Trade-wind cumuli constitute the cloud type with the highest frequency of occurrence on Earth, and it has been shown that their sensitivity to changing environmental conditions will critically influence the magnitude and pace of future global warming. Research over the last decade has pointed out the importance of the interplay between clouds, convection and circulation in controling this sensitivity. Numerical models represent this interplay in diverse ways, which translates into different responses of trade-cumuli to climate perturbations. Climate models predict that the area covered by shallow cumuli at cloud base is very sensitive to changes in environmental conditions, while process models suggest the opposite. To understand and resolve this contradiction, we propose to organize a field campaign aimed at quantifying the physical properties of trade-cumuli  as a function of the large-scale environment. Beyond a better understanding of clouds-circulation coupling processes, the campaign will provide a reference data set that may be used as a benchmark for advancing the modelling and the satellite remote sensing of clouds and circulation. It will also be an opportunity for complementary investigations such as evaluating model convective parameterizations or studying the role of ocean mesoscale eddies in air–sea interactions and convective organization. Of all the clouds that populate the Earth’s atmosphere, trade-cumuli count among the most fascinating expressions of the interplay between clouds and circulations. These broken shallow clouds form within the lowest kilometres of the atmosphere, influenced at their base by small-scale turbulent motions of the warm, moist surface layer, and at their top by the large-scale sinking motions of the warm and dry overlying free troposphere. If many of these clouds do not rise by more than a few hundred metres above their base, some reach higher levels  and in observations the cloud-base fraction of trade-wind cumuli appears to be much more resilient to changes in environmental conditions than in climate models, both in the current  held in December 2013 and August 2016 have since created an observational foothold to better understand the coupling between clouds and their environment  in 2010, and the two 4A (Elucidating the role of clouds-circulation coupling in climate), has been designed to take advantage of and extend these advances. Anchored at the BCO, it will measure clouds in the winter trades of the North Atlantic, windward of Barbados, in early 2020. EUREC4A will have two primary objectives:To quantify macrophysical properties of trade-wind cumuli as a function of the large-scale environment, andTo provide a reference data set that may be used as a benchmark for the modelling and the satellite observation of shallow clouds and circulation.To address these objectives EUREC4A will provide, for the first time, simultaneous measurement of cloud macrophysical properties , cloud radiative properties , convective activity , and the large-scale environment in which clouds and convection are embedded .A new field campaign, EUREC4A field campaign. In Sect. 4A will be an opportunity for complementary scientific investigations. We describe some of these possibilities as of EUREC4A++ in Sect. In Sect. 4A field campaign is to elucidate how the macrophysical properties of trade-cumuli depend on the dynamic and thermodynamic properties of the environment in which the clouds form. More specifically, EUREC4A aims to answer the following questions:What controls the convective mass flux, mesoscale organization, and depth of shallow clouds?How does the cumulus cloud amount in the trade-wind boundary layer vary with turbulence, convective mixing and large-scale circulations, and what impact does this variation have on the atmospheric radiation field?The core objective of the EUREC4A field campaign will take place in the lower Atlantic trades, over the ocean east of Barbados  at 9 km altitude , and will densely distribute dropsondes around the circles. The dropsondes will characterize the vertical thermodynamic structure of the trade-wind atmosphere and will make it possible to infer the vertical profile of large-scale divergence over the area Sect. . The advSimultaneously, the ATR-42 will characterize the shallow cumulus field and boundary-layer properties within the area through a series of low-level legs, flown primarily near the cloud-base level  over four weeks for operations out of Grantley Adams International Airport on Barbados. Ten HALO research flights from Barbados are envisioned, each with a duration of 9 h bracketing two 4-h flights of the ATR-42 (with a refuelling in between). The zone of operations will not change much from day to day, but owing to daily meteorological variability one may hope to sample different types of cloud conditions and organizations. On any given research flight the same cloud and environmental conditions will be observed for many hours by both aircraft, making it possible to characterize these conditions in a statistically consistent and representative way.In addition to the aircraft missions that will characterize clouds and their surrounding environment up to scales of O(100 km), surface and ship-based observations will be distributed over the area of and around flight operations augmenting measurements from the BCO so as to better characterize the surface and atmospheric environment of clouds on a scale of O(1000 km) and over a longer, uninterrupted time period, as well as strengthen the fidelity of the large-scale analyses.Meteor and Maria S. Merian), France , The Netherlands (Pelagia), the USA and Spain are pending. The research vessels will serve as advanced surface remote sensing platforms, atmosphere and ocean sounding stations, bases for fleets of autonomous vehicles, and means of laying down an array of drifters/floats or buoys.The large-scale array of observations will be comprised of three to five stations Fig. : the BarRadiosondes will be launched from each station to collect simultaneous measurements of profiles of air humidity, temperature, pressure and horizontal winds (derived from GPS measurements) from the surface through the lower stratosphere. The sounding data will be assimilated by weather centres, which will improve the quality of meteorological analyses for the period of the campaign and will help diagnose large-scale divergence and vertical motion over a range of scales larger than the zone of aircraft operations.4A).Measurements from research vessels are intended to be operated over a period of 3 to 5 weeks overlapping with the planned airborne observations. This will establish context for the aircraft missions relative to the seasonal march of the ITCZ and the evolving strength of overturning within the Hadley cell. Soundings will be launched with a minimum frequency of 6 per day to adequately sample the diurnal and semi-diurnal cycles, along with other subdaily variability. It will also make it possible to get thermodynamic data and large-scale divergence estimates up to the top of the atmosphere instead of up to 9 km  will provide the first space-borne vertically resolved radial  wind measurements; EarthCare , an imaging instrument with 15 m spatial resolution on-board Terra, plus a number of satellites from flagship space missions that we expect to be in orbit by the time of the campaign: 4A study area on 9 February 2017 is shown in Fig. 4A will be the first field study to investigate whether this organization matters for the statistical properties of the shallow cumulus field.Existing satellite imagery suggests that shallow cumuli exhibit a large range of mesoscale organizations from seemingly randomly distributed cloud clusters to wind-parallel street lines or arcs  can be measured using dropsondes,The distribution of clouds in the trade-wind boundary layer can be inferred from lidar-radar measurements, especially the cloud fraction near cloud base,The convective mass flux at cloud base can be inferred from the subcloud layer mass budget.In this section, we present arguments and results from ongoing analyses that show that the first of these premises appears sound, and we discuss how the other two are currently being tested, and how the experimental strategy might be adapted based on the outcome of these tests.The experimental strategy of the EURECD of the horizontal wind P is the atmospheric pressure. D and 4A will thus critically determine the success of the campaign.A main component of the large-scale mass, heat and moisture budgets is the large-scale vertical velocity D from horizontal wind measurements using:A is the area of the region enclosed by it . When applied to aircraft measurements, this method requires a stationary wind field but makes no other assumption about the structure of the wind field.Measurements of the large-scale vertical motion on the time and space scale of individual airborne observations have long been recognized as being essential to understand how cloudiness develops and to calculate the heat and moisture budgets of the lower troposphere, but so far generally thought to be impossible. During ATEX, BOMEX, ACE-I and DYCOMS-II campaigns, attempts were made to estimate the large-scale divergence from rawinsonde sounding networks and/or aircraft data at a particular level using the “line integral” method , HALO flew horizontal circles of 45–48 min (160 km diameter) at an altitude of 9 km. Twelve dropsondes  were released intensively along each circle, measuring the vertical profiles of pressure, temperature and humidity with an accuracy of 0.4 hPa, To answer this question, this methodology was tested during the NARVAL2 campaign, which consisted of ten research flights of HALO, and took place in the EURECD and D and D and D and To test the method, pairs of circles were flown in the same air mass . The idea was that if the wind field was sufficiently stationary, and the measurements by the sondes were physical, one would expect similar answers to arise between a pair of circles flown in the same airmass. Satellite imagery targeted the flights to regions of suppressed convection, with a relatively more active shallow cloud layer during the second pair of circles, with cloud tops reaching sometimes 2–3 km, than during the first pair, with cloud tops rarely exceeding 1.5 km . As shown in Fig. 4A will be optimized.Three further issues are currently being explored, also in combination with high-resolution simulations which will be used to emulate different sounding strategies: (1) The minimum number of sondes to be dropped along each circle to reach equivalent results, (2) the spatial scale over which the large-scale dynamics best correlates with the macrophysical cloud properties, and (3) the influence of vertical shear of the horizontal wind, which is much more pronounced during the winter season. Depending on the result of these investigations, the number of sondes to be dropped, as well as the size of the circular flights to be flown during EUREC4A strategy will be to measure the cloud fraction within the trade-wind boundary layer, especially around two critical levels: just above cloud base (around 1 km) and around the trade-inversion level (around 2 km).An additional important and novel element of the EUREC4A, we propose to use the ALiAS backscatter lidar , was pointing horizontally towards the port side of the ULA. The ULA flew a series of horizontal legs of rectangular shape within the subcloud layer and above cloud base within a field of shallow cumuli  is being considered to enhance the cloud detection range. The combination of lidar and radar measurements should further improve the restitution of the cloud mask over this distance.To test the approach, measurements from a field campaign which took place on 1–6 June 2017 in Ardèche  and during which a lidar was mounted horizontally on an Ultra-Light Aircraft (ULA) are being analysed. The lidar, an eye-safe 355-nm backscatter lidar similar to the ALiAS lidar Chazette  to be usThe feasibility of the approach will be further tested using LES and by applying to LES outputs the McRALI (Monte Carlo Radar and LIdar) simulator of the lidar and radar instruments on board the ATR-42. McRALI is a forward Monte Carlo model , and the microphysical properties will be derived from the combined analysis of radar-lidar measurements, passive radiometers and in situ measurements Sect. . VerticaFinally, measuring the radiative effects of clouds will be critical to assess the coupling between clouds and their large-scale environment. Vertically integrated estimates will be derived from broadband radiative fluxes measured near the surface, near the inversion level and in the upper troposphere, and vertical profiles of the radiative heating rate will be inferred from radiative transfer calculations using observed atmospheric and cloud properties.4A a direct measure of convective mixing will also be provided in terms of the area-averaged mass flux at, or near, cloud base, M. Two independent methods will be used to estimate M: one based on direct measurements of the fractional area covered by active clouds and of the vertical velocity within them; the other based on the mass budget of the subcloud layer.To test the hypothesis that lower-tropospheric mixing critically influences the trade-cumulus cloud fraction at cloud base  with the value that is diagnosed directly from model output of cloud-core vertical velocity and cloud-core area fraction. The quantitative consistency between both estimates is sensitive to the definition of 4A field campaign, the present method will be refined by defining D, which are associated with different precipitation fluxes and different degrees of convective organization.A preliminary analysis of large-eddy simulations representative of typical trade-cumulus conditions . It will help us to test the model physics further, and also better understand the cloud feedbacks produced by these models. Indeed, there is ample evidence that single-column simulations of shallow cumuli can help understand low-cloud feedback processes and their dependence on process representations  from EURECes Sect. .4A is expected to contribute to the evaluation of the cloud and wind retrievals from two new flagship satellite missions of the European Space Agency: ADM-Aeolus and EarthCARE, that will provide unprecedented information on clouds and circulation.Observations from field campaigns are not only fundamental to investigate the physics of trade-cumuli but also to test, and eventually improve, the instruments and algorithms of remote sensing that are used to observe the Earth from space. Beyond the evaluation of cloud retrievals from current satellites, EUREC4A, the instruments on-board HALO and the ATR-42 aircraft will sample almost the full spectrum of wavelengths of atmospheric electromagnetic radiation (from the UV to the microwave), making it possible to retrieve a wide range of geophysical properties. Moreover, the UV HSR Doppler wind lidar operating at 355-nm and the 95 GHz Doppler cloud radar will provide products comparable to those obtained from the ADM-Aeolus and EarthCARE satellites. When flying underneath the satellite orbits, it will thus be possible to make direct comparisons between airborne and space-borne measurements. The in situ observations will help interpret the remote sensing in terms of geophysical variables, and the comparison between airborne and space-borne measurements will help evaluate some of the limitations of the satellite remote sensing.During EUREC4A, jointly with high-resolution simulations from weather forecast models and LES simulations of the campaign area, will help quantify these different sources of uncertainty and test some of the hypotheses used in the cloud or wind retrieval algorithms. A few examples are given below.The main limitations of remote sensing are due to the lack of sensitivity of the sensors , the inability to exploit some measurements near the surface  and the poor spatial resolution of the measurements . For passive measurements, which have the best spatial coverage, a particular challenge is identifying sufficiently unique information to deconvolve the atmospheric vertical structure from signals that necessarily integrate over this structure. The synergy of in situ, airborne and space-borne measurements during EURECSatellite instruments like MODIS or MetOP measure radiances in different wavelength channels, and these measurements are used to retrieve cloud droplet number, cloud phase, optical thickness, and droplet or particle size at cloud top at a spatial resolution of about 1 km. This resolution is insufficient for the observation of shallow cumuli. The specMACS instrument on-board HALO Appendix  and may Another key property of clouds for which satellite retrievals remain very uncertain is the cloud liquid water path (LWP). Most of today’s knowledge on the global distribution of cloud liquid water is derived from polar orbiting satellites that measure radiances in the thermal infrared and microwave spectral regions. However, given the coarse spatial resolution of these measurements , the LWP retrievals critically depend on the estimated cloud fraction  or to generate precipitation fields (as done as part of the GPM mission), it is crucial to combine curtain measurements with observations from wide swath instruments. For this purpose, LES simulations are often used to get statistical information about the three-dimensional structure of the cloudy atmosphere. By providing the reference data set necessary to assess such statistics Sect. , EUREC4AFinally, the LNG (lidar) instrument on-board the ATR-42 will have the capability to mimic ADM-Aeolus measurements: the 355-nm HSR Doppler wind lidar of the satellite will point 35 deg from nadir  to derive profiles of the horizontal wind component, and will also regularly point to nadir for calibration. LNG measurements along the satellite orbits and in the same viewing direction, together with in situ measurements and other airborne observations, will help evaluate the L2A  and L2B  ADM-Aeolus products over distances of several hundreds of kilometres.4A campaign will provide an opportunity to address additional scientific issues. A few of them are mentioned below in the context of what we call EUREC4A++, but more are almost certain to arise in the next years.The intensive observations of the atmosphere and of the surface that will be collected during EURECIn addition to providing large-scale context for the aircraft missions, measurements by the large-scale sounding array will supplement (and test) meteorological analyses to help answer scientific questions such as: What is the role of transient disturbances and their influence over large-scale vertical motion in modulating convective mass flux and large-scale diabatic heating? What drives the diurnal cycle of vertical motion and clouds in the trades?Mounting evidence indicates that the Hadley cell over the remote oceans is characterized by a pronounced diurnal cycle in overturning motion, quite distinct from the influences of land . In this context, unravelling the impact of microphysical processes on cloud macrophysical properties or radiative fluxes is challenging because microphysics, cloud macrophysics and large-scale environmental conditions vary in concert. Given that the large-scale dynamical and thermodynamical conditions, and cloud macrophysical properties, will be quantified by EUREC4A will offer several opportunities for microphysical measurements: besides in situ liquid and total water content, cloud droplet size distribution and particle imaging on-board the ATR-42  and winds. Past studies have investigated which parameters that represent the large-scale atmospheric state may best predict low-level cloud amount (sometimes referred to as “cloud-controlling” factors). Although this is challenging within the trade-wind cumulus regime—there is no single strong predictor, and correlations on timescales less than a month are small—the correlation between low cloud amount and the near-surface wind speed appears one of the stronger correlations  numerical weather forecasts using the Advance Research Weather Research and Forecasting (WRF) model. By providing a reference data set for the evaluation of cloud, turbulence and convective parameterizations, EUREC4A will help improve the physics of the model, and eventually the quality of the rainfall forecasts.More specifically, EUREC4A can be used to test closure assumptions, as discussed, but measurements of convective fluxes would provide an opportunity to test how the convective scheme distributes the energy it carries across cloud base.Another important objective of the experiment is to provide field experimental data by which new and existing convective parameterizations can be tested. Measurements of mass fluxes during EURECWe know from many observations that the vertical enthalpy flux establishes a temperature lapse rate that is very close to moist adiabatic, and most existing schemes are designed to accomplish this. For this reason, comparing the parameterized enthalpy flux against observations is a weak test of performance. On the other hand, there is no corresponding universal water vapour profile, and it can be shown that the vertical flux of water depends on such processes as entrainment and cloud microphysics. For this reason, the vertical subgrid-scale water flux by a convection scheme also presents an opportunity for a strong test of convective schemes.4A, the density of the sondes, and the availability of water vapour lidar profiling, and the variety of radar products for estimating precipitation, should provide an excellent opportunity to constrain the water budget, perhaps to a degree that it can help test convective parameterizations. Fortunately, in the Tropics, fluctuations of moist static energy are strongly dominated by fluctuations in water vapour, because temperature perturbations are usually very small above the boundary layer. Thus, the moist static energy budget also offers and opportunity for deducing the convective flux of water vapour, principally by estimating the terms in the budget, or partially integrating measurements of the budget from the top of the atmosphere (or the surface) to the flight level, and then estimating the convective flux as a residual.Measuring the vertical flux of water in a field programme is extremely challenging, as the decisive component is the small residual between large, but opposed, vertical turbulence fluxes and those by precipitation. During EURECh is the moist static energy, 4A by obtaining more accurate estimates of vertical velocity as well as improved estimates of radiative and surface energy fluxes. By providing more accurate field data sets—ones satisfying column water and moist static energy budgets—more rigorous tests of cumulus parameterizations should be possible. During EUREC4A, these methods will be tested for regimes of shallow convection. If successful they could later be applied in regions of deep convection.Note that it will be possible to assess the overall quality of the field measurements needed to test convective schemes by verifying that:terms in . Hopeful4A will also be an opportunity to study ocean-atmosphere interactions in the Atlantic, especially the role of ocean mesoscale eddies. The ocean is a fundamentally turbulent fluid full of fine-scale structures such as eddies, fronts, jets and filaments  estimate the role of these eddies in modifying atmosphere-ocean coupling and in influencing the mesoscale organization of the atmosphere and shallow clouds in particular.Inspecting historical ship data in the EURECMoreover, a synoptical study from different research vessels measuring different mesoscale eddies across the experimental area will provide new information on water-mass characteristics advected by the regional eddies. These are of twofold importance, as they inform studies of mesoscale eddies in general, but also in a particularly interesting region where over a narrow zone of longitudes the upper and lower limbs of the Atlantic Meridional Overturning Circulation flow over one another. A relatively wide range of mesoscale eddy observations will provide quantitative assessments of their role in transport of mass, heat, freshwater, carbon and other biogeochemical variables enabling a measure of the role of the oceanic mesoscale in this overturning circulation.4A campaign. More information about the instrumentation and the measurements envisioned is given in Appendix The observing strategy will make use of near real-time satellite altimetry data  to identify ocean mesoscale eddies and then one of the ships will be used to survey the eddy and to deploy autonomous oceanographic observing platforms such as underwater electric gliders and wave-gliders. A second ship will characterize the surrounding background field in parallel. Vertical profiling of the water column  will be measured. Argo profiling floats will be deployed within anticyclonic eddies within the Guiana and North Equatorial currents in the year preceding the EUREC4A will help build a data set capable of evaluating a wholly new generation of coupled ocean-atmosphere models, ones capable of resolving (rather than parameterizing) both convective eddies (cumulus convection) in the atmosphere, and the mesoscale dynamics of the ocean.Together, and perhaps the biggest plus, is that oceanic and atmospheric data collected during EUREC4A will help train the next generation of regional climate scientists and operational forecasters, develop databases that will facilitate the dissemination and use of the data collected in the area during field studies, and will promote international partnership and collaboration networks.Building national and regional resilience to increasing climate variability, climate change and extreme weather events in the Caribbean includes increasing national and regional weather and climate data, related knowledge platforms and human capacity. By involving university students and other young scientists of the region in the field campaign and the long-term research activities related to it, EUREC4A campaign will test developing ideas about what controls the cloud amount in the trades. It should elucidate the role of convection and large-scale circulations in low-cloud feedbacks and thus address one of the central questions of the World Climate Research Programme’s Grand Challenge on Clouds, Circulation and Climate Sensitivity  and NARVAL2 (August 2016) campaigns, as well as extensive experience from process models. Ongoing analysis of these measurements and simulations are being used to test and refine the experimental strategy of EUREC4A so as to maximize the scientific gains from the planned measurements.By characterizing, for the first time, both the macrophysical properties of shallow cumuli and the large-scale environment in which convection and clouds are embedded, the EURECA compact and well-defined experimental strategy opens up the mission to other partners with complementary interests. This campaign should therefore be considered as an opportunity to nucleate larger international efforts and to underpin additional investigations ranging from factors influencing cloud microstructure and warm rain formation, to the role of mesoscale eddies in the ocean.


Wearable potentiometric sensors have received considerable attention owing to their great potential in a wide range of physiological and clinical applications, particularly involving ion detection in sweat. Despite the significant progress in the manner that potentiometric sensors are integrated in wearable devices, in terms of materials and fabrication approaches, there is yet plenty of room for improvement in the strategy adopted for the sample collection. Essentially, this involves a fluidic sampling cell for continuous sweat analysis during sport performance or sweat accumulation via iontophoresis induction for one-spot measurements in medical settings. Even though the majority of the reported papers from the last five years describe on-body tests of wearable potentiometric sensors while the individual is practicing a physical activity, the medical utilization of these devices has been demonstrated on very few occasions and only in the context of cystic fibrosis diagnosis. In this sense, it may be important to explore the implementation of wearable potentiometric sensors into the analysis of other biofluids, such as saliva, tears and urine, as herein discussed. While the fabrication and uses of wearable potentiometric sensors vary widely, there are many common issues related to the analytical characterization of such devices that must be consciously addressed, especially in terms of sensor calibration and the validation of on-body measurements. After the assessment of key wearable potentiometric sensors reported over the last five years, with particular attention paid to those for medical applications, the present review offers tentative guidance regarding the characterization of analytical performance as well as analytical and clinical validations, thereby aiming at generating debate in the scientific community to allow for the establishment of well-conceived protocols. T. TNatureex situ operation involving: the evaluation of the linear range of response  . T. T52]. TContinuing with pH monitoring, but this time with demonstrations of explanted rabbit and donated human hearts undergoing ischemia, Chung et al. reported a wearable containing interconnected arrays of miniaturized potentiometric pH sensors that are encapsulated in thin, low-modulus elastomers that would allow future non-invasive measurements on the surface of the beating heart . The pH in vitro test of this concept was carried out by means of a smartly designed experiment in which the diffusion of acid solution from a reservoir to a surrounding phosphate buffered saline (PBS) solution was monitored. After this test, the paper demonstrated several medical applications. Firstly, a balloon catheter pH sensor device was fabricated and used with a single ex vivo rabbit heart preparation, which underwent 30 min of global no-flow ischemia followed by reperfusion. The measured pH was stable at the beginning of the experiment, and it then decreased slowly over 30 min under ischemia and recuperated quickly up to stabilization upon reperfusion. All these variations were biologically justified. In addition, a skin-like stretchable membrane based on the pH arrays was also prepared (ex vivo rabbit heart preparations (n = 3) and a single human right ventricle preparation. Unique spatiotemporal mappings of pH were provided for stationary conditions, ischemia-reperfusion as well as different reperfusion times owing to the use of the wearable pH sensor. The authors envisioned other applications of the developed device for biological research, such as surgical tools and long-term implants, although they do not propose any validation of the ex vivo observations.The aim of having electrode arrays (30 pH sensors) is to provide a pH mapping of the organ. The first in vivo clinical application in domestic pigs. Thus, extracellular pH and In the context of monitoring ischemia-reperfusion events, Tahirbegi et al. reported on a sensor array of typical all-solid-state electrodes made of copper pins covered by ISMs for pH and ndoscopy . While tin vivo measurements and, therefore, the reliability of the observations could be questionable besides the successful demonstration of the electrode array operation. On the other hand, while the electrodes provide a continuous recording of the potential during intervention, pH and However, the analytical characterization of the electrodes is limited to the establishment of the calibration graph and between-electrode reproducibility, and there is no validation for in vivo experiments were carried out: gastric pH measurements , subcutaneous pH measurements by implanting the electrodes under the skin or by placing such electrodes under the skin using needles. The pH measured under the skin over 1 min displayed a value of 7.0 ± 0.1 and the gastric pH fluctuated from 1 to 3. Once more, the analytical characterization of the pH electrode is underestimated, and validation was not presented. Indeed, it is difficult to establish a validation protocol for this kind of measurement and possibly, in vitro accuracy assessments could be considered sufficient.The thread-based pH sensors reported by Mostafalu et al. could be also considered non-wearable devices because of the way in which they are implemented for on-body measurements . The aut2, over 1–5 min) with a short-lived effect, whereas pilocarpine and methacholine-based hydrogels ensure a long duration of secretion (>60 min). Importantly, later studies have shown the use of nicotinic cholinergic agonist, carbachol, to provide prolonged and localized sweat stimulation . A. AK+ detThe only example that we could find in the literature involving a wearable potentiometric sensor to analyze a biological fluid different than sweat and interstitial fluid is based on an intraoral device implemented in a porous dental retainer capable of analyzing n saliva  62]. Th. ThNa+ iper se.After this deep analysis of the selected recent contributions in the field of wearable potentiometric sensors for medical applications, it is worthwhile mentioning that only sweat detection of nophores , the lacIn addition, iontophoresis-induction for sweat collection seems to offer a successful approach to wearable potentiometric sensors for medical applications, rather than incorporating a sampling cell. Indeed, other wearable sensors have employed commercial iontophoresis units for sweat collection that may be further incorporated with potentiometric sensors . As an e applied . The autAs a general trend when developing a wearable potentiometric sensor, the analytical characterization of electrode performance is underestimated because it has been reported for regular electrodes prior to implementation into the wearable configuration. Thus, calibration curves of the electrodes outside the wearable device are always presented but other features that are important for the reliable quantification of the ion analyte concentration typically go unnoticed. Thereafter, it is essential to establish a validation protocol that allows for accuracy assessment.In this sense, we discuss in the following a number of issues related to the evaluation of the analytical performance of wearable potentiometric sensors as well as some guidelines that may help in further successful application to gather trustworthy medical information.The calibration curve selected to transform the potential readout of the wearable potentiometric sensors into the concentration of the ion analyte is crucial to obtain accurate results. There is a common practice of recording the calibration graph within the linear range of response just before the implementation of the electrodes into the wearable and then use the fitting  to calculate the concentration of the ion analyte in sweat. In general, the curve is based on three concentration points. However, this strategy has some issues that need to be clarified before accepting it as a universal approach for the calibration of the wearable. It is necessary to demonstrate that the recorded calibration does not vary owing to several reasons: (i) the implementation of the sampling approach, (ii) portability during on-body measurements and (iii) drift of the electrode response because of (bio)fouling or component leaching. As a consequence, a comparison of the calibration graph obtained before and after the incorporation of the sampling cell or absorbent pad, as well as before and after on-body measurements, is essential to confirm that the initial calibration graph can be used to calculate the concentration of the ion analyte in sweat in a reliable manner. Interestingly, resiliency tests based on the evaluation of the calibration graph before and after the electrodes face mimicked corporal movements , potentially reinforcing the right-directed use of the initial calibration graph.Concerning electrode drift, it is necessary there is an evaluation of this parameter in a medium-term experiment to establish if any correction of the calibration parameters is required. As on-body experiments with wearable potentiometric sensors for medical applications usually involve a period no longer than 1 h, we would suggest assessing the electrode drift  in artificial or real human sweat  over ca. 2 h for reliable assessment. In addition, the correction of the calibration slope with the temperature will offer a more reliable calculation of the concentration of the ion analyte. Indeed, a combination of both drift and temperature corrections have been already used for in situ environmental water measurements via potentiometric sensors ,74.Other matters surrounding the calibration graph is the selection of the background electrolyte and the use of either activity or concentration of the ion analyte. The use of artificial sweat (or other fluids) as background for the calibration graph is advantageous in that it allows the ionic strength to be known and, therefore, the interconversion concentration-activity can be easily determined through the two-parameter Debye−Hückel approximation . NonetheWhether all these aspects are considered in the elaboration of the calibration graph, quantitative results provided by a wearable potentiometric sensor will be more trustworthy, which is important for related clinical decision-making. Otherwise, the observed data may be interpreted only qualitatively, i.e., to identify critical cases with a probability of presenting a certain disease.Reversibility. The so-called ‘carry-over test’ evaluates the possibility of measuring increasing and decreasing steps in the ion analyte concentration . It is cResponse time inherent to the electrode and response time associated to the device involving the sample collection. When a sampling cell is used for this purpose, this latter comprises the time needed to fill the sensor compartment and depends on the sweat rate of the subject. It is here also critical to adopt a correction of the measurements depending on the sweat rate at each moment, just as in the case of the Javey group . NotablyOn the other hand, it is hard to assure on-body monitoring in real time because a certain amount of sample is always needed to fill the reservoir in which the sensors are embedded. Thereafter, the reservoir continuously renews the sweat, but this does not occur exactly at the same time the individual is sweating. Time is needed for the generated sweat to reach the sensors’ chamber and then each sensor , which involves a delay between the sweating process and data observation.In the case of an absorbent material coupled to iontophoresis-based sweat collection, the response time depends on the filling of the pad together with several minutes of potential recording .0 of the calibration graph by applying a controlled potential or current as well as short-circuiting . T. T57]. TConsidering an ideal case, first on-body trials should involve a system in which more than one electrode of the same type are included in the wearable in order to obtain reproducibility of the observations. Furthermore, it may be also interesting to incorporate a second reference electrode to confirm that the selected design provides a constant potential during on-body tests. These kinds of experiments will reinforce the veracity of the analytical measurements and, consequently, further decision-making by the physician will be more reliable.ex vivo tests. We are referring for example to transdermal detection of per se, as identified in the paper.Wearable device technology combined with potentiometric ion sensors adhering to an all-solid-state concept has demonstrable potential in the monitoring of physical status during sport performance as well as clinical medicine through sweat analysis. Current investigations involving physical activity focus on the development of a sampling cell that supplies real-time analysis of the sweat of the individual. In contrast, devices that have demonstrated successful gathering of medical information are based on iontophoresis-based sweat induction that allows obtaining one-spot ion analyte concentration as the average of the measurements over the portability of the sensor. As far as we know, wearable potentiometric sensors have only been applied for the diagnosis of cystic fibrosis via on-body measurements of In general, we have found a lack of rigorous assessment of the analytical performance of wearable potentiometric ion sensors, yet this is extremely important to assure minimum error in the final calculation of the concentration of the ion analyte. This is especially crucial when selecting the calibration protocol of the sensors. In addition, appropriate validation of on-body measurements has generally not been accomplished. With the present review, we are seeking to establish a tentative guidance for the successful characterization and validation of a wearable potentiometric ion sensor, or at least generate debate within the scientific community that allows for the establishment of a well-conceived analytical protocol. The immediate future of wearable potentiometric sensors should rely on the provision of validated and therefore trustable data, before opening the range of clinical targets.


Diabetes is a very complex condition affecting millions of people around the world. Its occurrence, always accompanied by sustained hyperglycemia, leads to many medical complications that can be greatly mitigated when the disease is treated in its earliest stage. In this paper, a novel sensing approach for the early non-invasive detection and monitoring of sustained hyperglycemia is presented. The sensing principle is based on millimeter-wave transmission spectroscopy through the skin and subsequent statistical analysis of the amplitude data. A classifier based on functional principal components for sustained hyperglycemia prediction was validated on a sample of twelve mice, correctly classifying the condition in diabetic mice. Using the same classifier, sixteen mice with drug-induced diabetes were studied for two weeks. The proposed sensing approach was capable of assessing the glycemic states at different stages of induced diabetes, providing a clear transition from normoglycemia to hyperglycemia typically associated with diabetes. This is believed to be the first presentation of such evolution studies using non-invasive sensing. The results obtained indicate that gradual glycemic changes associated with diabetes can be accurately detected by non-invasively sensing the metabolism using a millimeter-wave spectral sensor, with an observed temporal resolution of around four days. This unprecedented detection speed and its non-invasive character could open new opportunities for the continuous control and monitoring of diabetics and the evaluation of response to treatments (including new therapies), enabling a much more appropriate control of the condition. Over the years, technological advances have led to the enhancement of medical diagnosis, treatments and procedures, and improving quality of life for patients ,2,3. In Nowadays, the diagnosis and follow-up of diabetes are based on classical enzymatic methods, such as plasma glucose  or Oral Glucose Tolerance Test (OGTT)), and glycohemoglobin (A1c or HbA1c) measurements ,13,14. AThere are novel test methods for diabetes detection and monitoring focused on non-invasive blood glucose measurement based on IR technologies ,18,19, wIn this paper, which continues our previous work for the non-invasive detection of sustained hyperglycemia in animal models , a diffeThe motivation to employ millimeter-wave radiation for biomedical applications originates from its capability to penetrate and sense without harm the biological tissue and structures. In particular, the millimeter-wave frequency range exhibits great potential for the non-invasive blood glucose level monitoring ,24,25,26In our previous work, the hyperglycemia condition was clearly discriminated from normoglycemia and two different types of hyperglycemia were detected: Hyperglycemia caused by overfed animals (obese mice) and hyperglycemia due to diabetes condition (diabetic mice). In addition, it was proven that such discrimination using millimeter-wave spectroscopy sensing was not influenced by the instantaneous glucose level, skin thickness, or skin phenotypes ,28. The The biological samples studied here involve numerous metabolites and substances, which resonate at different partially overlapping frequencies when probed with electromagnetic waves. Therefore, the measured spectral response is analyzed here using a non-targeted metabolomic approach ,30,31. TIn this work, we provide evidence that the same approach can be employed with high accuracy for the early detection and monitoring of the hyperglycemia typically associated with diabetes, with unparalleled speed and time resolution. We refer here to these studies as longitudinal studies of hyperglycemia. The development of hyperglycemia in mice with induced diabetes could be identified even before the full diabetic state has been established. These results show that the sensing principle is very sensitive to metabolic changes associated to sustained hyperglycemia and this, consequently, demonstrates its great potential for both the early non-invasive detection of diabetes and the accurate monitoring of the disease. In fact, it enables the following of individuals in a timeline across the dynamic evolution of the diabetic state. In this paper, a preliminary validation test has been performed using a classifier based on functional principal components for hyperglycemia typically associated with diabetes. A validation test had been carried out on a population of 12 mice with six diabetic mice and six control mice (normoglycemic mice) obtaining a correct classification rate of 100%. Then, 16 mice with drug-induced diabetes were studied at different moments of their condition using the same predictor. These results have been evaluated to identify the mechanisms behind the metabolic sensing capabilities for monitoring the early development of hyperglycemia along 14 days after completion of the diabetes induction process.All the measurements were carried out on a group of mice representative of different glycemic states. Sample population was designed considering two important targets: Validate discrimination of hyperglycemia, typically associated with diabetes, on a test sample by using a classifier based on functional principal components, and, more importantly, study the spectral response over time on transition cases from normoglycemia to hyperglycemia, which determines the time resolution of the sensing approach.db/Lepdb [There are 2 main classes in the sample: Normoglycemia and hyperglycemia. Healthy mice were considered as normoglycemic cases and diabetic mice genetically mutated to be insulin-resistant Lepdb/Lepdb  as hyperFor the validation test, 2 samples from the mice population (training sample and test sample) were employed and measured separately. Two experiments were performed at different times. The training sample corresponded to the sample of the mice population measured and presented in our last publication . The tesIn the second experiment, 16 diabetized mice were also measured simultaneously with the 6 diabetic mice and 6 healthy mice (test sample) as reference. The experiment lasted 19 days and 4 measurements were performed. The measurements started on the last day of the treatment  and finished 14 days hereafter. During the experiment, 6 diabetized mice died before the 3rd measurement (10 days after treatment) due to the adverse effects of the drug .All animals were purchased from Elevage-Janvier  and housed individually in pathogen-free conditions at the Centro de Investigaciones Energéticas, Medioambientales, y Tecnológicas (CIEMAT) Laboratory Animals Facility (Spanish registration number 28079-21 A).All experimental procedures were carried out according to European and Spanish laws and regulations . Procedures were approved by the Animal Experimentation Ethical Committee of the CIEMAT according to all external and internal bio-safety and bio-ethics guidelines, and by Spanish competent authority with registered number PROEX 176/15.Firstly, it is important to highlight that the body hair from the back of the mice was regularly cut off to facilitate the handling of their skin. Besides this treatment, no special procedures were installed for the measurements. It has been proven earlier that the sensing approach was insensitive to the skin properties of the animals such as hairs ,28. ExceThe spectroscopic measurement was taken directly on a skin fold of the mice (non-invasively). A skin fold on the mice back was placed between 2 previously aligned straight cuts of a WR10 waveguide, as shown in All measurements were carried out by using a spectroscopy system , which iThe raw sensing data were processed using functional data analysis (FDA), which is a current topic in statistical mathematics of continuous signals. The digital acquisition of data implies that the spectral data were observed at a discrete set of frequencies thus that the sample data were given by The first step in the FDA is to obtain a functional data set from the spectra measured at discrete frequency points . To this end, the spectra are assumed to belong to a finite-dimensional space generated by a basis B-spline . This apB-spline . The degThe aim of this analysis was the discrimination of spectra according to their glycemic states (normoglycemia and hyperglycemia). Taking into account the small sample size, regression models are not feasible. As an alternative, we proposed a classifier based on Functional Principal Component Analysis (FPCA) .FPCA is an extension of the classical PCA (for multivariate data) to the FDA context. The functional principal components are generalized linear combinations of the curves, uncorrelated and with maximum variance. In general, the data set . All thedata set .As mentioned above, this work focuses on sensing the metabolic state during hyperglycemia in mice. Even more importantly, the work determines, how sensitive the proposed method is to detect glycemic changes associated with diabetes and analyzing the spectral response in the W-band. Hyperglycemia was first validated on an animal sample using functional principal component analysis. Subsequently, a group of mice with drug-induced diabetes was studied at different instances using the same methodology. The results obtained in both tests are shown below.A sample of 20 mice of different strains representative of equally distributed normoglycemia and hyperglycemia cases have been defined as the training sample and the second sample of 12 mice has been taken as the test sample. Both samples have been described in more details in Both the training sample and test sample were acquired using different signal power configurations due to different transmittance levels. As seen in The blindly determined animal scores after proper calibration of the system using the training sample are shown in As mentioned in the introduction, the temporal evolution of glycemic states  has not been reported yet using non-invasive techniques. With the described mm-wave spectroscopic sensing it was straightforward to measure the time evolution of the glycemic state of the various mouse groups, due to the stability of the instrument and the robustness of the FPCA approach, capable of blindly classifying the diabetic mice. Therefore, we have studied the sensitivity of the proposed approach to changes in glycemic states associated with diabetes on 16 mice with drug-induced diabetes see . These mIt is important to remark that the biological response of each mouse to the diabetes induction process may vary as some mice are more resistant to the drug (Streptozotocin). This biological variation is also captured by the proposed sensing system, as depicted in In this work, a non-invasive and reliable method for the assessment of sustained hyperglycemia typically associated with diabetes by sensing the metabolism has been validated. The sensing method relies on a mm-wave transmission spectrometer and FPCA approach. The FPCA approach has been tested on a sample of 12 mice with a 100% correct assignment rate. Even though samples involved in the results had different transmittance levels and biological diversity (different mice strains), clear discrimination was achieved, irrespective of the individual skin properties, demonstrating the reliability of the approach for hyperglycemia detection. Furthermore, high sensitivity and temporal accuracy for the monitoring of glycemic changes in mice has been experimentally demonstrated by a longitudinal study on a group of sixteen mice with drug-induced diabetes. The stability of the mm-wave instrument together with the robustness of the FPCA approach allows us to clearly track the evolution of mice with drug-induced diabetes from normoglycemia to hyperglycemia, enabling the prompt detection of new hyperglycemia cases. These unprecedented results support the great potential of the proposed method not only for the diagnosis of diabetes but also for the early detection of diabetes and monitoring glycemia evolution in diabetics with a resolution of a few days. Although the minimum length of time required for the method to detect glycemic changes is still to be evaluated, the results indicate that different hyperglycemic states associated with diabetes are detected with only four days of uncontrolled occurrence. The obtained results indicate that the proposed sensing approach offers a comparable measure to that provided by the HbA1c test, but the lead times are very short compared to the periods required for the HbA1c test. Therefore, a correlation study is currently performed between the spectral measure presented here and the glycated hemoglobin value in patients suffering Type 1 Diabetes. The spectroscopic system provides results in seconds and it is a highly reliable instrument not requiring frequent calibration. Moreover, the system is not based on disposables or consumable materials, reducing substantially the operational costs, which can be made very compact and realized cost-efficiently. Therefore, we consider that the presented approach has great potential in developing a new non-invasive technique to improve medical proceedings for combating diabetes mellitus.


An exponential increase in large-scale infrastructure facilitates the development of wireless passive sensors for permanent installation and in-service health monitoring. Due to their wireless, passive and cost-effective characteristics, ultra-high frequency (UHF) radio frequency identification (RFID) tag antenna based sensors are receiving increasing attention for structural health monitoring (SHM). This paper uses a circular patch antenna sensor with an open rectangular window for crack monitoring. The sensing mechanism is quantitatively studied in conjunction with a mode analysis, which can uncover the intrinsic principle for turning an antenna into a crack sensor. The robustness of the feature is examined when the variation of crack position associated with an aluminum sample and the antenna sensor is considered. The experimental results demonstrate a reasonable sensitivity and resolution for crack characterization. Structural health monitoring (SHM) enabling with wireless sensor networks (WSNs) is widely used for condition-based maintenance of large-scale infrastructure . DespitePower consumption and power harvesting/scavenging capability are two issues in the design and development of wireless passive sensors. Recently, simultaneous wireless power and information transfer (SWIPT) is receiving increasing attention in fifth generation 5G) cellular network ,5,6. BecG cellulaEnabling with power harvesting from electromagnetic (EM) source, radio frequency identification (RFID) tag antenna based sensors are a promising candidate to be developed into wireless passive sensors ,11,12. ASince the sensing information is extracted from EM signature of antenna sensors through backscattering communication in the UHF RFID band, the RFID sensing system is quite susceptible to interferences from wireless channel . This scBecause the detuning based antenna sensor detects defect through varying the tag antenna’s impedance and gain, its sensitivity, resolution and robustness are influenced by the following factors. First, the defect detection underneath the antenna sensor is closely related to its mode and relative position between antenna and defect. This challenges the practical installation when the location of defect is unknown in priori. Second, the basic EM signatures suitable for sensing purpose are constrained. More to the point, the EM signatures, for example, power and phase, transfer the sensing information through backscattering in an analog form; hence, the sensing information is quite susceptible to interference and noise from both wireless channel and receiver. Third, the limited bandwidth in the UHF band imposes a tradeoff between sensitivity and dynamic range under a constant distance constraint. In addition, the multiple influences from both sensing and communication needs physical-based signal processing method for reliable feature extraction .Benefiting from low profile and low cost, patch antennas were used for crack sensing . The senThe severity of the failure depends on both the crack length and orientation with respect to the loading direction. Longitudinal cracks are the most common and dangerous cracks because they can reduce a structure’s cross section and therefore reduce its structural capacity/integrity. A patch antenna sensor was proposed to monitor the growth of crack in a sub-mm resolution . The craIn addition, the length and orientation of the crack can be detected using a 2D grid of conventional dipole tags in the UHF band with a commercialized RFID reader . In spitAbove all, the feasibility of crack detection and characterization has been widely studied in the literature. However, the sensitivity and reliability of crack detection are tightly related to crack position with respect to antenna mode and the size of metal to be mounted. This paper aims to investigate the reliability of crack detection and characterization via the mode analysis of an antenna. The antenna sensor studied here is dedicated for monitoring the evolution of already existing cracks or of junctions prone to cracks . The resIn this section, we first describe an interrogation method based on a measurable EM signature, named threshold power to activate tag, in the downlink of the UHF RFID system. Then, one patch antenna with an open rectangular window is designed for sensitive crack sensing.Under the hypothesis of line-of-sight (LoS) propagation between reader and tag antennas, the threshold power to activate the tag in reader antenna, From the antenna theory, the radiating patch and the ground plane can form a resonant cavity, so the sensitive part of patch antennas can easily cover its underneath area. Increasing crack depth can increase the effective electrical length of the antenna and therefore leads a shift of resonance to the lower frequency region. By this way, the patch antenna can be easily turned into a crack sensor. Due to the proximity coupling, the sensing performance of an antenna sensor, however, depends on the crack position with respect to the antenna mode.In general, the crack position may be hard to be predicted. The variation of sensitivity with crack position will affect the reliability of crack characterization. Therefore, the linearity in the sensing area is of paramount importance for robust crack monitoring. In this paper, a circular patch is used as a radiator. A rectangular window is opened in the center of the patch to increase the sensitivity when crack grows as well as to improve the robustness with respect to crack position. Meanwhile, the antenna sensor is designed for conjugate impedance matching to the tag chip of NXP UCODE G2iM+, the input impedance and typical read sensitivity of which are 21.2 − j199.7 Ω and −17.6 dBm at 915 MHz, respectively. The geometry of the antenna sensor used in this paper is similar with . To reduw) of 2 mm and a variable depth of d. For reference convenience, the crack depth is represented d1 = 1 mm, d2 = 2 mm, d3 = 3 mm, d4 = 4 mm, d5 = 5 mm, respectively. The antenna sensor is directly put on the surface of the aluminum sample. The relative position between the antenna sensor and longitudinal crack moves from Δ = −6 mm to Δ = 0 mm for quantitative analysis of its robustness. Like any other sensor, the calibration is an important issue. Therefore, five positions in the backside of the aluminum sample corresponding to Δ = 0 were simulated to refer the healthy state (d0 = 0 mm) and also to study the influence of antenna performance with respect to the sample.The detailed size and simulation setup of the antenna sensor are shown in In this section, the current distribution is analyzed in conjunction with a parametric study to demonstrate a potential way leading to low-cost design of wireless passive sensors. The quality factor of the antenna is extracted and discussed to uncover the intrinsic sensing principle associated with further feature extraction.The simulated current distribution of the antenna sensor at the healthy state is displayed in In general, a presence of crack will disturb the field distribution between the metallic surface and radiating patch. This perturbation will affect the radiation and stored energies, therefore, the resistant and reactant parts of input impedance. x-direction) or moves outside of the patch, the crack cannot be detected.Q) and the loss tangent of the dielectric, that is On a lossy dielectric, the radiation efficiency of an antenna can be approximated using the antenna quality factor  of the antenna sensor is 7.0 MHz/mm.The simulated radiation pattern and peak realized gain , the fabrication error of the antenna and tolerance in the tag chip, the resonant frequency of the antenna sensor may shift . In addiThe sensing performance of RFID tag antenna based sensor will degrade when the crack is not at its optimal position. In this paper, a circular patch antenna sensor with a rectangular window has been utilized for metal-mountable applications. The variation in the crack position is examined for quantitative investigation of robust crack monitoring. In conjunction with mode analysis, we find that the crack growth will constantly reduce the quality factor and therefore improve the realized gain of the antenna, where the profile is a key factor to determine the tradeoff between sensing and communication. Meanwhile, the size of the metallic geometry that the antenna sensors are going to be mounted has significant influence on their radiation performance, for example, directivity and efficiency. The experimental results validate that the uncovered sensing mechanism can provide potential guidance for robust feature extraction in longitudinal crack monitoring.In this paper, the antenna sensor has been demonstrated to work on a small beam with longitudinal crack. However, the antenna sensor needs to be miniaturized to be mounted on a smaller beam; the beam may also become one piece of large-scale infrastructure. Without a reference tag, the antenna itself can be calibrated after the installation. Using the feature of resonant frequency, the monitoring may be taken automatically with unmanned vehicles in harsh environments.


Achieving good environmental status in the Baltic Sea region requires decision support tools which are based on scientific knowledge across multiple disciplines. Such tools should integrate the complexity of the ecosystem and enable exploration of different natural and anthropogenic pressures such as climate change, eutrophication and fishing pressures in order to compare alternative management strategies. We present a new framework, with a Baltic implementation of the spatially-explicit end-to-end Atlantis ecosystem model linked to two external models, to explore the different pressures on the marine ecosystem. The HBM-ERGOM initializes the Atlantis model with high-resolution physical-chemical-biological and hydrodynamic information while the FISHRENT model analyses the fisheries economics of the output of commercial fish biomass for the Atlantis terminal projection year. The Baltic Atlantis model composes 29 sub-areas, 9 vertical layers and 30 biological functional groups. The balanced calibration provides realistic levels of biomass for, among others, known stock sizes of top predators and of key fish species. Furthermore, it gives realistic levels of phytoplankton biomass and shows reasonable diet compositions and geographical distribution patterns for the functional groups. By simulating several scenarios of nutrient load reductions on the ecosystem and testing sensitivity to different fishing pressures, we show that the model is sensitive to those changes and capable of evaluating the impacts on different trophic levels, fish stocks, and fisheries associated with changed benthic oxygen conditions. We conclude that the Baltic Atlantis forms an initial basis for strategic management evaluation suited for conducting medium to long term ecosystem assessments which are of importance for a number of pan-Baltic stakeholders in relation to anthropogenic pressures such as eutrophication, climate change and fishing pressure, as well as changed biological interactions between functional groups. Understanding and quantifying the space- and time-varying intensity of human pressures and the resulting responses of marine ecosystems are essential for evaluating the impacts of human activities on the future provision of the goods and services we derive from the oceans –4. The BBesides fishery, eutrophication is a strong pressure on the Baltic Sea ecosystem. Studies of the biological effects of eutrophication in the Baltic Sea are numerous. Significant effects on primary production, both total area production and distribution in the water column, phytoplankton biomass, plankton community composition, water clarity and oxygen conditions have been documented e.g. –22). In . In 22])http://marine-opec.eu/).To consider several ecosystem drivers simultaneously, a possibility is to apply models that integrate a wide range of pressures and processes in a common framework that enables holistic evaluation , 7–8. Tohttp://www.marine-vectors.eu/) and the Baltic Sea (current study).To construct a holistic management evaluation platform, a new whole-of ecosystem and cyclic full-feed-back Atlantis model , 29 is hAlthough the Atlantis model is the core of the present approach, some more detailed information, which will improve this holistic management evaluation platform, is more extensively available through other existing models. The HBM-ERGOM provides the Baltic Atlantis with high-resolution physical-chemical-biological and hydrodynamic information of the calibration year (2005) and the Atlantis output from the terminal projection year is processed with the FISHRENT fisheries economic model. A schematic overview of the models and how they are linked with the Baltic Atlantis is shown in The Baltic Atlantis implementation will become one of the most comprehensive integrated, dynamic, and spatially explicit bio-economic modelling tools of a marine system available in this region at present. In this paper, we present the implementation and parametrization of the Baltic Atlantis (using revision number 6191 of the main release of the software). . We demoWe present a new framework, with a Baltic implementation of the spatially-explicit end-to-end Atlantis ecosystem model linked to two external models, to explore the different pressures on the marine ecosystem . AtlantiThe first link is between a biogeochemical-hydrodynamic model and Atlantis. Detailed input for the hydrographic part of the Baltic Atlantis model is provided by the HBM-ERGOM model system  consistiThe second link is between Atlantis and a bio-economic fisheries model. The Atlantis output of the terminal projection year feeds into the FISHRENT model , which iThe way the three models (HBM-ERGOM–Atlantis–FISHRENT) are connected is based on a one-way offline linking. Information is fed from one model to another without accounting for any potential dynamic coupling or feedback processes. Information about hydrodynamics obtained from the HBM-ERGOM model is passed on as input to the Baltic Atlantis for the 2005 calibration year, and information about changes in biological production obtained from the Baltic Atlantis is, with respect to fish species biomasses, passed on as input to the FISHRENT KWB model, as illustrated in Year 2005 is chosen as the initial conditions year for the Baltic Atlantis calibration because it is the most recent year with the greatest overlap of available information between all the biological variables and parameters used in the Baltic Atlantis model. Furthermore, year 2005 is characterized by lack of extreme events, in either physical forcing  or significant ecosystem changes. In absence of data or other model outputs from that period for a given variable or parameter, the temporal search radius is extended to one year before and after 2005 until the closest estimate in time is found. Spatially averaged data were then averaged per quarter whenever data was available at a seasonal resolution. The process of informing the large number of biological parameters in the Baltic Atlantis model was based on an extensive review of literature to minimize the number of poorly constrained parameters. In a majority of cases, previous estimates of equivalent model parameters were already reported , or it was possible to derive first order approximations from available data . However, there were also a few Atlantis-specific parameters which had to be provided. The process to find these is described further down.The HBM-ERGOM model  and the external tracers for the dynamic boundary Box 0 –represenollowing , in lineAnnual river run-off and nitrogen deposition flux estimates, derived from the Review of the Fifth Baltic Sea Pollution Load Compilation for the 2013 HELCOM Ministerial Meeting , are use3), ammonia (NH4), silicate (SiO4), dissolved oxygen (O2), detrital material (dissolved organic nitrogen (DON) + detrital silica + particulate organic matter: labile and refractory detritus), primary  and secondary pelagic producers .Besides the hydrographic parameters, the HBM-ERGOM also provided the information about initial condition values, more specifically for the winter 2005 initial conditions of nutrients (nitrate (NOwww.smhi.se) and ICES  databases, and supplemented by the results of an extensive literature review, covering a period from 2003 to 2007. Initial conditions for benthic deposit feeders, polychaetes, soft- and hard-substrate filter feeders came from the compilation of data obtained from SMHI, ICES, DCE  and HERTTA  databases. The data used covered a period from 2003 to 2007. Literature information on coverage and/or biomass was obtained to estimate initial conditions for spatial distribution of macroalgae )s of cod . This iss of cod . The ress of cod . As expes of cod . ObservaThe distribution of numbers per age group shows a realistic exponential decline for all the age disaggregated functional groups, where the youngest individuals of a population are prone to the highest mortality. The age distribution is most even for seals because they have the most homogeneous survival rates once they survive the first vulnerable year. The abundance of that first age group is determined by the recruitment. Considering that exact mechanisms controlling recruitment are still not fully understood despite abundant data available  and manThe spatial distribution shows no extinctions in any polygon for all the vertebrates, with biomass fluctuating seasonally. The higher fluctuations of the vertebrates represent migrations between spawning and feeding grounds. This is why for instance cod biomass in certain polygons reaches zero .Lack of cyanobacteria probably does not affect the secondary production in the model, because they are not an important food source for zooplankton. Sedimentation and subsequent degradation of cyanobacteria are also not included in Atlantis and may lead to slight underestimation of hypoxia in the open areas of the model. Not accounting for these phenomena is unlikely to compromise the results of the current analyses because the salinities in the Kattegat, Western Baltic regions and southern Baltic proper regions, except in the immediate vicinity of the coast, are beyond the typical <12 salinity range where cyanobacteria appear in the Baltic . FinallyFurthermore, HBM-ERGOM outputs reveal that in Kattegat and the Western Baltic there exist very sharp gradients between very narrow but highly productive zones and offshore areas with low annual average phytoplankton standing stocks. These features are unlikely to be fully captured in Baltic Atlantis without a more detailed map of time-varying riverine and point source inputs to the model, such as the one offered by the DK-QNP model used to force HBM-ERGOM. Although such high spatial resolution details need not be considered to force the dynamics of fisheries, they are more important in better constraining biogeochemical cycling, and its control on seasonal and inter-annual variability in primary production.The nutrient load reduction scenarios allowed us to test our newly developed model in its responsiveness to system disturbances. The nutrient load reduction scenarios where chosen because the Baltic ecosystem is already characterized as a highly eutrophic system , 16. TheIn the model, it is mainly the dietary interactions that determine the response of planktivorous and piscivorous fish biomass for the analyzed nutrient reduction scenarios. However, the model parameterization could not be equally well constrained for all groups and processes. For instance, the prey-predator interactions involving cod, sprat and herring are well informed using abundant field data and robust model results from the Baltic SMS or EwE. On the other hand, there is little data to quantitatively describe the dietary interactions of many benthic animals, or if locally available, the issue of extrapolating accurately over many types of habitats remains. Benthic organisms, especially in the coastal zones, are known to be susceptible to changes in ambient oxygen conditions , stronglFor all scenarios, the overall biomass decreases, with a stronger signal when there are large reductions in river load. This is in line with the results from  who usedSignificant changes in Nephrops and detritus biomasses were as expected for the nutrient load reduction scenarios. For scenario #3 and #5, Nephrops decreases around 20% due to a decrease in their main food source, detritus. Labile and refractory detritus are a pool of fixed nutrients from faeces and non-predation mortality products. The decrease of this detritus pool is caused by a decrease of production of the rest of the ecosystem due to the reduced river load. In the scenario following the Baltic action plan, the Nephrops stock is reduced by 11%, less than for other scenarios. Consequently, the model response is proportional to load reduction and shows expected patterns and levels of effects on the different functional groups given current knowledge. This can be seen in context of a general propagation of the effect of the river load reductions through the whole ecosystem. When the small changes in biomass, which are generated in the scenarios, accumulate, then this might lead to a more extensive change of the detritus pool. This in turn can have an effect on those groups feeding on detritus, such as filter feeders, polychaetes, deposit feeders and Nephrops. Those multitudes of interactions is an argument for using an end-to-end ecosystem model to comprehend the more realistic perception of effects of nutrient load reductions taking into consideration the broader and complex biological processes, effects and interactions.Distinct benthic oxygen concentration increases were simulated in many areas according to nutrient load reductions, especially in the Western Baltic and the Baltic proper areas while less distinct in the deeper areas . Oxygen Saduria entomon  of all active biological groups in the Baltic Atlantis model averaged over the last five years . For vertebrates, for which good constraints on abundance/biomass distributions were available, “x initial” factor difference as relative to initial/expected conditions is given as well.Table T. Total revenue (mill EUR) over the period 2012–2037 for the four fleet segments in each of the four scenarios. Revenue is shown over all waters shown, together with revenue in Kattegat and in the Western BalticTable U. Total fuel costs (mill EUR) over the period 2012–2037 for the four fleet segments in each of the four scenarios. Fuel costs are shown over all waters shown, together with fuel costs in Kattegat and in the Western BalticTable V. Total crew costs (mill EUR) over the period 2012–2037 for the four fleet segments in each of the four scenarios. Crew costs are shown over all waters shown, together with crew costs in Kattegat and in the Western BalticTable W. Total variable costs (mill EUR) over the period 2012–2037 for the four fleet segments in each of the four scenarios. Variable costs are shown over all waters shown, together with variable costs in Kattegat and in the Western BalticTable X. Total capital costs (mill EUR) over the period 2012–2037 for the four fleet segments in each of the four scenarios. Capital costs are shown over all waters shown, together with capital costs in Kattegat and in the Western BalticTable Y. Total fixed costs (mill EUR) over the period 2012–2037 for the four fleet segments in each of the four scenarios. Fixed costs are shown over all waters shown, together with fixed costs in Kattegat and in the Western BalticTable Z. Total profits (1000 EUR) (mill EUR) over the period 2012–2037 for the four fleet segments in each of the four scenarios. 'Profits are shown over all waters shown, together with profit in Kattegat and in the Western Baltic(ZIP)Click here for additional data file.


A tight coupling between the neuronal activity and the cerebral blood flow (CBF) is the motivation of many hemodynamic response (HR)-based neuroimaging modalities. The increase in neuronal activity causes the increase in CBF that is indirectly measured by HR modalities. Upon functional stimulation, the HR is mainly categorized in three durations: (i) initial dip, (ii) conventional HR , and (iii) undershoot. The initial dip is a change in oxygenation prior to any subsequent increase in CBF and spatially more specific to the site of neuronal activity. Despite additional evidence from various HR modalities on the presence of initial dip in human and animal species ; the existence/occurrence of an initial dip in HR is still under debate. This article reviews the existence and elusive nature of the initial dip duration of HR in intrinsic signal optical imaging (ISOI), functional magnetic resonance imaging (fMRI), and functional near-infrared spectroscopy (fNIRS). The advent of initial dip and its elusiveness factors in ISOI and fMRI studies are briefly discussed. Furthermore, the detection of initial dip and its role in brain-computer interface using fNIRS is examined in detail. The best possible application for the initial dip utilization and its future implications using fNIRS are provided. Over the last few decades, researchers in the neuroscience field have made significant advances in decoding thoughts based on brain activities. A complete understanding of the underlying neuronal mechanisms and signaling pathways is required to decode the brain. Therefore, interest in understanding the neurovascular coupling (NVC) has rapidly grown over the last years. NVC can be defined as a process that links the change in regional neuronal activity to the local cerebral blood flow (CBF) . A tightPosition emission tomography requires radioactive isotopes to monitor the hemodynamic response (HR) and metabolic changes associated with the neuronal activity, which limits its use in terms of continuous and repeated measurements . ISOI isHR-based modalities use the increase of blood flow (HbO/ΔHbO or/and HbR/ΔHbR) as an indirect marker for neuronal activity . HoweverThese neuroimaging modalities can also be used to provide patients a means of communication with the real world through a brain–computer interface (BCI). The main role of the BCI is to translate brain signals and generate reliable commands with high accuracy to control external devices like a robotic arm/leg or a wheelchair in a real environment for patients . Among aThis paper presents a review focusing on initial dip detection during the HR. First, the existence of initial dip and its elusive nature will be briefly discussed using ISOI and fMRI. We will then discuss in detail the existence of the initial dip using fNIRS and its role in BCI. Some possible contributing factors in the initial dip elusiveness, future implications, and extensions will also be presented.In ISOI, the onset of a neuronal activity-dependent oxygen delivery was first found to occur before the increase in the cerebral blood volume (CBV) and the CBF . Upon achttp://isiknowledge.com. The initial dip existence and its elusive nature in each modality are discussed herein separately in the subsequent sections.Figure After the inaugural work on the existence of an initial dip , MalonekThe controversy was started by raising doubt on the type of analysis used by 2) using an O2 microelectrode  was better localized in the spiking activity than the later phase of the response  reported a smaller duration of initial dip and proposed different mechanisms. To follow up on the discrepancies in the fMRI and fMRS data, The controversy around the initial dip continued to grow because many studies on animals were unable to detect the initial dip in different brain areas. Some fMRI studies detected the initial dip in the visual cortex of a cat , whereasTable As observed in Table The value of ΔCBV is slightly lower than ΔHbT, since ΔHbT is calculated as the sum of ΔHbO and ΔHbR as follows.Using Eqs. (1) and (3), the relationship between ΔCBV and ΔHbT is represented as .p =  in the phase plane can be calculated as follows.The magnitude and the phase of a vector The ratio of ΔCOE to ΔCBV  defines the degree of oxygen exchange. Therefore, ΔCOE represents the oxygen exchange in the blood vessels and thus also the neuronal activities . ΔCOE > Synthetic ΔHbO and ΔHbR trials were generated with the designed hemodynamic response function (dHRF) assuming a trial period of 35 s  to further elaborate the vector phase analysis. The dHRF-HbO was modeled by convolving three gamma functions with the trial period. Similarly, dHRF-HbR was generated by multiplying dHRF-HbO with a -1/3 factor . Figure The main issue in the vector phase analysis of q-steps ahead, the occurrence of initial dips. They were able to reduce the time lag in detecting an initial dip to approximately 0.9 s. The single threshold circle criteria in the vector phase diagram worked significantly well to reducing the detection time of brain activity in fNIRS BCI. However, large fluctuations of ΔHbO and ΔHbR above the threshold circle during the task period can still be interpreted as an initial dip.They proposed that this threshold circle can be used as a decision criterion for the initial dip occurrence. Their criteria for initial dip detection were (i) the trajectory must lie in any of Phases 2–5 , and (ii) the magnitude of the trajectory should deviate from the threshold circle. They also found the time of initial dip occurrences using the threshold circle in the vector diagram. Because of the inherent onset delay in fNIRS, they also proposed the usage of an auto-regressive moving average model with an exogenous input in combination with the vector phase analysis method to predict, p1 and SD, respectively, are the amplitude and the standard deviation of the conventional HR, and ρ is the ratio of the amplitude of the initial dip (p0) and p1. The value of ρ, p1, and SD can be determined through the averaging of the HRs over several trials from the most active channel for a given task. Once the experimental data is obtained, the radius (r2) can be calculated based on the averaged data and its SD for the specific tasks, measured locations, and subjects.where In The detection of initial dip in the HR can also be done using an initial-dip-based dHRF, which can be generated by convolving the canonical hemodynamic response function (cHRF) made with three gamma functions, denoted by h(k), with the stimulus period, u(k), as follows.where task and rest represent the task period and the rest period, respectively. Recalling that the most frequently used option for the modeling of cHRF is a gamma function , 1998, ti represents the number of gamma functions, iA is the amplitude, αi and βi tune the shape and the scale, respectively, and k is the time step. Then, t-statistics analysis can be used to estimate the initial dip in the HR by fitting the measured HR to the initial-dip-based dHRF. Please see where Some possible contributing factors in the elusive nature of initial dip could be from different species, anesthesia, different methodologies adopted, surgical procedures, and stimulation protocols [please see In general, a BCI scheme includes (i) signal acquisition and preprocessing, (ii) feature extraction, (iii) classification, and (iv) feedback. In the HR-based imaging for BCI, the detection of HRs  is the main focus on neuronal command interpretation . To the With the technical advances in MRI, a real-time fMRI can work as a closed-loop system that allows simultaneous acquisition, analysis, and visualization of brain images in real-time . The uniSeveral studies successfully demonstrated that the participants using real-time feedback in fMRI-BCI were able to perform voluntary self-regulation on a focused brain region, see details in Functional near-infrared spectroscopy has so far shown great potential for use as a portable device for BCI applications . However2+ ΔHbR2)1/2 to max{ΔHbO, ΔHbR} to the classification problem of three mental tasks that originated from the prefrontal cortex for BCI. They examined five features of ΔHbO during the initial dip phase: signal mean, signal minimum, signal peak, skewness, and kurtosis in different window sizes  to classify multiple tasks from the prefrontal cortex in an offline analysis. They concluded that the signal mean and the signal minimum as features for the initial dip worked well in the 0–2.5 s window to classify three prefrontal tasks using the LDA as a classifier. They demonstrated that the moving window size in the fNIRS-based BCI can be reduced to 2.5 s using the initial dip detection method. Similarly, another study used the mean value of ΔHbO and ΔHbR in the 0–2 s window as an initial dip feature for the classification of left- and right-hand movements  how to increase the classification accuracy, (ii) how to increase the number of brain commands for improving the degrees of freedom of an external device, and (iii) how to quickly decode the brain commands by reducing the delay. The initial dip can help address two out of these three issues for the BCI. First, the initial dip detection can reduce the detection time . Second, the generation of brain commands from a restricted brain region can become diverse, which consequentially results in an increased number of commands from a wider brain region, because the initial dip is spatially specific to regional neuron firing. The previous fNIRS studies Table  showed tPrevious fNIRS-BCI studies only used the constant DPF analysis to detect the initial dip. Figure The delay between the oxygen consumption and the additional blood flow results in the form of initial dip. It is not possible for the additional blood to arrive in from a too distal area to the epicenter of activation within a very short period of time , but it Finally, the current need is to understand how the brain works and how these neuroimaging modalities can be helpful for mankind. Considering that fMRI has high spatial, but low temporal resolution, further research by combining neuronal modalities  with the HR modalities might be a more promising brain diagnostic endeavor. The study by The ultimate goals of these HR-based neuroimaging modalities are (i) to provide an understanding of the NVC and (ii) how these modalities can be used as a means of communication to disabled persons, resulting in the betterment of humanity. Meanwhile, the spatial and temporal characteristics of the HR as an alternative to the neuronal activity are still being debated. Therefore, in this article, we presented a review on the existence and the elusive nature of the initial dip duration of HRs in ISOI, fMRI, and fNIRS. We discussed the brief story of the initial dip and the beginning of the controversy regarding the presence of the initial dip in ISOI/fMRI. We also presented the detection and the role of the initial dip in the brain–computer interface using fNIRS.2 microelectrode also showed evidence for prior oxygenation before the increase in the CBF that further confirmed the existence of the initial dip. Therefore, the detected initial dip using the abovementioned modalities is not likely to be an artifact. However, the discrepancy in detecting the initial dip is most likely caused by methodological, physiological, and modality differences.The initial dip was successfully detected in ISOI, fMRI, and fNIRS. Other techniques like phosphorous quenching and direct tissue-oxygen OFurthermore, the BCI seems to be a potential application for the initial dip utilization. Despite the low spatial resolution of fNIRS compared to ISOI and fMRI, fNIRS can be used for BCI applications with the advantage of providing simultaneous information on oxyhemoglobin and deoxy-hemoglobin, portability, and low cost. The use of the initial dip can help reduce the window size for generating the brain commands for BCI. Initial dips can also help increase the number of commands from a wide area because they are more spatially specific to the neuronal sites. Therefore, research on the initial dip must be continued, and more sophisticated methods of analysis must be developed to reduce the elusiveness surrounding the initial dip.K-SH conceived the topic and finalized the paper. AZ conducted the literature survey and wrote a preliminary version.The 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. The reviewer NN declared a past co-authorship with one of the authors K-SH to the handling Editor.