Agricultural adaptation is necessary to reduce the negative impacts of climate change on crop yields and to maintain food production. However, few studies have assessed the course of adaptation along with the progress of climate change in each of the current major food producing countries. Adaptation pathways, which describe the temporal sequences of adaptations, are helpful for illustrating the timing and intensity of the adaptation required. Here we present adaptation pathways in the current major wheat-producing countries, based on sequential introduction of the minimum adaptation measures necessary to maintain current wheat yields through the 21st century. We considered two adaptation options: (i) expanding irrigation infrastructure; and (ii) switching crop varieties and developing new heat-tolerant varieties. We find that the adaptation pathways differ markedly among the countries. The adaptation pathways are sensitive to both the climate model uncertainty and natural variability of the climate system, and the degree of sensitivity differs among countries. Finally, the negative impacts of climate change could be moderated by implementing adaptations steadily according to forecasts of the necessary future adaptations, as compared to missing the appropriate timing to implement adaptations. There are various options of agricultural adaptation to climate change. To reduce the negative impacts of climate change and obtain greater benefits, not only autonomous adaptations  but also planned adaptations that require substantial investment  are needed1Recent studies have analyzed climate-change impacts and the benefits of adaptation on crop yieldsAn effective way to examine the timing and intensity of adaptations is to describe the temporal sequences of the adaptations. The concept of describing a sequence of adaptation options over time, termed “adaptation pathways,” was recently proposed79In this study, we present nation-wise adaptation pathways for the global production of wheat, which is a staple crop worldwide. We developed adaptation pathways for the current major wheat-producing countries 16For MIROC-ESM, we used two extremely different radiative forcing scenarios of the Representative Concentration Pathways (RCPs): the RCP8.5 scenarioWe considered two adaptation options: (i) expanding irrigation infrastructure, with 13 intensity levels of adaptation ; and (ii) switching crop varieties and developing new heat-tolerant varieties, with 6 adaptation levels. We estimated country-based yield for all combinations of adaptation option and adaptation level (hereafter referred to as “adaptation set”), and then developed adaptation pathways by implementing a stronger and minimum-necessary adaptation set to avoid a yield decrease from that of the 1990 s (hereafter “current yield”) in each decade (see Methods). When examining planned adaptation, we assumed that adaptation levels are irreversible: once a certain level of adaptation is taken, then the lower adaptation levels cannot be used. For simplicity, we did not consider adaptation costs or socio-economic changes such as the change in demand, economic growth, and technological progress. In order to construct adaptive plans optimized for each country, region-specific adaptive capacity and criteria of decision-making need to be considered, which is beyond the scope of this study.Without adaptation , wheat yields will fall below the current level in most countries in the 21st century under the RCP8.5 scenario . This isWhen the minimum-necessary adaptation set  is implemented incrementally in each decade, the adaptation pathways under the RCP8.5 scenario of the MIROC-ESM projection result in the dark blue lines in In addition to using the MIROC-ESM model, we also developed adaptation pathways in the timely case under the RCP8.5 scenario with the other climate models and ensemble runs. Although at first glance the pathways appear quite different among the models and ensemble runs, we did find some common features in the selected options in several countries : (i) chaThe timing of the adaptation varies widely among the models and ensemble runs in these simulations. With regard to the benefit of adaptation, there are large uncertainties arising from climate model uncertainty and natural variability of the climate system , which lBecause we considered multiple adaptation options , multiple pathways of necessary adaptation could be described by prioritizing one of the adaptation options. In this section, we show effects of these adaptation prioritization strategies on the adaptation pathways, focusing on the results of MIROC-ESM. We also show the adaptation pathways under the different emissions scenario  based on the MIROC-ESM projection in the latter half of this section.The timely case previously mentioned is a non-prioritization case: the adaptation set that achieves the minimum increase in yield from the current level is chosen regardless of the kind of adaptation option. If either irrigation or crop varieties is preferentially chosen , the resulting adaptation pathways differ from the timely case . For exaThe necessary adaptation levels tend to be lower under the RCP2.6 scenario than under the RCP8.5 scenario, except in the United States and France . In RussThus far we have developed adaptation pathways to maintain current yields as the timely case and prioritized cases, and we have discussed the effects of climate-change uncertainties, adaptation strategies, and emissions scenarios on the adaptation pathways. Here we look at them from the viewpoint of performing a series of adaptation processes. In the cases examined above, we assumed that a large amount of adaptation could be promptly implemented within a decade. However, we must consider the feasible rate of adaptation, because planned adaptation requires both significant investment and substantial time to be developed. We should also consider the lead time to implement an adaptation, which means the time lag between the planning and the implementation of adaptation. Here we consider step-by-step adaptation pathways, which are those described by gradual implementation of the adaptation and considering a lead time to implement an adaptation. In this case, full adaptation would not be achieved immediately under an abrupt climate change, such that adaptation forecasts will become important. In the following, we discuss the advantage of forecasting necessary adaptations.If no forecast is conducted  and the amount of adaptation implemented is limited to one level per decade each for irrigation and crop variety, the adaptation pathways without prioritization result in the red dashed lines in The efficacy of forecast is obvious in all nine countries and in all models and ensemble runs . In ChinIn this study, we developed adaptation pathways in the current major wheat-producing countries, based on sequential introduction of the minimum adaptation measures necessary to maintain current wheat yields through the 21st century. The adaptation pathways revealed that the timing and intensity of adaptations required differs markedly among countries. The adaptation pathways are sensitive to both climate model uncertainty and natural variability of the climate system, and the degree of sensitivity differs among countries. In addition, we showed that forecasts of necessary adaptations are important to achieve the benefit of the adaptation pathways. Here we discuss several issues that must be considered to improve the approach proposed and adopted in this study, as well as the robustness of the results.First, analyses synthesizing multiple climate projections will be required. Although we employed multiple climate models and ensemble runs to show the impacts of their uncertainties on the adaptation pathways, we need both more projections and more comprehensive analyses to identify robust adaptation pathways that can overcome the uncertainties.Second, the availability and accessibility of adaptation levels assumed in this study include uncertainties. For example, the pathways in this study indicate when new crop varieties are required in addition to the existing crop varieties; however, it is uncertain whether the assumed new varieties will become a reality. Regarding irrigation, in the adaptation levels we included a large expansion of irrigation that may not be adopted due to economic limitations. The assumptions underlying the selectable adaptation levels need to be refined based on further empirical evidence.Third, under the given adaptation sets we assumed that farmers are always able to attain the highest yield by optimizing planting dates and wheat varieties. However, the rate at which farmers will adapt is uncertainFourth, we also assumed that maintaining the current yield will be the target in the future as well, but the amount of yield required would vary with changes in socio-economic conditions , wind speed (m/s), and diurnal temperature range (°C). The spatial resolution of final output yield is 2.5′ × 2.5′. To develop adaptation pathways, we aggregated grid-based yield into country-based yield.We calculated wheat yield with the M-GAEZ crop modelet al.The M-GAEZ model calculates wheat biomass based on the climatic variables, and it calculates wheat yield by imposing several constraints  and the harvest index on the biomass. The model also calculates the growing period of wheat based on the variety-specific growth cycle and climatic conditions, and judges whether the crop is able to grow or not based on the temperature profile in the grid cell during the growing period. In the M-GAEZ model, crops are assumed to be free from water stress when irrigation is applied; the negative impacts of a moisture deficit (related to evapotranspiration) can be fully avoided. (See Fischer At irrigation Level 0 (corresponding to no adaptation), the irrigated area is maintained as it is at present. To set irrigation from Levels 1 to 10, we increased the irrigated area ratio by 10% per adaptation level for crop lands where the present irrigated ratio is above zero. For Levels 11 and 12, in addition to increasing the ratio by 100% for crop lands where present irrigated ratio is above zero, we increased the ratio by 20% (for Level 11) and 50% (for Level 12) for presently non-irrigated crop lands .2 fertilization was taken into account by applying multipliers to the yield according to the mean atmospheric CO2 concentration in each decade, in a way similar to Masutomi et al.2 fertilization effect has large uncertainties.)The M-GAEZ model originally had 16 varieties of wheat, which are classified into four major cultivars , each of which has four minor varieties that differ in growth period. At variety Level 0, only four minor varieties of the current optimal cultivar (defined as the major cultivar that most frequently produced the highest yield from 1991 to 2000) are selectable to obtain the highest yield. At variety Level 1, all the 16 original varieties are selectable. To assume new heat-tolerant varieties, we conducted a sensitivity analysis by relaxing the limitations of high temperatures for the 16 varieties. From Levels 2 to 5, a set of 16 new varieties become selectable when the level rises to the next one. We removed the limitations of high temperatures at Level 5 ; wheat iIn the timely case, the adaptation set that has the minimum yield change from the current level is chosen in each decade from among the adaptation sets in which yield change is maintained at or above zero. In case there are only adaptation sets in which the yield change is below zero, the set that minimizes the yield decrease from the current level is chosen. The prioritized cases (prioritize irrigation case and prioritize variety case) are the same as the timely case except that the prioritized adaptation option continues to be chosen until the yield changes at any adaptation levels fall below zero, while the level of the other option is fixed. If the yield changes at any levels are below zero, then the other option rises by one level, and the process is repeated. In case there are only adaptation sets in which the yield change is below zero, the set that minimizes the yield decrease from the current level is chosen regardless of the options. In the forecast cases , we assumed that the lead time to introduce an adaptation after planning is 10 yr. In the non-forecast case, the adaptation set required in a decade is implemented in the next decade, because the adaptation starts to be developed in the current decade. In the 10-yr-forecast case, the adaptation set required in the next decade is forecast (and starts to be developed) and is implemented in the next decade. In the 20-yr-forecast case, the adaptation set required in the two decades ahead is forecast (and starts to be developed) and is implemented in the next decade. Even though implementation of adaptation is not necessary two decades ahead, the adaptation set is implemented if it is required in the next decade. The non-forecast case, 10-yr-forecast case, and 20-yr-forecast case are limited in the amount of adaptation implemented to one level per decade. The assumed cases mentioned above are summarized in Throughout the analyses, crop land area was fixed at the current condition26How to cite this article: Tanaka, A. et al. Adaptation pathways of global wheat production: Importance of strategic adaptation to climate change. Sci. Rep.5, 14312; doi: 10.1038/srep14312 (2015).


Assessment of cerebral venous return is growing interest for potential application in clinical practice. Doppler ultrasound (DUS) was used as a screening tool. However, three meta-analyses of qualitative DUS protocol demonstrate a big heterogeneity among studies. In an attempt to improve accuracy, several authors alternatively measured the flow rate, based on the product of the time average velocity with the cross-sectional area (CSA). However, also the quantification protocols lacked of the necessary accuracy. The reasons are as follows: (a) automatic measurement of the CSA assimilates the jugular to a circle, while it is elliptical; (b) the use of just a single CSA value in a pulsatile vessel is inaccurate; (c) time average velocity assessment can be applied only in laminar flow. Finally, the tutorial describes alternative ultrasound calculation of flow based on the Womersley method, which takes into account the variation of the jugular CSA overtime. In the near future, it will be possible to synchronize the electrocardiogram with the brain inflow (carotid distension wave) and with the outflow (jugular venous pulse) in order to nicely have a noninvasive ultrasound picture of the brain-heart axis. US jugular venous pulse may have potential use in neurovascular, neurocognitive, neurosensorial, and neurodegenerative disorders. In the last years, there was a growing interest in understanding the role of brain drainage in neurovascular and in neurodegenerative disorders. The description of chronic cerebrospinal venous insufficiency (CCSVI) leads numerous researchers to explore the role of restricted venous outflow in favouring multiple sclerosis (MS) –5, AlzheSince CCSVI straights the extracranial major veins of the neck, ultrasound echo color-Doppler (ECD) was chosen as a screening methodology, either because of the noninvasiveness or because it is widespread equipment. The screening was initially proposed through a qualitative investigation based on a list of five physiological criteria; subsequently, they were very well detailed in a consensus conference , 15. TheTo overcome the controversy, the ISNVD published a position paper which substantially proposes a multimodality diagnostic protocol for the diagnosis of CCSVI. The article discusses the advantages and the limits of the different techniques which can be used to assess cerebral venous return . AccordiHowever, ultrasound remains an ideal technique for screening, and several investigators tried to measure the jugular and vertebral vein flow by the means of ECD in order to substitute the operator dependent qualitative protocol with a more objective measurement of the venous flow –29.Q is the flow rate, v is the velocity expressed as time average velocity (TAV), and CSA is the cross-sectional area of the vessel under investigation.All the ECD equipment on the market allows applying the Poiseuille law for the assessment of flow: Practically the available ECD instruments permit measuring the flow automatically by the combination of the B-mode imaging with the Doppler spectra analysis. In Thanks to this technological possibility, some authors assessed the presence of CCSVI in healthy people and in neurodegenerative diseases, but again obtaining variable results –29.2 in supine versus 17 mm2 in upright, respectively.Flow quantification was always assessed, as anticipated above, by applying the formula of Poiseuille. Valdueza et al.  measurinThe observation of Valdueza was confirmed by several studies, which measured a smaller CSA in standing versus supine positions in the IJVs , 26–29. Recently, Monti et al. proposed a cut-off value of ≤503.24 mL/min as a differential value between supine and sitting positions of cerebral venous blood outflow as a diagnostic criterion of MS. More than 70% of MS patients fulfilled the cut-off value versus 29% of healthy controls and 43% of patients with other neurological diseases. Even this study shows significant overlapping between controls and neurological diseases.Since the inflow through the internal carotid and vertebral arteries is not significantly different with the head at 0° and 90°, respectively, the question is where is the blood lacking in sitting position? It has been hypothesized that the rest of the blood might be stored in the collateral veins, because the jugular flow increases passing from the upper to the lower segment of the neck .A lumped model, calculating the blood flowing in the collateral network, demonstrates that the increased flow, from the jaw to the chest, is due to the reentry of the collaterals into the main outflow route . The novHowever, by comparing the flow rate measured in the IJV in normal people, all published studies readily show differences, as well as very high standard deviations –31. ThisThe low reproducibility even among quantitative protocols for venous outflow measurement suggests technical problems linked with the current methodology. This is related to the method of measurement of the two variables which occurs for calculation of the flow rate. Since the TAV can be reliably measured exclusively from the Doppler spectrum registered in the longitudinal aspect of the vein, CSA is measured in this position using the cursor in the machine developed for diameter assessment from the B-mode image . It is aIn a recent study, by the means of repeated countered measure of the elliptical internal jugular vein, a significant risk of flow rate underestimation with the assumption of a cylindrical venous shape has been demonstrated,. In The second critical point of the current methodology is based on the assumption of just one constant measure of CSA over the time. On the contrary, the CSA of the jugular varies over the cardiac cycle, being a pulsatile large vein. It is known how CSA of the jugular significantly varies determining the so called phenomenon of the jugular venous pulse (JVP) , 33. AllFinally, the measure of TAV with the current ECD is very accurate if a laminar flow is present in the vein. In the terminal region, close to the valve and to the subclavian junction, all the investigators report the presence of turbulences, and the measure of flow is significantly different in this segment by comparing studies –29. In tSince the region more susceptible to intraluminal obstacles is the valvular region, an uncertain flow rate assessment in this region potentially leads to errors in screening CCSVI.In the previous paragraph it has been shown that the jugular vein is a pulsatile vessel. Consequently, the variation of the CSA over time significantly contributes to an inaccurate flow assessment when using just a single CSA value in measuring the flow. A complete and correct analysis of the IJV blood flow would take into account the pulsatile nature of this vein; to neglect this point will comport an error whose magnitude has to be established. The IJV pulsatility, the so-called jugular venous pulse (JVP), represents a corner stone of clinical medicine. But it is exactly the change in CSA over the cardiac cycle that we need for an accurate evaluation of the CSA.JVP is defined as the movement of expansion of the jugular veins due to changes in pressure in the right atrium. It provides valuable information about cardiac hemodynamics and filling pressure , charactJVP consists of three positive waves  and two negative waves (descents) (X and Y). The A wave corresponds to atrial contraction and is synchronized with the P wave of the electrocardiogram (ECG). Descent X corresponds to lowering of the atrioventricular septum, interrupted by a small positive wave C in relation to closure of the tricuspid valve; the third wave V corresponds to cardiac systole and is followed by the Y descent, which corresponds to opening of the tricuspid valve  32–36].–36.32–36r = 0.98) [The IJV is not only pulsatile, but one more important mechanical property of such vein is the distensibility. The latter was proven by the strong correlation between CSA and perimeter variation ( = 0.98) . When th = 0.98) ; therefo = 0.98) .In order to reliably derive the JVP through a sequence of CSA measurements of the jugular (US JVP), the subject is investigated with a high resolution real time B-mode video clip (about 24 frame∖sec), synchronized with an ECG trace. It has been recently demonstrated that US JVP represents a periodic signal that nicely reproduces the sequence of the five JVP waves, permitting a rapid, noninvasive assessment at bedside. Moreover, a semiautomatic tracing algorithm was developed to easily and rapidly derive US JVP in both research and clinical settings . Since cIn the present issue of Behavioural Neurology, Sisini et al. propose a novel methodology based on the ultrasonographic assessment of the jugular venous pulse (US JVP) . As repoFinally, the work of Sisini et al., although intriguing, is really preliminary. Speculatively, we may think that the sequential assessment of IJV CSA is less prone to error with respect to the current methodology. Quite recently, the clinical applicability of this novel method of assessment has been successfully tested, measuring the reproducibility as well as estimating the instrumental error of such a novel assessment . HoweverHistorically, the concept of the heart-brain connection was born by the observation that a generalized autonomic storm, which occurs as a result of a life-threatening stressor, will have both sympathetic and parasympathetic effects. The effects of the autonomic nervous system on both organs were extensively studied in the past. Interestingly, ECG anomalies seen in the context of stroke did not represent ischemic heart disease but are merely a manifestation of autonomic dysregulation, possibly caused by a lesion that affected the cortical representation of the autonomic nervous system. Brodmann area 13 on the orbital surface of the frontal lobe and area 24 on the anterior cingulate gyrus are considered the cortical centers for cardiovascular control.The heart-brain connection has many faces, but it can be divided into 3 major issues: the heart's effects on the brain , the brain's effects on the heart , and neurocardiac syndromes  .More recently, the heart-brain axis seems to play a major role in the development of Alzheimer's disease (AD) and vascular dementia (VD), in consequence of the strong association of the increased risk to develop neurocognitive problems in patients with cardiovascular disease –50. Epid


Purpose. The aim of this study was to show that individual adjustment of the curling behaviour of a preformed cochlear implant (CI) electrode array to the patient-specific shape of the cochlea can improve the insertion process in terms of reduced risk of insertion trauma. Methods. Geometry and curling behaviour of preformed, commercially available electrode arrays were modelled. Additionally, the anatomy of each small, medium-sized, and large human cochlea was modelled to consider anatomical variations. Finally, using a custom-made simulation tool, three different insertion strategies  insertion technique, an automated implementation of the AOS technique, and a manually optimized insertion process) were simulated and compared with respect to the risk of insertion-related trauma. The risk of trauma was evaluated using a newly developed “trauma risk” rating scale. Results. Using this simulation-based approach, it was shown that an individually optimized insertion procedure is advantageous compared with the AOS insertion technique. Conclusion. This finding leads to the conclusion that, in general, consideration of the specific curling behaviour of a CI electrode array is beneficial in terms of less traumatic insertion. Therefore, these results highlight an entirely novel aspect of clinical application of preformed perimodiolar electrode arrays in general. An essential, but also risky, step in cochlear implantation is the insertion of the electrode array (EA) of a cochlear implant into the helically shaped scala tympani. The scala tympani is one of three tubular lumens inside the auditory portion (cochlea) of the inner ear. At one side, it is bordered by a fragile membranous structure, called the basilar membrane, which divides the cross section of the cochlea almost in the middle. The basilar membrane plays a crucial role in the biomechanics and hydrodynamics of the inner ear and, therefore, in the mechanism of sound sensation. Located on top of the basilar membrane is the organ of Corti, which includes the hair cells and forms the neural receptor for sound waves. Physical integrity of the basilar membrane is thus essential for acoustic hearing.In hearing-impaired patients, the function of the hair cells, which convert acoustic signals into a neural response, is limited or completely absent. The latter case results in deafness. Otherwise, the degree of hearing loss depends on the amount of residual hearing and its usability for communication and environmental sound sensation. However, a useful and well-established surgical procedure—the implantation of an electronic device called a cochlear implant CI, see —is availThrough electrical stimulation of the auditory nerve, a CI bypasses damaged portions of the ear and provides a sense of sound to the recipient. For this purpose, the CI system includes a component known as the electrode array , which is inserted into the cochlea . This intracochlear portion is a thin, elongated silicone body incorporating embedded platinum contact electrodes. To achieve electrical stimulation of the auditory nerve, environmental sounds are recorded and converted into electrical signals by the CI system. Stimulus-correlated electrical signals are finally transferred to the electrode array; this in turn generates electrical fields in the surrounding tissue, including the fibres of the auditory nerve.Historically, only deaf patients were considered to be candidates for CI treatment. In the present day, inclusion criteria are continuously being expanded, so that individuals with substantial residual hearing are now also getting implants. There are two main reasons why a CI is recommended to these patients. The first is that, in most cases, residual hearing is in the low-frequency range. In contrast, hearing at the high-frequency range >1,000 Hz), including those frequencies essential for human speech, is not functional. These individuals are, therefore, excluded from day-to-day communication, a situation which cannot be improved by use of conventional hearing aids. The second reason is a strategy referred to as hybrid or electric acoustic stimulation (EAS). This involves the use of electrical stimulation via the CI to restore high-frequency hearing, with the residual hearing still being exploited and amplified for normal (acoustic) low-frequency hearing. A combination of both approaches to providing hearing sensation is known to deliver better hearing outcomes than electrical stimulation alone ,000 Hz, . This isIn general, existing electrode arrays can be divided into two main groups: those straight in shape and those with a preformed, moulded silicone body. Numerous straight electrode arrays have been developed in recent years. High flexibility, reduced cross-sectional area, and limited insertion depth are considered as essential features to meet the requirements of atraumatic insertion, and hence preservation of residual hearing and electric acoustic simulation. The main disadvantage is the final position at the lateral wall of the cochlea, which is a large distance away from the neural tissue that is the target for stimulation.In contrast, preformed electrode arrays are fabricated in a spiral configuration adjusted to the shape and size of an average human cochlea. As insertion into the cochlea initially requires a straight configuration, it is necessary to uncurl the electrode array and keep it straight prior to insertion. A commonly used mechanism is a thin but sufficiently stiff wire (stylet) inside the electrode array, which inhibits the curling forces of the spirally preformed and elastically deformed silicone body and the embedded platinum wires. During insertion this stiffening wire, the stylet is removed and the electrode array returns to its original helical shape.Originally, these preformed electrode arrays were designed for intracochlear placement next to the modiolus, which is why they are known as perimodiolar implants. The modiolus is the central axis of the cochlea and contains the neural tissue that is the target for stimulation by the CI. Therefore, close proximity of the electrode contacts to the inner wall of the cochlea is beneficial for electric stimulation , 9. ExamHowever, this perimodiolar design also has its drawbacks. In general, these electrode arrays have a larger diameter and (due to the stiffening wire) also exhibit greater overall stiffness than the thin and highly flexible straight models. Perimodiolar electrode arrays are thus associated with a higher risk of insertion trauma and are not normally used for patients with residual hearing. To overcome the disadvantages of additional stiffening elements (such as the stylet) with regard to residual hearing preservation, it would appear necessary to reduce the amount of contact between the implant and the intracochlear anatomical structures. One strategy could be to use robot assistance for insertion and to optimize its pose (position and orientation) with respect to the pose of the inner ear , 11. RedHowever, the integrated curling mechanism provides the opportunity to modify not only the pose but also the shape of the electrode array with regard to the individual anatomy. This entails the replacement of a uniform insertion technique (such as the Advanced Off-Stylet (AOS) technique; see Therefore, the aim of this study was to investigate whether, for the commercially available CA electrode array, an individually optimized insertion procedure is advantageous compared with the AOS insertion technique, which is recommended for all patients by the manufacturer, Cochlear Ltd. More generally, we wished to explore whether taking into account the curling behaviour of a CI electrode array is beneficial in terms of less traumatic insertion. In the light of this research question, we also investigated the situation when a minimally invasive approach to the cochlea is employed. This entails an alternative to the manually performed drilling of a large mastoid cavity . Instead, a single, straight drill hole should be used. This not only requires additional surgical assistance devices, which are currently under development by several research groups , 26–28: Irrespective of the surgical approach chosen, the findings of this research on individually optimized electrode insertion are also of interest for other projects dealing with the functionalization of CI electrode arrays using different curling mechanisms. In recent years, there has been an increasing interest in “active” or “steerable” CI electrode arrays, which involves investigation of different actuator principles to bring about a controllable shape change. The following are examples of these mechanisms: use of an embedded actuation strand as described by Zhang et al.  and ZhanIndividual adjustment of the curling behaviour of a preformed CI electrode array to the individual spiral shape of the cochlea can improve the insertion process in terms of reduced risk of insertion trauma.In contrast to manually controlled insertion, the automated insertion tool provides a means of adjusting the electrode's curling behaviour to the individual helical shape of the cochlea. The following working hypothesis was therefore proposed:In order to test the hypothesis, a principle subject to general consensus in CI research was applied, according to which insertion forces are the main indicator of the risk of insertion trauma and are directly correlated to it. From a mechanical point of view, however, insertion forces are primarily a result of contact or constraining forces between the implant and the surrounding anatomy. Thus, the degree of contact between both “objects” allows a qualitative conclusion concerning the insertion forces and ultimately, therefore, concerning the risk of trauma. As a first step towards the substantiation of the working hypothesis, proof has to be provided that, by means of the controlled and continuous adjustment of the shape of the electrode array to that of the cochlea, the degree and severity of contact between them can be reduced. This enables a direct conclusion to be made concerning reduction of trauma risk.For this purpose, the geometry and the curling behaviour of a commercially available CI electrode array were modelled, based on experimental data from a previous study . Additioμm thin platinum wire [The Contour Advance (CA) is a well-known and widely used preformed electrode array. Its silicone body is moulded in a precurved shape. Twenty-two half-banded platinum electrode contacts are embedded in it, each connected via a 25 num wire . TherefoAll electrode arrays employed in this study were provided by the manufacturer Cochlear Ltd. . They were rejected during the production process owing to electrical defects. With respect to mechanical properties, which are of relevance for this study, these electrode arrays are, however, identical to commercially delivered and clinically used ones. They differ from the  practice electrodes also provided by Cochlear Ltd. as, for example, part of surgical practice kits for teaching purposes and training courses. These practice electrodes are produced by a simpler manufacturing technique to be less expensive but therefore exhibit different curling behaviour than that of “real” implants. Practice electrodes were thus not usable for this kind of investigation .Together with the new electrode array, the AOS insertion technique was introduced to standardize the manual insertion procedure and to provide the surgeon with a straightforward and reliable modus operandi. This launch of a “self-curling” electrode array , in conjx-y plane, the movement of the electrode tip exhibits a typical sigmoidal curve  than does customary, clinically available computed tomography (CT) scanners. Using a threshold-based segmentation algorithm and manual refinement , 3D models of the human inner ear had been generated. Segmentation covered the entire bone-embedded spiral canal of the cochlea and not merely the scala tympani, as the basilar membrane is not visible in X-ray-based imaging. Each 3D model of the inner ear had been saved as STL files .Image data and segmentations of 23 human temporal bone specimens were available from former studies. These data were acquired using flat-panel-based volume computed tomography  , 38 at tThe present study is designed to take into consideration the anatomical variability of the human inner ear. In order to have a single parameter which characterizes differences in size, a measurement method introduced by Escudé et al.  was applA segmented cochlea was loaded as an STL file.A rotation axis through the modiolus was manually determined. It was employed to calculate a cutting plane which provides a cross-sectional view of the cochlea.This cutting plane can be rotated in equal steps , starting with a plane which passes through the round window niche.Two points were manually selected for each resulting cross-sectional view. One marked the outer and the other the inner contour of the cochlea.The CA electrode investigated shows planar  curling behaviour. This is common in perimodiolar cochlear implants for reasons of cost-effectiveness, as 3D curling behaviour requires separate products for left and right ears. The modelling of insertion behaviour was, therefore, initially also considered as a 2D problem. This leads to the necessity of transferring the 3D volume data for the three selected cochleae into a 2D representation of their geometry. For this purpose, custom-made software was employed , which was developed using C++ in Visual Studio  and VTK . This program enabled the following steps:By repeating steps (3) and (4), the spatial dimensions of the helical cochlear lumen were recorded as a 3D point cloud. Finally, these points were projected onto a plane  in order to obtain 2D curves describing the inner and outer contours of the cochlea see .x, Δy) and orientation (Δφ) relative to the cochlear contour. By using a slider at the bottom of the GUI, the user is able to control stylet retraction. The corresponding configuration of the electrode array is automatically loaded from the database . In this way, SimCInsert provides a fairly simple means of simulating the conventional AOS technique, while also allowing manual optimization of the insertion process.Both in order to model intracochlear curling behaviour and for the intended optimization of the insertion process, a simulation tool called “SimCInsert” was developed using MATLAB . The corresponding graphical user interface (GUI) is shown in base see . These “The conventional, manually performed AOS insertion technique, as recommended by the CI manufacturer Cochlear Ltd., served as a reference for the subsequent optimization of the insertion process. In this case, only the second phase, with actual stylet extraction, was taken into account. However, the instructions for the AOS insertion technique are idealized. In reality, the CA electrode array shows a banana-shaped starting configuration, as opposed to a straight one, even where the stylet is fully plugged in. Therefore, a completely rectilinear/linear insertion into the basal turn  is in reality not possible. Furthermore, each implant initially has a slightly different shape .xy plane. In this paper, the simulation of the manually performed AOS insertion technique is subsequently referred to as “manAOS.”Thus, for the simulation of the manually performed AOS technique, it was assumed that the surgeon adjusts the insertion process (irrespective of whether this is done intuitively or in a controlled manner). Although there are no “hard data,” this assumption is confirmed by observations in the operating theatre during cochlear implant (CI) surgery and the verbal reports of CI surgeons indicating that there is a slight compensatory movement when the initially curved electrode array is passed through the cochleostomy or the round window access. This manual adjustment is made possible by use of visual information through the surgical microscope, as well as haptic feedback. During the simulation, this compensatory movement was represented by a rotation in the y direction (Δy) and the rotation (Δφ) of the electrode array had to be kept constant after initial positioning. Only movement in the x direction (Δx) was used to insert the electrode array into the cochlear contour to the same extent as the stylet extraction. For evaluation of minimally invasive access, two parallel grey dashed lines in the main window of SimCInsert represent the edge of the drill hole or the guiding tube of the insertion tool.The situation modelled as a second scenario involved accessing the inner ear by means of automated insertion through a minimally invasive drill canal. In this case, the electrode array is gripped behind the last platinum contact and is advanced in a strongly linear fashion into the cochlea inside the guiding tube of the insertion tool. In terms of the modelling in SimCInsert, this means that throughout the remainder of the insertion process, values for both the position in the Finally, the insertion of the CA electrode array was manually optimized and tailored to the three different sizes of cochleae, representing the anatomical variation in human individuals. All insertion parameters could, therefore, be modified in order to optimize the location of the electrode array within the cochlea. In particular, it was no longer necessary to maintain the strong linear relationship between stylet extraction and implant feed as specified by the AOS technique.According to the initial working hypothesis, the aim of the optimization was to optimally tailor the curling of the implant to the individual anatomy of the inner ear at each stage of the overall insertion process. An optimum location within the cochlea was indicated by minimal overlap between the contour of the electrode array and the contours of the inner ear. A small amount of overlap was considered as equivalent to low contact forces (and hence low forces pertaining to insertion trauma) and vice versa.x), full insertion with complete stylet removal, and avoidance of abrupt changes in all insertion parameters. The latter was to ensure a well-adjusted and continuous insertion process which could be implemented by using, for example, an automated insertion tool and its programmable linear drives [This manual optimization was repeated for each stored configuration of the electrode array, that is, for all steps of stylet removal. Additional constraints were monotonic increase of implant feed  introduced and preferred  and four different electrode arrays in order to compare three different scenarios. As a reference, the manual procedure for inserting the Contour Advance (CA) electrode array using the Advance Off-Stylet technique (manAOS) was remodelled using SimCInsert. Applying the above-mentioned assumptions about the intuitive adjustment of the insertion process, the trauma risk of the insertion process is distributed as shown in In contrast to the manual approach, the automated procedure is inadequate with regard to the necessary adjustable positioning and orientation, especially when using minimally invasive access to the inner ear. Simulation of the autoAOS scenario results in the trauma risk as shown in While insertion processes using the conventional AOS technique are mainly characterized by trauma risk grades III and IV, it is possible to reduce the risk of insertion trauma by means of the individual optimization strategy introduced. The intracochlear curling caused by the stylet extraction and resulting from the individual optimization process is shown in Atraumatic insertion is a mandatory prerequisite for hybrid stimulation of patients with residual hearing. Generally, reducing the risk of iatrogenic trauma requires that the amount of interaction and resulting contact forces between the implant (here the intracochlear electrode array) and the surrounding anatomical structures  be diminished. One established strategy in cochlear implantation is to design very thin and flexible electrode arrays. This is done to limit the contact forces resulting from the extensive contact between these straight implants and the lateral wall of the cochlea. Another design strategy takes the shape of the inner ear into account: by producing helically preshaped electrode arrays, the aim from the outset was to reduce the amount of contact with the boundaries of the scala tympani. This was the purpose and motivation behind the introduction of the Contour Advance (CA) electrode.The new approach to reducing the risk of insertion trauma taken in this study goes beyond the isolated modification of the design of the electrode array. Instead, the essential aspects are, firstly, the individualization of the insertion process, which entails the consideration of individual anatomical constraints and, secondly, the optimization of the insertion process by tailoring the change in shape of the implant to the shape of the surrounding hollow organ.The necessary investigation of the CA's curling behaviour has already been performed and published . In the Comparison of different CA electrode arrays results in large variations. For optimized insertion, average values are less useful. Instead, the specific curling behaviour should be taken into consideration.Comparison of the curling behaviour of the same CA electrode array after repeated measurements produces fairly repeatable results.The shape of the CA electrode arrays does not fit the cochlear models employed. Instead, interference with the anatomical boundary can be observed. Therefore, a purely kinematic model cannot visualize the complex interaction as is possible with FEA.The optimization of controlled insertion of a movable electrode array is more effective if the array's orientation with respect to the cochlea can be changed.In contrast to the present study, their investigation was based on this line and did not consider the areal extent of the implant. However, it is striking that both independent investigations lead to several similar results and conclusions:x and Δy and the orientation Δφ as used in this study. The fourth parameter was an additional possible movement in the x direction. This investigation was carried out using the measured curling behaviour of a set of seven CA electrodes and a mathematical cochlear model describing an average human scala tympani. Although the simulated robot-assisted insertion process was not compared with a conventional approach, their findings support the idea of automated insertion incorporating the specific “shape kinematic” . The curling behaviour resulting from the Advanced Off-Stylet (AOS) technique was described as “incapable of not interfering to some degree with the inner wall of the scala tympani.” This is in accordance with the finding in this study that there is a fundamental mismatch between implant curling and cochlear shape. While the curling of the electrode array starts at the tip with immediate and full recovery of the final shape due to stylet extraction, the electrode array is at that time located in the basal part of the cochlea, which is only slightly curved compared with the apical shape. Only at the end of the insertion process do the shape of the implant and the shape of the cochlea exhibit their best fit .In the context of their research on robot assistance for CI electrode insertion, Pile et al.  studied The modelling of the electrode array based on the detected position of the platinum contact electrodes and the manually marked Softip proved to be useful . ThreshoA similar value is estimated for the modelling error of the inner ear. Modelling quality is directly correlated with the segmentation which is, in turn, directly related to the quality and resolution of the imaging technique. FpVCT, employed in this study, is of high quality  and provides voxels with an isometric size of 0.2 mm. However, this means that a shift of the segmentation boundary by one voxel causes a change in the size of the cochlea model . Additionally, there are errors due to the generation mesh, which triangulates the surface of the segmented object, as part of the export into the STL file.The biggest shortcoming of the inner ear modelling is the absence of soft-tissue information . Therefore, the basilar membrane is not visible and the segmentation is not limited to the  scala tympani. Instead, the complete bony labyrinth of the inner ear is utilized for the measurement as described in The main disadvantage of the simplified modelling approach used in SimCInsert is the lack of computational structural mechanics. Instead of a “physical” simulation, as is possible with finite element analysis (FEA), the superposition of the interacting objects (electrode array and cochlear anatomy) is only visualized. Thus, the deformation of the flexible electrode array as a result of direct contact with the rigid cochlear walls is not calculated and therefore not displayed. Instead, the contact between both objects is visualized only as an intersection of both contours.At an early stage of the project, an “objective” method of measurement was implemented in SimCInsert by calculating the depth of the intersection of the first contact area as the perpendicular distance between the farthest point of the contour of the electrode array and the cochlear contour. Although this method provided numerical values which were independent of the individual investigator, this approach was rejected because secondary contact of the implant inside the cochlea could not be taken into account. Thus, this measurement method is not suitable for assessing the overall intracochlear situation. Furthermore, numerical values misleadingly suggest accuracy. As there is no calculation of deformation, the correctness and validity of an “objective” measurement method of this nature are just as questionable as the preferred subjective rating method.On the other hand, it is an advantage of the presented rating scale that users can benefit from their background knowledge about the flexible behaviour of the electrode array, as had been observed during insertion experiments on artificial cochlear models in the past . Thus, tIt is important to bear in mind that the introduced “trauma risk” rating scale is usable only for estimating the potential risk, that is, for assessing the risk of insertion trauma in advance (prospective). In contrast to Eshragi's retrospective “trauma grade”, it is not possible to rate or even to predict actual damage to intracochlear structures.Therefore, it cannot be ruled out that a specific insertion, which is rated in the simulation with a high degree of “trauma risk,” could be completely atraumatic in the  case of an identical real insertion. Conversely, some uncertainty remains concerning whether a simulated insertion rated with a low risk of intracochlear trauma could lead to significant hearing loss, if it has been possible to exactly experimentally reproduce the simulation. Of course, the already-mentioned complexity of the implant-tissue interaction, the necessary simplifications for SimCInsert, and, finally, the fundamental limitations of the available analysis methods and technologies render such an experimental verification of the simulation results effectively impossible. To clarify the distinction regarding the actual trauma grade using Eshragi's rating scale, Roman numerals were used for the “trauma risk.”φ). Taking this compensation movement into consideration for the modelling of the manual procedure is therefore justified and necessary if realistic results are to be obtained. In consequence, it was supposed that an ideal straight-line insertion  does not correspond to reality. The quantitative extent of this compensation movement has not, however, yet been measured and is, hence, an aspect that is potentially controversial. However, feasible measurement technologies that address this issue  need to be very accurate, as well as small, lightweight, and inconspicuous, in order not to affect the surgeon's intuitive process. Thus, such technologies are currently not available.The simulation of the manually performed AOS insertion technique was based on the presumption that there is (intuitive) adjustment of the insertion process by the surgeon. This assumption was derived from observations, both directly in the operating theatre and using surgical videos. A compensation movement can be regularly observed, which is used by the surgeon to overcome the slight initial curvature of the electrode array when passing it through the incised round window membrane or the cochleostomy. Imperfect straightening of this kind can be found for all known perimodiolar electrode arrays and for certain straight ones . Due to its extent , this movement is of relevance for the insertion process. After projection of the movement into the 2D simulation environment SimCInsert, it is equivalent to pivoting around the cochleostomy  on the initial curved electrode array was not observed. Such an effect could only be (highly restrictively and indirectly) incorporated over the course of trauma risk assessment. In contrast, adequate consideration of a guiding tube in SimCInsert is possible only if separate series of measurements are available using mechanical guidance bars to limit the curling behaviour of the investigated electrode arrays during the measuring process. Alternatively, FE analysis is conceivable, which allows appropriate modelling of the restricted guidance of the tube .Of all three examined scenarios, the simulation of autoAOS represents the most consistent implementation of the AOS technique. Since stylet extraction and implant feed were the only two adjustable parameters , this is very much in accordance with the manufacturer's recommendations. It also corresponds to the situation when using an automated insertion tool and programs it according to the AOS standard. The integrated actuators will indeed implement the desired movements of implant and stylet in a precise but consistent manner. The insufficient initial straightening of the electrode array, combined with the lack of possibility of performing a compensation movement , leads to a high frequency of ratings with grade III or even IV.Individual results using autoAOS show the advantage of a straight starting configuration. The best outcomes were obtained with electrode array RE07. With the other electrode arrays, however, there are also phases of the insertion process without risk for hearing preservation (grades 0 and I). RE07 is characterized by the flattest curling profile and shows pronounced straightening in the initial phase. The shape of the “trauma risk” curve during insertion indicates that the process is less traumatic in the basal part of the cochlea than in the apical region see . These sx and Δφ for manAOS. It is therefore expected that, in practical implementation of autoAOS incorporating a guiding tube, the trauma risk for an insertion process of this kind (referred to as “minAOS”) is in the same range as manAOS.In practice, a major deficiency of preformed electrode arrays, namely, the insufficient initial straightening, can be compensated for by a guiding tube. This kind of mechanical straightening of the implants would have an impact on the intracochlear situation in the simulation with SimCInsert comparable to that of the adjustment of the intracochlear position of the electrode array toward a contactless midscala position using ΔNotwithstanding the inaccuracies involved in modelling of minAOS/autoAOS due to the insufficient consideration of the influence of a guiding tube, the results presented clearly demonstrate the advantages of individual optimization of the insertion process. Comparison of Figures It is noteworthy that the incidence of trauma risk grade IV is nearly equal in those cases with consistent (autoAOS) implementation and manual (manAOS) implementation of the AOS technique. This applies irrespectively of which electrode array (variations in curling behaviour) or which investigated cochlea  is used. The “intuitively optimized,” manual-insertion-only phases of the insertion process with grade ≤ III can be carried out in a more minimally traumatic manner. Only by considering information about both the individual anatomy and the specific curling behaviour of the inserted electrode array, as was carried out for optIns, is it possible to substantially reduce the risk of insertion trauma.This remarkable improvement in insertion behaviour with optIns is evident in the high percentage of grade 0 outcomes. For optIns, this degree of risk rating accounts, in all cases, for the largest portion of the total insertion process. After optimization, by adjusting the specific intracochlear curling behaviour of the electrode array to the individual anatomical constraints, the insertion process is unquestionably less risky than without optimization. The working hypothesis is thus substantiated.The summary of the results in Figures φ and Δy in comparison with the AOS technique. In subfigure (b), the same graphs are colour-coded by cochlear size, and in subfigure (c) equal colors indicate the same electrode array. Only in the second case can regularities be found in the insertion process supporting the conclusion of a greater impact of curling behaviour on the quality of the insertion process. In a converse consideration, this means that only if the curling behaviour of the used implant is known during preoperative planning can the insertion process be significantly optimized. Knowledge only of the individual anatomy (shape of the cochlea) does not allow prediction of the most useful insertion parameters for gentle and therefore less traumatic insertion.These findings are supported by a closer look at the insertion parameters, as provided in Figures The converse implication of this finding is that improvements to the electrode arrays, such as more predictable curling behaviour, a straight starting configuration, or even steerable electrodes for truly controlled insertion, have strong potential to enhance the insertion process. This primary importance of curling behaviour with regard to an optimization process for electrode insertion is an encouraging outcome in terms of clinical implementation. Even with the available electrode arrays, and later with technical advances to the implants, improved insertion is possible. Only when this optimization potential is fully exploited is a detailed consideration of the individual anatomy necessary for further improvements. Thus, innovative, clinically approved, high-resolution imaging methods to acquire detailed anatomical information on the patient are not absolutely essential in the short term. Improvement of the insertion process is already possible even before these become available. This is why optimization strategies regarding cochlear implant (CI) electrode insertion should address the implant's curling behaviour and curling mechanism.The outcomes of the optimization process also show that it was not possible in all cases to find a “contactless” shape and location for the electrode array inside the inner ear. There are two main reasons why individual optimization of the insertion process by using the CA electrode array is of only limited benefit. The first reason is related to the type of passive curling behaviour which can be found in that type of preformed electrode array. In consequence, that portion of the electrode array which is released from the stiffening effect of the stylet reverts immediately and completely into its manufactured shape. Thus, a characteristic aspect of curling behaviour in the CA electrode is the coiling which starts from the tip of the implant. However, this leads to a fundamental mismatch between the changes in the spiral shape of the electrode array and the spiral shape of the inner ear, one which cannot be overcome by the optimization process. While the electrode array is moved in the basal, and therefore only slightly curved, part of the inner ear, the electrode array already shows the final and maximum curvature in the tip region due to the onset of stylet extraction. Only with total insertion depth and in the final position shapes of the electrode array and the inner ear is there an ideal match.However, this confirmation is also limited, which leads to the second of the above-mentioned reasons: the average spiral shape with which the CA electrode is produced. The shape of the electrode array is neither individually produced, nor is it possible to individualize the curling behaviour itself . InsteaThe benefits of an individually optimized CI electrode insertion process will lead to noticeable and measurable advantages for the patient only if it can be transferred into clinical practice. As well as the challenges involved in enhancing the experimental prototypes of the automated insertion tool , 41 intoAlthough the white marker is a good and established indicator of initial insertion depth (the first step of the AOS technique), this can be improved by taking into account the individual length of the basal turn of the cochlea. As the length between electrode tip and white marker is not dependent on the curling profile, there are no relevant differences between different CA electrodes.A closer look at the relationship between implant feed and stylet extraction shows that there is uniform deviation from the original AOS technique after optimization. As Where the AOS technique was employed for the simulation, excessively deep insertion was frequently observed resulting in a large degree of contour damage/intersection. As already mentioned in (2), average limitation of the insertion depth may be expected to reduce insertion forces.As this entails higher complexity and additional effort, it is appropriate to consider the least time-consuming approach in using average data. This could involve one-off measurements of a representative number of electrode arrays and calculation of an average curling profile. In the course of the preoperative, patient-specific optimization process, this average curling profile needs only to be combined with individual image data for the cochlea. Although both Rau et al.  and PileIndividual determination of the curling behaviour of the electrode array.Design features:Insertion tool with guiding tube.Stiffer stylet for straighter starting configuration.New technologies to reduce variability.Automated manufacturing processes (batch processing) for higher reproducibility of curling behaviour.Active curling mechanism; steerable or controllable curling behaviour.However, the use of the CA electrode array in conjunction average values for curling behaviour has several drawbacks. It should not be forgotten that the CA was not originally designed for this concept. Two independently performed investigations showed high variability in curling behaviour, which limits the usefulness of previously experimentally determined average values. As a consequence, there would be large deviations between the planned and actually performed insertion with corresponding reductions in the benefit from a given optimization. For a comprehensively optimized insertion process, the determination of an averaged curling profile is not an option. In order that the advantages of individually optimized insertion can be fully exploited intraoperatively, it is necessary to compensate for the high amount of variability in curling behaviour. For this purpose, different strategies are under consideration which are listed below (sorted by increasing complexity):Clinical implementation in the near future can be achieved by individual determination of curling behaviour. This requires no changes in the design of the electrode array and only minor modifications of the certified manufacturing processes. As regards production, an assembling process already exists by which the stylet is integrated into the electrode array. The measurement can, therefore, be carried out by the CI manufacturer. After reloading of the stylet, the electrode array can be delivered together with the associated curling profile data. This approach is supported by two facts: first, the high degree of reproducibility of the curling behaviour after repeated extraction of the stylet , 11  drawbacks regarding insertion behaviour.A more forward-looking approach involves research activities in the field of CI electrode development which address how to obtain more controllable and steerable curling behaviour in order to perform a controllable insertion. Different curling mechanism or integrated actuators are currently under investigation, including embedded actuation strands , 25, fluIn this study, it was shown that the passive curling behaviour of clinically established cochlear implant (CI) electrode arrays holds potential for further optimization of the insertion process. By means of controlled, individualized tailoring of the movement and change in shape of the implant to the inner ear anatomy of a given patient, the insertion process can be optimized regarding a reduced risk of intracochlear damage. It is especially noteworthy that this improvement was achieved without any modifications or even development of new, active  electrode arrays with an integrated curling mechanism, but rather with a commercially available implant. Therefore, these findings highlight out an entirely novel aspect of clinical application of the Contour Advance (CA) in particular and preformed perimodiolar electrode arrays in general. Although this has not yet been investigated, it is self-evident that comparable improvement can also be achieved using other preformed CIs such as those incorporating MRA or HiFocus Helix electrodes.


Mantis shrimp and primates both possess good color vision, but the neural implementation in the two species is very different, a reflection of the largely unrelated evolutionary lineages of these creatures. Mantis shrimp have scanning compound eyes with 12 classes of photoreceptors, and have evolved a system to decode color information at the front-end of the sensory stream. Primates have image-focusing eyes with three classes of cones, and decode color further along the visual-processing hierarchy. Despite these differences, we report a fascinating parallel between the computational strategies at the color-decoding stage in the brains of stomatopods and primates. Both species appear to use narrowly tuned cells that support interval decoding color identification. In the second half of the 19th century, James Clerk Maxwell showed that people make color matches by equating light absorbed in each of three photoreceptor classes. Maxwell's results supported the idea that color is represented in the human brain by a linear three-dimensional (3-D) space in which distinct points correspond to different colors, while each point (color) within this space corresponds to an almost infinite number of physically distinct lights (metamers). For example, the single-wavelength yellow of the rainbow is indistinguishable from an appropriate mixture of wavelengths that separately appear red and green—both stimuli cause the same relative activation of the three cone types. Maxwell's discovery pointed to the critical role that neural comparison of photoreceptor outputs plays in determining what colors we see.When The eyes and photoreceptors of mantis shrimp and humans are clearly different, but are the neural strategies used to compute color that different? On the basis of physiological and anatomical research in macaque monkeys, a trichromat with color vision very similar to humans , we havehttp://i-perception.perceptionweb.com/journal/I/volume/5/article/i0662sas) shows the simulated responses of the whole population to each color stimulus. The cells have been sorted along the x-axis according to their color preferences: cells tuned to red are on the left, followed rightwards by cells tuned to orange, yellow and so on around the color circle. The stimulus is depicted by the red symbol, and the decoded color is simply the color preference of the cell with the maximum firing rate. For the first trial, the cell with the maximum firing is tuned to the stimulus color, showing that the simple decoding strategy worked. As the simulated stimulus changes from 1 to 45, even with this meager number of cells and stimuli, the population supports fairly accurate interval decoding of color. Since each cortical neuron receives thousands of synapses, and color cells are organized into local columns of similarly color-tuned cells, it may be unrealistic to restrict the decision to a single neuron's response. So we used the average of the responses of all cells with the same preferred color, and found that the decoding accuracy improved markedly (To test this idea, we used simulations to determine the extent to which primates could use narrowly tuned IT cells for an interval-color-decoding strategy similar to the one that is postulated to operate in the mantis shrimp. The strategy hypothesizes that the decoded color of a stimulus corresponds to the color preference of the IT neuron that produced the highest firing to the stimulus. In formal terms, this approach couples interval coding with a winner-take-all decision rule. For each of 279 posterior IT “glob” cells, based on responses to brief presentations of 45 colors measured with single-unit recording , we simumarkedly —right. Tmarkedly  that havmarkedly .It is intriguing to consider whether winner-take-all with IT cells represents a hard-wired approximation of optimal Bayesian decoding of the population of responses. If the neurons in the population have independent variability, then the population response probability will be the product of the Poisson probability of all the neurons. Applying Bayes' rule to get the probability of decoding a stimulus color given a pattern of population responses, leads to an expression for decoding that contains a term that represents multiplication of tuning curves raised by the number of spikes, and is the only term that depends on the pattern of responses on a trial. A cell that only fires if it gets spikes from two cells within a short time interval, will only fire for stimuli for which the tuning curves of the earlier cells overlap, i.e. the output tuning curve will look like a multiplication of the input tuning curves. Similarly, a cell that only fires if it receives a defined number of input spikes in a short interval, will have a tuning curve that looks like the input tuning curve raised to the power of the number of spikes . These oIn mantis shrimp, the cost of early functional specialization in the compound eye, and the sub-division of tasks to different eye areas , requireDespite tremendous differences in human versus mantis shrimp eye structure and brain circuitry, the striking similarity between the color sensitivities of primate IT neurons and stomatopod photoreceptors provides evidence of a common computational strategy across largely unrelated species. Interval decoding of color is an interesting example of independent evolutionary histories converging on the same robust computational principle, and may thus be worth emulating by machine vision systems designed to function in the real word.


Taenia solium, a zoonotic infection transmitted between humans and pigs, is considered an emerging infection in Sub-Saharan Africa, yet individual and community-level factors associated with the human infection with the larval stages (cysticercosis) are not well understood. This study aims to estimate the magnitude of association of individual-level and village-level factors with current human cysticercosis in 60 villages located in three Provinces of Burkina Faso.Baseline cross-sectional data collected between February 2011 and January 2012 from a large community randomized-control trial were used. A total of 3609 individuals provided serum samples to assess current infection with cysticercosis. The association between individual and village-level factors and the prevalence of current infection with cysticercosis was estimated using Bayesian hierarchical logistic models. Diffuse priors were used for all regression coefficients. The prevalence of current cysticercosis varied across provinces and villages ranging from 0% to 11.5%. The results obtained suggest that increased age, being male and consuming pork as well as a larger proportion of roaming pigs and percentage of sand in the soil measured at the village level were associated with higher prevalences of infection. Furthermore, consuming pork at another village market had the highest increased prevalence odds of current infection. Having access to a latrine, living in a household with higher wealth quintiles and a higher soil pH measured at the village level decreased the prevalence odds of cysticercosis.This is the first large-scale study to examine the association between variables measured at the individual-, household-, and village-level and the prevalence odds of cysticercosis in humans. Factors linked to people, pigs, and the environment were of importance, which further supports the need for a One Health approach to control cysticercosis infection. Taenia solium is an infection that is transmitted between pigs and humans. Humans may get infected with the larvae of Taenia solium, which results in cysticercosis, an infection common in pig farming communities where there is poor sanitation and free roaming pigs. Most published studies on this infection have included less participants covering a restricted geographic area, thereby resulting in a limited understanding of the important risk factors for infection. Our study aimed to examine important individual-, household- and village-level characteristics associated with current infection using baseline data from 3609 participants living in 60 villages across three provinces in Burkina Faso. Blood samples from village participants were taken to assess whether they were infected with cysticercosis. We found that eating pork, especially in other village’s markets, being older and male, living in a poorer household, not having access to a latrine, and living in a village where a larger percentage of pigs are left roaming were associated with infection. Soil pH and composition may also play a role in infection. Our results suggest that interventions that include human and veterinary health as well as environmental components should be considered to effectively control cysticercosis in such settings. Taenia solium cysticercosis, a zoonotic infection transmitted between humans and pigs, is considered as an emerging infection in Sub-Saharan Africa. In the Sahel and West Africa region, the pig population has increased by 23% between 1985 and 2005, the largest increase in all animal populations during that period [T. solium infection in humans and pigs. This is likely to have great consequences on public health since humans, when infected with the larval stages of the infection, may develop neurocysticercosis (NCC). NCC is a preventable cause of multiple neurological manifestations including epilepsy, severe chronic headaches, and focal deficits, to name but a few [ut a few –6.Serological studies using tests to detect antigens or antibodies have demonstrated the presence of the infection in humans  and pigsPrevious studies conducted in West Africa have included a small number of participants or of villages, limiting the ability to detect associations, and especially weaker ones, between village-level as well as individual-level variables and infection. A better understanding of individual and community-level factors associated with infection is essential to developing effective control strategies to reduce the burden of this devastating disease.The aim of this study is to estimate the magnitude of association of individual-, household- and village-level factors with current human cysticercosis infection in 60 villages located in three Provinces of Burkina Faso.This study reports on the baseline cross-sectional component of a large community randomized-control trial aimed at estimating the effectiveness of an educational package on reducing the cumulative incidence of current infection of human and porcine cysticercosis. The baseline cross-sectional study took place between February 2011 and January 2012.Institut Géographique du Burkina (from the year 2000); being separated from another participating village by at least 5 kilometers. A third village meeting all the eligibility criteria was also selected at random in each department as a replacement if the village initially sampled were to be found not eligible during the field visit . Only one village met the eligibility criteria in the Department of Zamo (Province of Sanguié). A village located in the Department of Pouni but right on the border with Zamo was selected as the second village for that Department. The location of all participating villages is illustrated on The provinces of Nayala (Region of Boucle du Mouhon), Boulkiemdé and Sanguié (Region of Centre-Ouest) were selected for inclusion in the study. Boulkiemdé and Sanguié are among the provinces with the largest number of pigs in the country  is defined here as a group of households living in a residential development, often fenced, where the authority of a concession chief is recognized. A household is defined as a socio-economic unit where members live together, share resources and satisfy the food and other essential needs of all members. In general, a household includes a man, his wife or wives, their children, and any other person who shares resources with other members of the household.A In each village, the research team of five or six interviewers started by visiting the concession of the village Chief. The field team moved counter clockwise to enumerate each concession. In each concession, starting on the right from the entrance, the field team enumerated each household, as well as the number of members and if someone raised piglets less than 12 months old or reproductive sows in each household.A stratified random sampling approach was adopted to select concessions. The strata were the presence of reproductive sows, piglets, or no pigs. First, the list of all concessions where there was at least one household raising sows was made and corresponding concession numbers were placed in a bag. A village member was asked to sample 10 numbers from the bag. If 10 or less concessions were raising sows, all of those concessions were invited to participate. Next, the numbers of all concessions where at least one household raised piglets aged 12 months or younger were placed in a bag, including concessions where sows were also raised but that were not selected in the previous step. A village member was asked to sample 30 additional numbers from the bag. If 30 or less concessions raised piglets less than 12 months of age, all of those concessions were invited to participate. Lastly, the numbers of all concessions not yet sampled were placed in a bag. A village member was asked to sample an additional 40 numbers. This resulted in the sampling of a total of 80 concessions in each village, with at least 10 concessions with sows and at least 30 concessions with piglets aged less than 12 months, except in a few villages in Nayala where there were less than 40 concessions raising pigs in the whole village. Once the Chief of a sampled concession gave his/her consent to participate in the study, he was asked to enumerate all households in the concession with the names of their Heads. Numbers corresponding to the households were placed in a bag and the chief of the concession was asked to sample one number from the bag, or, if there was only one household in the concession, that household was selected. The Chief of the selected household was asked for his consent to participate in the study and to enumerate all members of his household. Only one Chief of household refused participation in Boulkiemdé and asked that his father’s household be sampled instead of his, as a mark of respect for his elder. All household Chiefs consented to participate.Each eligible household member was allocated a number. The inclusion criteria for participants were that they were at least 5 years old, had lived in the village for at least 12 months and were not planning to move in the next three years. The head of the household was asked to pick a number from the bag. The person with the corresponding number was asked for his/her consent to participate in the study which included a screening questionnaire on epilepsy, progressively worsening severe chronic headaches as well as a blood sample to test for the presence of antigens to the larval stages of cysticercosis. Participation in the study involved answering the screening questionnaire and having blood collected three times in a three-year period for the purpose of the parent community-based randomized controlled trial. The sampling process (starting with the concession sampling) was repeated until 60 people consented to being screened and having blood collected three times over three years duration of the randomized trial. If the sampled person refused to consent to the serological component of the study, s/he was asked for his/her consent to participate in the screening-only study for a maximum of 20 screening-only participants per village. If the sampled individual did not consent to either the serological or screening study, the head of the household was asked to sample another number from the bag for that household until a consenting individual was found. There were a few refusals to the serological participation, and all cases were replaced as described above. No one refused to participate to the neurological component of the study.T. solium infection and life cycle, and screening questions on seizures, epilepsy, and severe chronic headaches. Since the focus of the current study is to estimate the magnitude of association between potential risk factors and current cysticercus infection, results from screening for epilepsy and progressively worsening severe chronic headaches are not reported. In addition, the Chief of each participating household was asked to list assets owned by members of the household . The mother of each household was asked questions about preparation of pork and access and use of latrines by members of the household. The building material of the house’s roof, floor and walls was also measured at that time. In each village, the owners of at most 10 sows and 30 piglets aged less than 12 months were interviewed regarding their pig management practices (at most 40 pig owners per village). All questionnaires were conducted and recorded on Personal Digital Assistants (PDAs). The PDAs recorded the geographical coordinates of each concession.Each consenting participant was asked to answer an individual questionnaire including questions about socio-demographic factors, pork consumption behavior, knowledge of et al. (2000) [We used indicators of wealth as suggested in Gwatkin . 2000)  to estim. (2000) ,20. Prin00  to es. (2000) . The impBetween 18 March and 25 November 2014, the field team returned to each village to take soil samples to measure soil composition and pH using the LaMotte Soil Texture Unit test (code 1067) and LaMotte pH Test kit (code 5024), respectively. The soil composition test estimates the percentage of sand, silt and clay in the soil. In each village, a soil sample was taken in each of the four cardinal directions (within 2 km) using a plastic pot filled to 125 ml, having scraped the soil surface to a depth of about 5 to 10 cm. The four samples were then thoroughly mixed, dried and cleaned of coarse elements such as stones. A subsample of this mixture (about 125 ml) was then taken and stored for analysis of soil composition and pH, according to LaMotte procedure.Institut de Recherche en Sciences de la Santé) in Bobo-Dioulasso every 4 to 8 weeks and kept thereon in a freezer at -20°C until analyses took place.After an average of 7 weeks (range of 0 to 140 days), a physician went to each village to take blood samples from the 60 participants who consented to the serological component of the study and to examine all participants who had screened positive for seizures, epilepsy or severe chronic headache. Any participant confirmed as having epileptic seizures, epilepsy or severe chronic headache who had not initially consented to the serological follow-up were asked to provide a blood sample for  diagnosis purposes. However, to avoid an over-selection of people with neurological symptoms in our analysis, only those who initially consented to the serological analysis component of the study are included in the analysis. Blood samples of 8 ml were drawn by venipuncture using a syringe, preferably at the antebrachium vein, using 10 ml Venosafe serum gel tubes. The tubes were placed in a cooler, left to decant, and the sera were collected and put in two pre-labelled tubes at the end of each day or the following day. The sera were placed in freezers (-20°C) at most three days after the blood draw. The sera were brought to the IRSS (T. solium using the B158/B60 enzyme-linked immunosorbent assay (ELISA) [The serum samples were tested for presence of excretory secretory circulating antigens of the metacestode of  (ELISA) . The tes (ELISA) .Descriptive analyses on the study population were first conducted, followed by assessing the association between each potential risk factor and the prevalence of current cysticercus infection at the individual-level and at the village-level. Household characteristics measured through the mother and chief questionnaires were attributed to each individual since only one individual was sampled per household (and concession). Consequently household-level variables were included at the individual-level in all analyses. All descriptive analyses were conducted in Stata 13.1.Data obtained from pig owners were considered as village-level variables. These included the percentage of pig owners letting their animals roam all seasons, practicing home slaughtering of pigs and asking for inspection at the time of slaughter. Soil composition, soil pH and the season when human samples were collected (dry vs wet) were also considered as village-level variables. The effect of the coverage of the 2012 filiariasis mass drug delivery campaign, which provided albendazole (400 mg) with ivermectin, obtained from the Ministry of Health, was also explored at the village-level.The effects of variables which may impact the contamination of the environment with human feces were explored at the individual-level and at the village-level. These included the use of latrines to defecate reported by interviewees, the access to a latrine as reported by the mother, the household wealth quintile , the knowledge about taeniasis including report of self-infection, and the reporting of pork consumption at home and outside the home.Individual-level variables explored that were not likely to directly influence environmental contamination included age, gender, education and occupation, although the effect of age was modelled separately for each province. Age was categorized because it was not linear in the logits.The only concession-level variable explored was the type of concession sampled .Given the sampling strategy, concession, household and individual characteristics were all attributed to the individual-level in the analysis. To take the stratified nature of the sampling into account, models including the type of concession sampled were run but did not modify the estimated medians and 95%BCI of the estimates. Hence, results from the simpler model are being reported here.Bayesian hierarchical logistic models were fitted to estimate the prevalence odds ratios between each variable of interest and the prevalence of current cysticercus infection. Some models were also run with Bayesian hierarchical log-binomial models and resulted in similar estimates when convergence was achieved. At the first level, current cysticercus infection was assumed to follow a Bernoulli distribution. The logit of this distribution was modeled using the individual-level variables and village-level random-effect intercepts. At the second level, each village-level intercept was assumed to follow a normal distribution. The mean of the random-effect intercepts were modelled as a linear regression using the village-level variables, including the province in some models. The effect of the provinces with a random-effect on villages was not important, and therefore all presented models exclude province effects. Diffuse priors were used for all regression coefficients. Missing independent variable values were imputed using the mean value of non-missing data, assuming an ignorable missingness mechanism. When the mean values varied by province, province-level means were used for imputation. Fit was measured by comparing deviances. Convergence was assessed by looking at the history and b Rubin Gelman plots. Some of the more complex models required large numbers of iterations and thinning of 100 to obtain stable estimates. All models were run in WinBUGS .The protocol and consent forms were approved by the University of Oklahoma Health Sciences Center Institutional Review Board and by the Centre MURAZ ethical review panel (Burkina Faso). All participants were read the consent form and any questions they had were answered to the best knowledge of the field staff. Each participant was given a bar of soap to thank them for their time. Information about the study provided in the consent forms were read and explained to each potential participant  by the field workers who took the time to answer all questions. Consenting participants signed the consent forms when able or put a cross when not. All consents were witnessed by a local villager. Children aged more than 10 were asked for their assent, but parents consented for all children aged less than 18 years old.A total of 4795 villagers consented to being screened for epilepsy and severe chronic headaches three times during the course of the parent community-based randomized trial. All three mother, chief of the household and individual questionnaires were missing for three individuals who were excluded from the analyses. Of the remaining 4792 participants, 4788, 4772 and 4778 had information from the chief questionnaire, mother questionnaire or individual questionnaire available, respectively. A total of 3609 participants consented to participate in the serological component of the parent randomized trial and provided sufficient blood at baseline to be analyzed. The characteristics of individuals participating in the serological and screening-only component of the study are described in A total of 120 individuals tested positive for current infection with cysticerci. The prevalence of current cysticercosis varied considerably across provinces and villages Figs  ranging The major differences in the three models come from the inclusion of the type of soil and soil pH. When these variables are excluded, the percentage of pigs not penned during the rainy season (i.e. left roaming or tethered) led to a weaker association with the prevalence odds of cysticercosis. An increase in the alkalinity of the soil was associated with a lower prevalence odds of cysticercosis. This effect was only noted when the percentage of silt or sand in the soil was also included in the model. We present here the effect of the percentage of sand, but the percentage of silt had an opposite effect of similar magnitude to that of sand.This cross-sectional study is the most widespread ever conducted, estimating factors associated with the prevalence of current infection of human cysticercosis. Our study is unique in its inclusion of 60 villages located in three provinces and the evaluation of over 3600 people living in these villages. The inclusion of only one individual per household and concession reduced the dependence among observations, thus maximizing the power to detect individual and household-level factors associated with the prevalence. Our hierarchical model also includes potential risk factors measured at the individual- and village-level, thus respecting the sample size of each unit. Finally, by including the village as random-effects, and having explored the impact of incorporating the type of concession which was part of the sampling scheme, we are effectively using a model-dependent approach to adjusting for the sampling scheme, thus reducing the potential biases which may be introduced by clustered sampling . To our We found that the prevalence of current infection with cysticercosis varied from 0% to 11.5% in the sampled 60 villages. These villages were sampled with the goal of conducting a community-based randomized controlled trial and participants were selected based on the presence of pig raising in their household. Therefore, the overall prevalence cannot be generalized to the three provinces nor to the country as a whole. Nonetheless, the village-level prevalences of current infection with cysticerci measured with the AgELISA are within the range of those reported by others using the same test in community-based studies conducted in three rural communities of West Cameroon  to 3%  depending on the locality) [% to 3%  was linked to an increase in inactivation rates of the eggs while the opposite was true for in an acidic environment (pH from 5.1 to 5.5) [This design also allowed us to find an association between the type of soil and the soil pH and the prevalence odds of current infection. An increase in the pH of the soil was associated with lower village-level prevalence odds of current infection. In an experimental study of inactivation of  to 5.5) . The soi to 5.5) . HoweverA self-report of a history of infection with taeniosis was associated with current infection with cysticerci only in univariate analyses. This association was confounded by age, and became non-significant in the hierarchical model also including pork management variable. Others had found associations between the self-report of taeniosis and exposure to cysticercosis in univariate analyses . This unThis study had some limitations. The most important one is that the soil samples were collected nearly three years after the baseline study, therefore, these associations should be interpreted with great care. This is why results were presented with and without including the soil analyses. Future studies using follow-up data of the randomized trial among the control group should be able to confirm (or not) this association. Only one person per household was sampled and therefore, factors affecting clusters within households could not be evaluated.In conclusion, this study is the first to assess the association between several individual-, household, and village-level variables and the prevalence odds of cysticercosis in humans at a large scale. We found that factors linked to people, pigs, and the environment were of importance. This further supports the need for a One Health approach to control this infection.S1 Checklist(DOC)Click here for additional data file.S1 DatasetTable vill_level with with percent of roaming pigs, soil pH level and percentage of sand in the soil by village.(XLS)Click here for additional data file.S1 Fig(JPG)Click here for additional data file.