Fragments Generated during Liquid Hydrogen Tank Explosions

Liquid hydrogen (LH2) may be employed to transport large quantities of pure hydrogen or be stored onboard of ships, airplanes and trains fuelled by hydrogen, thanks to its high density compared to gaseous compressed hydrogen. LH2 is a cryogenic fluid with an extremely low boiling point (-253°C at atmospheric pressure) that must be stored in double-walled vacuum insulated tanks to limit the boil-off formation. There is limited knowledge on the consequences of LH2 tanks catastrophic rupture. In fact, the yield of the consequences of an LH2 tank explosion (pressure wave, fragments and fireball) depend on many parameters such as tank dimension, filling degree, and tank internal conditions (temperature and pressure) prior the rupture. Only two accidents provoked by the rupture of an LH2 tank occurred in the past and a couple of experimental campaigns focussed on this type of accident scenario were carried out for LH2. The aim of this study is to analyse one of the LH2 tank explosion consequences namely the fragments. The longest horizontal and vertical ranges of the fragments thrown away from the blast wave are estimated together with the spatial distribution around the tank. Theoretical models are adopted in this work and validated with the experimental results. The proposed models can aid the risk analysis of LH2 storage technologies and provide critical insights to plan a prevention and mitigation strategy and improve the safety of hydrogen applications

17 Fertility and pregnancy issues in patients with lupus nephritis

Case 1: Pre-pregnancy counselling for women with lupus nephritis Liz Lightstone An African Caribbean woman was diagnosed with systemic lupus erythematosus (SLE) in 2009 aged 21 years. At that time, she had severe Class IV lupus nephritis (LN) with crescents and acute kidney injury and was treated with steroids and cyclophosphamide. She achieved good clinical remission and was maintained for several years on low-dose prednisolone, mycophenolate mofetil (MMF), hydroxychloroquine (HCQ) and irbesartan. Antiphospholipid and lupus anticoagulant were negative, she was anti Ro positive with no extra renal manifestations. She attended for pre-pregnancy counselling in July 2017 aged 29 years. She was off steroids but still taking MMF and irbesartan. Her creatinine was 97 umol/l with eGFR 70.8 mls/min (59 mls/min not corrected for race) and she had no proteinuria. Her labs at that time were ANA 1:320; dsDNA titer 10 units/ml; C3 normal; and C4 low 0.13 g/l. The counselling addressed fertility (in light of previous cyclophosphamide), contraception, as well as medicines management; in particular, what to stop (i.e. MMF and irbesartan), what to continue (i.e. HCQ) and what treatments might be added (i.e. azathioprine, aspirin, folic acid). The evidence base for advice regarding timing, risks to her and to the baby came from the PROMISSE study, metanalyses and the Italian series (Moroni G et al). Her key risk factors for adverse pregnancy outcomes were being non-white, on an antihypertensive, and having anti Ro antibodies but she was in a good remission from her lupus. I advised her to continue to use contraception whilst weaning off her MMF and to consider trying to conceive, if all remained well, when off her MMF for at least 3 months. She presented pregnant in December 2017 but had not stopped either her MMF or irbesartan, despite the advice to do so back in July that year. We discussed the risks to the baby of first trimester exposure and she declined termination. Coincident with the pregnancy, she was serologically more active, and became symptomatic with joint pains, rising creatinine and hypertension and developed significant proteinuria. During the workshop we will discuss the pros and cons of renal biopsy in pregnancy and how we managed a really major flare. Also, the difficulty of diagnosing pre-eclampsia in a patient with active LN. The pregnancy was ultimately successful. She was treated with rituximab and MMF post-partum and again advised regarding contraception. The story continues in 2020! Case 2: Lupus nephritis in pregnancy Angela Tincani Maria is a 39-year-old woman who consulted at 21 weeks of gestation for the sudden occurrence of proteinuria (3.8 g) during a previously uncomplicated pregnancy with normal fetal growth. She had a history of undifferentiated connective tissue disease, diagnosed in 1997, because of thrombocytopenia (48,000 platelets per microliter) and Raynaud's; positive ANA, anti U1RNP. She was successfully treated with corticosteroids, which were stopped in 2000. She has had Hashimoto thyroiditis, treated with levothyroxine since 2000. In 2014 she had vaginal delivery of a female baby at 40 weeks of an uncomplicated pregnancy without any treatment. In 2016 and 2017 she had three early miscarriages at 8, 7 and 9 weeks. During our first evaluation (29th March 2019), she presented acrocyanosis and modest feet oedema. Proteinuria was 4 g with normal renal function; positive ANA and anti Sm/RNP; low titer anti ds DNA; positive anti-cardiolipin and anti β2 glycoproptein1 IgG. In the last week she was treated with prednisone 50 mg/day plus low dose aspirin (LDA) and low molecular weight heparin (LMWH). Azathioprine (AZA) was added, but because of increasing proteinuria (9.8 g) one week later she was admitted to the Obstetric Department. She was given three small pulses of methylprednisolone (250 mg), AZA shifted to tacrolimus (3 mg/bd) and HCQ started. When discharged, prednisone was reduced to 25 mg/day; LMWH, LDA, HCQ, vitamin D and levothyroxine unchanged. Proteinuria rapidly decreased (1.3 g on 15th May and 0.260 g on 10th July). On 23rd July she had vaginal delivery at 38 weeks' gestation, her baby was 3.390 kg and 51 cm high; APGAR 10/10. Tacrolimus was suspended on the delivery day and the patient continued with prednisone 5 mg every other day with LMWH during puerperium. A subsequent kidney biopsy confirmed Class V glomerulonephritis. At last evaluation (October 2019), the patient and the baby were fine, urinalysis did not show proteinuria. Discussion Points Pre-pregnancy counselling for women with a history of LN Management of acute flares of LN in pregnancy Diagnosing pre-eclampsia in women with active LN Discuss the use of immunosuppressive medications in pregnancy Learning Objectives Explain the importance of pre-pregnancy counselling in women with LN Discuss the best management of flares of LN in pregnant women Discuss how to recognise pre-eclampsia in women with LN Distinguish lupus nephritis from APS nephropath

Design and proof of concept for multi degree of freedom hydrostatically coupled dielectric elastomer actuators with roto-translational kinematics for object handling

In this article we present an upgraded design of the existing push-pull hydrostatically coupled dielectric elastomer actuator (HC-DEA) for use in the field of soft manipulators. The new design has segmented electrodes, which stand as four independent elements on the active membrane of the actuator. When properly operated, the actuator can generate both out of plane and in-plane motions resulting in a multi-degrees of freedom soft actuator able to exert both normal pushes (like a traditional HC-DEA) and tangential thrusts. This novel design makes the actuator suitable for delicate flat object transportation. In order to use the actuator in soft systems, we experimentally characterized its electromechanical transduction and modeled its contact mechanics. Finally, we show that the proposed actuator can be employed as a modular unit to develop active surfaces for flat object roto-translation. © 2018 IOP Publishing Ltd

POS0724 GENDER DIFFERENCES IN THROMBOTIC PRIMARY ANTIPHOSPHOLIPID SYNDROME IN A LARGE COHORT OF PATIENTS FROM FOUR EUROPEAN CENTERS

Background:Autoimmune diseases occur more frequently in females and their course and severity can be affected by gender. Antiphospholipid syndrome (APS) is a systemic autoimmune disorder in which antiphospholipid antibodies (aPL) exert a pathogenic role resulting in vascular thrombosis and/or pregnancy morbidities. Data about gender differences in thrombotic APS (t-APS) are still scarce1,2.Objectives:To evaluate the differences in frequency, disease expression and severity between females and males affected by primary t-APS.Methods:Retrospective study enrolling subjects with a formal diagnosis of primary APS (Miyakis 2006) with vascular thrombosis at onset. Women who presented with obstetric events as first aPL-related manifestation were excluded. All the patients were followed from 1967 to 2019 in four European centers: three French centers and one Italian center.Results:The study included 433 patients (68% females, 32% males). Median age at t-APS onset [31 (24-46) vs 41 (29-53) years, p<0.001] and at diagnosis [34 (27-50) vs 46 (34-57) years, p<0.001] was significantly lower in females.The most common presenting manifestations were venous thrombosis (60%) followed by arterial events (37%) and catastrophic APS (3%). Venous events were more frequent in women as compared to men (64% vs 51% p:0.012 OR:1.7 [1.1-2.5]). Sites of venous thrombosis included: limbs (35%), pulmonary (17%), cerebral (3%), portal and inferior cava (2%) and retinal (1%) veins, without gender differences. The arterial events were more frequent among men (43% vs 34% p:0.053). Strokes (27%) and myocardial infarctions (4%) were the most frequent manifestations, followed by thrombosis of limbs (2%), retina (2%) and abdominal organs (1%). Noteworthy, only men presented with visceral ischemia.During the follow-up, new thrombosis occurred in 41% of patients (179/433). 33% out of them had at least two episodes and these occurred especially among males (22% vs 10% p:0.001 OR:2.5 [1.3-4.8]). New events were mostly of the same type, but ⅓ of patients presented a switch from venous to arterial side and viceversa, with no gender differences.Complete aPL profile was available in 357 subjects: 33% had single aPL positivity, 24% double positivity and 43% triple positivity, with no differences between women and men. About 80% of the patients had a concomitant risk factor (RF) for thrombosis. Established cardiovascular RFs were more represented among men as shown in table 1. In women, estrogenic exposure was the main RFs, present in almost 40% of them.Table 1.MALESn= 137FEMALESn= 296POR [IC 95%]Traditional cardiovascular RFs, n (%)Smoke66 (48)81 (27)<0.0012.5 [1.6-3.8]Arterial hypertension59 (43)75 (25)<0.0012.2 [1.5-3.4]Dyslipidemia52 (38)72 (24)0.0041.9 [1.2-2.9]Diabetes16 (12)15 (5)0.0142.5 [1.8-5.1]Obesity13 (10)38 (13)nsOther thrombophilic factors, n (%)Estrogenic stimuli*0116 (39)-Trauma / surgery / immobilization21 (15)32 (11)nsCongenital thrombophilia9/94 (10)33/204 (16)nsData were compared using contingency tables, p value was calculated with Chi-Squared or Fisher exact test. *= hormonal therapy, pregnancy, post-partumConclusion:This gender-oriented analysis of patients with primary t-APS showed that women had the first vascular event at a younger age and mostly on the venous side, while men presented mainly with arterial events, later in life and suffered from more recurrent events. No differences were observed in the distribution of the aPL profile. The different frequency of arterial and venous events in the two groups could be attributed mainly to the presence of additional RFs rather than to biological gender-specific issues. However, it should be underlined that some RFs, such as the use of estrogens or classic cardiovascular RFs, are exclusive or more represented in one gender rather than the other, making it difficult to assess the link of causality between gender and manifestations of t-APS.References:[1]JF de Carvalho. Rheumatol Int. 2011.[2]LJ Jara. Lupus. 2005.Disclosure of Interests:None declare

Identifying A Risk Profile For Thyroid Cancer.

The large use of simple and effective diagnostic tools has significantly contributed to the increase in diagnosis of thyroid cancer over the past years. However, there is compelling evidence that most micropapillary carcinomas have an indolent behavior and may never evolve into clinical cancers. Therefore, there is an urgent need for new tools able to predict which thyroid cancers will remain silent, and which thyroid cancers will present an aggressive behavior. There are a number of well-established clinical predictors of malignancy and recent studies have suggested that some of the patients laboratory data and image methods may be useful. Molecular markers have also been increasingly tested and some of them appear to be very promising, such as BRAF, a few GST genes and p53 polymorphisms. In addition, modern tools, such as immunocytochemical markers, and the measure of the fractal nature of chromatin organization may increase the specificity of the pathological diagnosis of malignancy and help ascertain the prognosis. Guidelines designed to select nodules for further evaluation, as well as new methods aimed at distinguishing carcinomas of higher aggressiveness among the usually indolent thyroid tumors are an utmost necessity.51713-2

Entanglement entropy in aperiodic singlet phases

We study the average entanglement entropy of blocks of contiguous spins in aperiodic XXZ chains which possess an aperiodic singlet phase at least in a certain limit of the coupling ratios. In this phase, where the ground state constructed by a real space renormalization group method, consists (asymptotically) of independent singlet pairs, the average entanglement entropy is found to be a piecewise linear function of the block size. The enveloping curve of this function is growing logarithmically with the block size, with an effective central charge in front of the logarithm which is characteristic for the underlying aperiodic sequence. The aperiodic sequence producing the largest effective central charge is identified, and the latter is found to exceed the central charge of the corresponding homogeneous model. For marginal aperiodic modulations, numerical investigations performed for the XX model show a logarithmic dependence, as well, with an effective central charge varying continuously with the coupling ratio.Comment: 18 pages, 9 figure

The pathogenic role of circulating Hashimoto's Thyroiditis-derived TPO-positive IgG on fetal loss in naïve mice

Problem: Antibody-mediated autoimmune diseases, such as autoimmune thyroid diseases (ATD), systemic lupus erythematosus (SLE), and antiphospholipid syndrome (APS), often are associated with recurrent fetal loss. One of the ATD is Hashimoto's thyroiditis which recently showed association with complications of pregnancy with increased levels of circulating autoantibodies reactive with epitopes on thyroid tissue such as thyroid peroxidase (anti-TPO). In retrospective study of sera analyses in patients with Hashimoto's thyroiditis, all patients had mainly elevated circulating anti-TPO autoantibodies. Aim: We assessed the potential of human anti-TPO highly positive IgG, derived from patients with Hashimoto's thyroiditis sera associated with complications of pregnancy, to cause directly complications of pregnancy in murine model. Method of study: Naïve ICR female mice, infused intravenously with 100&nbsp;μg of anti-TPO-positive IgG, showed increased fetal loss and embryo small for date (P&nbsp;&lt;.001) in comparison with mice passively transferred with commercial IgG or PBS. Moreover, we observed embryos small for date in the mice passively transferred with anti-TPO-positive IgG, exemplified by reduced weight of embryos and placentae (P&nbsp;=.001). Histopathological examination revealed delay in fetal development in 50% cases of anti-TPO-positive IgG-treated mice. Importantly, pathological changes in the transition zone, state of glycogen cells, and significant structural changes in the labyrinth part of placenta were observed in all anti-TPO-positive IgG samples. Conclusion: The current study shows in the first time, a direct proof of concept, on the association of human TPO-positive IgG from Hashimoto's thyroiditis patients on fetal loss induction in murine model

Primary antiphospholipid syndrome evolving into systemic lupus erythematosus: may antinucleosome antibodies be predictive?

Objective: It was reported by several groups that patients diagnosed as primary antiphospholipid syndrome (PAPS) had developed a full-blown systemic lupus erythematosus (SLE) even after many years of follow-up. Little is known about clinical and/or serological factors that may help predict such evolution. Antinucleosome antibodies (anti-NCS) were described to appear in early stages of SLE, in particular before anti-dsDNA antibodies. The aim of the study is to evaluate the prevalence of anti-NCS in a large cohort of PAPS patients. Methods: IgG and IgM anti-NCS antibodies were detected using a home made assay with H1-stripped chromatin as antigen. Sera from 106 PAPS patients were tested; 52 of them were also tested during the follow-up, at least 2 years apart form the basal sample. Results: Medium-high titre anti-NCS were found in nearly half of the patients (49/106, 46%), more frequently in those presenting features of "lupus like disease". Most of patients displayed an unchanged pattern of anti-NCS over time. We describe three cases of PAPS patients that developed SLE after many years of follow-up; high titre and low titre anti-NCS were present in two and one of them respectively several years before evolving into SLE. Conclusions: A significant proportion of PAPS patients displayed medium-high titre anti-NCS, suggesting that the autoimmune response against chromatin may be a relevant event not only in patients with SLE. Further studies are warranted to explore the predictive value of anti-NCS with respect to the evolution from PAPS to SLE