirt1, Pgc1α, Cpt1b, Mef2c, Myh1 and Myh2 gene expression levels as well as total oxidative phosphorylation (OXPHOS), mtTFA and GLUT4 protein expression levels in skeletal muscle in response to γCD. We could not fully establish the exact underlying molecular mechanisms of the fitness improvement by dietary γCD which warrants further investigations.

Chimeric mice with humanized liver were first established by transplanting primary human hepatocytes (PHHs) isolated from a Japanese 27-year-old donor into complementary DNA-urokinase-type plasminogen activator/severe combined immunodeficiency mice. The PHHs from the Japanese donor increased more than 100-fold in the mouse liver, and human hepatocytes purified from the chimeric mouse liver (hcPHs) were successfully transplanted into second-passaged mice. These PHHs and hcPHs can produce human albumin and preserve many liver-specific enzyme genes, which are important for liver function. Interestingly, hepatitis B virus can be infected with these chimeric mice; hepatitis B viral DNA and hepatitis B surface antigen levels were detectable. In conclusion, hcPHs can be an ideal cell source for analysis of human hepatocytes.

This study was designed to investigate ethnic differences in the pharmacokinetics (PKs) of moxifloxacin and its metabolites, M1 (sulfo conjugate) and M2 (acyl-glucuronate), among Japanese, Chinese, and Korean populations, following oral administration. We used a population PK modeling approach using data from a clinical study involving 79 healthy male volunteers. A comprehensive population PK model considering the PK mechanism of moxifloxacin and its metabolites was newly built. The structures of the final model were two-compartment for moxifloxacin and one-compartment for M1 and M2, with first-order absorption with lag time for all three compounds. The formation of M1 and M2 from moxifloxacin via a first-pass effect and subsequent metabolic clearance in the system were also modeled. Lean body mass on the central volume of distribution (V c ) and estimated glomerular filtration rate on renal clearance (CL r ) were identified as covariates of PKs of moxifloxacin. Additionally, bioavailability was slightly higher in Koreans, whereas CL r , non-renal clearance (CL nr ), and V c were slightly lower. Regarding M1 and M2, body surface area on CL r of M2 and UGT1A1*6 on F of M2 were modeled. Korean ethnicity was observed to influence CL nr of M2, F of M2, and the metabolic clearance of moxifloxacin to M2. However, the exposure levels of moxifloxacin, M1, and M2 in Koreans were comparable to those in Japanese and Chinese because the effects of Korean ethnicity on some PK parameters were counterbalanced. These results suggest that PKs for moxifloxacin and its metabolites among East Asian populations are essentially similar.

Elevated plasma levels of prebeta-1 high-density lipoprotein (HDL), the principal acceptor of cholesterol effluxed from macrophages, are associated with increased risk of atherosclerotic coronary heart disease and myocardial infarction.The objective of the study was to assess the effects on prebeta-1 HDL levels of 6-week moderate-dose statin treatment.We studied 101 patients (mean age 52.7 years; 53.5% female; 63 with primary hypercholesterolemia; 38 with combined hyperlipidemia) before and after treatment with statins. Mean atorvastatin potency equivalence was 23.6 mg/d. Prebeta-1 HDL plasma levels were measured by immunofixation of agarose gels using anti-apolipoprotein A-1 antibody.We observed a 42.0% reduction of low-density lipoprotein cholesterol (181 ± 56 vs 105 mg/dL, P .001). Triglyceride (TG) levels decreased by 22.3% (157 vs 122 mg/dL, P .001), HDL cholesterol levels remained similar (56.0 vs 57.1, P = NS). Levels of prebeta-1 HDL were significantly reduced by 17.9% after statin treatment (mean 11.4 vs 9.4 mg apoA-1/dL, P .001). The magnitude of this decrease was similar with each of 3 statins (atorvastatin, simvastatin, and rosuvastatin). The decrease in prebeta-1 HDL was strongly associated with the decline in TG, but not with the decline in low-density lipoprotein cholesterol.The association of high prebeta-1 HDL with coronary heart disease identifies it as an inferential measure of the rate of cholesterol efflux from the artery wall. Our observations demonstrate a reduction of prebeta-1 HDL with statin therapy, partially reflecting the reduced TGs, and probably reflecting a direct beneficial impact on cholesterol efflux.

PurposeThe purpose of this study was to examine the surgical outcome of posterior layer advancement of the lower eyelid retractors (LER) with transcanthal canthopexy for involutional lower eyelid entropion.Patients and methodsFifty-one eyelids of 41 patients with involutional entropion and vertical and horizontal laxities that underwent posterior layer advancement of the LER with transcanthal canthopexy were retrospectively reviewed. As a control, we also reviewed previously reported data from 47 entropic eyelids of 37 patients with vertical and horizontal laxities that were successfully corrected using LER advancement and a lateral tarsal strip procedure. Surgical success was defined as the normal eyelid position without contact of any cilia to the globe at the last follow-up examination.ResultsAll eyelids in the present study group were judged as successfully treated without recurrence after 13.9±9.2 months of follow up (mean±SD). The surgical time in the present study group (22.4±5.5 min) was significantly shorter than that in the control group (mean 31.3±4.9 min; P

Purpose Dental faculties in Japan have organised many short-term international exchange programs to enable their undergraduates to study abroad. However, not many students apply for those programs. In this present study, we attempted to clarify the factors that discourage undergraduate dental students from studying abroad. Methods We administered a questionnaire survey to 512 undergraduate dental students in three national universities located in different areas in Japan. Results Although 61.7% of the participants expressed interest in studying abroad, only 19.1% of them had prior experiences of study abroad or plans to do so. Their main worries were about lack of sufficient language ability in academic fields. Comparing those who were interested in studying abroad with those who were not revealed significant differences regarding their concern about lack of language ability and lack of specialised knowledge in dentistry. Participants who did not want to study abroad indicated that they did not perceive a purpose in doing so and cited not having foreign friends as a problem. Household income was significantly correlated with concerns about overall expenses. Conclusion Overall, language ability and academic knowledge appeared to be the two strongest factors affecting dental students’ consideration of studying abroad. Dental schools in Japan can use the findings of this study to improve their undergraduate exchange programs in such a way as to stimulate greater interest amongst their students.

The nonlinear evolution of electromagnetic instabilities in reversed shear plasmas is investigated by means of global gyrokinetic simulations. It is found that the kinetic infernal mode (KIM), which is a pressure-driven instability with low to intermediate toroidal mode number excited in a region of low magnetic shear, is unstable at high β, while the ion temperature gradient mode is unstable at low β, where β is the ratio of the plasma kinetic pressure to the magnetic pressure. The β threshold of the KIM is much lower than that of the kinetic ballooning mode (KBM) appearing in a normal shear plasma, while both the KIM and KBM are strong at the unfavorable curvature region, and the KIM has the same parity as the KBM. Nonlinear simulations show that the KIM gets saturated by exciting strong zonal flows and fluctuations of low toroidal mode number. The amplitude of the KIM turbulence is similar to that of the KBM turbulence in spite of the fact that the linear growth rate of the KIM is much higher than that of the KBM. This is because the excitation of zonal flows and fluctuations at low toroidal mode number is stronger in the reversed shear plasma than that of the normal shear plasma. On the other hand, the energy flux and particle flux due to the KIM turbulence are about two or three times larger than those by the KBM turbulence.

Background Patients with rheumatoid arthritis (RA) who achieved clinical remission sometimes have synovitis detected by joint ultrasonography (US) (1). This residual synovitis has been shown to be predictive of insidious radiographic progression, flares after tapering or cessation of DMARDs. Since it is difficult to examine all joints by US in daily clinical practice, several joint combinations have been proposed for optimal and/or feasible assessments of joint inflammation in patients with RA. Objectives To find the minimum number of paired joint set for US to predict clinically significant residual synovitis. Methods A comprehensive US assessment of joints was performed in 109 RA patients who achieved DAS28-CRP remission or low disease activity. Totally 40 (20 pairs) of joints including metacarpophalangeal (MCP) 1 to 5, proximal interphalangeal (PIP) 1 to 5, wrist, elbow, shoulder, knee, ankle, metatarsophalangeal (MTP) 1 to 5 joints were evaluated according to the EULAR recommendation (2). Residual synovitis was defined as synovial hypertrophy with grey scale (GS) score greater than 1 or GS score 1 with any power Doppler (PD) signal, using semi quantitative scoring system (scale 0 to 3). Results 73 of 109 patients (67%) had at least one residual synovitis, and 39 of 73 patients (53.4%) had residual synovitis at least two different joints. As shown in table 1, residual synovitis at wrist and knee joints were found in 54.8% and 53.4% of 73 patients respectively, while for residual synovitis of another joints were less than 20% of patients. Solitary residual synovitis was most frequent in wrist and knee joints. By adding and combining joints which frequently found to have residual synovitis, we found that combination of wrist, knee, ankle, elbow, MCP1, and MCP2 joints (6 pairs) could detect residual synovitis in 94.5% of patients (table 2). Using the fact that one patients can have more than one residual synovitis at different joints and the tendency of residual synovitis to be found at some particular joints, we might find minimum pairs set of joint ultrasonography to detect residual ultrasound-defined synovitis. This could minimise the efforts needed to perform thorough joint US, while keeping the sensitivity high enough to detect any residual synovitis. Conclusions Patients achieved DAS28-CRP remission often had residual synovitis. The residual synovitis had tendency to be distributed at wrist, knee, ankle, elbow, MCP1, and MCP2, joints frequently used in activities of daily life. We propose this combination of joints as the minimum paired joint set to predict ultrasonographic remission. References [1] Foltz V, et al. Arthritis & Rheumatology2012;64:67–76. [2] Backhaus M, et al. Ann Rheum Dis2001;60:641–649. Disclosure of Interest None declared

Background Biologics are effective for improving disease activity in patients with rheumatoid arthritis (RA). However, improved disease activity of RA alone does not always lead to high patient satisfaction. Objectives We evaluate which factors among items of disease activity and health status are correlated with improvement of patient satisfaction in patients with RA treated with biological agent. Methods Patients with RA who were planning to be treated with tocilizumab (TCZ) were enrolled in this study. Satisfaction, disease activity, and health status were assessed at week 0 and week 24 of TCZ therapy. Disease activity was evaluated using SJC, TJC, PGA, EGA and CDAI. Pain was also assessed using Visual Analogue Scale (VAS). Satisfaction and health status were assessed using the patient satisfaction score and the 5 components of the Arthritis Impact Measurement Scale 2 (AIMS-2). Multiple linear regression analysis was used to assess the correlation between changes in satisfaction, disease activity and health status adjusted for CDAI at weed 0. Also, Wilcoxon signed rank test was used to evaluate effect of TCZ on satisfaction, disease activity, and health status. Results Nineteen patients (male/female: 4/15) were evaluated. Patients’ data at baseline were as follows: mean of age (51.3), disease duration (7.6 years), SJC (12.2), TJC (9.6), PGA (47.9 mm), EGA (51.4 mm), CRP (2.9 mg/dl) and CDAI (10.2), respectively. SJC, TJC, PGA, CDAI and RA-pain showed a statistically significant decrease at week 24 compared to the baseline (p After adjusting for CDAT at week 0, the change in satisfaction from week 0 to week 24 showed statistically significant correlation with changes in PGA and pain-VAS (all p-values Conclusions Satisfaction was correlated with pain, PGA and psychological state in patients with RA treated with tocilizumab. On the other hand, satisfaction was not correlated with TJC, SJC and EGA. In other words, it appears that patient satisfaction is more closely linked with how symptoms are experienced physically and mentally. Further research into specific factors influencing the patients’ experience could shed more light on conditions for improving patients’ satisfaction and QOL. Disclosure of Interest None declared

The current study aimed to compare cytology using SurePathBetween January 2014 and December 2016, 57 patients underwent endoscopic retrograde cholangiopancreatography for the diagnosis of biliary disease. Biliary cytological samples were processed using SP-LBC and subsequently BTH was performed. A final diagnosis was confirmed by surgery (23 malignant cases) and clinical follow-up (34 benign and malignant cases): 18 extrahepatic cholangiocarcinoma; 17 intrahepatic/hilar cholangiocarcinoma (intra/H-CC); eight other malignant disease; and 14 benign biliary disease. The diagnoses made using SP-LBC and BTH were classified into four categories: (1) benign; (2) indeterminate; (3) suspicious for malignancy/malignant; and (4) inadequate. In addition, diagnostic accuracy was compared between SP-LBC and BTH.Although 23% (13/57) of BTH samples were classified as inadequate, all SP-LBC cases were classified as adequate. Among 43 malignant cases, 11 normal, four indeterminate and 28 suspicious for malignancy/malignant were found using SP-LBC (26%, 9% and 65%, respectively), in contrast to 10 inadequate, nine normal, 10 indeterminate and 14 suspicious for malignancy/malignant observed using BTH (23%, 21%, 23%, and 33%, respectively). The identification of malignant cells was strikingly different between SP-LBC and BTH. Furthermore, limited to intra/H-CC, accuracy was significantly higher using SP-LBC than using BTH (P .001).SP-LBC of the biliary tract is a useful and reliable method for diagnosing biliary malignant disease and has an advantage over BTH for detecting malignant cells and accurately diagnosing intra/H-CC.