Ready‐to‐use Therapeutic Food (RUTF) therapy is a standard protocol for treating children with severe acute malnutrition (SAM) admitted in Out‐Patient Therapeutic Programmes (OTP). The amount of RUTF to be consumed by a child is based on weight  as stipulated in the Kenya Integrated Management of Acute Malnutrition (IMAM) protocol for timely weight gain. There is limited information on the determinants of consumption of the correct amount of RUTF. This study sought to fill this gap by establishing the associations between the caregivers' and the child's characteristics and the amount of RUTF the child ate within a 24‐h recall period. We used a cross‐sectional study design and interviewed 200 caregivers of children 6–23 months of age admitted in four OTP centers in Nairobi Kenya. We used a researcher‐administered questionnaire to collect information from the caregivers. Seventy‐three percent of the children ate the recommended amount of RUTF. A smaller proportion (54.4%) of younger children (6–11 months of age) ate the recommended amount of RUTF compared to older children . The predictors of consumption of the correct amount of RUTF were child's birth order—firstborn  and children's age; 12–17 months old  and 18–23 months (AOR 6.19 95% CI: 2.62), indicating that firstborn and older children were more likely to consume the correct amounts of RUTF. Caregivers' knowledge and correct practices in feeding a child with RUTF also predicted the consumption of the correct amount of RUTF. In conclusion, maternal and child characteristics are determinants of the consumption of the correct amount of RUTF by children in OTP. Two‐hundred caregivers were assessed, where 73% of the children consumed the recommended amount of RUTF. A smaller proportion (54.4%) of children aged 6–11 months consumed the recommended amount of RUTF compared to older children. Predictors of amount of RUTF intake were child's birth order—firstborn  and children's age; 12–17 months  and 18–23 months (AOR 6.19 95% CI: 2.62) and caregivers' knowledge and practices in feeding a child with RUTF. None of the studies focused on the actual intake of the RUTF by the affected children and the factors determining achievement of adequate intake of RUTF. Consumption of an inadequate amount of RUTF by children with SAM translates to less nutrient intake per day, hence delaying recovery and lengthening the treatment period  guidelines , and illicit activities, for example, brewing unhygienic liquor. About half (51%) of residents in these informal settlements live in overcrowded conditions , insufficient education support, access challenges to appropriate health and nutrition services, lack of enough space for shelter, and insufficient finances are the most common challenges in these settlements  because it was necessary to target specifically the caregivers with children admitted to OTP with severe acute malnutrition, and it is these centers that have OTP services. We also considered homogeneity in living conditions  for the purposive sampling as all the four health facilities are situated in a strategic location where they serve the majority of families residing in the urban informal settlements. We recruited all the 200 caregivers and their children 6–23 months of age in the four OTP centers who were enrolled into the program at the time of the study and who met the inclusion criteria, upon obtaining their voluntary, informed consent  without complications, having passed the appetite test. Children with edema grade 1 (+) without any medical complications were included in the study. In all cases, voluntary informed consent was obtained from the caregiver. We had planned that should any child sampled for the study develop medical complications  during the time of the study and be referred to the stabilization/inpatient center before the caregiver was interviewed, the same would be excluded from the sample. However, there were no such cases and therefore we retained the 200 sample of caregivers and their children aged 6–23 months old.2.5Data collection was conducted by three research assistants with a Diploma level of qualification in Nutrition under the supervision of the researchers. The research assistants were trained by the researchers before data collection. The caregivers were interviewed face to face, using a researcher‐administered questionnaire. The questionnaire was content‐validated and pre‐tested with about 10 mothers who were not included in the main study. During this pre‐test, the test–retest method was used to ensure reliability, by conducting two interviews 7 days apart  protocols . Descriptive statistics  were used to describe the caregivers and child demographic characteristics and maternal knowledge and practices on feeding a child with SAM. The Caregivers' knowledge on feeding a child with SAM was based on eight knowledge items out of which the mean knowledge score was calculated. One point was awarded for each correct answers resulting in a total score of 8, whereas zero was awarded for incorrect answers, and thus the least score was zero. Chi‐square test was used to establish associations between categorical variables. Multiple logistic regression was performed to establish the determinants of consumption of the correct amount of RUTF in the last 24 h among the children with SAM. A 33.1A total of 200 caregivers with children aged 6–23 months consented and participated in the study, resulting in a 100% response rate. There was a relatively equal representation of both sexes of the children, 52% being female while 48% were male children. Most of the children with SAM (40.5%) were in the age bracket of 6–11 months followed by children 18–23 months of age (32%). Most (94%) of the caregivers were females, the majority being young mothers between 21 and 30 years of age. The mean age of the caregivers was 27.1 ± 7.6 years. Almost three‐quarters (73.0%) of the caregivers were married. A majority of the caregivers (71%) were either first‐ or second‐time mothers with one or two children. About half of the caregivers (47.5%) had a primary level of education, while 21% had completed secondary level of education. The main occupation for the caregivers was being a housewife (44.5%), followed by casual labor (29.5%). In terms of monthly income, 40.5% of the caregivers earned between 0 and 5000 Kenya shilling , 33.5% earned between 5001 and 10,000 Kenya shillings. In most households (70%), fathers were responsible for food provision. Most (97.5%) of the houses were iron‐sheet roofed and iron‐sheet‐walled (71.0%). In terms of flooring, 58.5% of the houses were concrete‐floored while the remaining 41.0% were earthen floors. Majority of the caregiver's (67.0%) used paraffin as a source of fuel, while 26.5% used charcoal. About half of the caregivers (50.5%) obtained water for domestic use from communal tap/pump while 48.0% obtained water piped from a tap outside their houses.2 = 5.816; p = .025) than the child who was ill. Children who were firstborn in the family were more likely to consume an adequate amount of RUTF . A greater proportion of children whose caregivers were housewives and casual laborers consumed the required amount of RUTF compared to those whose caregivers were engaged in formal employment or engaged in business . The children of caregivers with upper or secondary level education were significantly more likely to consume the correct amount of RUFT  than those whose caregivers had a lower level of education.Chi‐square test was conducted to show the association between the child's and caregiver's demographic and socio‐economic characteristics, with adequate consumption of RUTF. The consumption of the adequate amount of RUTF per day was significantly associated with children's birth order, child's morbidity status, the caregivers' occupation, and educational level. A child who was not sick the day before the interview was more likely to consume adequate amount of RUTF (χU‐test) was conducted to show the significant difference between child's and caregiver's characteristics and the consumption of adequate amount of RUTF. A significant difference was observed between the age of the child and consumption of adequate amount of RUTF. Among the children who consumed the adequate amount, majority of them were significantly older compared to those who did not consume the correct amount . Another significant difference was observed between the caregiver's age and consumption of adequate amount of RUTF. Majority of the children who consumed the correct amount of RUTF were from significantly older caregivers compared those who did not consume the correct amount . Table Mann–Whitney (3.2−1 day−1) as per the instructions given to them by the health workers. More than three‐quarters of the caregivers (77.6%) knew that plenty of drinking water should be given to the child immediately after taking the RUTF. Most of the caregivers (79.7%) knew that appropriate administration of RUTF with frequent breastfeeding alone without any additional solid or liquid food was enough to help the child regain normal weight and recover from severe malnutrition. All the mothers knew that a child should continue breastfeeding while undergoing treatment for severe acute malnutrition.A majority (88%) of the caregivers could explain that ready‐to‐use therapeutic food (RUTF) was the food used to treat children with SAM. The majority (87.3%) knew the number of RUTF sachets their children should be given per day based on their weight ; the correct amount of RUFT that the child should consume per day ; a child should be given water to drink immediately after feeding on RUTF ; and that RUTF should be kept in a clean and dry place to ensure safety were likely to consume the correct amount of RUTF  shown in Table On the whole, caregivers' knowledge was statistically significantly associated with the consumption of the correct amount of RUTF. Significant associations were observed for the children of caregivers who were knowledgeable on the following: the need to wash hands before handling and giving RUFT ; child was breastfed the previous day ; and child drank water during and after feeding on RUTF  as shown in Table Relationship between caregivers' feeding practices for a child with SAM and consumption of the adequate amount of RUTF was assessed using Chi‐square or Fisher's exact test. The following practices were statistically significantly associated with the consumption of correct amount of RUTF: washing of hands before handling and giving the RUTF sachets to the child  = 233.304, p‐value <.01, indicating that the model could distinguish between children who consumed the correct amount of RUTF and those who did not.Multiple logistic regression was performed to establish the predictors of consumption of the correct amount of RUTF in the last 24 h among the children. The model contained 13 independent variables which had an association with the consumption of the correct amount of RUTF in univariate analysis. After controlling for caregiver's age, since most of the caregivers were young (21–30 years of age), the full model containing all predictors was statistically significant, χChildren who were firstborn (first birth order) were 30 times more likely to consume the correct amount of RUTF while second birth order children were 13 times more likely to consume the correct amount of RUTF in the last 24 h , respectively, compared to those who were thirdborns. Older children age groups 12–17 months of age were five times more likely to consume the correct amount of RUTF while those 18–23 months of age were six times more likely to consume the correct amount of RUTF in the last 24 h compared to younger children . Children whose caregivers had knowledge on the need to wash hands before giving RUTF were 8.5 times more likely to consume the correct amount of RUTF than those whose caregivers did not have this knowledge . Children whose caregivers knew the importance of giving water to drink after RUTF feeding were 10 times more likely to consume the correct amount of RUTF compared to those whose mothers did not have this knowledge . Similarly, caregivers who knew the importance of storing RUTF in a cool dry place were 24 times more likely to feed their children the correct amount of RUTF compared to those who did not know safe storage . In terms of caregiver practice, children whose caregivers washed their hands before feeding them with RUTF were 11 times more likely to consume the correct amount of RUTF than those whose caregivers did not wash their hands . Children who were breastfed the previous day were 20 times more likely to consume the correct amount of RUTF compared to those who were not breastfed . Similarly, children who drank water while feeding on RUTF were 10 times more likely to consume the correct amount of RUTF compared to those who were not given water to drink during feeding . Children who were not sick the previous day were five times more likely to consume the correct amount of RUTF compared to those who suffered illness the previous day   protocols  survey in Samburu  in the caregiver's practices in the management of a child in OTP using the RUTF therapy over the period the child was admitted in the program. Data on the amount of RUTF consumed depended on the caregivers' recall and thus there was a likelihood of recall bias in the finding. Appropriate attention was given to ensure quality control of data by thorough training of the enumerators, and close supervision of all the study activities.5We conclude that both caregivers and child characteristics play a role in determining the amount of RUTF that a child consumes among the study population. Moreover, caregivers' knowledge and practices on feeding a child with SAM are also important predictors of consumption of adequate amount of RUTF. This study has demonstrated that the consumption of the adequate amount of RUTF by severe acutely malnourished children in OTP is not only dependent on access to the product. Despite all the children in the study having access to the correct amount of RUTF, about one‐quarter of the children did not consume the correct amount of the product implying that these children would not gain weight at the expected rate, and therefore stay longer in the program than recommended, thus rendering the program less cost‐effective. There is a need for in‐depth qualitative investigation to establish the barriers to the consumption of the correct amount of RUTF, however. The product is accessible at no cost, and the majority of the caregivers were knowledgeable about the feeding of children in OTP, and their practices on feeding the children were on the whole appropriate. The findings of this study provide valuable information on the research efforts in rehabilitating children with SAM.The authors declare that they have no conflict of interest.


Mice can react to threatening stimuli in ∼250 milliseconds •Mice learn to escape via the fastest route after ∼10 minutes in a new environment•Escape routes are learned during exploration and do not require threat exposure•Mice prefer escape routes that minimize path distance and angle to shelter•Fast route learning can be replicated by model-based reinforcement learning agents Claudi et al. show that mice combine fast spatial learning with innate rules to quickly learn the fastest escape route to shelter when there are multiple possible paths. Previous work has shown that in simple arenas, mice escape along a direct vector toward a memorized shelter locationright path = 0.79, 600 trials from 83 mice; right path = 0.486, arena 2: Pright path = 0.731, arena 3: Pright path = 0.807, arena 4: Pright path = 0.829, p = 1.76e−10, χ2 test). The preference for the shortest path could not be explained by mice being more familiar with the short arm nor by choosing the arm they entered the threat platform from . While the first is likely learned during natural exploration of the environment, the second could, in principle, be learned through repeated encounters with threat or be innate . To distinguish between these two alternatives, we computed path choice probabilities for the first trial of threat presentation (naïve) and compared them with the probabilities for trials after experience with threats (experienced). We found that the preference for shorter paths and smaller angles to shelter was already present in naïve trials and that path choice probabilities were similar between naïve and experienced trials A. In addright path = 0.641, flipped Pright path = 0.321, p = 0.0014, Fisher’s exact test; Combining rapid learning of path properties with an innate value function allows mice to select escape paths shortly after entering a novel environment. Next, we aimed to establish whether this can also support adaptive escape route selection in a dynamic environment. We built a version of arena 4 where the path lengths could be quickly flipped between left and right sides . After e,,Learning the shortest escape route in our experiments was a fast process, which contrasts with the large amount of training needed for some spatial navigation and decision-making tasks,free-exploration, where agents explored the environment freely under an epsilon-greedy policy for 250 episodes, and guided-exploration, where agents explored the environment in a single episode and moved through the maze following the exploration trajectory of individual mice recorded experimentally .Further information and requests for resources and reagents should be directed to and will be fulfilled by the lead contact, Tiago Branco  were single housed on a 12h light cycle and tested during the light phase. Mice from the same litter were randomly assigned to different experiments when possible. Most animals (78/119) were only used once, and the remaining were used for experiments on two arenas on different days. Mice that were used twice did not show any difference in escape response or arm choice probability compared to animals that were used only once. All experiments were performed under the UK Animals (Scientific Procedures) act of 1986 (PPL 70/7652 and PFE9BCE39).The behavioral arenas consisted of white acrylic platforms elevated 30cm from the floor. Each arena was composed of octagonal platforms (24cm in diameter) and connecting bridges of various lengths (10cm wide). For the experiment shown in Mice were presented with auditory stimuli consisting of three frequency modulated sweeps from 17 to 20 kHz of 3 seconds each at a sound pressure of 70–85dB as measured at the arena floor. In some experiments overhead visual stimuli were used. These were projected onto a screen positioned 1.8m above the arena floor and consisted of a dark circle (Weber contrast = −0.98) expanding over a period of 250ms.Experimental sessions were filmed at 30 or 40fps with an overhead camera (positioned 1.8m above the arena floor). At the start of each experimental session mice were allowed to freely explore the arena for a period of ∼10 minutes, during which they spontaneously found the shelter. For experiments where the configuration of the arena was reversed, we allowed mice to explore the new configuration for ∼15 minutes. The additional ∼5 minutes serve to compensate for the additional time the mice spend in the shelter after threat presentation and generate an amount of active exploration comparable to the baseline configuration. After the exploration period, threats  were presented repeatedly while the animals were on a designated threat platform and facing in the direction opposite from the shelter platform. A stimulus response was considered an escape if the mouse reached the shelter within 10 seconds from stimulus onset. The number of trials in each experimental session varied across mice. Experiments were terminated when mice either remained in the shelter continuously for 30 minutes or failed to escape in response to three consecutive stimuli. Some experiments were performed in total darkness (with auditory stimuli only). No difference in behavior was observed between lights on and lights off experiments and thus the two datasets were pooled.The position and orientation of mice in the arena was reconstructed using DeepLabCutAll analysis was carried out using custom Python code and used several software packages from Python’s scientific software ecosystem: NumPy,−8) reward was also delivered for any training step in which the agent moved to a new cell to encourage exploration.Three classes of Reinforcement Learning (RLThree different reinforcement learning model were used. All models shared the same environment (state space), actions space and reward function (with the exception of QTable as noted above). The three models were: QTable . If the agent reached the shelter location the simulation was marked successful, otherwise it was labelled as a failure. If the agent attempted an illegal move  the simulation was terminated and considered a failure. The agents were not allowed to use the experience from this evaluation simulation for learning.In the guided exploration training, RL agents followed the exploration trajectory from the experimental animals. Tracking data from each experiment’s exploration phase was registered to the grid world arena through an affine transformation . Tracking data was represented at a higher spatial resolution that the grid world arena and did not match the grid world arena layout perfectly (due to imperfect registration of the tracking data to the standard template). The first issue was resolved by assigning, for each frame in the tracking data, the grid world arena cell closest to it. Imperfect alignment and tracking errors could not be corrected in some experimental sessions and these were discarded, leaving 42 valid sessions. As mice often remained in the same location for extended periods of time during natural exploration , these periods were eliminated from the tracking data and only frames in which the mouse moved from one arena cell to another were kept. The tracking data was then used to guide the movement of all agents during the training phase. For a given session’s data, the agent was initialized at the arena location corresponding to the first frame in the tracking data. For each step, the location of the next arena cell was identified and the action leading from the agent’s current cell to the next was identified. The agent then performed the selected action, experienced rewards and learned, as it would have during free exploration. Thus, the main difference between the free and guided exploration paradigms was that in the guided exploration regime agents were not allowed to select which action to perform as this was determined by the tracking data.Once the agent followed each step from the tracking data the training phase was concluded. The agent was then initialized at the start location and allowed to act greedily following the value function it learned during training, with the goal of reaching the shelter location. If the goal was reached the simulation was classified as successful, otherwise it was classified as a failure. If the agent attempted an illegal move  the simulation was terminated and classified as a failure.To calculate the probability of escaping in response to the threat stimulus, the movement trajectories during the first 10s after stimulus onset were analyzed, and the fraction of trajectories terminating on the shelter platform was computed. For comparison, randomly selected time points in which the same animals where on the threat platform but not presented with a threatening stimulus were selected, and the fraction of shelter arrivals in this random sample was estimated too. The number of randomly selected time points matched the number of trials. Fisher’s exact test was used to determine the significance of the difference in number of shelter-arrival trajectories between stimuli and control groups.To determine the probability of escape along the dead-end arm in arena 1, all trials from experiments in the arena were pooled. The trajectory in the 10 seconds following threat presentation was analyzed to determine which arm the mouse first moved to after leaving the threat platform, and the probability of escape along each of the three arms  was then computed. To distinguish between trials in which the mice escaped vs trials in which the mouse ignored the stimulus but still moved away from the threat platform, we used two criteria. First, since escapes are characterized by a higher running speed than normal locomotion,To quantify the average heading direction during escape, movement trajectories from each arena were selected and grouped into left or right path escapes. The trajectories where then truncated to the frame in which the mouse left the threat platform and their duration normalized. The average heading direction at regular intervals across all trajectories in the same group was then computed.2 test was used to test whether the probability of escaping on the right vs left path was significantly different from chance for asymmetric arenas.To estimate the probability of escape along a given path, all trials from experiments on each arena were pooled and the probability of selecting the right or left arm was computed. To assess the effect of arena design on arm choice probability, a χIn experiments in which the arena design changed during the course of an experiment, trials were pooled across animals and grouped into baseline (before the change) and ‘flipped’ (after the change). Fisher’s exact test was used to determine whether the number of escapes along the right path differed between the baseline and flipped conditions.In addition to estimating the probability of selecting an arm, the posterior distribution of the probability value was estimated using a Bayesian model. The model had a Beta distribution prior  and a Binomial distribution as likelihood . The resulting posterior distribution is then a Beta distribution whose parameters are given by:th percentile interval were computed from this distribution.To compare the probability of selecting the right arm between naïve and experienced trials, for each arena the first escape trial for each mouse was classified as naïve while all other trials were classified as experienced. When a mouse was used for more than one experiment, only the first trial on the first experiment the mouse was used for was considered naïve. The probability of escaping along the right path was computed for the naïve trials. Because the number of experienced trials is larger than the naïve condition, to compare the probability of taking the right path between the two groups, experienced trials were randomly sampled without replacement to match the number of naïve trials in the same arena, and the probability of taking the right path was then computed. This procedure was repeated 10 times to generate a distribution of probability values, and the mean and 95To determine whether mice required repeated experience with threat to select the preferred escape path we identified the very first stimulus presentation of each animal. We grouped such “naïve” trials across individuals tested on the same experimental arena and estimated the probability of escape along the right path in this subset of the data. To compare naïve vs experienced (i.e. following the first encounter with threat) trials, we randomly sampled from the experienced trials from each arena matching the number of naïve trials in the same arena and we computed the probability of escape on the right arm. We repeated the sampling procedure 100 times to obtain a distribution of probability values for different random subsets.To quantify the change in probability of escape along the right path over time, for each arena we pooled all trials that occurred during the first 60 minutes from the start of the experiment. We then binned the trials based on the time since experiment start  and computed the posterior distribution of p(R) as described above.To quantify the number of trips between the shelter and the threat platform during exploration, the tracking trajectory corresponding to the exploration period (from start of the experiment to one frame before the first stimulus) was analyzed. For each frame, the mouse was assigned to one of four regions of interest  based on the coordinates of the tracking data registered to a standard template image as described above. A trip was ended when the mouse arrived at the shelter (threat) platform and started at the last frame in which the mouse was on the threat (shelter) platform. Incomplete trips (e.g.: the mouse left the shelter platform and returned to it without first reaching the threat platform) were discarded.To predict the probability of escaping along the right arm from trial data, a binomial generalized linear model (GLM) with a logit link faction was used  of the outcomes vector. For visualization, the mean and SEM accuracy at each training episodes were displayed following smoothing with a rolling mean filter with window width of 6 episodes.To quantify the performance of RL agents trained under the guided exploration regime, we trained 10 repetitions of each RL model on the tracking data from each experimental session. Under this regime, unlike in free exploration, training is fully deterministic because the actions are specified by the tracking data, the only variability emerges from the DYNA-Q model’s probabilistic sampling of its model at each training step. After training, all repetitions of each model were tested on their ability to navigate from the start to the threat location. The model was considered successful if at least 8/10 repetitions successfully reached the goal location.To produce the state occupancy heatmaps in


Photopsia is a photic phenomenon that can be associated with intraocular lenses after cataract surgery. To calculate the relative light intensity of photic effects observed after cataract surgery at the foveal region as the most sensitive region of the retina, photopsia was simulated using the ZEMAX optical design software. The simulations are based on the Liou-Brennan eye model with a pupil diameter of 4.5 mm and incorporating implanted IOLs. The hydrophilic IOLs implanted in the eye model have a power of 21 diopter (D) with an optic diameter of 6 mm and 7 mm. Four different intensity detectors are located in specific regions of the eye in this simulation. The ray-tracing analysis was carried out for variations of incident ray angle of 0° to 90°  in steps of 1°. Depending on the range of incident ray angle, the light intensity was detected at detectors located on the fovea, nasal side of the retina, or the edge surface of the IOLs. Some portion of the input light was detected at specific incident angles in the foveal region. By altering the IOLs edge design to a fully reflective or anti-reflective surface, the range over which the light intensity is detected on the fovea can be shifted. Additionally, with the absorbing edge design, no intensity was detected at the foveal region for incident ray angles larger than 5°. Therefore an absorbing edge design can make photic effects less disturbing for patients. In this phenomenon light which is not directly correlated to an object is detected in the visual field. Clinical studies show that the photic effects caused by photopsia are mostly located in the temporal visual field. This effect has been named r et al. . Masket r et al.  and Hollr et al. , 4.Generally, patients do not suffer from photic effects after intraocular lens implantation. A few cases with these symptoms do not feel disturbed and they can tolerate this phenomenon , 6. HoweIn the literature, several explanations for this phenomenon such as defects in the IOL optics during manufacturing, central optical defects during folding and injection , IOL matIn our previous study, we modelled the impact of the edge design of intraocular lenses (IOL) on the location, shape and relative intensity of photic effects at different regions of the retina .In this paper, we have simulated the photic effects after cataract surgery in different regions of the pseudophakic eye. The main objective of this study is to calculate the relative light intensity of the photic effects on the foveal region as the most sensitive part of the retina, in order to better understand the effect of incident angles on the fixed eye model. Therefore we have defined our model based on parameters derived from the schematic model eye. Moreover, we have simulated the impact of the IOL edge design on the relative light intensity of the photic effects on the fovea.This study was registered at the local ethics committee of the Medical Association of Saarland .In this study, a pseudophakic eye model based on the Liou-Brennan schematic model eye introduced in 1997 was used for simulation . Liou-BrThe cornea of this model is defined by two rotationally symmetric surfaces (the front and back surface) with radii of 7.77 mm and 6.40 mm and asphericity of -0.18 and -0.60, respectively. The interspace between corneal surfaces is 0.5 mm with a refractive index of 1.376. The retina in defined by a half sphere with a radius of 12 mm and the fovea as the intersection of the visual axis and the retina with a diameter of 1.5 mm. The pupil diameter used in this model is 4.5 mm.According to the schematic model eye of Liou & Brennan, all optical elements  are centred on the ‘optical axis’. The pupil is somehow decentered by 0.5 mm in the nasal direction with respect to the optical axis to consider the incident ray angle of 5° from the nasal direction, as given by the model eye.In this model, two acrylic hydrophilic IOLs with a refractive power of 21 D and refractive index of 1.458 are aligned with their equator in the equatorial plane of the crystalline lens of the eye model.The front surface of the IOLs is defined by a spherical surface and the back surface by an aspherical surface optimized for 0.26 μm spherical aberration in the total eye model. These IOLs have a sharp circular optical edge with a thickness of 0.3 mm and optical diameters of 6 mm and 7 mm respectively. Finally, after IOL implantation in the model, the anterior chamber depth of the model eye is about 4 mm.In our simulation we used these model eye data as a baseline and varied the incident ray angle to determine the critical ray incidence where (unwanted) light effects at the foveal region are observed. To analyse the intensity of photic effects, four different light detectors are placed on different regions of the eye model. A circular light detector is located at the pupil to calculate the total intensity of light passing through the pupil. This detector is named as ’’Detector-P’’.A second detector that named as ’’Detector-N’’ is located at the periphery of the nasal side of the retina and calculates the light intensity passing through the interspace between iris and IOL without hitting the lens.Another detector is located at the edge surface of the IOLs and measures the intensity of the light hitting the lens edge surface. This detector is named ’’Detector-E’’.Finally, the last detector named ’’Detector-F’’ is located at the foveal region to calculate the light intensity of the photic effects at the fovea.Since the foveal region is the most sensitive region of the retina, even low intensities of light uncorrelated to the object space may cause optical disturbance for patients. The closer to the fovea, the more sensitive is the retinal surface.To evaluate the contribution of the edge surface properties of the IOL on the intensity of the photic effects at the foveal region (Detector-F), three different edge designs with fully reflective, anti-reflective, and absorbing surfaces respectively were simulated.With specular reflecting and anti-reflecting IOL edges, the effects of internal specular reflection and transmission are highlighted, respectively. By simulating an IOL with an absorbing edge, light transmission through and reflection off the edge is suppressed. These simulations provide insight to study the transmission, reflection, and absorption of the edge surface separately.Ray tracing was performed to calculate the intensity of photic effects reaching the foveal and retinal surface in comparison to the total power passing through the pupil. All of the simulations were carried out using the non-sequential ray-tracing mode of the ZEMAX professional ray-tracing software .A collimated light pencil with 5 million rays from an extended light source is used to analyse the intensity of photic effects. The rays are distributed homogeneously over the pupil, and there is no weighting in their distribution function.Rays from 0° to 90° degrees from the temporal direction in steps of 1° with respect to the visual axis  were traced temporally through the pupil to evaluate the intensity of the photic effects on the different detectors.For each incident angle, the intensity obtained by the detectors are documented and referenced to the light intensity passing through the pupil.With increasing incident ray angle, the total intensity of light decreases, but the difference between the normalised intensity of the light passing through the pupil and the cosine squared function increases.It can be seen that rays passing through the interspace between IOL and pupil are detected for incident ray angles exceeding the critical angles 44° and 55° for IOLs with an optical diameter of 6 mm and 7 mm, respectively. The light intensity increases with the angle of incidence from these critical angles to 90°.In this figure, rays from the incident angle of 42° start to interact with the edges of 6 mm IOL, and the rays from the incident of 48° start to interact with edges of 7 mm IOL. With increasing angle of incidence, the detected intensity at the edges initially increases dramatically, and then the intensity fluctuates slightly.For small incident ray angles from 0° to 5°, almost all of the light passing through the pupil reaches the foveal region. For larger incident ray angles the light intensity on the foveal region decreases down to 0.001% of the light intensity passing through the pupil. In the range from 60° to 70°, about one percent of the total input light is detected at the foveal region.In this figure, it can be observed that from incident ray angles between 70° to 80° about one percent of the light at the foveal region is detected. For the IOLs with 6 mm and 7 mm optical diameter, 0.3% of the input light is detected at angles of 77° to 78° respectively.Finally, In this figure, no intensity is detected at the fovea for incident ray angles exceeding 50°.There have been several studies focused on IOL design and position to reduce photic effects . HolladaStandard ray-tracing techniques show that different incident angles cause the incoming light to be directed to various regions of the retinal surface. The intensity and location of these rays depend on how they interact with the IOL surfaces . There is expected to be a correlation between the location of the photic effects and the amount of disturbance for the patients because different regions on the retina are differently sensitive to light.In In Figs In By changing the edge design from a fully reflective to an anti-reflective surface, the photic effects are detected within a different range of incident angles.For incident ray angles in a range between 0° and 50°, the light intensities shown in Figs Finally, Clinical studies in the future will be needed to prove the validity of our simulation model in a clinical environment.This study has the character of a pilot study and our principal aim has been to demonstrate the applicability of this concept. Our model in this study is based on the Liou-Brennan schematic model eye. This model reflects only an average geometry of a human eye. Since we would expect the behaviour of photic effects to vary across eyes with different proportions and corneal shape as well as pupil sizes/locations, it can be concluded that our results cannot be generalised to all human eyes on the basis of the current study alone.S1 Data(XLSX)Click here for additional data file.


Caenorhabditis elegans. The robot interacts with the environment through a sensor that transmits the information to sensory neurons, while motor neurons outputs are connected to wheels. This is enough to allow emergent robot actions in complex environments, such as avoiding collisions with obstacles. Working with robotic models makes it possible to simultaneously keep track of the dynamics of all the neurons and also register the actions of the robot in the environment in real time, while avoiding the complex technicalities of simulating a real environment. This allowed us to identify several relevant features of the neural dynamics associated with the emergent actions of the robot, some of which have already been observed in biological worms. These results suggest that some basic aspects of behaviors observed in living beings are determined by the underlying structure of the associated neural network.We analyze the neural dynamics and their relation with the emergent actions of a robotic vehicle that is controlled by a neural network numerical simulation based on the nervous system of the nematode  Drosophila melanogaster  . When a neuron Sj surpasses the threshold it fires, distributing the signal to its Si neighbors, and resetting its state to zero. The neurons are updated in the following way:The neurons evolve in the numerical simulation with discrete time steps. At each time step all the neurons add their input signals up to a given threshold value , Ω2 = 0.332 ± 0.003 Hz  and Ω3 = 0.496 ± 0.004 Hz :Following the same procedure we also performed a similar principal component analysis. As in Kato et al. , each of1 (green), Ω2 (blue), and Ω3 (red) already presented in 1, presents a broad distribution of neuron weights. For higher frequencies the neurons present a stronger segregation toward extreme PC1 values. In fact, both Ω2 and Ω3 are clearly divided into two smaller subclusters: one with only positive and another with only negative PC1 values. This segregation reflects differences in the firing times of the neurons. In each cluster the firing times of the neurons are proximal. In contrast, when one compares the signals of neurons between clusters a shift in their relative phase is observed. The largest shift occurs for extreme PC values, when the neurons in the different subclusters of the same frequency oscillate mostly in antiphase , Ω2 (blue), and Ω3 (red). In each figure, the results are contrasted with the fractions of events for the whole experiment (gray bars). Note that a significant increase in forward events is observed when the neurons with the largest positive PC1 fire  can be found at: All authors contributed to manuscript revision, read, and approved the submitted version.


Type 2 diabetes (T2D) is an archetypical chronic condition of significant prevalence. Yet the concept of cure in the context of T2D reveals an interplay between the medical imagination and clinical realities that can shift the course of a patient's care. There are two domains in which cure is sociologically constructed: the professional domain occupied by clinicians treating people with T2D, and the lay domain occupied by T2D patients. Lay epistemologies of cure tend to be focused on modifying the experience of having T2D, while professional epistemologies tend to focus on modifying the disease through medical treatment. The objective of this study is to explore the role of the concept of cure in the context of type 2 diabetes, a model for chronic disease.Through surveys and interviews of T2D patients, providers and researchers at an urban academic medical centre, I explore the perspectives and attitudes each group have towards the concept of cure in T2D. Semi‐structured interviews of T2D professionals and patient surveys consisting of free response questions and Likert scale items were thematically analysed for perspectives on cure in T2D.Sixteen T2D patients met inclusion criteria and consented to the survey and ten T2D professionals were interviewed. Cure is conceived of heterogeneously both within and between epistemologies. Patients carry hopes of cure predicated on eliminating the unpleasant experiences of T2D and its treatments, while T2D professionals tend to avoid invoking the concept of cure, at least to patients, on grounds of clinical uncertainty. However, the concept of cure is a significant motivator of treatment in both lay and professional epistemologies.Different viewpoints on cure in T2D present an opportunity for shared meaning and decision making between patients and their providers that can frame the best possible outcome for patient care. Fox notes that, ‘the word “cure” generates strong negative feelings in some professionals working in the field, because they doubt the concept of a cure for this condition’.The literature shows differing attitudes towards cure in T2D both between and within T2D professionals and patients. This depends on the understanding of what T2D is, or ontology of T2D, which will determine how one knows T2D is cured, or epistemology of cure. In the professional domain, where T2D is clinically diagnosed based on techniques consistent with the biomedical model of medicine, the curability of T2D is disputed. In the clinical landscape of T2D, the technical editor of However, in the field of bariatric surgery, cure for T2D is discussed in the context of a surgical approach to treating T2D, an anatomical rather than molecular modification of the cause of T2D. An outcome frequently reported with bariatric surgery is apparent resolution of T2D, or removing the need for T2D treatment, at a rate of up to 80%.The curability of T2D is a nontrivial problem for T2D patients, who may largely rely on a lay epistemology of cure based on an ontology rooted in the personal experience of having T2D. T2D, how it came to be and its consequences, is largely personalized in the lay domain, such as through experiencing individual stress rather than describing a molecular pathophysiology.1.‘Building behavioural autonomy’ as a process of growing confidence to engage in health behaviours that are independent of those of other people.2.‘Behavioural contagion’ describing how one's new health behaviours tend to affect those of other people.3.‘From rigid to flexible restraint’, reflecting the changes in attitudes and behaviours required for a successful adaptation from weight loss to weight maintenance.4.‘Shift in identity’, representing changes in the participants' perceptions of themselves.No matter how a person developed T2D, having it cured is an important goal and there is some flexibility with how that may be achieved. A survey distributed to T2D patients found that the highest priority question is: ‘Can T2D be cured or reversed, what is the best way to achieve this and is there a point beyond which the condition cannot be reversed?’.These themes appear independent from the clinical and technical discussions of cure in T2D in the professional domain and support an internal locus of control for patients. Behavioural autonomy suggests that an aspect of cure involves independence from the healthcare system and the ability to make healthy choices through self‐care.This qualitative study evaluates the attitudes of T2D patients and the providers that treat them and do research on their condition at an urban academic medical centre. The aim of this study is to clarify different perspectives about cure in the chronic condition of T2D and to identify commonalities that may help facilitate clearer communication about goals of care for T2D.22.1This qualitative study was approved by the University of Chicago Biological Sciences Division Institutional Review Board. Participants were recruited and interviewed or surveyed from January to March 2020. It was explained to participants that they were being surveyed about their goals of care for T2D and experience living with T2D.Diabetes Care Profile,The study had two arms, one for recruiting T2D patients to fill out a survey and the other for interviewing T2D clinicians and researchers. In the patient arm, patients were recruited from the clinic population at the Kovler Diabetes Center at the University of Chicago Medical Center following an endocrinology appointment from five different providers once a week for 3 months. Potential participants were screened by their provider to participate in a survey and then were formally consented after their appointment. The inclusion criteria were adults 18 years or older with a diagnosis of T2D and actively undergoing T2D treatment. Demographic data such as race and gender were not collected as the goal of this study was to characterize the personal experiences of T2D patients rather than to analyze demographic differences regarding those experiences. The survey is based on questions from the T2D clinicians and researchers at the University of Chicago were recruited through email for an approximately 30‐min interview and an effort was made to include a diverse selection of T2D experts. The specialisations of faculty interviewed ranged from endocrinology, biomedical research, bariatric surgery and weight management. In semi‐structured interviews using a grounded theory approach to develop a theory of T2D cure, participants were asked questions on three themes: (1) about their perspective on the curability of T2D, (2) how a cure could be achieved and (3) communicating information about T2D treatment to patients. The interview guide is provided in the appendix.2.2Patients were asked if they were willing to fill out a survey asking about their views and experiences with type 2 diabetes care. If the patient agreed to participate, they filled out anonymous surveys at a quiet library adjacent to the Kovler Center on paper or at their own convenience through an identical online Qualtrics survey. Patients were instructed to fill out as much of the survey as they wanted and incomplete surveys were included in the study. The survey consisted of four free‐response questions asking patients about their experience of T2D and what a cure for T2D, if there is one, would look like to them. The rest of the survey consisted of nine 5‐point Likert‐scale questions . Interviews were audio recorded in the participant's private office. Survey responses and interview audio files were stored securely in a locked and encrypted Dropbox database.2.3Patient survey responses were thematically analysed for perspectives on the characteristics, outlook and influences on the concept of cure in T2D. All interview audio files were imported into Sonix and transcribed using Sonix's artificial intelligence programme. Once the transcription was complete, researcher David Zhao read the transcript while listening to the recording to correct spelling and grammatical errors, insert punctuation and anonymize the transcriptions. Interviewees were given the opportunity to review their interview transcripts and make corrections. Transcripts were thematically analysed by coding for topics, issues, similarities and differences revealed through the participants' narratives and interpreted by the researcher to understand the perspectives of cure in T2D in the professional epistemology. For example, perspectives were categorized on the appropriateness of using the word cure in T2D as well as their justifications.33.1Sixteen patients filled out surveys at the Kovler Diabetes Center. Of those, two surveys were incomplete, although the Likert items were completed in every survey. All 16 surveys are included in the analysis of the Likert items displayed in Table 3.2A total of 81% of patients viewed that their life would significantly improve if they were cured of T2D. About 75% of patients agreed or strongly agreed that they initially sought treatment to be cured of their T2D, which is in concordance with high agreement that a cure improving overall well‐being .In my patients who have been recently diagnosed with type two diabetes, I use the word remission and the understanding that genetic defect or predisposition for their pancreas not to be able to meet demand if you stress it out again.I think that when you say cured it makes it sound like there's like no underlying problem to begin with. And I feel like a lot of these patients have like this underlying whatever environment being relatively toxic for individuals who have a propensity to develop type two diabetes, a substantial amount of the control is not really there.I think that the Remission is an important term that takes into account uncertainty in T2D due to multiple factors. Interviewed healthcare practitioners acknowledge the ideal of cure as a permanent resolution. One endocrinologist stipulated that if clinicians use cure for T2D, they ‘have to emphasize the fact that maybe it's not permanent…when I think about cure, I always think of it as a permanent thing or something that's likely to be’. Many interviewees did not find cure to be appropriate to promise in patient interactions (theme 3) for various reasons:The general consensus among these participants is the thought that there is always a risk of the disease or contributing factors, like obesity, returning or persisting. These may be outside the control of either the patient or clinician. An endocrinologist summarizes the potential to misrepresent any expectation of cure: ‘What I'm concerned about is that if we use the word cure, we're going to think that individual then will not expect to at anytime in his or her life have high blood sugar from type two diabetes’. The fear of many providers is that using the word cure from the professional perspective will suggest to patients that they will have to do less in terms of managing their T2D. This may be why healthcare practitioners often prefer remission, because it is less ambiguous than cure at communicating the uncertainty and risk in T2D prognosis. With remission, a patient may still have to watch their weight to minimize the chances of recurrence, but with cure a patient might think that no matter their weight control behaviour, their T2D will never return. A contrary thought is that the term cure can be more useful than remission because cure can serve as a signal of hope for patients. A bariatric surgeon acknowledges that ‘from a clinical standpoint, remission is a more accurate terminology, right. But I do think that the lines that we use to communicate to patients and the context of hope and change is really important too’.3.4Patient conceived lifestyle and pharmacological T2D cures are at odds with expert beliefs about how the lifestyle and pharmacological aspects of T2D treatment interact. Responses regarding to the second theme of how cure could be achieved acknowledge the necessity to modify the molecular pathophysiology of T2D. From the perspective of an interviewed bariatric surgeon on pharmacological interventions, to cure T2D, the treatment has ‘to change…the complexity of something like eating behaviours and, and glucose homoeostasis, it's not going to be a single pathway, a single drug sort of response because there's so many different inputs’. Another endocrinologist explains that a single miracle drug is unlikely to come to fruition because even newer drugs are not addressing the underlying causes of T2D; they are not ‘disease modifying agents’. Current treatments do not address the underlying cause of T2D but rather focus on symptom management and maintaining blood glucose homoeostasis.In terms of the aesthetics of cure, or the imagined modality of cure, patients have a tendency to envision cure being in the form of a pill, or a lifestyle change, or even shots or a patch Table . Interes4T2D patients and professionals have different perspectives on the curability of and the characteristics of cure in T2D. Patients base their perspectives from their experiences with and without T2D, the suffering and hope engendered by the process of contending with T2D. Clinicians and researchers tend to draw from the perspective of scientific medicine to deliver treatment within ethical and technical boundaries. As a result, there is heterogeneity in the conception of cure in chronic disease. Cure may be defined clinically, with varying thresholds and tolerances, as well as in terms of lifestyle or pharmacological independence. To complicate matters, the wide use of alternative terms to cure  among interviewees and in the literature without clear distinctions between each further reflects the great uncertainty in T2D outcomes. There is also variation in a T2D patient's ability to adhere to interventions, background and underlying risks that must be considered.Perspectives of cure in T2D are dependent on perceived experience, which shape the concept of cure in lay epistemology in response to the uncertainty of the disease's outcome. For patients, cure is simultaneously nostalgic, while also hopeful for the future with the return of freedom and normalcy. Canguilhem referred to this as ‘the general and persistent tendency to conceive the cure as an end to a disturbance and a return to an anterior order’.While to the traditional medical eye a cure was the effect of a treatment of the cause and functioned to sanction the validity of a diagnosis and the ensuing prescription—hence of the doctor's own worth—to the psychoanalytic eye, a cure became the sign of the patient's rediscovered capacity finally to be done with his own difficulties. A cure was no longer commanded externally; it became an initiative recuperated by the patient.The concept of cure is linked to clinical uncertaintySince the management of weight, blood sugar levels and even medication is primarily the responsibility of the patient, do any of the clinical indicators of diabetes matter if the patient simply feels cured, whatever metric they decide to substantiate that on? It may be that the role of the healthcare professional is to mediate clinical realities with patient ideals about T2D care, not to determine whether a patient is cured of T2D.An example of bridging expectations and perspectives about the concept of cure in T2D could be a discussion on the role of bariatric surgery in T2D treatment. A study found that few patients with T2D viewed bariatric surgery as a safe treatment for T2D and there was no mention of bariatric surgery among patients in this study.The role of a medical professional when dealing in the mutual conceptualisation of cure with their patients is to balance communicating clinical realities—such as underlying risk, complications and treatment guidelines—to the patient, while also acknowledging patient goals and values. This requires a shared decision making where the provider elicits the patient's explanatory model of their own illness, their T2D ontology, in to understand their beliefs and personal narratives about why they have T2D and how they may overcome it.Surveyed patients had high trust in their providers, both in their words of advice and ability to treat their T2D. This trust is important as it most likely moderates the high initial patient expectation for cure and the reluctance of providers to talk about a cure for T2D. In another study in Scotland, T2D patients found that the perceptions about T2D can be mutually informing during interactions with health services.This study has several limitations. First, participants were recruited from one academic medical centre in the Midwest. Although multiple specialities were represented, all the patients surveyed were recruited at the Kovler Diabetes Center at the University of Chicago Medical Center, a clinic in an urban setting. Regional differences may account for different perceptions, for example, through different standard of care practices for T2D in different medical centres. Second, demographic data such as age, gender, education background and ethnicity were not collected. It is possible that differences in these backgrounds could explain the development of participant perspectives. Additionally, clinical indicators of patients' T2D describing the severity and duration of their illness was not collected. How long and how much a patient has suffered from T2D may impact their ideas about cure. Given that the patients were recruited at a diabetes clinic in a tertiary healthcare institution, rather than a primary care clinic, it is likely that these patients have been referred for complex management of their diabetes and may have more severe presentations of T2D. The third limitation was the lack of interview data from patients. The decision to give patients a brief survey instead of an interview was made in the interest of a patient's privacy and time since they were recruited following an outpatient endocrinology appointment. However, interviews could have added additional richness to the patient perspective. Finally, the small sample size of patients and experts who participated means these findings are preliminary and exploratory.In conclusion, providers are in the position to empower T2D patients towards obtaining their goals, and to frame the problem as well as the solution. T2D professionals can help manage expectations in the management and outcomes of T2D through education and communication. However, cure is not always explicitly discussed between providers and patients. Clinicians may even avoid the use of the word cure entirely, but patients will often come in with a preconceived expectation about the image of cure. The goal should not be to avoid the topic of cure in T2D altogether. However, to avoid potentially dangerous confusion, it is paramount that communication is focused on understanding what others think about cure in addition to one's own assumptions and perspective, identifying common conceptions, mediating differences and establishing roles to achieve the mutually constructed goal, which may not necessarily be a cure. Talking about cure does not always result in cure, but it may result in other positive outcomes, such as finding what it means to thrive with a chronic condition like T2D. The ideal cure may invoke a defining, straightforward goal of medicine, but the interpretations of cure in the context of a chronic disease such as T2D reveal that cure is not a deterministic or concrete goal, but a concept that can be leveraged to the benefit of treatment.The author declare no conflict of interest to disclose.Supporting information.Click here for additional data file.


Hydrodissection, a technique for performing morphological dissection between the target tissues via injection, has attracted attention in recent years. However, high-quality evidence is available only for a few entrapment neuropathies, such as carpal tunnel syndrome, and further case studies are needed for other diseases. This case report presents the first case of hydrodissection of the ventral ramus of the spinal nerve, which innervates the abdominal wall, to improve abdominal pain. A 59-year-old Japanese man with a history of cerebral infarction and dyslipidemia presented to the emergency department with the chief complaint of left upper abdominal pain that began two days earlier. The pain radiated to the left side of the back and left axilla. The abdomen was flat and soft with no tenderness on examination, and the pinch test was negative. However, Carnett's sign was observed in the left upper abdomen, and the location of the left upper abdominal pain and that of the radiating pain were consistent with the ninth thoracic vertebra (Th9) dermatome; thus, the cause of the left upper abdominal pain was determined to be the ventral ramus of the spinal nerve of Th9. Two weeks of physical therapy and lifestyle guidance were ineffective; therefore, hydrodissection of the transversus abdominis plane (TAP) between the myofascia of the internal oblique muscle and that of the transversus abdominis at the Th9 level using a 23G 60 mm needle under ultrasound guidance was planned. The abdominal pain immediately improved after hydrodissection, and the patient was able to work without pain. Thus, ultrasound-guided TAP hydrodissection with a low-concentration local anesthetic is effective in the treatment of abdominal pain caused by the entrapment of the ventral ramus of the spinal nerve due to adhesions between the myofascia of the internal oblique muscle and that of the transversus abdominis. This condition should be termed ventral ramus of spinal nerve entrapment syndrome (VERNES), and this concept and TAP hydrodissection must be made known to the public.  Peripheral nerve blocks for paresthesia and analgesia are frequently used in operating rooms and pain clinics. Hydrodissection, an injection technique seemingly similar to peripheral nerve blocks, has been attracting attention in recent years . The devThe patient was a 59-year-old Japanese man with a more than 10-year history of cerebral infarction and dyslipidemia. He had no physical disability from the stroke. He was receiving aspirin, pitavastatin calcium hydrate, irbesartan, and amlodipine besylate. He had no history of smoking but drank about 350 mL of canned beer once a week. The patient worked at a dyeing factory. His work was strenuous and required lifting and carrying an 18-L square can by hand and agitating liquids in a large bathtub while bending forward. He often experienced left upper abdominal pain for about 30 minutes at work, and the sensation was similar to a muscle being squeezed in the abdomen. The maximum pain rating was 8/10 on the numerical rating scale (NRS), and the patient was unable to move. The pain radiated to the left side of the back and left axilla. Occasionally, the pain was perceived even at rest. The pain was often relieved on nonworking days. Vomiting, nausea, cold sweats, or chest pain was not present.The vital signs at presentation were as follows: body temperature 36.5 °C, blood pressure 115/68 mmHg, heart rate 72 beats/minute, and saturation of oxygen 99% (room air). Physical examination revealed no significant findings related to the head, neck, chest, or extremities. There was no weakness in the extremities. The abdomen was flat and soft with no tenderness, there were no tender points on the body surface, and the pinch test was negative. Guarding was not present. However, Carnett's sign was positive , and theThis case report is the first to adopt ultrasound-guided TAP hydrodissection using a low-concentration local anesthetic for the entrapment of the ventral ramus of the spinal nerve due to adhesion of TAP between the myofascia of the internal oblique muscle and that of the transversus abdominis.The left upper abdominal pain was determined to have originated from the ventral ramus of the spinal nerve based on the physical examination, medical history, and ultrasound findings. Carnett’s sign, which was observed in this case, is a method for determining whether the pain originates from the abdominal wall or cavity . The patTAP block is a technique similar to TAP hydrodissection and is used commonly in anesthesiology for peripheral nerve block of the ventral ramus of the spinal nerve running through TAP ,3. PeripAn extension tube was attached between the 23G 60 mm needle and syringe as the injection tool in this case, and the person performing the injection held the needle and asked an assistant to hold the syringe and inject the solution. By using an assistant and attaching the extension tube, the distance from the injection site to the hand was shortened than that when one person was to hold the syringe with the needle and inject alone. We believe that doing so improves the manipulation of the needle.Some patients with neuropathy due to entrapment of the ventral ramus of the spinal nerve, as in this case, remain undiagnosed. This condition should be termed ventral ramus of spinal nerve entrapment syndrome (VERNES), and this concept and TAP hydrodissection must be made known to the public. In recent years, cases of hydrodissection treatment for nerve entrapment have been reported in various diseases, such as piriformis syndrome , occipitThe symptoms caused by entrapment of the ventral ramus of the spinal nerve due to adhesions between the myofascia of the internal oblique muscle and that of the transversus abdominis are known as VERNES. Ultrasound-guided TAP hydrodissection with a low concentration of a local anesthetic may be effective in the treatment of VERNES. Hydrodissection may also be successful in treating other types of unreported inter-myofascial nerve entrapment, and further case reports and larger scale studies are needed.


There is a need to develop a new device to evaluate and monitor the condition of human skin and make it possible to measure the skin in the diary because the current accuracy of water content measurement in the stratum corneum by capacitance and conductance measurement sensor that are used as the gold standard is insufficient.The electrostatic sensor is composed of a thin silicone gum sheet and a copper film. In the experiment, skin conditions on six positions such as the forearm, upper arm, and face of a test subject before and after tape stripping are measured by the electrostatic sensor and a commercial sensor. Skin conditions on the forearm of five subjects before and after pasted distilled water were measured by their sensors.P < 0.01 before and after skin stripping. There were increases in the voltage and the moisture with P < 0.01 before and after pasted distilled water.The voltages measured by the electrostatic sensor and moisture measured by a commercial sensor are increased with It is suggested that it is possible to measure the moisture on the upper layer of the skin by the electrostatic sensor. Several instrumentations have been developed and used for evaluating and monitoring the skin condition. Contact type instruments such as the Corneometer  and moisture checker  based on capacitance measurement and Skicon  of conductance measurement are widely used as the gold standard for skin water content measurement.The final purpose of our study is to develop a new sensing device for skin condition evaluation including the depth profiling water content. A new sensing method based on the electrostatic induction for this purpose was proposed2Figure 33.1Figure Figure 3.22Figure 3.3Figure 44.1Figure t‐test at a significance probability of 0.01. Therefore, the change in the skin condition caused by the stripping was detected using the electrostatic sensor. It was found that the surface layer of the skin was stripped and the inside of stratum corneum that was more hydrated than the surface layer was barely formed. It was estimated that the increase in the moisture detected by the commercial sensor was caused by the inside of the stratum corneum which was generally more hydrated than the surface.From Figure 4.2Figure In these experiments, the measurement accuracy was insufficient. The inaccuracy was mainly caused by the unstable contact face and the angle between the sensor and the skin. Therefore, future work will involve stabilizing the contact force and contact angle by improving the mechanism of linear movement.5In this paper, a handy‐type electrostatic sensor was evaluated. In the experiments, the voltage measured using the electrostatic sensor and the moisture measured using a commercial sensor at six different sensing areas on the skin, including the upper arm, forearm, and cheek of the subject, were measured before and after skin stripping. In addition, the skin on the forearm was also measured using the proposed and commercial sensors before and after filter paper containing distilled water was pasted to the skin. The results indicated the electrostatic sensor has the potential for detecting the moisture on the upper layer of the skin.


Tracking systems such as Radixact Synchrony change the planned delivery of radiation during treatment to follow the target. This is typically achieved without considering the location changes of organs at risk (OARs). The goal of this work was to develop a novel 4D dose accumulation framework to quantify OAR dose deviations due to the motion and tracked treatment. The framework obtains deformation information and the target motion pattern from a four‐dimensional computed tomography dataset. The helical tomotherapy treatment plan is split into 10 plans and motion correction is applied separately to the jaw pattern and multi‐leaf collimator (MLC) sinogram for each phase based on the location of the target in each phase. Deformable image registration (DIR) is calculated from each phase to the references phase using a commercial algorithm, and doses are accumulated according to the DIR. The effect of motion synchronization on OAR dose was analyzed for five lung and five liver subjects by comparing planned versus synchrony‐accumulated dose. The motion was compensated by an average of 1.6 cm of jaw sway and by an average of 5.7% of leaf openings modified, indicating that most of the motion compensation was from jaw sway and not MLC changes. OAR dose deviations as large as 19 Gy were observed, and for all 10 cases, dose deviations greater than 7 Gy were observed. Target dose remained relatively constant (D95% within 3 Gy), confirming that motion‐synchronization achieved the goal of maintaining target dose. Dose deviations provided by the framework can be leveraged during the treatment planning process by identifying cases where OAR doses may change significantly from their planned values with respect to the critical constraints. The framework is specific to synchronized helical tomotherapy treatments, but the OAR dose deviations apply to any real‐time tracking technique that does not consider location changes of OARs. The jaws correct for motion in the IEC‐Y direction (superior/inferior [sup/inf]) by continuously swaying.Synchrony is a real‐time motion tracking system for helical tomotherapy treatments available on the Radixact linear accelerator .The goal of the tracking is to keep target dose the same as planned despite the motion. However, most motion tracking systems such as Synchrony do not consider the location and shape changes of organs at risk (OARs) when compensating the treatment. Therefore, a method to calculate OAR dose deviations after motion correction is of interest. In motion gating systems, the planned treatment is always delivered with the patient at the same respiratory phase. In this case, OAR doses can be more accurately estimated with the original 3D treatment plan because OARs are in a similar position during that specific respiratory phase. OAR doses are not as easily calculated for tracking treatments as the patient is treated at all phases of the respiratory cycle.There have been several studies demonstrating Synchrony's ability to accurately correct the treatment for target motion.Calculating dose to OARs from tracking treatments requires deformation information as OARs typically do not move rigidly with the target, especially for treatment sites in the thorax or abdomen.The goal of this work was to develop a novel, in‐house 4D dose accumulation framework capable of calculating doses from motion‐synchronized helical tomotherapy treatments and to use the framework to calculate dose deviations to OARs for lung and liver subjects. The framework is specific to synchronized helical tomotherapy treatments, but the results on OAR dose deviations apply to any real‐time tracking treatment techniques.2Obtain input data: 4DCT images and helical tomotherapy treatment plan.Get 3D location of the target on each phase of the 4DCT.Assume respiratory phase pattern from mathematical function or chest amplitude data.Split treatment plan into 10 plans based on respiratory phase pattern.Apply MLC corrections to each of the 10 plans.Apply jaw corrections to each of the 10 plans.Calculate dose for each plan on corresponding 4DCT phase.Calculate deformable image registration (DIR) between each phase and reference phase.Map the dose to the reference phase using DIR.Sum doses to create Synchrony‐accumulated dose.Compare Synchrony‐accumulated dose to static planned dose.The framework was used to calculate dose deviations for five lung and five liver stereotactic body radiation therapy (SBRT) patients previously treated at our institution with non‐Synchrony respiratory management. The specifics of the workflow may change for other institutions as protocols, software, and data storage types may differ. However, the general concept of the workflow will remain the same. This work focuses on lung SBRT treatments as these often necessitate intrafraction respiratory motion management.2.1The inputs to the framework are a helical tomotherapy treatment plan and a 4DCT dataset. The treatment plan is a plan that is intended to be treated with Synchrony and is planned on one of the phases of the 4DCT scan, designated as the reference phase. The reference phase is often the maximum inspiration or exhalation phase; however, using a mid‐ventilation phase will maximize the range of motion that can be correctedPatient selection was performed using the recommendations from Chen et al., including a diameter of solid tumor 2–8 cm, magnitude of tumor motion in sup/inf direction less than 4 cm, and high rigidity of the target.Clinically, the subjects included in this work were treated with tight margins (3–5 mm) using a gated delivery. For this work, they were replanned for helical tomotherapy delivery on Radixact using 5‐mm gross tumor volume (GTV) to planning target volume (PTV) margins and the same clinical objectives as their original treatment plan. The prescriptions for each subject are shown in Table 2.22n).The motion compensated treatment plan was generated using the target location at every point during the treatment. The target location was obtained by contouring the target on the reference phase, transferring the target to the other phases with DIR, and obtaining the centroid of the contour on each phase. Figure 2.3The next step was to split the original planned sinogram into 10 sinograms, shown in Figure 2.4The next step was to apply motion corrections to the planned collimation. The corrections were calculated using software from the vendor that contains the motion‐tracking algorithm. Information about the algorithm is provided by Schnarr et al. or can be found in the Radixact Physics Essentials Guide.X direction is corrected, but motion in IEC‐Z is not. An example of applying motion corrections to the MLC sinogram is shown in Figure Motion corrections were applied separately for the MLC sinogram and jaw pattern. MLC corrections were applied based on the beams eye view of the target motion, which is dependent on gantry angle and is consistent with the behavior during treatment. For example, if the gantry is at 0 degree (pointing down), motion in the IEC‐Y positions from Figure Lastly, the jaw positions for each of the 10 plans were modified based on the location of the target in each phase, similar to the MLC compensation. In Figure The plans were calculated on the corresponding 4DCT phases. The calculations were performed with the tomotherapy convolution/superposition (C/S) algorithm using the same beam model as the clinical dose calculations. Dose was calculated at each sub‐projection, or 153 discrete projection angles per gantry rotation.2.53 or smaller and each registration for all subjects was reviewed and refined with the Reg Reveal and Reg Refine tools in MIM, which allow the user to modify and improve the quality of the registration in different regions.Once doses were calculated, DIR was used to transfer the dose from each phase of the 4DCT to the reference phase. For the example cases in this work, DIR was performed in MIM, which uses an intensity‐based free‐form deformation algorithm with a sum of squared differences as a similarity measurement.The recommendations of Task Group 132 should be followed to verify the accuracy of the DIR, which includes commissioning/verification of the algorithm and patient‐specific verification of each registration.In addition, several steps were taken to verify the accuracy of the DIR for each example case.2.6Once all DIR transformations had been verified and doses had been transferred to the reference phase, the doses were summed, resulting in the Synchrony‐accumulated dose. Prior to calculation, the Radixact couch was added to each phase of the 4DCT to match the position of the couch on the planning image, which was performed using the MATLAB. The dose was scaled by the number of fractions to result in the total dose distribution, which assumes that the patient breathes the same and the dose is delivered the same each fraction. All results in this work were for the full prescription and not individual fractions.Lastly, the planned and Synchrony‐accumulated doses were compared. This is analogous to comparing the planned and delivered doses, where the Synchrony‐accumulated dose is the best approximation of the dose delivered with tracking active. For the examples in this work, the doses were compared using differences in OAR dose metrics typically used for lung and liver SBRT plan evaluation at our institution.To validate the accuracy of the dose calculation and accumulation, a test case was performed following all the same steps of the framework but using the reference phase image for each of the 10 images in the framework instead of the original 10 phases of the 4DCT with varying anatomy. The accumulated dose distribution was compared to the planned dose and no dose difference was found, which provided confidence in the accuracy of the framework.3Y motion of the tumor. The maximum range the jaws can mechanically move is 2.5 cm for the 2.5‐cm jaw setting and 4 cm for the 1‐cm jaw setting. The percent of leaf openings modified was calculated by comparing the pre‐synchronized sinograms to the synchronized sinograms. Only nonzero leaf openings in the pre‐synchronized sinogram are considered in the calculation. If the percent of leaf openings modified is 10%, it indicates that for 90% of the leaf openings (and approximately 90% of the time), there was insufficient motion in the axial plane to warrant MLC shifts. The most MLC leaf shifts occurred for Lung 3, despite not having the largest amplitudes in X and Z. This is because this value depends not only on the range of motion in X and Z, but also the relative centering of the target in the reference phase. If the target is not in the center of the range of motion in the axial plane in the reference phase, the target will spend more time off‐axis and more leaf openings will be modified than if centered. Overall, jaw motion accounts for the majority of the changes to the treatment plan as most patients  have a majority of motion in the Y direction.Table 3 was 20.0 Gy and the Synchrony‐accumulated dose was 18.1 Gy. Therefore, the dose deviation is −1.9 Gy, which is −9.4% compared to the planned dose of 20.0 Gy or −4.0% compared to the objective of 47.0 Gy.Tables For the lung subjects, 21 of 35 OAR dose differences were greater than 5% deviation compared to the plan dose. When the difference is compared to the objective dose, 11 of 35 OAR dose differences were greater than 5% deviation. For the liver subjects, 7 of 30 OAR dose differences compared to planned were greater than 5% deviation and 3 of 30 OAR dose differences compared to the objective were greater than 5% deviation.Body maximum dose differences were tabulated as an indication of the magnitude of differences that were observed in the body, which may not be represented in a single slice of the dose difference distribution or in the volumetric dose metrics. The maximum dose difference in the body was on average 10.9 ± 3.9 Gy among the 10 subjects and the minimum difference (most negative) in the body was on average −9.0 ± 3.4 Gy. The locations of the differences are generally in anatomy that is in field for one plan but out of field for the other. These values indicate how OAR doses may be much larger or smaller than planned for any given subject. The largest positive dose deviation for any subject was 19.8 Gy for Liver 5, which occurred inside healthy liver tissue. The largest negative dose deviation for any subject was −14.7 Gy for Lung 4, which occurred inside healthy lung tissue.Although investigating target dose was not the goal of this work, the GTV and PTV doses were included in Tables 3 or less) for these structures was −5.6% relative to the plan and −2.5% relative to the objective. This is caused by the synchronization spreading out the radiation field, therefore blurring the dose to static structures and reducing maximum doses.In general, there was a decrease in maximum dose metrics for the Synchrony accumulation compared to the plan. This is especially true for structures that are relatively static compared to the tumor such as the skin, spinal cord, chest wall, esophagus, and heart. The average dose difference among all subjects and all max dose metrics .magnitude of dose differences is more complex and necessitates the accumulation calculations.One may attempt to predict the location of dose deviations to OARs due to respiration provided enough spatial information is known. If the displacement between the target and an OAR is nonrigid, that is, the distance between the two changes as a function of respiratory phase, the OAR dose may change from the tracked treatment. For example, if the static plan is generated at the end of exhale phase and the target is in the middle of the liver, one can expect the primary beam to be directed more inferior than planned because the target will spend more time inferior due to motion of the diaphragm pushing the liver and tumor inferior. Static structures inferior to the transverse locations of the target in the reference phase may receive higher dose than planned and static structures superior may receive less dose than planned. This warrants careful choice of the reference phase. If the reference phase is mid‐ventilation, the target will move in both directions and if the reference phase is at end of inhale or end of exhale, the target will only move in one direction relative to the reference phase. However, one must know how the OAR moves in relation to the tumor. Also, predicting the within the field and penumbra, which are much smaller than changes to the dose distribution due to changes to the field (such as jaw sway).The results showed that the dose to the GTV is maintained more closely than the PTV, which is expected as the purpose of the PTV is to expand the GTV to account for uncertainties and ensure the prescription is delivered to the GTV.The first uncertainty that should be considered is the uncertainty of the 4DCT itself. These datasets are often noisy, which can cause differences in radiological pathlengths even if the anatomy is perfectly static. Artifacts are also common due to discrete binning of projections and the breathing motion,It is critical that the patient is aligned before treatment at the same phase of respiration that was used as the reference 4DCT phase for the calculations. For example, if the patient will be aligned before the treatment using a maximum inhalation breath hold scan, then the maximum inhale 4DCT phase should be used as the reference phase for the calculations. If a different phase is used, then the calculations may not be as representative of dose deviations that can be expected. Also, the patient may breathe differently during the treatment than during the 4DCT simulation. However, the 4DCT is the most commonly applied approximation of how the patient will breathe during the treatment. Breath‐coaching could be used to minimize this difference. It is not expected that the phase and shape of the patient's respiration will have a large effect on the overall dose distribution as the target is still limited to 10 locations based on the 4DCT data and therefore the shape of respiration only adjusts the amount of time spent in each of the 10 phases. Overall, the calculations should be viewed as the best approximation of what will be delivered to the patient from the tracked treatment and not the exact dose delivery.5Dose distributions calculated for tracking treatments assume that OARs move rigidly with the target. In this work, we developed an in‐house dose accumulation framework to quantify the inaccuracy introduced by that assumption for a subset of clinical examples of nonrigid body deformation. Doses were reduced in static OARs within the same transverse slice as the target observed in its reference phase. This is the consequence of allowing the jaw to sway to track the sup/inf motion of the target. This also caused doses to static OARs superior or inferior to the transverse slice of the target to increase as tracking may make them in field for a portion of the treatment. Lastly, differences in OAR doses between the planned and the synchronized deliveries can be leveraged during the treatment planning process. This could be done prior to the initial treatment fraction based on population statistics for motion models, during online adaptive radiation therapy, and/or offline adaptation based on estimates of accumulated dose. Target dose remained relatively constant, confirming that the goal of tracking was achieved. The current work demonstrates that OAR dose deviations should be considered for real‐time tracking systems in addition to maintaining target dose, which has been the focus of most measurements and investigations prior to this work.John E. Bayouth has ownership interest in MR Guidance, LLC, which has business activity with a company that utilizes image guided radiation therapy technology . Although this project was not sponsored externally, the data was collected on a Radixact system (Accuray Inc.) provided to UW–Madison under a research agreement . Randall Kimple is supported in part by the University of Wisconsin Carbone Cancer Center Support Grant (No. P30 CA014520). The remaining authors have no conflicts of interest to disclose.The authors confirm contribution to the paper as follows: study conception and design: Ferris WS, Bayouth JE, Chao EH; data collection: Ferris WS; analysis and interpretation of the results: all authors; draft manuscript preparation: Ferris WS; all authors reviewed the results and approved the final version of the manuscript.Supporting InformationClick here for additional data file.