D Lert

G Costagliola

R Pialoux

P M Landman

L Girard

Slama

V Supervie

L Assoumou

R Breban

F Lert

D Costagliola

G Pialoux

R Landman

P M Girard

L Slama

Risk of HIV transmission during combined ART initiation for HIV-infected persons with severe immunosuppression

Risk of HIV transmission during combined ART initiation for HIV-infected persons with severe immunosuppression

V Supervie, L Assoumou, R Breban, F

Introduction

Early initiation of effective combination antiretroviral therapies (cART) dramatically improves the prognosis of HIV-infected patients and, by suppressing plasma HIV viral load (pVL), markedly reduces sexual transmission of HIV. [START_REF] Cohen | Antiretroviral Therapy for the Prevention of HIV-1 Transmission[END_REF][START_REF] Eshleman | Treatment as Prevention: Characterization of Partner Infections in the HIV Prevention Trials Network 052 Trial[END_REF][START_REF] Lundgren | Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection[END_REF][START_REF] Temprano | A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa[END_REF] However, despite cART success, late presentation for HIV care remains common in most settings, [START_REF] Lahuerta | Advanced HIV disease at entry into HIV care and initiation of antiretroviral therapy during 2006-2011: findings from four sub-saharan African countries[END_REF][START_REF] Cohere ; Mocroft | Late presentation for HIV care across Europe: update from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) study, 2010 to 2013[END_REF] including high-income countries. [START_REF] Cohere ; Mocroft | Late presentation for HIV care across Europe: update from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) study, 2010 to 2013[END_REF] More than 30% of patients presenting for care in Europe have advanced HIV disease, defined as CD4 counts <200 cells/mm 3 or AIDS-defining disease. [START_REF] Cohere ; Mocroft | Late presentation for HIV care across Europe: update from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) study, 2010 to 2013[END_REF] Advanced stage of infection is typically accompanied with high level of pVL, which requires longer time to achieve viral suppression upon cART initiation. [START_REF] Khatchatourian | Impact of baseline viral load and time to viral suppression on subsequent virologic rebound according to first-line antiretroviral therapy (cART)[END_REF][START_REF] Santoro | Impact of pre-therapy viral load on virological response to modern first-line HAART[END_REF] Thus, persons presenting for care with severe immunosuppression may be at high risk to transmit HIV before and after cART initiation, as high pVL implies high risk of sexual HIV transmission. [START_REF] Quinn | Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group[END_REF] Recent studies in low and middle-income countries showed that HIV transmission risk persists during the first 6 months of cART. [START_REF] Eshleman | Treatment as Prevention: Characterization of Partner Infections in the HIV Prevention Trials Network 052 Trial[END_REF][START_REF] Mujugira | HIV Transmission Risk Persists During the First 6 Months of Antiretroviral Therapy[END_REF] However, little is known about the risk of HIV transmission before, and after, cART initiation for individuals presenting for care with severe immunosuppression, notably in high-income countries. Quantifying these risks is critical for HIVinfected patients and their partners, as well as for clinicians and health care policymakers to implement interventions aiming at reducing the risk of onward HIV transmission and accelerating care entry. Here, we used virological and behavioral data collected within the framework of the IMEA 040 DATA trial [START_REF] Slama | Efficacy and safety of once-daily ritonavirboosted atazanavir or darunavir in combination with a dual nucleos(t)ide analogue backbone in HIV-1-infected combined ART (cART)-naive patients with severe immunosuppression: a 48 week, non-comparative, randomized, multicentre trial (IMEA 040 DATA trial)[END_REF] to quantify, for individuals presenting for care with severe immunosuppression, the risk of HIV transmission before and within the first 48 weeks of cART initiation.

Methods

Study population

The IMEA 040 DATA trial has been described previously. [START_REF] Slama | Efficacy and safety of once-daily ritonavirboosted atazanavir or darunavir in combination with a dual nucleos(t)ide analogue backbone in HIV-1-infected combined ART (cART)-naive patients with severe immunosuppression: a 48 week, non-comparative, randomized, multicentre trial (IMEA 040 DATA trial)[END_REF] Between April 2011 and January 2013, 120 patients were enrolled into an open-label, non-comparative, randomized, multicenter trial to evaluate the efficacy and tolerability of atazanavir/ritonavir or darunavir/ritonavir as first-line therapy, each in combination with two nucleos(t)ide reverse transcriptase inhibitors. Levels of pVL and CD4 cell counts were assessed at treatment initiation, defined as week (W) 0, and weeks 2, 4, 12, 24, 36 and 48. In addition to assessing the efficacy of cART regimens, an ancillary study was conducted to collect information on sexual behaviors at W0, W24 and W48, using self-reported questionnaires (see Supplementary data) based on 4week recall. Questions covered sexual activity and condomless sex with main, regular and casual partners as well as partner's HIV status (positive/negative/unknown).

Ethics

The trial respected good clinical practices and the ethical principles of the Declaration of Helsinki. The Ile de France XI ethics review committee approved the study (number 10062) and all the patients gave their written informed consent before participation. The study was registered with ClinicalTrials.gov (NCT01928407).

Analysis

To assess HIV transmission risk before and after cART initiation we evaluated two measures for each patient (i.e. trial participant) who participated to the ancillary study: the per-act risk of HIV transmission and the monthly rate of HIV transmission. Note that we could not ascertain whether HIV seroconversions occurred among partners of trial participants since only trial participants (and not their partners) were followed up during this study. The per-act risk of HIV transmission was estimated for each patient using the dose-response relation between pVL and risk of HIV transmission, [START_REF] Quinn | Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group[END_REF] whether or not the patient reported any sexual activity. The per-act probability of HIV transmission was shown to increase by a factor of 2.45 (95% confidence interval (CI): 1.85-3.26) for each log (base 10) increment in pVL, as expressed by the equation: 12 β1 = 2.45 log 10 (V 1 /V 0 ) β0, where V0 is the average pVL during untreated chronic HIV infection, β0 is the per-act probability of HIV transmission from a person with pVL V0, and β1 is the per-act transmission probability corresponding to pVL V1. We assumed that V0 was 4.5 log10 copies/mL, [START_REF] Wilson | Relation between HIV viral load and infectiousness: a model-based analysis[END_REF] and β0 was equal to 0.001 for heterosexuals [START_REF] Supervie | Heterosexual risk of HIV transmission per sexual act under combined antiretroviral therapy: systematic review and bayesian modeling[END_REF] and 0.01 for MSM. [START_REF] Wilson | Relation between HIV viral load and infectiousness: a model-based analysis[END_REF] Regarding the parameter determining the increase in transmission probability with each one-log increment in pVL, each individual was assigned a value sampled from a normal distribution with mean 2.45 and standard deviation 0.35, corresponding to the 95% CI. The risk of HIV transmission was neglected for undetectable pVL, defined as plasma HIV-RNA concentrations below 50 copies/mL. [START_REF] Eshleman | Treatment as Prevention: Characterization of Partner Infections in the HIV Prevention Trials Network 052 Trial[END_REF] We combined virological and behavioral data to quantify, for each patient the monthly rate of HIV transmission using the formula: C=CM+CR+CC where CM, CR and CC were the monthly rates of HIV transmission to HIV-negative main, regular and casual partners, respectively. Monthly rates for each kind of partnership were calculated using the binomial

formula: 1 -(1 -β1) n-k (1 -(1-e)β1
) k where e was the per-act condom efficacy, n was the number of sex acts over the last 4 weeks, and k was the number of sex acts protected by condom over the last 4 weeks. We assumed that the per-act condom efficacy was 75% (95 CI: 63-83), [START_REF] Supervie | Heterosexual risk of HIV transmission per sexual act under combined antiretroviral therapy: systematic review and bayesian modeling[END_REF] and thus we assigned a per-act condom efficacy value to each individual, that was sampled from a normal distribution with mean 0.75 and standard deviation 0.05, corresponding to the 95% CI.

Partners of unknown status were assumed to be HIV-negative.

We performed sensitivity analyses where we assumed that the per-act risk of HIV transmission during each sexual intercourse was reduced by 95% for all patients. This analysis corresponds to an optimistic scenario where all couples would consistently and correctly use prevention, i.e. condoms [START_REF] Pinkerton | Effectiveness of condoms in preventing HIV transmission[END_REF] or pre-exposure prophylaxis (PrEP), [START_REF] Molina | On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection[END_REF][START_REF] Molina | On Demand PrEP With Oral TDF-FTC in the Open-Label Phase of the ANRS IPERGAY Trial[END_REF] to reduce the risk of HIV transmission. Then we compared estimates obtained under this scenario with those in the baseline analysis to estimate the percentage reduction in the monthly rates of HIV transmission within the optimistic scenario.

Analyses were conducted using Matlab R2015b and IBM SPSS Statistics version 24. Since, viral decay dynamics were similar for the two first-line therapies (atazanavir/ritonavir versus darunavir/ritonavir), we did not stratify the analysis according to the therapy. Generalized estimating equations models were used to analyze changes in parameters over time.

Results

Eighty-four patients participated to the survey and completed at least one of the three questionnaires. Among participants, 56% were heterosexual (24 male, 23 female) and 44% MSM (Table 1). Median time from HIV diagnosis to cART initiation was 4 weeks. At cART initiation (W0), median CD4 cell count was 71 cells/mm 3 and median pVL was 5.4 log10 for heterosexuals, and respectively 89 cells/mm 3 and 5.2 log10 for MSM.

Using data on pVL at W0, we estimated that the median per-act risk of HIV transmission at cART initiation was more than seven times higher for MSM than for heterosexuals (0.0172 (IQR: 0.0141-0.0282) versus 0.0023 (IQR: 0.0015-0.0029), p<0.001, Figure 1, A andB). The percentage of patients with unsuppressed viral load (pVL>50 copies/mL) decreased from 100% at cART initiation to 78% (95% CI 64-89%) at W12, 38% (95% CI 25-54%) at W24 and 27% (95% CI 16-43%) at W48 for heterosexuals (p<0.001) and respectively 73% (95% CI 56-86%), 33% (95% CI 18-50%) and 8% (95% CI 2-22%) for MSM (p<0.001). Among those who remained virologically unsuppressed, pVL considerably declined within the first 12 weeks of cART -median pVL was 2.3 log10 (IQR: 2.1-2.5) for heterosexuals and 2.2 log10 (IQR: 1.9-2.5) for MSM at W12 --and then remained relatively stable (data not shown). This translated into a reduction of the per-act risk of HIV transmission for virologically unsuppressed individuals, with estimated median values, at W12, of 0.0001 (IQR: 0.0001-0.0002) for heterosexuals (p<0.001 versus W0, Figure 1A) and 0.0010 (IQR: 0.0000-0.0017) for MSM (p<0.001 versus W0, Figure 1B), and mean reductions, when compared to W0, of 90% (86-94%) for heterosexuals and 92% (91-94%) for MSM.

Patients' characteristics of sexual behavior before and after cART initiation are summarized in Table 1. Over the course of treatment, the percentage of patients reporting sex with HIV-negative or unknown serostatus (HNUS) partners increased, from 23% (95% CI 10-42%) at cART initiation to 42% (95% CI 25-61%) at W48 for heterosexuals (p=0.042) and, respectively, from 41% (95% CI 21-64%) to 73% (95% CI 52-88%) for MSM (p=0.004). Among patients reporting sex with HNUS partners, the percentage of those who reported condomless sex decreased from 43% (95% CI 10-82%) at cART initiation to 14% (95% CI 2-43%) at W48 for heterosexuals (p=0.124) and, respectively, from 56% (95% CI 21-86%) to 32% (95% CI 13-57%) for MSM (p=0.224).

By combining virological and behavioral data, we found that during the month before treatment, 23% (95% CI 10-42%) of heterosexuals (Figure 1C) and 41% (95% CI 21-64%) of MSM (Figure 1D) were virologically unsuppressed and had sex with HNUS partners. Among these patients, estimated median monthly rate of HIV transmission was almost 30 times higher for MSM than heterosexuals, (0.0540 (IQR: 0.0339-0.0742) versus 0.0018 (IQR: 0.0014-0.0191), p=0.008, Figure 1, C andD). Over the course of cART, the percentage of HIV-infected patients who remained virologically unsuppressed and had sex with HNUS partners decreased to reach 16% (95% CI 5-33%) (p=0.291) at W24 and 9% (95% CI 2-24%) (p=0.109) at W48 for heterosexuals and respectively 25% (95% CI 11-45%) (p=0.234) and 4% (95% CI 0-20%) (p=0.010) for MSM. Estimated median monthly rates of HIV transmission for these patients decreased to 0.0001 (IQR: 0.0001-0.0006) for heterosexuals (p=0.053) and 0.0024 (IQR: 0.0017-0.0038) for MSM (p<0.001) at W24 and then remained stable, corresponding to mean reductions, relative to W0, of 95% (87-100%) for heterosexuals and 98% (95-100%) for MSM. Under an optimistic scenario, i.e. assuming that the per-act risk of HIV transmission during each sexual intercourse reduced by 95% for all patients, the estimated median monthly rate of HIV transmission, among patients who were virologically unsuppressed and had sex with HNUS partners, was 0.0003 (IQR: 0.0002-0.0010) for heterosexuals and 0.0049 (IQR: 0.0037-0.0072) for MSM at cART initiation (p=0.016). This rate decreased to 0.00003 (IQR: 0.00003-0.00013) for heterosexuals (p=0.205) and 0.0004 (IQR: 0.0002-0.0005) for MSM (p<0.001) at W24 and then remained stable. Thus, under the optimistic scenario, the monthly rate of HIV transmission at cART initiation was reduced by 93% (85-100%) for heterosexuals and 98% (95-100%) for MSM at W24, compared to the baseline analysis.

Discussion

With an estimated median value of 5%, we found that the monthly rate of HIV transmission before cART initiation was particularly high for MSM -thirty times higher than for heterosexuals -reflecting higher self-reported sexual activity for MSM than heterosexuals but, above all, higher per-act risk of HIV transmission for MSM than heterosexuals. Indeed, taken alone, the higher sexual activity for MSM than heterosexuals contributes to increase the median value of the monthly rate of HIV transmission by a factor 3 while the higher per-act risk of HIV transmission for MSM than heterosexuals contributes to increase this median value by a factor 10 (results not shown). Although sexual activity increased after cART initiation, and more than a third of individuals remained virologically unsuppressed (pVL>50 copies/mL) after 24 weeks of cART, the risk of HIV transmission significantly decreased, as early as 12 weeks of cART, and by ∼95% after 24 weeks of cART, even for those who remained virologically unsuppressed. In addition, we found that the monthly rate of HIV transmission before and after cART initiation could be significantly decreased (from 93% to 98%) if all patients or their partners would use consistently and correctly an HIV prevention method, i.e. condoms [START_REF] Pinkerton | Effectiveness of condoms in preventing HIV transmission[END_REF] or PrEP. [START_REF] Molina | On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection[END_REF][START_REF] Molina | On Demand PrEP With Oral TDF-FTC in the Open-Label Phase of the ANRS IPERGAY Trial[END_REF] The main limitation of our study is the sample size. In addition, our estimates of the risk of HIV transmission before cART initiation may have limited application for patients at less advanced stages of HIV infection, when pVL is usually lower, or for undiagnosed HIV infections, when sexual activity may be higher. The main strength of our study is the collection at regular and close time intervals of detailed behavioral and virological data, to inform and reinforce public health policies.

Our findings show a high risk of onward transmission before and within the first weeks of cART initiation for individuals presenting for care with severe immunosuppression, and persistence of a risk of HIV transmission, though at a substantially reduced level, beyond 24 weeks of cART for some individuals. Hence, our study enforces the need to implement effective HIV testing strategies, with a focus on individuals with low HIV testing uptake, and cART initiation as soon as possible. Furthermore, at cART initiation, communicating about this risk and providing counseling on how to reduce this risk, e.g. by improving condom use or offering PrEP to HIV-negative partners, is essential to reduce the risk of onward transmission until achieving full viral suppression. Partner notification assistance programs, which are not implemented in France, should also be evaluated. This could allow earlier HIV diagnosis for partners of newly diagnosed HIV cases and provide an opportunity to offer PrEP to HIV-negative partners in serodiscordant couples until the HIV-positive partner achieves full viral suppression. In addition, investigating whether faster viral suppression could be achieved for severely immunosuppressed individuals using new drugs, such as integrase inhibitor, is important to reduce the risk of onward transmission after cART initiation.

Figure 1 :

 1 Figure 1: Risk of HIV transmission before and after treatment initiation.

Figure 1 326ESSAI└─┴─┴─┘

 1 Figure 1

Table 1 :

 1 Baseline and sexual behavior characteristics of the 84 patients

	Heterosexuals	MSM
	n=47 (56%)	n=37 (44%)

Acknowledgements

We would like to thank all patients who participated in this study. IMEA 040 DATA Study group: CHU de Martinique (André Cabié, Sylvie Abel, Patrick Hochedez, Sandrine Pierre-François, Benoît Rozé); CHU Pitié-Salpétrière (Médecine Interne: Anne Simon, Catherine Lupin; Maladies Infectieuses: Christine Katlama, Marc Antoine Valentin; Immunologie: Brigitte Autran, Assia Samri; Virologie: Sidonie Lambert, Anne Geneviève Marcelin); CHU Bichat (Roland Landman, V. Joly, Zélie Julia, Stanislas Harent, Emmanuelle Papot, Bao-Chau Phung; Laboratoire Pharmaco-Toxicologie: Gilles Peytavin, Patrick Lê Minh); CHU Lariboisière (Agathe Rami, Myriam Diemer, Maguy Parrinello); CHU Louis Mourier (I. Cahitte, Feng Zeng, E. Mortier); CHU Tenon (Gilles Pialoux, Thomas L′Yavanc, Guillaume Le Loup, Philippe Bonnard, Marie Gisèle Lebrette, Julie Chas, Valérie Berrebi, Nadège Velazquez, Anne Adda); CHU Necker (Claudine Duvivier, Fatima Touam, Olivier Lortholary, Michka Shoai-Tehrani, Claire Rouzaud); Hôpital Dupuytren Service des Maladies Infectieuses et Tropicales (Eric Denes, Sophie Ducroux-Roubertou, Hélène Durox, Claire Genet, Jean-Philippe Rogez, Sylvie Rogez, Jose Pascual); CHU Hôpital Européen Georges Pompidou (Laurence Weiss, Juliette Pavie, Erila Bourzam); CH Perpignan (Hugues Aumaître, Milagros Ferreyra, Matthieu Saada, Martine Malet); CHU Avicenne, Service des Maladies Infectieuses et Tropicales (Christia Palacios, Patricia Honore, Irene Zamord); CHU Raymond Poincaré (Huguette Berthe, Stéphanie Landowski, Pierre de Truchis); CHD Vendée (Philippe Perre); CHU Saint Antoine (Pierre-Marie Girard, Nadia Valin, Pauline Campa, Bénédicte Lefebvre, Jean-Luc Meynard, Michèle Pauchard, Laure Surgers).

Funding section

The IMEA 040 DATA trial was funded by a research grant from Bristol-Myers Squibb to the IMEA foundation.

Transparency declarations

VS has served on advisory boards for ViiV Healthcare (2016) and reports lecture fees from Gilead (2014, 2015) and MSD (2014)

Supplementary Data

The English-translated version of the survey questionnaires completed at W0 and W24 are available as Supplementary data. Note that the same questionnaires were given at W24 and W48. Thank you, the questionnaire will remain confidential, put it in the envelope.

QVAS


Christophe Journeau
email: christophe.journeau@cea.fr

Justine Zanini

Emmanuel Excoffier
email: emmanuel.excoffier@cea.fr

Véronique Testud
email: veronique.testud@cea.fr

Emmanuelle Brackx
email: emmanuelle.brackx@cea.fr

Christophe Chagnot
email: christophe.chagnot@cea.fr

Ioanna Doyen
email: ionna.doyen@cea.fr

Emmanuel Porcheron
email: emmanuel.porcheron@irsn.fr

Damien Roulet
email: rouletd@onet.fr

Aerosols released during the laser cutting of a Fukushima Daiichi debris simulant

Keywords: Fukushima Daiichi, Aerosols, Debris cutting, Fission Product simulants

INTRODUCTION

The 2018 Technical Strategic Plan for decommissioning of the Fukushima Daiichi (1F) Nuclear Power Station [START_REF] Ndf | Technical Strategic Plan 2018 for Decommissioning of the Fukushima Daiichi Nuclear Power Station[END_REF] indicates that the policy on Fukushima Daiichi fuel debris retrieval will "combine optimum retrieval methods suitable for the part of each unit where fuel debris is expected to be present, instead of making an assumption that all the fuel debris is to be taken out using a single method". Cutting fuel debris (solidified corium) is an important issue and several techniques including mechanical and thermal cutting are being studied for (see e.g. 2, 3). The laser technique is well adapted to the cutting of corium which has an irregular shape and heterogeneous composition. In addition, the laser cutting technique induces the lowest material mass removed and the lowest mass of re-suspended aerosol during the cutting, comparatively to others cutting techniques (grinder, plasma torch, arc air, arc saw, reciprocating saw) [START_REF] Pilot | Measurement of secondary emissions during laser cutting of steel equipments[END_REF].

Several R&D projects have therefore been launched and subsidized by the Japanese government to study potential techniques. In this framework, a French consortium (ONET Technologies, CEA and IRSN) has been selected among others to implement R&D related to the laser cutting of 1F fuel debris and related dust collection technology [START_REF] George | Benefits from developments in the field of Decommissioning for Fukushima Daiichi fuel debris retrieval: Remote-Controlled Laser Cutting Process[END_REF].

Asides from experimental optimization of the laser-cutting technique on commercially-available samples such as electrofused zirconia, steel and zirconium plates, one specificity of our approach is to have specifically fabricated simulant of Fukushima-Daiichi fuel debris [START_REF] Journeau | Fabricating Fukushima Daiichi in-vessel and ex-vessel fuel debris simulants for the development and qualification of laser cutting technique[END_REF] that have in a second part been subjected to laser cutting in our facility while aerosol production [START_REF] Porcheron | Analysis of aerosol emission and dispersion during the laser cutting of Fukushima fuel debris simulants[END_REF] has been analyzed. As the laser cutting experimental works could not be carried out at this stage in a laboratory were uranium can be manipulated, a simulant corium debris has been manufactured based on hafnium oxide while the fission products were replaced by the same elements but with their natural isotopic composition [START_REF] Journeau | Fukushima Daiichi fuel debris simulant materials for the development of cutting and collection technologies[END_REF]. In a first section the experiments will be described. Then, the aerosols analyses will be presented. Finally, thermodynamic calculations will be presented and compared with experimental results.

EXPERIMENTS

Corium Debris Simulant Manufacture

The ex-vessel debris simulant has been fabricated at PLINIUS platform during the test VF-03(Vulcano Fukushima test number 3) [START_REF] Journeau | Fabricating Fukushima Daiichi in-vessel and ex-vessel fuel debris simulants for the development and qualification of laser cutting technique[END_REF]. It simulates a debris from interaction between the molten core and the concrete in the sump of Fukushima Daiichi Unit 1 (1F1) based on the MAAP LP case in Robb et al. [START_REF] Robb | Ex-Vessel Core Melt Modeling Comparison between MELTSPREAD-CORQUENCH and MELCOR 2.1[END_REF] modelling of MCCI taking into account the Fukushima Daiichi concrete composition reported by Kitagaki et al. [START_REF] Kitagaki | Research Approach of MCCI products characterization for debris removal[END_REF] and the fission product composition 10 years after shutdown from Nishihara [START_REF] Nishihara | Estimation of Fuel Compositions in Fukushima-Daiichi Nuclear Power Plant[END_REF].

To facilitate cutting and avoid radioactive releases, hafnium has been chosen as for uranium and plutonium has been replaced by cerium because their thermal properties are close. The replacement of uranium by hafnium has been made with respect to the assessment of the efficiency of thermal cutting by laser: indeed, uranium and hafnium dioxides have similar melting temperatures and thermal properties [START_REF] Journeau | Fukushima Daiichi fuel debris simulant materials for the development of cutting and collection technologies[END_REF]. Unfortunately, it has not been possible to find a good simulant of uranium regarding the volatilization of oxides. Capriotti et al. [START_REF] Capriotti | A laser heating study of CeO2 solid/liquid transition: challenges related to a refractory compound with a very high oxygen pressure[END_REF] have shown that "many similarities exist between the system Pu-O and the system Ce-O, even in the very high temperature behavior" and that "CeO2 displays … a melting behaviour which has been recently proven to be typical of other similar metal-oxygen systems such as

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Ca-O, Np-O and Pu-O". Therefore cerium has been used in this work as surrogate of plutonium. Ruthenium has also been removed because of its chemical toxicity in oxidizing conditions and rhodium because of its cost.

The ex-vessel fuel debris are made from:

 Fuel (uranium + non-volatilized fission products),  Zircalloy (Zr + Sn)oxidized at a level depending on the unit accident scenario,  Steel (containing 10.2 wt% Cr and 5.1wt% Ni) coming from the vessel internals, the vessel and concrete reinforcement bars ,  Concrete decomposition products (SiO2, Al2O3, CaO...) and oxygen from concrete water. Table 1 lists in details the materials which has been introduced in the load. Steel has been introduced as steel balls while the other elements have been introduced as powders. After melting, two phases have segregated: a small heavier metallic phase and an oxidic debris.

Aerosol Collection during Laser-Cutting of the Fuel Debris Simulant

Laser-cutting of this MCCI oxidic debris simulant (Figure 1) has been performed in air at CEA DELIA laser shot unit of the ALTEA platform (Figure 2 left). A Trumpf 8002-type 1030-nm laser souce with continuous power of 8 kW is connected by optical fibers to CEA laser head . Two comporessed air jet flows are provided, one around the laser head and one at 45° from the corium surface. The laser cutting has been conducted in air as well as under various depths of water.

Aerosol characterization is carried out through the measurements of the mass concentration, the particle size distribution and the composition of the aerosols that is sampled in the aerosol test section connected to exhaust line of the DELIA laser cutting cell [START_REF] Porcheron | Analysis of aerosol emission and dispersion during the laser cutting of Fukushima fuel debris simulants[END_REF]. Different instruments are implemented on the aerosol

Aerosol Collection and Analyses

The quartz filters (Figure 3 left) used for the global mass concentration measurement have been analyzed

to determine the aerosol chemical composition (corresponding to the 30 nm-10 µm range). After the retrieval of the particle deposits and dissolution of the material (Figure 3 right), the remaining solutions were analyzed by means of ICP-MS and ICP-AES techniques depending on the elements to be measured.

Results of the chemical analysis are presented in Figure 4 for three test conditions: one in air, two underwater with different pool heights above the sample. Results are expressed in terms of relative masses of each element considered in the analyzed samples.

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For instance, for the case in air, the major constituents of the resuspended aerosols are iron (36 wt%), chromium (23 wt%), tin (8 wt%), boron (8 wt%), nickel (7 wt%), zirconium and calcium (4 wt%), caesium and molybdenum (both 3 wt%). Uncertainties of 1/10 th of the measured concentration are estimated on these measurements. As the filter is made of quartz, it is not possible to measure the fraction of silicon in the collected aerosols. From the analysis of the aerosols collected on impactors, silicon represents 17 to 33 wt% of the aerosols depending on the test configuration.

MODELLING

The modelling is made under the assumption that the aerosols are formed from the condensation of the vapors produced by the fuel debris when it is heated by the laser beam. Thermodynamic equilibrium calculations have been carried out using GEMINI2 and the NUCLEA14 database [START_REF] Nishihara | Estimation of Fuel Compositions in Fukushima-Daiichi Nuclear Power Plant[END_REF].

These calculation assume that the molten material is at a homogeneous temperature which is fitted with experimental results. Oxygen and Argon are added to represent air. The element Argon was used as surrogate for the nitrogen in the air. In other terms, the effect of nitride is neglected. Some elements has been substituted by others because they are not present in the database:

 Zirconium replaces, mole by mole, Hafnium,  Chromium replaces Molybdenum,  Lanthanum is surrogate for Praseodymium, Cerium, Yttrium, Samarium, Neodymium  Silver replaces Tellurium and Palladium,  Indium is simulating Tin.

The composition of the oxidic debris simulant has been determined from the load composition (Table I) and from measured compositions of samples from the oxide, metal and aerosols produced during the melting phase. Table 5 presents the load in grams for each element from the database in the cases considered for calculation. It corresponds to 8.2 kg of oxidic debris with 1.44 kg of air (1.2 m 3 at 298 K; 15 wt%). This quantity of air has been determined by trial and error in order to best fit the measured composition for the major elements. For this composition, the liquidus temperature has been computed to be around 1980 K Figure 5 shows the measured proportions of the major elements. The major element is iron followed by chromium tin and boron. Proportions in the vapor phase from thermodynamic equilibrium calculations at various temperatures are also plotted. At low temperatures (1500 K), silver (representing tellurium) is almost the only vapor. At higher temperatures (2500-3000 K) iron, chromium nickel, boron and indium have important contributions. Assuming equilibrium at 2800-2900 K (800-900 K above liquidus) provides a reasonable correspondence between calculation and experiment, except for Ni which is overestimated in these calculations. The major computed vapor phases at 2800 K are BO2 (5 mbar), SiO (3 mbar), Ni (2 mbar), CrO2 (1 mbar), B2O3 (1 mbar) and FeO (1 mbar). For the less volatile elements, Figure 6 compares computations and measurements. There is a clear underestimation of the released fraction of lanthanide, barium and strontium. This is only marginally modified by modifying the calculation temperature. Modification of the quantity of air in equilibrium with the heated fuel debris simulant (Figure 7) was also not able to sufficiently increase the fraction of these elements while it affected the ratios of the major components. Even though these fission product elements contribute to only 11 wt% of the aerosols, they carry most of its radioactivity. Further work is thus necessary.

The effect of the replacement of uranium by hafnium (or zirconium) has also been evaluated. Figure 8 presents two calculations for which the unique difference is that each mole of uranium has been replaced by a mole of zirconium (representing hafnium). Uranium becomes the major element of the vapour phase and with a 50-times increase in the computed mass fraction. The major uranium-bearing gas species is uranium trioxide (with a vapour pressure of 23 mbar), uranium dioxide being much less present (0.5 mbar), whereas only dioxide is indeed present for the composition with hafnium. Indeed, uranium dioxide is known to have an important noncongruent evaporation [START_REF] Brykin | Calculation of vapor composition produced by incongruent laser vaporization of uranium dioxide in vacuum[END_REF] leading in this case to the release of gaseous UO3.

Being the major element of vapour phase, uranium-containing vapours also affects the releases of other elements, not only by modifying the total vapour mass fraction): for instance computed Lanthanide and Barium releases are divided by 3, while Boron releases are divided by 6. On the opposite, mass fractions of Nickel and Tellurium (modelled by Silver) do not significantly vary between these two calculations. As there are still large uncertainties on these calculations and no experiments on which to compare them, it is therefore recommended to conduct cutting tests on prototypic fuel debris simulants containing (depleted) uranium dioxide to confirm or infirm these results. An intermediate first test could be to collect and analyse aerosols above pools of molten fuel debris simulants with uranium or hafnium at 2800 K.

CONCLUSIONS

In order to develop a safe laser-cutting technology for the retrieval of Fukushima Daiichi fuel debris, simulant fuel debris materials have been manufacture at CEA Cadarache and laser-cut at CEA Saclay. The emitted aerosols have been collected thanks to quartz filters which have been analyzed by ICP-AES and ICP-MS after dissolution at CEA Marcoule.

For a Molten Core Concrete Interaction simulant block cut in air, the major constituents of the aerosols are iron, chromium, silicon, tin, boron and nickel. Radioelements appear in much lower proportions.

Thermodynamic equilibrium calculations indicate that the major element proportions found in the aerosols approximately correspond to the fractions in the vapor in equilibrium with the molten fuel debris simulant at a temperature of about 2800 K. It must be stated that the collected fractions of the medium and low volatility elements (tellurium, lanthanides, strontium, barium) are larger than those computed with this equilibrium calculation, even when the temperature or the quantity of air in interaction with the melt is varied.

Another result of these calculations is the fact that uranium is expected to release much more vapor (that will later form aerosols) than hafnium while hafnium dioxide was used as simulant of uranium dioxide for its physical properties. This is linked to the important non-congruent evaporation of UO2 [START_REF] Brykin | Calculation of vapor composition produced by incongruent laser vaporization of uranium dioxide in vacuum[END_REF]. It is thus recommended to complement the presented results with new experiments on prototypic fuel debris simulants containing (depleted) uranium dioxide.

4 / 11 test

 411 section to provide together real time and integrated measurements of aerosol characteristics (Figure2right).

Figure 1 :Figure 2 :

 12 Figure 1: View of partially cut fuel debris simulant (in its ceramic crucible)

Figure 3 :Figure 4 :

 34 Figure 3 : Aerosol filter from VF03 laser cutting before and after solubilization

Figure 5 :Figure 6 :

 56 Figure 5: Mass fractions of the major constituents of the aerosols: Calculations vs measurements In stands for Sn, Ag for Te, Zr for Zr and Hf.

Figure 7 :Figure 8 :

 78 Figure 7: Effect of mass fraction of air in equilibrium with fuel debris simulant on the mass fraction of low volatility elements in the vapour phase (excluding Ar, O and Si)

Table I : Ex-vessel simulant load composition (in g per 10 kg) [6]

 I

		For 10 000 g	wt%		For 10 000 g	wt%
	HfO2	2 036.62 g	20.366% Fe2O3	286.37 g	2.864%
	CeO2	18.47 g	0.185% Nd2O3	8.93 g	0.089%
	ZrO2	1 240.32 g	12.403% MoO2	8.46 g	0.085%
	SnO	15.80 g	0.158%	Cs2O	5.04 g	0.050%
	B4C	17.36 g	0.174%	Ba	3.33 g	0.033%
	Cr2O3	58.11 g	0.581% La2O3	2.66 g	0.027%
	Fe	630.09 g	6.301%	PdO	2.55 g	0.026%
	FeO	1 177.76 g	11.778% Pr2O3	2.45 g	0.024%
	Ni	52.04 g	0.520% Sm2O3	1.83 g	0.018%
	SiO2	3 039.51 g	30.395%	Sr	1.47 g	0.015%
	Al2O3	758.62 g	7.586%	Y2O3	1.15 g	0.012%

The 9TH European Review Meeting on Severe Accident Research (ERMSAR2019) Log Number: 092 Clarion Congress Hotel, Prague, Czech Republic, March 18-20, 2019 6/11

	100,0000%													in air
														under 1/2 depth water
	10,0000%													under full depth water
	Al	Mg	Hf	B	Zr	Cr	Fe	Ni	Ca	Sn	Ce	Cs	La	Mo	Nd	Pd	Pr	Sm	Sr	Te	Y	Ba

Table II : Composition used for calculations of the ex-vessel oxidic simulant in air

 II

	Element Mass (g)
	Zr	1628.16
	Fe	1336.96
	Si	1284.73
	Ca	242.46
	Al	359.64
	Cr	246.96
	Ba	2.67
	Ni	49.29
	La	25.88
	In	8
	Ag	0.06
	B	10.03
	Sr	1.44
	Ar	1600
	O	3208.00
		7/11

Review Meeting on Severe Accident Research (ERMSAR2019) Log Number: 092 Clarion Congress Hotel, Prague, Czech Republic, March 18-20, 2019 9/11

	The 9TH European
	1,E-01
	1,E-02
	1,E-03
	1,E-04
	1,E-05
	1,E-06
	Zr+Hf	Te	AL	LA	BA	CA	SR
	2800 K		2900 K	3000 K	Measurement

ACKNOWLEDGMENTS

This work has been carried out thanks to the subsidized project of Decommissioning and Contaminated Water Management (Advancement of Fundamental Technologies for Retrieval of Fuel Debris and Internal Structures) funded by the Japanese Ministry of Economy, Trade and Industry (METI) and managed by the Mitsubishi Research Institute (MRI).