M Dentan

P Moreau

F.-P P Pellissier

B Santraine

J Bucalossi

V Malherbe

T Thery

G Gasiot

P Roche

M Cecchetto

R Garcia

S Moindjie

D Munteanu

J L Autran

Fusion Neutron-Induced Soft Errors During Long Pulse D-D Plasma Discharges in the WEST Tokamak

Keywords: Complementary metal-oxide-semiconductor (CMOS), deuterium-deuterium (D-D), deuterium-tritium (D-T), fusion, neutron, real-time experiment, single-event effects (SEEs), soft-error

We have performed real-time soft error rate (SER) measurements on bulk 65 nm static random-access memories (SRAMs) during deuterium-deuterium (D-D) plasma operation at W-tungsten-Environment in Steady-state Tokamak (WEST). The present measurement campaign was characterized by the production of several tens of long pulse discharges (~60 s) and by a total neutron fluence (at the level of the circuits under test) up to ~10 9 n.cm -2 , improving the error statistics by a factor of more than 6 with respect to the first measurements obtained in 2020. The experimental results demonstrate the occurrence of bursts of singleevent upsets (SEUs) during the most efficient shots and 12% of multiple cell upset (MCU) events. Time-resolved data also show that MCUs are preferentially detected in the last part of these long pulses, providing further evidence that higher energy neutrons, initiated by deuterium-tritium (D-T) reactions due to triton burnup in the D-D plasma, may play a role in the production of MCUs that cannot be attributed in such large proportions to "low energy" neutrons produced in D-D reactions.

I. INTRODUCTION HE WEST tokamak

 [START_REF] West | W Environment in Steady-State Tokamak[END_REF]is a research device operated by CEA-IRFM and designed to develop the technology necessary for fusion power [START_REF] Morse | Nuclear Fusion[END_REF]. WEST serves as a complementary research tool to the International Thermonuclear Experimental Reactor, the ITER project [START_REF]Unlimited Energy[END_REF], with a focus on testing new materials, exploring new plasma confinement regimes, and developing steady-state operation [START_REF] Bucalossi | The WEST project: Testing ITER divertor high heat flux component technology in a steady state tokamak environment[END_REF]. While WEST uses deuterium-deuterium (D-D) plasma and ITER will work with deuterium-tritium (D-T) plasma, the research conducted at the WEST tokamak can still provide valuable insights into the behavior of high-temperature plasmas Manuscript received September 29, 2023. This work was supported in part by EUROfusion Work-Package "Preparation of ITER Operation" (PrIO).

S. Moindjie and D. Munteanu are with Aix-Marseille University and CNRS, IM2NP (UMR 7334), F-13397 Marseille, France. J.L. Autran is with Aix-Marseille University and CNRS, IM2NP (UMR 7334), F-13397 Marseille, France, and also with Univ. Rennes, CNRS, IPR (UMR 6251), 35 042 Rennes Cedex, France. (e-mail: jean-luc.autran@univamu.fr).

and the development of new materials and technologies for future fusion reactors. D-D reactions will therefore be used during ITER development and commissioning before introducing tritium fuel. Because both D-D and D-T operations produce a high flux of energetic neutrons, creating a residual neutron field outside the reaction chamber [START_REF] Kos | Analysis of DD, TT and DT Neutron Streaming Experiments with the ADVANTG Code[END_REF][START_REF] Wesson | Tokamaks[END_REF], the electronics for command control and diagnosis of all future fusion devices will be exposed to nuclear radiation and negatively affected by this environment. Investigations are necessary to quantify such radiation effects on electronics devices, circuits and systems in the perspective of qualification procedures and guidelines [START_REF] Dentan | Preliminary Study of Electronics Reliability in ITER Neutron Environment[END_REF].

In 2020-2021, we conducted the very first real-time soft-error rate (RT-SER) characterization of complementary metal-oxidesemiconductor (CMOS) bulk 65-nm static random-access memories (SRAMs) subjected to fusion neutrons during D-D plasma operation at WEST (C5 campaign) [START_REF] Autran | Real-Time Characterization of Neutron-Induced SEUs in Fusion Experiments at WEST Tokamak During D-D Plasma Operation[END_REF]. The test equipment, installed in the experimental hall in the proximity of the tokamak, was irradiated during machine shots ranging from 1 to 18 s in duration. A total of 48 bit flips were detected for a cumulated neutron fluence of 1.43×10 8 n.cm -2 at the device level obtained after 1,252 s (0.348 h) of machine operation [START_REF] Autran | Real-Time Characterization of Neutron-Induced SEUs in Fusion Experiments at WEST Tokamak During D-D Plasma Operation[END_REF]. The C5 campaign was an initial effort to evaluate neutron-induced single-event upsets (SEUs) in SRAM circuits [START_REF] Munteanu | Modeling and simulation of single-event effects in digital devices and ICs[END_REF] exposed to the radiation environment near a nuclear fusion device. The aim was to provide early insight into the reliability of ITER electronics, as the machine is scheduled to operate with nuclear plasma in 2035. This approach was similar to previous studies using a nuclear fission reactor as the neutron source, as explained in [START_REF] Batista | Test results of an ITER relevant FPGA when irradiated with neutrons[END_REF] and [START_REF] Batista | SEU mitigation exploratory tests in a ITER related FPGA[END_REF].

In this work, new real-time SER measurements with the same setup have been performed during the WEST C7 experimental campaign. This latter was characterized by a series of very long pulses (up to 109 s) and very efficient D-D plasma discharges (up to 10 14 neutrons per shot). This article presents the new experimental results obtained under these conditions, which are characterized by an improved statistics of single-event upset (SEU) events, with more than 6 times more bit flips than during the C5 campaign. The article is organized as follows. Experimental details and setups are summarized in Section II. Experimental data obtained during the WEST C7 experimental campaign, including machine pulse characterization and realtime SER measurements, are presented in detail in Section III. Finally, these new results, obtained with the improved statistics, are compared with numerical simulations in Section IV. A detailed discussion of these results in light of the physics and operation of the tokamak is also included.

II. EXPERIMENTAL DETAILS

The RT-SER test setup used for the C5 campaign (see details in [START_REF] Autran | Real-Time Characterization of Neutron-Induced SEUs in Fusion Experiments at WEST Tokamak During D-D Plasma Operation[END_REF]) has been reused in the same experimental conditions for the present work at a distance of 5.2 m from the center of the tokamak (position P3 in [START_REF] Autran | Real-Time Characterization of Neutron-Induced SEUs in Fusion Experiments at WEST Tokamak During D-D Plasma Operation[END_REF], see Fig. 1). This RT-SER test bench fully complies with all Joint Electron Device Engineering Council (JEDEC) standard JESD89B [START_REF] Standard | Measurement and Reporting of Alpha Particle and Terrestrial Cosmic Ray-Induced Soft Errors in Semiconductor Devices[END_REF] specifications. We recall here that the setup contains 384 SRAM circuits manufactured by STMicroelectronics in 65 nm bulk CMOS using a borosilicate glass-free process. Each test chip contains 8.5 Mbits of single-port SRAM (without deep-Nwell) with a bit cell area of 0.525 μm 2 , operated under a nominal core voltage of 1.2 V. This 65nm CMOS bulk SRAM has been extensively characterized under different radiation conditions (neutrons, heavy ions, alpha particles) in previous studies [START_REF] Autran | Altitude and underground real-time SER characteri-zation of CMOS 65 nm SRAM[END_REF][START_REF] Autran | Altitude and underground real-time SER testing of SRAMs manufactured in CMOS bulk 130, 65 and 40 nm[END_REF][START_REF] Autran | ASTEP (2005-2015): Ten years of soft error and atmospheric radiation characterization on the plateau de Bure[END_REF][START_REF] Giot | Heavy ion testing and 3-D simulations of multiple cell upset in 65 nm standard SRAMs[END_REF]. It has also been numerically simulated in 3D using Technology Computer-Aided Design (TCAD) tools. During measurements, the tester scans the full memory array (384×8.5×1024 2 = 3.422 Gbit) one time every 2.5 s. The SRAM circuits with their upper face oriented toward the center of the machine were placed in the equatorial plane of the tokamak.

The neutron flux monitoring during the machine shots were obtained from the WEST fission chambers (CAF) positioned around the tokamak (Fig. 1). During the C5 campaign, we performed neutron metrology using a commercial DIAMON Fission chamber (✕3) a Fig. 2. Neutron fluence at the level of the test bench (SRAM circuits) estimated from CAF measurements using the numerical model described in [START_REF] Autran | Real-Time Characterization of Neutron-Induced SEUs in Fusion Experiments at WEST Tokamak During D-D Plasma Operation[END_REF] (see Fig. 1) versus direct measurements obtained with the DIAMON spectrometer. During C7 campaign, shot neutron fluences are all above 10 5 n/cm 2 that corresponds to the domain of the curve where CAF versus DIAMON correlation is excellent.

neutron spectrometer [START_REF] Pola | DIAMON: A portable, real-time and direction-aware neutron spectrometer for field characterization and dosimetry[END_REF] to accurately determine the neutron fluence at the level of the test bench. From CAF data and using a numerical model described in [START_REF] Autran | Real-Time Characterization of Neutron-Induced SEUs in Fusion Experiments at WEST Tokamak During D-D Plasma Operation[END_REF], we were able to predict the neutron fluence at the level of the test bench with a good agreement with respect to fluences measured using the DIAMON spectrometer. Fig. 2 shows the correlation between neutron fluences determined from CAF measurements using the numerical model [START_REF] Autran | Real-Time Characterization of Neutron-Induced SEUs in Fusion Experiments at WEST Tokamak During D-D Plasma Operation[END_REF] and measured by the DIAMON spectrometer at the level of the exposed circuits. The graph shows that for CAF neutron fluences above a few 10 4 n/cm 2 , the correlation between CAF and DIAMON extracted neutron fluences is excellent and in the ratio 1:1. Below a few 10 4 n/cm 2 , the correlation is much weaker, or even erroneous, as this area of the distribution clearly corresponds to the shortest machine shots (typically < 3 s), which produced the fewest neutrons during the C5 campaign (see Fig. 6 in [START_REF] Autran | Real-Time Characterization of Neutron-Induced SEUs in Fusion Experiments at WEST Tokamak During D-D Plasma Operation[END_REF]). This has a double impact on the flux measurement estimated by DIAMON, since the number of neutrons detected is low and the measurement time (integration time) very short. The spectrum calculated by DIAMON and its integral to obtain the total neutron flux are therefore systematically underestimated in this case. Fortunately, for the C7 campaign, virtually all shot neutron fluences are above 10 5 n/cm 2 , corresponding to the region of the curve where the correlation between CAF and DIAMON is precisely 1:1.

III. EXPERIMENTAL RESULTS

The RT-SER test equipment was installed and operated for six weeks during the WEST C7 campaign with a full capacity of 3.422 Gbit. A total of 623 machine shots were produced during this period for a cumulated duration of 12 637 s and a cumulated neutron fluence (at the level of the circuits under test) of 1.21×10 9 n.cm -2 . 198 shots were identified to have induced SEUs. Figs. 3 (a), (b) and (c) show the distribution of the number of neutrons produced during shots, the distribution of shot durations, and neutron fluence per shot for all the events, respectively. Machine shots during which SEU events have been detected in coincidence with the neutron flux are indicated in red. Fig. 4 combines data of Figs. 3(a) and 3(b) to show the number of neutrons produced per shot versus shot durations. On the one hand, 130 (90%) on the 144 shots having produced more than 10 13 neutrons induced SEU(s). On the other hand, only 11 pulses (3.3%) on the 333 having produced less than 10 12 neutrons induced SEU(s). There is clearly a threshold effect between 10 12 and 10 13 neutrons/shot for the production of SEUs.

Concerning the single-bit upset (SBU), multiple cell upset (MCU) and bit flip distributions, a total of 230 SBUs, 20 MCUs of multiplicity 2 [noted MCU(2)], 13 MCUs of multiplicity 3 [MCU [START_REF]Unlimited Energy[END_REF]] and a single MCU of multiplicity 10 [MCU [START_REF] Batista | Test results of an ITER relevant FPGA when irradiated with neutrons[END_REF]] have been detected in coincidence with machine shots, representing a total of 319 bit flips.

Two additional events [1 SBU and 1 MCU(2)] were detected during machine shutdown, which roughly corresponds to the test bench's SER in the natural radiation background, taking into account both cosmic rays and traces of alpha particle emitters in circuit materials [START_REF] Autran | Altitude and underground real-time SER testing of SRAMs manufactured in CMOS bulk 130, 65 and 40 nm[END_REF].

Fig. 5 shows the bit flip distribution as a function of the cumulated neutron fluence evaluated at the level of the circuits for all the events detected during the WEST C7 campaign. By comparison, we plotted the 48 bit flips detected during the C5 campaign for a cumulated neutron fluence of 1.43×10 8 n.cm -2 reached at the end of the campaign. The bit flip statistics has been improved by a factor 6.7 in C7 with respect to C5. Such a higher statistics can explain the detection of a rare MCU event with a multiplicity of 10. This MCU is characterized with all adjacent cells in the physical plan of the memory circuit.

Table I compares results obtained during the two campaigns in terms of SBU and MCU ratio. SBUs (resp. MCUs) represent »88% (resp. »12%) of the detected events, these ratios are virtually identical for both campaigns, that demonstrates a good repeatability of both irradiation conditions and measurements.

With respect to a reference neutron flux of 20 n•cm -2 h -1 , the tokamak radiation environment gives an acceleration factor of real-time experiment equal to AF = 2.5×10 7 . The corresponding bit flip SER in the tokamak radiation environment is equal to n-SER = 4.0×10 7 Failure In Time (FIT)/Mbit and the bit flip neutron cross section for SRAM in the tokamak field is σn = 7.3×10 -17 cm 2 /bit. Another important and new result obtained in the present work concerns the occurrence of multiple SEU events, that we called "burst events" during the same machine shots. On 198 shots having produced SEUs, 56 shots (among the most efficient in terms of neutron production) resulted in multiple SEU events, i.e., 2 or more SBUs, MCUs or a combination of SBUs and MCUs detected in coincidence with a given shot. Fig. 6 shows the histograms characterizing these burst events in terms of number of bit flips. Double SBU events have been detected during 26 machine shots, triple SBUs five times and quadruple SBU one time.

Due to the short reading/verification cycle of our test bench (as we mentioned, the full memory plan is scanned one time every 2.5 s), the occurrence of multiple events can be resolved in time during a machine shot if the clock of the tester is synchronized with the clock of the tokamak facility. Such a synchronization was done via regular verifications and updating (if necessary) of the PC clock to the time delivered by the tokamak control room. Fig. 7 shows the time distribution of the occurrence of all the SBUs and MCU events of multiplicities 2 and ³3 during the machine shots. On the horizontal scale, a time occurrence of 0 % (resp. 100 %) means that the event occurs at the beginning (resp. at the end) of the machine shot. Apart from the uncertainty introduced by the memory array reading time, these histograms show a clear difference between the time distribution of SBUs and MCUs during pulses: SBUs are distributed more or less uniformly from the beginning to the end of pulses, while MCUs are predominantly produced during the second half and end of pulses. For the MCU(2), no events are detected in the first 20% of the pulses. Of the 19 MCU(2), only 6 events are detected in the first half of the pulses, and the remaining 13 events in the second half (including 5 at the end of the pulses). For MCU(3), the asymmetry is even more pronounced: no events are detected in the first 30% of the pulses, and of the 14 events detected, only 2 events are detected in the first half of the pulses, while the other 11 events are detected in the second half and near the end (8 over 80% of the pulse duration).

IV. DISCUSSION

These new experimental results obtained during the WEST C7 campaign confirm and bring new elements about the possible role of triton burn-up neutrons in the production of SEUs, a mechanism that was invoked in [START_REF] Autran | Real-Time Characterization of Neutron-Induced SEUs in Fusion Experiments at WEST Tokamak During D-D Plasma Operation[END_REF] to explain the occurrence of MCU events in previous experiments. Once the D-D fusion is correctly initiated at the beginning of a machine shot, the concentration of 1 MeV tritons (which are produced in one of the two D-D reactions) rapidly increases in the plasma, making D-T fusion possible. For memory, the D-D fusion follows the two main reactions with equal probability of occurrence:

(1) and D-T fusion follows the main reaction:

(2) This process is known as "triton burn-up" and 14-MeV neutrons produced in D-T reactions that occur in deuterium discharges are called "triton burn-up neutrons" (TBNs) [START_REF] Sjöstrand | Triton burn-up neutron emission in JET low current plasmas[END_REF].

In our previous work related to the C5 campaign [START_REF] Autran | Real-Time Characterization of Neutron-Induced SEUs in Fusion Experiments at WEST Tokamak During D-D Plasma Operation[END_REF], we have shown by both monoenergetic experiments and numerical simulations that such "high energy" D-T neutrons induce much more MCU events in the 65 nm SRAM circuit under test than the primary 2.45 MeV neutrons produced in D-D reactions (in the absence of significant bipolar amplification). On the one hand, we observed 37 MCUs for 4.17×10 7 n.cm -2 of pure 14 MeV neutrons at the Accelerator for Metrology and Neutron applications for external DosimEtry (AMANDE) facility [START_REF] Amande | Monoenergetic neutron fields, AMANDE facility[END_REF] with the same setup. At 2.06 MeV, only a single MCU(2) was observed in a total of 35 events for a neutron fluence of 1.45×10 7 n.cm -2 . On the other hand, always in [START_REF] Autran | Real-Time Characterization of Neutron-Induced SEUs in Fusion Experiments at WEST Tokamak During D-D Plasma Operation[END_REF], we reported the modeling and simulation of the 65 nm SRAM exposed to monoenergetic neutrons from 1 MeV to 14 MeV (in steps of 1 MeV) using the Monte Carlo simulation code TIARA [START_REF] Thery | TIARA: Industrial platform for Monte Carlo single-event simulations in planar bulk, FD-SOI, and FinFET[END_REF]. The results of these simulations are shown in Fig. 14 of Ref. [START_REF] Autran | Real-Time Characterization of Neutron-Induced SEUs in Fusion Experiments at WEST Tokamak During D-D Plasma Operation[END_REF]. Data show that for neutrons of 3 MeV energy, MCUs represent less than 0.5% of the events, and approximately 9.5% at 14 MeV [START_REF] Autran | Real-Time Characterization of Neutron-Induced SEUs in Fusion Experiments at WEST Tokamak During D-D Plasma Operation[END_REF].

In the current work, 34 MCUs events have been detected for a total neutron fluence of 1.21×10 9 n.cm -2 at the device level. The combination of these different experimental and simulation results suggest that "high-energy" neutrons produced in D-T reactions should represent between 2.4 and 3.3% of the total fluence of neutrons (issued from D-D and D-T reactions) estimated at the circuit level. Fig. 8 shows bit flip distributions obtained by numerical simulation [START_REF] Moindjie | Multi-Poisson process analysis of real-time soft-error rate measurements in bulk 65 nm and 40 nm SRAMs[END_REF] for different D-T/D-D neutron fluence ratios ranging from 0% to 5 %. These simulations are based on a multi-Poisson process describing the occurrence of SBUs and MCUs as independent Poisson processes running in parallel with distinct event rates estimated from previous results. Without the contributions of "highenergy" neutrons produced in D-T reactions, there is an evident deficit of bit flips for a cumulated neutron fluence corresponding to that estimated at the circuit level for the C7 campaign (1.21×10 9 n.cm -2 ). Increasing the fraction of neutrons issued from D-T reactions causes MCU events to occur. Experimental data is well fitted with the bit flip distribution simulated with a ratio equal to 2.7 %, confirming the raw extraction from MCU statistics.

Nevertheless, this percentage seems slightly higher than the percentage of pure D-T neutrons predicted by tokamak physics (in deuterium plasma discharges in magnetic confinement fusion experiments, the typical triton burnup ratio is 1 % [START_REF] Ogawa | Timeresolved secondary triton burnup 14 MeV neutron measurement by a new scintillating fiber detector in middle total neutron emission ranges in deuterium large helical device plasma experiments[END_REF]). Triton burnup ratio reported in several studies are typically between 0.5 and 3% [START_REF] Sjöstrand | Triton burn-up neutron emission in JET low current plasmas[END_REF][START_REF] Ogawa | Timeresolved secondary triton burnup 14 MeV neutron measurement by a new scintillating fiber detector in middle total neutron emission ranges in deuterium large helical device plasma experiments[END_REF][START_REF] Nemtsev | Study of the triton-burnup process in different JET scenarios using neutron monitor based on CVD diamond[END_REF]. As explained in [START_REF] Ogawa | Timeresolved secondary triton burnup 14 MeV neutron measurement by a new scintillating fiber detector in middle total neutron emission ranges in deuterium large helical device plasma experiments[END_REF], the production of 14 MeV neutrons depends on the conditions of 1.01 MeV triton confinement and thermalization. Such a process is easy to achieve in pulses with higher plasma current to reduce triton Larmor radius (i.e., the radius of circular motion of the tritons in the magnetic field developed in the tokamak; it plays a critical role in the behavior of charged particles in the plasma): there is a correlation between the measured D-T/D-D ratio and the plasma current or electron temperature.

Another experimental observation supporting the role of neutrons emitted from D-T reactions in the production of MCUs is the occurrence of these events with a certain delay from the beginning of the pulses and mostly at the end of the pulses, as clearly shown in Fig. 7 for MCU events. This result is consistent with the fact that the triton concentration in the plasma increases from the beginning of a shot [START_REF] Sjöstrand | Triton burn-up neutron emission in JET low current plasmas[END_REF] (the TBN emission also goes with some delay relative to the birth time of triton). During a pulse, the plasma is enriched with tritium, which favors the production of 14 MeV neutrons, and therefore, the probability of producing MCUs is maximum when the tritium concentration reaches its maximum, i.e., after a certain delay from the beginning of the plasma pulse and rather in its second half. Although the measurements were performed on another tokamak under possibly different operating conditions, Fig. 2 in [START_REF] Nemtsev | Study of the triton-burnup process in different JET scenarios using neutron monitor based on CVD diamond[END_REF] shows time-resolved profiles of D-D, D-T and D-T/D-D ratios during a D-D discharge at the JET tokamak. The D-T/D-D ratio exhibits a peak at the end of the machine shot, reaching 1.5% for a low plasma current (1.5 MA). Fig. 3 in [START_REF] Nemtsev | Study of the triton-burnup process in different JET scenarios using neutron monitor based on CVD diamond[END_REF] shows that increasing the plasma current to 6 MA leads to a D-T/D-D ratio larger than 3%. Qualitatively speaking, similar time evolution and magnitude of this D-T/D-D ratio in the WEST tokamak should explain the occurrences as well as the time distributions of the observed MCUs in the present experiment. A possible contribution of additional "high-energy" photoneutrons in the total neutron fluence at the device level, induced by runaway energetic electrons, may be also invoked to explain these results [START_REF] Breizman | Physics of runaway electrons in tokamaks[END_REF].

V. CONCLUSION

This work presents experimental results on the RT-SER characterization of bulk 65 nm static random-access memories (SRAMs) exposed to neutrons produced during D-D plasma operation of a tokamak machine at the WEST facility. It significantly improves the previous preliminary experimental results obtained at WEST and goes further in the analysis with a possible link to the physics and operation of the machine. The present measurement campaign at WEST was characterized by the production of several tens of long pulse discharges (~60 s) and by an effective neutron fluence up to ~10 9 n.cm -2 at the device level, improving the error statistics by a factor of more than 6 with respect to the first measurements. Our results highlight the occurrence of bursts of single-event upsets during the most efficient shots and a production of about 12% of multiple-cell upset events. The synchronization of the RT-SER computer clock with the time delivered by the tokamak control room allowed us to show that MCUs are preferentially detected in the second half of the machine pulses, providing further evidence that higher energy neutrons, possibly initiated by D-T reactions due to triton burn-up in the D-D plasma, may play a role in the production of MCUs that cannot be attributed in such large proportions to "low-energy" neutrons produced in D-D reactions.

Fig. 1 .

 1 Fig.1. Photographs of the tokamak (a), (b) with the real-time test setup (c) installed at the position P3 in front of the quesot center P0 in the tokamak equatorial plan; (d) Schematic top view of the tokamak with the definition of distances. The neutron fluence f at the level of the SRAM circuits under test was estimated from the response of three groups of fission chambers positioned at 120° around the tokamak vacuum chamber. These fission chambers integrate the total number of neutrons Ne produced in the whole tokamak chamber during a machine shot.

b

  Neutron fluence (n/cm 2 ) in P 3

Fig. 3 .

 3 Fig. 3. (a) Distribution of the number of neutrons produced during machine shots, (b) distribution of shot durations (b), and (c) distribution of neutron fluence per shot for all the shots of the WEST C7 campaign (six weeks). Machine shots where SEU events have been detected in coincidence with the neutron flux are shown in red.

Fig. 4 .

 4 Fig. 4. Distribution of the number of neutrons produced during machine shots versus shot duration for all the shots of the WEST C7 campaign. Machine shots during which SEU events have been detected in coincidence with the neutron flux are indicated in red.

Fig. 5 .

 5 Fig. 5. Bit flip distribution as a function of neutron fluence for all the events detected during the WEST C7 and C5 campaigns. The linear fit corresponds to the extraction of the bit flip SER for data related to C7.

Fig. 6 .

 6 Fig. 6. Histogram of shots characterized by the occurrence at least of 2 bit flips as a function of the number of bit flips detected during the shots. A 2 bit flip occurrence can corresponds to 2 SBUs or 1 MCU(2), a triple bit flip occurrence to 3 SBUs, 1 SBU and 1 MCU(2) or 1 MCU(3), and so on.

  flip per multiple event shots

Fig. 7 .

 7 Fig. 7. Time distribution of the occurrence of SBUs and MCU events of multiplicities 2 and ³3 during the machine shots. A time occurrence of 0 % (resp. 100 %) means that the event occurs at the beginning (resp. at the end) of the machine shot.

Fig. 8 .

 8 Fig. 8. Comparison between experimental and simulated bit flip distributions for the C7 campaign. Numerical curves have been obtained for different values of the D-T/D-D ratio (0 %, 1 %, 2.7 % and 5 %) and scaled for 3.422 Gbit of SRAM memory.

TABLE I SUMMARY

 I OF C5 AND C7 CAMPAIGNS IN TERMS OF SEUS

		C7 campaign	C5 campaign
		(2023)	(2021)
	Maximum shot durations (s)	109	18
	Maximum neutrons/shot (tokamak)	5×10 13	1×10 13
	Cumulated neutron fluence (n.cm -2 ) at device level	1.21×10 9	1.43×10 8
	Single Bit Upsets (SBU)	230 (87.1 %)	36 (87.8 %)
	MCU events	34 (12.9 %)	5 (12.2 %)
	MCU(2)	20	3
	MCU(3)	13	2
	MCU(>3)	1 MCU(10)	0
	Total SBU + MCU events	264	41
	Total bit-flips	319	48

ACKNOWLEDGMENTS

The authors would like to thank the technical staff of the WEST tokamak facility for their technical support during all the irradiation campaign. This work was supported in part by EUROfusion Work-Package "Preparation of ITER Operation" (PrIO). EUROfusion Consortium is funded by the European Union via the Euratom Research and Training Programme (Grant Agreement No 101052200 -EUROfusion). We would like to express our special thanks to Dr. Xavier Litaudon (CEA/IRFM) for his strong support.


Ali Gharib

Francesca Casagli

Walid Djema

Pedro Moñino Fernandez

Rocca Chin-On

Olivier Bernard

Validation of a simple and adaptive prediction model for temperature in outdoor microalgae cultivation systems

à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Validation of a simple and adaptive prediction model for temperature in outdoor microalgae cultivation systems

Gharib A. 1 , Casagli F. 1 , Djema W. 1 , Moñino Fernandez P. 2 , Chin-On R. Microalgae are unicellular autotrophic organisms that have the potential to be used for various biotechnological applications like biofuel or wastewater treatment in large scale production systems. The dynamics of microalgae growth in outdoor systems are strongly dependent on light and temperature and thus on meteorology. In fact, they are the main drivers of the growth rate of microalgae and further of the process productivity.

Based on heat transfer modeling, numerous thermal models have been created for simple reactor geometries (usually for raceway ponds), that deliver accurate temperature predictions. However, these models require a lot of physical constants and a costly setup process. As a consequence, we developed a new generic non-linear model which overcomes these difficulties and is more suitable for control purposes.

The novelty of this model is the flexibility to adapt to any cultivation system by using a small data set to identify the parameters of the model.

Figure 1 :

 1 Figure 1: Using a data-set of 4 days (200 points) to fit the reduced-model to measured data from a raceway pond reactor in south of France

  2 , Bernard O. 1 ,

	1 Université Côte d'Azur, Inria, INRAE, CNRS, Sorbonne Université,Biocore Team, France
	2 Wageningen University, Bioprocess Engineering, Netherlands,


Bernard Canaud

Jeroen Kooman

Andrew Davenport

David Campo

Eric Carreel

Marion Morena-Carrere

Jean-Paul Cristol

Bernard Canaud1

Jeroen Kooman3

Andrew Davenport4

David Campo5

Eric Carreel5

Jean-Paul Cristol6

Digital health technology to support

Digital health technology to support care and improve outcomes of chronic kidney disease patients: as a case illustration, the Withings toolkit health sensing tools Introduction

Cardiovascular disease (CVD) is a major burden in dialysis dependent, chronic kidney disease (CKD5D) patients [START_REF] Parikh | Cardiovascular disease risk factors in chronic kidney disease: overall burden and rates of treatment and control[END_REF]. Mortality from cardiovascular disease is 10 to 20 times higher in CKD5D patients than in the general population matched for age and gender [START_REF] Foley | Epidemiology of cardiovascular disease in chronic renal disease[END_REF]. The pathophysiologic link between CVD and CKD is well established involving multiple factors including dialysis prescription and monitoring [START_REF] Menon | Cardiovascular risk factors in chronic kidney disease[END_REF]. Severe CVD events are the main cause of death in CKD5D patients [START_REF] Carrero | Cardiovascular and noncardiovascular mortality among men and women starting dialysis[END_REF]. Deaths from cardiovascular disease accounted for 48% of all deaths, including arrhythmias, cardiac arrest, congestive heart failure (CHF), acute myocardial infarction (AMI), and atherosclerotic heart disease (ASHD) in the annual USRDS 2019 report [START_REF] Usrds | USRDS annual data[END_REF]. Interestingly, arrhythmias and cardiac arrest represented 50% of all cardiac deaths.

It is widely recognized that chronic kidney disease patients represent a high cardiovascular risk population [START_REF] Parikh | Cardiovascular disease risk factors in chronic kidney disease: overall burden and rates of treatment and control[END_REF][START_REF] Provenzano | Epidemiology of cardiovascular risk in chronic kidney disease patients: the real silent killer[END_REF]. Several factors contribute to this vulnerability including traditional ones namely age, gender, life-style and comorbidities, and nontraditional ones such as nephropathy, volume overload, hypertension, uremic and metabolic disorders, uremic cardiomyopathy and renal replacement modality [START_REF] Levin | Identification of patients and risk factors in chronic kidney disease-evaluating risk factors and therapeutic strategies[END_REF]. These are summarized in Figure 1. It is not our intention to review all these factors, but rather to highlight the fact that CKD5D patient management and dialysis modality are modifiable factors that may have a strong influence on patient outcomes [START_REF] Canaud | Dialysis prescription: a modifiable risk factor for chronic kidney disease patients[END_REF].

By triggering cardiac events, conventional thrice weekly hemodialysis is a significant potential disease modifier as indicated by recent studies. Large cohort studies have shown that interdialytic periods, in particular those with the longest interval (2 days break), increased the risk for hospitalization and mortality by 20 to 40% [START_REF] Foley | Long interdialytic interval and mortality among patients receiving hemodialysis[END_REF][START_REF] Hakmei | Length of interdialytic intervals affects morbidity and mortality in chronic haemodialysis patients[END_REF][START_REF] Fotheringham | The mortality and hospitalization rates associated with the long interdialytic gap in thriceweekly hemodialysis patients[END_REF]. Importantly, these risks are much greater in the 12 hours following the hemodialysis session (early) and in the 12 hours preceding the next hemodialysis session (late). These findings suggest that two different mechanisms are likely involved: the early one would favor a role for rapid fluid and electrolyte shifts along with changes in cardiac structure and perfusion and sympathetic vagal nervous system imbalance [START_REF] Brunelli | Serum-to-dialysate potassium gradient and its association with shortterm outcomes in hemodialysis patients[END_REF][START_REF] Hecking | Predialysis serum sodium level, dialysate sodium, and mortality in maintenance hemodialysis patients: the dialysis outcomes and practice patterns study (DOPPS)[END_REF][START_REF] Laitinen | Sympathovagal balance is major determinant of short-term blood pressure variability in healthy subjects[END_REF]; the late one would favor a role for fluid overload, hypertension and hyperkalemia [START_REF] Wong | Interdialytic weight gain: trends, predictors, and associated outcomes in the international dialysis outcomes and practice patterns study (DOPPS)[END_REF][START_REF] Rhee | Serum potassium and the long interdialytic interval: minding the gap[END_REF][START_REF] Zoccali | Chronic fluid overload and mortality in ESRD[END_REF]. Recent prospective studies using either skin surface patch or implantable loop recorders allowing continuous electrocardiogram (ECG) recording brought new insights into this problem [START_REF] Rogovoy | Hemodialysis procedure-associated autonomic imbalance and cardiac arrhythmias: insights from continuous 14-day ECG monitoring[END_REF]. Based on ambulatory ECG monitoring, it was shown that clinically significant arrhythmias were quite common and more frequent in hemodialysis patients than expected [START_REF] Sacher | Cardiac rhythm disturbances in hemodialysis patients: early detection using an implantable loop recorder and correlation with biological and dialysis parameters[END_REF][START_REF] Kalra | Arrhythmia in hemodialysis patients and its relation to sudden death[END_REF]. It is interesting noting that among clinically symptomatic arrhythmias, bradycardias, which sometimes were a harbinger of asystole, were more frequently observed than ventricular tachycardia and also that these rhythmic disorders were strongly related to the dialysis cycle. Next to this, studies with implantable loop recorders also showed that atrial fibrillation was prevalent in nearly 30% of dialysis patients, and episodes of atrial fibrillation (AF) related to the dialysis cycle. Although the optimal treatment strategy for AF in patients on HD remains under discussion, these findings are of relevance, as AF in patients with CKD 5D is strongly associated with mortality.

In this context, it appears of utmost importance to bring a closer attention to CVD monitoring in caring for CKD5D patients to ensure early and appropriate interventions to improve their outcomes [START_REF] Shafi | Mapping progress in reducing cardiovascular risk with kidney disease: sudden cardiac death[END_REF]. Technological advances had led to the development of new home-used, selfoperated, connected medical devices, which offer convenient and new tools for monitoring patients in a fully automated and ambulatory mode during the interdialytic period for CKD5D patients.

In this narrative essay, we discuss the clinical potential of pervasive wearable sensors for monitoring ambulatory dialysis patients. On purpose, we selected Withings' as specific digital health care equipment for our case illustration. We recognized that several digital remote monitoring equipment are available on the market (i.e., Apple, Samsung, Gyant, Medopad, Chronisense Medical, iHealth, Vitls) that have their own unique features and specific applications. To our knowledge however, these companies don't provide yet a comprehensive and combined approach of monitoring chronic ambulatory patients in their various vital dimensions (i.e., weight, blood pressure, fluid status, heart rhythm, sleep disorders). In addition, these companies are not capturing, analyzing data in a centralized cloud-based system, able to empower patients or support healthcare professionals in their decision making. Withings' provides today a toolkit digital medical health device with remote patient monitoring system, cloud-based advanced analytic system, supported by clinical validation that may be easily implemented in daily practice.

Digital health tools: the example of Withings as a multiplexed integrated web-based architecture system Analytic description: pervasive and non-intrusive connected tools

Withings, an electronics company has pioneered several devices aimed at facilitating the remote monitoring of chronically ill patients. Withings tool kit digital devices and their potential use in dialysis patients are presented in Figure 2.

Scanwatch© is an analog watch, which can allow the patient to record a 30 second single-lead ECG and make spot measurements of their peripheral oxygen saturation (SpO2), while in the background, heart rate is measured intermittently and physical activity (steps) measured continuously. This device analyzes the ECG signals, calculates the heart rate (robust mean over 30 seconds), and classifies the rhythm into one of the following categories: AF, Sinus Rhythm, Noise, Inconclusive1 . Scanwatch uses three types of sensors: i) dry electrodes (ECG), ii) optical sensors (SpO2 and pulse rate), iii) accelerometer (physical activity). The accuracy of SpO 2 measurement was assessed with a standardized protocol (ISO 80601-2-61:2017) during mild, moderate and severe hypoxias against gold-standard SaO 2 . The accuracy was good: 3% root mean square deviation (RMSE) (N = 14 patients and 275 blood samples) [START_REF] Kirszenblat | Validation of the withings ScanWatch as a wrist-worn reflective pulse oximeter: prospective interventional clinical study[END_REF]. Rhythm classification by the Scanwatch was compared to the diagnosis by cardiologists on simultaneously taken 12-lead ECGs (AF: n=100, normal sinus rhythm: n=113, other arrhythmia: n=45). 6.9% (18/262) were classified as Noise by the algorithm. Excluding patients with a reference diagnosis of other arrhythmias than AF or a noisy recording, the sensitivity for AF detection was 0.963 (95% CI lower boundary 0.894), with a specificity of 1.000 (95% CI limits of agreement 0.967) [START_REF] Campo | Atrial fibrillation detection with an analog smartwatch: prospective clinical study and algorithm validation[END_REF].

The BPM Connect© is an oscillometric blood pressure monitor. Its accuracy and precision were assessed in the general population as well as in pregnant women, including those with pre-eclampsia (24-26). In the general population (N = 85), for validation criterion 1, the mean difference ± SD between the reference and device measured blood pressure (BP) values was 0.6 ± 5.3 mmHg for systolic blood pressure (SBP) and 2.1 ± 4.3 mmHg for diastolic blood pressure (DBP). For criterion 2, the SD of the mean BP differences between the test device and reference BP per subject was 4.2/3.6 mmHg (SBP/DBP) [START_REF] Topouchian | Accuracy of the withings BPM connect device for self-blood pressure measurements in general population -validation according to the association for the advancement of medical Instrumentation/European society of Hypertension/International organization for standardization universal standard[END_REF]. In pregnant women, the mean differences between the mercury standard oscillograph and device BP values in pregnancy (n = 45) were -0.5 ± 5.7 mmHg for systolic BP (SBP) and -0.8 ± 3.8 mmHg for diastolic BP (DBP). In the subgroup of preeclamptic patients (n = 15), the mean differences were 0.14 ± 5.5 mmHg for SBP and 0.39 ± 3.7 mmHg for DBP [START_REF] Zelveian | Clinical accuracy of the withings BPM connect for self-blood pressure measurements in pregnancy and pre-eclampsia: validation according to the association for the advancement of medical Instrumentation/European society of Hypertension/ International organization for standardization universal standard[END_REF].

Bodyscan© is conceived as a health station. Besides measuring weight, it performs multifrequency segmental bioimpedance analysis and outputs the content of (mass and %) fat, visceral fat, lean tissues, muscles, total water, extra-cellular and intra-cellular water; it performs a 30 seconds 6-lead ECG (4 limb electrodes are placed, 2 on the glass plate and 2 on the handle), and calculates heart rate and classifies the rhythm into one of four categories (AF, Sinus Rhythm, Noise, Inconclusive 2 ); it estimates the aortic Pulse Wave Velocity (PWV) 3 and computes a Vascular Age 4 and it assesses the sudomotor function, an early indicator of peripheral neuropathy 5 . The ECG classification by Bodyscan was compared to the diagnosis by cardiologists on simultaneously taken 12-lead ECGs (AF: n=82, normal sinus rhythm: n=131, other arrhythmia: n=12, uninterpretable: n=8). 8.4% of the recordings were classified as Noise by the algorithm. Excluding patients with a reference diagnosis of other arrhythmias than AF or an uninterpretable recording, the sensitivity for AF detection was 0.98 (95% CI lower bound 0.92), and the specificity was 1.0 (95% CI lower bound 0.98) [Personal Communication]. PWV was compared to the carotid-Bodyscan© is conceived as a health station. Besides measuring weight, it performs multifrequency segmental bioimpedance analysis and outputs the content of (mass and %) fat, visceral fat, lean tissues, muscles, total water, extra-cellular and intra-cellular water; it performs a 30 seconds 6-lead ECG (4 limb electrodes are placed, 2 on the glass plate and 2 on the handle), and calculates heart rate and classifies the rhythm into one of four categories (AF, Sinus Rhythm, Noise, Inconclusive2 ); it estimates the aortic Pulse Wave Velocity (PWV) 3 and computes a Vascular Age4 and it assesses the sudomotor function, an early indicator of peripheral neuropathy 5 Bodyscan's measurement of the sudomotor (sweating) function was compared to the Sudoscan (Impeto Medical) (N=147). The sensitivity and specificity to classify with respect to (wrt) a neuropathy score of 70 (no neuropathy vs mild neuropathy) were 0.91 (95% CI lower bound 0.83) and 0.966 (95% CI lower bound 0.881) respectively, and the sensitivity and specificity to classify wrt a neuropathy score of 50 (mild vs severe neuropathy) were 0.915 (95% CI lower bound 0.796) and 0.990 (95% CI lower bound 0.946) [in preparation].

The Sleep Analyzer© consists of an air inflated pad connected to a pressure sensor. The pressure signal is decomposed into three channels: movement, respiration, and heart beats. In addition, a microphone permits detection of snoring and snorting. The device provides data on sleep (time asleep, sleep efficiency, wake periods and sleep stages), pulse rate and respiration rate, and computes an apnea-hypopnea index (not available in the US). The Sleep Analyzer was included in a polysomnography (PSG) study involving 42 participants in a sleep laboratory. The respiratory rate had a bias of -0.06 breaths per minutes and 95% limits of agreement (LOA) of [-0.6; 0.5] breath per minute. The heart rate had a bias of -0.8 and a 95% LOA of [-4.3; 2.7] beats per minute [START_REF] Yang | Pneumatic sensor for cardiorespiratory monitoring during sleep[END_REF]. Patients suspected to have obstructive sleep apnea syndrome completed a night at a sleep clinic with a simultaneous PSG and recording with the Sleep Analyzer (N=180). The sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC) at thresholds of apnea-hypopnea index ≥ 15 events/h were, respectively, Se 15 = 88.0%, Sp 15 = 88.6%, and AUROC 15 = 0.926. At the threshold of apnea-hypopnea index ≥ 30 events/h, results were Se 30 = 86.0%, Sp 30 = 91.2%, AUROC30 =0.954. The average total sleep time from PSG and the Withings Sleep Analyzers was 366.6 (61.2) and 392.4 (67.2) minutes, sleep efficiency was 82.5% (11.6) and 82.6% (11.6), and wake after sleep onset was 62.7 (48.0) and 45.2 (37.3) minutes, respectively [START_REF] Edouard | Validation of the withings sleep analyzer, an under-the-mattress device for the detection of moderate-severe sleep apnea syndrome[END_REF].

Advanced analytics: expert systems, threshold alarms

These devices are installed with WiFi or Bluetooth, and some are also available in a cellular version (Scanwatch, Sleep Analyzer, BPM Connect, scale Body Pro, Thermo, and a glucometer) 6 provided with Withings Remote Patient Monitoring (RPM©) solution. In this RPM solution, devices are pre-configured, shipped to the patient, and immediately available for use. After each measurement, the devices analyze the data and upload the results (e.g., SpO2, body composition) to Withings HDS servers. Data visualization can be reviewed by the patient using the Withings Health Mate application on a smartphone, or with a web interface. Health Care Professionals (HCP) can also visualize their patient's data via the Withings webbased RPM interface. Withings RPM can be integrated to virtually any electronic health care report. Patient's data confidentiality and security are ensured through an ISO 27001 certified hosting infrastructure and strictly following international general data protection regulation (i.e., GDPR). This is presented in Figure 2.

Feedback and alarm sent to user and reference center

Patients and clinicians can consult their data in the Withings Health Mate© application if not using the RPM solution application. In the RPM solution, patients are guided by a digital assistant (application on a smartphone), to maintain their adherence to monitoring on a daily basis. The digital assistant educates patients about the program and helps tracking, and a HIPAA compliant proactive phone support is provided to help patients who have not been able to activate their device. A setup confirmation is sent when devices are first installed.

Finally, it reminds patients to take their readings, and shares tips on how to build a habit. TheHCP-facing interface of the RPM is organized to display a complete history of the patients: all the health data from day one, alerts history, recent team notes, and current procedural technology (CPT) code completion history.

Clinical potential of digital remote tools: the example of dialysisdependent chronic kidney disease patients' management, the case for Withings technology

Remote monitoring of changes in volume status, vital signs (blood pressure, heart rate, respiration rate, oxygen saturation), sleep quality and physical activity are among the most useful and valuable when assessing ambulatory CKD5D patients [START_REF] Fung | Electrocardiographic patch devices and contemporary wireless cardiac monitoring[END_REF]. Withings' digital health toolkit devices offer a fully automated, unobtrusive and remote monitoring of the main vital functions in ambulatory subjects. These unique features provide a multidimensional assessment of ambulatory CKD5D patients covering most physiologic functions, detecting unexpected disorders (i.e., volume overload, arrhythmias) and finally helping physicians to judge patient's response to treatment and recommendations. Among the various options provided with Withings' digital health toolkit devices, we have briefly summarized some of the currently explored areas and potential fields for future clinical applications. Their potential use to support care of dialysis patients is presented in Figure 3.

Volume overload (VO) is a major cardiovascular risk factor for CKD5D patients. Chronic VO has been recognized as being a leading cause of hypertension and cardiac remodeling being independently associated with poor outcomes in dialysis patients [START_REF] Dekker | Impact of fluid status and inflammation and their interaction on survival: a study in an international hemodialysis patient cohort[END_REF][START_REF] Dekker | Interactions between malnutrition, inflammation, and fluid overload and their associations with survival in prevalent hemodialysis patients[END_REF][START_REF] Dekker | Fluid overload and inflammation axis[END_REF][START_REF] Van Der Sande | Using bioimpedance spectroscopy to assess volume status in dialysis patients[END_REF]. In addition, VO and pulmonary edema are leading causes of hospitalization [START_REF] Plantinga | Burden and correlates of readmissions related to pulmonary edema in US hemodialysis patients: a cohort study[END_REF][START_REF] Plantinga | Posthospitalization dialysis facility processes of care and hospital readmissions among hemodialysis patients: a retrospective cohort study[END_REF]. Therefore, it seems crucial to carefully monitor volume status and blood pressure changes to avoid complications associated with volume overload. Volume changes may be easily assessed on a daily basis by means of a digital scale and/or multifrequency bioimpedance analyzer integrated into a digital scale. By combining this with daily blood pressure measurement given by the BPM Connect, it becomes possible to have an extensive hemodynamic assessment of CKD5D patients throughout the dialysis week. Permanent ambulatory respiratory rate and ECG measurements may also provide complementary information on patient volume overload and pulmonary edema risk. Chan et al. used a wearable patch biosensor to determine respiratory rates for remote patient monitoring and respiratory disease screening [START_REF] Chan | Wireless patch sensor for remote monitoring of heart rate, respiration, activity, and falls[END_REF]. For this purpose, they developed and validated an algorithm in a small population of 15 elderly subjects performing the different activities of daily living. Recognizing that volume overload contributes to reduced oxygenation, it can be anticipated that permanent monitoring of oxygen saturation (SpO2) may facilitate early detection and disease severity of volume overload. From a clinical perspective, by combining changes in bioimpedance scale, respiratory rate, oxygen saturation and ECG data generated by Withings' toolkit, one can reasonably expect enhancing accuracy of detecting early volume overload in ambulatory CKD5D patients and to correct it before congestive heart failure develops, so avoiding acute hospital admission.

Arrhythmia is observed in 30 to 40% of established CKD5D patients leading potentially to life threatening complications including sudden death [START_REF] Charytan | Arrhythmia and sudden death in hemodialysis patients: protocol and baseline characteristics of the monitoring in dialysis study[END_REF]. It is well recognized that several pro-arrhythmic risk factors coexist in this population. However, the central abnormality that predisposes to arrhythmias is the cardiomyopathy, which is highly susceptible to abnormal ventricular conduction either spontaneously or via additional triggers such as dialysis-induced circulatory stress or electrolyte fluxes [START_REF] Selby | The acute cardiac effects of dialysis[END_REF][START_REF] Ja3rd | Novel wireless devices for cardiacmonitoring[END_REF]. It has been also shown that some ECG abnormalities are prone to life-threatening arrhythmias that include heart-rate variability (HRV), ventricular late potentials, and QT interval prolongation. Using continuous ECG monitoring either with patch-based or implanted loop recording, it was shown that arrhythmias are more frequent than expected and ventricular tachycardia and/or tachyarrhythmia were the most frequent but clinically serious events were mainly observed with bradyarrhythmia's [START_REF] Roberts | A systematic review of the incidence of arrhythmias in hemodialysis patients undergoing longterm monitoring with implantable loop recorders[END_REF]. Roy-Chaudhury et al. have identified in a prospective study performed in 66 hemodialysis patients using an implantable loop recorder (ILR), that clinically serious arrhythmias (CSA) occurred in 67% of patients [START_REF] Roy-Chaudhury | Primary outcomes of the monitoring in dialysis study indicate that clinically significant arrhythmias are common in hemodialysis patients and related to dialytic cycle[END_REF]. Interestingly, arrhythmic disorders were distributed as follows: 77.3% had non-sustained ventricular arrhythmias, 20% had bradycardia, 9% had a systolic events and only one episode of sustained ventricular tachycardia was observed. Furthermore, it has been shown that arrhythmias were strongly related to the dialysis cycle. Prevalence of arrhythmia was highest during the first dialysis session of the week and also increased during the last 12 hours of each inter-dialytic interval and particularly with the longer interdialytic interval. In addition, electrolyte fluxes and dialysis prescription were associated with significant impacts on the incidence of arrhythmias. Sacher et al. provided further insights in a prospective study including 71 hemodialysis patients using an ILR device [START_REF] Sacher | Cardiac rhythm disturbances in hemodialysis patients: early detection using an implantable loop recorder and correlation with biological and dialysis parameters[END_REF][START_REF] Roy-Chaudhury | Primary outcomes of the monitoring in dialysis study indicate that clinically significant arrhythmias are common in hemodialysis patients and related to dialytic cycle[END_REF]. Twelve patients (17%) had a past history of AF or flutter. During a mean follow-up period of 21.3 months, 16 patients died (14% patient years), 7 (44%) of cardiovascular causes and 4 sudden deaths occurred, with progressive bradycardia followed by asystole. De novo AF or flutter was diagnosed in 14 patients (20%). The incidence of patients presenting with clinically serious event and ventricular arrhythmia was 14% and 9% patient-years, respectively. In multivariate analyses, they identified several pro-arrhythmic risk factors that included high plasma potassium, low bicarbonate, high hemoglobin, high blood pressure, longer interdialytic period, history of coronary artery disease, previous arrhythmias and diabetes mellitus. Furthermore, specific risk associated with ventricular arrhythmia was low plasma potassium, no antiarrhythmic drugs and past history of arrhythmias [START_REF] Sacher | Cardiac rhythm disturbances in hemodialysis patients: early detection using an implantable loop recorder and correlation with biological and dialysis parameters[END_REF][START_REF] Roy-Chaudhury | Primary outcomes of the monitoring in dialysis study indicate that clinically significant arrhythmias are common in hemodialysis patients and related to dialytic cycle[END_REF].

Early detection of clinically serious arrhythmias potentially leading to cardiac arrest in high risk CKD5D patient is clearly an unmet medical need that requires more appropriate wearable and ultralight tools. Now, it remains to be proved in the clinical setting of hemodialysis that wireless patch device may offer comparable information to implantable wire loop recorders in an easier and more cost-effective manner [START_REF] Fung | Electrocardiographic patch devices and contemporary wireless cardiac monitoring[END_REF][START_REF] Ja3rd | Novel wireless devices for cardiacmonitoring[END_REF]. From a clinical perspective, detection of clinically significant arrhythmias will lead to revision of renal replacement treatment options (i.e., intensive dialysis, dialysate electrolyte prescription) and referral to cardiology expertise to mitigate cardiac risk (i.e., medication, implantable pacemaker or defibrillator).

Sleep disorders are common and more frequent in CKD5 patients on maintenance hemodialysis than in the general population [START_REF] Murtagh | The prevalence of symptoms in end-stage renal disease: a systematic review[END_REF][START_REF] Weisbord | Renal provider recognition of symptoms in patients on maintenance hemodialysis[END_REF][START_REF] Sabbatini | Insomnia in maintenance haemodialysis patients[END_REF]. In brief, among most frequently reported symptoms are insomnia (69%), obstructive sleep apnea syndrome (OSAS) (24%), restless leg syndrome (RLS) (18%) and excessive daytime sleepiness (EDS) (12%). Furthermore, sleep disorders are strongly associated with poor health-related quality of life (i.e., fatigue) and poor patient outcomes (i.e., higher cardiac burden) [START_REF] Iliescu | Quality of sleep and health-related quality of life in haemodialysis patients[END_REF][START_REF] Mucsi | Restless legs syndrome, insomnia and quality of life in patients on maintenance dialysis[END_REF]. Several risk factors have been identified including non-modifiable factors (e.g., obesity, diabetes, chronic kidney disease) and modifiable factors in particular dialysis adequacy (e.g., volume overload, hypertension, anemia, albumin). Automated prediction of apnea-hypopnea index and detection of sleep apnea is an interesting approach to reduce a newly identified cardiovascular risk factor in CKD5D population. Apnea-Hypopnea Index (AHI) assesses severity of this disorder by measuring number of apnea or hypopnea events per hour. Usually, between 2% and 5% of adult women and 3% to 7% of adult men have sleep apnea syndrome (SAPS). Selvaraj et al. have used a patch biosensor to estimate the apnea-hypopnea index in a cohort of high risk subjects [START_REF] Selvaraj | Detection of sleep apnea on a per-second basis using respiratory signals[END_REF]. For this purpose, they developed an algorithm using features provided by statistical and filtering dispersion analysis of the nasal airflow respiration signals. Based on this algorithm, they computed apnea or hypopnea occurrences on a per-second basis and compared the predictive value of their algorithm to the 'gold standard' relying on a polysomnography (PSG) record. Interestingly, they showed that the predictive value of the patch biosensor was comparable to the apnea-hypopnea index obtained with the PSG. The authors confirmed that patch biosensor can be used in sleep apnea syndrome screening as an inexpensive and convenient solution for recurrent sleep apnea evaluation. In addition, it has been shown recently that about 10% of hemodialysis patients presented with prolonged and relatively severe hypoxemia during dialysis sessions. Hypoxemic patients have higher mortality risk estimated around 20% at one year [START_REF] Campos | Intradialytic hypoxemia in chronic hemodialysis patients[END_REF][START_REF] Meyring-Wösten | Intradialytic hypoxemia and clinical outcomes in patients on hemodialysis[END_REF]. Now, it remains to be shown that wearable wireless bed patch biosensors (sleep analyzer) have the same accuracy in CKD5D patients. From a clinical perspective, patients presenting with high apnea-hypopnea index and/or prolonged hypoxia may benefit from intermittent continuous positive airway pressure (CPAP) devices and/or oxygen therapy to mitigate this cardiac risk.

Impaired physical activity is a key feature of adults with advanced CKD, and is associated with poor outcome and increased mortality [START_REF] Broers | Physical activity in end-stage renal disease patients: the effects of starting dialysis in the first 6 months after the transition period[END_REF][START_REF] Wilkinson | Prevalence and correlates of physical activity across kidney disease stages: an observational multicentre study[END_REF]. The physical fitness in aged dialysis patients is so reduced that it impinges on ability to perform everyday activities of life and domestic tasks and increases the risk of falls. An increasing number of studies have stressed health benefits of regular exercise training programs to the point that they are perceived as a cornerstone of therapy [START_REF] Huang | Exercise training and outcomes in hemodialysis patients: systematic review and meta-analysis[END_REF][START_REF] Heiwe | Exercise training for adults with chronic kidney disease[END_REF][START_REF] Clarkson | Exercise interventions for improving objective physical function in patients with end-stage kidney disease on dialysis: a systematic review and meta-analysis[END_REF][START_REF] Deligiannis | Exercise training in dialysis patients: impact on cardiovascular and skeletal muscle health[END_REF]. Monitoring physical activity and guiding physical exercise training in an adapted and structured way are of crucial importance in this frail population. In this context, wearable wireless connected patch sensors provide monitoring to achieve this goal in an easy and transparent way. Using a wireless patch sensor, Selvaraj et al. have assessed and confirmed performances and accuracy of such device in measuring vital signs [START_REF] Selvaraj | Long-term remote monitoring of vital signs using a wireless patch sensor[END_REF]. In this study, 76 senior participants were included and were followed up to 3603 days.

The results confirmed not only wearability and usability of the wireless biosensor at home over the longer term but also showed the clinical value in the early detection of falls. Usually, experiments target young participants and some activities of daily living in assessing the specificity and sensitivity of fall detection systems. The Selvaraj study has also shown the suitability of wireless patch sensor in elderly participants for long-term monitoring at home. In another study, Chan et al. compared accuracy of a wireless patch sensor with more conventional medical devices [START_REF] Chan | Wireless patch sensor for remote monitoring of heart rate, respiration, activity, and falls[END_REF]. In brief, they confirmed that patch connected biosensor provides similar results than larger and traditional tools in measuring physical activity and vital signs.

Protein energy wasting (PEW) is more common in advanced CKD and dialysis patients (20-50%) and also associated with an increased risk of morbidity and mortality [START_REF] Carrero | Global prevalence of protein-energy wasting in kidney disease: a meta-analysis of contemporary observational studies from the international society of renal nutrition and metabolism[END_REF][START_REF] Koppe | Kidney cachexia or protein-energy wasting in chronic kidney disease: facts and numbers[END_REF]. Early recognition and treatment of malnutrition are essential to improve the outcome of CKD and dialysis patients. Assessment of PEW relies on a series of markers including clinical and anthropometric signs (weight loss, low body mass index, lean tissue mass), laboratory investigations (albumin, transthyretin), dietary survey (protein and energy intake) and instrument tools (bioimpedance, energy expenditure) [START_REF] Fouque | A proposed nomenclature and diagnostic criteria for protein-energy wasting in acute and chronic kidney disease[END_REF][START_REF] Obi | Latest consensus and update on proteinenergy wasting in chronic kidney disease[END_REF]. Diagnosis of PEW is usually recognized by health care professionals as cumbersome or made at a too late stage. In this context, wearable patch wireless sensor devices might offer a new and convenient tool for an early detection of reduced daily energy expenditure and physical activity. Furthermore, the combined use with body composition analyzer using bioimpedance assessments will track lean tissue mass wasting. Selvaraj et al. have used a wireless patch biosensor for assessing energy expenditure (EE) rate and total daily energy expenditure (TEE) in a cohort of 32 ambulatory subjects aged 21 to 72 years old with a wide range of body mass index [START_REF] Selvaraj | Performance of energy expenditure assessment using a chestworn wireless patch sensor. 2014 4th international conference on wireless mobile communication and healthcare -transforming healthcare through innovations in mobile and wireless technologies[END_REF]. Their results confirmed that patch biosensors allow accurate measurement of EE and TEE and provide a reliable and non-constraining tool for such assessments. Now, it remains to be proved that accuracy of such wearable patch devices equally works in CKD5D patients, that requires further validation studies. Falls among aged CKD5D patients are a serious concern since they have significant impact on quality of life and mortality [START_REF] Cook | Falls and fall-related injuries in older dialysis patients[END_REF]. Falls are also a significant cause of morbidity that contributes to a substantial burden to health care costs. Although falls may be predicted or minimized, they are not totally preventable. Fall reduction in elderly CKD5D patients is an important focus for health care researcher [START_REF] Kutner | Falls among hemodialysis patients: potential opportunities for prevention?[END_REF][START_REF] Papakonstantinopoulou | Risk of falls in chronic kidney disease[END_REF]. Narasimhan et al. used a biosensor to automatically detect human falls [START_REF] Narasimhan | Skin-contact sensor for automatic fall detection[END_REF]. The tri-axial accelerometer, Bluetooth Low Energy transceiver, and microcontroller found in the sensor can detect a possible fall if there is impact and the person lies horizontally after the fall. Furthermore, the activity after the fall must be below the threshold. The study recruited 15 elderly volunteers to perform activities of daily living and 10 volunteers to perform intentional falls using a gymnastics mat. The algorithm developed offered 100% specificity and 99% sensitivity. From a clinical perspective, digital remote self-operated tools may provide an easy means to monitor physical activity and energy expenditure on one hand, and to activate patients through personalized coaching and training through advice on the other.

Expected results and future development

Increasing advances in technology, especially electronics and computerization, will lead to a new generation and wider availability of such pervasive health sensing and digital technology at an acceptable cost, that will allow extensive noninvasive monitoring of fragile CKD5D patients at home. As discussed earlier, regular monitoring of vital functions may help care givers to improve the management of dialysis patients by providing early alert to serious events such as volume overload and/ or arrhythmias before life-threatening complications occur.

By combining remote extensive multiplexed sensing technology and advanced analytics relying on cloud computing and artificial intelligence, and RPM management, Withings' tool kit potentially offers today a convenient and cost competitive means of improving care of CKD patients. Newer generations of this highly sophisticated technology should provide a major step towards precise and personalized medicine. It has potential to improve patient perception, to reduce cardiovascular burden and finally to reduce costs associated with hospitalization.

In the future, it remains to be determined how these tools work for CKD patients and which category of patients will benefit more from this wearable sensing and digital technology. Further studies are needed to identify potential clinical benefits and to position these tools in the clinical management of CKD patients, and in particular in the renal replacement therapy field.

Take home message

Digital self-operated tools such as Withings's toolkit provide a new and integrated approach for monitoring ambulatory dialysis patients. A number of these devices are already commercially available and potentially offer a fully automated, unobtrusive and remote monitoring of main vital functions in ambulatory subjects. It was not our intent to compare accuracy and usability of these digital health tools, but rather to use case of on one comprehensive and integrated digital health toolkit system in improving care of CKD patients. These unique features provide a multidimensional way of assessing ambulatory CKD5D patients covering most of the relevant physiologic functionalities, detecting unexpected disorders (i.e., volume overload, arrhythmias, sleep disorders), providing alarms to patients and supervising clinical center and finally supporting physicians to judge patient responses to treatment and recommendations. Although this new technology has the potential to improve the quality of care for CKD5D patients, further studies are required to confirm the prospective clinical benefits of this rapidly developing technology.

  . The ECG classification by Bodyscan was compared to the diagnosis by cardiologists on simultaneously taken 12-lead ECGs (AF: n=82, normal sinus rhythm: n=131, other arrhythmia: n=12, uninterpretable: n=8). 8.4% of the recordings were classified as Noise by the algorithm. Excluding patients with a reference diagnosis of other arrhythmias than AF or an uninterpretable recording, the sensitivity for AF detection was 0.98 (95% CI lower bound 0.92), and the specificity was 1.0 (95% CI lower bound 0.98) [Personal Communication]. PWV was compared to the carotid-femoral PWV measured with a Sphygmocor by trained specialists in general population. The bias was 0.25 m•s -1 and the SE was 1.39 m•s -1 . This agreement with Sphygmocor is "acceptable" according to the ARTERY classification (29).

'Noise' is an output given if the quality of the recording is too poor to classify the rhythm with confidence. 'Inconclusive' is the output when the rhythm cannot be classified as either AF or Sinus Rhythm with enough confidence. This may happen when the heart rate is < 50 bpm or > 150 bpm, or in the presence of another arrhythmia than AF.

Cf footnote 1.

The ballistocardiogram, recorded as small variations of weight produced by the recoil of the center of mass upon the ejection of blood into the aorta, gives a proximal time point. An impedance plethysmogram of the foot (measuring the variations of conductivity) gives a distal time point. A model using these time points and the height of the patient was trained to output the carotid-femoral PWV measured with a Sphigmocor (AtCor Medical).

The Vascular Age is the chronological age of the patient corrected by a PWV-dependent factor.

It combines reverse iontophoresis, i.e., migration of some ions from the human skin to the electrodes in contact with the sole of the feet, and steady multiple chronovoltammetry, which is the application of rectangular direct current (DC) voltages of varying amplitudes. A time/ampere curve is recorded. Electrochemical skin conductance (ESC) in the hands and feet, i. e., the ratio between current generated and the constant DC voltage stimulus, is calculated and compared to normal values.

Availability of the cellular devices depends on the geographical area. The RPM application is available in Europe but not in the US.

Challenges and threats of digital health technology

The introduction of a new technology, particularly in patient care, is always subject to caution, fears or even doubts by medical community experts. This is the case for digital health systems and particularly for pervasive remote monitoring devices that bring another level of complexity to patient management. In this paragraph, we provide few thoughts about challenges and threats related to the intrusion of digital health technology in tomorrow medical field.

On one end, there are some challenges that deserve to be highlighted: Firstly, amount of big data generated by these devices when used on a daily basis; Secondly, usability of this information by users and care givers; Thirdly, reliability of medical information generated and transmitted to care professionals; Fourthly, safety of patients' data protection system; Fifthly, integration of these tools in standard of care and patient workflow.

On the other end, there are also threats that need to be underlined: Firstly, reliability of information captured and transmitted to care givers; Secondly, data interpretation and translation in an active patient management plan; Thirdly, patient burned out associated with continuous monitoring perceived as too intrusive; Fourthly, economical value based of this remote digital health technology must be assessed more precisely; Fifthly, excessive reliance on digital health system may lead to loss of medical expertise or doctor/patient interaction, this is a risk.

All these challenges and threats must be kept in mind since they will deserve more attention and evaluation in the future. It is not our purpose to elaborate further on these topics, due to space restriction, but also because we are at the dawn of new technological revolution in the health care system, and answers will be provided with more extensive use of these digital health tools.

Author contributions

All authors contributed to the article and approved the submitted version.

Conflict of interest

DC, ER are employees and/or stockholder from Withings. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.