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This article presents a method to experimentally estimate the direct and cross-coupled dynamic coefficients of tilting-pad journal bearings of vertical hydro-generators and other similar rotating machinery for damage detection purposes. Based on a simplified second-order model of a journal bearing in the state-space, the method employs only the usually monitored vibrations, the shaft radial relative, and the bearing radial absolute vibrations originated by the hydro-generator residual unbalance or by hydraulic excitations in the turbine rotor. This article shows that the method was successfully tested using the shaft and bearing vibration signals synthesized by a mathematical model of a 700 MW hydro-generator, even when these signals are contaminated with random noise. This article also shows the method’s performance when applied to real vibration signals acquired from the modeled hydro-generator. Finally, it discusses the possible measures to improve the method’s efficiency.

Background: To clarify the changes in the echo intensity (EI) in the prefemoral fat pad (PFP) and identify the relationship between the PFP and clinical features of knee osteoarthritis (OA). Methods: Twenty-six women with knee OA (mean age: 76 years) and 17 healthy women (mean age: 73 years) were enrolled. The Kellgren and Lawrence grading scale was used for the radiographic evaluation of knee OA. The EI of the PFP was measured as grayscale values. The change ratio of the anteroposterior PFP length during quadriceps contraction was measured. Knee range of motion and pain (100-mm visual analog scale) were evaluated. Results: The EI was significantly higher in the OA group than in the healthy group (P < 0.001). The change ratio of the PFP in the OA group was significantly lower than that in the healthy group (P < 0.001). The ranges of knee flexion and extension were correlated with the EI of the PFP (both P < 0.01) and the change ratio of the PFP (both P < 0.01). There was no significant correlation observed with knee pain. Conclusion: Hyperechoic changes and a decreased change ratio of the PFP were observed in the patients with knee OA. High EI and decreased morphological PFP changes were associated with decreased ranges of motion.

While many academic conferences are transitioning to online events, this article aims to share several strategies used by the organizers of a well-established online-only conference. The Teaching, Colleges, and Community (TCC) Worldwide Online Conference recently celebrated its 25th anniversary. After a brief review of TCC’s history, four strategies that organizers have identified as helping conference goers feel oriented, welcomed, connected and engaged are described. These strategies include offering a “pre-conference” orientation, including regional keynote speakers, creating opportunities for informal exchange, and encouraging participation with digital credentials.

Funding Acknowledgements Type of funding sources: None. Background Occurrence of ventricular tachycardias (VT) has been related to changes in sympathetic innervation and myocardial tissue in ischemic cardiomyopathy. In non-ischemic cardiomyopathy (NICM) patients with VT, the relation between global cardiac sympathetic innervation and non-ischemic fibrosis is less clear. The current gold standard in electrophysiology to identify non-ischemic fibrosis relies on unipolar endocardial voltage mapping. Objective To establish the relationship between global cardiac sympathetic innervation and global fibrosis. Methods 29 patients (93% male, 58 ± 14 years, mean LVEF 38%±13) from the ‘Leiden Nonischemic Cardiomyopathy Study’ undergoing VT ablation between 2011-2018 were included. Endocardial voltage mapping was performed and the mean endocardial unipolar voltage (UV) was taken as a surrogate for global fibrosis. Global cardiac sympathetic innervation was analyzed by 123-I-MIBG imaging using heart-to-mediastinum ratio (HMR). A cut-off of 1.8 was used to delineate between normal (>1.8) and denervated ( Results For patients with global cardiac sympathetic denervation a linear relationship was present between HMR and mean UV (R = 0.5278, P = 0.0431. There was no significant linear relationship for patients with normal cardiac sympathetic innervation between HMR and mean UV (R=-0.1696, P = 0.5795). Conclusion Global cardiac sympathetic denervation is related to myocardial fibrosis in patients with NICM and VT. The data support an interplay between denervation and fibrosis which may contribute to arrhythmogeneity, as observed in ICM. Abstract Figure.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation - Projektnummer 447558597) Background Among patients with non-ischemic cardiomyopathy (NICM) two dominant ventricular tachycardia (VT) substrate locations, namely anteroseptal (AS) and inferolateral (IL), have been identified. The poor outcome after catheter ablation of AS substrates (ASS) compared to IL substrates (ILS) has been attributed to its deep intramural location. However, region specific tissue charateristics, including sympathetic innervation, as important determinant of arrhythmogeneity, may also contribute to the outcome disparity. Aim To evaluate the association between regional sympathetic denervation, myocardial fibrosis and VT substrates according to two dominant VT substrate locations. Methods Twenty-nine patients from the ‘Leiden Nonischemic Cardiomyopathy Study’, who underwent electroanatomical substrate mapping and radiofrequency catheter ablation (RFCA), LGE-CMR and 123-I-MIBG imaging between 2011-2018 were included. The 16-segment model was used to describe the distribution of endocardial low unipolar voltage (UV Results Ten patients had a dominant ASS, 12 patients a dominant ILS and 1 patient had ASS and ILS; 6 patients had other VT substrate locations. All but one patient with ASS and one with ILS also showed corresponding low UV (=surrogate for fibrosis) in segments with VT substrates. Eight patients with IL VT substrates but only 4 with AS substrates showed corresponding LGE in the VT related segments. All patients with inferolateral VT substrates showed sympathetic denervation in IL segments (100% matching segments), but only 3/11 (27%) with anteroseptal substrates had sympathetic denervation in AS segments (P = 0.0002). UV was not significantly different between matching (VT substrate and denervation) and not matching ASS segments (5.74 ± 2.69 mV vs. 4.64 ± 1.85 mV, P = 0.78) and between matching ASS and ILS segments (5.74 ± 2.69 mV vs. 7.61 ± 2.91, P = 0.43). LGE location was matching with sympathetic denervation in all patients with ILS but only in 33% of patients with ASS. Conclusion Despite low endocardial UV (=surrogate for fibrosis) for AS and IL segments harboring VT substrates, regional sympathetic denervation coincided with fibrosis only for IL VT substrates. The mismatch between regional fibrosis and preserved innervation for AS VT substrates may contribute to a VT substrate difficult to control by RFCA.

Funding Acknowledgements Type of funding sources: None. Background Patients with dilated cardiomyopathy (DCM) and ventricular tachyarrhythmias (VT) are at risk for heart failure (HF) death. Global left ventricular endocardial voltage may reflect the amount of excitable viable myocardium and identify patients at risk for rapid progression to end-stage HF. Aim To determine if volume-weighted endocardial voltage, as a surrogate for the total excitable viable myocardium, predicts mortality in patients with DCM and VT. Methods Consecutive patients with DCM, who underwent high-density endocardial voltage mapping for VT or PVC ablation (2012-2018), were included. Mapping data were transferred from CARTO to ParaView after excluding valve areas. The volume-weighted UV and BV (vwUV, vwBW) were calculated by mathematically integrating the UV and BV over the whole LV (thereby correcting for mapping density heterogeneity) divided by the endocardial LV surface area and corrected for LV wall thickness determined by echocardiography. The prognostic values of vwUV and vwBV for cardiac function and cardiac death were evaluated. Results One hundred three patients (VT, n = 83 and PVC, n = 20; age, 57 ± 14yrs; LVEF, 39 ± 13%; [likely] pathogenic genetic variants 33 [32%]; amiodarone use 36 [35%]) were included. VwUV and vwBV were 9.94 ± 3.42 and 4.70 ± 1.46. During a median follow-up of 24 months, cardiac mortality was 18% (end-stage HF 16/19, the median time to death 5.7 months). Patients who died had a significantly lower vwUV and vwBV (vwUV 5.62 ± 0.93 vs. 10.91 ± 3.10, P 5% and transition to HFrEF) occurred in 22% and was strongly related with a low vwUV (6.65 ± 1.15 vs. 10.08 ± 2.92, P = 0.02, Figure B left). Furthermore, in patients with HFrEF, a significant LVEF improvement (defined as an EF increase >5% and transition to HFmrEF) was noted in 32% and was correlated with a high vwUV (11.68 ± 2.70 vs. 8.62 ± 2.69, P = 0.002, Figure B right). Conclusion VwUV is a newly proposed surrogate for the amount of LV viable myocardium, available from routine endocardial mapping and an excellent parameter to identify patients with DCM at high risk for rapid progression to HF-related death. Abstract Figure. vwUV and outcomes

IntroductionDirect-to-family clinical trials efficiently provide data while reducing the participation burden for children and their families. Although these trials can offer significant advantages over traditional clinical trials, the process of designing and implementing direct-to-family studies is poorly defined, especially in children with rheumatic disease. This paper provides lessons learnt from the design and implementation of a self-controlled, direct-to-family pilot trial aimed to evaluate the effects of a medication management device on adherence to hydroxychloroquine in paediatric SLE.MethodsSeveral design features accommodate a direct-to-family approach. Participants meeting eligibility criteria from across the USA were identified a priori through a disease registry, and all outcome data are collected remotely. The primary outcome (medication adherence) is evaluated using electronic medication event-monitoring, plasma drug levels, patient questionnaires and pill counts. Secondary and exploratory endpoints include (1) lupus disease activity measured by a remote SLE Disease Activity Index examination and the Systemic Lupus Activity Questionnaire; and (2) hydroxychloroquine pharmacokinetics and pharmacodynamics. Recruitment of the initial target of 20 participants was achieved within 10 days. Due to initial recruitment success, enrolment was increased to 26 participants. Additional participants who were interested were placed on a waiting list in case of dropouts during the study.Discussion and disseminationDirect-to-family trials offer several advantages but present unique challenges. Lessons learnt from the protocol development, design, and implementation of this trial will inform future direct-to-family trials for children and adults with rheumatic diseases. Additionally, the data collected remotely in this trial will provide critical information regarding the accuracy of teleresearch in lupus, the impact of adherence to hydroxychloroquine on disease activity and a pharmacokinetic analysis to inform paediatric-specific dosing of hydroxychloroquine.Trial registration numberClinicalTrials.gov Registry (NCT04358302).

CD69 is an activation marker on leukocytes. Early studies showed that the CD69+ cells were detected in the lung of patients with asthmatic and eosinophilic pneumonia, suggesting that CD69 might play crucial roles in the pathogenesis of such inflammatory diseases, rather than simply being an activation marker. Intensive studies using mouse models have since clarified that CD69 is a functional molecule regulating the immune responses. We discovered that Myosin light chain 9, 12a, 12b (Myl9/12) are ligands for CD69 and that platelet-derived Myl9 forms a net-like structure (Myl9 nets) that is strongly detected inside blood vessels in inflamed lung. CD69-expressing activated T cells attached to the Myl9 nets can thereby migrate into the inflamed tissues through a system known as the CD69-Myl9 system. In this review, we summarize the discovery of the CD69-Myl9 system and discuss how this system is important in inflammatory immune responses. In addition, we discuss our recent finding that CD69 controls the exhaustion status of tumor-infiltrating T cells and that the blockade of the CD69 function enhances anti-tumor immunity. Finally, we discuss the possibility of CD69 as a new therapeutic target for patients with intractable inflammatory disorders and tumors.

The numbers of patients with inflammatory bowel disease (IBD), such as ulcerative colitis (UC) and Crohn’s disease (CD), have been increasing over time, worldwide; however, the pathogenesis of IBD is multifactorial and has not been fully understood. Myosin light chain 9 and 12a and 12b (Myl9/12) are known as ligands of the CD69 molecule. They create “Myl9 nets” that are often detected in inflamed site, which play a crucial role in regulating the recruitment and retention of CD69-expressing effector cells in inflamed tissues. We demonstrated the strong expression of Myl9/12 in the inflamed gut of IBD patients and mice with DSS-induced colitis. The administration of anti-Myl9/12 Ab to mice with DSS-induced colitis ameliorated the inflammation and prolonged their survival. The plasma Myl9 levels in the patients with active UC and CD were significantly higher than those in patients with disease remission, and may depict the disease severity of IBD patients, especially those with UC. Thus, our results indicate that Myl9/12 are involved in the pathogenesis of IBD, and are likely to be a new therapeutic target for patients suffering from IBD.

integration requires development of low thermal budget process modules. High-quality SiO 2 interfacial layer (IL), obtained up to now only by high-temperature (≥850°C) oxidation or exposure, is crucial for pMOS NBTI reliability. In unannealed IL’s grown at reduced temperatures, we show that unrelaxed interface strain induces high defect densities, with physics-based NBTI modeling suggesting excessive hydroxyl-E’ defect formation due to Si-O bond stretch. Based on ab-initio theoretical insights, we demonstrate an atomic hydrogen treatment to passivate SiO 2 defects at low temperatures (100-300°C), which is shown to be vastly more effective than high pressure molecular hydrogen exposure, and to yield an SiO 2 quality and reliability surpassing a 900°C oxide.

The iris pattern has significantly improved the biometric recognition field due to its high level of stability and uniqueness. Such physical feature has played an important role in security and other related areas. However, presentation attacks, also known as spoofing techniques, can be used to bypass the biometric system with artifacts such as printed images, artificial eyes, and textured contact lenses. To improve the security of these systems, many liveness detection methods have been proposed, and the first Internacional Iris Liveness Detection competition was launched in 2013 to evaluate their effectiveness. In this paper, we propose a hyperparameter tuning of the CASIA algorithm, submitted by the Chinese Academy of Sciences to the third competition of Iris Liveness Detection, in 2017. The modifications proposed promoted an overall improvement, with an 8.48% Attack Presentation Classification Error Rate (APCER) and 0.18% Bonafide Presentation Classification Error Rate (BPCER) for the evaluation of the combined datasets. Other threshold values were evaluated in an attempt to reduce the trade-off between the APCER and the BPCER on the evaluated datasets and worked out successfully., Comment: Accepted for presentation at the International Conference on Computer Vision Theory and Applications (VISAPP 2020)

We report the case of painful snapping pes syndrome caused by the gracilis tendon. A 26-year-old man presented with acute right knee pain and restricted extension. Although snapping could not be reproduced due to severe pain, the snapping of the gracilis tendon could be specifically diagnosed using ultrasonography and lidocaine injection. Because of the failure of conservative treatment, surgery was performed. The distal attachment of the gracilis tendon was released, and the symptom disappeared quickly. There was no recurrence at the 10-month follow-up.

The integration of a three-layer BEOL process which includes an intermediate 21 nm pitch level, relevant for the 3 nm technology node, is demonstrated. A full barrier-less Ruthenium (Ru) dual-damascene (DD) metallization allowed to test different dimensions of minimum island, via extension and tip-to-tip (T2T). Five-track place and route (PNR) and SRAM constructions were realized with the self-aligned block (SAB) technique. Stacked vias showed resistance modulation with the size of the minimum island due to the change in via chamfer. High aspect ratio supervias (SV), to bypass M2 and directly link M1 to M3, were tested with different metallization schemes. Line-to-line and T2T reliability tests passed the 10- year lifetime predictions. Finally, electromigration (EM) tests on SV showed no failures after 140 hours of accelerated stress conditions.

Background In patients with non-ischemic cardiomyopathy (NICM), non-inducibility after catheter ablation has been associated with lower VT recurrence rates. We hypothesized that induced VT pleomorphism (PL-VT) may be indicative for a complex VT substrate that might be associated with poor ablation outcome independently of non-inducibility at the end of the procedure. Methods Consecutive patients with left-dominant NICM undergoing VT ablation (2008–2018) were included. All patients underwent genetic screening. PL-VT was defined as occurrence of ≥1 morphologically distinct QRS lasting for ≥6 consecutive beats during the same induced VT episode. Complete acute success was defined as non-inducibility of any VT at the end of procedure. Results Eighty-five patients (56±15 yrs, LVEF 38±12%), inducible for 365 VTs (median 3/patient, IQR 1–6) were included. PL-VT was observed in 29 patients (34%). Patients with PL-VT had more often anteroseptal substrates, a higher number of induced VTs, and larger endocardial bipolar ( Figure 1 Conclusions Induced PL-VT was not associated with acute outcome but higher VT recurrence rate after catheter ablation in patients with NICM. Moreover, co-existence of PL-VT and persistent VT inducibility identifies patients at highest risk for VT recurrence whereas non-inducible patients without PL-VT have a favorable prognosis.

Background and purpose Many reports have examined electrocardiographic (ECG) changes after subarachnoid hemorrhage from long ago; however, there are few reports on the prognosis of patients who have an ECG abnormality. Therefore, in this study, the prognoses of patients with subarachnoid hemorrhage showing abnormal ECG findings were retrospectively analyzed. Methods Over 30 months from January 2014 to June 2016, 199 patients (mean age, 61.1±17.0 years; 46.7% male) admitted with a subarachnoid hemorrhage (SAH) were enrolled. To assess the mechanism underlying abnormal ECG in the SAH, predictor variables, such as demographics (age, sex, and body surface area), hemodynamics (heart rate and systolic blood pressure), blood biochemical results, neurological assessments (Glasgow Coma Scale), and computed tomography (CT) severity classification (World Federation of Neurosurgical Societies classification) were recorded. The subarachnoid hemorrhage was classified into either the cerebral aneurysm rupture group (N=132) or traumatic subarachnoid hemorrhage group (N=67) and analyzed. Results In the cerebral aneurysm rupture group, the QT prolongation was significantly increased compared with the traumatic subarachnoid hemorrhage group (424.8±87.7 ms vs. 400.5±95.8 ms, P Conclusions Significantly prolonged QT and ST changes are noted in patients with severe aneurysmal subarachnoid hemorrhage. The cause of the ECG abnormality in subarachnoid hemorrhage patients is not yet understood. A small number of experimental animal models have shown that electrocardiogram abnormalities associated with subarachnoid hemorrhage develop in the brain stem, and an autonomic nerve abnormality may also be involved. A D-dimer is positively correlated with both aneurysm trauma and traumatic subarachnoid hemorrhage and may be used for auxiliary diagnosis of a subarachnoid hemorrhage.

Background: In normal knees, quadriceps contraction changes the shape of the prefemoral fat pad (PFP). However, in persons with knee osteoarthritis (OA), the functional or morphological changes of the PFP are unclear. This study aimed to clarify the morphological changes in the PFP in individuals with knee OA through ultrasonography. Materials and Methods: Participants were divided into the OA (36 knees; mean age, 74 years), elderly (31 knees; mean age, 70 years), and young (26 knees; mean age, 21 years) groups. The anteroposterior (AP) length of the PFP before and during isometric quadriceps contraction at 0°, 30°, 60°, and 90° knee flexion was measured ultrasonographically. The difference between the maximum and minimum length values, change in length, was also measured. These parameters were compared among the three groups. In the OA group, correlations between the parameters and clinical features (knee pain; visual analog scale, knee range of motion [ROM], Kellgren and Lawrence (K/L) grade, and intercondylar distance) were examined by Spearman and Pearson's correlation coefficient tests. Results: The AP lengths of the PFP before contraction were significantly lower in the OA group than in elderly group and young group at 30° (6.9 ± 2.5 vs. 12.0 ± 3.6 or 11.1 ± 2.7 mm, respectively; in order P = 0.014, P = 0.006) and 60° (6.5 ± 2.0 vs. 9.7 ± 2.5 or 9.1 ± 2.7 mm, respectively; both P < 0.001). The AP lengths of the PFP during contraction were significantly lower in the OA group than in elderly group and young group at 0° (6.7 ± 2.3 vs. 8.8 ± 3.7 or 9.1 ± 1.6 mm, respectively; both P < 0.001), 30° (7.9 ± 2.6 vs. 12.9 ± 3.7 or 13.0 ± 2.6 mm, respectively; both P < 0.001), and 60° (7.1 ± 2.5 vs. 13.5 ± 2.6 or 13.6 ± 3.0 mm, respectively; both P < 0.001). The change in length before maximum isometric quadriceps contraction was significantly lower in the knee OA group than in both elderly and young groups (3.3 ± 1.9 vs. 8.4 ± 2.5 or 6.8 ± 3.0 mm, respectively; both P < 0.001). The change in length during contraction was also significantly lower in the knee OA group than in both the elderly and young groups (3.9 ± 2.3 vs. 8.7 ± 2.3 or 8.9 ± 2.0 mm, respectively; both P < 0.001). In the OA group, change in length during contraction was significantly associated with knee pain (r = −0.476, P = 0.007), knee ROM (r = 0.388, P = 0.019), and Kellgren and Lawrence grade (r = −0.357, P = 0.045). Conclusions: In knee OA, movement of PFP was decreased more than healthy participants. In the knee OA group, the decrease of the morphological change of the PFP showed the relationship between VAS score, knee extension ROM, intercondylar distance (ICD), and K/L grade. An evaluation to the PFP may be required in individuals with knee OA.

Resumen Antecedentes La presencia de fibrosis hepatica es el denominador comun de numerosas enfermedades cronicas del higado que pueden evolucionar a fibrosis y a hepatocarcinoma. Las mas importantes por su frecuencia son las hepatitis virales y el higado graso no alcoholico, cuya prevalencia aumenta en proporciones epidemicas. La biopsia hepatica, aun cuando imperfecta, continua siendo el estandar de oro que tiende a ser reemplazado en muchas situaciones clinicas por metodos de imagen no invasivos. Objetivos Describir la experiencia obtenida en nuestro departamento de imagen con la tecnica de elastografia por resonancia magnetica, analizar y comentar los resultados publicados por otros autores en la literatura reciente en gastroenterologia, hepatologia y radiologia, complementada con una busqueda en PubMed de los ultimos 10 anos. Resultados y conclusiones La elastografia por resonancia magnetica es un metodo no invasivo y eficaz, cuyos resultados tienen concordancia con la biopsia hepatica, presenta superioridad sobre los metodos de elastografia por ultrasonido debido a que evalua un volumen mucho mayor de tejido hepatico y muestra la distribucion de las lesiones que, a menudo, es heterogenea. La mayor ventaja del protocolo de resonancia magnetica descrito estriba en cuantificar en la misma sesion, ademas de la fibrosis, el contenido de grasa y de hierro, lo cual se realiza en una exploracion dirigida especificamente a este fin, en un tiempo de 25 min y a un costo-beneficio favorable para el paciente y la institucion.

Background The presence of liver fibrosis is the common denominator in numerous chronic liver diseases that can progress to fibrosis and hepatocellular carcinoma. Most important, with respect to frequency, are viral hepatitis and non-alcoholic fatty liver disease, the prevalence of which is increasing in epidemic proportions. Liver biopsy, albeit imperfect, continues to be the criterion standard, but in many clinical situations tends to be replaced with noninvasive imaging methods. Objectives The aim of the present article was to describe our imaging department experience with magnetic resonance elastography and to analyze and discuss recently published results in gastroenterology, hepatology, and radiology from other authors in the literature, complemented with a PubMed search covering the last 10 years. Results and conclusions Magnetic resonance elastography is an efficacious, noninvasive method with results that are concordant with liver biopsy. It is superior to ultrasound elastography because it evaluates a much greater volume of hepatic tissue and shows the often heterogeneous lesion distribution. The greatest advantage of the magnetic resonance protocol described is the fact that it quantifies fibrosis, fat content, and iron content in the same 25 min examination specifically directed for that purpose, resulting in a favorable cost-benefit ratio for the patient and/or institution.

This paper presents a plasmonic circuit that has been monolithically integrated with electronic devices on a silicon substrate and then discusses the concept behind this circuit. To form the proposed circuit, two plasmonic waveguides and a detector are integrated with metal–oxide–semiconductor field-effect transistors (MOSFETs) on the substrate. In the circuit, intensity signals or coherent plasmonic signals are generated by coherent light at an operating wavelength at which silicon is transparent, and these signals propagate along the waveguides before they are converted into electrical signals by the detector. These electrical intensity and coherent signals then drive the MOSFETs during both DC and AC operation. The measured performances of the devices indicate that surface plasmon polaritons propagate on the metal surface at the speed of light and drive the electronic devices without any absorption in the silicon.

Background While the number of rheumatoid arthritis (RA) surgeries has been declining due to advances in pharmacotherapies for RA, forefoot surgeries are on the rise. In recent years, the common use of joint ultrasonography in RA consultations has led to the early detection of synovitis. However, little is known about how much forefoot deformities such as hallux valgus and metatarsophalangeal (MTP) joint dislocation are affected by synovitis in the forefoot of RA patients. Objectives The present study examined factors involved in forefoot deformity among patients with foot synovitis identified on joint ultrasound. Methods Subjects (71 patients, 91 feet) were RA patients who had undergone foot joint ultrasonography more than 2 years earlier and underwent standing X-rays of the feet before and after ultrasonography. Surgery cases were excluded. Mean age was 64.9 years (range, 15-90 years). Disease stage was Stage 1 in 14 patients, Stage 2 in 14 patients, Stage 3 in 16 patients, and Stage 4 in 27 patients. According to the Steinbrocker functional classification, RA was Class 1 in 45 patients, Class 2 in 19 patients, Class 3 in 6 patients and Class 4 in 1 patient. Twenty-five patients had been administered biological drugs. At the time of joint ultrasonography, patients were questioned regarding whether they had any complaints involving the forefoot, midfoot or hindfoot (noted separately). The following scans were performed: forefoot (MTP joints 1-5); midfoot (calcaneocuboid, calcaneocuboid and cuneonavicular joints) and hindfoot (peroneal muscle tendon, talocrural joint, talocalcaneal joint and posterior tibial muscle tendon). Foot deformity score (FDS) (hallux valgus angle + first-second intermetatarsal angle [M1M2 angle] + first-fifth intermetatarsal angle [M1M5 angle]) was used as the benchmark for forefoot deformity, and an increase >5° was considered to indicate worsening deformity. Results Forefoot deformity had progressed in 25 patients. Mid- and hindfoot synovitis and the presence of complaints were not associated with deformity. However, significant worsening of FDS was observed in patients with forefoot synovitis or forefoot complaints. While no difference in age, disease activity, biologic disease-modifying antirheumatic drug usage or health assessment questionnaire results were seen in the advanced deformity group, duration of disease was significantly shorter in this group. Conclusion Mid- and hindfoot synovitis was unrelated to forefoot deformity. MTP joint synovitis in the forefoot was related to forefoot deformity. Continuous synovitis in the forefoot must damage the articular capsule and ligament structure, leading to progression of deformity. As shown by the short duration of the disease in the advanced deformity group, deformity may progress in the early stages among patients with forefoot deformity. Disclosure of Interests None declared

Background Treatment outcomes for rheumatoid arthritis (RA) have been improved by advances in drugs. In daily clinical practice, treatment outcomes are assessed with both inflammatory findings and based on swollen joints (SJ), tender joints (TJ), a patient’s global assessment on visual analogue scale (GVAS) score, a physician’s GVAS score, etc. Although composite measures indicate suppressed inflammatory or articular symptoms, many patients show no improvement in GVAS scores. The reported residual symptoms include morning stiffness (MS), pain (P), and dullness (D). Objectives We investigated the residual symptoms of patients achieving low disease activity (LDA) or complete remission (CR). Methods His study included 111 RA patients who received outpatient treatment at our department (31 men and 80 women). The mean age was 65.1 (range, 27–89) years. The disease stages were distributed as follows: 36 patients with Stage 1, 23 patients with Stage 2, 20 patients with Stage 3, and 32 patients with Stage 4. The severity of dysfunction was distributed as follows: Class 1 in 73 patients, Class 2 in 25 patients, Class 3 in 11 patients, and Class 4 in 2 patients (Steinbrocker classification). Based on the disease activity score in 28 joints using the erythrocyte sedimentation rate, disease activity was graded as CR in 54 patients, LDA in 19, moderate disease activity in 37, and high disease activity in 1. Questionnaire forms were used to assess the presence or absence and duration of MS and the presence or absence and severity of P (Pain VAS) and of D (Dullness VAS). These variables were assessed to determine how they were associated with clinical outcome measures, drugs, and surgery. Results The following residual symptoms were observed in 73 patients who achieved the treatment target of LDA or CR: MS in 34 patients (46.6%), P in 48 (65.6%), and D in 38 (52.8%). In the LDA+CR group, the Pain VAS (P Conclusion Residual symptoms were frequently observed even in patients achieving LDA or CR, which is regarded as the treatment target. Because P and D were significantly correlated with the GVAS, relief of these residual symptoms is expected to improve treatment effects. Although D was relieved by bDMARDs, further studies on the treatment of residual P in patients achieving LDA or CR are necessary. Disclosure of Interests None declared

Swimming pool disinfection byproducts (DBPs) are becoming increasingly common worldwide. Precise exposure and health risk assessment for DBPs in swimming pool water with optimized parameters for local and specific population is more urgently needed. This study aimed to determine the levels of trihalomethanes (THMs) and haloacetic acids (HAAs) in 16 public indoor swimming pools in Shanghai, China. Swimming habits were also investigated to obtain more accurate exposure assessment parameters. Precise exposure assessment through multiple pathways, resulting cancer risk, and disability-adjusted life years (DALYs) were assessed. Results indicated that the highest total level of THMs and HAAs occurred in autumn. The surveyed swimmers 9-17 years of age had higher average daily dose (ADD) of DBPs than swimmers ≥18 years of age. The total lifetime cancer risk (LCR) attributable to THMs and HAAs exceeded 10-6, which represents a negligible risk level (NRL). The cancer risk from inhalation exposure predominantly by THMs contributed more than 99% of the total risk. Annual disease burden was 19.0 person-years attributed to exposure of DBPs in swimming pool water in Shanghai. This study provides a paradigm and strategic reference of precise exposure assessments, risk assessments, and disease burden estimation of hazards in swimming pool water for other regions.

Background:Natural Killer Cells are innate immune system cells important in host defenses against viruses and tumor cells. Two subpopulations are well described: NK CD56bright CD16neg (NK56++16-) which is less frequent in peripheral blood (PB) and associated with high cytokine production, and NK56dim16pos (NK56+16+), more frequent in PB and associated with high cytotoxic activity. In allogeneic hematopoietic stem cell transplantation (allo-HSCT), NK cells are important for infection control, and also for the disease control. The mismatch between donor NK cell receptors and host HLA may lead to a stronger graft versus leukemia (GVL), possibly modulating graft versus host disease (GVHD). However, only a few studies evaluated NK subpopulations recovery after HSCT and the impact on transplant outcomes. Objectives: The aim of the study was to analyze NK cells subpopulations reconstitution after HSCT and their possible impact on HSCT endpoints: relapse, GVHD (acute and chronic), transplantation related mortality and overall survival. Patients and Methods: Overall, 77 patients from 4 HSCT centers (60 % male, median age 17 years, range 1-74), receiving bone marrow (BM, 47%), umbilical cord (UCB, 30%) or peripheral blood (PB, 23%) from unrelated (80%) or related donors (20%) were studied. The most common diagnosis was acute leukemia (AML 38%, ALL 34%). Most patients received myeloablative conditioning (MAC) regimens (61%). Antithymocyte globulin (ATG) was used in 27 patients (35%) and total body irradiation (TBI) in 40 (52%). Median follow up time was 82 months (22-107). NK subpopulations were quantified by multiparametric flow cytometry at engraftment and days 3, 7, 14, 21 and 60 after engraftment. We have then elaborated graphs plotting cells counts over time (until 60 days) and calculated the area over the curve (AOC) for each subpopulation [NK56++16- (NK56-index) and NK56+16+ cells (NK16-index)], considering 0.5x10e9/L as cut-off value for both subpopulations. A higher AOC represents a more profound NK deficiency. Using receiver operating characteristic (ROC) curves we determined cut offs for the AOC that could provide the best correlation with survival. Results:The overall survival (OS) in 80 months was significantly worse in patients with NK56 deficiency, defined by a NK56-index > 14592.31 cells/mm3.days (29% x 73% for non- deficient, p=0.0001, Figure 1). NK56 deficient patients also had a higher cumulative incidence (CI) of non-relapse related mortality (NRM: 35% x 15%, p=0.03, Figure 2). GVHD (acute or chronic) was similar between low NK56-index and high NK-56 index patients. In multivariate analysis, high NK56index remained significantly associated with worse OS [hazard ratio (HR) 3.5; 95% confidence interval (95%CI) 1.6-7.6], and higher NRM (HR 2.9; 95%CI 1.0-8.0). There were no significant correlations between NK16-index with any of the analyzed HSCT outcomes. Conclusion: A higher NK56-index is significantly associated with worse outcome in long term survival and non relapse related mortality in patients submitted to allogeneic hematopoietic stem cell transplantation. This strategy might be helpful in identifying risk groups and possible earlier therapeutic interventions. Disclosures No relevant conflicts of interest to declare.

Background: Most studies in immune reconstitution after allogeneic hematologic stem cell transplantation (alloHSCT) focus on adaptive immunity, particularly in lymphocyte recovery. Classical monocytes (cMo) are part of the innate immunity, playing an important role in the defense against fungal and bacterial infections. The innate and adaptive immunity are closely related, and non-classical monocytes (ncMo) participate in this connection, regulating T cell response. However, the role of these cells in the graft versus tumor effect and graft versus host disease (GVHD) is still unclear. Objectives: The aim of the study was to investigate cMo and ncMo reconstitution after alloHSCT and a possible impact of these cells subsets on acute and chronic GVHD, relapse, non-relapse related mortality (NRM) and overall survival (OS). Patients and Methods: This is a retrospective analysis of 77 patients who underwent alloHSCT in 4 different transplant centers in Brazil. Peripheral blood samples were collected from patients at neutrophil engraftment (NE) and 3, 7, 14, 21, and 42 days after NE. The cMo (DR+, CD11c+, CD14+, CD16-) and ncMo (DR+, CD11c+, CD14-, CD16+) were classified and analyzed by 8-color multiparametric flow cytometry (FACSCanto II). In order to analyze the possible impact of duration and severity of monocytopenia after transplant, we calculated then the 'mono-index' and the 'ncMo-index', based on the area over the curve (AOC) of absolute cMO counts (AMC) and absolute ncMo counts, respectively, considering a horizontal line of AMC 0.5x10e9/L as cut-off value for both subpopulations. Results: The medium follow up was 82 months. Out of 77 patients, 46 (60%) were male, and the median age was 17 years (range: 1-74). The stem cell source was bone marrow in 36 (47%), cord blood in 23 (30%), and peripheral blood in 18 (23%); and donors were matched unrelated in 61 (79%), and matched related in 16 (21%) cases. Most patients received myeloablative conditioning (n=47, 61%); and acute leukemia was the most common diagnosis (72%). A total of 40 (52%) patients received total body irradiation (TBI), and 27 (35%) patients received antithymocyte globulin (ATG). We calculated the possible impact of cMo at all timepoints and found no differences in the main outcomes between patients with lower or higher counts. We then analyzed the AOC of all cMo counts (the mono-index). A higher index represents a more severe deficiency of cMo. We then used the receiver operating characteristic (ROC) curve to define the cut-off value of 14234.4 cells/days x mm3 to discriminate patients as cMo deficient (n=31, 40%) or non-deficient (n=46, 60%). Non relapse mortality (NRM) at 6 years was higher in cMo deficient patients calculated by the mono-index (40% vs. 16% for non-deficient, p=0.02, Figure 1). Deficient patients also had worse OS at 6 years (58% vs. 37% for non-deficient, p=0.03, Figure 2). In multivariate analyses, cMo deficiency calculated by the mono-index remained significantly associated with NRM (hazard ratio 3.07, 95% confidence interval) and OS (HR 2.05, 95%CI 1.20-7.85). We observed no impact of mono-index on acute or chronic GVHD or relapse. We observed no impact of the ncMo counts at all timepoints or the ncMo-index in any of the analyzed outcomes. Conclusion: cMo deficiency calculated by the mono-index can predict mortality in alloHSCT. Mono-Index is an inexpensive, accessible and easy to perform tool that might help clinicians in predicting unfavorable outcomes. Further studies are needed to confirm these findings and to test how different transplant strategies or therapeutic changes might interfere with monocytes recovery in alloHSCT. Disclosures No relevant conflicts of interest to declare.

The introduction of immune checkpoint inhibitors in cancer treatment highlights the negative regulation of anti-tumor immunity, such as effector T-cell exhaustion in the tumor microenvironment. However, the mechanisms underlying the induction and prevention of T-cell exhaustion remain largely unknown. We found that CD69, a type II glycoprotein known to regulate inflammation through T-cell migration and retention in tissues, plays an important role in inducing the exhaustion of tumor-infiltrating T cells. Cd69-/- mice showed reduced tumor growth and metastasis in a 4T1-luc2 murine breast cancer model, in which increased numbers of tumor-infiltrating lymphocytes, relatively little T-cell exhaustion, and enhanced IFNγ production were observed. Anti-CD69 monoclonal antibody treatment attenuated the T-cell exhaustion and tumor progression in tumor-bearing mice. These findings highlight a novel role of CD69 in controlling the tumor immune escape mediated by T-cell exhaustion and indicate that CD69 is a novel target for cancer immunotherapy.

Purpose Percutaneous driveline infection is a major complication after left ventricular assist device (LVAD) implantation, causing pump infection. Therefore, the precise diagnosis and evaluation of driveline infection are important. Recently, Fluor-18-fluorodeoxyglucose positron emission tomography is used for diagnosis of LVAD-specific and related infections. However, the role of Gallium-67 single-photon emission computed tomography (Ga-SPECT)-CT has not been fully elucidated. We investigated whether Ga-SPECT-CT predicts outcomes of patients with LVAD-specific percutaneous driveline infection. Methods Thirty-six patients with implantable continuous-flow LVAD, who underwent Ga-SPECT-CT to diagnose and evaluate percutaneous driveline infections, were enrolled and divided into uptake and no-uptake groups based on tracer concentration uptake on Ga-SPECT-CT. Main outcomes were surgical intervention (debridement, translocation of driveline exit site or pump exchange) and driveline-infection-caused readmission. Results Uptake on Ga-SPECT-CT revealed in 22 patients and regions of uptake were 9 (41%) driveline exit site, 10 (45%) subcutaneous driveline tunnel, and 3 (14%) sub-rectus driveline tunnel. No significant differences were noted in patient characteristics, wound appearance, and blood test. The prevalence of positive skin culture of driveline exit site as well as usage and duration of antibiotics did not differ (uptake vs no-uptake: 21/22, 95% vs 12/14, 86%, P = 0.30; 20/22, 91%, vs 11/14, 79%, P = 0.30; 20 vs 17 days, P = 0.19, respectively). However, the uptake group had a higher 1-year event rate (surgical intervention: 32% vs 0%, P = 0.037; readmission: 74% vs 6.9%, P = 0.0016). Conclusion Ga-SPECT-CT predicts surgical intervention and readmission in patients with LVAD-specific percutaneous driveline infection. Driveline infections with uptake on Ga-SPECT-CT require aggressive treatment including early surgical treatment.